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Sample records for agrb null mutants

  1. Molecular characterization of an atl null mutant of Staphylococcus aureus.

    PubMed

    Takahashi, Junko; Komatsuzawa, Hitoshi; Yamada, Sakuo; Nishida, Tetsuya; Labischinski, Harald; Fujiwara, Tamaki; Ohara, Masaru; Yamagishi, Jun-ichi; Sugai, Motoyuki

    2002-01-01

    atl is a gene encoding a bifunctional peptidoglycan hydrolase of Staphylococcus aureus. The gene product of atl is a 138 kDa protein that has an amidase domain and a glucosaminidase domain, and undergoes processing to generate two major peptidoglycan hydrolases, a 51 kDa glucosaminidase and a 62 kDa amidase in culture supernatant. An atl null mutant was isolated by allelic replacement and characterized. The mutant grew in clusters and sedimented when grown in broth culture. Analysis of peptidoglycan prepared from the wild type and the mutant revealed that there were no differences in muropeptide composition or in glycan chain length distribution. On the other hand, the atl mutation resulted in pleiotropic effects on cell surface nature. The mutant cells showed complete inhibition of metabolic turnover of cell wall peptidoglycan and revealed a rough outer cell wall surface. The mutation also decreased the amount of protein non-covalently bound to the cell surface and altered the protein profile, but did not affect proteins covalently associated with the cell wall. Lysis of growing cells treated with otherwise lytic concentration of penicillin G was completely inhibited in the mutant, but that of non-growing cells was not affected by the mutation. The atl mutation did not significantly affect the ability of S. aureus to provoke an acute infection when inoculated intraperitoneally in a mouse sepsis model. These results further support the supposition that atl gene products are involved in cell separation, cell wall turnover and penicillin-induced lysis of the cells. PMID:12437027

  2. Impairment in motor learning of somatostatin null mutant mice.

    PubMed

    Zeyda, T; Diehl, N; Paylor, R; Brennan, M B; Hochgeschwender, U

    2001-07-01

    Somatostatin was first identified as a hypothalamic factor which inhibits the release of growth hormone from the anterior pituitary (somatotropin release inhibitory factor, SRIF). Both SRIF and its receptors were subsequently found widely distributed within and outside the nervous system, in the adult as well as in the developing organism. Reflecting this wide distribution, somatostatin has been implicated regulating a diverse array of biological processes. These include body growth, homeostasis, sensory perception, autonomous functions, rate of intestinal absorption, behavior, including cognition and memory, and developmental processes. We produced null mutant mice lacking somatostatin through targeted mutagenesis. The mutant mice are healthy, fertile, and superficially indistinguishable from their heterozygous and wildtype littermates. A 'first round' phenotype screen revealed that mice lacking somatostatin have elevated plasma growth hormone levels, despite normal body size, and have elevated basal plasma corticosterone levels. In order to uncover subtle and unexpected differences, we carried out a systematic behavioral phenotype screen which identified a significant impairment in motor learning revealed when increased demands were made on motor coordination. Motor coordination and motor learning require an intact cerebellum. While somatostatin is virtually absent from the adult cerebellum, the ligand and its receptor(s) are transiently expressed at high levels in the developing cerebellum. This result suggests the functional significance of transient expression of SRIF and its receptors in the development of the cerebellum. PMID:11430867

  3. Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Signore, M.; Simeone, A.

    2001-01-01

    We investigated the development of inner ear innervation in Otx1 null mutants, which lack a horizontal canal, between embryonic day 12 (E12) and postnatal day 7 (P7) with DiI and immunostaining for acetylated tubulin. Comparable to control animals, horizontal crista-like fibers were found to cross over the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 null mutants had a small patch of sensory hair cells at this position. Measurement of the area of the utricular macula suggested it to be enlarged in Otx1 null mutants. We suggest that parts of the horizontal canal crista remain incorporated in the utricular sensory epithelium in Otx1 null mutants. Other parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajectory as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the dorsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 is not directly involved in sensory hair cell formation of the horizontal canal but affects the segregation of the horizontal canal crista from the utricle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal canal morphogenesis as well as morphogenesis of these foramina.

  4. Zn2+ Uptake in Streptococcus pyogenes: Characterization of adcA and lmb Null Mutants

    PubMed Central

    Tedde, Vittorio; Rosini, Roberto; Galeotti, Cesira L.

    2016-01-01

    An effective regulation of metal ion homeostasis is essential for the growth of microorganisms in any environment and in pathogenic bacteria is strongly associated with their ability to invade and colonise their hosts. To gain a better insight into zinc acquisition in Group A Streptococcus (GAS) we characterized null deletion mutants of the adcA and lmb genes of Streptococcus pyogenes strain MGAS5005 encoding the orthologues of AdcA and AdcAII, the two surface lipoproteins with partly redundant roles in zinc homeostasis in Streptococcus pneumoniae. Null adcA and lmb mutants were analysed for their capability to grow in zinc-depleted conditions and were found to be more susceptible to zinc starvation, a phenotype that could be rescued by the addition of Zn2+ ions to the growth medium. Expression of AdcA, Lmb and HtpA, the polyhistidine triad protein encoded by the gene adjacent to lmb, during growth under conditions of limited zinc availability was examined by Western blot analysis in wild type and null mutant strains. In the wild type strain, AdcA was always present with little variation in expression levels between conditions of excess or limited zinc availability. In contrast, Lmb and HtpA were expressed at detectable levels only during growth in the presence of low zinc concentrations or in the null adcA mutant, when expression of lmb is required to compensate for the lack of adcA expression. In the latter case, Lmb and HtpA were overexpressed by several fold, thus indicating that also in GAS AdcA is a zinc-specific importer and, although it shares this function with Lmb, the two substrate-binding proteins do not show fully overlapping roles in zinc homeostasis. PMID:27031880

  5. ‘Transient’ Genetic Suppression Facilitates Generation of Hexose Transporter Null Mutants in Leishmania mexicana

    PubMed Central

    Feng, Xiuhong; Rodriguez-Contreras, Dayana; Polley, Tamsen; Lye, Lon-Fye; Scott, David; Burchmore, Richard J.S.; Beverley, Stephen M.; Landfear, Scott M.

    2012-01-01

    Summary The genome of Leishmania mexicana encompasses a cluster of three glucose transporter genes designated LmxGT1, LmxGT2, and LmxGT3. Functional and genetic studies of a cluster null mutant (Δlmxgt1-3) have dissected the roles of these proteins in Leishmania metabolism and virulence. However, null mutants were recovered at very low frequency, and comparative genome hybridizations revealed that Δlmxgt1-3 mutants contained a linear extrachromosomal 40 kb amplification of a region on chromosome 29 not amplified in WT parasites. These data suggested a model where this 29–40k amplicon encoded a second site suppressor contributing to parasite survival in the absence of GT1-3 function. To test this, we quantified the frequency of recovery of knockouts in the presence of individual overexpressed ORFs covering the 29–40k amplicon. The data mapped the suppressor activity to PIFTC3, encoding a component of the intraflagellar transport pathway. We discuss possible models by which PIFTC3 might act to facilitate loss of GTs specifically. Surprisingly, by plasmid segregation we showed that continued PIFTC3 overexpression was not required for Δlmxgt1-3 viability. These studies provide the first evidence that genetic suppression can occur by providing critical biological functions transiently. This novel form of genetic suppression may extend to other genes, pathways and organisms. PMID:23170981

  6. Superoxide Dismutase (Sod-1) Null Mutants of Neurospora Crassa: Oxidative Stress Sensitivity, Spontaneous Mutation Rate and Response to Mutagens

    PubMed Central

    Chary, P.; Dillon, D.; Schroeder, A. L.; Natvig, D. O.

    1994-01-01

    Enzymatic superoxide-dismutase activity is believed to be important in defense against the toxic effects of superoxide. Although superoxide dismutases are among the best studied proteins, numerous questions remain concerning the specific biological roles of the various superoxide-dismutase types. In part, this is because the proposed damaging effects of superoxide are manifold, ranging from inactivation of certain metabolic enzymes to DNA damage. Studies with superoxide-deficient mutants have proven valuable, but surprisingly few such studies have been reported. We have constructed and characterized Neurospora crassa mutants that are null for sod-1, the gene that encodes copper-zinc superoxide dismutase. Mutant strains are sensitive to paraquat and elevated oxygen concentrations, and they exhibit an increased spontaneous mutation rate. They appear to have near wild-type sensitivities to near- and far-UV, heat shock and γ-irradiation. Unlike the equivalent Saccharomyces cerevisiae mutant and the sodA sodB double mutant of Escherichia coli, they do not exhibit aerobic auxotrophy. These results are discussed in the context of an attempt to identify consensus phenotypes among superoxide dismutase-deficient mutants. N. crassa sod-1 null mutant strains were also employed in genetic and subcellular fractionation studies. Results support the hypothesis that a single gene (sod-1), located between Fsr-12 and leu-3 on linkage group I, is responsible for most or all CuZn superoxide dismutase activity in this organism. PMID:8088518

  7. Cardiac hypertrophy in anion exchanger 1-null mutant mice with severe hemolytic anemia.

    PubMed

    Alvarez, Bernardo V; Kieller, Dawn M; Quon, Anita L; Robertson, Murray; Casey, Joseph R

    2007-03-01

    Anion exchanger 1 (AE1; SLC4A1), the plasma membrane Cl(-)/HCO(3)(-) exchanger of erythrocytes, is also expressed in heart. The aim of this study was to assess the role of AE1 in heart function through study of AE1-null (AE1(-/-)) mice, which manifest severe hemolytic anemia resulting from erythrocyte fragility. Heart weight-to-body weight ratios were significantly higher in the AE1(-/-) mice than in wild-type (AE1(+/+)) littermates at both 1-3 days postnatal (3.01 +/- 0.38 vs. 1.45 +/- 0.04) and at 7 days postnatal (9.45 +/- 0.53 vs. 4.13 +/- 0.41), indicating that loss of AE1 led to cardiac hypertrophy. Heterozygous (AE1(+/-)) mice had no signs of cardiac hypertrophy. Morphology of the adult AE1(-/-) mutant heart revealed an increased left ventricular mass, accompanied by increased collagen deposition and fibrosis. M-mode echocardiography revealed dysfunction of the AE1(-/-) hearts, including dilated left ventricle end diastole and systole and expanded left ventricular mass compared with AE1(+/+) hearts. Expression of intracellular pH-regulatory mechanisms in the hypertrophic myocardium of neonate AE1(-/-) mutant mice was indistinguishable from AE1(+/-) and AE1(+/+) mice, as assessed by quantitative real-time RT-PCR. Confocal immunofluorescence revealed that, in normal mouse myocardium, AE1 is sarcolemmal, whereas AE3 and slc26a6 are found both at the sarcolemma and in internal membranes (T tubules and sarcoplasmic reticulum). These results indicate that AE1(-/-) mice, which suffer from severe hemolytic anemia and spherocytosis, display cardiac hypertrophy and impaired cardiac function, reminiscent of findings in patients with hereditary abnormalities of red blood cells. No essential role for AE1 in heart function was found. PMID:17056673

  8. Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism.

    PubMed

    Ju, Anes; Hammerschmidt, Kurt; Tantra, Martesa; Krueger, Dilja; Brose, Nils; Ehrenreich, Hannelore

    2014-08-15

    Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell adhesion molecules. Loss-of-function mutations of NLGN4 are among the most frequent, known genetic causes of heritable autism. Adult Nlgn4 null mutant (Nlgn4(-/-)) mice are a construct valid model of human autism, with both genders displaying a remarkable autistic phenotype, including deficits in social interaction and communication as well as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonatal and juvenile Nlgn4(-/-) mice have not been reported yet. The present study has been designed to systematically investigate in male and female Nlgn4(-/-) pups versus wildtype littermates (WT, Nlgn4(+/+)) developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development, followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexes and neuromotor coordination, did not yield any differences between Nlgn4(-/-) and their WT littermates. USV in pups (PND8-9) in response to brief separation from their mothers revealed remarkable gender effects, and a genotype influence in females regarding latency to first call. In juveniles (PND22-23), USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotype effect with reduced USV in Nlgn4(-/-) mice, and again a more prominent phenotype in females. Together, these data support an early manifestation of communication deficits in Nlgn4(-/-) mice that appear more pronounced in immature females with their overall stronger USV as compared to males. PMID:24855039

  9. Cognition and Mood-Related Behaviors in L3mbtl1 Null Mutant Mice

    PubMed Central

    Shen, Erica Y.; Jiang, Yan; Mao, Wenjie; Futai, Kensuke; Hock, Hanno; Akbarian, Schahram

    2015-01-01

    Alterations in histone lysine methylation and epigenetic regulators of gene expression could play a role in the neurobiology and treatment of patients diagnosed with mood spectrum disorder, including depression and anxiety. Mutations and altered expression of various lysine methyltransferases (KMTs) and demethylases (KDMs) have been linked to changes in motivational and emotional behaviors in preclinical model systems. However, it is not known whether regulators operating downstream of histone lysine methylation could affect mood-related behavior. Malignant Brain Tumor (MBT) domain ‘chromatin reader’ proteins bind to methylated histone lysine residues and associate with chromatin remodeling complexes to facilitate or repress gene expression. MBT proteins, including the founding member, L3mbtl1, maintain high levels of expression in neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide range of tests exploring cognition and mood-relevant behaviors at baseline and in the context of social isolation, as a stressor to elicit depression-related behavior in susceptible mice. L3mbtl1 loss-of-function was associated with significant decreases in depression and and anxiety in some of the behavioral paradigms. This was not associated with a more generalized neurological dysfunction because cognition and memory remained unaltered in comparison to controls. These findings warrant further investigations on the role of MBT chromatin reader proteins in the context of emotional and affective behaviors. PMID:25849281

  10. Functional consequences of stably expressing a mutant calsequestrin (CASQ2D307H) in the CASQ2 null background

    PubMed Central

    Kalyanasundaram, Anuradha; Viatchenko-Karpinski, Serge; Belevych, Andriy E.; Lacombe, Veronique A.; Hwang, Hyun Seok; Knollmann, Björn C.; Gyorke, Sandor

    2012-01-01

    The role of calsequestrin (CASQ2) in cardiac sarcoplasmic reticulum (SR) calcium (Ca2+) transport has gained significant attention since point mutations in CASQ2 were reported to cause ventricular arrhythmia. In the present study, we have critically evaluated the functional consequences of expressing the CASQ2D307H mutant protein in the CASQ2 null mouse. We recently reported that the mutant CASQ2D307H protein can be stably expressed in CASQ2 null hearts, and it targets appropriately to the junctional SR (Kalyanasundaram A, Bal NC, Franzini-Armstrong C, Knollmann BC, Periasamy M. J Biol Chem 285: 3076–3083, 2010). In this study, we found that introduction of CASQ2D307H protein in the CASQ2 null background partially restored triadin 1 levels, which were decreased in the CASQ2 null mice. Despite twofold expression (relative to wild-type CASQ2), the mutant protein failed to increase SR Ca2+ load. We also found that the Ca2+ transient decays slower in the CASQ2 null and CASQ2D307H cells. CASQ2D307H myocytes, when rhythmically paced and challenged with isoproterenol, exhibit spontaneous Ca2+ waves similar to CASQ2 null myocytes; however, the stability of Ca2+ cycling was increased in the CASQ2D307H myocytes. In the presence of isoproterenol, Ca2+-transient amplitude in CASQ2D307H myocytes was significantly decreased, possibly indicating an inherent defect in Ca2+ buffering capacity and release from the mutant CASQ2 at high Ca2+ concentrations. We also observed polymorphic ventricular tachycardia in the CASQ2D307H mice, although lesser than in the CASQ2 null mice. These data suggest that CASQ2D307H point mutation may affect Ca2+ buffering capacity and Ca2+ release. We propose that poor interaction between CASQ2D307H and triadin 1 could affect ryanodine receptor 2 stability, thereby increasing susceptibility to delayed afterdepolarizations and triggered arrhythmic activity. PMID:21984545

  11. Metabolic and Phenotypic Differences between Mice Producing a Werner Syndrome Helicase Mutant Protein and Wrn Null Mice.

    PubMed

    Aumailley, Lucie; Garand, Chantal; Dubois, Marie Julie; Johnson, F Brad; Marette, André; Lebel, Michel

    2015-01-01

    Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase, WRN. Mice lacking part of the helicase domain of the WRN orthologue exhibit many phenotypic features of WS, including metabolic abnormalities and a shorter mean life span. In contrast, mice lacking the entire Wrn protein (i.e. Wrn null mice) do not exhibit a premature aging phenotype. In this study, we used a targeted mass spectrometry-based metabolomic approach to identify serum metabolites that are differentially altered in young Wrn helicase mutant and Wrn null mice. An antibody-based quantification of 43 serum cytokines and markers of cardiovascular disease risk complemented this study. We found that Wrn helicase mutants exhibited elevated and decreased levels, respectively, of the anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IL-18. Wrn helicase mutants also exhibited an increase in serum hydroxyproline and plasminogen activator inhibitor-1, markers of extracellular matrix remodeling of the vascular system and inflammation in aging. We also observed an abnormal increase in the ratio of very long chain to short chain lysophosphatidylcholines in the Wrn helicase mutants underlying a peroxisome perturbation in these mice. Remarkably, the Wrn mutant helicase protein was mislocalized to the endoplasmic reticulum and the peroxisomal fractions in liver tissues. Additional analyses with mouse embryonic fibroblasts indicated a severe defect of the autophagy flux in cells derived from Wrn helicase mutants compared to wild type and Wrn null animals. These results indicate that the deleterious effects of the helicase-deficient Wrn protein are mediated by the dysfunction of several cellular organelles. PMID:26447695

  12. Metabolic and Phenotypic Differences between Mice Producing a Werner Syndrome Helicase Mutant Protein and Wrn Null Mice

    PubMed Central

    Aumailley, Lucie; Garand, Chantal; Dubois, Marie Julie; Johnson, F. Brad; Marette, André; Lebel, Michel

    2015-01-01

    Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase, WRN. Mice lacking part of the helicase domain of the WRN orthologue exhibit many phenotypic features of WS, including metabolic abnormalities and a shorter mean life span. In contrast, mice lacking the entire Wrn protein (i.e. Wrn null mice) do not exhibit a premature aging phenotype. In this study, we used a targeted mass spectrometry-based metabolomic approach to identify serum metabolites that are differentially altered in young Wrn helicase mutant and Wrn null mice. An antibody-based quantification of 43 serum cytokines and markers of cardiovascular disease risk complemented this study. We found that Wrn helicase mutants exhibited elevated and decreased levels, respectively, of the anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IL-18. Wrn helicase mutants also exhibited an increase in serum hydroxyproline and plasminogen activator inhibitor-1, markers of extracellular matrix remodeling of the vascular system and inflammation in aging. We also observed an abnormal increase in the ratio of very long chain to short chain lysophosphatidylcholines in the Wrn helicase mutants underlying a peroxisome perturbation in these mice. Remarkably, the Wrn mutant helicase protein was mislocalized to the endoplasmic reticulum and the peroxisomal fractions in liver tissues. Additional analyses with mouse embryonic fibroblasts indicated a severe defect of the autophagy flux in cells derived from Wrn helicase mutants compared to wild type and Wrn null animals. These results indicate that the deleterious effects of the helicase-deficient Wrn protein are mediated by the dysfunction of several cellular organelles. PMID:26447695

  13. Kharon1 Null Mutants of Leishmania mexicana Are Avirulent in Mice and Exhibit a Cytokinesis Defect within Macrophages

    PubMed Central

    Sanchez, Marco A.; Valli, Jessica; Gluenz, Eva; Landfear, Scott M.

    2015-01-01

    In a variety of eukaryotes, flagella play important roles both in motility and as sensory organelles that monitor the extracellular environment. In the parasitic protozoan Leishmania mexicana, one glucose transporter isoform, LmxGT1, is targeted selectively to the flagellar membrane where it appears to play a role in glucose sensing. Trafficking of LmxGT1 to the flagellar membrane is dependent upon interaction with the KHARON1 protein that is located at the base of the flagellar axoneme. Remarkably, while Δkharon1 null mutants are viable as insect stage promastigotes, they are unable to survive as amastigotes inside host macrophages. Although Δkharon1 promastigotes enter macrophages and transform into amastigotes, these intracellular parasites are unable to execute cytokinesis and form multinucleate cells before dying. Notably, extracellular axenic amastigotes of Δkharon1 mutants replicate and divide normally, indicating a defect in the mutants that is only exhibited in the intra-macrophage environment. Although the flagella of Δkharon1 amastigotes adhere to the phagolysomal membrane of host macrophages, the morphology of the mutant flagella is often distorted. Additionally, these null mutants are completely avirulent following injection into BALB/c mice, underscoring the critical role of the KHARON1 protein for viability of intracellular amastigotes and disease in the animal model of leishmaniasis. PMID:26266938

  14. Toll-Like Receptor 4 Mutant and Null Mice Retain Morphine-Induced Tolerance, Hyperalgesia, and Physical Dependence

    PubMed Central

    Mattioli, Theresa Alexandra; Leduc-Pessah, Heather; Skelhorne-Gross, Graham; Nicol, Christopher J. B.; Milne, Brian; Trang, Tuan; Cahill, Catherine M.

    2014-01-01

    The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4). Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal) were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (−) naloxone, an opioid receptor antagonist, and (+) naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence. PMID:24824631

  15. The effect of Clostridium perfringens type C strain CN3685 and its isogenic beta toxin null mutant in goats.

    PubMed

    Garcia, J P; Beingesser, J; Fisher, D J; Sayeed, S; McClane, B A; Posthaus, H; Uzal, F A

    2012-06-15

    Clostridium perfringens type C is an important cause of enteritis and/or enterocolitis in several animal species, including pigs, sheep, goats, horses and humans. The disease is a classic enterotoxemia and the enteric lesions and associated systemic effects are thought to be caused primarily by beta toxin (CPB), one of two typing toxins produced by C. perfringens type C. This has been demonstrated recently by fulfilling molecular Koch's postulates in rabbits and mice. We present here an experimental study to fulfill these postulates in goats, a natural host of C. perfringens type C disease. Nine healthy male or female Anglo Nubian goat kids were inoculated with the virulent C. perfringens type C wild-type strain CN3685, an isogenic CPB null mutant or a strain where the cpb null mutation had been reversed. Three goats inoculated with the wild-type strain presented abdominal pain, hemorrhagic diarrhea, necrotizing enterocolitis, pulmonary edema, hydropericardium and death within 24h of inoculation. Two goats inoculated with the CPB null mutant and two goats inoculated with sterile culture media (negative controls) remained clinically healthy during 24h after inoculation and no gross or histological abnormalities were observed in the tissues of any of them. Reversal of the null mutation to partially restore CPB production also increased virulence; 2 goats inoculated with this reversed mutant presented clinical and pathological changes similar to those observed in goats inoculated with the wild-type strain, except that spontaneous death was not observed. These results indicate that CPB is required for C. perfringens type C to induce disease in goats, supporting a key role for this toxin in natural C. perfringens type C disease pathogenesis. PMID:22296994

  16. The effect of Clostridium perfringens type C strain CN3685 and its isogenic beta toxin null mutant in goats

    PubMed Central

    Garcia, J. P.; Beingesser, J.; Fisher, D. J.; Sayeed, S.; McClane, B. A.; Posthaus, H.; Uzal, F. A.

    2012-01-01

    Clostridium perfringens type C is an important cause of enteritis and/or enterocolitis in several animal species, including pigs, sheep, goats, horses and humans. The disease is a classic enterotoxemia and the enteric lesions and associated systemic effects are thought to be caused primarily by beta toxin (CPB), one of two typing toxins produced by C. perfringens type C. This has been demonstrated recently by fulfilling molecular Koch’s postulates in rabbits and mice. We present here an experimental study to fulfill these postulates in goats, a natural host of C. perfringens type C disease. Nine healthy male or female Anglo Nubian goat kids were inoculated with the virulent C. perfringens type C wild-type strain CN3685, an isogenic CPB null mutant or a strain where the cpb null mutation had been reversed. Three goats inoculated with the wild-type strain presented abdominal pain, hemorrhagic diarrhea, necrotizing enterocolitis, pulmonary edema, hydropericardium and death within 24 h of inoculation. Two goats inoculated with the CPB null mutant and two goats inoculated with sterile culture media (negative controls) remained clinically healthy during 24 h after inoculation and no gross or histological abnormalities were observed in the tissues of any of them. Reversal of the null mutation to partially restore CPB production also increased virulence; 2 goats inoculated with this reversed mutant presented clinical and pathological changes similar to those observed in goats inoculated with the wild-type strain, except that spontaneous death was not observed. These results indicate that CPB is required for C. perfringens type C to induce disease in goats, supporting a key role for this toxin in natural C. perfringens type C disease pathogenesis. PMID:22296994

  17. Phenotypic rescue by a bovine transgene in a Cu/Zn superoxide dismutase-null mutant of Drosophila melanogaster

    SciTech Connect

    Reveillaud, I.; Kongpachith, A.; Fleming, J.E.

    1994-02-01

    Null mutants for Cu/Zn superoxide dismutase (CuZnSOD) in Drosophila melanogaster are male sterile, have a greatly reduced adult life span, and are hypersensitive to paraquat. We have introduced a synthetic bovine CuZnSOD transgene under the transcriptional control of the D. melanogaster 5C actin promoter into a CuZnSOD-null mutant of D. melanogaster. This was carried out by P-element-mediated transformation of the Drosophila-bovine CuZnSOD transgene into a CuZnSOD{sup +} recipient strain followed by genetic crossing of the transgene into a strain carrying the CuZnSOD-null mutation, cSOD{sup n108}. The resulting transformants express bovine CuZnSOD exclusively to about 30% of normal Drosophila CuZnSOD levels. Expression of the Drosophila-bovine CuZnSOD transgene in the CuZnSOD-null mutant rescues male fertility and resistance to paraquat to apparently normal levels. However, adult life span is restored to only 30% of normal, and resistance to hyperoxia is 90% of that found in control flies. This striking differential restoration of pleiotropic phenotypes could be the result of a threshold of CuZnSOD expression necessary for normal male fertility and resistance to the toxicity of paraquat or hyperoxia which is lower than the threshold required to sustain a normal adult life span. Alternatively, the differential rescue of fertility, resistance to active oxygen, and life span might indicate different cell-specific transcriptional requirements for these functions which are normally provided by the control elements of the native CuZnSOD gene but are only partly compensated for by the transcriptional control elements of the actin 5C promoter. 29 refs., 5 figs., 1 tab.

  18. Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation

    PubMed Central

    2011-01-01

    Background Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy. Results In this study, we tested the ability of a Leishmania infantum deletion mutant, lacking both HSP70-II alleles (ΔHSP70-II), to provide protection against Leishmania infection in the L. major-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-Leishmania IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (Mesocricetus auratus), infected with mutant parasites did not develop any sign of pathology. Conclusions The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis. PMID:21794145

  19. Characterization of a Null Allelic Mutant of the Rice NAL1 Gene Reveals Its Role in Regulating Cell Division

    PubMed Central

    Jiang, Dan; Fang, Jingjing; Lou, Lamei; Zhao, Jinfeng; Yuan, Shoujiang; Yin, Liang; Sun, Wei; Peng, Lixiang; Guo, Baotai; Li, Xueyong

    2015-01-01

    Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1) show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1), nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogenous expression of NAL1 in fission yeast (Schizosaccharomyces pombe) further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division. PMID:25658704

  20. Characterization of a null allelic mutant of the rice NAL1 gene reveals its role in regulating cell division.

    PubMed

    Jiang, Dan; Fang, Jingjing; Lou, Lamei; Zhao, Jinfeng; Yuan, Shoujiang; Yin, Liang; Sun, Wei; Peng, Lixiang; Guo, Baotai; Li, Xueyong

    2015-01-01

    Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1) show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1), nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogeneous expression of NAL1 in fission yeast (Schizosaccharomyces pombe) further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division. PMID:25658704

  1. Phenotypic and expression analysis of a novel spontaneous myosin VI null mutant mouse.

    PubMed

    Mochizuki, Eiji; Okumura, Kazuhiro; Ishikawa, Masashi; Yoshimoto, Sachi; Yamaguchi, Junya; Seki, Yuta; Wada, Kenta; Yokohama, Michinari; Ushiki, Tatsuo; Tokano, Hisashi; Ishii, Rie; Shitara, Hiroshi; Taya, Choji; Kitamura, Ken; Yonekawa, Hiromichi; Kikkawa, Yoshiaki

    2010-01-01

    In humans, hearing is a major factor in quality of life. Mouse models are important tools for the discovery of genes responsible for genetic hearing loss, often enabling analysis of the processes that regulate the onset of deafness in humans. Thus far, at least 400 deafness mutants have been discovered in laboratory mouse populations and used in the study of deafness. Here we report the discovery of a new spontaneous recessive Rinshoken shaker/waltzer (rsv) mutant derived from our in-house C57BL/6J stock, which exhibits circling and/or head-tossing behaviour and complete lack of auditory brain response to any sound pressure. The hearing and balance phenotypes are associated with structural defects, in particular, disorganisation and fusion of stereocilia in the inner ear hair cells. Two sets of intersubspecific N(2) mice were generated for the positional cloning of the rsv mutation. The mutant locus was mapped to a 4.8-Mb region of chromosome 9, which contains myosin VI (Myo6), a gene responsible for deafness in humans and Snell's waltzer mutation in mice. The rsv mutant showed reduced expressions of Myo6 mRNA and MYO6 protein in the inner ear. Moreover, no immunoreactivity was observed in the cochlear and vestibular hair cells in the rsv mutant mice. We sequenced the genomic region (30,154 bp) of Myo6, including all coding exons, a non-coding exon, UTRs and the Myo6 promoter; however, no mutation was discovered in these regions. We therefore speculate that loss of MYO6 expression might cause shaker/waltzer behaviour and deafness in the rsv mutant; also, loss of MYO6 expression might be the result of mutations in an unidentified regulatory region(s) of the gene. PMID:20224170

  2. Generation of rac3 Null Mutant Mice: Role of Rac3 in Bcr/Abl-Caused Lymphoblastic Leukemia

    PubMed Central

    Cho, Young Jin; Zhang, Bin; Kaartinen, Vesa; Haataja, Leena; de Curtis, Ivan; Groffen, John; Heisterkamp, Nora

    2005-01-01

    Numerous studies indirectly implicate Rac GTPases in cancer. To investigate if Rac3 contributes to normal or malignant cell function, we generated rac3 null mutants through gene targeting. These mice were viable, fertile, and lacked an obvious external phenotype. This shows Rac3 function is dispensable for embryonic development. Bcr/Abl is a deregulated tyrosine kinase that causes chronic myelogenous leukemia and Ph-positive acute lymphoblastic leukemia in humans. Vav1, a hematopoiesis-specific exchange factor for Rac, was constitutively tyrosine phosphorylated in primary lymphomas from Bcr/Abl P190 transgenic mice, suggesting inappropriate Rac activation. rac3 is expressed in these malignant hematopoietic cells. Using lysates from BCR/ABL transgenic mice that express or lack rac3, we detected the presence of activated Rac3 but not Rac1 or Rac2 in the malignant precursor B-lineage lymphoblasts. In addition, in female P190 BCR/ABL transgenic mice, lack of rac3 was associated with a longer average survival. These data are the first to directly show a stimulatory role for Rac in leukemia in vivo. Moreover, our data suggest that interference with Rac3 activity, for example, by using geranyl-geranyltransferase inhibitors, may provide a positive clinical benefit for patients with Ph-positive acute lymphoblastic leukemia. PMID:15964830

  3. A small GTP-binding protein from Arabidopsis thaliana functionally complements the yeast YPT6 null mutant.

    PubMed Central

    Bednarek, S Y; Reynolds, T L; Schroeder, M; Grabowski, R; Hengst, L; Gallwitz, D; Raikhel, N V

    1994-01-01

    A clone designated A.t.RAB6 encoding a small GTP-binding protein was isolated from a cDNA library of Arabidopsis thaliana leaf tissue. The predicted amino acid sequence was highly homologous to the mammalian and yeast counterparts, H.Rab6 and Ryh1/Ypt6, respectively. Lesser homology was found between the predicted Arabidopsis protein sequence and two small GTP-binding proteins isolated from plant species (44% homology to Zea mays Ypt1 and 43% homology to Nicotiana tabacum Rab5). Conserved stretches in the deduced amino acid sequence of A.t.Rab6 include four regions involved in GTP-binding, an effector region, and C-terminal cysteine residues required for prenylation and subsequent membrane attachment. Northern blot analysis demonstrated that A.t.Rab6 mRNA was expressed in root, leaf, stem, and flower tissues from A. thaliana with the highest levels present in roots. Escherichia coli produced histidine-tagged A.t.Rab6 protein-bound GTP, whereas a mutation in one of the guanine nucleotide-binding sites (asparagine122 to isoleucine) rendered it incapable of binding GTP. Functionally, the A.t.RAB6 gene was able to complement the temperature-sensitive phenotype of the YPT6 null mutant in yeast. The isolation of this gene will aid in the dissection of the machinery involved in soluble protein sorting at the trans-Golgi network of plants. PMID:8159788

  4. Attenuated Reactive Gliosis and Enhanced Functional Recovery Following Spinal Cord Injury in Null Mutant Mice of Platelet-Activating Factor Receptor.

    PubMed

    Wang, Yuanyi; Gao, Zhongwen; Zhang, Yiping; Feng, Shi-Qing; Liu, Yulong; Shields, Lisa B E; Zhao, Ying-Zheng; Zhu, Qingsan; Gozal, David; Shields, Christopher B; Cai, Jun

    2016-07-01

    Platelet-activating factor (PAF) is a unique phosphoglycerine that mediates the biological functions of both immune and nervous systems. Excessive PAF plays an important role in neural injury via its specific receptor (PAFR). In this study, we hypothesized that PAF signaling activates reactive gliosis after spinal cord injury (SCI), and blocking the PAF pathway would modify the glia scar formation and promote functional recovery. PAF microinjected into the normal wild-type spinal cord induced a dose-dependent activation of microglia and astrocytes. In the SCI mice, PAFR null mutant mice showed a better functional recovery in grip and rotarod performances than wild-type mice. Although both microglia and astrocytes were activated after SCI in wild-type and PAFR null mutant mice, expressions of IL-6, vimentin, nestin, and GFAP were not significantly elevated in PAFR null mutants. Disruption of PAF signaling inhibited the expressions of proteoglycan CS56 and neurocan (CSPG3). Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at 7 dpi but more NFH-labeled axons at 28 dpi was found in the area adjacent to the epicenter in PAFR null mutant SCI mice. Moreover, treatment with PAFR antagonist Ginkgolide B (GB) at the chronic phase rather than acute phase enhanced the functional recovery in the wild-type SCI mice. These findings suggest that PAF signaling participates in reactive gliosis after SCI, and blocking of this signaling enhances functional recovery and to some extent may promote axon regrowth. PMID:26084439

  5. Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets

    PubMed Central

    Zhou, Lili; Summa, Keith C.; Olker, Christopher; Vitaterna, Martha H.; Turek, Fred W.

    2016-01-01

    Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ε) is a canonical circadian clock gene. Null and tau mutations in CK1ε show distinct effects on circadian period. To investigate the role of CK1ε in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1ε−/− and CK1εtau/tau mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1εtau/tau mice on a 24 hr LD cycle, a separate set of CK1εtau/tau mice were tested under both diet conditions on a 20 hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1ε−/− and CK1εtau/tau mutants on a 24 hr LD cycle and CK1εtau/tau mice on a 20 hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1εtau/tau mice on a 20 hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1ε involved in the integration of circadian biology and metabolic physiology. PMID:27144030

  6. Characterization of a New Pink-Fruited Tomato Mutant Results in the Identification of a Null Allele of the SlMYB12 Transcription Factor.

    PubMed

    Fernandez-Moreno, Josefina-Patricia; Tzfadia, Oren; Forment, Javier; Presa, Silvia; Rogachev, Ilana; Meir, Sagit; Orzaez, Diego; Aharoni, Aspah; Granell, Antonio

    2016-07-01

    The identification and characterization of new tomato (Solanum lycopersicum) mutants affected in fruit pigmentation and nutritional content can provide valuable insights into the underlying biology, as well as a source of new alleles for breeding programs. To date, all characterized pink-pigmented tomato fruit mutants appear to result from low SlMYB12 transcript levels in the fruit skin. Two new mutant lines displaying a pink fruit phenotype (pf1 and pf2) were characterized in this study. In the pf mutants, SlMYB12 transcripts accumulated to wild-type levels but exhibited the same truncation, which resulted in the absence of the essential MYB activation domain coding region. Allelism and complementation tests revealed that both pf mutants were allelic to the y locus and showed the same recessive null allele in homozygosis: Δy A set of molecular and metabolic effects, reminiscent of those observed in the Arabidopsis (Arabidopsis thaliana) myb11 myb12 myb111 triple mutant, were found in the tomato Δy mutants. To our knowledge, these have not been described previously, and our data support the idea of their being null mutants, in contrast to previously described transcriptional hypomorphic pink fruit lines. We detected a reduction in the expression of several flavonol glycosides and some associated glycosyl transferases. Transcriptome analysis further revealed that the effects of the pf mutations extended beyond the flavonoid pathway into the interface between primary and secondary metabolism. Finally, screening for Myb-binding sites in the candidate gene promoter sequences revealed that 141 of the 152 co-down-regulated genes may be direct targets of SlMYB12 regulation. PMID:27208285

  7. A human FSHB transgene encoding the double N-glycosylation mutant (Asn(7Δ) Asn(24Δ)) FSHβ subunit fails to rescue Fshb null mice.

    PubMed

    Wang, Huizhen; Butnev, Vladimir; Bousfield, George R; Kumar, T Rajendra

    2016-05-01

    Follicle-stimulating hormone (FSH) is a gonadotrope-derived heterodimeric glycoprotein. Both the common α- and hormone-specific β subunits contain Asn-linked N-glycan chains. Recently, macroheterogeneous FSH glycoforms consisting of β-subunits that differ in N-glycan number were identified in pituitaries of several species and subsequently the recombinant human FSH glycoforms biochemically characterized. Although chemical modification and in vitro site-directed mutagenesis studies defined the roles of N-glycans on gonadotropin subunits, in vivo functional analyses in a whole-animal setting are lacking. Here, we have generated transgenic mice with gonadotrope-specific expression of either an HFSHB(WT) transgene that encodes human FSHβ WT subunit or an HFSHB(dgc) transgene that encodes a human FSHβ(Asn7Δ 24Δ) double N-glycosylation site mutant subunit, and separately introduced these transgenes onto Fshb null background using a genetic rescue strategy. We demonstrate that the human FSHβ(Asn7Δ 24Δ) double N-glycosylation site mutant subunit, unlike human FSHβ WT subunit, inefficiently combines with the mouse α-subunit in pituitaries of Fshb null mice. FSH dimer containing this mutant FSHβ subunit is inefficiently secreted with very low levels detectable in serum. Fshb null male mice expressing HFSHB(dgc) transgene are fertile and exhibit testis tubule size and sperm number similar to those of Fshb null mice. Fshb null female mice expressing the mutant, but not WT human FSHβ subunit-containing FSH dimer are infertile, demonstrate no evidence of estrus cycles, and many of the FSH-responsive genes remain suppressed in their ovaries. Thus, HFSHB(dgc) unlike HFSHB(WT) transgene does not rescue Fshb null mice. Our genetic approach provides direct in vivo evidence that N-linked glycans on FSHβ subunit are essential for its efficient assembly with the α-subunit to form FSH heterodimer in pituitary. Our studies also reveal that N-glycans on FSHβ subunit are

  8. Decrease in Leaf Sucrose Synthesis Leads to Increased Leaf Starch Turnover and Decreased RuBP-limited Photosynthesis But Not Rubisco-limited Photosynthesis in Arabidopsis Null Mutants of SPSA1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    SPS (Sucrose phosphate synthase) isoforms from dicots cluster into families A, B and C. In this study, we investigated the individual effect of null mutations of each of the four SPS genes in Arabidopsis (spsa1, spsa2, spsb and spsc) on photosynthesis and carbon partitioning. Null mutants spsa1 and ...

  9. Rescue of Drosophila labial null mutant by the chicken ortholog Hoxb-1 demonstrates that the function of Hox genes is phylogenetically conserved.

    PubMed

    Lutz, B; Lu, H C; Eichele, G; Miller, D; Kaufman, T C

    1996-01-15

    Hox complexes are important players in the establishment of the body plan of invertebrates and vertebrates. Sequence comparison demonstrates a remarkable phylogenetic conservation of key structural features of Hox genes. The correlation between the physical order of genes along the chromosomes and their domains of function along the body axis is conserved between arthropods and vertebrates. Ectopic expression experiments suggest that the functions of homeo proteins also are conserved between invertebrates and vertebrates. However, it remains an open question whether vertebrate Hox genes expressed under the control of Drosophila regulatory sequences can substitute the function of Drosophila Hox genes. We have studied this issue with the Drosophila labial (lab) gene and its chicken ortholog gHoxb-1. We fused the entire protein-coding region of gHoxb-1 with previously identified regulatory sequences of lab. This approach places gHoxb-1 into the normal embryonic spatiotemporal context in which lab acts. Ten transgenic lines carrying gHoxb-1 were established and tested for their ability to rescue lab null mutant animals. Eight lines rescued with high efficiency, embryonic lethality, and abnormal head morphogenesis, two defects observed in lab null mutant embryos. The rescue with the gHoxb-1 minigene was close to the efficiency of that obtained with the Drosophila lab minigene. This indicates that gHoxb-1 protein can regulate lab target genes and thereby restore embryonic viability. This is striking, as Lab and gHoxb-1 proteins are divergent except for their homeo domains and a short stretch of amino acids amino-terminal to the homeo domain. Our findings demonstrate a functional conservation of the lab class homeo proteins between insects and vertebrates and support the view that function of Hox genes resides in relatively few conserved motifs and largely in the homeo domain. PMID:8566751

  10. An Arabidopsis pex10 Null Mutant Is Embryo Lethal, Implicating Peroxisomes in an Essential Role during Plant Embryogenesis1

    PubMed Central

    Sparkes, Imogen A.; Brandizzi, Federica; Slocombe, Stephen P.; El-Shami, Mahmoud; Hawes, Chris; Baker, Alison

    2003-01-01

    Peroxisomes participate in many important functions in plants, including seed reserve mobilization, photorespiration, defense against oxidative stress, and auxin and jasmonate signaling. In mammals, defects in peroxisome biogenesis result in multiple system abnormalities, severe developmental delay, and death, whereas in unicellular yeasts, peroxisomes are dispensable unless required for growth of specific substrates. PEX10 encodes an integral membrane protein required for peroxisome biogenesis in mammals and yeast. To investigate the importance of PEX10 in plants, we characterized a Ds insertion mutant in the PEX10 gene of Arabidopsis (AtPEX10). Heterozygous AtPEX10::dissociation element mutants show normal vegetative phenotypes under optimal growth conditions, but produce about 20% abnormal seeds. The embryos in the abnormal seeds are predominantly homozygous for the disruption allele. They show retarded development and some morphological abnormalities. No viable homozygous mutant plants were obtained. AtPEX10 fused to yellow fluorescent protein colocalized with green fluorescent protein-serine-lysine-leucine, a well-documented peroxisomal marker, suggesting that AtPEX10 encodes a peroxisomal protein that is essential for normal embryo development and viability. PMID:14576288

  11. Defective Hyphal Induction of a Candida albicans Phosphatidylinositol 3-Phosphate 5-Kinase Null Mutant on Solid Media Does Not Lead to Decreased Virulence

    PubMed Central

    Augsten, Martin; Hübner, Claudia; Nguyen, Monika; Künkel, Waldemar; Härtl, Albert; Eck, Raimund

    2002-01-01

    A phosphatidylinositol 3-phosphate [PI(3)P] 5-kinase gene (CaFAB1) of the most important human pathogenic yeast, Candida albicans, was cloned and sequenced. An open reading frame was detected which encodes a 2,369-amino-acid protein with a calculated molecular mass of 268 kDa and a relative isoelectric point of 6.76. This protein exhibits 38% overall amino acid sequence identity with Saccharomyces cerevisiae Fab1p. We localized the CaFAB1 gene on chromosome R. To determine the influence of the PI(3)P 5-kinase CaFab1p on processes involved in C. albicans morphogenesis and pathogenicity, we sequentially disrupted both copies of the gene. Homozygous deletion of C. albicans CaFAB1 resulted in a mutant strain which exhibited defects in morphogenesis. A Cafab1 null mutant had enlarged vacuoles, an acidification defect, and increased generation times and was unable to form hyphae on different solid media. The sensitivities to hyperosmotic and high-temperature stresses, adherence, and virulence compared to those of wild-type strain SC5314 were not affected. PMID:12117957

  12. Thermodynamics of charge separation of photosystem I in the menA and menB null mutants of Synechocystis sp. PCC 6803 determined by pulsed photoacoustics.

    PubMed

    Hou, Harvey J M; Shen, Gaozhong; Boichenko, Vladimir A; Golbeck, John H; Mauzerall, David

    2009-03-01

    When the biosynthesis of phylloquinone is inhibited in Synechocystis sp. PCC 6803 by interrupting the menA or the menB gene, photosystem I (PS I) recruits plastoquinone-9 (A(P)) to occupy the A(1) sites. In PS I from the menA and menB null mutants, forward electron transfer from the quinone to the FeS clusters occurs approximately 1000 times slower than in wild-type PS I [Semenov, A. Yu., Vassiliev, I. R., van der Est, A., Mamedov, M. D., Zybailov, B., Shen, G., Stehlik, D., Diner, B. A., Chitnis, P. R., and Golbeck, J. H. (2000) J. Biol. Chem. 275, 23429-23438]. To investigate the effect on thermodynamics, the enthalpy and volume changes of charge separation in PS I in the menA and menB mutants were measured using pulsed time-resolved photoacoustics on the nanosecond and microsecond time scales. The observed thermodynamic data are the same for the menA and menB mutants. This is expected because the recruited quinone (A(P)) is the same in both mutants. The volume change of PS I from the mutants following charge separation on both time scales was -17 +/- 2 A(3), less than that of the wild type, -21 A(3). The quantum yield of charge separation was found to be slightly lower (85 +/- 9%) than that of wild-type PS I (96 +/- 10%). The observed reaction is assigned to the formation of P(700)(+)A(P)(-) from P(700)*A(P). An enthalpy change (DeltaH) of -0.69 +/- 0.07 eV was obtained for this reaction. In contrast, a larger enthalpy change -0.8 eV for the formation of P(700)(+)A(1)(-) from P(700)* and an apparent entropy change (TDeltaS, T = 25 degrees C) of -0.2 eV were obtained in wild-type PS I [Hou, H. J. M., and Mauzerall, D. (2006) J. Am. Chem. Soc. 128, 1580-1586]. Taking the free energy to be -0.70 eV in PS I of the mutants, the apparent entropy is close to zero in the mutants. Since the apparent entropy change for the overall reaction of the production of P(700)(+)F(A/B)(-) from P(700)* is very likely the same as that of the wild type, +0.35 eV, this implies that the

  13. Cell wall monoglycine cross-bridges and methicillin hypersusceptibility in a femAB null mutant of methicillin-resistant Staphylococcus aureus.

    PubMed Central

    Strandén, A M; Ehlert, K; Labischinski, H; Berger-Bächi, B

    1997-01-01

    The femAB operon is involved in the formation of the characteristic pentaglycine side chain of the staphylococcal peptidoglycan. Allele replacement of the femAB operon with the tetracycline resistance determinant tetK in a methicillin-resistant Staphylococcus aureus strain resulted in impaired growth, methicillin hypersusceptibility, and lysostaphin resistance. The usual pentaglycine cross-bridges were replaced by monoglycine bridges exclusively, and cross-linking of the peptidoglycan strands was drastically reduced. Complementation of the femAB null mutant by either femA or femAB resulted in the extension of the cross-bridges to a triglycine or a pentaglycine, respectively. This finding suggests that FemA is responsible for the formation of glycines 2 and 3, and FemB is responsible for formation of glycines 4 and 5, of the pentaglycine side chain of the peptidoglycan precursor. Moreover, it can be deduced that addition of the first glycine must occur by a femAB-independent mechanism. PMID:8981974

  14. Modified Clp Protease Complex in the ClpP3 Null Mutant and Consequences for Chloroplast Development and Function in Arabidopsis1[C][W][OA

    PubMed Central

    Kim, Jitae; Olinares, Paul Dominic; Oh, Soo-hyun; Ghisaura, Stefania; Poliakov, Anton; Ponnala, Lalit; van Wijk, Klaas J.

    2013-01-01

    The plastid ClpPRT protease consists of two heptameric rings of ClpP1/ClpR1/ClpR2/ClpR3/ClpR4 (the R-ring) and ClpP3/ClpP4/ClpP5/ClpP6 (the P-ring) and peripherally associated ClpT1/ClpT2 subunits. Here, we address the contributions of ClpP3 and ClpP4 to ClpPRT core organization and function in Arabidopsis (Arabidopsis thaliana). ClpP4 is strictly required for embryogenesis, similar to ClpP5. In contrast, loss of ClpP3 (clpp3-1) leads to arrest at the hypocotyl stage; this developmental arrest can be removed by supplementation with sucrose or glucose. Heterotrophically grown clpp3-1 can be transferred to soil and generate viable seed, which is surprising, since we previously showed that CLPR2 and CLPR4 null alleles are always sterile and die on soil. Based on native gels and mass spectrometry-based quantification, we show that despite the loss of ClpP3, modified ClpPR core(s) could be formed, albeit at strongly reduced levels. A large portion of ClpPR subunits accumulated in heptameric rings, with overaccumulation of ClpP1/ClpP5/ClpP6 and ClpR3. Remarkably, the association of ClpT1 to the modified Clp core was unchanged. Large-scale quantitative proteomics assays of clpp3-1 showed a 50% loss of photosynthetic capacity and the up-regulation of plastoglobules and all chloroplast stromal chaperone systems. Specific chloroplast proteases were significantly up-regulated, whereas the major thylakoid protease (FtsH1/FtsH2/FtsH5/FtsH8) was clearly unchanged, indicating a controlled protease network response. clpp3-1 showed a systematic decrease of chloroplast-encoded proteins that are part of the photosynthetic apparatus but not of chloroplast-encoded proteins with other functions. Candidate substrates and an explanation for the differential phenotypes between the CLPP3, CLPP4, and CLPP5 null mutants are discussed. PMID:23548781

  15. Overproduction of CcmG and CcmFHRc Fully Suppresses the c-Type Cytochrome Biogenesis Defect of Rhodobacter capsulatus CcmI-Null Mutants

    PubMed Central

    Sanders, Carsten; Deshmukh, Meenal; Astor, Doniel; Kranz, Robert G.; Daldal, Fevzi

    2005-01-01

    Gram-negative bacteria like Rhodobacter capsulatus use intertwined pathways to carry out the posttranslational maturation of c-type cytochromes (Cyts). This periplasmic process requires at least 10 essential components for apo-Cyt c chaperoning, thio-oxidoreduction, and the delivery of heme and its covalent ligation. One of these components, CcmI (also called CycH), is thought to act as an apo-Cyt c chaperone. In R. capsulatus, CcmI-null mutants are unable to produce c-type Cyts and thus sustain photosynthetic (Ps) growth. Previously, we have shown that overproduction of the putative heme ligation components CcmF and CcmHRc (also called Ccl1 and Ccl2) can partially bypass the function of CcmI on minimal, but not on enriched, media. Here, we demonstrate that either additional overproduction of CcmG (also called HelX) or hyperproduction of CcmF-CcmHRc is needed to completely overcome the role of CcmI during the biogenesis of c-type Cyts on both minimal and enriched media. These findings indicate that, in the absence of CcmI, interactions between the heme ligation and thioreduction pathways become restricted for sufficient Cyt c production. We therefore suggest that CcmI, along with its apo-Cyt chaperoning function, is also critical for the efficacy of holo-Cyt c formation, possibly via its close interactions with other components performing the final heme ligation steps during Cyt c biogenesis. PMID:15937187

  16. A null mutation in VAMP1/synaptobrevin is associated with neurological defects and prewean mortality in the lethal-wasting mouse mutant.

    PubMed

    Nystuen, Arne M; Schwendinger, Jamie K; Sachs, Andrew J; Yang, Andy W; Haider, Neena B

    2007-01-01

    The soluble N-ethylmaleimide sensitive factor attachment receptors are a large family of membrane-associated proteins that are critical for Ca(2+)-mediated synaptic vesicle release. This family includes the VAMP, synaptosomal-associated protein, and syntaxin proteins. In this report, we describe a mutation in vesicle-associated membrane protein 1(VAMP1)/synaptobrevin in the mouse neurological mutant lethal-wasting (lew). The lethal-wasting mutant phenotype is characterized by a general lack of movement and wasting, eventually leading to death before weaning. Mutants are visibly immobile and lay on their side by postnatal day 10 (P10). Before this stage, mutants can be identified by a failure to attempt to right themselves. Affected mice die on average at P15. We used a positional cloning strategy to identify the mutation associated with this neurological phenotype. Lethal wasting had previously been linked to chromosome 6. We further narrowed the genetic disease interval and selected a small number of candidate genes for mutation screening. Genes were evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) to detect differences in their expression levels between control and mutant brain ribonucleic acid (RNA) samples. VAMP1 mRNA was found to be significantly downregulated in the lethal-wasting brain compared to wild-type littermates. Subsequently, a nonsense mutation was identified in the coding region of the gene. This mutation is predicted to truncate approximately half of the protein; however, Western blot analysis showed that no protein is detectable in the mutant. VAMP1 is selectively expressed in the retina and in discrete areas of the brain including the zona incerta and rostral periolivary region, although no gross histological abnormalities were observed in these tissues. Taken together, these data indicate that VAMP1 has a vital role in a subset of central nervous system tissues. PMID:17102983

  17. KRE5 Gene Null Mutant Strains of Candida albicans Are Avirulent and Have Altered Cell Wall Composition and Hypha Formation Properties

    PubMed Central

    Herrero, Ana B.; Magnelli, Paula; Mansour, Michael K.; Levitz, Stuart M.; Bussey, Howard; Abeijon, Claudia

    2004-01-01

    The UDP-glucose:glycoprotein glucosyltransferase (UGGT) is an endoplasmic reticulum sensor for quality control of glycoprotein folding. Saccharomyces cerevisiae is the only eukaryotic organism so far described lacking UGGT-mediated transient reglucosylation of N-linked oligosaccharides. The only gene in S. cerevisiae with similarity to those encoding UGGTs is KRE5. S. cerevisiae KRE5 deletion strains show severely reduced levels of cell wall β-1,6-glucan polymer, aberrant morphology, and extremely compromised growth or lethality, depending on the strain background. Deletion of both alleles of the Candida albicans KRE5 gene gives rise to viable cells that are larger than those of the wild type (WT), tend to aggregate, have enlarged vacuoles, and show major cell wall defects. C. albicans kre5/kre5 mutants have significantly reduced levels of β-1,6-glucan and more chitin and β-1,3-glucan and less mannoprotein than the WT. The remaining β-1,6-glucan, about 20% of WT levels, exhibits a β-1,6-endoglucanase digestion pattern, including a branch point-to-linear stretch ratio identical to that of WT strains, suggesting that Kre5p is not a β-1,6-glucan synthase. C. albicans KRE5 is a functional homologue of S. cerevisiae KRE5; it partially complements both the growth defect and reduced cell wall β-1,6-glucan content of S. cerevisiae kre5 viable mutants. C. albicans kre5/kre5 homozygous mutant strains are unable to form hyphae in several solid and liquid media, even in the presence of serum, a potent inducer of the dimorphic transition. Surprisingly the mutants do form hyphae in the presence of N-acetylglucosamine. Finally, C. albicans KRE5 homozygous mutant strains exhibit a 50% reduction in adhesion to human epithelial cells and are completely avirulent in a mouse model of systemic infection. PMID:15590817

  18. Early passage neonatal and adult keratinocytes are sensitive to apoptosis induced by infection with an ICP27-null mutant of herpes simplex virus 1.

    PubMed

    Pradhan, Prajakta; Nguyen, Marie L

    2013-02-01

    Herpes simplex virus 1 (HSV-1) is a enveloped, double stranded DNA virus that is the causative agent of various diseases including cold sores, encephalitis, and ocular keratitis. Previous research has determined that HSV-1 modulates cellular apoptotic pathways. Apoptosis is triggered in infected cells early in infection; however, later in the infection the apoptotic response is suppressed due to the expression of several viral apoptotic antagonists. This sets us a delicate balance between pro- and anti-apoptotic processes during the lytic phase of infection. Several studies have demonstrated that the apoptotic balance can be shifted during infection of certain cell types, leading to apoptosis of the infected cells (HSV-1-dependent apoptosis). For example, HEp-2 cells infected with an ICP27-null recombinant HSV-1 virus undergo HSV-1-dependent apoptosis. Differences in the sensitivity to HSV-1-dependent apoptosis have been revealed. Although many tumor cells have been found to be highly sensitive to this apoptotic response, with the exception hematological cells, all primary human cells tested prior to this study have been shown to be resistant to HSV-1-dependent apoptosis. Here, we demonstrate that early passage neonatal and adult human keratinocytes, which are usually the first cells to encounter HSV-1 in human infection and support the lytic stage of the life cycle, display membrane blebbing and ballooning, chromatin condensation, caspase activation, and cleavage of cellular caspase substrates when infected with an ICP27-null recombinant of HSV-1. Furthermore, caspase activation is needed for the efficient apoptotic response. These results suggest that apoptotic machinery may be a target for modulating HSV-disease in patients. PMID:23090729

  19. Arabidopsis AtDjA3 Null Mutant Shows Increased Sensitivity to Abscisic Acid, Salt, and Osmotic Stress in Germination and Post-germination Stages

    PubMed Central

    Salas-Muñoz, Silvia; Rodríguez-Hernández, Aída A.; Ortega-Amaro, Maria A.; Salazar-Badillo, Fatima B.; Jiménez-Bremont, Juan F.

    2016-01-01

    DnaJ proteins are essential co-chaperones involved in abiotic and biotic stress responses. Arabidopsis AtDjA3 gene encodes a molecular co-chaperone of 420 amino acids, which belongs to the J-protein family. In this study, we report the functional characterization of the AtDjA3 gene using the Arabidopsis knockout line designated j3 and the 35S::AtDjA3 overexpression lines. Loss of AtDjA3 function was associated with small seed production. In fact, j3 mutant seeds showed a reduction of 24% in seed weight compared to Col-0 seeds. Expression analysis showed that the AtDjA3 gene was modulated in response to NaCl, glucose, and abscisic acid (ABA). The j3 line had increased sensitivity to NaCl and glucose treatments in the germination and cotyledon development in comparison to parental Col-0. Furthermore, the j3 mutant line exhibited higher ABA sensitivity in comparison to parental Col-0 and 35S::AtDjA3 overexpression lines. In addition, we examined the expression of ABI3 gene, which is a central regulator in ABA signaling, in j3 mutant and 35S::AtDjA3 overexpression lines. Under 5 μM ABA treatment at 24 h, j3 mutant seedlings displayed higher ABI3 expression, whereas in 35S::AtDjA3 overexpression lines, ABI3 gene expression was repressed. Taken together, these results demonstrate that the AtDjA3 gene is involved in seed development and abiotic stress tolerance. PMID:26941772

  20. Diguanylate Cyclase Null Mutant Reveals That C-Di-GMP Pathway Regulates the Motility and Adherence of the Extremophile Bacterium Acidithiobacillus caldus

    PubMed Central

    Castro, Matías; Deane, Shelly M.; Ruiz, Lina; Rawlings, Douglas E.; Guiliani, Nicolas

    2015-01-01

    An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process. PMID:25689133

  1. Diguanylate cyclase null mutant reveals that C-Di-GMP pathway regulates the motility and adherence of the extremophile bacterium Acidithiobacillus caldus.

    PubMed

    Castro, Matías; Deane, Shelly M; Ruiz, Lina; Rawlings, Douglas E; Guiliani, Nicolas

    2015-01-01

    An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process. PMID:25689133

  2. Role of the Agr-like quorum-sensing system in regulating toxin production by Clostridium perfringens type B strains CN1793 and CN1795.

    PubMed

    Chen, Jianming; McClane, Bruce A

    2012-09-01

    Clostridium perfringens type B causes enteritis and enterotoxemia in domestic animals. By definition, these bacteria must produce alpha toxin (CPA), beta toxin (CPB) and epsilon toxin (ETX) although most type B strains also produce perfringolysin O (PFO) and beta2 toxin (CPB2). A recently identified Agr-like quorum-sensing (QS) system in C. perfringens controls all toxin production by surveyed type A, C, and D strains, but whether this QS is involved in regulating toxin production by type B strains has not been explored. Therefore, the current study introduced agrB null mutations into type B strains CN1795 and CN1793. Both type B agrB null mutants exhibited reduced levels of CPB, PFO, and CPA in their culture supernatants, and this effect was reversible by complementation. The reduced presence of CPB in culture supernatant involved decreased cpb transcription. In contrast, the agrB null mutants of both type B strains retained wild-type production levels of ETX and CPB2. In a Caco-2 cell model of enteritis, culture supernatants of the type B agrB null mutants were less cytotoxic than supernatants of their wild-type parents. However, in an MDCK cell in vitro model for enterotoxemic effects, supernatants from the agrB null mutants or wild-type parents were equally cytotoxic after trypsin activation. Coupling these and previous results, it is now evident that strain-dependent variations exist in Agr-like QS system regulation of C. perfringens toxin production. The cell culture results further support a role for trypsin in determining which toxins contribute to disease involving type B strains. PMID:22689820

  3. Role of the Agr-Like Quorum-Sensing System in Regulating Toxin Production by Clostridium perfringens Type B Strains CN1793 and CN1795

    PubMed Central

    Chen, Jianming

    2012-01-01

    Clostridium perfringens type B causes enteritis and enterotoxemia in domestic animals. By definition, these bacteria must produce alpha toxin (CPA), beta toxin (CPB) and epsilon toxin (ETX) although most type B strains also produce perfringolysin O (PFO) and beta2 toxin (CPB2). A recently identified Agr-like quorum-sensing (QS) system in C. perfringens controls all toxin production by surveyed type A, C, and D strains, but whether this QS is involved in regulating toxin production by type B strains has not been explored. Therefore, the current study introduced agrB null mutations into type B strains CN1795 and CN1793. Both type B agrB null mutants exhibited reduced levels of CPB, PFO, and CPA in their culture supernatants, and this effect was reversible by complementation. The reduced presence of CPB in culture supernatant involved decreased cpb transcription. In contrast, the agrB null mutants of both type B strains retained wild-type production levels of ETX and CPB2. In a Caco-2 cell model of enteritis, culture supernatants of the type B agrB null mutants were less cytotoxic than supernatants of their wild-type parents. However, in an MDCK cell in vitro model for enterotoxemic effects, supernatants from the agrB null mutants or wild-type parents were equally cytotoxic after trypsin activation. Coupling these and previous results, it is now evident that strain-dependent variations exist in Agr-like QS system regulation of C. perfringens toxin production. The cell culture results further support a role for trypsin in determining which toxins contribute to disease involving type B strains. PMID:22689820

  4. A Human Cytomegalovirus gO-Null Mutant Fails To Incorporate gH/gL into the Virion Envelope and Is Unable To Enter Fibroblasts and Epithelial and Endothelial Cells▿

    PubMed Central

    Wille, Paul T.; Knoche, Amber J.; Nelson, Jay A.; Jarvis, Michael A.; Johnson, David C.

    2010-01-01

    Human cytomegalovirus (HCMV) depends upon a five-protein complex, gH/gL/UL128-131, to enter epithelial and endothelial cells. A separate HCMV gH/gL-containing complex, gH/gL/gO, has been described. Our prevailing model is that gH/gL/UL128-131 is required for entry into biologically important epithelial and endothelial cells and that gH/gL/gO is required for infection of fibroblasts. Genes encoding UL128-131 are rapidly mutated during laboratory propagation of HCMV on fibroblasts, apparently related to selective pressure for the fibroblast entry pathway. Arguing against this model in the accompanying paper by B. J. Ryckman et al. (J. Virol., 84:2597-2609, 2010), we describe evidence that clinical HCMV strain TR expresses a gO molecule that acts to promote endoplasmic reticulum (ER) export of gH/gL and that gO is not stably incorporated into the virus envelope. This was different from results involving fibroblast-adapted HCMV strain AD169, which incorporates gO into the virion envelope. Here, we constructed a TR gO-null mutant, TRΔgO, that replicated to low titers, spread poorly among fibroblasts, but produced normal quantities of extracellular virus particles. TRΔgO particles released from fibroblasts failed to infect fibroblasts and epithelial and endothelial cells, but the chemical fusogen polyethylene glycol (PEG) could partially overcome defects in infection. Therefore, TRΔgO is defective for entry into all three cell types. Defects in entry were explained by observations showing that TRΔgO incorporated about 5% of the quantities of gH/gL in extracellular virus particles compared with that in wild-type virions. Although TRΔgO particles could not enter cells, cell-to-cell spread involving epithelial and endothelial cells was increased relative to TR, apparently resulting from increased quantities of gH/gL/UL128-131 in virions. Together, our data suggest that TR gO acts as a chaperone to promote ER export and the incorporation of gH/gL complexes into the HCMV

  5. A human cytomegalovirus gO-null mutant fails to incorporate gH/gL into the virion envelope and is unable to enter fibroblasts and epithelial and endothelial cells.

    PubMed

    Wille, Paul T; Knoche, Amber J; Nelson, Jay A; Jarvis, Michael A; Johnson, David C

    2010-03-01

    Human cytomegalovirus (HCMV) depends upon a five-protein complex, gH/gL/UL128-131, to enter epithelial and endothelial cells. A separate HCMV gH/gL-containing complex, gH/gL/gO, has been described. Our prevailing model is that gH/gL/UL128-131 is required for entry into biologically important epithelial and endothelial cells and that gH/gL/gO is required for infection of fibroblasts. Genes encoding UL128-131 are rapidly mutated during laboratory propagation of HCMV on fibroblasts, apparently related to selective pressure for the fibroblast entry pathway. Arguing against this model in the accompanying paper by B. J. Ryckman et al. (J. Virol., 84:2597-2609, 2010), we describe evidence that clinical HCMV strain TR expresses a gO molecule that acts to promote endoplasmic reticulum (ER) export of gH/gL and that gO is not stably incorporated into the virus envelope. This was different from results involving fibroblast-adapted HCMV strain AD169, which incorporates gO into the virion envelope. Here, we constructed a TR gO-null mutant, TRDeltagO, that replicated to low titers, spread poorly among fibroblasts, but produced normal quantities of extracellular virus particles. TRDeltagO particles released from fibroblasts failed to infect fibroblasts and epithelial and endothelial cells, but the chemical fusogen polyethylene glycol (PEG) could partially overcome defects in infection. Therefore, TRDeltagO is defective for entry into all three cell types. Defects in entry were explained by observations showing that TRDeltagO incorporated about 5% of the quantities of gH/gL in extracellular virus particles compared with that in wild-type virions. Although TRDeltagO particles could not enter cells, cell-to-cell spread involving epithelial and endothelial cells was increased relative to TR, apparently resulting from increased quantities of gH/gL/UL128-131 in virions. Together, our data suggest that TR gO acts as a chaperone to promote ER export and the incorporation of g

  6. lagC-null and gbf-null cells define key steps in the morphogenesis of Dictyostelium mounds.

    PubMed

    Sukumaran, S; Brown, J M; Firtel, R A; McNally, J G

    1998-08-01

    The transition to multicellularity is a key feature of the Dictyostelium life cycle, and two genes, gbf and lagC, are known to play pivotal roles in regulating this developmental switch. lagC-null and gbf-null cells fail to induce cell-type-specific genes ordinarily expressed during multicellular development. The null mutants also share a similar morphological phenotype: mutant cells repeatedly aggregate to form a loose mound, disperse, and reform a mound, rather than proceeding to form a tip. To characterize defects in morphogenesis in these mutants, we examined cell motion in the mutant mounds. In analogy with the failed transition in gene expression, we found that lagC-null and gbf-null mounds failed to make a morphogenetic transition from random to rotational motion normally observed in the parent strain. One reason for this was the inability of the mutant mounds to establish a single, dominant signaling-wave center. This defect of lagC-null or gbf-null cells could be overcome by the addition of adenosine, which alters cAMP signaling, but then even in the presence of apparently normal signaling waves, cell motility was still aberrant. This motility defect, as well as the signaling-wave defect, could be overcome in lagC-null cells by overexpression of GBF, suggesting that lagC is dispensable if GBF protein levels are high enough. This set of morphogenetic defects that we have observed helps define key steps in mound morphogenesis. These include the establishment of a dominant signaling-wave center and the capacity of cells to move directionally within the cell mass in response to guidance cues. PMID:9698452

  7. Under light limiting growth, CpcB lyase null mutants of the Cyanobacterium Synechococcus sp. PCC 7002 are capable of producing pigmented beta phycocyanin but with altered chromophore function.

    PubMed

    Derks, Allen K; Vasiliev, Serguei; Bruce, Doug

    2008-11-11

    Phycobilisomes are the major light-harvesting complexes for cyanobacteria, and phycocyanin is the primary phycobiliprotein of the phycobilisome rod. Phycocyanobilin chromophores are covalently bonded to the phycocyanin beta subunit (CpcB) by specific lyases which have been recently identified in the cyanobacterium Synechococcus sp. PCC 7002. Surprisingly, we found that mutants missing the CpcB lyases were nevertheless capable of producing pigmented phycocyanin when grown under low-light conditions. Absorbance measurements at 10 K revealed the energy states of the beta phycocyanin chromophores to be slightly shifted, and 77 K steady state fluorescence emission spectroscopy showed that excitation energy transfer involving the targeted chromophores was disrupted. This evidence indicates that the position of the phycocyanobilin chromophore within the binding domain of the phycocyanin beta subunit had been modified. We hypothesize that alternate, less specific lyases are able to add chromophores, with varying effectiveness, to the beta binding sites. PMID:18925744

  8. Radiant Temperature Nulling Radiometer

    NASA Technical Reports Server (NTRS)

    Ryan, Robert (Inventor)

    2003-01-01

    A self-calibrating nulling radiometer for non-contact temperature measurement of an object, such as a body of water, employs a black body source as a temperature reference, an optomechanical mechanism, e.g., a chopper, to switch back and forth between measuring the temperature of the black body source and that of a test source, and an infrared detection technique. The radiometer functions by measuring radiance of both the test and the reference black body sources; adjusting the temperature of the reference black body so that its radiance is equivalent to the test source; and, measuring the temperature of the reference black body at this point using a precision contact-type temperature sensor, to determine the radiative temperature of the test source. The radiation from both sources is detected by an infrared detector that converts the detected radiation to an electrical signal that is fed with a chopper reference signal to an error signal generator, such as a synchronous detector, that creates a precision rectified signal that is approximately proportional to the difference between the temperature of the reference black body and that of the test infrared source. This error signal is then used in a feedback loop to adjust the reference black body temperature until it equals that of the test source, at which point the error signal is nulled to zero. The chopper mechanism operates at one or more Hertz allowing minimization of l/f noise. It also provides pure chopping between the black body and the test source and allows continuous measurements.

  9. Designing with null flux coils

    SciTech Connect

    Davey, K.R.

    1997-09-01

    Null flux were suggested by Danby and Powell in the late 1960`s as a useful means for realizing induced lift with little drag. As an array of alternating magnets is translated past a set of null flux coils, the currents induced in these coils act to vertically center the magnets on those coils. At present, one Japanese MAGLEV system company and two American-based companies are employing either null flux or flux eliminating coils in their design for high speed magnetically levitated transportation. The principle question addressed in paper is: what is the proper choice of coil length to magnet length in a null flux system? A generic analysis in the time and frequency domain is laid out with the intent of showing the optimal design specification in terms of coil parameters.

  10. On spinors and null vectors

    NASA Astrophysics Data System (ADS)

    Budinich, Marco

    2014-03-01

    We investigate the relations between spinors and null vectors in Clifford algebra of any dimension with particular emphasis on the conditions that a spinor must satisfy to be simple (also: pure). In particular, we prove: (i) a new property for null vectors: each of them bisects spinor space into two subspaces of equal size; (ii) that simple spinors form one-dimensional subspaces of spinor space; (iii) a necessary and sufficient condition for a spinor to be simple that generalizes a theorem of Cartan and Chevalley which becomes a corollary of this result. We also show how to write down easily the most general spinor with a given associated totally null plane. This paper is dedicated to the memory of my father Paolo Budinich who passed away in November 2013 not before transferring to me his enthusiasm for simple spinors.

  11. NULL convention floating point multiplier.

    PubMed

    Albert, Anitha Juliette; Ramachandran, Seshasayanan

    2015-01-01

    Floating point multiplication is a critical part in high dynamic range and computational intensive digital signal processing applications which require high precision and low power. This paper presents the design of an IEEE 754 single precision floating point multiplier using asynchronous NULL convention logic paradigm. Rounding has not been implemented to suit high precision applications. The novelty of the research is that it is the first ever NULL convention logic multiplier, designed to perform floating point multiplication. The proposed multiplier offers substantial decrease in power consumption when compared with its synchronous version. Performance attributes of the NULL convention logic floating point multiplier, obtained from Xilinx simulation and Cadence, are compared with its equivalent synchronous implementation. PMID:25879069

  12. NULL Convention Floating Point Multiplier

    PubMed Central

    Ramachandran, Seshasayanan

    2015-01-01

    Floating point multiplication is a critical part in high dynamic range and computational intensive digital signal processing applications which require high precision and low power. This paper presents the design of an IEEE 754 single precision floating point multiplier using asynchronous NULL convention logic paradigm. Rounding has not been implemented to suit high precision applications. The novelty of the research is that it is the first ever NULL convention logic multiplier, designed to perform floating point multiplication. The proposed multiplier offers substantial decrease in power consumption when compared with its synchronous version. Performance attributes of the NULL convention logic floating point multiplier, obtained from Xilinx simulation and Cadence, are compared with its equivalent synchronous implementation. PMID:25879069

  13. Fracture characterisation using geoelectric null-arrays

    NASA Astrophysics Data System (ADS)

    Falco, Pierik; Negro, François; Szalai, Sándor; Milnes, Ellen

    2013-06-01

    The term "geoelectric null-array" is used for direct current electrode configurations yielding a potential difference of zero above a homogeneous half-space. This paper presents a comparative study of the behaviour of three null-arrays, midpoint null-array (MAN), Wenner-γ null-array and Schlumberger null-array in response to a fracture, both in profiling and in azimuthal mode. The main objective is to determine which array(s) best localise fractures or best identify their orientation. Forward modelling of the three null-arrays revealed that the Wenner-γ and Schlumberger null-arrays localise vertical fractures the most accurately, whilst the midpoint null-array combined with the Schlumberger null-array allows accurate orientation of a fracture. Numerical analysis then served as a basis to interpret the field results. Field test measurements were carried out above a quarry in Les Breuleux (Switzerland) with the three null-arrays and classical arrays. The results were cross-validated with quarry-wall geological mapping. In real field circumstances, the Wenner-γ null-array proved to be the most efficient and accurate in localising fractures. The orientations of the fractures according to the numerical results were most efficiently determined with the midpoint null-array, whilst the Schlumberger null-array adds accuracy to the results. This study shows that geoelectrical null-arrays are more suitable than classical arrays for the characterisation of fracture geometry.

  14. Modified sympathetic nerve regulation in AKAP5-null mice.

    PubMed

    Han, Chong; Tomita, Hirofumi; Ohba, Takayoshi; Nishizaki, Kimitaka; Ogata, Yoshiki; Matsuzaki, Yasushi; Sawamura, Daisuke; Yanagisawa, Teruyuki; Osanai, Tomohiro; Imaizumi, Tadaatsu; Matsubara, Atsushi; Adachi, Takeshi; Ono, Kyoichi; Okumura, Ken; Murakami, Manabu

    2016-01-22

    Genetic analyses have revealed an important association between A-kinase anchoring proteins (AKAPs) and the intracellular calcium modulating system. AKAP5, also known as AKAP79/150, is an anchoring protein between PKA and voltage-dependent calcium channels, ryanodine receptor-2, phospholamban and other molecules. The aim of the present study was to elucidate the physiological importance of AKAP5 in the creation of cardiac rhythm using AKAP5-null mice. ECG analysis showed a normal sinus rhythm and a decreased responsiveness to isoproterenol in AKAP5-null mice compared with wild-type mice. Analysis of heart rate variability revealed that the R-R interval was unstable in AKAP5-null mutants and that the low-frequency components had decreased, indicating that the tonus of the sympathetic nervous system was affected. Furthermore, the atrium of the AKAP5-null mice showed a decreased positive inotropic response to isoproterenol, indicating the involvement of AKAP5 in a PKA-dependent pathway. Thus, our present study revealed that AKAP5 plays a significant role in the regulation of sympathetic nerve activities. PMID:26713362

  15. Proliferation, differentiation and apoptosis in connexin43-null osteoblasts

    NASA Technical Reports Server (NTRS)

    Furlan, F.; Lecanda, F.; Screen, J.; Civitelli, R.

    2001-01-01

    Osteoblasts are highly coupled by gap junctions formed primarily by connexin43 (Cx43). We have shown that interference with Cx43 expression or function disrupts transcriptional regulation of osteoblast genes, and that deletion of Cx43 in the mouse causes skeletal malformations, delayed mineralization, and osteoblast dysfunction. Here, we studied the mechanisms by which genetic deficiency of Cx43 alters osteoblast development. While cell proliferation rates were similar in osteoblastic cells derived from calvaria of Cx43-null and wild type mice, camptothecin-induced apoptosis was 3-fold higher in mutant compared to wild type osteoblasts. When grown in mineralizing medium, Cx43-null cells were able to produce mineralized matrix but it took one week longer to reach the same mineralization levels as in normal cells. Likewise, expression of alkaline phosphatase activity per cell--a marker of osteoblast differentiation--was maximal only 2 weeks later in Cx43-null relative to wild-type cells. These observations suggest that Cx43 is important for a normal and timely development of the osteoblastic phenotype. Delayed differentiation and increase programmed cell death may explain the skeletal phenotype of Cx43-null mice.

  16. Nulling at the Keck Interferometer

    NASA Technical Reports Server (NTRS)

    Colavita, M. Mark; Serabyn, Gene; Wizinowich, Peter L.; Akeson, Rachel L.

    2006-01-01

    The nulling mode of the Keck Interferometer is being commissioned at the Mauna Kea summit. The nuller combines the two Keck telescope apertures in a split-pupil mode to both cancel the on-axis starlight and to coherently detect the residual signal. The nuller, working at 10 um, is tightly integrated with the other interferometer subsystems including the fringe and angle trackers, the delay lines and laser metrology, and the real-time control system. Since first 10 um light in August 2004, the system integration is proceeding with increasing functionality and performance, leading to demonstration of a 100:1 on-sky null in 2005. That level of performance has now been extended to observations with longer coherent integration times. An overview of the overall system is presented, with emphasis on the observing sequence, phasing system, and differences with respect to the V2 system, along with a presentation of some recent engineering data.

  17. Balloon Exoplanet Nulling Interferometer (BENI)

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Ford, Holland; Petro, Larry; Herman, Jay; Rinehart, Stephen; Carpenter, Kenneth; Marzouk, Joe

    2009-01-01

    We evaluate the feasibility of using a balloon-borne nulling interferometer to detect and characterize exosolar planets and debris disks. The existing instrument consists of a 3-telescope Fizeau imaging interferometer with 3 fast steering mirrors and 3 delay lines operating at 800 Hz for closed-loop control of wavefront errors and fine pointing. A compact visible nulling interferometer is under development which when coupled to the imaging interferometer would in-principle allow deep suppression of starlight. We have conducted atmospheric simulations of the environment above 100,000 feet and believe balloons are a feasible path forward towards detection and characterization of a limited set of exoplanets and their debris disks. Herein we will discuss the BENI instrument, the balloon environment and the feasibility of such as mission.

  18. Null Arguments in German Child Language.

    ERIC Educational Resources Information Center

    Hamann, Cornelia

    1996-01-01

    Investigates the 10% to 20% null subject stage in 3-year-olds in Germany and shows that this stage, though long, is not final. Findings indicate that children in this phase use structures found neither in the state of early null subjects nor in adult German, namely, postverbal referential null subjects. Further study is proposed. (94 references)…

  19. Broken chiral symmetry on a null plane

    SciTech Connect

    Beane, Silas R.

    2013-10-15

    On a null-plane (light-front), all effects of spontaneous chiral symmetry breaking are contained in the three Hamiltonians (dynamical Poincaré generators), while the vacuum state is a chiral invariant. This property is used to give a general proof of Goldstone’s theorem on a null-plane. Focusing on null-plane QCD with N degenerate flavors of light quarks, the chiral-symmetry breaking Hamiltonians are obtained, and the role of vacuum condensates is clarified. In particular, the null-plane Gell-Mann–Oakes–Renner formula is derived, and a general prescription is given for mapping all chiral-symmetry breaking QCD condensates to chiral-symmetry conserving null-plane QCD condensates. The utility of the null-plane description lies in the operator algebra that mixes the null-plane Hamiltonians and the chiral symmetry charges. It is demonstrated that in a certain non-trivial limit, the null-plane operator algebra reduces to the symmetry group SU(2N) of the constituent quark model. -- Highlights: •A proof (the first) of Goldstone’s theorem on a null-plane is given. •The puzzle of chiral-symmetry breaking condensates on a null-plane is solved. •The emergence of spin-flavor symmetries in null-plane QCD is demonstrated.

  20. Increased Oxidative Stress Impairs Adipose Tissue Function in Sphingomyelin Synthase 1 Null Mice

    PubMed Central

    Nishimura, Naotaka; Gotoh, Tomomi; Watanabe, Ken; Ikeda, Kazutaka; Garan, Yohei; Taguchi, Ryo; Node, Koichi; Okazaki, Toshiro; Oike, Yuichi

    2013-01-01

    Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we found that SMS1 null mice showed lipodystrophic phenotype. Mutant mice showed up-regulation of plasma triglyceride concentrations accompanied by reduction of white adipose tissue (WAT) as they aged. Lipoprotein lipase (LPL) activity was severely reduced in mutant mice. In vivo analysis indicated that fatty acid uptake in WAT but not in liver decreased in SMS1 null compared to wild-type mice. In vitro analysis using cultured cell revealed that SMS1 depletion reduced fatty acid uptake. Proteins extracted from WAT of mutant mice were severely modified by oxidative stress, and up-regulation of mRNAs related to apoptosis, redox adjustment, mitochondrial stress response and mitochondrial biogenesis was observed. ATP content of WAT was reduced in SMS1 null mice. Blue native gel analysis indicated that accumulation of mitochondrial respiratory chain complexes was reduced. These results suggest that WAT of SMS1 null mice is severely damaged by oxidative stress and barely functional. Indeed, mutant mice treated with the anti-oxidant N-acetyl cysteine (NAC) showed partial recovery of lipodystrophic phenotypes together with normalized plasma triglyceride concentrations. Altogether, our data suggest that SMS1 is crucial to control oxidative stress in order to maintain WAT function. PMID:23593476

  1. Increased oxidative stress impairs adipose tissue function in sphingomyelin synthase 1 null mice.

    PubMed

    Yano, Masato; Yamamoto, Tadashi; Nishimura, Naotaka; Gotoh, Tomomi; Watanabe, Ken; Ikeda, Kazutaka; Garan, Yohei; Taguchi, Ryo; Node, Koichi; Okazaki, Toshiro; Oike, Yuichi

    2013-01-01

    Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we found that SMS1 null mice showed lipodystrophic phenotype. Mutant mice showed up-regulation of plasma triglyceride concentrations accompanied by reduction of white adipose tissue (WAT) as they aged. Lipoprotein lipase (LPL) activity was severely reduced in mutant mice. In vivo analysis indicated that fatty acid uptake in WAT but not in liver decreased in SMS1 null compared to wild-type mice. In vitro analysis using cultured cell revealed that SMS1 depletion reduced fatty acid uptake. Proteins extracted from WAT of mutant mice were severely modified by oxidative stress, and up-regulation of mRNAs related to apoptosis, redox adjustment, mitochondrial stress response and mitochondrial biogenesis was observed. ATP content of WAT was reduced in SMS1 null mice. Blue native gel analysis indicated that accumulation of mitochondrial respiratory chain complexes was reduced. These results suggest that WAT of SMS1 null mice is severely damaged by oxidative stress and barely functional. Indeed, mutant mice treated with the anti-oxidant N-acetyl cysteine (NAC) showed partial recovery of lipodystrophic phenotypes together with normalized plasma triglyceride concentrations. Altogether, our data suggest that SMS1 is crucial to control oxidative stress in order to maintain WAT function. PMID:23593476

  2. Visible Nulling Coronagraph Testbed Results

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Melnick, Gary; Tolls, Volker; Woodruff, Robert; Vasudevan, Gopal; Rizzo, Maxime; Thompson, Patrick

    2009-01-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a NASA Astrophysics Strategic Mission Concept study and a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC would provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 5-year mission lifetime. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables starlight suppression in broadband light from 480-960 nm. To demonstrate the VNC approach and advance it's technology readiness we have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed.

  3. Parasitic interference in nulling interferometry

    NASA Astrophysics Data System (ADS)

    Matter, A.; Defrère, D.; Danchi, W. C.; Lopez, B.; Absil, O.

    2013-05-01

    Nulling interferometry aims to detect faint objects close to bright stars. Its principle is to produce a destructive interference along the line of sight so that the stellar flux is rejected, while the flux of the off-axis source can be transmitted. In practice, various instrumental perturbations can degrade the nulling performance. Any imperfection in phase, amplitude or polarization produces a spurious flux that leaks to the interferometer output and corrupts the transmitted off-axis flux. One of these instrumental perturbations is the crosstalk phenomenon, which occurs because of multiple parasitic reflections inside transmitting optics, and/or diffraction effects related to beam propagation along finite size optics. It can include a crosstalk of a beam with itself, and a mutual crosstalk between different beams. This can create a parasitic interference pattern, which degrades the intrinsic transmission map - or intensity response - of the interferometer. In this context, we describe how this instrumental effect impairs the performance of a Bracewell interferometer. A simple formalism is developed to derive the corresponding modified intensity response of the interferometer, as a function of the two parameters of interest: the crosstalk level (or contamination rate) and the phase shift between the primary and secondary - parasitic - beams. We then apply our mathematical approach to a few scientific cases, both analytically and using the GENIESIM simulation software, adapted to handle coherent crosstalk. Our results show that a coherent crosstalk level of about 1 per cent implies a 20 per cent drop of the signal-to-noise ratio at most. Careful attention should thus be paid to reduce the crosstalk level inside an interferometric instrument and ensure an instrumental stability that provides the necessary sensitivity through calibration procedures.

  4. Optimal Beam Combiner Design for Nulling Interferometers

    NASA Astrophysics Data System (ADS)

    Guyon, Olivier; Mennesson, Bertrand; Serabyn, Eugene; Martin, Stefan

    2013-08-01

    A scheme to optimally design a beam combiner is discussed for any predetermined fixed geometry nulling interferometer aimed at detection and characterization of exoplanets with multiple telescopes or a single telescope (aperture masking). We show that considerably higher order nulls can be achieved with 1D (one-dimensional) interferometer geometries than possible with 2D (two-dimensional) geometries with the same number of apertures. Any 1D interferometer with N apertures can achieve a 2(N - 1)-order null, while the order of the deepest null for a random 2D aperture geometry interferometer is the order of the Nth term in the Taylor expansion of ei(x2+y2) around x = 0, y = 0 (2nd order null for N = 2,3 4th order null for N = 4,5,6). We also show that an optimal beam combiner for nulling interferometry relies on only 0 or π phase shifts. Examples of nulling interferometer designs are shown to illustrate these findings.

  5. Nulling interferometry: symmetry requirements and experimental results

    NASA Astrophysics Data System (ADS)

    Serabyn, Eugene

    2000-07-01

    This paper provides a derivation from first principles of the stringent symmetry and stability requirements which deep stellar nulling demands, and also includes a brief status report on recent nulling results obtained with the Jet Propulsion Laboratory's fiber-coupled rotational-shearing interferometer. To date, the deepest transient nulls obtained (at red wavelengths) are 2 X 10-6 with a laser diode source, and 1.4 X 10-5 with a single- polarization thermal white-light source filtered to provide an 18% passband. In addition, both the laser and white light nulls have been stabilized to the 10-4 level. This visible wavelength laboratory nuller thus meets essentially all of the performance goals for the planned nulling experiment on board NASA's Space Interferometer Mission, with the sole exception of dual-polarization operation.

  6. Automatic null ellipsometry with an interferometer

    SciTech Connect

    Watkins, Lionel R.

    2009-11-10

    A new approach to automatic null ellipsometry is described in which the analyzer of a traditional polarizer compensator sample analyzer (PCSA) null ellipsometer is replaced with a heterodyne Michelson interferometer. One arm of this interferometer is modified such that it produces a fixed, linearly polarized reference beam, irrespective of the input polarization state. This beam is recombined interferometrically with the measurement beam and spatially separated into its p and s polarizations. The relative phase of the resulting temporal fringes is a linear function of the polarizer azimuthal angle P, and thus this component can be driven to its null position without iteration. Once at null, the azimuthal angle of the reflected, linearly polarized light is trivially determined from the relative amplitude of the fringes. Measurements made with this instrument on a native oxide film on a silicon wafer were in excellent agreement with those made with a traditional PCSA null ellipsometer.

  7. Nulling interferometry without achromatic phase shifters.

    PubMed

    Mieremet, Arjan L; Braat, Joseph J M

    2002-08-01

    In the infrared wavelength region, a typical star is approximately a million times brighter than the planet that surrounds it, which is a major problem when we attempt to detect exoplanets in a direct manner. Nulling interferometry is a technique that one can use to solve this problem by attenuating the stellar light and enhancing that of the planet. Generally, deep nulling is achieved by use of achromatic phase shifters (APSs). Unfortunately, the technology needed to build these APSs is not yet fully developed. We show that deep nulling can also be achieved by using delay lines only. We investigate the nulling depth as a function of the width of the wavelength interval and the number of telescopes. We also show that we can obtain nulling depths of less than 10(-6), which are required for exoplanet detection. Furthermore, we investigate the properties of the transmission map and make a comparison between our system and an APS system. PMID:12153105

  8. Characterization of the treefrog null allele

    SciTech Connect

    Guttman, S.I. . Dept. of Zoology)

    1990-12-01

    As part of the authors intensive year-long baseline ecological study, they characterized the degree of genetic polymorphism and heterozygosity in selected Feed Materials Production Center (FMPC) populations using electrophoretic techniques. These data are being used as an indicator of stress by comparing populations on and off the FMPC site. The current study was initiated to determine whether this GPI null allele is lethal, when homozygous, in spring peepers. Also, a sampling protocol was implemented to determine whether a linear effect occurs relative to the frequency of the null allele offsite and to determine the origination site of the null allele. 18 refs., 2 figs., 4 tabs.

  9. Null-strut calculus. II. Dynamics

    SciTech Connect

    Kheyfets, A.; LaFave, N.J.; Miller, W.A. )

    1990-06-15

    In this paper, we continue from the preceding paper to develop a fully functional Regge calculus geometrodynamic algorithm from the null-strut-calculus construction. The developments discussed include (a) the identification of the Regge calculus analogue of the constraint and evolution equations on the null-strut lattice, (b) a description of the Minkowski solid geometry for the simplicial blocks of the null-strut lattice, (c) a description of the evolution algorithm for the geometrodynamic scheme and an analysis of its consistency, and (d) a presentation of the dynamical degrees of freedom for a simplicial hypersurface and the description of an initial-value prescription. To demonstrate qualitatively this new approach to geometrodynamics, we present the most simple application of null-strut calculus that we know of---the Friedmann cosmology using the three-boundary of a 600-cell simplicial polytope to model the simplicial hypersurface.

  10. Null structure groups in eleven dimensions

    SciTech Connect

    Cariglia, Marco; Mac Conamhna, Oisin A. P.

    2006-02-15

    We classify all the structure groups which arise as subgroups of the isotropy group (Spin(7)xR{sup 8})xR, of a single null Killing spinor in 11 dimensions. We construct the spaces of spinors fixed by these groups. We determine the conditions under which structure subgroups of the maximal null structure group (Spin(7)xR{sup 8})xR may also be embedded in SU(5), and hence the conditions under which a supersymmetric spacetime admits only null, or both timelike and null, Killing spinors. We discuss how this purely algebraic material will facilitate the direct analysis of the Killing spinor equation of 11 dimensional supergravity, and the classification of supersymmetric spacetimes therein.

  11. On the Penrose inequality along null hypersurfaces

    NASA Astrophysics Data System (ADS)

    Mars, Marc; Soria, Alberto

    2016-06-01

    The null Penrose inequality, i.e. the Penrose inequality in terms of the Bondi energy, is studied by introducing a functional on surfaces and studying its properties along a null hypersurface Ω extending to past null infinity. We prove a general Penrose-type inequality which involves the limit at infinity of the Hawking energy along a specific class of geodesic foliations called Geodesic Asymptotically Bondi (GAB), which are shown to always exist. Whenever this foliation approaches large spheres, this inequality becomes the null Penrose inequality and we recover the results of Ludvigsen–Vickers (1983 J. Phys. A: Math. Gen. 16 3349–53) and Bergqvist (1997 Class. Quantum Grav. 14 2577–83). By exploiting further properties of the functional along general geodesic foliations, we introduce an approach to the null Penrose inequality called the Renormalized Area Method and find a set of two conditions which imply the validity of the null Penrose inequality. One of the conditions involves a limit at infinity and the other a restriction on the spacetime curvature along the flow. We investigate their range of applicability in two particular but interesting cases, namely the shear-free and vacuum case, where the null Penrose inequality is known to hold from the results by Sauter (2008 PhD Thesis Zürich ETH), and the case of null shells propagating in the Minkowski spacetime. Finally, a general inequality bounding the area of the quasi-local black hole in terms of an asymptotic quantity intrinsic of Ω is derived.

  12. Phase-only nulling for transmit antenna

    NASA Astrophysics Data System (ADS)

    Hussain, Moayyed A.; Yu, Kai-Bor

    1999-11-01

    This paper describes a technique for transmit antenna nulling for low-cost large sparse phased array radar system. Radar system described includes an array of elemental antennas, each with a transmit/receive (T/R) module. The T/R modules are operated at or near maximum output to achieve maximum CD-to-RF efficiency. A phase controller controls the phase shift, which are imparted by each module to its signal, to form a mainbeam and its associated sidelobes. A perturbation phase generator adds phase shifts computed, to form wide nulls in the sidelobe structure. The nulls are achieved at very minimal loss of gain, in the order of fraction of a dB. The speed of obtaining these nulls in real time allows a rapid steering of these nulls in a hostile environment. The thinned aperture allow designing a light weigh mobile system. In radar context, these nulls may be placed on a source of ground clutter, a set of jammers or a set of undesirable radio sources.

  13. Proof of the quantum null energy condition

    NASA Astrophysics Data System (ADS)

    Bousso, Raphael; Fisher, Zachary; Koeller, Jason; Leichenauer, Stefan; Wall, Aron C.

    2016-01-01

    We prove the quantum null energy condition (QNEC), a lower bound on the stress tensor in terms of the second variation in a null direction of the entropy of a region. The QNEC arose previously as a consequence of the quantum focusing conjecture, a proposal about quantum gravity. The QNEC itself does not involve gravity, so a proof within quantum field theory is possible. Our proof is somewhat nontrivial, suggesting that there may be alternative formulations of quantum field theory that make the QNEC more manifest. Our proof applies to free and super-renormalizable bosonic field theories, and to any points that lie on stationary null surfaces. An example is Minkowski space, where any point p and null vector ka define a null plane N (a Rindler horizon). Given any codimension-2 surface Σ that contains p and lies on N , one can consider the von Neumann entropy Sout of the quantum state restricted to one side of Σ . A second variation Sout'' can be defined by deforming Σ along N , in a small neighborhood of p with area A . The QNEC states that ⟨Tk k(p )⟩≥ℏ/2 π lim A →0 Sout''/A .

  14. Three-dimensional null point reconnection regimes

    SciTech Connect

    Priest, E. R.; Pontin, D. I.

    2009-12-15

    Recent advances in theory and computational experiments have shown the need to refine the previous categorization of magnetic reconnection at three-dimensional null points--points at which the magnetic field vanishes. We propose here a division into three different types, depending on the nature of the flow near the spine and fan of the null. The spine is an isolated field line which approaches the null (or recedes from it), while the fan is a surface of field lines which recede from it (or approach it). So-called torsional spine reconnection occurs when field lines in the vicinity of the fan rotate, with current becoming concentrated along the spine so that nearby field lines undergo rotational slippage. In torsional fan reconnection field lines near the spine rotate and create a current that is concentrated in the fan with a rotational flux mismatch and rotational slippage. In both of these regimes, the spine and fan are perpendicular and there is no flux transfer across spine or fan. The third regime, called spine-fan reconnection, is the most common in practice and combines elements of the previous spine and fan models. In this case, in response to a generic shearing motion, the null point collapses to form a current sheet that is focused at the null itself, in a sheet that locally spans both the spine and fan. In this regime the spine and fan are no longer perpendicular and there is flux transfer across both of them.

  15. Two roads to the null energy condition

    NASA Astrophysics Data System (ADS)

    Parikh, Maulik

    2015-11-01

    The null energy condition has sweeping consequences in general relativity. I argue here that it has been misunderstood as a property exclusively of matter, when in fact it arises only in a theory of both matter and gravity. I then derive an equivalent geometric formulation of the null energy condition from worldsheet string theory, where it arises beautifully as simple Einstein’s equations in two dimensions. But further, I show that this condition also has a thermodynamic origin, following from a local version of the second law of thermodynamics, applied to gravitational entropy. Thus, far from being an incidental property of matter, the validity of the null energy condition hints at the deep dual origins of gravity.

  16. Null surfaces in static space-times

    NASA Astrophysics Data System (ADS)

    Vollick, Dan N.

    2015-07-01

    In this paper I consider surfaces in a space-time with a Killing vector ξ α that is time-like and hypersurface-orthogonal on one side of the surface. The Killing vector may be either time-like or space-like on the other side of the surface. It has been argued that the surface is null if ξ α ξ α → 0 as the surface is approached from the static region. This implies that, in a coordinate system adapted to ξ, surfaces with g tt = 0 are null. In spherically symmetric space-times the condition g rr = 0 instead of g tt = 0 is sometimes used to locate null surfaces. In this paper I examine the arguments that lead to these two different criteria and show that both arguments are incorrect. A surface ξ = const has a normal vector whose norm is proportional to ξ α ξ α . This lead to the conclusion that surfaces with ξ α ξ α = 0 are null. However, the proportionality factor generally diverges when g tt = 0, leading to a different condition for the norm to be null. In static spherically symmetric space-times this condition gives g rr = 0, not g tt = 0. The problem with the condition g rr = 0 is that the coordinate system is singular on the surface. One can either use a nonsingular coordinate system or examine the induced metric on the surface to determine if it is null. By using these approaches it is shown that the correct criteria is g tt = 0. I also examine the condition required for the surface to be nonsingular.

  17. Characterization of the treefrog null allele, 1991

    SciTech Connect

    Guttman, S.I.

    1992-04-01

    Spring peeper (Hyla crucifer) tadpoles collected from the waste storage area during the Biological and Ecological Site Characterization of the Feed Materials Production Center (FEMP) in 1986 and 1987 appeared to be unique. A null (inactive) allele was found at the glucose phosphate isomerase enzyme locus in significant frequencies (approximately 20%) each year; this allele did not appear to occur in the offsite sample collected approximately 15km from the FEMP. Null alleles at this locus have not been reported in other amphibian populations; when they have been found in other organisms they have invariably been lethal in the homozygous condition.

  18. Null-strut calculus. I. Kinematics

    SciTech Connect

    Kheyfets, A.; LaFave, N.J.; Miller, W.A. )

    1990-06-15

    This paper describes the kinematics of null-strut calculus---a 3+1 Regge calculus approach to general relativity. We show how to model the geometry of spacetime with simplicial spacelike three-geometries (TET's) linked to earlier'' and later'' momentumlike lattice surfaces (TET{sup *}) entirely by light rays or null struts.'' These three-layered lattice spacetime geometries are defined and analyzed using combinatorial formulas for the structure of polytopes. The following paper in this series describes how these three-layered spacetime lattices are used to model spacetimes in full conformity with Einstein's theory of gravity.

  19. Null-broadening in a waveguide.

    PubMed

    Kim, J S; Hodgkiss, W S; Kuperman, W A; Song, H C

    2002-07-01

    Null-broadening, introduced in plane wave beamforming, is extended to an ocean waveguide in the context of matched field processing. The method is based on the minimum variance processor with white noise constraint and the distribution of fictitious sources using the theory of waveguide invariants. The proposed method is demonstrated in simulation as well as with data collected during the SWellEx-96 experiment. As another application, it is shown that the width of a null can be controlled in an adaptive time reversal mirror with a source-receive array. PMID:12141344

  20. Polarization nulling interferometry for exoplanet detection.

    PubMed

    Spronck, Julien; Pereira, Silvania F; Braat, Joseph J M

    2006-04-01

    We introduce a new concept of nulling interferometer without any achromatic device, using polarization properties of light. This type of interferometer should enable a high rejection ratio in a theoretically unlimited spectral band. We analyze several consequences of the proposed design, notably, the possibility of fast internal modulation. PMID:19516397

  1. A Philosophical Critique of Null Hypothesis Testing.

    ERIC Educational Resources Information Center

    Orey III, Michael A.; And Others

    1989-01-01

    An attempt is made to clarify the philosophical foundations of the debate over research methodology appropriate for psychology in particular and the utility of null hypothesis testing in general. The article also relates the debate to education and suggests that the debate is far from settled. (IAH)

  2. Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency

    PubMed Central

    King, Dale E.; Silverman, Richard M.; Miedel, Mark T.; Luke, Cliff J.; Perlmutter, David H.; Silverman, Gary A.; Pak, Stephen C.

    2015-01-01

    α1-antitrypsin deficiency (ATD) predisposes patients to both loss-of-function (emphysema) and gain-of-function (liver cirrhosis) phenotypes depending on the type of mutation. Although the Z mutation (ATZ) is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels) or null (<1% normal levels) alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype) induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS), showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of different AT

  3. Current progress on TPFI nulling architectures at Jet Propulsion Laboratory

    NASA Technical Reports Server (NTRS)

    Gappinger, Robert O.; Wallace, J. Kent; Bartos, Randall D.; Macdonald, Daniel R.; Brown, Kenneth A.

    2005-01-01

    Infrared interferometric nulling is a promising technology for exoplanet detection. Nulling research for the Terrestrial Planet Finder Interferometer has been exploring a variety of interferometer architectures at the Jet Propulsion Laboratory (JPL).

  4. Perturbative gauge theory at null infinity

    NASA Astrophysics Data System (ADS)

    Adamo, Tim; Casali, Eduardo

    2015-06-01

    We describe a theory living on the null conformal boundary I of four-dimensional Minkowski space, the states of which include the radiative modes of Yang-Mills theory. The action of a Kac-Moody symmetry algebra on the correlators of these states leads to a Ward identity for asymptotic "large" gauge transformations which is equivalent to the soft gluon theorem. The subleading soft gluon behavior is also obtained from a Ward identity for charges acting as vector fields on the sphere of null generators of I . Correlation functions of the Yang-Mills states are shown to produce the full classical S-matrix of Yang-Mills theory. The model contains additional states arising from nonunitary gravitational degrees of freedom, indicating a relationship with the twistor string of Berkovits and Witten.

  5. Adaptive Nulling for the Terrestrial Planet Finder Interferometer

    NASA Technical Reports Server (NTRS)

    Peters, Robert D.; Lay, Oliver P.; Jeganathan, Muthu; Hirai, Akiko

    2006-01-01

    A description of adaptive nulling for Terrestrial Planet Finder Interferometer (TPFI) is presented. The topics include: 1) Nulling in TPF-I; 2) Why Do Adaptive Nulling; 3) Parallel High-Order Compensator Design; 4) Phase and Amplitude Control; 5) Development Activates; 6) Requirements; 7) Simplified Experimental Setup; 8) Intensity Correction; and 9) Intensity Dispersion Stability. A short summary is also given on adaptive nulling for the TPFI.

  6. Starlight Nulling Technology at the Jet Propulsion Laboratory

    NASA Technical Reports Server (NTRS)

    Martin, Stefan

    2007-01-01

    The current interests in extra-solar planet detection and space-based and ground-based interferometry for astronomical observations has led to the development of a number of nulling instrument designs at the Jet Propulsion Laboratory (JPL) and elsewhere. This paper summarizes briefly JPL's efforts in nulling interferometry to date and consists of illustrations of some key nulling activities. Basic layouts of nulling testbeds are described and key applications discussed.

  7. Optimized Null Model for Protein Structure Networks

    PubMed Central

    Lappe, Michael; Pržulj, Nataša

    2009-01-01

    Much attention has recently been given to the statistical significance of topological features observed in biological networks. Here, we consider residue interaction graphs (RIGs) as network representations of protein structures with residues as nodes and inter-residue interactions as edges. Degree-preserving randomized models have been widely used for this purpose in biomolecular networks. However, such a single summary statistic of a network may not be detailed enough to capture the complex topological characteristics of protein structures and their network counterparts. Here, we investigate a variety of topological properties of RIGs to find a well fitting network null model for them. The RIGs are derived from a structurally diverse protein data set at various distance cut-offs and for different groups of interacting atoms. We compare the network structure of RIGs to several random graph models. We show that 3-dimensional geometric random graphs, that model spatial relationships between objects, provide the best fit to RIGs. We investigate the relationship between the strength of the fit and various protein structural features. We show that the fit depends on protein size, structural class, and thermostability, but not on quaternary structure. We apply our model to the identification of significantly over-represented structural building blocks, i.e., network motifs, in protein structure networks. As expected, choosing geometric graphs as a null model results in the most specific identification of motifs. Our geometric random graph model may facilitate further graph-based studies of protein conformation space and have important implications for protein structure comparison and prediction. The choice of a well-fitting null model is crucial for finding structural motifs that play an important role in protein folding, stability and function. To our knowledge, this is the first study that addresses the challenge of finding an optimized null model for RIGs, by

  8. Null conformal Killing-Yano tensors and Birkhoff theorem

    NASA Astrophysics Data System (ADS)

    Ferrando, Joan Josep; Sáez, Juan Antonio

    2016-04-01

    We study the space-times admitting a null conformal Killing-Yano tensor whose divergence defines a Killing vector. We analyze the similarities and differences with the recently studied non null case (Ferrando and Sáez in Gen Relativ Gravit 47:1911, 2015). The results by Barnes concerning the Birkhoff theorem for the case of null orbits are analyzed and generalized.

  9. Toroidally symmetric plasma vortex at tokamak divertor null point

    NASA Astrophysics Data System (ADS)

    Umansky, M. V.; Ryutov, D. D.

    2016-03-01

    Reduced MHD equations are used for studying toroidally symmetric plasma dynamics near the divertor null point. Numerical solution of these equations exhibits a plasma vortex localized at the null point with the time-evolution defined by interplay of the curvature drive, magnetic restoring force, and dissipation. Convective motion is easier to achieve for a second-order null (snowflake) divertor than for a regular x-point configuration, and the size of the convection zone in a snowflake configuration grows with plasma pressure at the null point. The trends in simulations are consistent with tokamak experiments which indicate the presence of enhanced transport at the null point.

  10. Magnetic Null Points in Kinetic Simulations of Space Plasmas

    NASA Astrophysics Data System (ADS)

    Olshevsky, Vyacheslav; Deca, Jan; Divin, Andrey; Peng, Ivy Bo; Markidis, Stefano; Innocenti, Maria Elena; Cazzola, Emanuele; Lapenta, Giovanni

    2016-03-01

    We present a systematic attempt to study magnetic null points and the associated magnetic energy conversion in kinetic particle-in-cell simulations of various plasma configurations. We address three-dimensional simulations performed with the semi-implicit kinetic electromagnetic code iPic3D in different setups: variations of a Harris current sheet, dipolar and quadrupolar magnetospheres interacting with the solar wind, and a relaxing turbulent configuration with multiple null points. Spiral nulls are more likely created in space plasmas: in all our simulations except lunar magnetic anomaly (LMA) and quadrupolar mini-magnetosphere the number of spiral nulls prevails over the number of radial nulls by a factor of 3-9. We show that often magnetic nulls do not indicate the regions of intensive energy dissipation. Energy dissipation events caused by topological bifurcations at radial nulls are rather rare and short-lived. The so-called X-lines formed by the radial nulls in the Harris current sheet and LMA simulations are rather stable and do not exhibit any energy dissipation. Energy dissipation is more powerful in the vicinity of spiral nulls enclosed by magnetic flux ropes with strong currents at their axes (their cross sections resemble 2D magnetic islands). These null lines reminiscent of Z-pinches efficiently dissipate magnetic energy due to secondary instabilities such as the two-stream or kinking instability, accompanied by changes in magnetic topology. Current enhancements accompanied by spiral nulls may signal magnetic energy conversion sites in the observational data.

  11. System and Method for Null-Lens Wavefront Sensing

    NASA Technical Reports Server (NTRS)

    Hill, Peter C. (Inventor); Thompson, Patrick L. (Inventor); Aronstein, David L. (Inventor); Bolcar, Matthew R. (Inventor); Smith, Jeffrey S. (Inventor)

    2015-01-01

    A method of measuring aberrations in a null-lens including assembly and alignment aberrations. The null-lens may be used for measuring aberrations in an aspheric optic with the null-lens. Light propagates from the aspheric optic location through the null-lens, while sweeping a detector through the null-lens focal plane. Image data being is collected at locations about said focal plane. Light is simulated propagating to the collection locations for each collected image. Null-lens aberrations may extracted, e.g., applying image-based wavefront-sensing to collected images and simulation results. The null-lens aberrations improve accuracy in measuring aspheric optic aberrations.

  12. Characterization of a Replication-Incompetent Pseudorabies Virus Mutant Lacking the Sole Immediate Early Gene IE180

    PubMed Central

    Wu, Brendan W.

    2014-01-01

    ABSTRACT The alphaherpesvirus pseudorabies virus (PRV) encodes a single immediate early gene called IE180. The IE180 protein is a potent transcriptional activator of viral genes involved in DNA replication and RNA transcription. A PRV mutant with both copies of IE180 deleted was constructed 20 years ago (S. Yamada and M. Shimizu, Virology 199:366–375, 1994, doi:10.1006/viro.1994.1134), but propagation of the mutant depended on complementing cell lines that expressed the toxic IE180 protein constitutively. Recently, Oyibo et al. constructed a novel set of PRV IE180 mutants and a stable cell line with inducible IE180 expression (H. Oyibo, P. Znamenskiy, H. V. Oviedo, L. W. Enquist, A. Zador, Front. Neuroanat. 8:86, 2014, doi:10.3389/fnana.2014.00086), which we characterized further here. These mutants failed to replicate new viral genomes, synthesize immediate early, early, or late viral proteins, and assemble infectious virions. The PRV IE180-null mutant did not form plaques in epithelial cell monolayers and could not spread from primary infected neurons to second-order neurons in culture. PRV IE180-null mutants lacked the property of superinfection exclusion. When PRV IE180-null mutants infected cells first, subsequent superinfecting viruses were not blocked in cell entry and formed replication compartments in epithelial cells, fibroblasts, and neurons. Cells infected with PRV IE180-null mutants survived as long as uninfected cells in culture while expressing a fluorescent reporter gene. Transcomplementation with IE180 in epithelial cells restored all mutant phenotypes to wild type. The conditional expression of PRV IE180 protein enables the propagation of replication-incompetent PRV IE180-null mutants and will facilitate construction of long-term single-cell-infecting PRV mutants for precise neural circuit tracing and high-capacity gene delivery vectors. PMID:25389174

  13. A mutant of the Arabidopsis thaliana Toc159 gene accumulates reduced levels of linolenic acid and monogalactosyldiacylglycerol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have shown that a null mutant of Arabidopsis that lacks Toc159 receptor is impaired in chloroplast biogenesis and incapable of importing photosynthetic proteins. The mutant is referred to as plastid protein import 2 or ppi2, and has an albino phenotype. In this study, we measured ...

  14. Displacing Unpredictable Nulls in Antenna Radiation Patterns

    NASA Technical Reports Server (NTRS)

    Lux, James; Schaefer, Mark

    2005-01-01

    A method of maintaining radio communication despite the emergence of unpredictable fades and nulls in the radiation pattern of an antenna has been proposed. The method was originally intended to be applied in the design and operation of a radio antenna aboard a robotic exploratory vehicle on a remote planet during communication with a spacecraft in orbit around the planet. The method could also be applied in similar terrestrial situations for example, radio communication between two ground vehicles or between a ground vehicle and an aircraft or spacecraft. The method is conceptually simple, is readily adaptable to diverse situations, and can be implemented without adding greatly to the weight, cost, power demand, or complexity of a system to which it may be applied. The unpredictable fades and nulls in an antenna radiation pattern arise because of electromagnetic interactions between the antenna and other objects within the near field of the antenna (basically, objects within a distance of a few wavelengths). These objects can include general vehicle components, masts, robotic arms, other antennas, the ground, and nearby terrain features. Figure 1 presents representative plots of signal strength versus time during a typical pass of a spacecraft or aircraft through the far field of such an antenna, showing typical nulls and fades caused by nearby objects. The traditional approach to ensuring reliability of communication in the presence of deep fades calls for increasing the effective transmitter power and/or reducing the receiver noise figure at the affected ground vehicle, possibly in combination with appropriate redesign of the equipment at the spacecraft or aircraft end of the communication link. These solutions can be expensive and/or risky and, depending on the application, can add significantly to weight, cost, and power demand. The proposed method entails none of these disadvantages.

  15. Null generation using discs on a reflector

    NASA Astrophysics Data System (ADS)

    Rudisill, M. D.

    1984-12-01

    It has been shown possible experimentally to produce nulls in the pattern of a prime focus reflector antenna using discs mounted on the dish. A model of this antenna system is developed to evaluate optimal configurations and ideal performance. Aperture integration is the method of analysis used. Discs' effects are modeled as a phase shift on the aperture. No secondary effects, such as diffraction, are considered. Based on the model developed, guidelines are presented for antenna design. A computer code was written to implement the model and a prediction of antenna the system's performance is presented.

  16. Null Energy Condition in Dynamic Wormholes

    SciTech Connect

    Hochberg, D.; Visser, M.

    1998-07-01

    We extend previous proofs that violations of the null energy condition are a generic and universal feature of traversable wormholes to completely nonsymmetric time-dependent wormholes. We show that the analysis can be phrased purely in terms of local geometry at and near the wormhole throat, and we do not have to make any technical assumptions about asymptotic flatness or other global properties. A key aspect of the analysis is the demonstration that time-dependent wormholes have {ital two} throats, one for each direction through the wormhole, and that the two throats coalesce only for the case of a static wormhole. {copyright} {ital 1998} {ital The American Physical Society}

  17. Polyhedra in spacetime from null vectors

    NASA Astrophysics Data System (ADS)

    Neiman, Yasha

    2014-01-01

    We consider convex spacelike polyhedra oriented in the Minkowski space. These are the classical analogues of spinfoam intertwiners. We point out a parametrization of these shapes using null face normals, with no constraints or redundancies. Our construction is dimension-independent. In 3+1d, it provides the spacetime picture behind a well-known property of the loop quantum gravity intertwiner space in spinor form, namely that the closure constraint is always satisfied after some SL(2, C) rotation. As a simple application of our variables, we incorporate them in a 4-simplex action that reproduces the large-spin behavior of the Barrett-Crane vertex amplitude.

  18. Precise null deletion mutations of the mycothiol synthesis genes reveal their role in isoniazid and ethionamide resistance in Mycobacterium smegmatis.

    PubMed

    Xu, Xia; Vilchèze, Catherine; Av-Gay, Yossef; Gómez-Velasco, Anaximandro; Jacobs, William R

    2011-07-01

    Mycothiol (MSH; AcCys-GlcN-Ins) is the glutathione analogue for mycobacteria. Mutations in MSH biosynthetic genes have been associated with resistance to isoniazid (INH) and ethionamide (ETH) in mycobacteria, but rigorous genetic studies are lacking, and those that have been conducted have yielded different results. In this study, we constructed independent null deletion mutants for all four genes involved in the MSH biosynthesis pathway (mshA, mshB, mshC, and mshD) in Mycobacterium smegmatis and made complementing constructs in integrating plasmids. The resulting set of strains was analyzed for levels of MSH, INH resistance, and ETH resistance. The mshA and mshC single deletion mutants were devoid of MSH production and resistant to INH, whereas the mshB deletion mutant produced decreased levels of MSH yet was sensitive to INH, suggesting that MSH biosynthesis is essential for INH susceptibility in M. smegmatis. Further evidence supporting this conclusion was generated by deleting the gene encoding the MSH S-conjugate amidase (mca) from the ΔmshB null mutant. This double mutant, ΔmshB Δmca, completely abolished MSH production and was resistant to INH. The mshA, mshC, and mshB single deletion mutants were also resistant to ETH, indicating that ETH resistance is modulated by the level of MSH in M. smegmatis. Surprisingly, the mshD deletion mutant lacked MSH production but was sensitive to both INH and ETH. The drug sensitivity was likely mediated by the compensated synthesis of N-formyl-Cys-GlcN-Ins, previously demonstrated to substitute for MSH in an mshD mutant of M. smegmatis. We conclude that MSH or N-formyl-Cys-GlcN-Ins is required for susceptibility to INH or ETH in M. smegmatis. PMID:21502624

  19. A Nulling Coronagraph for TPF-C

    NASA Technical Reports Server (NTRS)

    Shao, Michael; Levine, Bruce Martin; Wallace, James Kent; Orton, Glenn S.; Schmidtlin, Edouard; Lane, Benjamin F.; Seager, Sara; Tolls, Volker; Lyon, Richard G.; Samuele, Rocco; Tenerelli, Domenick J.; Woodruff, Robert; Ge, Jian

    2006-01-01

    The nulling coronagraph is one of 5 instrument concepts selected by NASA for study for potential use in the TPF-C mission. This concept for extreme starlight suppression has two major components, a nulling interferometer to suppress the starlight to 10(sup -10) per airy spot within 2 (lamda)/D of the star, and a calibration interferometer to measure the residual scattered starlight. The ability to work at 2 (lamda)/D dramatically improves the science throughput of a space based coronagraph like TPF-C. The calibration interferometer is an equally important part of the starlight suppression system. It measures the measures the wavefront of the scattered starlight with very high SNR, to 0.05nm in less than 5 minutes on a 5mag star. In addition, the post coronagraph wavefront sensor will be used to measure the residual scattered light after the coronagraph and subtract it in post processing to 12x10(sup -11) to enable detection of an Earthlike planet with a SNR of 510.

  20. Off-Axis Nulling Transfer Function Measurement: A First Assessment

    NASA Technical Reports Server (NTRS)

    Vedova, G. Dalla; Menut, J.-L.; Millour, F.; Petrov, R.; Cassaing, F.; Danchi, W. C.; Jacquinod, S.; Lhome, E.; Lopez, B.; Lozi, J.; Marcotto, A.; Parisot, J.; Reess, J.-M.

    2013-01-01

    We want to study a polychromatic inverse problem method with nulling interferometers to obtain information on the structures of the exozodiacal light. For this reason, during the first semester of 2013, thanks to the support of the consortium PERSEE, we launched a campaign of laboratory measurements with the nulling interferometric test bench PERSEE, operating with 9 spectral channels between J and K bands. Our objective is to characterise the transfer function, i.e. the map of the null as a function of wavelength for an off-axis source, the null being optimised on the central source or on the source photocenter. We were able to reach on-axis null depths better than 10(exp -4). This work is part of a broader project aiming at creating a simulator of a nulling interferometer in which typical noises of a real instrument are introduced. We present here our first results.

  1. Decreased sensory responses in osteocalcin null mutant mice imply neuropeptide function.

    PubMed

    Patterson-Buckendahl, Patricia; Sowinska, Agnieszka; Yee, Stephanie; Patel, Dhara; Pagkalinawan, Stephen; Shahid, Muhammad; Shah, Ankit; Franz, Christopher; Benjamin, Daniel E; Pohorecky, Larissa A

    2012-07-01

    Osteocalcin, the most abundant member of the family of extracellular mineral binding gamma-carboxyglutamic acid proteins is synthesized primarily by osteoblasts. Its affinity for calcium ions is believed to limit bone mineralization. Several of the numerous hormones that regulate synthesis of osteocalcin, including glucocorticoids and parathyroid hormone, are also affected by stressful stimuli that require energy for an appropriate response. Based on our observations of OC responding to stressful sensory stimuli, the expression of OC in mouse and rat sensory ganglia was confirmed. It was thus hypothesized that the behavioral responses of the OC knockout mouse to stressful sensory stimuli would be abnormal. To test this hypothesis, behaviors related to sensory aspects of the stress response were quantified in nine groups of mice, aged 4-14 months, comparing knockout with their wild-type counterparts in six distinctly different behavioral tests. Resulting data indicated the following statistically significant differences: open field grooming frequency following saline injection, wild-type > knockout; paw stimulation with Von Frey fibers, knockout < wild-type; balance beam, knockout mobility < WT; thermal sensitivity to heat (tail flick), knockout < wild-type; and cold, knockout < wild-type. Insignificant differences in hanging wire test indicate that these responses are unrelated to reduced muscle strength. Each of these disparate environmental stimuli provided data indicating alterations of responses in knockout mice that suggest participation of osteocalcin in transmission of information about those sensory stimuli. PMID:22350212

  2. Findings from a Three Year Survey of Coronal Null Points

    NASA Astrophysics Data System (ADS)

    Freed, Michael; Longcope, Dana; McKenzie, David Eugene

    2014-06-01

    We report the findings from a comprehensive coronal magnetic null point survey created by Potential Field Source Surface (PFSS) modeling & Solar Dynamic Observatory/Atmospheric Imaging Assembly (SDO/AIA) observations. Locations of magnetic null points in the corona were predicted from the PFSS model from Carrington Rotation 2098 to 2139 and manually compared to contrast enhanced SDO/AIA images in 171 angstroms. Statistical results will be presented that illustrate the characteristics associated with the observed and predicted null points. These characteristics include the radial & latitudinal distribution; eigenvalues associated with null point structure; and the effect spine orientation has on observability.

  3. A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors

    SciTech Connect

    Brune, W.; Saul, M.; Becker, C.M.

    1996-05-01

    Dominant missense mutations in the human glycine receptor (GlyR) {alpha}1 subunit gene (GLRA1) give rise to hereditary hyperekplexia. These mutations impair agonist affinities and change conductance states of expressed mutant channels, resulting in a partial loss of function. In a recessive case of hyperekplexia, we found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child is homozygous for this GLRA1{sup null} allele consistent with a complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brain-stem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1{sup spd-ot}), the loss of the GlyR {alpha}1 subunit is effectively compensated in man. 38 refs.

  4. A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors.

    PubMed Central

    Brune, W.; Weber, R. G.; Saul, B.; von Knebel Doeberitz, M.; Grond-Ginsbach, C.; Kellerman, K.; Meinck, H. M.; Becker, C. M.

    1996-01-01

    Dominant missense mutations in the human glycine receptor (GlyR) alpha 1 subunit gene (GLRA1) give rise to hereditary hyperekplexia. These mutations impair agonist affinities and change conductance states of expressed mutant channels, resulting in a partial loss of function. In a recessive case of hyperekplexia, we found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child is homozygous for this GLRA1(null) allele consistent with a complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brain-stem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1 spd-ot), the loss of the GlyR alpha 1 subunit is effectively compensated in man. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8651283

  5. Nulling Infrared Radiometer for Measuring Temperature

    NASA Technical Reports Server (NTRS)

    Ryan, Robert

    2003-01-01

    A nulling, self-calibrating infrared radiometer is being developed for use in noncontact measurement of temperature in any of a variety of industrial and scientific applications. This instrument is expected to be especially well-suited to measurement of ambient or near-ambient temperature and, even more specifically, for measuring the surface temperature of a natural body of water. Although this radiometer would utilize the long-wavelength infrared (LWIR) portion of the spectrum (wavelengths of 8 to 12 m), its basic principle of operation could also be applied to other spectral bands (corresponding to other temperature ranges) in which the atmosphere is transparent and in which design requirements for sensitivity and temperature-measurement accuracy could be satisfied.

  6. String spectra near some null cosmological singularities

    SciTech Connect

    Madhu, Kallingalthodi; Narayan, K.

    2009-06-15

    We construct cosmological spacetimes with null Kasner-like singularities as purely gravitational solutions with no other background fields turned on. These can be recast as anisotropic plane-wave spacetimes by coordinate transformations. We analyze string quantization to find the spectrum of string modes in these backgrounds. The classical string modes can be solved for exactly in these time-dependent backgrounds, which enables a detailed study of the near-singularity string spectrum, (time-dependent) oscillator masses, and wave functions. We find that for low-lying string modes (finite oscillation number), the classical near-singularity string mode functions are nondivergent for various families of singularities. Furthermore, for any infinitesimal regularization of the vicinity of the singularity, we find a tower of string modes of ultrahigh oscillation number which propagate essentially freely in the background. The resulting picture suggests that string interactions are non-negligible near the singularity.

  7. Exoplanet detection using a nulling interferometer.

    PubMed

    Cagigal, M; Canales, V

    2001-07-01

    The detection of extra solar planets is a topic of growing interest, which stretches current technology and knowledge to their limits. Indirect measurement confirms the existence of a considerable number. However, direct imaging is the only way to obtain information about the nature of these planets and to detect Earth-like planets, which could support life. The main problem for direct imaging is that planets are associated with a much brighter source of light. Here, we propose the use of the nulling interferometer along with a photon counting technique called Dark Speckle. Using a simple model the behavior of the technique is predicted. The signal-to-noise ratio estimated confirms that it is a promising way to detect faint objects. PMID:19421271

  8. Technology Advancement of the Visible Nulling Coronagraph

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Thompson, Patrick; Bolcar, Matt; Madison, Timothy; Woodruff, Robert; Noecker, Charley; Kendrick, Steve

    2010-01-01

    The critical high contrast imaging technology for the Extrasolar Planetary Imaging Coronagraph (EPIC) mission concept is the visible nulling coronagraph (VNC). EPIC would be capable of imaging jovian planets, dust/debris disks, and potentially super-Earths and contribute to answering how bright the debris disks are for candidate stars. The contrast requirement for EPIC is 10(exp 9) contrast at 125 milli-arseconds inner working angle. To advance the VNC technology NASA/Goddard Space Flight Center, in collaboration with Lockheed-Martin, previously developed a vacuum VNC testbed, and achieved narrowband and broadband suppression of the core of the Airy disk. Recently our group was awarded a NASA Technology Development for Exoplanet Missions to achieve two milestones: (i) 10(exp 8) contrast in narrowband light, and, (ii) 10(ecp 9) contrast in broader band light; one milestone per year, and both at 2 Lambda/D inner working angle. These will be achieved with our 2nd generation testbed known as the visible nulling testbed (VNT). It contains a MEMS based hex-packed segmented deformable mirror known as the multiple mirror array (MMA) and coherent fiber bundle, i.e. a spatial filter array (SFA). The MMA is in one interferometric arm and works to set the wavefront differences between the arms to zero. Each of the MMA segments is optically mapped to a single mode fiber of the SFA, and the SFA passively cleans the sub-aperture wavefront error leaving only piston, tip and tilt error to be controlled. The piston degree of freedom on each segment is used to correct the wavefront errors, while the tip/tilt is used to simultaneously correct the amplitude errors. Thus the VNT controls both amplitude and wavefront errors with a single MMA in closed-loop in a vacuum tank at approx.20 Hz. Herein we will discuss our ongoing progress with the VNT.

  9. Glomerular injury is exacerbated in diabetic integrin alpha1-null mice.

    PubMed

    Zent, R; Yan, X; Su, Y; Hudson, B G; Borza, D-B; Moeckel, G W; Qi, Z; Sado, Y; Breyer, M D; Voziyan, P; Pozzi, A

    2006-08-01

    Excessive glomerular collagen IV and reactive oxygen species (ROS) production are key factors in the development of diabetic nephropathy. Integrin alpha1beta1, the major collagen IV receptor, dowregulates collagen IV and ROS production, suggesting this integrin might determine the severity of diabetic nephropathy. To test this possibility, wild-type and integrin alpha1-null mice were rendered diabetic with streptozotocin (STZ) (100 mg/kg single intraperitoneal injection), after which glomerular filtration rate (GFR), glomerular collagen deposition, and glomerular basement membrane (GBM) thickening were evaluated. In addition, ROS and collagen IV production by mesangial cells as well as their proliferation was measured in vitro. Diabetic alpha1-null mice developed worse renal disease than diabetic wild-type mice. A significant increase in GFR was evident in the alpha1-null mice at 6 weeks after the STZ injection; it started to decrease by week 24 and reached levels of non-diabetic mice by week 36. In contrast, GFR only increased in wild-type mice at week 12 and its elevation persisted throughout the study. Diabetic mutant mice also showed increased glomerular deposition of collagen IV and GBM thickening compared to diabetic wild-type mice. Primary alpha1-null mesangial cells exposed to high glucose produced more ROS than wild-type cells, which led to decreased proliferation and increased collagen IV synthesis, thus mimicking the in vivo finding. In conclusion, this study suggests that lack of integrin alpha1beta1 exacerbates the glomerular injury in a mouse model of diabetes by modulating GFR, ROS production, cell proliferation, and collagen deposition. PMID:16775606

  10. Proof of the averaged null energy condition in a classical curved spacetime using a null-projected quantum inequality

    NASA Astrophysics Data System (ADS)

    Kontou, Eleni-Alexandra; Olum, Ken D.

    2015-12-01

    Quantum inequalities are constraints on how negative the weighted average of the renormalized stress-energy tensor of a quantum field can be. A null-projected quantum inequality can be used to prove the averaged null energy condition, which would then rule out exotic phenomena such as wormholes and time machines. In this work we derive such an inequality for a massless minimally coupled scalar field, working to first order of the Riemann tensor and its derivatives. We then use this inequality to prove the averaged null energy condition on achronal geodesics in a curved background that obeys the null convergence condition.

  11. Tightness of stability bounds by null space property

    NASA Astrophysics Data System (ADS)

    Chen, Xuemei; Wang, Rongrong

    2015-08-01

    The null space property (NSP) and the restricted isometry property (RIP) are two properties which have received considerable attention in the compressed sensing literature. It is known that the null space property guarantees a less than ideal stability result. In this paper, we show that this bound is actually tight by specific construction, which implies a fundamental difference between NSP and RIP.

  12. Visual and Plastic Arts in Teaching Literacy: Null Curricula?

    ERIC Educational Resources Information Center

    Wakeland, Robin Gay

    2010-01-01

    Visual and plastic arts in contemporary literacy instruction equal null curricula. Studies show that painting and sculpture facilitate teaching reading and writing (literacy), yet such pedagogy has not been formally adopted into USA curriculum. An example of null curriculum can be found in late 19th - early 20th century education the USA…

  13. Survey of Coronal Null Points with SDO/AIA & WSO

    NASA Astrophysics Data System (ADS)

    Freed, Michael; McKenzie, D. E.; Longcope, D.

    2013-07-01

    Magnetic fields in the corona can be approximated by using PFSS (Potential Field Source Surface) model in conjunction with magnetogram measurements of the photosphere. This approach is incorporated here to find locations of magnetic null points in the solar corona. Observations from WSO (Wilcox Solar Observatory) provide the necessary harmonic coefficients for a PFSS model. We located all magnetic null points in the PFSS model going back to Carrington Rotation 2098. The time and location where they cross the West limb is compared to high resolution observations made by SDO/AIA. Variations in predicted and observed null point locations, and estimates of the duration of each null, will be examined. This work will provide a catalog of coronal nulls observed by SDO that can be examined further for interesting dynamical behavior or variations in neighboring plasma.

  14. The Visible Nulling Coronagraph--Architecture Definition and Technology Development

    NASA Technical Reports Server (NTRS)

    Shao, Michael; Levine, B. Martin; Wallace, J. Kent; Liu, Duncan T.; Schmidtlin, Edouard; Serabyn, Eugene; Mennesson, Bertrand; Green, Joseph J.; Aguayo, Francisco; Fregoso, S. Felipe; Lane, Benjamin F.; Samuele, Rocco; Tuttle, Carl

    2005-01-01

    This paper describes the advantages of visible direct detection and spectroscopy of Earth-like extrasolar planets using a nulling coronagraph instrument behind a moderately sized single aperture space telescope. Our concept synthesizes a nulling interferometer by shearing the telescope pupil, with the resultant producing a deep null. We describe nulling configurations that also include methods to mitigate stellar leakage, such as spatial filtering by a coherent array of single mode fibers, and post-starlight suppression wavefront sensing and control. With diffraction limited telescope optics and similar quality components in the optical train (lambda/20), suppression of the starlight to 1e-10 is readily achievable. We describe key features of the architecture and analysis, present latest results of laboratory measurements demonstrating achievable null depth and component development, and discuss future key technical milestones.

  15. Null hypersurfaces in generalized Robertson-Walker spacetimes

    NASA Astrophysics Data System (ADS)

    Navarro, Matias; Palmas, Oscar; Solis, Didier A.

    2016-08-01

    We study the geometry of null hypersurfaces M in generalized Robertson-Walker spacetimes. First we characterize such null hypersurfaces as graphs of generalized eikonal functions over the fiber and use this characterization to show that such hypersurfaces are parallel if and only if their fibers are also parallel. We further use this technique to construct several examples of null hypersurfaces in both de Sitter and anti de Sitter spaces. Then we characterize all the totally umbilical null hypersurfaces M in a Lorentzian space form (viewed as a quadric in a semi-Euclidean ambient space) as intersections of the space form with a hyperplane. Finally we study the totally umbilical spacelike hypersurfaces of null hypersurfaces in space forms and characterize them as planar sections of M.

  16. Wormholes minimally violating the null energy condition

    SciTech Connect

    Bouhmadi-López, Mariam; Lobo, Francisco S N; Martín-Moruno, Prado E-mail: fslobo@fc.ul.pt

    2014-11-01

    We consider novel wormhole solutions supported by a matter content that minimally violates the null energy condition. More specifically, we consider an equation of state in which the sum of the energy density and radial pressure is proportional to a constant with a value smaller than that of the inverse area characterising the system, i.e., the area of the wormhole mouth. This approach is motivated by a recently proposed cosmological event, denoted {sup t}he little sibling of the big rip{sup ,} where the Hubble rate and the scale factor blow up but the cosmic derivative of the Hubble rate does not [1]. By using the cut-and-paste approach, we match interior spherically symmetric wormhole solutions to an exterior Schwarzschild geometry, and analyse the stability of the thin-shell to linearized spherically symmetric perturbations around static solutions, by choosing suitable properties for the exotic material residing on the junction interface radius. Furthermore, we also consider an inhomogeneous generalization of the equation of state considered above and analyse the respective stability regions. In particular, we obtain a specific wormhole solution with an asymptotic behaviour corresponding to a global monopole.

  17. The curious case of null warped space

    NASA Astrophysics Data System (ADS)

    Anninos, Dionysios; Compère, Geoffrey; de Buyl, Sophie; Detournay, Stéphane; Guica, Monica

    2010-11-01

    We initiate a comprehensive study of a set of solutions of topologically massive gravity known as null warped anti-de Sitter spacetimes. These are pp-wave extensions of three-dimensional anti-de Sitter space. We first perform a careful analysis of the linearized stability of black holes in these spacetimes. We find two qualitatively different types of solutions to the linearized equations of motion: the first set has an exponential time dependence, the second — a polynomial time dependence. The solutions polynomial in time induce severe pathologies and moreover survive at the non-linear level. In order to make sense of these geometries, it is thus crucial to impose appropriate boundary conditions. We argue that there exists a consistent set of boundary conditions that allows us to reject the above pathological modes from the physical spectrum. The asymptotic symmetry group associated to these boundary conditions consists of a centrally-extended Virasoro algebra. Using this central charge we can account for the entropy of the black holes via Cardy's formula. Finally, we note that the black hole spectrum is chiral and prove a Birkoff theorem showing that there are no other stationary axisymmetric black holes with the specified asymptotics. We extend most of the analysis to a larger family of pp-wave black holes which are related to Schrödinger spacetimes with critical exponent z.

  18. A Null Model for Pearson Coexpression Networks

    PubMed Central

    Gobbi, Andrea; Jurman, Giuseppe

    2015-01-01

    Gene coexpression networks inferred by correlation from high-throughput profiling such as microarray data represent simple but effective structures for discovering and interpreting linear gene relationships. In recent years, several approaches have been proposed to tackle the problem of deciding when the resulting correlation values are statistically significant. This is most crucial when the number of samples is small, yielding a non-negligible chance that even high correlation values are due to random effects. Here we introduce a novel hard thresholding solution based on the assumption that a coexpression network inferred by randomly generated data is expected to be empty. The threshold is theoretically derived by means of an analytic approach and, as a deterministic independent null model, it depends only on the dimensions of the starting data matrix, with assumptions on the skewness of the data distribution compatible with the structure of gene expression levels data. We show, on synthetic and array datasets, that the proposed threshold is effective in eliminating all false positive links, with an offsetting cost in terms of false negative detected edges. PMID:26030917

  19. Null fields in the outer Jovian magnetosphere: ULYSSES observations

    NASA Astrophysics Data System (ADS)

    Haynes, P. L.; Balogh, A.; Dougherty, M. K.; Southwood, D. J.; Fazakerley, A.

    1994-03-01

    This paper reports on a magnetic field phenomenon, hereafter referred to as null fields, which were discovered during the inbound pass of the recent flyby of Jupiter by the Ulysses spacecraft. These null fields which were observed in the outer dayside magnetosphere are characterised by brief but sharp decreases of the field magnitude to values less than 1 nT. The nulls are distinguished from the current sheet signatures characteristic of the middle magnetosphere by the fact that the field does not reverse across the event. A field configuration is suggested that accounts for the observed features of the events.

  20. Molecular basis for the CAT-2 null phenotype in maize

    SciTech Connect

    Bethards, L.A.; Scandalios, J.G.

    1988-01-01

    Previous reports have described several maize lines whose developmental patterns of catalase gene expression vary from the typical maize line, W64A. Among these variants are the lines A16 and A338, both found to be null for the CAT-2 protein. Identification of a third CAT-2 null line, designated A340, is described. RNA blots and S1 nuclease protection analysis, using (/sup 32/P)-labeled dCTP, indicate that all three CAT-2 null lines produce a similarly shortened Cat2 transcript. The molecular basis for this aberrant Cat2 transcript is discussed.

  1. A boundary term for the gravitational action with null boundaries

    NASA Astrophysics Data System (ADS)

    Parattu, Krishnamohan; Chakraborty, Sumanta; Majhi, Bibhas Ranjan; Padmanabhan, T.

    2016-07-01

    Constructing a well-posed variational principle is a non-trivial issue in general relativity. For spacelike and timelike boundaries, one knows that the addition of the Gibbons-Hawking-York (GHY) counter-term will make the variational principle well-defined. This result, however, does not directly generalize to null boundaries on which the 3-metric becomes degenerate. In this work, we address the following question: What is the counter-term that may be added on a null boundary to make the variational principle well-defined? We propose the boundary integral of 2 √{-g} ( Θ +κ ) as an appropriate counter-term for a null boundary. We also conduct a preliminary analysis of the variations of the metric on the null boundary and conclude that isolating the degrees of freedom that may be fixed for a well-posed variational principle requires a deeper investigation.

  2. A null-steering viewpoint of interferometric SAR

    SciTech Connect

    BICKEL,DOUGLAS L.

    2000-05-02

    Interferometric synthetic aperture radar (IFSAR) extends the two-dimensional imaging capability of traditional synthetic aperture radar to three-dimensions by using an aperture in the elevation plane to estimate the 3-D structure of the target. The operation of this additional aperture can be viewed from a null-steering point of view, rather than the traditional phase determination point of view. Knowing that IFSAR can be viewed from the null-steering perspective allows one to take advantage of the mathematical foundation developed for null-steering arrays. In addition, in some problems of interest in IFSAR the null-steering perspective provides better intuition and suggests alternative solutions. One example is the problem of estimating building height where layover is present.

  3. Radiant Temperature Nulling Radiometer and Polarization Enhanced Thermal Radiometer

    NASA Technical Reports Server (NTRS)

    Bailey, John

    2002-01-01

    The two radiometers profiled in this viegraph presentation, the Radiant Temperature Nulling Radiometer and the Polarization Enhanced Thermal Radiometer, were developed for the calibration of remote sensing equipment. This presentation profiles the theory and components of each type of radiometer.

  4. Another Nulling Hall-Effect Current-Measuring Circuit

    NASA Technical Reports Server (NTRS)

    Thibodeau, Phillip E.; Sullender, Craig C.

    1993-01-01

    Lightweight, low-power circuit provides noncontact measurement of alternating or direct current of many ampheres in main conductor. Advantages of circuit over other nulling Hall-effect current-measuring circuits is stability and accuracy increased by putting both analog-to-digital and digital-to-analog converters in nulling feedback loop. Converters and rest of circuit designed for operation at sampling rate of 100 kHz, but rate changed to alter time or frequency response of circuit.

  5. Antimultipath communication by injecting tone into null in signal spectrum

    NASA Technical Reports Server (NTRS)

    Davarian, Faramaz (Inventor)

    1987-01-01

    A transmitter for digital radio communication creates a null by balanced encoding of data modulated on an RF carrier, and inserts a calibration tone within the null. This is accomplished by having the calibration tone coincide in phase and frequency with the transmitted radio frequency output, for coherent demodulation of data at the receiver where the tone calibration signal is extracted and used for multipath fading compensation.

  6. Experimental Progress and Results of a Visible Nulling Coronagraph

    NASA Technical Reports Server (NTRS)

    Samuele, Rocco; Wallace, J. Kent; Schmidtlin, Edouard; Shao, Mike; Levine, B. Martin; Fregoso, Santos

    2007-01-01

    The crux of visible exoplanet detection is overcoming significant star-planet contrast ratios on the order of 10(exp -7) to 10(exp -10)-at very small angular separations. We are developing an interferometric nulling coronagraph designed to achieve a 10(exp -6) contrast ratio at a working science bandpass of 20% visible light. Achieving large, broadband suppression requires a pseudo-achromatic phase flip, while maintaining a strict error budget. Recent results from our nulling interferometer testbed yield contrast ratios at the 1.05x10(exp -6) level, with a 15% visible bandpass. This result is at 65% of our final bandpass requirement, although limitations of our current configuration make major hardware changes essential to broadening the bandpass. We make the argument that broadening the bandpass should not necessarily adversely affect the null depth until beyond the 20% visible light level. Using the same setup we are able to reach monochromatic null depths of 1.11x10(exp -7) (?= 638 nm)averaged over three seconds. This paper will describe our experimental approach for achieving deep broadband nulls, as well as error considerations and limitations, and the most recent results for our nulling coronagraph testbed.

  7. Context-specific protection of TGFα null mice from osteoarthritis

    PubMed Central

    Usmani, Shirine E.; Ulici, Veronica; Pest, Michael A.; Hill, Tracy L.; Welch, Ian D.; Beier, Frank

    2016-01-01

    Transforming growth factor alpha (TGFα) is a growth factor involved in osteoarthritis (OA). TGFα induces an OA-like phenotype in articular chondrocytes, by inhibiting matrix synthesis and promoting catabolic factor expression. To better understand TGFα’s potential as a therapeutic target, we employed two in vivo OA models: (1) post-traumatic and (2) aging related OA. Ten-week old and six-month old male Tgfa null mice and their heterozygous (control) littermates underwent destabilization of the medial meniscus (DMM) surgery. Disease progression was assessed histologically using the Osteoarthritis Research Society International (OARSI) scoring system. As well, spontaneous disease progression was analyzed in eighteen-month-old Tgfa null and heterozygous mice. Ten-week old Tgfa null mice were protected from OA progression at both seven and fourteen weeks post-surgery. No protection was seen however in six-month old null mice after DMM surgery, and no differences were observed between genotypes in the aging model. Thus, young Tgfa null mice are protected from OA progression in the DMM model, while older mice are not. In addition, Tgfa null mice are equally susceptible to spontaneous OA development during aging. Thus, TGFα might be a valuable therapeutic target in some post-traumatic forms of OA, however its role in idiopathic disease is less clear. PMID:27457421

  8. Context-specific protection of TGFα null mice from osteoarthritis.

    PubMed

    Usmani, Shirine E; Ulici, Veronica; Pest, Michael A; Hill, Tracy L; Welch, Ian D; Beier, Frank

    2016-01-01

    Transforming growth factor alpha (TGFα) is a growth factor involved in osteoarthritis (OA). TGFα induces an OA-like phenotype in articular chondrocytes, by inhibiting matrix synthesis and promoting catabolic factor expression. To better understand TGFα's potential as a therapeutic target, we employed two in vivo OA models: (1) post-traumatic and (2) aging related OA. Ten-week old and six-month old male Tgfa null mice and their heterozygous (control) littermates underwent destabilization of the medial meniscus (DMM) surgery. Disease progression was assessed histologically using the Osteoarthritis Research Society International (OARSI) scoring system. As well, spontaneous disease progression was analyzed in eighteen-month-old Tgfa null and heterozygous mice. Ten-week old Tgfa null mice were protected from OA progression at both seven and fourteen weeks post-surgery. No protection was seen however in six-month old null mice after DMM surgery, and no differences were observed between genotypes in the aging model. Thus, young Tgfa null mice are protected from OA progression in the DMM model, while older mice are not. In addition, Tgfa null mice are equally susceptible to spontaneous OA development during aging. Thus, TGFα might be a valuable therapeutic target in some post-traumatic forms of OA, however its role in idiopathic disease is less clear. PMID:27457421

  9. Loss of BRCA1-A Complex Function in RAP80 Null Tumor Cells

    PubMed Central

    Cho, Kathleen; Yu, Xiaochun

    2012-01-01

    Receptor Associated Protein 80 (RAP80) is a subunit of the BRCA1-A complex and targets BRCA1 to DNA damage sites in response to DNA double strand breaks. Since mutations of BRCA1 are associated with familial ovarian cancers, we screened 26 ovarian cancer-derived cell lines for RAP80 mutations and found that TOV-21G cells harbor a RAP80 mutation (c.1107G >A). This mutation generates a stop codon at Trp369, which deletes the partial AIR region and the C-terminal zinc fingers of RAP80. Interestingly, both the mutant and wild type alleles of RAP80 lose their expression due to promoter hypermethylation, suggesting that TOV-21G is a RAP80-null cell line. In these cells, not only is the BRCA1-A complex disrupted, but the relocation of the remaining subunits in the BRCA1-A complex including BRCA1, CCDC98, NBA1, BRCC36 and BRE is significantly suppressed. Moreover, TOV-21G cells are hypersensitive to ionizing radiation, which is due to the compromised DNA damage repair capacity in these cells. Reconstitution of TOV-21G cells with wild type RAP80 rescues these cellular defects in response to DNA damage. Thus, our results demonstrate that RAP80 is a scaffold protein in the BRCA1-A complex. Identification of TOV-21G as a RAP80 null tumor cell line will be very useful for the study of the molecular mechanism in DNA damage response. PMID:22792303

  10. Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

    PubMed

    Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

    2016-02-01

    This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. PMID:26724401

  11. Measurement Via Optical Near-Nulling and Subaperture Stitching

    NASA Technical Reports Server (NTRS)

    Forbes, Greg; De Vries, Gary; Murphy, Paul; Brophy, Chris

    2012-01-01

    A subaperture stitching interferometer system provides near-nulling of a subaperture wavefront reflected from an object of interest over a portion of a surface of the object. A variable optical element located in the radiation path adjustably provides near-nulling to facilitate stitching of subaperture interferograms, creating an interferogram representative of the entire surface of interest. This enables testing of aspheric surfaces without null optics customized for each surface prescription. The surface shapes of objects such as lenses and other precision components are often measured with interferometry. However, interferometers have a limited capture range, and thus the test wavefront cannot be too different from the reference or the interference cannot be analyzed. Furthermore, the performance of the interferometer is usually best when the test and reference wavefronts are nearly identical (referred to as a null condition). Thus, it is necessary when performing such measurements to correct for known variations in shape to ensure that unintended variations are within the capture range of the interferometer and accurately measured. This invention is a system for nearnulling within a subaperture stitching interferometer, although in principle, the concept can be employed by wavefront measuring gauges other than interferometers. The system employs a light source for providing coherent radiation of a subaperture extent. An object of interest is placed to modify the radiation (e.g., to reflect or pass the radiation), and a variable optical element is located to interact with, and nearly null, the affected radiation. A detector or imaging device is situated to obtain interference patterns in the modified radiation. Multiple subaperture interferograms are taken and are stitched, or joined, to provide an interferogram representative of the entire surface of the object of interest. The primary aspect of the invention is the use of adjustable corrective optics in the

  12. Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities.

    PubMed

    Kerr, Emma M; Gaude, Edoardo; Turrell, Frances K; Frezza, Christian; Martins, Carla P

    2016-03-01

    The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations. A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations. We recently showed that advanced lung tumours from Kras(G12D/+);p53-null mice frequently exhibit Kras(G12D) allelic enrichment (Kras(G12D)/Kras(wild-type) > 1) (ref. 7), implying that mutant Kras copy gains are positively selected during progression. Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct. In particular, Kras(G12D/G12D) cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous non-small-cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of Kras(G12D) copy gain), but not in the corresponding early tumours (Kras(G12D) heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content. We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression. PMID:26909577

  13. Interferometric nulling of four channels with integrated optics.

    PubMed

    Errmann, Ronny; Minardi, Stefano; Labadie, Lucas; Muthusubramanian, Balaji; Dreisow, Felix; Nolte, Stefan; Pertsch, Thomas

    2015-08-20

    Nulling interferometry has been identified as a competitive technique for the detection of extrasolar planets. In its basic form, the technique consists of combining out-of-phase a single pair of telescopes to effectively null the light of a bright star and reveal the dim glow of the companion. However, in order to mitigate the effect of the stellar leaks through the interferometer, a broad angular central null is required. The hierarchical combination of several pairs of telescopes can accomplish this task. We have manufactured and tested with monochromatic light an integrated optics component, which combines a linear array of four telescopes in the nulling mode envisaged by Angel and Woolf [Astroph. J.475, 373-379 (1997).10.1086/apj.1997.475.issue-1ASJOAB0004-637X]. By simulating in the laboratory the motion of a star in the sky, we could measure the expected angular transmission of the four-telescope nuller. Moreover, the tests have demonstrated a broad nulling scaling as the fourth power of the baseline delay. PMID:26368784

  14. Achromatic phase shifts utilizing dielectric plates for nulling interferometery

    NASA Astrophysics Data System (ADS)

    Morgan, R. M.; Burge, J. M.

    1998-12-01

    Schemes for detecting planets around other stars using interferometery have been developed which rely on a half wave phase delay to shift the central constructive fringe of an interferometer to a deep, destructive null fringe. To achieve the sensitivity and spectroscopy desired for exo-planets observations, such a null must be achromatic over a broad spectral region. One method for creating such a half wave phase delay achromatically involves the use of pairs of dielectric, plane parallel plates, analogous to the use of two types of glass in an achromatic lens. An analysis of the technique is presented with solutions using single plates to achieve null fringes to a cancellation of 10 exp -4 in the visible, near infrared, and mid infrared for null. Solutions using two matched materials show that nulls to a depth of 10 exp -6 are achievable in 2 um bands in the 7-17 um regime, or to a depth of 10 exp -5 over the entire 7-17 um band. Experimental results using a single plate of BK7 in the visible spectrum verify the technique.

  15. Do Null Subjects (mis-)Trigger Pro-drop Grammars?

    PubMed

    Frazier, Lyn

    2015-12-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [−pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing their grammars to a [−pro] setting. Mack et al. (J Memory Lang 67(1):211-223, 2012) showed that sentences with noise covering the subject are analyzed as having null subjects more often with a first person pronoun and with a present tense--properties correlated with more predictable referents--compared to a third person pronoun and past tense. However, those results might in principle have been due to reporting null subjects for verbs that often occur with null subjects. An experiment is reported here in which comparable results are found for sentences containing nonsense verbs. Participants preferred a null subject more often for first person present tense sentences than for third person past tense sentences. The results are as expected if participants are responding to predictability, the likelihood of reduction, rather than to lexical statistics. The results are argued to be important in removing a class of mis-triggering examples from the language acquisition problem. PMID:25086703

  16. Ballooning modes localized near the null point of a divertor

    SciTech Connect

    Farmer, W. A.

    2014-04-15

    The stability of ballooning modes localized to the null point in both the standard and snowflake divertors is considered. Ideal magnetohydrodynamics is used. A series expansion of the flux function is performed in the vicinity of the null point with the lowest, non-vanishing term retained for each divertor configuration. The energy principle is used with a trial function to determine a sufficient instability threshold. It is shown that this threshold depends on the orientation of the flux surfaces with respect to the major radius with a critical angle appearing due to the convergence of the field lines away from the null point. When the angle the major radius forms with respect to the flux surfaces exceeds this critical angle, the system is stabilized. Further, the scaling of the instability threshold with the aspect ratio and the ratio of the scrape-off-layer width to the major radius is shown. It is concluded that ballooning modes are not a likely candidate for driving convection in the vicinity of the null for parameters relevant to existing machines. However, the results place a lower bound on the width of the heat flux in the private flux region. To explain convective mixing in the vicinity of the null point, new consideration should be given to an axisymmetric mixing mode [W. A. Farmer and D. D. Ryutov, Phys. Plasmas 20, 092117 (2013)] as a possible candidate to explain current experimental results.

  17. Visible Nulling Coronagraphy Testbed Development for Exoplanet Detection

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Thompson, Patrick; Chen, Andrew; Petrone, Peter; Booth, Andrew; Madison, Timothy; Bolcar, Matthew; Noecker, M. Charley; Kendrick, Stephen; Melnick, Gary; Tolls, Volker

    2010-01-01

    Three of the recently completed NASA Astrophysics Strategic Mission Concept (ASMC) studies addressed the feasibility of using a Visible Nulling Coronagraph (VNC) as the prime instrument for exoplanet science. The VNC approach is one of the few approaches that works with filled, segmented and sparse or diluted aperture telescope systems and thus spans the space of potential ASMC exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies and has developed an incremental sequence of VNC testbeds to advance the this approach and the technologies associated with it. Herein we report on the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under high bandwidth closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible light nulling milestones of sequentially higher contrasts of 10(exp 8) , 10(exp 9) and 10(exp 10) at an inner working angle of 2*lambda/D and ultimately culminate in spectrally broadband (>20%) high contrast imaging. Each of the milestones, one per year, is traceable to one or more of the ASMC studies. The VNT uses a modified Mach-Zehnder nulling interferometer, modified with a modified "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. Discussed will be the optical configuration laboratory results, critical technologies and the null sensing and control approach.

  18. Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation

    PubMed Central

    Cheung, Aaron Y.L.; Horvath, Lindsay M.; Grafodatskaya, Daria; Pasceri, Peter; Weksberg, Rosanna; Hotta, Akitsu; Carrel, Laura; Ellis, James

    2011-01-01

    Rett syndrome (RTT) is a neurodevelopmental autism spectrum disorder that affects girls due primarily to mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). The majority of RTT patients carry missense and nonsense mutations leading to a hypomorphic MECP2, while null mutations leading to the complete absence of a functional protein are rare. MECP2 is an X-linked gene subject to random X-chromosome inactivation resulting in mosaic expression of mutant MECP2. The lack of human brain tissue motivates the need for alternative human cellular models to study RTT. Here we report the characterization of a MECP2 mutation in a classic female RTT patient involving rearrangements that remove exons 3 and 4 creating a functionally null mutation. To generate human neuron models of RTT, we isolated human induced pluripotent stem (hiPS) cells from RTT patient fibroblasts. RTT-hiPS cells retained the MECP2 mutation, are pluripotent and fully reprogrammed, and retained an inactive X-chromosome in a nonrandom pattern. Taking advantage of the latter characteristic, we obtained a pair of isogenic wild-type and mutant MECP2 expressing RTT-hiPS cell lines that retained this MECP2 expression pattern upon differentiation into neurons. Phenotypic analysis of mutant RTT-hiPS cell-derived neurons demonstrated a reduction in soma size compared with the isogenic control RTT-hiPS cell-derived neurons from the same RTT patient. Analysis of isogenic control and mutant hiPS cell-derived neurons represents a promising source for understanding the pathogenesis of RTT and the role of MECP2 in human neurons. PMID:21372149

  19. Behavioral phenotype of maLPA1-null mice: increased anxiety-like behavior and spatial memory deficits

    PubMed Central

    Santin, L.J.; Bilbao, A.; Pedraza, C.; Matas-Rico, E.; López-Barroso, D.; Castilla-Ortega, E.; Sánchez-López, J.; Riquelme, R.; Varela-Nieto, I.; de la Villa, P.; Suardíaz, M.; Chun, J.; De Fonseca, F. Rodriguez; Estivill-Torrús, G.

    2016-01-01

    Lysophosphatidic acid (LPA) has emerged as a new regulatory molecule in the brain. Recently, some studies have demonstrated a role for this molecule and its LPA1 receptor in the regulation of plasticity and neurogenesis in the adult brain. However, no systematic studies have been conducted to investigate whether the LPA1 receptor is involved in behavior. Here we studied the phenotype of maLPA1–null mice, which bear a targeted deletion at the lpa1 locus, in a battery of tests examining neurologic performance, habituation in exploratory behavior in response to low and mild anxiety environments and spatial memory. MaLPA1-null mutants showed deficits in both olfaction and somesthesis, but not in retinal or auditory functions. Sensorimotor coordination was impaired only in the equilibrium and grasping reflexes. The mice also showed impairments in neuromuscular strength and analgesic response. No additional differences were observed in the rest of the tests used to study sensoriomotor orientation, limb reflexes, and coordinated limb use. At behavioral level, maLPA1-null mice showed an impaired exploration in the open field and increased anxiety-like response when exposed to the elevated plus maze. Furthermore, the mice exhibit impaired spatial memory retention and reduced use of spatial strategies in the Morris water maze. We propose that the LPA1 receptor may play a major role in both spatial memory and response to anxiety-like conditions. PMID:19689455

  20. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  1. Phenotypic Characterization of Mice Heterozygous for a Null Mutation of Glutamate Carboxypeptidase II

    PubMed Central

    Han, Liqun; Picker, Jonathan D.; Schaevitz, Laura R.; Tsai, Guochuan; Feng, Jiamin; Jiang, Zhichun; Chu, Hillary C.; Basu, Alo C.; Berger-Sweeney, Joanne; Coyle, Joseph T.

    2009-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed glutamate signaling resulting in hypofunction of NMDA receptors has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-glutamate (NAAG) into glutamate and N-acetyl-aspartate (NAA). NAAG is a neuropeptide that is an NMDA receptor antagonist as well as an agonist for the metabotropic glutamate receptor-3 (mGluR3), which inhibits glutamate release. The aggregate effect of NAAG is thus to attenuate NMDA receptor activation. To manipulate the expression of GCP II, loxP sites were inserted flanking exon 1 and 2, which were excised by crossing with a Cre-expressing mouse. The mice heterozygous for this deletion showed a 50% reduction in the expression level of protein and functional activity of GCP II in brain samples. Heterozygous mutant crosses did not yield any homozygous null animals at birth or as embryos (N >200 live births and fetuses). These data are consistent with the previous report that GCP II homozygous mutant mice generated by removing exons 9 and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that GCP II plays an essential role early in embryonic development. Heterozygous mice, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory. PMID:19347959

  2. Phenotypic characterization of mice heterozygous for a null mutation of glutamate carboxypeptidase II.

    PubMed

    Han, Liqun; Picker, Jonathan D; Schaevitz, Laura R; Tsai, Guochuan; Feng, Jiamin; Jiang, Zhichun; Chu, Hillary C; Basu, Alo C; Berger-Sweeney, Joanne; Coyle, Joseph T

    2009-08-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed glutamate signaling resulting in hypofunction of N-methyl-D-aspartate receptors (NMDAR) has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-glutamate (NAAG) into glutamate and N-acetyl-aspartate. NAAG is a neuropeptide that is an NMDAR antagonist as well as an agonist for the metabotropic glutamate receptor-3 (mGluR3), which inhibits glutamate release. The aggregate effect of NAAG is thus to attenuate NMDAR activation. To manipulate the expression of GCP II, LoxP sites were inserted flanking exons 1 and 2, which were excised by crossing with a Cre-expressing mouse. The mice heterozygous for this deletion showed a 50% reduction in the expression level of protein and functional activity of GCP II in brain samples. Heterozygous mutant crosses did not yield any homozygous null animals at birth or as embryos (N > 200 live births and fetuses). These data are consistent with the previous report that GCP II homozygous mutant mice generated by removing exons 9 and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that GCP II plays an essential role early in embryonic development. Heterozygous mice, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory. PMID:19347959

  3. Double null hamiltonian dynamics and the gravitational degrees of freedom

    NASA Astrophysics Data System (ADS)

    Vickers, J. A.

    2011-12-01

    In this paper we review the Hamiltonian description of General Relativity using a double null foliation. We start by looking at the 2+2 version of geometrodynamics and show the role of the conformal 2-structure of the 2-metric in encoding (through the shear) the 2 gravitational degrees of freedom. In the second part of the paper we consider instead a canonical analysis of a double null 2+2 Hamiltonian description of General Relativity in terms of self-dual 2-forms and the associated SO(3) connection variables. The algebra of first class constraints is obtained and forms a Lie algebra that consists of two constraints that generate diffeomorphisms in the two surface, a constraint that generates diffeomorphisms along the null generators and a constraint that generates self-dual spin and boost transformations.

  4. sirt1-null mice develop an autoimmune-like condition

    SciTech Connect

    Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

    2008-10-01

    The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease.

  5. On the geometry of null hypersurfaces in Minkowski space

    NASA Astrophysics Data System (ADS)

    Navarro, Matias; Palmas, Oscar; Solis, Didier A.

    2014-01-01

    The present work is divided into three parts. First we study the null hypersurfaces of the Minkowski space R1n+2, classifying all rotation null hypersurfaces in R1n+2. In the second part we start our analysis of the submanifold geometry of the null hypersurfaces. In the particular case of the (n+1)-dimensional light cone, we characterize its totally umbilical spacelike hypersurfaces, show the existence of non-totally umbilical ones and give a uniqueness result for the minimal spacelike rotation surfaces in the 3-dimensional light cone. In the third and final part we consider an isolated umbilical point on a spacelike surface immersed in the 3-dimensional light cone of R14 and obtain the differential equation of the principal configuration associated to this point, showing that every classical generic Darbouxian principal configuration appears in this context.

  6. Null but not void: considerations for hypothesis testing.

    PubMed

    Shaw, Pamela A; Proschan, Michael A

    2013-01-30

    Standard statistical theory teaches us that once the null and alternative hypotheses have been defined for a parameter, the choice of the statistical test is clear. Standard theory does not teach us how to choose the null or alternative hypothesis appropriate to the scientific question of interest. Neither does it tell us that in some cases, depending on which alternatives are realistic, we may want to define our null hypothesis differently. Problems in statistical practice are frequently not as pristinely summarized as the classic theory in our textbooks. In this article, we present examples in statistical hypothesis testing in which seemingly simple choices are in fact rich with nuance that, when given full consideration, make the choice of the right hypothesis test much less straightforward. Published 2012. This article is a US Government work and is in the public domain in the USA. PMID:22807023

  7. Unicorns do exist: a tutorial on "proving" the null hypothesis.

    PubMed

    Streiner, David L

    2003-12-01

    Introductory statistics classes teach us that we can never prove the null hypothesis; all we can do is reject or fail to reject it. However, there are times when it is necessary to try to prove the nonexistence of a difference between groups. This most often happens within the context of comparing a new treatment against an established one and showing that the new intervention is not inferior to the standard. This article first outlines the logic of "noninferiority" testing by differentiating between the null hypothesis (that which we are trying to nullify) and the "nill" hypothesis (there is no difference), reversing the role of the null and alternate hypotheses, and defining an interval within which groups are said to be equivalent. We then work through an example and show how to calculate sample sizes for noninferiority studies. PMID:14733457

  8. Fully achromatic nulling interferometer (FANI) for high SNR exoplanet characterization

    NASA Astrophysics Data System (ADS)

    Hénault, François

    2015-09-01

    Space-borne nulling interferometers have long been considered as the best option for searching and characterizing extrasolar planets located in the habitable zone of their parent stars. Solutions for achieving deep starlight extinction are now numerous and well demonstrated. However they essentially aim at realizing an achromatic central null in order to extinguish the star. In this communication is described a major improvement of the technique, where the achromatization process is extended to the entire fringe pattern. Therefore higher Signal-to-noise ratios (SNR) and appreciable simplification of the detection system should result. The basic principle of this Fully achromatic nulling interferometer (FANI) consists in inserting dispersive elements along the arms of the interferometer. Herein this principle is explained and illustrated by a preliminary optical system design. The typical achievable performance and limitations are discussed and some initial tolerance requirements are also provided.

  9. Statefinder hierarchy: An extended null diagnostic for concordance cosmology

    SciTech Connect

    Arabsalmani, Maryam; Sahni, Varun

    2011-02-15

    We show how higher derivatives of the expansion factor can be developed into a null diagnostic for concordance cosmology ({Lambda}CDM). It is well known that the Statefinder - the third derivative of the expansion factor written in dimensionless form, a{sup (3)}/aH{sup 3}, equals unity for {Lambda}CDM. We generalize this result and demonstrate that the hierarchy, a{sup (n)}/aH{sup n}, can be converted to a form that stays pegged at unity in concordance cosmology. This remarkable property of the Statefinder hierarchy enables it to be used as an extended null diagnostic for the cosmological constant. The Statefinder hierarchy combined with the growth rate of matter perturbations defines a composite null diagnostic which can distinguish evolving dark energy from {Lambda}CDM.

  10. Magnetoacoustic Waves in Stratified Atmospheres with a Magnetic Null Point

    NASA Astrophysics Data System (ADS)

    Tarr, Lucas A.; Linton, Mark; Leake, James E.

    2016-05-01

    Magnetic fields strongly modify the propagation of MHD waves from the photosphere to the low corona, as can be shown exactly for the most simple case of a uniform magnetic field and isothermally stratrified atmosphere. For slightly more realistic scenarios, where both the atmospheric parameters and the magnetic field vary spatially, the linear MHD equations typically cannot be solved analytically. We use the Lagrangian Remap code--a nonlinear, shock-capturing MHD code--to study the propagation of initially acoustic wavepackets through a model 2D atmosphere that includes a gravitationally stratified chromosphere, transition region, and low corona. The magnetic field is formed by three photospheric concentrations and includes a single magnetic null point, resulting in an inhomogeneous system with a magnetic dome topology. A portion of an introduced wavepacket will refract toward the null due to the varying Alfven speed. Waves incident on the equipartition contour surrounding the null, where the sound and Alfven speeds coincide, partially transmit, reflect, and mode convert between branches of the local dispersion relation. Outward propagating slow modes generated during conversion become strongly concentrated along the set of field lines passing near the null. Acoustic energy is beamed back downwards towards each photospheric foot point, and upwards along one separatrix that exits the top of the numerical domain. Changes in the dominant restoring force for the wavepacket, between the Lorentz and pressure gradient forces, lead to a buildup of current density along topologically important features of the system (the null point and its four separatrices) and can drive reconnection at the null point itself. Ohmic dissipation of the currents locally heats the plasma. We find that the amount of current accumulation depends on where the centroid of a wavepacket initial crosses the photosphere, but does not simply coincide with regions of open versus closed magnetic field or

  11. Retention of crab larvae in a coastal null zone

    NASA Astrophysics Data System (ADS)

    Tilburg, Charles E.; Dittel, Ana I.; Epifanio, Charles E.

    2007-05-01

    Alongshelf transport in the southern Middle Atlantic Bight is forced by buoyancy-driven currents originating in three large estuaries along the bight. These currents are strongest in the coastal ocean near the southern terminus of each estuary, while the analogous region on the northern side is characterized by weak subtidal flow. We used a combination of field observations and numerical modeling to test the hypothesis that these regions of weak subtidal flow are coastal null zones that serve as retention areas for larvae. The field study consisted of a four-day, shipboard investigation of the distribution of blue crab larvae ( Callinectes sapidus) near the mouth of Delaware Bay (˜39°N, 75°W) in late summer, 2004. Hydrographic surveys of the study site were conducted with a hull-mounted, surface-measuring system. Results showed a sharp boundary between the null zone and the buoyancy-driven current to the south. Blue crab larvae were collected in surface plankton tows along a 30-km transect that encompassed these two areas. Stations with higher densities of larvae were clustered in the null zone during both ebb and flood tides. A numerical model was used to examine the physical mechanisms responsible for the observed distribution. Model results agreed with the field survey and showed that simulated larvae are aggregated in the null zone. The simulations also demonstrated that larvae spawned within the null zone have a much greater probability of settling in juvenile nursery habitat within the bay. The close agreement between field and model results provides consistent support for the hypothesis that coastal null zones associated with the buoyancy-driven circulation of large estuaries may allow retention of larvae in the vicinity of the natal spawning population.

  12. Adaptive Nulling for the Terrestrial Planet Finder Interferometer

    NASA Technical Reports Server (NTRS)

    Jeganathan, Muthu; Hirai, Akiko; Lay, Oliver P.; Peters, Robert D.

    2006-01-01

    Deep, stable starlight nulls are needed for the direct detection of Earth-like planets and require careful control of the intensity and phases of the beams that are being combined. We are testing a novel compensator based on a deformable mirror to correct the intensity and phase at each wavelength and polarization across the nulling bandwidth. We have successfully demonstrated intensity and phase control using a deformable mirror across a 100nm wide band in the near-IR, and are in the process of conducting experiments in the mid-IR wavelengths. This paper covers the current results and in the mid-IR.

  13. Null geodesics in a magnetically charged stringy black hole spacetime

    NASA Astrophysics Data System (ADS)

    Kuniyal, Ravi Shankar; Uniyal, Rashmi; Nandan, Hemwati; Purohit, K. D.

    2016-04-01

    We study the null geodesics of a four-dimensional magnetic charged black hole spacetime arising in string theory. The behaviour of effective potential in view of the different values of black hole parameters are analysed in the equatorial plane. The possible orbits for null geodesics are also discussed in view of the different values of the impact parameter. We have also calculated the frequency shift of photons in this spacetime. The results are compared to those obtained for the electrically charged stringy black hole spacetime and the Schwarzschild black hole spacetime in general relativity.

  14. Rapamycin requires AMPK activity and p27 expression for promoting autophagy-dependent Tsc2-null cell survival.

    PubMed

    Campos, Tania; Ziehe, Javiera; Fuentes-Villalobos, Francisco; Riquelme, Orlando; Peña, Daniela; Troncoso, Rodrigo; Lavandero, Sergio; Morin, Violeta; Pincheira, Roxana; Castro, Ariel F

    2016-06-01

    Tuberous sclerosis complex (TSC) disease results from inactivation of the TSC1 or TSC2 gene, and is characterized by benign tumors in several organs. Because TSC tumorigenesis correlates with hyperactivation of mTORC1, current therapies focus on mTORC1 inhibition with rapamycin or its analogs. Rapamycin-induced tumor shrinkage has been reported, but tumor recurrence occurs on withdrawal from rapamycin. Autophagy has been associated with development of TSC tumors and with tumor cell survival during rapamycin treatment. mTORC1 and AMPK directly inhibit and activate autophagy, respectively. AMPK is hyperactivated in TSC cells and tumors, and drives cytoplasmic sequestration of the cell-cycle inhibitor p27KIP (p27). Whether AMPK and p27 are involved in rapamycin-induced autophagy and survival of TSC cells remain unexplored. Here, we show that inhibition of AMPK by compound C or by shRNA-mediated depletion of LKB1 reduces activation of autophagy by rapamycin in Tsc2-null cells. Similarly, shRNA-mediated depletion of p27 inhibited rapamycin-induced autophagy. In support of p27 lying downstream of AMPK on the activation of autophagy in Tsc2-null cells, a p27 mutant that preferentially localizes in the cytosol recovered the effect of rapamycin on autophagy in both p27- and LKB1-depleted cells, but a nuclear p27 mutant was inactive. Finally, we show that p27-dependent activation of autophagy is involved in Tsc2-null cell survival under rapamycin treatment. These results indicate that an AMPK/p27 axis is promoting a survival mechanism that could explain in part the relapse of TSC tumors treated with rapamycin, exposing new avenues for designing more efficient treatments for TSC patients. PMID:26975583

  15. Testing the null hypothesis: the forgotten legacy of Karl Popper?

    PubMed

    Wilkinson, Mick

    2013-01-01

    Testing of the null hypothesis is a fundamental aspect of the scientific method and has its basis in the falsification theory of Karl Popper. Null hypothesis testing makes use of deductive reasoning to ensure that the truth of conclusions is irrefutable. In contrast, attempting to demonstrate the new facts on the basis of testing the experimental or research hypothesis makes use of inductive reasoning and is prone to the problem of the Uniformity of Nature assumption described by David Hume in the eighteenth century. Despite this issue and the well documented solution provided by Popper's falsification theory, the majority of publications are still written such that they suggest the research hypothesis is being tested. This is contrary to accepted scientific convention and possibly highlights a poor understanding of the application of conventional significance-based data analysis approaches. Our work should remain driven by conjecture and attempted falsification such that it is always the null hypothesis that is tested. The write up of our studies should make it clear that we are indeed testing the null hypothesis and conforming to the established and accepted philosophical conventions of the scientific method. PMID:23249368

  16. Circumpulsar Asteroids: Inferences from Nulling Statistics and High Energy Correlations

    NASA Astrophysics Data System (ADS)

    Shannon, Ryan; Cordes, J. M.

    2006-12-01

    We have proposed that some classes of radio pulsar variability are associated with the entry of neutral asteroidal material into the pulsar magnetosphere. The region surrounding neutron stars is polluted with supernova fall-back material, which collapses and condenses into an asteroid-bearing disk that is stable for millions of years. Over time, collisional and radiative processes cause the asteroids to migrate inward until they are heated to the point of ionization. For older and cooler pulsars, asteroids ionize within the large magnetospheres and inject a sufficient amount of charged particles to alter the electrodynamics of the gap regions and modulate emission processes. This extrinsic model unifies many observed phenomena of variability that occur on time scales that are disparate with the much shorter time scales associated with pulsars and their magnetospheres. One such type of variability is nulling, in which certain pulsars exhibit episodes of quiescence that for some objects may be as short as a few pulse periods, but, for others, is longer than days. Here, in the context of this model, we examine the nulling phenomenon. We analyze the relationship between in-falling material and the statistics of nulling. In addition, as motivation for further high energy observations, we consider the relationship between the nulling and other magnetospheric processes.

  17. Reassessing the Null-Subject Parameter in Second Language Acquisition.

    ERIC Educational Resources Information Center

    Lantolf, James P.

    A study is presented that examines the null-subject parameter (NSP) and that seeks to attain the following objectives: (1) to assess the validity of the implicational hierarchy for the NSP, especially as proposed by Liceras (1989); and (2) to determine if there is any evidence to support the theory of the Weaker Logical Problem of Acquisition…

  18. Self-Nulling Beam Combiner Using No External Phase Inverter

    NASA Technical Reports Server (NTRS)

    Bloemhof, Eric E.

    2010-01-01

    A self-nulling beam combiner is proposed that completely eliminates the phase inversion subsystem from the nulling interferometer, and instead uses the intrinsic phase shifts in the beam splitters. Simplifying the flight instrument in this way will be a valuable enhancement of mission reliability. The tighter tolerances on R = T (R being reflection and T being transmission coefficients) required by the self-nulling configuration actually impose no new constraints on the architecture, as two adaptive nullers must be situated between beam splitters to correct small errors in the coatings. The new feature is exploiting the natural phase shifts in beam combiners to achieve the 180 phase inversion necessary for nulling. The advantage over prior art is that an entire subsystem, the field-flipping optics, can be eliminated. For ultimate simplicity in the flight instrument, one might fabricate coatings to very high tolerances and dispense with the adaptive nullers altogether, with all their moving parts, along with the field flipper subsystem. A single adaptive nuller upstream of the beam combiner may be required to correct beam train errors (systematic noise), but in some circumstances phase chopping reduces these errors substantially, and there may be ways to further reduce the chop residuals. Though such coatings are beyond the current state of the art, the mechanical simplicity and robustness of a flight system without field flipper or adaptive nullers would perhaps justify considerable effort on coating fabrication.

  19. Traversable wormholes: Minimum violation of the null energy condition revisited

    SciTech Connect

    Zaslavskii, O. B.

    2007-08-15

    It was argued in literature that traversable wormholes can exist with an arbitrarily small violation of null energy conditions. I show that if the amount of exotic material near the wormhole throat tends to zero, either this leads to a horn instead of a wormhole or the throat approaches the horizon in such a way that infinitely large stresses develop on the throat.

  20. Do Null Subjects (Mis-)Trigger Pro-Drop Grammars?

    ERIC Educational Resources Information Center

    Frazier, Lyn

    2015-01-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [[superscript -]pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing…

  1. White-Light Nulling Interferometers for Detecting Planets

    NASA Technical Reports Server (NTRS)

    Mennesson, Bertrand; Serabyn, Eugene; Shao, Michael; Levine, Bruce

    2004-01-01

    A report proposes the development of a white-light nulling interferometer to be used in conjunction with a singleaperture astronomical telescope that would be operated in outer space. When such a telescope is aimed at a given star, the interferometer would suppress the light of that star while passing enough light from planets (if any) orbiting the star, to enable imaging or spectroscopic examination of the planets. In a nulling interferometer, according to the proposal, scattered light would be suppressed by spatial filtering in an array of single-mode optical fibers rather than by requiring optical surfaces to be accurate within 1/4,000 wavelength as in a coronagraph or an apodized telescope. As a result, angstrom-level precision would be needed in only the small nulling combiner, and not in large, meter-sized optics. The nulling interferometer could work as an independent instrument in space or in conjunction with a coronagraphic system to detect planets outside our solar system.

  2. Null Objects in Second Language Acquisition: Grammatical vs. Performance Models

    ERIC Educational Resources Information Center

    Zyzik, Eve C.

    2008-01-01

    Null direct objects provide a favourable testing ground for grammatical and performance models of argument omission. This article examines both types of models in order to determine which gives a more plausible account of the second language data. The data were collected from second language (L2) learners of Spanish by means of four oral…

  3. Null Lens Assembly for X-Ray Mirror Segments

    NASA Technical Reports Server (NTRS)

    Robinson, David W.

    2011-01-01

    A document discusses a null lens assembly that allows laser interferometry of 60 deg. slumped glass mirror segments used in x-ray mirrors. The assembly consists of four lenses in precise alignment to each other, with incorporated piezoelectric nanometer stepping actuators to position the lenses in six degrees of freedom for positioning relative to each other.

  4. Progress in broadband infrared nulling technology for TPF

    NASA Technical Reports Server (NTRS)

    Wallace, J. Kent; Brown, Ken; Bartos, Randall; Gappinger, Robert; Loya, Frank; Macdonald, Dan; Moser, Steve; Negron, John

    2005-01-01

    TPF-I has set for itself a host of challenging technical milestones along its path to demonstrating the feasibility of infrared nulling for planet detection Progress in each of these areas of technical development will be reviewed as well as progress in meeting the overarching technical milestones.

  5. Null point of discrimination in crustacean polarisation vision.

    PubMed

    How, Martin J; Christy, John; Roberts, Nicholas W; Marshall, N Justin

    2014-07-15

    The polarisation of light is used by many species of cephalopods and crustaceans to discriminate objects or to communicate. Most visual systems with this ability, such as that of the fiddler crab, include receptors with photopigments that are oriented horizontally and vertically relative to the outside world. Photoreceptors in such an orthogonal array are maximally sensitive to polarised light with the same fixed e-vector orientation. Using opponent neural connections, this two-channel system may produce a single value of polarisation contrast and, consequently, it may suffer from null points of discrimination. Stomatopod crustaceans use a different system for polarisation vision, comprising at least four types of polarisation-sensitive photoreceptor arranged at 0, 45, 90 and 135 deg relative to each other, in conjunction with extensive rotational eye movements. This anatomical arrangement should not suffer from equivalent null points of discrimination. To test whether these two systems were vulnerable to null points, we presented the fiddler crab Uca heteropleura and the stomatopod Haptosquilla trispinosa with polarised looming stimuli on a modified LCD monitor. The fiddler crab was less sensitive to differences in the degree of polarised light when the e-vector was at -45 deg than when the e-vector was horizontal. In comparison, stomatopods showed no difference in sensitivity between the two stimulus types. The results suggest that fiddler crabs suffer from a null point of sensitivity, while stomatopods do not. PMID:24737768

  6. Connexin Mutants and Cataracts

    PubMed Central

    Beyer, Eric C.; Ebihara, Lisa; Berthoud, Viviana M.

    2013-01-01

    The lens is a multicellular, but avascular tissue that must stay transparent to allow normal transmission of light and focusing of it on the retina. Damage to lens cells and/or proteins can cause cataracts, opacities that disrupt these processes. The normal survival of the lens is facilitated by an extensive network of gap junctions formed predominantly of connexin46 and connexin50. Mutations of the genes that encode these connexins (GJA3 and GJA8) have been identified and linked to inheritance of cataracts in human families and mouse lines. In vitro expression studies of several of these mutants have shown that they exhibit abnormalities that may lead to disease. Many of the mutants reduce or modify intercellular communication due to channel alterations (including loss of function or altered gating) or due to impaired cellular trafficking which reduces the number of gap junction channels within the plasma membrane. However, the abnormalities detected in studies of other mutants suggest that they cause cataracts through other mechanisms including gain of hemichannel function (leading to cell injury and death) and formation of cytoplasmic accumulations (that may act as light scattering particles). These observations and the anticipated results of ongoing studies should elucidate the mechanisms of cataract development due to mutations of lens connexins and abnormalities of other lens proteins. They may also contribute to our understanding of the mechanisms of disease due to connexin mutations in other tissues. PMID:23596416

  7. The appearance, motion, and disappearance of three-dimensional magnetic null points

    SciTech Connect

    Murphy, Nicholas A.; Parnell, Clare E.; Haynes, Andrew L.

    2015-10-15

    While theoretical models and simulations of magnetic reconnection often assume symmetry such that the magnetic null point when present is co-located with a flow stagnation point, the introduction of asymmetry typically leads to non-ideal flows across the null point. To understand this behavior, we present exact expressions for the motion of three-dimensional linear null points. The most general expression shows that linear null points move in the direction along which the magnetic field and its time derivative are antiparallel. Null point motion in resistive magnetohydrodynamics results from advection by the bulk plasma flow and resistive diffusion of the magnetic field, which allows non-ideal flows across topological boundaries. Null point motion is described intrinsically by parameters evaluated locally; however, global dynamics help set the local conditions at the null point. During a bifurcation of a degenerate null point into a null-null pair or the reverse, the instantaneous velocity of separation or convergence of the null-null pair will typically be infinite along the null space of the Jacobian matrix of the magnetic field, but with finite components in the directions orthogonal to the null space. Not all bifurcating null-null pairs are connected by a separator. Furthermore, except under special circumstances, there will not exist a straight line separator connecting a bifurcating null-null pair. The motion of separators cannot be described using solely local parameters because the identification of a particular field line as a separator may change as a result of non-ideal behavior elsewhere along the field line.

  8. Thermodynamical interpretation of the geometrical variables associated with null surfaces

    NASA Astrophysics Data System (ADS)

    Chakraborty, Sumanta; Padmanabhan, T.

    2015-11-01

    The emergent gravity paradigm interprets gravitational field equations as describing the thermodynamic limit of the underlying statistical mechanics of microscopic degrees of freedom of the spacetime. The connection is established by attributing a heat density T s to the null surfaces where T is the appropriate Davies-Unruh temperature and s is the entropy density. The field equations can be obtained from a thermodynamic variational principle which extremizes the total heat density of all null surfaces. The explicit form of s determines the nature of the theory. We explore the consequences of this paradigm for an arbitrary null surface and highlight the thermodynamic significance of various geometrical quantities. In particular, we show that (a) a conserved current, associated with the time development vector in a natural fashion, has direct thermodynamic interpretation in all Lanczos-Lovelock models of gravity; (b) one can generalize the notion of gravitational momentum, introduced in T. Padmanabhan, [arXiv:1506.03814] to all Lanczos-Lovelock models of gravity such that the conservation of the total momentum leads to the relevant field equations; (c) the thermodynamic variational principle which leads to the field equations of gravity can also be expressed in terms of the gravitational momentum in all Lanczos-Lovelock models; and (d) three different projections of gravitational momentum related to an arbitrary null surface in the spacetime lead to three different equations, all of which have thermodynamic interpretation. The first one reduces to a Navier-Stokes equation for the transverse drift velocity. The second can be written as a thermodynamic identity T d S =d E +P d V . The third describes the time evolution of the null surface in terms of suitably defined surface and bulk degrees of freedom. The implications are discussed.

  9. Identification of several gy4 nulls from the USDA soybean germplasm collection provides new genetic resources for the development of high-quality tofu cultivars.

    PubMed

    Kim, Won-Seok; Ho, Heo Jae; Nelson, Randall L; Krishnan, Hari B

    2008-12-10

    Tofu, a cheese-like food made by curdling soy milk, is a major dietary staple of Asian countries. Consumption of tofu and other soy products is steadily increasing in North America due to its well-known health benefits. Soybean A(5), A(4), and B(3) peptide null lines 'Enrei' and 'Raiden' are commonly utilized in breeding programs to develop high-quality tofu cultivars. To expand the genetic diversity it is desirable to identify and utilize other A(5), A(4), and B(3) null genotypes in the development of improved tofu cultivars that are adapted to North American conditions. In this study were screened diverse soybean accessions from the USDA Soybean Germplasm Collection to identify Gy4 mutants, the locus that controls A(5), A(4), and B(3) peptide production. Analysis of total seed proteins from 485 soybean lines by SDS-PAGE enabled the identification of 38 accessions that lacked the A(5), A(4), and B(3) peptides. These accessions showed marked differences in seed size and seed coat color and represented different maturity groups ranging from 0 to IX. To ascertain the molecular basis for the lack of A(5), A(4), and B(3) peptides in the newly identified Gy4 mutants, the nucleotide sequence of a portion of the Gy4 gene was determined from eight soybean accessions representing different maturity groups. These eight Gy4 mutants revealed a single point mutation that changed the translation initiation codon ATG to ATA, resulting in the A(5), A(4), and B(3) null phenotype. The newly identified Gy4 mutants from this study will enable plant breeders to expand the genetic diversity of North American food-quality soybeans and also aid in the development of hypoallergenic soybeans. PMID:18991447

  10. Detection and characterization of mammalian DNA polymerase beta mutants by functional complementation in Escherichia coli.

    PubMed Central

    Sweasy, J B; Loeb, L A

    1993-01-01

    We have designed and utilized a bacterial complementation system to identify and characterize mammalian DNA polymerase beta mutants. In this complementation system, wild-type rat DNA polymerase beta replaces both the replicative and repair functions of DNA polymerase I in the Escherichia coli recA718 polA12 double mutant; our 263 DNA polymerase beta mutants replace E. coli polymerase I less efficiently or not at all. Of the 10 mutants that have been shown to contain DNA sequence alterations, 2 exhibit a split phenotype with respect to complementation of the growth defect and methylmethanesulfonate sensitivity of the double mutant; one is a null mutant. The mutants possessing a split phenotype contain amino acid residue alterations within a putative nucleotide binding site of DNA polymerase beta. This approach for the isolation and evaluation of mutants of a mammalian DNA polymerase in E. coli may ultimately lead to a better understanding of the mechanism of action of this enzyme and to precisely defining its role in vertebrate cells. Images Fig. 2 PMID:8506308

  11. Reduced wheel running and blunted effects of voluntary exercise in LPA1-null mice: The importance of assessing the amount of running in transgenic mice studies

    PubMed Central

    Castilla-Ortega, Estela; Rosell-Valle, Cristina; Blanco, Eduardo; Pedraza, Carmen; Chun, Jerold; de Fonseca, Fernando Rodríguez; Estivill-Torrús, Guillermo; Santín, Luis J.

    2014-01-01

    This work was aimed to assess whether voluntary exercise rescued behavioral and hippocampal alterations in mice lacking the lysophosphatidic acid LPA1 receptor (LPA1-null mice), studying the potential relationship between the amount of exercise performed and its effects. Normal and LPA1-null mice underwent 23 days of free wheel running and were tested for open-field behavior and adult hippocampal neurogenesis (cell proliferation, immature neurons, cell survival). Running decreased anxiety-like behavior in both genotypes but increased exploration only in the normal mice. While running affected all neurogenesis-related measures in normal mice (especially in the suprapyramidal blade of the dentate gyrus), only a moderate increase in cell survival was found in the mutants. Importantly, the LPA1-nulls showed notably reduced running. Analysis suggested that defective running in the LPA1-null mice could contribute to explain the scarce benefit of the voluntary exercise treatment. On the other hand, a literature review revealed that voluntary exercise is frequently used to modulate behavior and the hippocampus in transgenic mice, but half of the studies did not assess the quantity of running, overlooking any potential running impairments. This study adds evidence to the relevance of the quantity of exercise performed, emphasizing the importance of its assessment in transgenic mice research. PMID:24055600

  12. The zebrafish early arrest mutants.

    PubMed

    Kane, D A; Maischein, H M; Brand, M; van Eeden, F J; Furutani-Seiki, M; Granato, M; Haffter, P; Hammerschmidt, M; Heisenberg, C P; Jiang, Y J; Kelsh, R N; Mullins, M C; Odenthal, J; Warga, R M; Nüsslein-Volhard, C

    1996-12-01

    This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but conditionally lethal: mutant cells, most of which lyse, sometimes survive to become notochord, muscles, or, in rare cases, large neurons, all cell types which become postmitotic in the gastrula. Some of the genes of the early arrest group may be necessary for progression though the cell cycle; if so, the survival of early differentiating cells may be based on having their terminal mitosis before the zygotic requirement for these genes. PMID:9007229

  13. Metabolic phenotype of phosphoglucose isomerase mutants of Corynebacterium glutamicum.

    PubMed

    Marx, Achim; Hans, Stephan; Möckel, Bettina; Bathe, Brigitte; de Graaf, Albert A; McCormack, Ashling C; Stapleton, Cliona; Burke, Kevin; O'Donohue, Michael; Dunican, L K

    2003-09-01

    A series of experiments reported in the literature using fluxomics as an efficient functional genomics tool revealed that the L-lysine production of the Corynebacterium glutamicum strain MH20-22B correlates with the extent of intracellular NADPH supply. Some alternative metabolic engineering strategies to increase intracellular NADPH supply in the C. glutamicum strain DSM5715 were considered and finally the redirection of carbon flux through the pentose phosphate pathway with two NADPH generating enzymatic reactions was favored. Elsewhere, the construction of a phosphoglucose isomerase (Pgi) null mutant of the C. glutamicum strain DSM5715 has been described by utilizing genetic engineering as well as some aspects of its metabolic phenotype. Most interestingly, it was shown that not only could the L-lysine formation be increased by 1.7-fold but the by-product concentration for the null mutant strain was also able to be drastically reduced. In this publication we discuss this metabolic phenotype in detail and present additional data on by-product formation as well as yield considerations. Results from isotope based metabolic flux analysis in combination with considerations on NADPH metabolism clearly exclude the existence of Pgi isoenzymes in C. glutamicum strain DSM5715. The genome region containing the pgi gene was analyzed. It cannot be excluded that polar effects might have been caused by the disruption of the pgi gene and might have contributed to the observed metabolic phenotype of C. glutamicum Pgi mutants. We illustrate growth characteristics of a Pgi mutant of an industrial L-lysine production strain. A reduced growth rate and a biphasic growth behavior was observed. The importance of NADPH reoxidation for well balanced growth in Pgi mutants is discussed. Another phosphoglucose isomerase mutant of C. glutamicum has been described in literature with which an increase in L-lysine yield from 42 to 52% was observed. This finding highlights the general potential

  14. Defective intestinal amino acid absorption in Ace2 null mice.

    PubMed

    Singer, Dustin; Camargo, Simone M R; Ramadan, Tamara; Schäfer, Matthias; Mariotta, Luca; Herzog, Brigitte; Huggel, Katja; Wolfer, David; Werner, Sabine; Penninger, Josef M; Verrey, François

    2012-09-15

    Mutations in the main intestinal and kidney luminal neutral amino acid transporter B(0)AT1 (Slc6a19) lead to Hartnup disorder, a condition that is characterized by neutral aminoaciduria and in some cases pellagra-like symptoms. These latter symptoms caused by low-niacin are thought to result from defective intestinal absorption of its precursor L-tryptophan. Since Ace2 is necessary for intestinal B(0)AT1 expression, we tested the impact of intestinal B(0)AT1 absence in ace2 null mice. Their weight gain following weaning was decreased, and Na(+)-dependent uptake of B(0)AT1 substrates measured in everted intestinal rings was defective. Additionally, high-affinity Na(+)-dependent transport of L-proline, presumably via SIT1 (Slc6a20), was absent, whereas glucose uptake via SGLT1 (Slc5a1) was not affected. Measurements of small intestine luminal amino acid content following gavage showed that more L-tryptophan than other B(0)AT1 substrates reach the ileum in wild-type mice, which is in line with its known lower apparent affinity. In ace2 null mice, the absorption defect was confirmed by a severalfold increase of L-tryptophan and of other neutral amino acids reaching the ileum lumen. Furthermore, plasma and muscle levels of glycine and L-tryptophan were significantly decreased in ace2 null mice, with other neutral amino acids displaying a similar trend. A low-protein/low-niacin diet challenge led to differential changes in plasma amino acid levels in both wild-type and ace2 null mice, but only in ace2 null mice to a stop in weight gain. Despite the combination of low-niacin with a low-protein diet, plasma niacin concentrations remained normal in ace2 null mice and no pellagra symptoms, such as photosensitive skin rash or ataxia, were observed. In summary, mice lacking Ace2-dependent intestinal amino acid transport display no total niacin deficiency nor clear pellagra symptoms, even under a low-protein and low-niacin diet, despite gross amino acid homeostasis alterations

  15. Null fluids: A new viewpoint of Galilean fluids

    NASA Astrophysics Data System (ADS)

    Banerjee, Nabamita; Dutta, Suvankar; Jain, Akash

    2016-05-01

    In this article, we study a Galilean fluid with a conserved U (1 ) current up to anomalies. We construct a relativistic system, which we call a null fluid and show that it is in one-to-one correspondence with a Galilean fluid living in one lower dimension. The correspondence is based on light cone reduction, which is known to reduce the Poincaré symmetry of a theory to Galilean in one lower dimension. We show that the proposed null fluid and the corresponding Galilean fluid have exactly same symmetries, thermodynamics, constitutive relations, and equilibrium partition to all orders in the derivative expansion. We also devise a mechanism to introduce U (1 ) anomaly in even dimensional Galilean theories using light cone reduction, and study its effect on the constitutive relations of a Galilean fluid.

  16. Time travel in transformation optics: Metamaterials with closed null geodesics

    NASA Astrophysics Data System (ADS)

    Boston, S. Reece

    2015-06-01

    We apply the methods of transformation optics to theoretical descriptions of spacetimes that support closed null geodesic curves. The metric used is based on frame dragging spacetimes, such as the van Stockum dust or the Kerr black hole. Through transformation optics, this metric is analogous to a material that in theory should allow for communication between past and future. Presented herein is a derivation and description of the spacetime and the resulting permeability, permittivity, and magnetoelectric couplings that a material would need in order for light in the material to follow closed null geodesics. We also address the paradoxical implications of such a material and demonstrate why such a material would not actually result in a violation of causality. A full derivation of the Plebanski equations is also included.

  17. Two new molecular bases for the Dombrock null phenotype.

    PubMed

    Rios, Maria; Storry, Jill R; Hue-Roye, Kim; Chung, Amy; Reid, Marion E

    2002-06-01

    Red blood cells (RBCs) with the Do(null) phenotype lack all antigens in the Dombrock blood group system, i.e. Do(a), Do(b), Gy(a), Hy and Jo(a). Sequence analysis of DNA from one proband with the Do(null) phenotype revealed a single nucleotide mutation of t to c in the donor splice site of DO (IVS1 + 2t > c), with outsplicing of exon 2. Analysis of a second proband revealed a homozygous nonsense mutation 442 C > T in exon 2 predicting a premature stop codon (Gln148 Stop). The molecular bases described in these two probands provide an explanation for the lack of Do glycoprotein on their RBCs. PMID:12028057

  18. Modifications of the Schwarzschild null geodesics in effective field theories

    SciTech Connect

    Ahmadi, N.

    2009-12-15

    In this paper the dynamics of Schwarzschild null geodesics in the context of low-energy effective field theories incorporating some interactions violating the equivalence principle is examined. Nonperturbed geodesics are expressed in terms of a convenient set of constants called orbital elements. The modifications introduced by the effective interactions are treated as small perturbations, then the method of variation of parameters is employed to find the evolution of the orbital elements for the true worldlines. We next focus our discussion on the geometry of nondispersive photon orbits and highlight the importance of different orbital elements in long-term change of the orbit. This calculation shows that nondispersive forces acting on null geodesics drive a secular growth of the positional elements. As an application of our results we examine the evolution of mean orbital elements in the semiclassical theory of quantum gravitational optics and show that the averaged correction terms are within the range of the uncertainty principle.

  19. Advances in corneal topography measurements with conical null-screens

    NASA Astrophysics Data System (ADS)

    Campos-García, Manuel; Cossio-Guerrero, Cesar; Huerta-Carranza, Oliver; Moreno-Oliva, Víctor I.

    2015-09-01

    In this work we report the design of a null-screen for corneal topography. To avoid the difficulties in the alignment of the test system due to the face contour (eyebrows, nose, or eyelids), we design a conical null-screen with a novel radial points distribution drawn on it in such a way that its image, which is formed by reflection on the test surface, becomes an exact array of circular spots if the surface is perfect. Additionally, an algorithm to compute the sagittal and meridional radii of curvature for the corneal surface is presented. The sagittal radius is obtained from the surface normal, and the meridional radius is calculated from a function fitted to the derivative of the sagittal curvature by using the surfacenormals raw data. Experimental results for the testing a calibration spherical surface are shown. Also, we perform some corneal topography measurements.

  20. Holographic proof of the quantum null energy condition

    NASA Astrophysics Data System (ADS)

    Koeller, Jason; Leichenauer, Stefan

    2016-07-01

    We use holography to prove the quantum null energy condition (QNEC) at leading order in large N for CFTs and relevant deformations of CFTs in Minkowski space which have Einstein gravity duals. Given any codimension-two surface Σ which is locally stationary under a null deformation in the direction k at the point p , the QNEC is a lower bound on the energy-momentum tensor at p in terms of the second variation of the entropy to one side of Σ : ⟨Tk k⟩≥S''/2 π √{h } . In a CFT, conformal transformations of this inequality give results which apply when Σ is not locally stationary. The QNEC was proven previously for free theories, and taken together with our result this provides strong evidence that the QNEC is a true statement about quantum field theory in general.

  1. A phenotypic null hypothesis for the genetics of personality.

    PubMed

    Turkheimer, Eric; Pettersson, Erik; Horn, Erin E

    2014-01-01

    We review the genetically informed literature on the genetics of personality. Over the past century, quantitative genetic studies, using identical and fraternal twins, have demonstrated that differences in human personality are substantially heritable. We focus on more contemporary questions to which that basic observation has led. We examine whether differences in the heritability of personality are replicable across different traits, samples, and studies; how the heritability of personality relates to its reliability; and how behavior genetics can be employed in studies of validity, and we discuss the stability of personality in genetic and environmental variance. The appropriate null hypothesis in behavior genetics is not that genetic or environmental influence on personality is zero. Instead, we offer a phenotypic null hypothesis, which states that genetic variance is not an independent mechanism of individual differences in personality but rather a reflection of processes that are best conceptualized at the phenotypic level. PMID:24050184

  2. Higher-dimensional evolving wormholes satisfying the null energy condition

    NASA Astrophysics Data System (ADS)

    Zangeneh, Mahdi Kord; Lobo, Francisco S. N.; Riazi, Nematollah

    2014-07-01

    In this work, we consider the possibility of expanding wormholes in higher dimensions, which is an important ingredient of modern theories of fundamental physics. An important motivation is that nontrivial topological objects such as microscopic wormholes may have been enlarged to macroscopic sizes in an expanding inflationary cosmological background. Since the Ricci scalar is only a function of time in standard cosmological models, we use this property as a simplifying assumption. More specifically, we consider a particular class of wormhole solutions corresponding to the choice of a spatially homogeneous Ricci scalar. The possibility of obtaining solutions with normal and exotic matter is explored and we find a variety of solutions including those in four dimensions that satisfy the null energy condition in specific time intervals. In particular, for five dimensions, we find solutions that satisfy the null energy condition throughout the respective evolution.

  3. Axon and muscle spindle hyperplasia in the myostatin null mouse

    PubMed Central

    Elashry, Mohamed I; Otto, Anthony; Matsakas, Antonios; El-Morsy, Salah E; Jones, Lisa; Anderson, Bethan; Patel, Ketan

    2011-01-01

    Germline deletion of the myostatin gene results in hyperplasia and hypertrophy of the tension-generating (extrafusal) fibres in skeletal muscle. As this gene is expressed predominantly in myogenic tissues it offers an excellent model with which to investigate the quantitative relationship between muscle and axonal development. Here we show that skeletal muscle hyperplasia in myostatin null mouse is accompanied by an increase in nerve fibres in major nerves of both the fore- and hindlimbs. We show that axons within these nerves undergo hypertrophy. Furthermore, we provide evidence that the age-related neural atrophic process is delayed in the absence of myostatin. Finally, we show that skeletal muscle hyperplasia in the myostatin null mouse is accompanied by an increase in the number of muscle spindles (also called stretch receptors or proprioceptors). However, our work demonstrates that the mechanisms regulating intrafusal fibre hyperplasia and hypertrophy differ from those that control the aetiology of extrafusal fibres. PMID:21208206

  4. Quantization of black hole entropy from unstable circular null geodesics

    NASA Astrophysics Data System (ADS)

    Wei, Shao-Wen; Liu, Yu-Xiao; Fu, Chun-E.

    2016-04-01

    The quasinormal mode frequencies can be understood from the massless particles trapped at the unstable circular null geodesics and slowly leaking out to infinity. Based on this viewpoint, in this paper, we semiclassically construct the entropy spectrum of the static and stationary black holes from the null geodesics. The result shows that the spacing of the entropy spectrum only depends on the property of the black hole in the eikonal limit. Moreover, for a black hole far from the extremal case, the spacing is found to be smaller than 2πħ for any dimension, which is very different from the result of the previous work by using the usual quasinormal mode frequencies.

  5. Exact Null Controllability of a Nonlinear Thermoelastic Contact Problem

    SciTech Connect

    Sivergina, Irina F. Polis, Michael P.

    2005-01-15

    We study the controllability properties of a nonlinear parabolic system that models the temperature evolution of a one-dimensional thermoelastic rod that may come into contact with a rigid obstacle. Basically the system dynamics is described by a one-dimensional nonlocal heat equation with a nonlinear and nonlocal boundary condition of Newmann type.We focus on the control problem and treat the case when the control is distributed over the whole space domain. In this case the system is proved to be exactly null controllable provided the parameters of the system are smooth.The proof is based on changing the control variable and using Aubin's Compactness Lemma to obtain an invariant set for the linearized controllability map. Then, by proving that the found solution is sufficiently smooth, we get the null controllability for the original system.

  6. Uniqueness of Kerr space-time near null infinity

    SciTech Connect

    Wu Xiaoning; Bai Shan

    2008-12-15

    We reexpress the Kerr metric in standard Bondi-Sachs coordinates near null infinity I{sup +}. Using the uniqueness result of the characteristic initial value problem, we prove the Kerr metric is the only asymptotically flat, stationary, axially symmetric, type-D solution of the vacuum Einstein equation. The Taylor series of Kerr space-time is expressed in terms of Bondi-Sachs coordinates, and the Newman-Penrose constants have been calculated.

  7. Nulling Hall-Effect Current-Measuring Circuit

    NASA Technical Reports Server (NTRS)

    Sullender, Craig C.; Vazquez, Juan M.; Berru, Robert I.

    1993-01-01

    Circuit measures electrical current via combination of Hall-effect-sensing and magnetic-field-nulling techniques. Known current generated by feedback circuit adjusted until it causes cancellation or near cancellation of magnetic field produced in toroidal ferrite core by current measured. Remaining magnetic field measured by Hall-effect sensor. Circuit puts out analog signal and digital signal proportional to current measured. Accuracy of measurement does not depend on linearity of sensing components.

  8. Somatic-cell mutation induced by short exposures to cigarette smoke in urate-null, oxidative stress-sensitive Drosophila.

    PubMed

    Uchiyama, Tomoyo; Koike, Ryota; Yuma, Yoko; Okamoto, Keinosuke; Arimoto-Kobayashi, Sakae; Suzuki, Toshinori; Negishi, Tomoe

    2016-01-01

    We previously reported that a urate-null strain of Drosophila is hypersensitive to cigarette smoke (CS), and we suggested that CS induces oxidative stress in Drosophila because uric acid is a potent antioxidant. Although the carcinogenic risk of CS exposure is widely recognized; documentation of in vivo genotoxic activity of environmental CS, especially gaseous-phase CS, remains inconclusive. To date, somatic-cell mutations in Drosophila resulting from exposure to CS have not been detected via the somatic mutation and recombination test (wing spot test) with wild-type flies, a widely used Drosophila assay for the detection of somatic-cell mutation; moreover, genotoxicity has not been documented via a DNA repair test that involves DNA repair-deficient Drosophila. In this study, we used a new Drosophila strain (y v ma-l; mwh) to examine the mutagenicity induced by gaseous-phase CS; these flies are urate-null due to a mutation in ma-l, and they are heterozygous for multiple wing hair (mwh), a mutation that functions as a marker for somatic-cell mutation. In an assay with this newly developed strain, a superoxide anion-producing weed-killer, paraquat, exhibited significant mutagenicity; in contrast, paraquat was hardly mutagenic with a wild-type strain. Drosophila larvae were exposed to CS for 2, 4 or 6h, and then kept at 25°C on instant medium until adulthood. After eclosion, mutant spots, which consisted of mutant hairs on wings, were scored. The number of mutant spots increased significantly in an exposure time-dependent manner in the urate-null females (ma-l (-/-)), but not in the urate-positive females (ma-l (+/-)). In this study, we showed that short-term exposure to CS was mutagenic in this in vivo system. In addition, we obtained suggestive data regarding reactive oxygen species production in larva after CS exposure using the fluorescence probe H2DCFDA. These results suggest that oxidative damage, which might be countered by uric acid, was partly responsible

  9. An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure.

    PubMed

    Harris, Muriel J; Juriloff, Diana M

    2010-08-01

    The number of mouse mutants and strains with neural tube defects (NTDs) now exceeds 240, including 205 representing specific genes, 30 for unidentified genes, and 9 multifactorial strains. These mutants identify genes needed for embryonic neural tube closure. Reports of 50 new NTD mutants since our 2007 review (Harris and Juriloff, 2007) were considered in relation to the previously reviewed mutants to obtain new insights into mechanisms of NTD etiology. In addition to null mutations, some are hypomorphs or conditional mutants. Some mutations do not cause NTDs on their own, but do so in digenic, trigenic, and oligogenic combinations, an etiology that likely parallels the nature of genetic etiology of human NTDs. Mutants that have only exencephaly are fourfold more frequent than those that have spina bifida aperta with or without exencephaly. Many diverse cellular functions and biochemical pathways are involved; the NTD mutants draw new attention to chromatin modification (epigenetics), the protease-activated receptor cascade, and the ciliopathies. Few mutants directly involve folate metabolism. Prevention of NTDs by maternal folate supplementation has been tested in 13 mutants and reduces NTD frequency in six diverse mutants. Inositol reduces spina bifida aperta frequency in the curly tail mutant, and three new mutants involve inositol metabolism. The many NTD mutants are the foundation for a future complete genetic understanding of the processes of neural fold elevation and fusion along mechanistically distinct cranial-caudal segments of the neural tube, and they point to several candidate processes for study in human NTD etiology. PMID:20740593

  10. Non-null annular subaperture stitching interferometry for aspheric test

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Liu, Dong; Shi, Tu; Yang, Yongying; Chong, Shiyao; Miao, Liang; Huang, Wei; Shen, Yibing; Bai, Jian

    2015-10-01

    A non-null annular subaperture stitching interferometry (NASSI), combining the subaperture stitching idea and non-null test method, is proposed for steep aspheric testing. Compared with standard annular subaperture stitching interferometry (ASSI), a partial null lens (PNL) is employed as an alternative to the transmission sphere, to generate different aspherical wavefronts as the references. The coverage subaperture number would thus be reduced greatly for the better performance of aspherical wavefronts in matching the local slope of aspheric surfaces. Instead of various mathematical stitching algorithms, a simultaneous reverse optimizing reconstruction (SROR) method based on system modeling and ray tracing is proposed for full aperture figure error reconstruction. All the subaperture measurements are simulated simultaneously with a multi-configuration model in a ray-tracing program, including the interferometric system modeling and subaperture misalignments modeling. With the multi-configuration model, full aperture figure error would be extracted in form of Zernike polynomials from subapertures wavefront data by the SROR method. This method concurrently accomplishes subaperture retrace error and misalignment correction, requiring neither complex mathematical algorithms nor subaperture overlaps. A numerical simulation exhibits the comparison of the performance of the NASSI and standard ASSI, which demonstrates the high accuracy of the NASSI in testing steep aspheric. Experimental results of NASSI are shown to be in good agreement with that of Zygo® VerifireTM Asphere interferometer.

  11. Adult sulfatide null mice maintain an increased number of oligodendrocytes

    PubMed Central

    Shroff, S; Pomicter, AD; Fox, MA; Henderson, SC; Dupree, JL

    2015-01-01

    The galactolipids galactocerebroside and sulfatide have been implicated in oligodendrocyte development and myelin formation. Much of the evidence for these galactolipid functions has been derived from antibody and chemical perturbation of cultured oligodendrocytes. Recently, we have observed abundant, unstable myelin and an increased number of oligodendrocytes in mice incapable of synthesizing the myelin galactolipids galactocerebroside and sulfatide. We have also reported that mice lacking sulfatide but that synthesize normal levels of galactocerebroside generate myelin with unstable paranodes while Hirahara et al. (2004) have shown an enhanced population of oligodendrocytes in the forebrain, medulla and cerebellum in immature sulfatide null mice. Here, we demonstrate that an increase in the number of oligodendrocytes in sulfatide null mice is not transient but is maintained through, at least, 7 months of age. Moreover, we demonstrate that the enhanced oligodendrocyte population results from, at least in part, increased cell survival. Finally, sulfatide null oligodendrocytes exhibit decreased morphological complexity, a feature which may relate to increased oligodendrocyte survival. PMID:19224580

  12. High-power, null-type, inverted pendulum thrust stand.

    PubMed

    Xu, Kunning G; Walker, Mitchell L R

    2009-05-01

    This article presents the theory and operation of a null-type, inverted pendulum thrust stand. The thrust stand design supports thrusters having a total mass up to 250 kg and measures thrust over a range of 1 mN to 5 N. The design uses a conventional inverted pendulum to increase sensitivity, coupled with a null-type feature to eliminate thrust alignment error due to deflection of thrust. The thrust stand position serves as the input to the null-circuit feedback control system and the output is the current to an electromagnetic actuator. Mechanical oscillations are actively damped with an electromagnetic damper. A closed-loop inclination system levels the stand while an active cooling system minimizes thermal effects. The thrust stand incorporates an in situ calibration rig. The thrust of a 3.4 kW Hall thruster is measured for thrust levels up to 230 mN. The uncertainty of the thrust measurements in this experiment is +/-0.6%, determined by examination of the hysteresis, drift of the zero offset and calibration slope variation. PMID:19485530

  13. Reverse optimization reconstruction method in non-null aspheric interferometry

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Liu, Dong; Shi, Tu; Yang, Yongying; Chong, Shiyao; Shen, Yibing; Bai, Jian

    2015-10-01

    Aspheric non-null test achieves more flexible measurements than the null test. However, the precision calibration for retrace error has always been difficult. A reverse optimization reconstruction (ROR) method is proposed for the retrace error calibration as well as the aspheric figure error extraction based on system modeling. An optimization function is set up with system model, in which the wavefront data from experiment is inserted as the optimization objective while the figure error under test in the model as the optimization variable. The optimization is executed by the reverse ray tracing in the system model until the test wavefront in the model is consistent with the one in experiment. At this point, the surface figure error in the model is considered to be consistent with the one in experiment. With the Zernike fitting, the aspheric surface figure error is then reconstructed in the form of Zernike polynomials. Numerical simulations verifying the high accuracy of the ROR method are presented with error considerations. A set of experiments are carried out to demonstrate the validity and repeatability of ROR method. Compared with the results of Zygo interferometer (null test), the measurement error by the ROR method achieves better than 1/10λ.

  14. Molecular basis for the catalytic inactivity of a naturally occurring near-null variant of human ALOX15.

    PubMed

    Horn, Thomas; Ivanov, Igor; Di Venere, Almerinda; Kakularam, Kumar Reddy; Reddanna, Pallu; Conrad, Melanie L; Richter, Constanze; Scheerer, Patrick; Kuhn, Hartmut

    2013-12-01

    Mammalian lipoxygenases belong to a family of lipid-peroxidizing enzymes, which have been implicated in cardiovascular, hyperproliferative and neurodegenerative diseases. Here we report that a naturally occurring mutation in the hALOX15 gene leads to expression of a catalytically near-null enzyme variant (hGly422Glu). The inactivity may be related to severe misfolding of the enzyme protein, which was concluded from CD-spectra as well as from thermal and chemical stability assays. In silico mutagenesis experiments suggest that most mutations at hGly422 have the potential to induce sterical clash, which might be considered a reason for protein misfolding. hGly422 is conserved among ALOX5, ALOX12 and ALOX15 isoforms and corresponding hALOX12 and hALOX5 mutants also exhibited a reduced catalytic activity. Interestingly, in the hALOX5 Gly429Glu mutants the reaction specificity of arachidonic acid oxygenation was shifted from 5S- to 8S- and 12R-H(p)ETE formation. Taken together, our data indicate that the conserved glycine is of functional importance for these enzyme variants and most mutants at this position lose catalytic activity. PMID:23958500

  15. Variational principle for gravity with null and non-null boundaries: a unified boundary counter-term

    NASA Astrophysics Data System (ADS)

    Parattu, Krishnamohan; Chakraborty, Sumanta; Padmanabhan, T.

    2016-03-01

    It is common knowledge that the Einstein-Hilbert action does not furnish a well-posed variational principle. The usual solution to this problem is to add an extra boundary term to the action, called a counter-term, so that the variational principle becomes well-posed. When the boundary is spacelike or timelike, the Gibbons-Hawking-York counter-term is the most widely used. For null boundaries, we had proposed a counter-term in a previous paper. In this paper, we extend the previous analysis and propose a counter-term that can be used to eliminate variations of the "off-the-surface" derivatives of the metric on any boundary, regardless of its spacelike, timelike or null nature.

  16. ECB deacylase mutants

    DOEpatents

    Arnold, Frances H.; Shao, Zhixin; Zhao, Huimin; Giver, Lorraine J.

    2002-01-01

    A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

  17. Pla2g16 phospholipase mediates gain-of-function activities of mutant p53.

    PubMed

    Xiong, Shunbin; Tu, Huolin; Kollareddy, Madhusudhan; Pant, Vinod; Li, Qin; Zhang, Yun; Jackson, James G; Suh, Young-Ah; Elizondo-Fraire, Ana C; Yang, Peirong; Chau, Gilda; Tashakori, Mehrnoosh; Wasylishen, Amanda R; Ju, Zhenlin; Solomon, Hilla; Rotter, Varda; Liu, Bin; El-Naggar, Adel K; Donehower, Lawrence A; Martinez, Luis Alfonso; Lozano, Guillermina

    2014-07-29

    p53(R172H/+) mice inherit a p53 mutation found in Li-Fraumeni syndrome and develop metastatic tumors at much higher frequency than p53(+/-) mice. To explore the mutant p53 metastatic phenotype, we used expression arrays to compare primary osteosarcomas from p53(R172H/+) mice with metastasis to osteosarcomas from p53(+/-) mice lacking metastasis. For this study, 213 genes were differentially expressed with a P value <0.05. Of particular interest, Pla2g16, which encodes a phospholipase that catalyzes phosphatidic acid into lysophosphatidic acid and free fatty acid (both implicated in metastasis), was increased in p53(R172H/+) osteosarcomas. Functional analyses showed that Pla2g16 knockdown decreased migration and invasion in mutant p53-expressing cells, and vice versa: overexpression of Pla2g16 increased the invasion of p53-null cells. Furthermore, Pla2g16 levels were increased upon expression of mutant p53 in both mouse and human osteosarcoma cell lines, indicating that Pla2g16 is a downstream target of the mutant p53 protein. ChIP analysis revealed that several mutant p53 proteins bind the Pla2g16 promoter at E26 transformation-specific (ETS) binding motifs and knockdown of ETS2 suppressed mutant p53 induction of Pla2g16. Thus, our study identifies a phospholipase as a transcriptional target of mutant p53 that is required for metastasis. PMID:25024203

  18. Null controllable region of delta operator systems subject to actuator saturation

    NASA Astrophysics Data System (ADS)

    Yang, Hongjiu; Yan, Ce; Xia, Yuanqing; Zhang, Jinhui

    2016-07-01

    In this paper, we give exact description of null controllable regions for delta operator systems subject to actuator saturation. The null controllable region is in terms of a set of extremal trajectories of anti-stable subsystems. For the delta operator system with real eigenvalues or complex eigenvalues, the description is simplified to an explicit formula which is used to characterise the boundary of a null controllable region. The relations of null controllable regions are shown separately for continuous-time systems, discrete-time systems and delta operator systems. Two numerical examples are given to illustrate the effectiveness of the proposed techniques on null controllable regions.

  19. Decreased virus population diversity in p53-null mice infected with weakly oncogenic Abelson virus.

    PubMed

    Marchlik, Erica; Kalman, Richard; Rosenberg, Naomi

    2005-09-01

    The Abelson murine leukemia virus (Ab-MLV), like other retroviruses that contain v-onc genes, arose following a recombination event between a replicating retrovirus and a cellular oncogene. Although experimentally validated models have been presented to address the mechanism by which oncogene capture occurs, very little is known about the events that influence emerging viruses following the recombination event that incorporates the cellular sequences. One feature that may play a role is the genetic makeup of the host in which the virus arises; a number of host genes, including oncogenes and tumor suppressor genes, have been shown to affect the pathogenesis of many murine leukemia viruses. To examine how a host gene might affect an emerging v-onc gene-containing retrovirus, we studied the weakly oncogenic Ab-MLV-P90A strain, a mutant that generates highly oncogenic variants in vivo, and compared the viral populations in normal mice and mice lacking the p53 tumor suppressor gene. While variants arose in both p53+/+ and p53-/- tumors, the samples from the wild-type animals contained a more diverse virus population. Differences in virus population diversity were not observed when wild-type and null animals were infected with a highly oncogenic wild-type strain of Ab-MLV. These results indicate that p53, and presumably other host genes, affects the selective forces that operate on virus populations in vivo and likely influences the evolution of oncogenic retroviruses such as Ab-MLV. PMID:16140739

  20. Lack of Major Genome Instability in Tumors of p53 Null Rats

    PubMed Central

    Hermsen, Roel; Toonen, Pim; Kuijk, Ewart; Youssef, Sameh A.; Kuiper, Raoul; van Heesch, Sebastiaan; de Bruin, Alain; Cuppen, Edwin; Simonis, Marieke

    2015-01-01

    Tumorigenesis is often associated with loss of tumor suppressor genes (such as TP53), genomic instability and telomere lengthening. Previously, we generated and characterized a rat p53 knockout model in which the homozygous rats predominantly develop hemangiosarcomas whereas the heterozygous rats mainly develop osteosarcomas. Using genome-wide analyses, we find that the tumors that arise in the heterozygous and homozygous Tp53C273X mutant animals are also different in their genomic instability profiles. While p53 was fully inactivated in both heterozygous and homozygous knockout rats, tumors from homozygous animals show very limited aneuploidy and low degrees of somatic copy number variation as compared to the tumors from heterozygous animals. In addition, complex structural rearrangements such as chromothripsis and breakage-fusion-bridge cycles were never found in tumors from homozygous animals, while these were readily detectable in tumors from heterozygous animals. Finally, we measured telomere length and telomere lengthening pathway activity and found that tumors of homozygous animals have longer telomeres but do not show clear telomerase or alternative lengthening of telomeres (ALT) activity differences as compared to the tumors from heterozygous animals. Taken together, our results demonstrate that host p53 status in this rat p53 knockout model has a large effect on both tumor type and genomic instability characteristics, where full loss of functional p53 is not the main driver of large-scale structural variations. Our results also suggest that chromothripsis primarily occurs under p53 heterozygous rather than p53 null conditions. PMID:25811670

  1. EGFRvIII and c-Met pathway inhibitors synergize against PTEN-null/EGFRvIII+ glioblastoma xenografts

    PubMed Central

    Lal, Bachchu; Goodwin, Courtney R.; Sang, Yingying; Foss, Catherine A.; Cornet, Kathrine; Muzamil, Sameena; Pomper, Martin G.; Kim, Jin; Laterra, John

    2010-01-01

    Receptor tyrosine kinase (RTK) systems, such as hepatocyte growth factor (HGF) and its receptor c-Met, and EGFR, are responsible for the malignant progression of multiple solid tumors. Recent research shows that these RTK systems co-modulate overlapping and dynamically adaptable oncogenic downstream signaling pathways. This paper investigates how EGFRvIII, a constitutively active EGFR deletion mutant, alters tumor growth and signaling responses to RTK inhibition in PTEN-null/HGF+/c-Met+ glioma xenografts. We show that a neutralizing anti-HGF mAb (L2G7) potently inhibits tumor growth and the activation of Akt and MAPK in PTEN-null/HGF+/c-Met+/EGFRvIII−U87 glioma xenografts (U87wt). Isogenic EGFRvIII+ U87 xenografts (U87-EGFRvIII), which grew 5-times more rapidly than U87-wt xenografts, were unresponsive to EGFRvIII inhibition by erlotinib and were only minimally responsive to anti-HGF mAb. EGFRvIII-expression diminished the magnitude of Akt inhibition and completely prevented MAPK inhibition by L2G7. Despite the lack of response to L2G7 or erlotinib as single agents, their combination synergized to produce substantial anti-tumor effects (inhibited tumor cell proliferation, enhanced apoptosis, arrested tumor growth, prolonged animal survival), against subcutaneous and orthotopic U87-EGFRvIII xenografts. The dramatic response to combining HGF:c-Met and EGFRvIII pathway inhibitors in U87-EGFRvIII xenografts occurred in the absence of Akt and MAPK inhibition. These findings show that combining c-Met and EGFRvIII pathway inhibitors can generate potent anti-tumor effects in PTEN-null tumors. They also provide insights into how EGFRvIII and c-Met may alter signaling networks and reveal the potential limitations of certain biochemical biomarkers to predict the efficacy of RTK inhibition in genetically diverse cancers. PMID:19584231

  2. Genetic analysis of salt-tolerant mutants in Arabidopsis thaliana.

    PubMed Central

    Quesada, V; Ponce, M R; Micol, J L

    2000-01-01

    Stress caused by the increased salinity of irrigated fields impairs plant growth and is one of the major constraints that limits crop productivity in many important agricultural areas. As a contribution to solving such agronomic problems, we have carried out a large-scale screening for Arabidopsis thaliana mutants induced on different genetic backgrounds by EMS treatment, fast neutron bombardment, or T-DNA insertions. From the 675,500 seeds we screened, 17 mutant lines were isolated, all but one of which yielded 25-70% germination levels on 250 mm NaCl medium, a condition in which their ancestor ecotypes are unable to germinate. Monogenic recessive inheritance of NaCl-tolerant germination was displayed with incomplete penetrance by all the selected mutants, which fell into five complementation groups. These were named SALOBRENO (SAN) and mapped relative to polymorphic microsatellites, the map positions of three of them suggesting that they are novel genes. Strains carrying mutations in the SAN1-SAN4 genes display similar responses to both ionic effects and osmotic pressure, their germination being NaCl and mannitol tolerant but KCl and Na(2)SO(4) sensitive. In addition, NaCl-, KCl-, and mannitol-tolerant as well as abscisic-acid-insensitive germination was displayed by sañ5, whose genetic and molecular characterization indicates that it carries an extremely hypomorphic or null allele of the ABI4 gene, its deduced protein product lacking the APETALA2 DNA binding domain. PMID:10629000

  3. Defects in Hemopoietic Stem Cell Activity in Ikaros Mutant Mice

    PubMed Central

    Nichogiannopoulou, Aliki; Trevisan, Maryanne; Neben, Steve; Friedrich, Christoph; Georgopoulos, Katia

    1999-01-01

    Here we provide evidence that the Ikaros family of DNA binding factors is critical for the activity of hemopoietic stem cells (HSCs) in the mouse. Mice homozygous for an Ikaros null mutation display a >30-fold reduction in long-term repopulation units, whereas mice homozygous for an Ikaros dominant negative mutation have no measurable activity. The defect in HSC activity is also illustrated by the ability of wild-type marrow to repopulate unconditioned Ikaros mutants. A progressive reduction in multipotent CFU-S14 (colony-forming unit-spleen) progenitors and the earliest erythroid-restricted precursors (BFU-E [burst-forming unit-erythroid]) is also detected in the Ikaros mutant strains consistent with the reduction in HSCs. Nonetheless, the more mature clonogenic erythroid and myeloid precursors are less affected, indicating either the action of a compensatory mechanism to provide more progeny or a negative role of Ikaros at later stages of erythromyeloid differentiation. In Ikaros mutant mice, a decrease in expression of the tyrosine kinase receptors flk-2 and c-kit is observed in the lineage-depleted c-kit+Sca-1+ population that is normally enriched for HSCs and may in part contribute to the early hemopoietic phenotypes manifested in the absence of Ikaros. PMID:10544193

  4. Genes and Alcohol Consumption: Studies with Mutant Mice.

    PubMed

    Mayfield, J; Arends, M A; Harris, R A; Blednov, Y A

    2016-01-01

    In this chapter, we review the effects of global null mutant and overexpressing transgenic mouse lines on voluntary self-administration of alcohol. We examine approximately 200 publications pertaining to the effects of 155 mouse genes on alcohol consumption in different drinking models. The targeted genes vary in function and include neurotransmitter, ion channel, neuroimmune, and neuropeptide signaling systems. The alcohol self-administration models include operant conditioning, two- and four-bottle choice continuous and intermittent access, drinking in the dark limited access, chronic intermittent ethanol, and scheduled high alcohol consumption tests. Comparisons of different drinking models using the same mutant mice are potentially the most informative, and we will highlight those examples. More mutants have been tested for continuous two-bottle choice consumption than any other test; of the 137 mouse genes examined using this model, 97 (72%) altered drinking in at least one sex. Overall, the effects of genetic manipulations on alcohol drinking often depend on the sex of the mice, alcohol concentration and time of access, genetic background, as well as the drinking test. PMID:27055617

  5. Characterization of a compensatory mutant of Leishmania major that lacks ether lipids but exhibits normal growth, and G418 and hygromycin resistance.

    PubMed

    Zufferey, Rachel; Bibis, Stergios S; Zhu, Tongtong; Dhalladoo, Subbhalakshmi

    2012-03-01

    Ether glycerolipid biosynthesis in Leishmania major initiates with the acylation of dihydroxyacetonephosphate by the glycosomal dihydroxyacetonephosphate acyltransferase LmDAT. We previously reported that a null mutant of LmDAT is severely affected in logarithmic growth, survival during stationary phase, and in virulence in mice. In addition, it lacks all ether glycerolipids, produces altered forms of the ether-lipid based virulence factors lipophosphoglycan and increased levels of GPI-anchored protein gp63. Here, we describe the characterization of a compensatory mutant of a null strain of LmDAT, Δlmdat/Δlmdat(rev). Similarly to the null mutant, the Δlmdat/Δlmdat(rev) strain formed altered forms of lipophosphoglycan and increased levels of gp63, and was avirulent in mice infection. Further, dihydroxyacetonephosphate acyltransferase activity was absent in the revertant clone, indicating that a mutation in another acyltransferase gene did not confer dihydroxyacetonephosphate specificity. In contrast, the revertant grew normally but still exhibited poor survival during stationary phase. In addition, agarose gel analysis of its genomic DNA failed to detect any amplified DNA. Surprisingly, its sensitivity to aminoglycoside based antibiotics G418 and hygromycin was lower than that of the null mutant, wild type and complemented line. PMID:22306069

  6. Fibronectin induction abrogates the BRAF inhibitor response of BRAF V600E/PTEN-null melanoma cells

    PubMed Central

    Fedorenko, Inna V.; Abel, Ethan V.; Koomen, John M.; Fang, Bin; Wood, Elizabeth R.; Chen, Y. Ann; Fisher, Kate J.; Iyengar, Sanjana; Dahlman, Kimberly B.; Wargo, Jennifer A.; Flaherty, Keith T.; Sosman, Jeffrey A.; Sondak, Vernon K.; Messina, Jane L.; Gibney, Geoffrey T.; Smalley, Keiran S.M.

    2015-01-01

    The mechanisms by which some melanoma cells adapt to BRAF inhibitor therapy are incompletely understood. In the present study, we used mass spectrometry-based phosphoproteomics to determine how BRAF inhibition remodeled the signaling network of melanoma cell lines that were BRAF-mutant and PTEN-null. Short-term BRAF inhibition was associated with marked changes in fibronectin-based adhesion signaling that were PTEN-dependent. These effects were recapitulated through BRAF siRNA knockdown and following treatment with chemotherapeutic drugs. Increased fibronectin expression was also observed in mouse xenograft models as well as specimens from melanoma patients undergoing BRAF inhibitor treatment. Analysis of a melanoma TMA showed loss of PTEN expression to predict for a lower overall survival, with a trend for even lower survival being seen when loss of fibronectin was included in the analysis. Mechanistically, the induction of fibronectin limited the responses of these PTEN-null melanoma cell lines to vemurafenib, with enhanced cytotoxicity observed following the knockdown of either fibronectin or its receptor α5β1 integrin. This in turn abrogated the cytotoxic response to BRAF inhibition via increased AKT signaling, which prevented the induction of cell death by maintaining the expression of the pro-survival protein Mcl-1. The protection conveyed by the induction of fibronectin expression could be overcome through combined treatment with a BRAF and PI3K inhibitor. PMID:26073081

  7. Fibronectin induction abrogates the BRAF inhibitor response of BRAF V600E/PTEN-null melanoma cells.

    PubMed

    Fedorenko, I V; Abel, E V; Koomen, J M; Fang, B; Wood, E R; Chen, Y A; Fisher, K J; Iyengar, S; Dahlman, K B; Wargo, J A; Flaherty, K T; Sosman, J A; Sondak, V K; Messina, J L; Gibney, G T; Smalley, K S M

    2016-03-10

    The mechanisms by which some melanoma cells adapt to Serine/threonine-protein kinase B-Raf (BRAF) inhibitor therapy are incompletely understood. In the present study, we used mass spectrometry-based phosphoproteomics to determine how BRAF inhibition remodeled the signaling network of melanoma cell lines that were BRAF mutant and PTEN null. Short-term BRAF inhibition was associated with marked changes in fibronectin-based adhesion signaling that were PTEN dependent. These effects were recapitulated through BRAF siRNA knockdown and following treatment with chemotherapeutic drugs. Increased fibronectin expression was also observed in mouse xenograft models as well as specimens from melanoma patients undergoing BRAF inhibitor treatment. Analysis of a melanoma tissue microarray showed loss of PTEN expression to predict for a lower overall survival, with a trend for even lower survival being seen when loss of fibronectin was included in the analysis. Mechanistically, the induction of fibronectin limited the responses of these PTEN-null melanoma cell lines to vemurafenib, with enhanced cytotoxicity observed following the knockdown of either fibronectin or its receptor α5β1 integrin. This in turn abrogated the cytotoxic response to BRAF inhibition via increased AKT signaling, which prevented the induction of cell death by maintaining the expression of the pro-survival protein Mcl-1. The protection conveyed by the induction of FN expression could be overcome through combined treatment with a BRAF and PI3K inhibitor. PMID:26073081

  8. Increased lipolysis and altered lipid homeostasis protect y-synuclein null mutant mice from diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. In neurons a-synuclein promotes assembly of SNARE complexes required for fusion of synaptic vesicles with the plasma membrane during neurotransmitter release. Y-synuclein is highly expressed ...

  9. Broadband Achromatic Phase Shifter for a Nulling Interferometer

    NASA Technical Reports Server (NTRS)

    Bolcar, Matthew R.; Lyon, Richard G.

    2011-01-01

    Nulling interferometry is a technique for imaging exoplanets in which light from the parent star is suppressed using destructive interference. Light from the star is divided into two beams and a phase shift of radians is introduced into one of the beams. When the beams are recombined, they destructively interfere to produce a deep null. For monochromatic light, this is implemented by introducing an optical path difference (OPD) between the two beams equal to lambda/2, where lambda is the wavelength of the light. For broadband light, however, a different phase shift will be introduced at each wavelength and the two beams will not effectively null when recombined. Various techniques have been devised to introduce an achromatic phase shift a phase shift that is uniform across a particular bandwidth. One popular technique is to use a series of dispersive elements to introduce a wavelength-dependent optical path in one or both of the arms of the interferometer. By intelligently choosing the number, material and thickness of a series of glass plates, a nearly uniform, arbitrary phase shift can be introduced between two arms of an interferometer. There are several constraints that make choosing the number, type, and thickness of materials a difficult problem, such as the size of the bandwidth to be nulled. Several solutions have been found for bandwidths on the order of 20 to 30 percent (Delta(lambda)/lambda(sub c)) in the mid-infrared region. However, uniform phase shifts over a larger bandwidth in the visible regime between 480 to 960 nm (67 percent) remain difficult to obtain at the tolerances necessary for exoplanet detection. A configuration of 10 dispersive glass plates was developed to be used as an achromatic phase shifter in nulling interferometry. Five glass plates were placed in each arm of the interferometer and an additional vacuum distance was also included in the second arm of the interferometer. This configuration creates a phase shift of pi radians with

  10. Progranulin null mutations in both sporadic and familial frontotemporal dementia.

    PubMed

    Le Ber, Isabelle; van der Zee, Julie; Hannequin, Didier; Gijselinck, Ilse; Campion, Dominique; Puel, Michèle; Laquerrière, Annie; De Pooter, Tim; Camuzat, Agnès; Van den Broeck, Marleen; Dubois, Bruno; Sellal, François; Lacomblez, Lucette; Vercelletto, Martine; Thomas-Antérion, Catherine; Michel, Bernard-François; Golfier, Véronique; Didic, Mira; Salachas, François; Duyckaerts, Charles; Cruts, Marc; Verpillat, Patrice; Van Broeckhoven, Christine; Brice, Alexis

    2007-09-01

    Frontotemporal dementia (FTD) is the second most frequent type of neurodegenerative dementias. Mutations in the progranulin gene (GRN, PGRN) were recently identified in FTDU-17, an FTD subtype characterized by ubiquitin-immunoreactive inclusions and linkage to chromosome 17q21. We looked for PGRN mutations in a large series of 210 FTD patients (52 familial, 158 sporadic) to accurately evaluate the frequency of PGRN mutations in both sporadic and familial FTD, and FTD with associated motoneuron disease (FTD-MND), as well as to study the clinical phenotype of patients with a PGRN mutation. We identified nine novel PGRN null mutations in 10 index patients. The relative frequency of PGRN null mutations in FTD was 4.8% (10/210) and 12.8% (5/39) in pure familial forms. Interestingly, 5/158 (3.2%) apparently sporadic FTD patients carried a PGRN mutation, suggesting the possibility of de novo mutations or incomplete penetrance. In contrast, none of the 43 patients with FTD-MND had PGRN mutations, supporting that FTDU-17 and FTD-MND are genetically distinct. The clinical phenotype of PGRN mutation carriers was particular because of the wide range in onset age and the frequent occurrence of early apraxia (50%), visual hallucinations (30%), and parkinsonism (30%) during the course of the disease. This study supports that PGRN null mutations represent a more frequent cause of FTD than MAPT mutations (4.8% vs. 2.9%) but are not responsible for FTD-MND. It also demonstrates that half of the patients with a PGRN mutation in our series had no apparent family history of dementia. Taking this into account, genetic testing should be now considered more systematically, even in patients without obvious familial history of FTD. PMID:17436289

  11. Vacuum Nuller Testbed Performance, Characterization and Null Control

    NASA Technical Reports Server (NTRS)

    Lyon, R. G.; Clampin, M.; Petrone, P.; Mallik, U.; Madison, T.; Bolcar, M.; Noecker, C.; Kendrick, S.; Helmbrecht, M. A.

    2011-01-01

    The Visible Nulling Coronagraph (VNC) can detect and characterize exoplanets with filled, segmented and sparse aperture telescopes, thereby spanning the choice of future internal coronagraph exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has developed a Vacuum Nuller Testbed (VNT) to advance this approach, and assess and advance technologies needed to realize a VNC as a flight instrument. The VNT is an ultra-stable testbed operating at 15 Hz in vacuum. It consists of a MachZehnder nulling interferometer; modified with a "W" configuration to accommodate a hexpacked MEMS based deformable mirror (DM), coherent fiber bundle and achromatic phase shifters. The 2-output channels are imaged with a vacuum photon counting camera and conventional camera. Error-sensing and feedback to DM and delay line with control algorithms are implemented in a real-time architecture. The inherent advantage of the VNC is that it is its own interferometer and directly controls its errors by exploiting images from bright and dark channels simultaneously. Conservation of energy requires the sum total of the photon counts be conserved independent of the VNC state. Thus sensing and control bandwidth is limited by the target stars throughput, with the net effect that the higher bandwidth offloads stressing stability tolerances within the telescope. We report our recent progress with the VNT towards achieving an incremental sequence of contrast milestones of 10(exp 8) , 10(exp 9) and 10(exp 10) respectively at inner working angles approaching 2A/D. Discussed will be the optics, lab results, technologies, and null control. Shown will be evidence that the milestones have been achieved.

  12. TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts

    PubMed Central

    Kucab, Jill E.; van Steeg, Harry; Luijten, Mirjam; Schmeiser, Heinz H.; White, Paul A.; Phillips, David H.; Arlt, Volker M.

    2015-01-01

    Somatic mutations in the tumour suppressor gene TP53 occur in more than 50% of human tumours; in some instances exposure to environmental carcinogens can be linked to characteristic mutational signatures. The Hupki (human TP53 knock-in) mouse embryo fibroblast (HUF) immortalization assay (HIMA) is a useful model for studying the impact of environmental carcinogens on TP53 mutagenesis. In an effort to increase the frequency of TP53-mutated clones achievable in the HIMA, we generated nucleotide excision repair (NER)-deficient HUFs by crossing the Hupki mouse with an Xpa-knockout (Xpa-Null) mouse. We hypothesized that carcinogen-induced DNA adducts would persist in the TP53 sequence of Xpa-Null HUFs leading to an increased propensity for mismatched base pairing and mutation during replication of adducted DNA. We found that Xpa-Null Hupki mice, and HUFs derived from them, were more sensitive to the environmental carcinogen benzo[a]pyrene (BaP) than their wild-type (Xpa-WT) counterparts. Following treatment with the reactive metabolite of BaP, benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), Xpa-WT and Xpa-Null HUF cultures were subjected to the HIMA. A significant increase in TP53 mutations on the transcribed strand was detected in Xpa-Null HUFs compared to Xpa-WT HUFs, but the TP53-mutant frequency overall was not significantly different between the two genotypes. BPDE induced mutations primarily at G:C base pairs, with approximately half occurring at CpG sites, and the predominant mutation type was G:C > T:A in both Xpa-WT and Xpa-Null cells. Further, several of the TP53 mutation hotspots identified in smokers’ lung cancer were mutated by BPDE in HUFs (codons 157, 158, 245, 248, 249, 273). Therefore, the pattern and spectrum of BPDE-induced TP53 mutations in the HIMA are consistent with TP53 mutations detected in lung tumours of smokers. While Xpa-Null HUFs exhibited increased sensitivity to BPDE-induced damage on the transcribed strand, NER-deficiency did not

  13. Null controllability in a fluid-solid structure model

    NASA Astrophysics Data System (ADS)

    Raymond, J.-P.; Vanninathan, M.

    We consider a system coupling the Stokes equations in a two-dimensional domain with a structure equation which is a system of ordinary differential equations corresponding to a finite dimensional approximation of equations modeling deformations of an elastic body or vibrations of a rigid body. For that system we establish a null controllability result for localized distributed controls acting only in the fluid equations and there is no control in the solid part. This controllability result follows from a Carleman inequality that we prove for the adjoint system.

  14. Optical fiber null coupler sensor for damage detection using ultrasonic

    NASA Astrophysics Data System (ADS)

    Xuan, HaiFeng; Liao, Yanbiao; Zhang, Ming; Lai, Shu R.

    2005-02-01

    A novel optical fiber null coupler (OFNC) sensor based on acousto-optic interaction is developed, which can be used in the structure health monitoring of the medical materials. The OFNC sensors can be response to 10MHz supersonic wave, and their signal-to noise ratio are higher then Piezo Ceramic Transducers(PZT). A kind of Perspex with a 1mm hole is employed as the sample, where the OFNC sensor is glued on, and the reflected signal of ultrasonic wave by the hole is detected .

  15. Novel aspects of COP9 signalosome functions revealed through analysis of hypomorphic csn mutants

    PubMed Central

    Parker, Jane E

    2009-01-01

    The COP9 signalosome (CSN) is a conserved eukaryotic protein complex implicated in the regulation of cullin-RING type E3 ubiquitin ligases by cleaving the small peptide RUB/Nedd8 from cullins. However, detailed analysis of CSN physiological functions in Arabidopsis has been hampered by the early seedling-lethality of csn null mutants. We and others have now identified a number of viable hypomorphic csn mutants which start to reveal novel CSN-dependent activities in adult Arabidopsis plants.1 Here, we present a detailed comparative analysis of the csn5a-1 and csn2-5 mutants as a mean to improve understanding of CSN functions in plant cells. Our observations point to CSN-independent activities of CSN5 and suggest a role of the CSN in cytoskeleton assembly/organization. PMID:19847120

  16. Reexamination of alcohol dehydrogenase structural mutants in Drosophila using protein blotting

    SciTech Connect

    Hollocher, H.; Place, A.R.

    1987-06-01

    Using protein blotting and an immuno-overlay procedure, the authors have reexamined the cross-reacting material produced by ADH null-activity mutants generated with ethyl methanesulfonate (EMS). Of the 13 mutants, 11 have an immunodetectable polypeptide of wild-type size. The native and urea denatured isoelectric points (pI) establish that 7 of 13 of the mutations have no effect on protein charge. The electrophoretic mobilities of each variant on increasing percent acrylamide gels (Ferguson analysis), reveal that 9 of the 11 immunodetectable mutations have retained the ability form dimers under native conditions. None of the inactive mutant proteins has the ability to form the adduct-bound isozyme. The authors have found no correlation between protein pI and i vivo stability. The observed frequencies of specific charge class alterations do not dispute the propensity of G:A transitions previously found for EMS mutagenesis.

  17. Fast and Efficient Screening for Wheat Loss-of-Gene Mutants Using Multiplexed Melt Curve Analyses

    PubMed Central

    Mieog, Jos C.; Ral, Jean-Philippe F.

    2016-01-01

    This study describes a new approach in the screening for loss-of-gene mutants in Heavy Ion Bombardment (HIB) mutant populations of genetically complex organisms such as hexaploid bread wheat using multiplexed single-color (SYBR Green) melt curve analyses. The assay was set up for three target genes to test its validity and applicability. For each gene, three genome-specific primer pairs (one for each genome) with distinct melt curves were developed and multiplexed. This allowed screening for “single null mutants” (plants with the target gene deleted in one of the three genomes) for all three genomes in a single reaction. The first two genes (α-Amylase 3 and Epsilon Cyclase) were used to test the approach as HIB null lines for all three genomes were already available for these. The third assay was successfully applied to identify new single null lines of the target gene α-Amylase 2 in an in-house HIB wheat collection. The use of SYBR Green greatly reduced the time and/or cost investment compared to other techniques and the approach proved highly suitable for high-throughput applications. PMID:27459606

  18. Extrasolar Planetary Imaging Coronagraph: Visible Nulling Coronagraph Testbed Results

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.

    2008-01-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC will provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 3-year mission lifetime ( 5 year goal) and will revisit planets at least three times at intervals of 9 months. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables high order starlight suppression in broadband light. To demonstrate the VNC approach and advance it's technology readiness the NASA Goddard Space Flight Center and Lockheed-Martin have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed,

  19. Generation of mice with a conditional Lbh null allele.

    PubMed

    Lindley, Linsey E; Briegel, Karoline J

    2013-07-01

    Limb bud and heart (LBH) is a developmentally expressed, tissue-specific transcription cofactor in vertebrates that acts in the WNT signaling pathway, a genetic program critical for embryogenesis and adult tissue homeostasis. Aberrant gain-of-function of LBH is implicated in both human congenital disease and cancer. The normal physiological function of LBH has remained elusive owing to a lack of genetic loss-of-function models. Here, we have generated mice with a conditional null allele of Lbh by flanking exon 2 with loxP sites (Lbh(flox)). Homozygous Lbh(flox) and Lbh(loxP) mice, in which the Neo cassette was removed through FLPe-mediated recombination, were viable and fertile, indicating that these conditional Lbh alleles are fully functional. Lbh(loxP) mice were then crossed with a Rosa26-Cre line, resulting in ubiquitous deletion of exon 2 and abolishment of LBH protein expression. Mice homozygous for the Lbh null allele (Lbh(Δ)(2)) displayed normal embryonic development and postnatal growth with morphologies indistinguishable from wild-type littermates. However, mammary gland development, which occurs primarily after birth, was perturbed. Thus, the conditional Lbh allele will be a valuable tool to uncover the currently unknown tissue-specific roles of LBH in postnatal development and disease. PMID:23495064

  20. Conceptual design of the ALADDIN Antarctic nulling interferometer

    NASA Astrophysics Data System (ADS)

    Barillot, Marc; Courteau, Pascal; Absil, Olivier; Coudé du Foresto, Vincent; Swain, Mark

    2006-06-01

    It is commonly accepted that highly challenging planet finding missions such as Darwin and TPF need precursors on the ground, for both technological demonstration and study of the exozodiacal clouds around potential targets. A first instrument, GENIE, designed to be implemented in the interferometric laboratory of the VLTI, was studied by ESA and scientific/industrial teams. In this paper we present a concept for ALADDIN, an operational nulling instrument to be implemented at Dome C in Antarctica, and discuss the comparison with GENIE from the instrumental point of view. Our preliminary design involves moderate ~1m size telescopes mounted on a 40m long rotating beam allowing baselines up to 30m and feeding a 2-arm nulling beam combiner. When compared to GENIE, the rotating beam design has the advantage of removing the need for both long-stroke delay line and dispersion control equipments. As a side effect, the instrumental arrangement of ALADDIN finds itself more representative of what Darwin will be. Furthermore, critical issues like phase control, photometric balance and instrumental background suppression are expected to be relaxed by the improved atmospheric conditions, lower temperature, and simpler optical trains. Calibration of geometrical stellar leakage will make advantage of the continuously adjustable baseline. As results, a simpler instrument showing improved performance is expected. In conclusion, we see our ALADDIN concept as a valuable alternative to GENIE, with a quite stronger scientific potential and a considerably simplified instrumental design.

  1. Osteoclast differentiation and function in aquaglyceroporin AQP9 null mice

    PubMed Central

    Liu, Yangjian; Song, Linhua; Wang, Yiding; Rojek, Aleksandra; Nielsen, Søren; Agre, Peter; Carbrey, Jennifer M.

    2008-01-01

    Background Information Osteoclasts are cells specialized for bone resorption and play important roles in bone growth and calcium homeostasis. Differentiation of osteoclasts involves fusion of bone marrow macrophage mononuclear precursors in response to extracellular signals. A dramatic increase in osteoclast cell volume occurs during osteoclast biogenesis and is believed to be mediated by Aquaporin 9 (AQP9), a membrane protein that can rapidly transport water and other small neutral solutes across cell membranes. Results Here we report an increase in expression of AQP9 during differentiation of a mouse macrophage cell line into osteoclasts. Bone marrow macrophages from wild type and AQP9 null mice differentiate into osteoclasts that have similar morphology, contain comparable numbers of nuclei, and digest synthetic bone to the same extent. Bones from wild type and AQP9 null mice contain similar numbers of osteoclasts and have comparable density and structure as measured by X-ray absorptiometry and micro-computed tomography. Conclusions Our data confirm that AQP9 expression rises during osteoclast biogenesis but indicate that AQP9 is not essential for osteoclast function or differentiation under normal physiological conditions. PMID:18666888

  2. Exoplanet detection and characterization via parallel broadband nulling coronagraphy

    NASA Astrophysics Data System (ADS)

    Hicks, Brian A.

    2016-01-01

    The contrast and angular resolution required to directly image and characterize mature exoplanetary systems place stringent requirements on the space-based telescopes and starlight suppression systems needed to study spatial distributions of debris disks, exozodiacal dust, and individual planets at multiple epochs in their orbits. A nulling interferometer (nuller) is a coronagraphic suppression system that can be used with all telescope types, including those with obscured and segmented apertures envisioned for upcoming and future observatories. One of the challenges for detection and characterization of exoplanetary signals is achieving high contrast with broad spectral coverage. This work presents design concepts for broadband nulling over four parallel ˜20% bandpasses spanning the visible spectrum. Contrast-limiting effects of stellar angular extent, residual chromaticity of broadband phase shifters, and aperture diffraction are considered to reach simultaneous ≲2×10-8 contrast over separations spanning 0.2 to 0.9 arc sec for a 2.4-m telescope observing a Sun-like star at 10 pc. With added dark hole wavefront control and postprocessing point spread function subtraction techniques to further reduce scattered starlight, such a system could be capable of detecting the very the nearest Earth-like exoplanets and spectral characterization of several nearby extrasolar gas giants.

  3. Adaptive Nulling: A New Enabling Technology for Interferometric Exoplanet

    NASA Technical Reports Server (NTRS)

    Lay, Oliver P.; Jeganathan, Muthu; Peters, Robert

    2003-01-01

    Deep, stable nulling of starlight requires careful control of the amplitudes and phases of the beams that are being combined. The detection of earth-like planets using the interferometer architectures currently being considered for the Terrestrial Planet Finder mission require that the E-field amplitudes are balanced at the level of approx. 0.1%, and the phases are controlled at the level of 1 mrad (corresponding to approx.1.5 nm for a wavelength of 10 microns). These conditions must be met simultaneously at all wavelengths across the science band, and for both polarization states, imposing unrealistic tolerances on the symmetry between the optical beamtrains. We introduce the concept of a compensator that is inserted into the beamtrain, which can adaptively correct for the mismatches across the spectrum, enabling deep nulls with realistic, imperfect optics. The design presented uses a deformable mirror to adjust the amplitude and phase of each beam as an arbitrary function of wavelength and polarization. A proof-of-concept experiment will be conducted at visible/near-IR wavelengths, followed by a system operating in the Mid-IR band.

  4. Geometry of extended null supersymmetry in M theory

    SciTech Connect

    Conamhna, Oisin A.P. Mac

    2006-02-15

    For supersymmetric spacetimes in 11 dimensions admitting a null Killing spinor, a set of explicit necessary and sufficient conditions for the existence of any number of arbitrary additional Killing spinors is derived. The necessary and sufficient conditions are comprised of algebraic relationships, linear in the spinorial components, between the spinorial components and their first derivatives, and the components of the spin connection and four-form. The integrability conditions for the Killing spinor equation are also analyzed in detail, to determine which components of the field equations are implied by arbitrary additional supersymmetries and the four-form Bianchi identity. This provides a complete formalism for the systematic and exhaustive investigation of all spacetimes with extended null supersymmetry in 11 dimensions. The formalism is employed to show that the general bosonic solution of 11 dimensional supergravity admitting a G{sub 2} structure defined by four Killing spinors is either locally the direct product of R{sup 1,3} with a seven-manifold of G{sub 2} holonomy, or locally the Freund-Rubin direct product of AdS{sub 4} with a seven-manifold of weak G{sub 2} holonomy. In addition, all supersymmetric spacetimes admitting a (G{sub 2}xR{sup 7})xR{sup 2} structure are classified.

  5. Adding light to the gravitational waves on the null cone

    NASA Astrophysics Data System (ADS)

    Babiuc, Maria

    2014-03-01

    Recent interesting astrophysical observations point towards a multi-messenger, multi-wavelength approach to understanding strong gravitational sources, like compact stars or black hole collisions, supernovae explosions, or even the big bang. Gravitational radiation is properly defined only at future null infinity, but usually is estimated at a finite radius, and then extrapolated. Our group developed a characteristic waveform extraction tool, implemented in an open source code, which computes the gravitational waves infinitely far from their source, in terms of compactified null cones, by numerically solving Einstein equation in Bondi space-time coordinates. The goal is extend the capabilities of the code, by solving Einstein-Maxwell's equations together with the Maxwell's equations, to obtain the energy radiated asymptotically at infinity, both in gravitational and electromagnetic waves. The purpose is to analytically derive and numerically calculate both the gravitational waves and the electromagnetic counterparts at infinity, in this characteristic framework. The method is to treat the source of gravitational and electromagnetic radiation as a black box, and therefore the code will be very flexible, with potentially large applicability.

  6. A search for optical beacons: implications of null results.

    PubMed

    Blair, David G; Zadnik, Marjan G

    2002-01-01

    Over the past few years a series of searches for interstellar radio beacons have taken place using the Parkes radio telescope. Here we report hitherto unpublished results from a search for optical beacons from 60 solar-type stars using the Perth-Lowell telescope. We discuss the significance of the null results from these searches, all of which were based on the interstellar contact channel hypothesis. While the null results of all searches to date can be explained simply by the nonexistence of electromagnetically communicating life elsewhere in the Milky Way, four other possible explanations that do not preclude its existence are proposed: (1) Extraterrestrial civilizations desiring to make contact through the use of electromagnetic beacons have a very low density in the Milky Way. (2) The interstellar contact channel hypothesis is incorrect, and beacons exist at frequencies that have not yet been searched. (3) The search has been incomplete in terms of sensitivity and/or target directions: Beacons exist, but more sensitive equipment and/or more searching is needed to achieve success. (4) The search has occurred before beacon signals can be expected to have arrived at the Earth, and beacon signals may be expected in the future. Based on consideration of the technology required for extraterrestrial civilizations to identify target planets, we argue that the fourth possibility is likely to be valid and that powerful, easily detectable beacons could be received in coming centuries. PMID:12530240

  7. Deficits in memory and motor performance in synaptotagmin IV mutant mice

    PubMed Central

    Ferguson, Gregory D.; Anagnostaras, Stephan G.; Silva, Alcino J.; Herschman, Harvey R.

    2000-01-01

    Synaptotagmin (Syt) IV is a synaptic vesicle protein. Syt IV expression is induced in the rat hippocampus after systemic kainic acid treatment. To examine the functional role of this protein in vivo, we derived Syt IV null [Syt IV(−/−)] mutant mice. Studies with the rotorod revealed that the Syt IV mutants have impaired motor coordination, a result consistent with constitutive Syt IV expression in the cerebellum. Because Syt IV is thought to modulate synaptic function, we also have examined Syt IV mutant mice in learning and memory tests. Our studies show that the Syt IV mutation disrupts contextual fear conditioning, a learning task sensitive to hippocampal and amygdala lesions. In contrast, cued fear conditioning is normal in the Syt IV mutants, suggesting that this mutation did not disrupt amygdala function. Conditioned taste aversion, which also depends on the amygdala, is normal in the Syt IV mutants. Consistent with the idea that the Syt IV mutation preferentially affects hippocampal function, Syt IV mutant mice also display impaired social transmission of food preference. These studies demonstrate that Syt IV is critical for brain function and suggest that the Syt IV mutation affects hippocampal-dependent learning and memory, as well as motor coordination. PMID:10792055

  8. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome.

    PubMed Central

    Lewis, S E; Erickson, R P; Barnett, L B; Venta, P J; Tashian, R E

    1988-01-01

    Electrophoretic screening of (C57BL/6J x DBA/2J)F1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (CA II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could not be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus. Images PMID:3126501

  9. Functional complementation of Leishmania (Leishmania) amazonensis AP endonuclease gene (lamap) in Escherichia coli mutant strains challenged with DNA damage agents

    PubMed Central

    Verissimo-Villela, Erika; Kitahara-Oliveira, Milene Yoko; dos Reis, Ana Beatriz de Bragança; Albano, Rodolpho Mattos; Da-Cruz, Alda Maria; Bello, Alexandre Ribeiro

    2016-01-01

    During its life cycle Leishmania spp. face several stress conditions that can cause DNA damages. Base Excision Repair plays an important role in DNA maintenance and it is one of the most conserved mechanisms in all living organisms. DNA repair in trypanosomatids has been reported only for Old World Leishmania species. Here the AP endonuclease from Leishmania (L.) amazonensis was cloned, expressed in Escherichia coli mutants defective on the DNA repair machinery, that were submitted to different stress conditions, showing ability to survive in comparison to the triple null mutant parental strain BW535. Phylogenetic and multiple sequence analyses also confirmed that LAMAP belongs to the AP endonuclease class of proteins. PMID:27223868

  10. Error analysis and system optimization of non-null aspheric testing system

    NASA Astrophysics Data System (ADS)

    Luo, Yongjie; Yang, Yongying; Liu, Dong; Tian, Chao; Zhuo, Yongmo

    2010-10-01

    A non-null aspheric testing system, which employs partial null lens (PNL for short) and reverse iterative optimization reconstruction (ROR for short) technique, is proposed in this paper. Based on system modeling in ray tracing software, the parameter of each optical element is optimized and this makes system modeling more precise. Systematic error of non-null aspheric testing system is analyzed and can be categorized into two types, the error due to surface parameters of PNL in the system modeling and the rest from non-null interferometer by the approach of error storage subtraction. Experimental results show that, after systematic error is removed from testing result of non-null aspheric testing system, the aspheric surface is precisely reconstructed by ROR technique and the consideration of systematic error greatly increase the test accuracy of non-null aspheric testing system.

  11. Nonchemotactic Mutants of Escherichia coli

    PubMed Central

    Armstrong, John B.; Adler, Julius; Dahl, Margaret M.

    1967-01-01

    We have isolated 40 mutants of Escherichia coli which are nonchemotactic as judged by their failure to swarm on semisolid tryptone plates or to make bands in capillary tubes containing tryptone broth. All the mutants have normal flagella, a fact shown by their shape and reaction with antiflagella serum. All are fully motile under the microscope and all are sensitive to the phage chi. Unlike its parent, one of the mutants, studied in greater detail, failed to show chemotaxis toward oxygen, glucose, serine, threonine, or aspartic acid. The failure to exhibit chemotaxis does not result from a failure to use the chemicals. The swimming of this mutant was shown to be random. The growth rate was normal under several conditions, and the growth requirements were unchanged. Images PMID:5335897

  12. Chromatism compensation in wide-band nulling interferometry for exoplanet detection.

    PubMed

    Spronck, Julien; Pereira, Silvania F; Braat, Joseph J M

    2006-02-01

    We introduce the concept of chromatism compensation in nulling interferometry that enables a high rejection ratio in a wide spectral band. Therefore the achromaticity condition considered in most nulling interferometers can be relaxed. We show that this chromatism compensation cannot be applied to a two-beam nulling interferometer, and we make an analysis of the particular case of a three-telescope configuration. PMID:16485668

  13. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras.

    PubMed

    Keighren, Margaret A; Flockhart, Jean H; West, John D

    2016-01-01

    The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1(-/-) null mouse embryos die but a previous study showed that some homozygous Gpi1(-/-) null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1(-/-)↔Gpi1(c/c) chimaera with functional Gpi1(-/-) null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1(-/-) null cells in adult Gpi1(-/-)↔Gpi1(c/c) chimaeras and determine if Gpi1(-/-) null germ cells are functional. Analysis of adult Gpi1(-/-)↔Gpi1(c/c) chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1(-/-) null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1(-/-) null oocytes in one female Gpi1(-/-)↔Gpi1(c/c) chimaera were functional and provided preliminary evidence that one male putative Gpi1(-/-)↔Gpi1(c/c) chimaera produced functional spermatozoa from homozygous Gpi1(-/-) null germ cells. Although the male chimaera was almost certainly Gpi1(-/-)↔Gpi1(c/c), this part of the study is considered preliminary because only blood was typed for GPI. Gpi1(-/-) null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1(-/-) null germ cells, it successfully identified functional Gpi1(-/-) null oocytes and revealed that some Gpi1(-/-) null cells could survive in many adult tissues. PMID:27103217

  14. A glutathione reductase mutant of yeast accumulates high levels of oxidized glutathione and requires thioredoxin for growth.

    PubMed Central

    Muller, E G

    1996-01-01

    A glutathione reductase null mutant of Saccharomyces cerevisiae was isolated in a synthetic lethal genetic screen for mutations which confer a requirement for thioredoxin. Yeast mutants that lack glutathione reductase (glr1 delta) accumulate high levels of oxidized glutathione and have a twofold increase in total glutathione. The disulfide form of glutathione increases 200-fold and represents 63% of the total glutathione in a glr1 delta mutant compared with only 6% in wild type. High levels of oxidized glutathione are also observed in a trx1 delta, trx2 delta double mutant (22% of total), in a glr1 delta, trx1 delta double mutant (71% of total), and in a glr1 delta, trx2 delta double mutant (69% of total). Despite the exceptionally high ratio of oxidized/reduced glutathione, the glr1 delta mutant grows with a normal cell cycle. However, either one of the two thioredoxins is essential for growth. Cells lacking both thioredoxins and glutathione reductase are not viable under aerobic conditions and grow poorly anaerobically. In addition, the glr1 delta mutant shows increased sensitivity to the thiol oxidant diamide. The sensitivity to diamide was suppressed by deletion of the TRX2 gene. The genetic analysis of thioredoxin and glutathione reductase in yeast runs counter to previous studies in Escherichia coli and for the first time links thioredoxin with the redox state of glutathione in vivo. Images PMID:8930901

  15. Motility mutants of Dictyostelium discoideum

    PubMed Central

    1982-01-01

    We describe six motility mutants of Dictyostelium discoideum in this report. They were identified among a group of temperature-sensitive growth (Tsg) mutants that had been previously isolated using an enrichment for phagocytosis-defective cells. The Tsg mutants were screened for their ability to produce tracks on gold-coated cover slips, and several strains were found that were temperature-sensitive for migration in this assay. Analysis of spontaneous Tsg+ revertants of 10 migration-defective strains identified six strains that co-reverted the Tsg and track formation phenotypes. Characterization of these six strains indicated that they were defective at restrictive temperature in track formation, phagocytosis of bacteria, and pseudopodial and filopodial activity, while retaining normal rates of oxygen consumption and viability. Because they had lost this group of motile capabilities, these strains were designated motility mutants. The Tsg+ revertants of these mutants, which coordinately recovered all of the motile activities, were found at frequencies consistent with single genetic events. Analysis of the motility mutants and their revertants suggests a relationship between the motility mutations in some of these strains and genes affecting axenic growth. PMID:7118999

  16. Null Mutations of NT-3 and Bax Affect Trigeminal Ganglion Cell Number but Not Brainstem Barrelette Pattern Formation

    PubMed Central

    Mosconi, Tony; Arends, J.J.; Jacquin, Mark F.

    2014-01-01

    Trigeminal ganglion (TG) neurons innervate the grid-like array of whisker follicles on the face of the mouse. Central TG axons project to the trigeminal (V) brainstem nuclear complex, including the nucleus principalis (PrV), and the spinal subnucleus interpolaris (SpVi), where they innervate barrelettes that are organized in a pattern that recapitulates the whisker pattern on the face. Neurotrophin-3 (NT-3) supports a population of TG cells that supply slowly adapting mechanoreceptors in the whisker pad. We examined mice at embryonic day 17 (E17) and on the day of birth (P0) with null mutations of NT-3, Bax, a proapoptotic gene associated with naturally occurring cell death, and Bax/NT-3 double knockout mutants to determine if: 1) the number of TG cells would be reduced; 2) eliminating the Bax gene would rescue the NT-3 dependent neurons; and 3) the central projections of the rescued axons in the Bax/NT-3 double knockout mice would fail to develop the barrelette patterns in the PrV and SpVi subnuclei. In mice at E17, NT-3−/− mutants had 65% fewer TG neurons than found in age matched wild-type (WT) mice, and at P0, the number was reduced by 55% (p < 0.001 for both). Bax null mutant mice at E17 had 132% of the WT number of TG cells (p < 0.001), although the numbers returned to WT levels by P0. Bax/NT-3 double knockout mice at E17 had TG cell numbers equal to those seen in WT, but the double knockout failed to retain WT TG neuron numbers in P0 mice (39% fewer cells; p < 0.001). In all cases of reduced experimental neuron numbers, and in the E17 Bax−/− mice with supernumerary cells, the barrelette patterns in the PrV and SpVi were normal. Only a slight qualitative reduction in overall barrelette field area and clarity of barrelettes were seen. These results suggest that NT-3 is not necessary for barrelette pattern formation in the brainstem. PMID:23614607

  17. Principles: when there should be no difference--how to fail to reject the null hypothesis.

    PubMed

    Lew, Michael J

    2006-05-01

    It is common to perform experiments in which a 'success' is claimed when the null hypothesis is discarded. However, there is a category of experiment that has become important in which a success is when the null hypothesis is not rejected. Failing to discard the null hypothesis is different from proving it to be valid, a distinction that is particularly important in experiments in which any inadequacy of experimental design or implementation enhances the likelihood of a success. The appropriate analysis of such experiments tests for evidence of the validity of the null hypothesis rather than simply failing to find evidence against it. PMID:16595154

  18. Alignment of optical system components using an ADM beam through a null assembly

    NASA Technical Reports Server (NTRS)

    Hayden, Joseph E. (Inventor); Olczak, Eugene G. (Inventor)

    2010-01-01

    A system for testing an optical surface includes a rangefinder configured to emit a light beam and a null assembly located between the rangefinder and the optical surface. The null assembly is configured to receive and to reflect the emitted light beam toward the optical surface. The light beam reflected from the null assembly is further reflected back from the optical surface toward the null assembly as a return light beam. The rangefinder is configured to measure a distance to the optical surface using the return light beam.

  19. A matrix model for the null-brane

    NASA Astrophysics Data System (ADS)

    Robbins, Daniel

    The null-brave quotient is a simple smooth time-dependent solution of string or M-theory. By tuning a parameter, this background develops a big crunch/big bang type singularity. We construct a matrix model description of this background as a Yang-Mills theory on a time-dependent space-time. This dual description provides a non-perturbative framework to study the fate of space-times with cosmological singularities. We study the dynamics of this theory, including particle production and the one-loop effective action for Higgs VEVs in the theory, and we present some evidence that space-time itself breaks down, even while the underlying theory remains unitary and well-defined. Finally, we speculate about which lessons can be carried over to more general situations and propose several future directions for research.

  20. Null polarimetry near shot noise limit at 1 Hz

    NASA Astrophysics Data System (ADS)

    He, Dechao; Xie, Boya; Feng, Sheng

    2016-04-01

    We describe the principle and report on the realization of a null polarimeter with two demonstrated features: (1) the sensitivity of the system is near shot noise limit and (2) quasi-stationary signals at 1 Hz can be measured without signal modulation. The achieved single-pass sensitivity is 7 × 10-9 rad/ √{ Hz } with a pair of Glan-Taylor polarizers, which should be of great interest for experiments such as observation of vacuum magnetic birefringence and search for new particles. The system is brought near its shot noise limit by appropriate polarization control and coherent heterodyne detection of light, resulting in a sensitivity improvement by two orders of magnitude in comparison with the case of no control on light polarization.

  1. Solvable null model for the distribution of word frequencies

    NASA Astrophysics Data System (ADS)

    Fontanari, J. F.; Perlovsky, L. I.

    2004-10-01

    Zipf’s law asserts that in all natural languages the frequency of a word is inversely proportional to its rank. The significance, if any, of this result for language remains a mystery. Here we examine a null hypothesis for the distribution of word frequencies, a so-called discourse-triggered word choice model, which is based on the assumption that the more a word is used, the more likely it is to be used again. We argue that this model is equivalent to the neutral infinite-alleles model of population genetics and so the degeneracy of the different words composing a sample of text is given by the celebrated Ewens sampling formula [Theor. Pop. Biol. 3, 87 (1972)], which we show to produce an exponential distribution of word frequencies.

  2. Polarization interferometric nulling coronagraph for high-contrast imaging.

    PubMed

    Murakami, Naoshi; Yokochi, Kaito; Nishikawa, Jun; Tamura, Motohide; Kurokawa, Takashi; Takeda, Mitsuo; Baba, Naoshi

    2010-06-01

    We propose a novel, high-contrast imager called a polarization interferometric nulling coronagraph (PINC) for direct detection of extrasolar planets. The PINC uses achromatic half-wave plates (HWPs) installed in a fully symmetric beam combiner based on polarizing beam splitters. Jones calculus suggests that a stellar halo suppression level of 10(-10) can be achieved at 5 lambda/D for a broad wavelength range from 1.6 to 2.2 microm by using Fresnel-rhomb HWPs made of BK7. Laboratory experiments on the PINC used two laser light sources (wavelengths of lambda=532 and 671 nm), and we obtained a halo suppression level of approximately 10(-6) at 5 lambda/D for both wavelengths. PMID:20517351

  3. Null polarimetry near shot noise limit at 1 Hz.

    PubMed

    He, Dechao; Xie, Boya; Feng, Sheng

    2016-04-01

    We describe the principle and report on the realization of a null polarimeter with two demonstrated features: (1) the sensitivity of the system is near shot noise limit and (2) quasi-stationary signals at 1 Hz can be measured without signal modulation. The achieved single-pass sensitivity is 7 × 10(-9) rad/Hz with a pair of Glan-Taylor polarizers, which should be of great interest for experiments such as observation of vacuum magnetic birefringence and search for new particles. The system is brought near its shot noise limit by appropriate polarization control and coherent heterodyne detection of light, resulting in a sensitivity improvement by two orders of magnitude in comparison with the case of no control on light polarization. PMID:27131649

  4. Dilute Aperture Visible Nulling Coronagraph Imaging (DAViNCI)

    NASA Technical Reports Server (NTRS)

    Shao, Michael; Levine, B. M.; Vasisht, G.; Lane, B. F.; Woodruff, R.; Vasudevan, G.; Samuele R.; Harvey, K.; Clampin, M.; Lyon, R.; Guyon, O.; Tolls, V.

    2008-01-01

    The presentation focuses on instrument and mission overview, science case, Team X study, and technology status. Topics include DAViNCI study milestones, number of targets versus inner working angle, planet orbit and IWA, combiner/nuller instrument, DAViNCI Team X costs, technology status and near future plans, and deep laser null 1.23 x 10(exp -7) suppression. Summary points are: dilute aperture concept advantages, lower cost than a comparable 7-8m coronagraph working at 2 lambda/D, technology progress prior to 2008 was seriously limited by available funding but showed 1e-y suppression (2006) of laser light needed for 1e-9 to approximately 1e-10 contrast, and current technology effort is off to a fast date with a demonstration of less than 100pm wavefront measurement in Nov 08.

  5. Five-dimensional null and time-like supersymmetric geometries

    NASA Astrophysics Data System (ADS)

    Pasini, Giulio; Shahbazi, C. S.

    2016-09-01

    We show that there exist supersymmetric solutions of five-dimensional, pure, { N }=1 supergravity such that the norm of the supersymmetric Killing vector, built out of the Killing spinor, is a real not-everywhere analytic function such that all its derivatives vanish at a point where the Killing vector field becomes null. The norm of the Killing vector field then is not an analytic function on a neighborhood around this point. We explicitly construct such solutions by using a multi-center Gibbons–Hawking base. Although many of these solutions have infinite charges, we find explicit examples with finite charges that asymptote to {{AdS}}3× {S}2 and discuss their physical interpretation.

  6. Null space and resolution in dynamic computerized tomography

    NASA Astrophysics Data System (ADS)

    Hahn, Bernadette N.

    2016-02-01

    One major challenge in computerized tomography is to image objects which change during the data acquisition and hence lead to inconsistent data sets. Motion artefacts in the reconstructions can be reduced by applying specially adapted algorithms which take the dynamic behaviour into account. Within this article, we analyse the achievable resolution in the dynamic setting in case of two-dimensional affine deformations. To this end, we characterize the null space of the operator describing the dynamic case, using its singular value decomposition and a necessary dynamic consistency condition. This shows that independent of any reconstruction method, the specimen’s dynamics results in a loss of resolution compared to the stationary setting. Our theoretical results are illustrated at a numerical example.

  7. Status of the Visible Nulling Coronagraph Technology Demonstration Program

    NASA Technical Reports Server (NTRS)

    Clampin, M.; Lyon, R.

    2012-01-01

    We report on the development, sensing and control of the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraphy (VNC) for exoplanet detection and characterization. The VNC is one of the few approaches that works with filled, segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be flown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center has an established effort to develop VNC technologies, and an incremental sequence of testbeds to advance this approach and its critical technologies. We will highlight results demonstrating the achievement of our TDEM contrast milestones, and highlight the performance of our wavefront sensing and control concept.

  8. Recent Contrast Measurements Made Using the PICTURE Visible Nulling Coronagraph

    NASA Astrophysics Data System (ADS)

    Mendillo, Christopher Bernard; Douglas, Ewan S.; Finn, Susanna C.; Hicks, Brian; Martel, Jason; Cook, Timothy; Chakrabarti, Supriya

    2014-06-01

    The PICTURE-B (Planetary Imaging Concept Testbed Using a Rocket Experiment - B) sounding rocket mission will use a visible nulling coronagraph to directly image the exozodiacal dust disk of Epsilon Eridani (K2V, 3.22 pc) in reflected visible light down to an inner radius of 1.5 AU (1.7 λ/D). This mission will demonstrate a number of key technologies for future space-based direct exoplanet imaging missions. These include: wavefront sensing and control using deformable mirrors in space, a lightweight SiC 0.5 meter primary mirror and a milliarcsecond-class fine pointing system. The mission is scheduled for launch in October, 2014. We present laboratory contrast measurements made using the PICTURE-B instrument and model predictions of exozodiacal dust detection limits based on these measurements.

  9. Power spectrum nulls due to nonstandard inflationary evolution

    NASA Astrophysics Data System (ADS)

    Goswami, Gaurav; Souradeep, Tarun

    2011-01-01

    The simplest models of inflation based on slow roll produce nearly scale invariant primordial power spectra (PPS). But there are also numerous models that predict radically broken scale invariant PPS. In particular, markedly cuspy dips in the PPS correspond to nulls where the perturbation amplitude, hence PPS, goes through a zero at a specific wave number. Near this wave number, the true quantum nature of the generation mechanism of the primordial fluctuations may be revealed. Naively these features may appear to arise from fine-tuned initial conditions. However, we show that this behavior arises under fairly generic set of conditions involving super-Hubble scale evolution of perturbation modes during inflation. We illustrate this with the well-studied examples of punctuated inflation and the Starobinsky-break model.

  10. On the null trajectories in conformal Weyl gravity

    SciTech Connect

    Villanueva, J.R.; Olivares, Marco E-mail: marco.olivaresrubilar@gmail.com

    2013-06-01

    In this work we find analytical solutions to the null geodesics around a black hole in the conformal Weyl gravity. Exact expressions for the horizons are found, and they depend on the cosmological constant and the coupling constants of the conformal Weyl gravity. Then, we study the radial motion from the point of view of the proper and coordinate frames, and compare it with that found in spacetimes of general relativity. The angular motion is also examined qualitatively by means of an effective potential; quantitatively, the equation of motion is solved in terms of wp-Weierstrass elliptic function. Thus, we find the deflection angle for photons without using any approximation, which is a novel result for this kind of gravity.

  11. Review of OCA activities on nulling testbench PERSEE

    NASA Astrophysics Data System (ADS)

    Hénault, François; Girard, Paul; Marcotto, Aurélie; Mauclert, Nicolas; Bailet, Christophe; Clausse, Jean-Michel; Mourard, Denis; Rabbia, Yves; Roussel, Alain; Barillot, Marc; Cassaing, Frédéric; Le Duigou, Jean-Michel

    2010-07-01

    We present a review of our activities on PERSEE (Pégase Experiment for Research and Stabilization of Extreme Extinction) at Observatoire de la Côte d'Azur (OCA). PERSEE is a laboratory testbench aiming at achieving a stabilized nulling ratio better than 10-4 in the astronomical bands K and M, in presence of flight-representative spacecraft perturbations. The bench has been jointly developed by a Consortium of six French institutes and companies, among which OCA was responsible for the star simulator and of the opto-mechanical studies, procurement and manufacturing of the optical train. In this communication are presented the alignment and image quality requirements and the optomechanical design of the illumination module and main optical train, including a periscope Achromatic Phase Shifter (APS), tip-tilt mirrors used to introduce and then compensate for dynamic disturbances, delay lines, beam compressors and fiber injection optics. Preliminary test results of the star simulator are also provided.

  12. Histone H1 null vertebrate cells exhibit altered nucleosome architecture

    PubMed Central

    Hashimoto, Hideharu; Takami, Yasunari; Sonoda, Eiichiro; Iwasaki, Tomohito; Iwano, Hidetomo; Tachibana, Makoto; Takeda, Shunichi; Nakayama, Tatsuo; Kimura, Hiroshi; Shinkai, Yoichi

    2010-01-01

    In eukaryotic nuclei, DNA is wrapped around an octamer of core histones to form nucleosomes, and chromatin fibers are thought to be stabilized by linker histones of the H1 type. Higher eukaryotes express multiple variants of histone H1; chickens possess six H1 variants. Here, we generated and analyzed the phenotype of a complete deletion of histone H1 genes in chicken cells. The H1-null cells showed decreased global nucleosome spacing, expanded nuclear volumes, and increased chromosome aberration rates, although proper mitotic chromatin structure appeared to be maintained. Expression array analysis revealed that the transcription of multiple genes was affected and was mostly downregulated in histone H1-deficient cells. This report describes the first histone H1 complete knockout cells in vertebrates and suggests that linker histone H1, while not required for mitotic chromatin condensation, plays important roles in nucleosome spacing and interphase chromatin compaction and acts as a global transcription regulator. PMID:20156997

  13. Dinucleotide controlled null models for comparative RNA gene prediction

    PubMed Central

    Gesell, Tanja; Washietl, Stefan

    2008-01-01

    Background Comparative prediction of RNA structures can be used to identify functional noncoding RNAs in genomic screens. It was shown recently by Babak et al. [BMC Bioinformatics. 8:33] that RNA gene prediction programs can be biased by the genomic dinucleotide content, in particular those programs using a thermodynamic folding model including stacking energies. As a consequence, there is need for dinucleotide-preserving control strategies to assess the significance of such predictions. While there have been randomization algorithms for single sequences for many years, the problem has remained challenging for multiple alignments and there is currently no algorithm available. Results We present a program called SISSIz that simulates multiple alignments of a given average dinucleotide content. Meeting additional requirements of an accurate null model, the randomized alignments are on average of the same sequence diversity and preserve local conservation and gap patterns. We make use of a phylogenetic substitution model that includes overlapping dependencies and site-specific rates. Using fast heuristics and a distance based approach, a tree is estimated under this model which is used to guide the simulations. The new algorithm is tested on vertebrate genomic alignments and the effect on RNA structure predictions is studied. In addition, we directly combined the new null model with the RNAalifold consensus folding algorithm giving a new variant of a thermodynamic structure based RNA gene finding program that is not biased by the dinucleotide content. Conclusion SISSIz implements an efficient algorithm to randomize multiple alignments preserving dinucleotide content. It can be used to get more accurate estimates of false positive rates of existing programs, to produce negative controls for the training of machine learning based programs, or as standalone RNA gene finding program. Other applications in comparative genomics that require randomization of multiple

  14. Cadmium modulates adipocyte functions in metallothionein-null mice

    SciTech Connect

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.

  15. Long-term improvements in sensory inhibition with gestational choline supplementation linked to α7 nicotinic receptors through studies in Chrna7 null mutation mice.

    PubMed

    Stevens, Karen E; Choo, Kevin S; Stitzel, Jerry A; Marks, Michael J; Adams, Catherine E

    2014-03-13

    Perinatal choline supplementation has produced several benefits in rodent models, from improved learning and memory to protection from the behavioral effects of fetal alcohol exposure. We have shown that supplemented choline through gestation and lactation produces long-term improvement in deficient sensory inhibition in DBA/2 mice which models a similar deficit in schizophrenia patients. The present study extends that research by feeding normal or supplemented choline diets to DBA/2 mice carrying the null mutation for the α7 nicotinic receptor gene (Chrna7). DBA/2 mice heterozygotic for Chrna7 were bred together. Dams were placed on supplemented (5 gm/kg diet) or normal (1.1 gm/kg diet) choline at mating and remained on the specific diet until offspring weaning. Thereafter, offspring were fed standard rodent chow. Adult offspring were assessed for sensory inhibition. Brains were obtained to ascertain hippocampal α7 nicotinic receptor levels. Choline-supplemented mice heterozygotic or null-mutant for Chrna7 failed to show improvement in sensory inhibition. Only wildtype choline-supplemented mice showed improvement with the effect solely through a decrease in test amplitude. This supports the hypothesis that gestational-choline supplementation is acting through the α7 nicotinic receptor to improve sensory inhibition. Although there was a significant gene-dose-related change in hippocampal α7 receptor numbers, binding studies did not reveal any choline-dose-related change in binding in any hippocampal region, the interaction being driven by a significant genotype main effect (wildtype>heterozygote>null mutant). These data parallel a human study wherein the offspring of pregnant women receiving choline supplementation during gestation, showed better sensory inhibition than offspring of women on placebo. PMID:24462939

  16. Over-fitting Time Series Models of Air Pollution Health Effects: Smoothing Tends to Bias Non-Null Associations Towards the Null.

    EPA Science Inventory

    Background: Simulation studies have previously demonstrated that time-series analyses using smoothing splines correctly model null health-air pollution associations. Methods: We repeatedly simulated season, meteorology and air quality for the metropolitan area of Atlanta from cyc...

  17. How to find magnetic null and construct field topology with MMS data?

    NASA Astrophysics Data System (ADS)

    Fu, Huishan; Vaivads, Andris; Khotyaintsev, Yuri; Olshevsky, Vyacheslav; Andre, Mats; Cao, Jinbin; Huang, Shiyong; Retino, Alessandro; Eastwood, Jonathan

    2015-04-01

    In this study, we apply a new method'Taylor expansion'to find magnetic null and construct magnetic field topology, in order to use it with the data from the forth-coming MMS mission. We compare this method with the previously used Poincare index (PI), and find that they are generally consistent, except that the PI method can only find a null inside the spacecraft (SC) tetrahedron, while the Taylor expansion can find a null both inside and outside the tetrahedron and also deduce its drift velocity. Taylor expansion can also: (1) avoid the limitations of PI method such as data resolution, instrument uncertainty (Bz offset), and SC separation; (2) identify 3D null types (A, B, As, and Bs) and determine whether these types can degenerate into 2D (X and O); (3) construct the magnetic field topology. We quantitively test the accurateness of Taylor expansion in positioning magnetic null and constructing field topology, by using the data from 3D kinetic simulations. The influences of SC separation (from 0.05 to 1 di) and null-SC distance (from 0 to 1 di) on the accurateness are both considered. We find that: (1) for single null, the method is accurate when the SC separation is smaller than 1 di, and the null-SC distance is smaller than 0.5 di (weakly chaotic reconnection) or 0.25 di (strongly chaotic reconnection); (2) for null pair, the accurateness is same as the single-null situation, except at the null-null line, where the field is nonlinear. We invent a parameter ξ ≡|(λ1 + λ2 + λ3)|/ |λ|max to quantify the quality of the method'the smaller this parameter the better the results. Comparing to the previously used one (η ≡|downtriangle -B|/ |downtriangle × B |), this parameter is more relevant. Using the new method, we construct the magnetic field topology around a radial-type null and a spiral-type null, and find that the topologies are well consistent with those predicted in theory. This means that our method is reliable. We therefore suggest using this

  18. Abnormal Synaptic Vesicle Biogenesis in Drosophila Synaptogyrin Mutants

    PubMed Central

    Stevens, Robin J.; Akbergenova, Yulia; Jorquera, Ramon A.; Littleton, J. Troy

    2012-01-01

    Sustained neuronal communication relies on the coordinated activity of multiple proteins that regulate synaptic vesicle biogenesis and cycling within the presynaptic terminal. Synaptogyrin and synaptophysin are conserved MARVEL domain-containing transmembrane proteins that are among the most abundant synaptic vesicle constituents, although their role in the synaptic vesicle cycle has remained elusive. To further investigate the function of these proteins, we generated and characterized a synaptogyrin (gyr) null mutant in Drosophila, whose genome encodes a single synaptogyrin isoform and lacks a synaptophysin homolog. We demonstrate that Drosophila synaptogyrin plays a modulatory role in synaptic vesicle biogenesis at larval neuromuscular junctions. Drosophila lacking synaptogyrin are viable and fertile and have no overt deficits in motor function. However, ultrastructural analysis of gyr larvae revealed increased synaptic vesicle diameter and enhanced variability in the size of synaptic vesicles. In addition, the resolution of endocytic cisternae into synaptic vesicles in response to strong stimulation is defective in gyr mutants. Electrophysiological analysis demonstrated an increase in quantal size and a concomitant decrease in quantal content, suggesting functional consequences for transmission caused by the loss of synaptogyrin. Furthermore, high-frequency stimulation resulted in increased facilitation and a delay in recovery from synaptic depression, indicating that synaptic vesicle exo-endocytosis is abnormally regulated during intense stimulation conditions. These results suggest that synaptogyrin modulates the synaptic vesicle exo-endocytic cycle and is required for the proper biogenesis of synaptic vesicles at nerve terminals. PMID:23238721

  19. Language Learnability and Empirical Plausibility: Null Subjects and Indirect Negative Evidence.

    ERIC Educational Resources Information Center

    Saleemi, Anjum P.

    Children's ability to learn aspects of their language in the absence of supportive evidence is discussed. Specifically, the learnability of null subjects in languages in which they appear is examined when indirect negative evidence is present. It is concluded that parameters such as the null subject parameter may not generate languages, strictly…

  20. Qualification of a Null Lens Using Image-Based Phase Retrieval

    NASA Technical Reports Server (NTRS)

    Bolcar, Matthew R.; Aronstein, David L.; Hill, Peter C.; Smith, J. Scott; Zielinski, Thomas P.

    2012-01-01

    In measuring the figure error of an aspheric optic using a null lens, the wavefront contribution from the null lens must be independently and accurately characterized in order to isolate the optical performance of the aspheric optic alone. Various techniques can be used to characterize such a null lens, including interferometry, profilometry and image-based methods. Only image-based methods, such as phase retrieval, can measure the null-lens wavefront in situ - in single-pass, and at the same conjugates and in the same alignment state in which the null lens will ultimately be used - with no additional optical components. Due to the intended purpose of a Dull lens (e.g., to null a large aspheric wavefront with a near-equal-but-opposite spherical wavefront), characterizing a null-lens wavefront presents several challenges to image-based phase retrieval: Large wavefront slopes and high-dynamic-range data decrease the capture range of phase-retrieval algorithms, increase the requirements on the fidelity of the forward model of the optical system, and make it difficult to extract diagnostic information (e.g., the system F/#) from the image data. In this paper, we present a study of these effects on phase-retrieval algorithms in the context of a null lens used in component development for the Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission. Approaches for mitigation are also discussed.

  1. Overt vs. Null Direct Objects in Spoken Brazilian Portuguese: A Semantic/Pragmatic Account.

    ERIC Educational Resources Information Center

    Schwenter, Scott A.; Silva, Glaucia

    2002-01-01

    Examines the semantic/pragmatic constraints on null objects spoken in Brazilian Portuguese (BP) in detail, and situates BP null objects in the broader crosslinguistic perspective of differential object marking. Demonstrates that semantic/pragmatic dimensions of animacy and specificity, and in particular their interaction, must be taken into…

  2. Agreement and Null Subjects in German L2 Development: New Evidence from Reaction-Time Experiments.

    ERIC Educational Resources Information Center

    Clahsen, Harald; Hong, Upyong

    1995-01-01

    Reports on reaction time experiments investigating subject-verb agreement and null subjects in 33 Korean learners of German and a control group of 20 German native speakers. Results found that the two phenomena do not covary in the Korean learners, indicating that properties of agreement and null subjects are acquired separately from one another.…

  3. A Minimalist Approach to Null Subjects and Objects in Second Language Acquisition

    ERIC Educational Resources Information Center

    Park, H.

    2004-01-01

    Studies of the second language acquisition of pronominal arguments have observed that: (1) L1 speakers of null subject languages of the Spanish type drop more subjects in their second language (L2) English than first language (L1) speakers of null subject languages of the Korean type and (2) speakers of Korean-type languages drop more objects than…

  4. Corneal Opacity in Lumican-Null Mice: Defects in Collagen Fibril Structure and Packing in the Posterior Stroma

    PubMed Central

    Chakravarti, Shukti; Petroll, W. Matthew; Hassell, John R.; Jester, James V.; Lass, Jonathan H.; Paul, Jennifer; Birk, David E.

    2015-01-01

    Purpose Gene targeted lumican-null mutants (lumtm1sc/lumtm1sc) have cloudy corneas with abnormally thick collagen fibrils. The purpose of the present study was to analyze the loss of transparency quantitatively and to define the associated corneal collagen fibril and stromal defects. Methods Backscattering of light, a function of corneal haze and opacification, was determined regionally using in vivo confocal microscopy in lumican-deficient and wild-type control mice. Fibril organization and structure were analyzed using transmission electron microscopy. Biochemical approaches were used to quantify glycosaminoglycan contents. Lumican distribution in the cornea was elucidated immunohistochemically. Results Compared with control stromas, lumican-deficient stromas displayed a threefold increase in backscattered light with maximal increase confined to the posterior stroma. Confocal microscopy through-focusing (CMTF) measurement profiles also indicated a 40% reduction in stromal thickness in the lumican-null mice. Transmission electron microscopy indicated significant collagen fibril abnormalities in the posterior stroma, with the anterior stroma remaining relatively unremarkable. The lumican-deficient posterior stroma displayed a pronounced increase in fibril diameter, large fibril aggregates, altered fibril packing, and poor lamellar organization. Immunostaining of wild-type corneas demonstrated high concentrations of lumican in the posterior stroma. Biochemical assessment of keratan sulfate (KS) content of whole eyes revealed a 25% reduction in KS content in the lumican-deficient mice. Conclusions The structural defects and maximum backscattering of light clearly localized to the posterior stroma of lumican-deficient mice. In normal mice, an enrichment of lumican was observed in the posterior stroma compared with that in the anterior stroma. Taken together, these observations indicate a key role for lumican in the posterior stroma in maintaining normal fibril

  5. Why Are Flare Ribbons Associated with the Spines of Magnetic Null Points Generically Elongated?

    NASA Astrophysics Data System (ADS)

    Pontin, David; Galsgaard, Klaus; Démoulin, Pascal

    2016-08-01

    Coronal magnetic null points exist in abundance, as demonstrated by extrapolations of the coronal field, and have been inferred to be important for a broad range of energetic events. These null points and their associated separatrix and spine field lines represent discontinuities of the field line mapping, making them preferential locations for reconnection. This field line mapping also exhibits strong gradients adjacent to the separatrix (fan) and spine field lines, which can be analysed using the "squashing factor", Q. In this article we analyse in detail the distribution of Q in the presence of magnetic nulls. While Q is formally infinite on both the spine and fan of the null, the decay of Q away from these structures is shown in general to depend strongly on the null-point structure. For the generic case of a non-radially-symmetric null, Q decays most slowly away from the spine or fan in the direction in which |{B}| increases most slowly. In particular, this demonstrates that the extended elliptical high-Q halo around the spine footpoints observed by Masson et al. ( Astrophys. J. 700, 559, 2009) is a generic feature. This extension of the Q halos around the spine or fan footpoints is important for diagnosing the regions of the photosphere that are magnetically connected to any current layer that forms at the null. In light of this, we discuss how our results can be used to interpret the geometry of observed flare ribbons in circular ribbon flares, in which typically a coronal null is implicated. We conclude that both the physics in the vicinity of the null and how this is related to the extension of Q away from the spine or fan can be used in tandem to understand observational signatures of reconnection at coronal null points.

  6. Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans.

    PubMed

    Gunalan, Karthigayan; Lo, Eugenia; Hostetler, Jessica B; Yewhalaw, Delenasaw; Mu, Jianbing; Neafsey, Daniel E; Yan, Guiyun; Miller, Louis H

    2016-05-31

    The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand-receptor pairs for invasion. PMID:27190089

  7. Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

    PubMed Central

    Gunalan, Karthigayan; Lo, Eugenia; Hostetler, Jessica B.; Yewhalaw, Delenasaw; Mu, Jianbing; Neafsey, Daniel E.; Yan, Guiyun; Miller, Louis H.

    2016-01-01

    The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand–receptor pairs for invasion. PMID:27190089

  8. Why Are Flare Ribbons Associated with the Spines of Magnetic Null Points Generically Elongated?

    NASA Astrophysics Data System (ADS)

    Pontin, David; Galsgaard, Klaus; Démoulin, Pascal

    2016-06-01

    Coronal magnetic null points exist in abundance, as demonstrated by extrapolations of the coronal field, and have been inferred to be important for a broad range of energetic events. These null points and their associated separatrix and spine field lines represent discontinuities of the field line mapping, making them preferential locations for reconnection. This field line mapping also exhibits strong gradients adjacent to the separatrix (fan) and spine field lines, which can be analysed using the "squashing factor", Q. In this article we analyse in detail the distribution of Q in the presence of magnetic nulls. While Q is formally infinite on both the spine and fan of the null, the decay of Q away from these structures is shown in general to depend strongly on the null-point structure. For the generic case of a non-radially-symmetric null, Q decays most slowly away from the spine or fan in the direction in which |{B}| increases most slowly. In particular, this demonstrates that the extended elliptical high- Q halo around the spine footpoints observed by Masson et al. (Astrophys. J. 700, 559, 2009) is a generic feature. This extension of the Q halos around the spine or fan footpoints is important for diagnosing the regions of the photosphere that are magnetically connected to any current layer that forms at the null. In light of this, we discuss how our results can be used to interpret the geometry of observed flare ribbons in circular ribbon flares, in which typically a coronal null is implicated. We conclude that both the physics in the vicinity of the null and how this is related to the extension of Q away from the spine or fan can be used in tandem to understand observational signatures of reconnection at coronal null points.

  9. Spatial effects in real networks: Measures, null models, and applications

    NASA Astrophysics Data System (ADS)

    Ruzzenenti, Franco; Picciolo, Francesco; Basosi, Riccardo; Garlaschelli, Diego

    2012-12-01

    Spatially embedded networks are shaped by a combination of purely topological (space-independent) and space-dependent formation rules. While it is quite easy to artificially generate networks where the relative importance of these two factors can be varied arbitrarily, it is much more difficult to disentangle these two architectural effects in real networks. Here we propose a solution to this problem, by introducing global and local measures of spatial effects that, through a comparison with adequate null models, effectively filter out the spurious contribution of nonspatial constraints. Our filtering allows us to consistently compare different embedded networks or different historical snapshots of the same network. As a challenging application we analyze the World Trade Web, whose topology is known to depend on geographic distances but is also strongly determined by nonspatial constraints (degree sequence or gross domestic product). Remarkably, we are able to detect weak but significant spatial effects both locally and globally in the network, showing that our method succeeds in retrieving spatial information even when nonspatial factors dominate. We finally relate our results to the economic literature on gravity models and trade globalization.

  10. Identification of Siglec-1 null individuals infected with HIV-1

    PubMed Central

    Martinez-Picado, Javier; McLaren, Paul J.; Erkizia, Itziar; Martin, Maureen P.; Benet, Susana; Rotger, Margalida; Dalmau, Judith; Ouchi, Dan; Wolinsky, Steven M.; Penugonda, Sudhir; Günthard, Huldrych F.; Fellay, Jacques; Carrington, Mary; Izquierdo-Useros, Nuria; Telenti, Amalio

    2016-01-01

    Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals. PMID:27510803

  11. Characterization of deformable elastic lenses using PDI and null screen

    NASA Astrophysics Data System (ADS)

    Santiago Alvarado, A.; Granados Agustín, F. S.; Vázquez Montiel, S.; Campos García, M.; Dìaz Uribe, R.

    2009-06-01

    In recent years there has been a considerable increase in the use of variable focal length lenses (VFLL), due to the fact that they are used as micro lenses in photographic cameras, endoscope, etc. The VFLL's come mainly in three types, one of them are formed of two transparent elastic membranes with a liquid medium between them, those made of an elastic material inside a mount which allow radial forces to be applied on its perimeter, and finally those which are made of a dielectric liquid medium. In these VFLL always have a mechanism that allows the shape of the lens and its geometrical parameters can be changed. In this study, we implement a mechanical mount to applied radial force, in the perimeter of a solid elastic lens. We measure the aberrations of wavefront present in deformable solid elastic lens (VFLL), when we change the radial forces applied on its borders. The wave sensor used were the Point Diffraction Interferometer (PDI) and null screen tests. Theoretical and experimental results are presented.

  12. Identification of Siglec-1 null individuals infected with HIV-1.

    PubMed

    Martinez-Picado, Javier; McLaren, Paul J; Erkizia, Itziar; Martin, Maureen P; Benet, Susana; Rotger, Margalida; Dalmau, Judith; Ouchi, Dan; Wolinsky, Steven M; Penugonda, Sudhir; Günthard, Huldrych F; Fellay, Jacques; Carrington, Mary; Izquierdo-Useros, Nuria; Telenti, Amalio

    2016-01-01

    Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals. PMID:27510803

  13. Cosmologies with null singularities and their gauge theory duals

    SciTech Connect

    Das, Sumit R.; Michelson, Jeremy; Narayan, K.; Trivedi, Sandip P.

    2007-01-15

    We investigate backgrounds of Type IIB string theory with null singularities and their duals proposed in S. R. Das, J. Michelson, K. Narayan, S. P. Trivedi, hep-th/0602107. The dual theory is a deformed N=4 Yang-Mills theory in 3+1 dimensions with couplings dependent on a lightlike direction. We concentrate on backgrounds which become AdS{sub 5}xS{sup 5} at early and late times and where the string coupling is bounded, vanishing at the singularity. Our main conclusion is that in these cases the dual gauge theory is nonsingular. We show this by arguing that there exists a complete set of gauge invariant observables in the dual gauge theory whose correlation functions are nonsingular at all times. The two-point correlator for some operators calculated in the gauge theory does not agree with the result from the bulk supergravity solution. However, the bulk calculation is invalid near the singularity where corrections to the supergravity approximation become important. We also obtain pp-waves which are suitable Penrose limits of this general class of solutions, and construct the matrix membrane theory which describes these pp-wave backgrounds.

  14. Magnetic flipping - Reconnection in three dimensions without null points

    NASA Technical Reports Server (NTRS)

    Priest, E. R.; Forbes, T. G.

    1992-01-01

    In three dimensions, magnetic reconnection may take place in a sheared magnetic field at any singular field line, where the nearby field has X-type topology in planes perpendicular to the field line and where an electric field is present parallel to the field line. In the ideal region around the singular line there will, in general, be singularities in the plasma flow and electric field, both at the singular line and at 'magnetic flipping layers', which are remnants of local magnetic separatrices. In the absence of a three-dimensional magnetic neutral point or null point, reconnection of field lines can still occur by a process of magnetic flipping, in which the plasma crosses the flipping layers but the field lines rapidly flip along them by magnetic diffusion. Depending on the boundary conditions, there may be two or four flipping layers which converge on the singular line. A boundary layer analysis of a flipping layer is given, in which the magnetic field parallel to the layer decreases as one crosses it while the plasma pressure (or magnetic pressure associated with the field along the singular line) increases. The width of the flipping layer decreases with distance from the singular line.

  15. Aspects of QCD current algebra on a null plane

    NASA Astrophysics Data System (ADS)

    Beane, S. R.; Hobbs, T. J.

    2016-09-01

    Consequences of QCD current algebra formulated on a light-like hyperplane are derived for the forward scattering of vector and axial-vector currents on an arbitrary hadronic target. It is shown that current algebra gives rise to a special class of sum rules that are direct consequences of the independent chiral symmetry that exists at every point on the two-dimensional transverse plane orthogonal to the lightlike direction. These sum rules are obtained by exploiting the closed, infinite-dimensional algebra satisfied by the transverse moments of null-plane axial-vector and vector charge distributions. In the special case of a nucleon target, this procedure leads to the Adler-Weisberger, Gerasimov-Drell-Hearn, Cabibbo-Radicati and Fubini-Furlan-Rossetti sum rules. Matching to the dispersion-theoretic language which is usually invoked in deriving these sum rules, the moment sum rules are shown to be equivalent to algebraic constraints on forward S-matrix elements in the Regge limit.

  16. A Null Relationship between Media Multitasking and Well-Being

    PubMed Central

    Shih, Shui-I

    2013-01-01

    There is a rapidly increasing trend in media-media multitasking or MMM (using two or more media concurrently). In a recent conference, scholars from diverse disciplines expressed concerns that indulgence in MMM may compromise well-being and/or cognitive abilities. However, research on MMM's impacts is too sparse to inform the general public and policy makers whether MMM should be encouraged, managed, or minimized. The primary purpose of the present study was to develop an innovative computerized instrument – the Survey of the Previous Day (SPD) – to quantify MMM as well as media-nonmedia and nonmedia-nonmedia multitasking and sole-tasking. The secondary purpose was to examine whether these indices could predict a sample of well-being related, psychosocial measures. In the SPD, participants first recalled (typed) what they did during each hour of the previous day. In later parts of the SPD, participants analysed activities and their timing and duration for each hour of the previous day, while relevant recall was on display. Participants also completed the Media Use Questionnaire. The results showed non-significant relationship between tasking measures and well-being related measures. Given how little is known about the associations between MMM and well-being, the null results may offer some general reassurance to those who are apprehensive about negative impacts of MMM. PMID:23691236

  17. Identifying True Cortical Interactions in MEG using the Nulling Beamformer

    PubMed Central

    Hui, Hua Brian; Pantazis, Dimitrios; Bressler, Steven L.; Leahy, Richard M.

    2009-01-01

    Modeling functional brain interaction networks using non-invasive EEG and MEG data is more challenging than using intracranial recording data. This is because most interaction measures are not robust to the cross-talk (interference) between cortical regions, which may arise due to the limited spatial resolution of EEG/MEG inverse procedures. In this paper we describe a modified beam-forming approach to accurately measure cortical interactions from EEG/MEG data, designed to suppress cross-talk between cortical regions. We estimate interaction measures from the output of the modified beamformer and test for statistical significance using permutation tests. Since the underlying neuronal sources and their interactions are unknown in real MEG data, we demonstrate the performance of the proposed beamforming method in a novel simulation scheme, where intracranial recordings from a macaque monkey are used as neural sources to simulate realistic MEG signals. The advantage of this approach is that local field potentials are more realistic representations of true neuronal sources than simulation models and therefore are more suitable to indicate the performance of our nulling beamforming method. PMID:19896541

  18. Invariance Techniques And High-Resolution Null Steering

    NASA Astrophysics Data System (ADS)

    Roy, R.; Kailath, T.

    1988-02-01

    Over the past several decades, a significant amount of research has been performed in the area of high-resolution signal parameter estimation. It is a problem of significance in many signal processing applications including direction-of-arrival estimation in which the locations of multiple sources whose radiation is received by an array of sensors are sought. Much of the research has focussed on approaches based on the formation of optimal weight or copy vectors, procedures derived from the conventional practice of beamforming. This class of approached to parameter estimation problems has come to be known as high-resolution spectral analysis/beamforming since the introduction of the maximum entropy (MEM) method by Burg in 1967, and the maximum-likelihood (ML) method by Capon in 1969. These techniques provide increased resolution and accuracy over their predecessors (including conventional beamforming, but suffer from model mismatch. MUSIC and ESPRIT are recently developed geometric techniques that exploit the underlying model and thereby achieve significant improvements in performance. In this paper, these techniques are summarized. From basic physical principles, it is shown that ESPRIT is actually a multidimensional null steering algorithm, an interpretation with significant intuitive appeal. Finally, optimal signal copy vectors that naturally arise from the algorithm are presented, and their properties as beamforming vectors for this class of problems are discussed.

  19. The topoisomerase I gene from Ustilago maydis: sequence, disruption and mutant phenotype.

    PubMed Central

    Gerhold, D; Thiyagarajan, M; Kmiec, E B

    1994-01-01

    The Ustilago maydis genomic TOP1 gene encoding DNA topoisomerase I was cloned by amplifying a gene fragment using the polymerase chain reaction, and using this fragment to search a genomic DNA library by hybridization. The predicted peptide sequence exhibited 30-40% identity to other eukaryotic TOP1 genes, yet differed in several features. First, an unusually long acidic region was identified near the amino terminus (28/29 residues are acidic), which resembles other nucleolar peptide motifs. Second, an atypical carboxy-terminal 'tail', absent in other TOP1 genes, followed the active site tyrosine residue. A top1 gene disruption mutant was constructed by replacing the genomic TOP1 gene, with a top1::HygR null allele. This mutant lost the abundant topoisomerase I activity evident in wild-type U.maydis, and displayed a subtle coloration phenotype evident during cell senescence. Images PMID:7937091

  20. DNA replication defect in Salmonella typhimurium mutants lacking the editing (epsilon) subunit of DNA polymerase III.

    PubMed Central

    Lifsics, M R; Lancy, E D; Maurer, R

    1992-01-01

    In Salmonella typhimurium, dnaQ null mutants (encoding the epsilon editing subunit of DNA polymerase III [Pol III]) exhibit a severe growth defect when the genetic background is otherwise wild type. Suppression of the growth defect requires both a mutation affecting the alpha (polymerase) subunit of DNA polymerase III and adequate levels of DNA polymerase I. In the present paper, we report on studies that clarify the nature of the physiological defect imposed by the loss of epsilon and the mechanism of its suppression. Unsuppressed dnaQ mutants exhibited chronic SOS induction, indicating exposure of single-stranded DNA in vivo, most likely as gaps in double-stranded DNA. Suppression of the growth defect was associated with suppression of SOS induction. Thus, Pol I and the mutant Pol III combined to reduce the formation of single-stranded DNA or accelerate its maturation to double-stranded DNA. Studies with mutants in major DNA repair pathways supported the view that the defect in DNA metabolism in dnaQ mutants was at the level of DNA replication rather than of repair. The requirement for Pol I was satisfied by alleles of the gene for Pol I encoding polymerase activity or by rat DNA polymerase beta (which exhibits polymerase activity only). Consequently, normal growth is restored to dnaQ mutants when sufficient polymerase activity is provided and this compensatory polymerase activity can function independently of Pol III. The high level of Pol I polymerase activity may be required to satisfy the increased demand for residual DNA synthesis at regions of single-stranded DNA generated by epsilon-minus pol III. The emphasis on adequate polymerase activity in dnaQ mutants is also observed in the purified alpha subunit containing the suppressor mutation, which exhibits a modestly elevated intrinsic polymerase activity relative to that of wild-type alpha. Images PMID:1400246

  1. Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones

    PubMed Central

    Gordo-Gilart, Raquel; Andueza, Sara; Hierro, Loreto; Jara, Paloma; Alvarez, Luis

    2016-01-01

    Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.G68R, p.G228R, p.D459H, and p.A934T resulted in retention of ABCB4 in the endoplasmic reticulum, thus failing to target the plasma membrane. In the present study, we tested the ability of two compounds with chaperone-like activity, 4-phenylbutyrate and curcumin, to rescue these ABCB4 mutants by assessing their effects on subcellular localization, protein maturation, and phospholipid efflux capability. Incubation of transfected cells at a reduced temperature (30°C) or exposure to pharmacological doses of either 4-PBA or curcumin restored cell surface expression of mutants G228R and A934T. The delivery of these mutants to the plasma membrane was accompanied by a switch in the ratio of mature to inmature protein forms, leading to a predominant expression of the mature protein. This effect was due to an improvement in the maturation rate and not to the stabilization of the mature forms. Both mutants were also functionally rescued, displaying bile salt-dependent phospholipid efflux activity after addition of 4-PBA or curcumin. Drug-induced rescue was mutant specific, given neither 4-PBA nor curcumin had an effect on the ABCB4 mutants G68R and A934T. Collectively, these data indicate that the functionality of selected trafficking-defective ABCB4 mutants can be recovered by chemical chaperones through restoration of membrane localization, suggesting a potential treatment for patients carrying such mutations. PMID:26900700

  2. Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones.

    PubMed

    Gordo-Gilart, Raquel; Andueza, Sara; Hierro, Loreto; Jara, Paloma; Alvarez, Luis

    2016-01-01

    Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.G68R, p.G228R, p.D459H, and p.A934T resulted in retention of ABCB4 in the endoplasmic reticulum, thus failing to target the plasma membrane. In the present study, we tested the ability of two compounds with chaperone-like activity, 4-phenylbutyrate and curcumin, to rescue these ABCB4 mutants by assessing their effects on subcellular localization, protein maturation, and phospholipid efflux capability. Incubation of transfected cells at a reduced temperature (30°C) or exposure to pharmacological doses of either 4-PBA or curcumin restored cell surface expression of mutants G228R and A934T. The delivery of these mutants to the plasma membrane was accompanied by a switch in the ratio of mature to inmature protein forms, leading to a predominant expression of the mature protein. This effect was due to an improvement in the maturation rate and not to the stabilization of the mature forms. Both mutants were also functionally rescued, displaying bile salt-dependent phospholipid efflux activity after addition of 4-PBA or curcumin. Drug-induced rescue was mutant specific, given neither 4-PBA nor curcumin had an effect on the ABCB4 mutants G68R and A934T. Collectively, these data indicate that the functionality of selected trafficking-defective ABCB4 mutants can be recovered by chemical chaperones through restoration of membrane localization, suggesting a potential treatment for patients carrying such mutations. PMID:26900700

  3. Why are flare ribbons generically elongated in configurations with magnetic null points?

    NASA Astrophysics Data System (ADS)

    Pontin, David Iain; Galsgaard, Klaus; Demoulin, Pascal

    2016-05-01

    Coronal magnetic null points exist in abundance as demonstrated by extrapolations of the coronal field, and have been inferred to be important for a broad range of energetic events. These null points and their associated separatrix and spine field lines represent discontinuities of the field line mapping, making them preferential locations for reconnection in the corona. In addition, the field line mapping in the vicinity of these null points exhibits strong gradients as measured by the “squashing factor”, Q. We demonstrate that the extension of the Q halos around the spine/fan footpoints is in general important for diagnosing the regions of the photosphere that are magnetically connected to any current layer that forms at the null. In light of this, we discuss the extent to which our results can be used to interpret the geometry of observed flare ribbons in events in which a coronal null is implicated. We conclude that together the physics in the vicinity of the null and how this is related to the extension of Q away from the spine/fan can be used in tandem to understand observational signatures of reconnection at coronal null points.

  4. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

    2000-01-01

    Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

  5. Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

    PubMed Central

    Carbrey, Jennifer M.; Song, Linhua; Zhou, Yao; Yoshinaga, Masafumi; Rojek, Aleksandra; Wang, Yiding; Liu, Yangjian; Lujan, Heidi L.; DiCarlo, Stephen E.; Nielsen, Søren; Rosen, Barry P.; Agre, Peter; Mukhopadhyay, Rita

    2009-01-01

    Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO2, AQP9-null mice suffer reduced survival rates (LD50, 12 mg/kg) compared with WT mice (LD50, 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10–20 times more arsenic than WT mice. Within hours after NaAsO2 injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only ≈10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity. PMID:19805235

  6. Investigation of nulling and subpulse drifting properties of PSR J1727-2739

    NASA Astrophysics Data System (ADS)

    Wen, Z. G.; Wang, N.; Yuan, J. P.; Yan, W. M.; Manchester, R. N.; Yuen, R.; Gajjar, V.

    2016-08-01

    Aims: We intend to study of the nulling and subpulse drifting in PSR J1727-2739 in detail to investigate its radiation properties. Methods: The observations were carried out on 20 March, 2004 using the Parkes 64-m radio telescope with a central frequency of 1518 MHz. A total of 5568 single pulses were analysed. Results: This pulsar shows well-defined nulls with lengths lasting from 6 to 281 pulses and separated by burst phases ranging from 2 to 133 pulses. We estimate a nulling fraction of around 68%. No emission in the average pulse profile integrated over all null pulses is detected with significance above 3σ. Most transitions from nulls to bursts are within a few pulses, whereas the transitions from bursts to nulls exhibit two patterns of decay; these transitions either decrease gradually or rapidly. In the burst phase, we find that there are two distinct subpulse drift modes with vertical spacing between the drift bands of 9.7 ± 1.6 and 5.2 ± 0.9 pulse periods, while sometimes there is a third mode with no subpulse drifting. Some mode transitions occur within a single burst, while others are separated by nulls. Different modes have different average pulse profiles. Possible physical mechanisms are discussed.

  7. A Sall4 Mutant Mouse Model Useful for Studying the Role of Sall4 in Early Embryonic Development and Organogenesis

    PubMed Central

    Warren, Madhuri; Wang, Wei; Spiden, Sarah; Chen-Murchie, Dongrong; Tannahill, David; Steel, Karen P.; Bradley, Allan

    2008-01-01

    Summary SALL4 is a homologue of the Drosophila homeotic gene spalt, a zinc finger transcription factor, required for inner cell mass proliferation in early embryonic development. It also interacts with other transcription factors to control the development of the anorectal region, kidney, heart, limbs, and brain. Truncating mutations in SALL4 cause Okihiro syndrome, manifest as Duane anomaly, radial ray defects and sensorineural and conductive deafness. We report the characterization of a novel murine Sall4 null allele created by bacterial recombineering in ES cells. Homozygous mutant mice exhibit early embryonic lethality. Heterozygous mutant mice recapitulate phenotypic features of Okihiro syndrome including deafness, lower anogenital tract abnormalities, renal hypoplasia, anencephaly, Hirschprung’s disease, and skeletal defects. This phenotype shows important differences in cardiac and ear manifestations to previously characterized Sall4 mutant alleles and should prove useful for the investigation of the influence of modifier alleles and protein interactions on the transcriptional regulatory function of Sall4. PMID:17216607

  8. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

    PubMed Central

    Soenjaya, Y.; Foster, B.L.; Nociti, F.H.; Ao, M.; Holdsworth, D.W.; Hunter, G.K.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP

  9. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

    PubMed

    Soenjaya, Y; Foster, B L; Nociti, F H; Ao, M; Holdsworth, D W; Hunter, G K; Somerman, M J; Goldberg, H A

    2015-09-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the

  10. Integrated optics for nulling interferometry in the thermal infrared

    NASA Astrophysics Data System (ADS)

    Barillot, Marc; Barthelemy, Eleonore; Broquin, Jean-Emmanuel; Frayret, Jérôme; Grelin, Jérôme; Hawkins, Gary; Kirschner, Volker; Parent, Gilles; Pradel, Annie; Rossi, Emmanuel; Vigreux, Caroline; Zhang, Shaoqian; Zhang, Xianghua

    2008-07-01

    Modal filtering is based on the capability of single-mode waveguides to transmit only one complex amplitude function to eliminate virtually any perturbation of the interfering wavefronts, thus making very high rejection ratios possible in a nulling interferometer. In the present paper we focus on the progress of Integrated Optics in the thermal infrared [6-20μm] range, one of the two candidate technologies for the fabrication of Modal Filters, together with fiber optics. In conclusion of the European Space Agency's (ESA) "Integrated Optics for Darwin" activity, etched layers of chalcogenide material deposited on chalcogenide glass substrates was selected among four candidates as the technology with the best potential to simultaneously meet the filtering efficiency, absolute and spectral transmission, and beam coupling requirements. ESA's new "Integrated Optics" activity started at mid-2007 with the purpose of improving the technology until compliant prototypes can be manufactured and validated, expectedly by the end of 2009. The present paper aims at introducing the project and the components requirements and functions. The selected materials and preliminary designs, as well as the experimental validation logic and test benches are presented. More details are provided on the progress of the main technology: vacuum deposition in the co-evaporation mode and subsequent etching of chalcogenide layers. In addition, preliminary investigations of an alternative technology based on burying a chalcogenide optical fiber core into a chalcogenide substrate are presented. Specific developments of anti-reflective solutions designed for the mitigation of Fresnel losses at the input and output surface of the components are also introduced.

  11. Null Mutations in LTBP2 Cause Primary Congenital Glaucoma

    PubMed Central

    Ali, Manir; McKibbin, Martin; Booth, Adam; Parry, David A.; Jain, Payal; Riazuddin, S. Amer; Hejtmancik, J. Fielding; Khan, Shaheen N.; Firasat, Sabika; Shires, Mike; Gilmour, David F.; Towns, Katherine; Murphy, Anna-Louise; Azmanov, Dimitar; Tournev, Ivailo; Cherninkova, Sylvia; Jafri, Hussain; Raashid, Yasmin; Toomes, Carmel; Craig, Jamie; Mackey, David A.; Kalaydjieva, Luba; Riazuddin, Sheikh; Inglehearn, Chris F.

    2009-01-01

    Primary congenital glaucoma (PCG) is an autosomal-recessive condition characterized by high intraocular pressure (IOP), usually within the first year of life, which potentially could lead to optic nerve damage, globe enlargement, and permanent loss of vision. To date, PCG has been linked to three loci: 2p21 (GLC3A), for which the responsible gene is CYP1B1, and 1p36 (GLC3B) and 14q24 (GLC3C), for which the genes remain to be identified. Here we report that null mutations in LTBP2 cause PCG in four consanguineous families from Pakistan and in patients of Gypsy ethnicity. LTBP2 maps to chromosome 14q24.3 but is around 1.3 Mb proximal to the documented GLC3C locus. Therefore, it remains to be determined whether LTBP2 is the GLC3C gene or whether a second adjacent gene is also implicated in PCG. LTBP2 is the largest member of the latent transforming growth factor (TGF)-beta binding protein family, which are extracellular matrix proteins with multidomain structure. It has homology to fibrillins and may have roles in cell adhesion and as a structural component of microfibrils. We confirmed localization of LTBP2 in the anterior segment of the eye, at the ciliary body, and particularly the ciliary process. These findings reveal that LTBP2 is essential for normal development of the anterior chamber of the eye, where it may have a structural role in maintaining ciliary muscle tone. PMID:19361779

  12. Lateral shearing with a pair of double Fresnel rhombs for nulling interferometry.

    PubMed

    Baba, Naoshi; Kobayashi, Keita; Kogoma, Yusuke; Murakami, Naoshi

    2011-09-15

    A lateral-shearing interferometer with a pair of double Fresnel rhombs is proposed. Use of Fresnel rhombs enables us to accomplish simultaneously lateral shearing and achromatic nulling. Nulling interferometry with lateral shearing is one of the basic methods for searching directly for extrasolar planets with a segmented-mirror telescope. Here the Thirty-Meter Telescope is considered as a model of a segmented-mirror telescope. Our computer simulations show high extinction for the K-band (2.0-2.4 μm). Optical experiments are conducted to verify the lateral shearing and nulling with a pair of double Fresnel rhombs. PMID:21931407

  13. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras

    PubMed Central

    Keighren, Margaret A.; Flockhart, Jean H.

    2016-01-01

    ABSTRACT The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1−/− null mouse embryos die but a previous study showed that some homozygous Gpi1−/− null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1−/−↔Gpi1c/c chimaera with functional Gpi1−/− null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1−/− null cells in adult Gpi1−/−↔Gpi1c/c chimaeras and determine if Gpi1−/− null germ cells are functional. Analysis of adult Gpi1−/−↔Gpi1c/c chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1−/− null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1−/− null oocytes in one female Gpi1−/−↔Gpi1c/c chimaera were functional and provided preliminary evidence that one male putative Gpi1−/−↔Gpi1c/c chimaera produced functional spermatozoa from homozygous Gpi1−/− null germ cells. Although the male chimaera was almost certainly Gpi1−/−↔Gpi1c/c, this part of the study is considered preliminary because only blood was typed for GPI. Gpi1−/− null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1−/− null germ cells, it successfully identified functional Gpi1−/− null oocytes and revealed that some Gpi1−/− null cells could survive in many adult tissues. PMID:27103217

  14. Visualization of redundancy resolution for kinematically redundant robots through the Jacobian null space

    NASA Technical Reports Server (NTRS)

    Chen, Yu-Che; Walker, Ian D.; Cheatham, John B., Jr.

    1992-01-01

    We present a unified formulation for the inverse kinematics of redundant arms, based on a special formulation of the null space of the Jacobian. By extending (appropriately re-scaling) previously used null space parameterizations, we obtain, in a unified fashion, the manipulability measure, the null space projector, and particular solutions for the joint velocities. We obtain the minimum norm pseudo-inverse solution as a projection from any particular solution, and the method provides an intuitive visualization of the self-motion. The result is a computationally efficient, consistent approach to computing redundant robot inverse kinematics.

  15. lon incompatibility associated with mutations causing SOS induction: null uvrD alleles induce an SOS response in Escherichia coli.

    PubMed

    SaiSree, L; Reddy, M; Gowrishankar, J

    2000-06-01

    The uvrD gene in Escherichia coli encodes a 720-amino-acid 3'-5' DNA helicase which, although nonessential for viability, is required for methyl-directed mismatch repair and nucleotide excision repair and furthermore is believed to participate in recombination and DNA replication. We have shown in this study that null mutations in uvrD are incompatible with lon, the incompatibility being a consequence of the chronic induction of SOS in uvrD strains and the resultant accumulation of the cell septation inhibitor SulA (which is a normal target for degradation by Lon protease). uvrD-lon incompatibility was suppressed by sulA, lexA3(Ind(-)), or recA (Def) mutations. Other mutations, such as priA, dam, polA, and dnaQ (mutD) mutations, which lead to persistent SOS induction, were also lon incompatible. SOS induction was not observed in uvrC and mutH (or mutS) mutants defective, respectively, in excision repair and mismatch repair. Nor was uvrD-mediated SOS induction abolished by mutations in genes that affect mismatch repair (mutH), excision repair (uvrC), or recombination (recB and recF). These data suggest that SOS induction in uvrD mutants is not a consequence of defects in these three pathways. We propose that the UvrD helicase participates in DNA replication to unwind secondary structures on the lagging strand immediately behind the progressing replication fork, and that it is the absence of this function which contributes to SOS induction in uvrD strains. PMID:10809694

  16. Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1.

    PubMed

    Heinrich, Garrett; Russo, Lucia; Castaneda, Tamara R; Pfeiffer, Verena; Ghadieh, Hilda E; Ghanem, Simona S; Wu, Jieshen; Faulkner, Latrice D; Ergün, Süleyman; McInerney, Marcia F; Hill, Jennifer W; Najjar, Sonia M

    2016-05-20

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1(-/-)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(-/-) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid β-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(-/-) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty-acid synthase activity could underlie altered energy balance in these mice. PMID:27002145

  17. Arabidopsis mutants impaired in cosuppression.

    PubMed Central

    Elmayan, T; Balzergue, S; Béon, F; Bourdon, V; Daubremet, J; Guénet, Y; Mourrain, P; Palauqui, J C; Vernhettes, S; Vialle, T; Wostrikoff, K; Vaucheret, H

    1998-01-01

    Post-transcriptional gene silencing (cosuppression) results in the degradation of RNA after transcription. A transgenic Arabidopsis line showing post-transcriptional silencing of a 35S-uidA transgene and uidA-specific methylation was mutagenized using ethyl methanesulfonate. Six independent plants were isolated in which uidA mRNA accumulation and beta-glucuronidase activity were increased up to 3500-fold, whereas the transcription rate of the 35S-uidA transgene was increased only up to threefold. These plants each carried a recessive monogenic mutation that is responsible for the release of silencing. These mutations defined two genetic loci, called sgs1 and sgs2 (for suppressor of gene silencing). Transgene methylation was distinctly modified in sgs1 and sgs2 mutants. However, methylation of centromeric repeats was not affected, indicating that sgs mutants differ from ddm (for decrease in DNA methylation) and som (for somniferous) mutants. Indeed, unlike ddm and som mutations, sgs mutations were not able to release transcriptional silencing of a 35S-hpt transgene. Conversely, both sgs1 and sgs2 mutations were able to release cosuppression of host Nia genes and 35S-Nia2 transgenes. These results therefore indicate that sgs mutations act in trans to impede specifically transgene-induced post-transcriptional gene silencing. PMID:9761800

  18. Problem-Solving Test: Tryptophan Operon Mutants

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  19. Chromosome instability mutants of Saccharomyces cerevisiae that are defective in microtubule-mediated processes.

    PubMed Central

    Hoyt, M A; Stearns, T; Botstein, D

    1990-01-01

    By using a multiply marked supernumerary chromosome III as an indicator, we isolated mutants of Saccharomyces cerevisiae that display increased rates of chromosome loss. In addition to mutations in the tubulin-encoding TUB genes, we found mutations in the CIN1, CIN2, and CIN4 genes. These genes have been defined independently by mutations causing benomyl supersensitivity and are distinct from other known yeast genes that affect chromosome segregation. Detailed phenotypic characterization of cin mutants revealed several other phenotypes similar to those of tub mutants. Null alleles of these genes caused cold sensitivity for viability. At 11 degrees C, cin mutants arrest at the mitosis stage of their cell cycle because of loss of most microtubule structure. cin1, cin2, and cin4 mutations also cause defects in two other microtubule-mediated processes, nuclear migration and nuclear fusion (karyogamy). Overproduction of the CIN1 gene product was found to cause the same phenotype as loss of function, supersensitivity to benomyl. Our findings suggest that the CIN1, CIN2, and CIN4 proteins contribute to microtubule stability either by regulating the activity of a yeast microtubule component or as structural components of microtubules. Images PMID:2403635

  20. Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant.

    PubMed

    Daviaud, Nicolas; Chen, Karen; Huang, Yong; Friedel, Roland H; Zou, Hongyan

    2016-08-01

    Mammalian cortical expansion is tightly controlled by fine-tuning of proliferation and differentiation of neural progenitors in a region-specific manner. How extrinsic cues interface with cell-intrinsic programs to balance proliferative versus neurogenic decisions remains an unsolved question. We examined the function of Semaphorin receptors Plexin-B1 and -B2 in corticogenesis by generating double mutants, whereby Plexin-B2 was conditionally ablated in the developing brain in a Plexin-B1 null mutant background. Absence of both Plexin-Bs resulted in cortical thinning, particularly in the caudomedial cortex. Plexin-B1/B2 double, but not single, mutants exhibited a reduced neural progenitor pool, attributable to decreased proliferation and an altered division mode favoring cell cycle exit. This resulted in deficient production of neurons throughout the neurogenic period, proportionally affecting all cortical laminae. Consistent with the in vivo data, cultured neural progenitors lacking both Plexin-B1 and -B2 displayed decreased proliferative capacity and increased spontaneous differentiation. Our study therefore defines a novel function of Plexin-B1 and -B2 in transmitting extrinsic signals to maintain proliferative and undifferentiated states of neural progenitors. As single mutants displayed no apparent cortical defects, we conclude that Plexin-B1 and -B2 play redundant or compensatory roles during forebrain development to ensure proper neuronal production and neocortical expansion. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 882-899, 2016. PMID:26579598

  1. Isolation and characterization of a mutant defective in triacylglycerol accumulation in nitrogen-starved Chlamydomonas reinhardtii.

    PubMed

    Hung, Chun-Hsien; Kanehara, Kazue; Nakamura, Yuki

    2016-09-01

    Triacylglycerol (TAG), a major source of biodiesel production, accumulates in nitrogen-starved Chlamydomonas reinhardtii. However, the metabolic pathway of starch-to-TAG conversion remains elusive because an enzyme that affects the starch degradation is unknown. Here, we isolated a new class of mutant bgal1, which expressed an overaccumulation of starch granules and defective photosynthetic growth. The bgal1 was a null mutant of a previously uncharacterized β-galactosidase-like gene (Cre02.g119700), which decreased total β-galactosidase activity 40% of the wild type. Upon nitrogen starvation, the bgal1 mutant showed decreased TAG accumulation mainly due to the reduced flux of de novo TAG biosynthesis evidenced by increased unsaturation of fatty acid composition in TAG and reduced TAG accumulation by additional supplementation of acetate to the culture media. Metabolomic analysis of the bgal1 mutant showed significantly reduced levels of metabolites following the hydrolysis of starch and substrates for TAG accumulation, whereas metabolites in TCA cycle were unaffected. Upon nitrogen starvation, while levels of glucose 6-phosphate, fructose 6-phosphate and acetyl-CoA remained lower, most of the other metabolites in glycolysis were increased but those in the TCA cycle were decreased, supporting TAG accumulation. We suggest that BGAL1 may be involved in the degradation of starch, which affects TAG accumulation in nitrogen-starved C. reinhardtii. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:27060488

  2. Dynamics-independent null experiment for testing time-reversal invariance

    NASA Astrophysics Data System (ADS)

    Arash, Firooz; Moravcsik, Michael J.; Goldstein, Gary R.

    1985-06-01

    It is shown that it is impossible to construct, in any reaction in atomic, nuclear, or particle physics, a null experiment that would unambiguously test the validity of time-reversal invariance independently of dynamical assumptions.

  3. High-resolution adaptive nulling performance for a lightweight agile EHF multiple beam antenna

    NASA Astrophysics Data System (ADS)

    Fenn, A. J.; Johnson, J. R.; Rispin, L. W.; Cummings, W. C.; Potts, B. M.

    The design and experimental performance of a lightweight high-resolution adaptive nulling extremely high-frequency multiple beam antenna (MBA) are addressed. A 127-beam MBA and a four-channel RF nulling network operating over the 43.5-to-45.5-GHz band were used to adaptively null a jammer in anechoic chamber measurements. Lightweight waveguide transmission lines together with ferrite switches were used to select beam ports from the 127-beam MBA. The MBA was designed to provide simultaneous coverage for three communications system users while providing pattern discrimination or nulling of jammers located within 0.1 deg of the user. Cancellation greater than 30 dB when operating in a wideband mode was experimentally demonstrated.

  4. Addressing the "Null Curriculum": Teaching about Genocides Other than the Holocaust.

    ERIC Educational Resources Information Center

    Totten, Samuel

    2001-01-01

    Describes the idea of the null curriculum in the context of teaching about genocide. Explores obstacles that prevent educators from teaching about genocides other than the Holocaust. Explains how teachers can begin teaching about other genocides in their classrooms. (CMK)

  5. Asymptotical null structure of an electro-vacuum spacetime with a cosmological constant

    NASA Astrophysics Data System (ADS)

    He, Xiaokai; Cao, Zhoujian; Jing, Jiliang

    2016-05-01

    Bondi-Sachs (BS) framework is a powerful tool to analyze the asymptotical null structure of a spacetime. Based on Bondi’s outgoing boundary condition, the asymptotical null structure of an electro-vacuum spacetime without a cosmological constant has been constructed clearly. Recently more and more observations imply that the Einstein equation should be modified with an nonzero cosmological constant. It is interesting to investigate the asymptotical null structure of a spacetime with a cosmological constant. In this paper, we extend our previous result from vacuum case to electro-vacuum case. We find that the gravitational sector of the asymptotical null structure depends strongly on the boundary conditions, while the electrical sector is independent of the boundary condition.

  6. ON THE NATURE OF RECONNECTION AT A SOLAR CORONAL NULL POINT ABOVE A SEPARATRIX DOME

    SciTech Connect

    Pontin, D. I.; Priest, E. R.; Galsgaard, K.

    2013-09-10

    Three-dimensional magnetic null points are ubiquitous in the solar corona and in any generic mixed-polarity magnetic field. We consider magnetic reconnection at an isolated coronal null point whose fan field lines form a dome structure. Using analytical and computational models, we demonstrate several features of spine-fan reconnection at such a null, including the fact that substantial magnetic flux transfer from one region of field line connectivity to another can occur. The flux transfer occurs across the current sheet that forms around the null point during spine-fan reconnection, and there is no separator present. Also, flipping of magnetic field lines takes place in a manner similar to that observed in the quasi-separatrix layer or slip-running reconnection.

  7. Null test of the cosmic curvature using H (z ) and supernovae data

    NASA Astrophysics Data System (ADS)

    Cai, Rong-Gen; Guo, Zong-Kuan; Yang, Tao

    2016-02-01

    We introduce a model-independent approach to the null test of the cosmic curvature, which is geometrically related to the Hubble parameter H (z ) and luminosity distance dL(z ). Combining the independent observations of H (z ) and dL(z ), we use the model-independent smoothing technique, Gaussian processes, to reconstruct them and determine the cosmic curvature ΩK(0 ) in the null test relation. The null test is totally geometrical and does not assume any cosmological model. We show that the cosmic curvature ΩK(0 )=0 is consistent with current observational data sets, falling within the 1 σ limit. To demonstrate the effect on the precision of the null test, we produce a series of simulated data of the models with different ΩK(0 ). Future observations in better quality can provide a greater improvement to constrain or refute the flat universe with ΩK(0 )=0 .

  8. Vlasov Fluid stability of a 2-D plasma with a linear magnetic field null

    SciTech Connect

    Kim, J.S.

    1984-01-01

    Vlasov Fluid stability of a 2-dimensional plasma near an O type magnetic null is investigated. Specifically, an elongated Z-pinch is considered, and applied to Field Reversed Configurations at Los Alamos National Laboratory by making a cylindrical approximation of the compact torus. The orbits near an elliptical O type null are found to be very complicated; the orbits are large and some are stochastic. The kinetic corrections to magnetohydrodynamics (MHD) are investigated by evaluating the expectation values of the growth rates of a Vlasov Fluid dispersion functional by using a set of trial functions based on ideal MHD. The dispersion functional involves fluid parts and orbit dependent parts. The latter involves phase integral of two time correlations. The phase integral is replaced by the time integral both for the regular and for the stochastic orbits. Two trial functions are used; one has a large displacement near the null and the other away from the null.

  9. Non-null testing for aspheric surfaces using elliptical sub-aperture stitching technique.

    PubMed

    Zhao, Zixin; Zhao, Hong; Gu, Feifei; Du, Hubing; Li, Kaixing

    2014-03-10

    We propose an elliptical sub-aperture stitching (ESAS) method to measure the aspheric surfaces. In our method, the non-null configuration is used to overcome the disadvantages of the null testing. By adding the dynamic tilt, the different local nearly null fringe patterns are obtained and the corresponding phase data in the elliptical masks is extracted with negligible retrace errors. In order to obtain the full aperture result, a stitching algorithm is developed to stitch all the phase data together. We firstly show the principle of our method. Then the performance of the proposed method is analyzed by simulation experiments. In the end, practical examples are given to demonstrate the correctness of the proposed method. The stitching result shows a good agreement with the full-aperture null testing result. PMID:24663891

  10. Theoretical and experimental arguments suporting the non-null photonic mass hypothesis

    NASA Astrophysics Data System (ADS)

    Popescu, Silvestru; Griga, Violeta

    The authors review the problem of the photonic non-null mass since Kobzarev and Okun' papres till Goldhaber and Nieto's papers. A calculus is made for the electromagnetic field in a spherical cavity supposing that the photonic mass is non-null. It is shown, that the force between the center of the sphere and the sphere's surface is null, while the force between any other point inside and a point on the sphere is non-null. A review of the experimental results has been given also. A more accurate stile will be desired for Physicists names as well as for some physical notions. As well the upper limit for the photonic mass as obtained in Pioneer 10 experiment (1974) is 8x10^-52 Kg not 10^-52 Kg. The authors are asked to be more accurate in their writings.

  11. Divertor with a third-order null of the poloidal field

    SciTech Connect

    Ryutov, D. D.; Umansky, M. V.

    2013-09-15

    A concept and preliminary feasibility analysis of a divertor with the third-order poloidal field null is presented. The third-order null is the point where not only the field itself but also its first and second spatial derivatives are zero. In this case, the separatrix near the null-point has eight branches, and the number of strike-points increases from 2 (as in the standard divertor) to six. It is shown that this magnetic configuration can be created by a proper adjustment of the currents in a set of three divertor coils. If the currents are somewhat different from the required values, the configuration becomes that of three closely spaced first-order nulls. Analytic approach, suitable for a quick orientation in the problem, is used. Potential advantages and disadvantages of this configuration are briefly discussed.

  12. Drosophila atonal fully rescues the phenotype of Math1 null mice: new functions evolve in new cellular contexts

    NASA Technical Reports Server (NTRS)

    Wang, Vincent Y.; Hassan, Bassem A.; Bellen, Hugo J.; Zoghbi, Huda Y.

    2002-01-01

    Many genes share sequence similarity between species, but their properties often change significantly during evolution. For example, the Drosophila genes engrailed and orthodenticle and the onychophoran gene Ultrabithorax only partially substitute for their mouse or Drosophila homologs. We have been analyzing the relationship between atonal (ato) in the fruit fly and its mouse homolog, Math1. In flies, ato acts as a proneural gene that governs the development of chordotonal organs (CHOs), which serve as stretch receptors in the body wall and joints and as auditory organs in the antennae. In the fly CNS, ato is important not for specification but for axonal arborization. Math1, in contrast, is required for the specification of cells in both the CNS and the PNS. Furthermore, Math1 serves a role in the development of secretory lineage cells in the gut, a function that does not parallel any known to be served by ato. We wondered whether ato and Math1 might be more functionally homologous than they appear, so we expressed Math1 in ato mutant flies and ato in Math1 null mice. To our surprise, the two proteins are functionally interchangeable.

  13. Null mutation of peroxisome proliferator-activated receptor-interacting protein in mammary glands causes defective mammopoiesis.

    PubMed

    Qi, Chao; Kashireddy, Papreddy; Zhu, Yiwei Tony; Rao, Sambasiva M; Zhu, Yi-Jun

    2004-08-01

    To investigate the role of nuclear receptor coactivator peroxisome proliferator-activated receptor-interacting protein (PRIP) in mammary gland development, we generated a conditional null mutation of PRIP in mammary glands. In PRIP-deficient mammary glands, the elongation of ducts during puberty was not affected, but the numbers of ductal branches were decreased, a condition that persisted long after puberty, indicating that the potential of ductal branching was impaired. During pregnancy, PRIP-deficient mammary glands exhibited decreased alveolar density. The lactating PRIP-deficient glands contained scant lobuloalveoli with many adipocytes, whereas the wild type glands were composed of virtually no adipocytes but mostly lobuloalveoli. As a result, PRIP mammary-deficient glands could not produce enough milk to nurse all the pups during lactation. The ductal branching of mammary glands in response to estrogen treatment was attenuated in PRIP mutant glands. Whereas the proliferation index was similar between wild type and PRIP-deficient glands, increased apoptosis was observed in PRIP-deficient glands. PRIP-deficient glands expressed increased amphiregulin, transforming growth factor-alpha, and betacellulin mRNA as compared with wild type glands. The differentiated function of PRIP-deficient mammary epithelial cells was largely intact, as evidenced by the expression of abundant beta-casein, whey acidic protein (WAP), and WDNM1 mRNA. We conclude that PRIP is important for normal mammary gland development. PMID:15161927

  14. Dynamic Stability of Lateral and Yawing Motions in the Double Null-Flux EDS System

    NASA Astrophysics Data System (ADS)

    Murai, Toshiaki; Yoshioka, Hiroshi; Sugino, Motohiko

    The double null-flux electro-dynamic suspension (EDS) in the superconducting maglev has the coupling lateral and yawing stiffness, which does not coincide with each other, so special attention should be paid to the dynamic stability of lateral and yawing motions. This paper describes their intrinsic dynamic stability by analyzing the lateral and yawing motions of bogie levitated by the double null-flux EDS.

  15. Delayed development of specific thyroid hormone-regulated events in transthyretin null mice

    PubMed Central

    Monk, Julie A.; Sims, Natalie A.; Dziegielewska, Katarzyna M.; Weiss, Roy E.; Ramsay, Robert G.

    2013-01-01

    Thyroid hormones (THs) are vital for normal postnatal development. Extracellular TH distributor proteins create an intravascular reservoir of THs. Transthyretin (TTR) is a TH distributor protein in the circulatory system and is the only TH distributor protein synthesized in the central nervous system. We investigated the phenotype of TTR null mice during development. Total and free 3′,5′,3,5-tetraiodo-l-thyronine (T4) and free 3′,3,5-triiodo-l-thyronine (T3) in plasma were significantly reduced in 14-day-old (P14) TTR null mice. TTR null mice also displayed a delayed suckling-to-weaning transition, decreased muscle mass, delayed growth, and retarded longitudinal bone growth. In addition, ileums from postnatal day 0 (P0) TTR null mice displayed disordered architecture and contained fewer goblet cells than wild type. Protein concentrations in cerebrospinal fluid from P0 and P14 TTR null mice were higher than in age-matched wild-type mice. In contrast to the current literature based on analyses of adult TTR null mice, our results demonstrate that TTR has an important and nonredundant role in influencing the development of several organs. PMID:23092911

  16. [Development of a new type soybean germplasm with null lipoxygenase isozymes].

    PubMed

    Han, Fen-Xia; Ding, An-Lin; Sun, Jun-Ming; Li, Gui-Ying

    2005-02-01

    Soybean protein is a kind of high-quality protein composed of balanced amino acids. It contains all kinds of amino acids, especially eight amino acids necessary for human, but also contains some components that are not good for human and affect food quality, such as Lipoxygenase (Lox) and Trypsin inhibitor (Ti). Nutritional value and processing quality of soybean can be improved by means of development of new variety with null Lox and Ti. In this paper, a new type soybean germplasm with null lipoxygenase isozymes was developed by Institute of Crop Sciences, Chinese Academy of Agricultural Sciences through years of biochemical marker assistant selection for null lipoxygenase by means of isoelectric focusing-polyacrylamid gel electrophoresis (IEF-PAGE) in the hybrid progenies of "96P17" (Female parent, a null lipoxygenase 2.3 line) and "93704" (Male parent, a null lipoxygenase 1.3 line). It is the first new soybean germplasm with null Lox1.2.3 genes in our country, which will contribute to soybean breeding for high quality, soybean production and utilization. In this paper, the development process of new type soybean germplasm is described. PMID:15759868

  17. Location of the non-tidal current null zone in northern San Francisco Bay

    USGS Publications Warehouse

    Peterson, D.H.; Conomos, T.J.; Broenkow, W.W.; Doherty, P.C.

    1975-01-01

    Variations in Sacramento-San Joaquin River discharge into northern San Francisco Bay causes shifts in location of the bottom density current null zone. At a river flow of 2000 m3/s this null zone is approximately 20 km from the seaward end of the estuary, whereas at a river flow of 100 m3/s it is 80 km from the seaward end; the corresponding distances of salinity penetration are approximately 40 and 90 km from the seaward end. Seaward of the null zone, during low (summer) river discharge conditions, the inward-flowing bottom density current appears typically strong (5-15 cm/s) relative to the outward-flowing river current (river discharge per unit cross-channel area) of <2 cm/s. Landward from this null zone the average river current increases with decreasing cross-channel area. This circulation implies that during the summer water within the null zone has the longest average advective replacement time relative to water seaward or landward of the null zone. ?? 1975.

  18. pyNSMC: A Python Module for Null-Space Monte Carlo Uncertainty Analysis

    NASA Astrophysics Data System (ADS)

    White, J.; Brakefield, L. K.

    2015-12-01

    The null-space monte carlo technique is a non-linear uncertainty analyses technique that is well-suited to high-dimensional inverse problems. While the technique is powerful, the existing workflow for completing null-space monte carlo is cumbersome, requiring the use of multiple commandline utilities, several sets of intermediate files and even a text editor. pyNSMC is an open-source python module that automates the workflow of null-space monte carlo uncertainty analyses. The module is fully compatible with the PEST and PEST++ software suites and leverages existing functionality of pyEMU, a python framework for linear-based uncertainty analyses. pyNSMC greatly simplifies the existing workflow for null-space monte carlo by taking advantage of object oriented design facilities in python. The core of pyNSMC is the ensemble class, which draws and stores realized random vectors and also provides functionality for exporting and visualizing results. By relieving users of the tedium associated with file handling and command line utility execution, pyNSMC instead focuses the user on the important steps and assumptions of null-space monte carlo analysis. Furthermore, pyNSMC facilitates learning through flow charts and results visualization, which are available at many points in the algorithm. The ease-of-use of the pyNSMC workflow is compared to the existing workflow for null-space monte carlo for a synthetic groundwater model with hundreds of estimable parameters.

  19. Proving the achronal averaged null energy condition from the generalized second law

    SciTech Connect

    Wall, Aron C.

    2010-01-15

    A null line is a complete achronal null geodesic. It is proven that for any quantum fields minimally coupled to semiclassical Einstein gravity, the averaged null energy condition (ANEC) on null lines is a consequence of the generalized second law of thermodynamics for causal horizons. This result is shown to leading order in Planck's constant for perturbations to classical backgrounds satisfying the null energy condition. Auxiliary assumptions include CPT and the existence of a suitable renormalization scheme for the generalized entropy. Although the ANEC can be violated on general geodesics in curved spacetimes, as long as the ANEC holds on null lines there exist theorems showing that semiclassical gravity should satisfy positivity of energy, topological censorship, and should not admit closed timelike curves. It is pointed out that these theorems fail once the linearized graviton field is quantized, because then the renormalized shear-squared term in the Raychaudhuri equation can be negative. A 'shear-inclusive' generalization of the ANEC is proposed to remedy this, and is proven under an additional assumption about perturbations to horizons in classical general relativity.

  20. Losses at magnetic nulls in pulsed-power transmission line systems

    NASA Astrophysics Data System (ADS)

    Mendel, C. W.; Pointon, T. D.; Savage, M. E.; Seidel, D. B.; Magne, I.; Vézinet, R.

    2006-04-01

    Pulsed-power systems operating in the terawatt regime must deal with large electron flows in vacuum transmission lines. In most parts of these transmission lines the electrons are constrained by the self-magnetic field to flow parallel to the conductors. In very low impedance systems, such as those used to drive Z-pinch radiation sources, the currents from multiple transmission lines are added together. This addition necessarily involves magnetic nulls that connect the positive and negative electrodes. The resultant local loss of magnetic insulation results in electron losses at the anode in the vicinity of the nulls. The lost current due to the magnetic null might or might not be appreciable. In some cases the lost current due to the null is not large, but is spatially localized, and may create a gas and plasma release from the anode that can lead to an excessive loss, and possibly to catastrophic damage to the hardware. In this paper we describe an analytic model that uses one geometric parameter (aside from straightforward hardware size measurements) that determines the loss to the anode, and the extent of the loss region when the driving source and load are known. The parameter can be calculated in terms of the magnetic field in the region of the null calculated when no electron flow is present. The model is compared to some experimental data, and to simulations of several different hardware geometries, including some cases with multiple nulls, and unbalanced feeds.

  1. Premeiotic germ cell defect in seminiferous tubules of Atm-null testis

    SciTech Connect

    Takubo, Keiyo . E-mail: keiyot@gmail.com; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio . E-mail: sudato@sc.itc.keio.ac.jp

    2006-12-29

    Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16{sup Ink4a} activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16{sup Ink4a}-mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16{sup Ink4a}-mediated senescence.

  2. Losses at magnetic nulls in pulsed-power transmission line systems

    SciTech Connect

    Mendel, C.W. Jr.; Pointon, T.D.; Savage, M.E.; Seidel, D.B.; Magne, I.; Vezinet, R.

    2006-04-15

    Pulsed-power systems operating in the terawatt regime must deal with large electron flows in vacuum transmission lines. In most parts of these transmission lines the electrons are constrained by the self-magnetic field to flow parallel to the conductors. In very low impedance systems, such as those used to drive Z-pinch radiation sources, the currents from multiple transmission lines are added together. This addition necessarily involves magnetic nulls that connect the positive and negative electrodes. The resultant local loss of magnetic insulation results in electron losses at the anode in the vicinity of the nulls. The lost current due to the magnetic null might or might not be appreciable. In some cases the lost current due to the null is not large, but is spatially localized, and may create a gas and plasma release from the anode that can lead to an excessive loss, and possibly to catastrophic damage to the hardware. In this paper we describe an analytic model that uses one geometric parameter (aside from straightforward hardware size measurements) that determines the loss to the anode, and the extent of the loss region when the driving source and load are known. The parameter can be calculated in terms of the magnetic field in the region of the null calculated when no electron flow is present. The model is compared to some experimental data, and to simulations of several different hardware geometries, including some cases with multiple nulls, and unbalanced feeds.

  3. Losses at magnetic nulls in pulsed-power transmission line systems.

    SciTech Connect

    Magne, I.; Savage, Mark Edward; Seidel, David Bruce; Mendel, Clifford Will, Jr.; Pointon, Timothy David; Vezinet, R.

    2004-08-01

    Pulsed-power systems operating in the terawatt regime must deal with large electron flows in vacuum transmission lines. In most parts of these transmission lines the electrons are constrained by the self-magnetic field to flow parallel to the conductors. In very low impedance systems, such as those used to drive Z-pinch radiation sources, the currents from multiple transmission lines are added together. This addition necessarily involves magnetic nulls that connect the positive and negative electrodes. The resultant local loss of magnetic insulation results in electron losses at the anode in the vicinity of the nulls. The lost current due to the magnetic null might or might not be appreciable. In some cases the lost current due to the null is not large, but is spatially localized, and may create a gas and plasma release from the anode that can lead to an excessive loss, and possibly to catastrophic damage to the hardware. In this paper we describe an analytic model that uses one geometric parameter (aside from straightforward hardware size measurements) that determines the loss to the anode, and the extent of the loss region when the driving source and load are known. The parameter can be calculated in terms of the magnetic field in the region of the null calculated when no electron flow is present. The model is compared to some experimental data, and to simulations of several different hardware geometries, including some cases with multiple nulls, and unbalanced feeds.

  4. The Identification of Zebrafish Mutants Showing Alterations in Senescence-Associated Biomarkers

    PubMed Central

    Uchiyama, Junzo; Koshimizu, Eriko; Qi, Jie; Nanjappa, Purushothama; Imamura, Shintaro; Islam, Asiful; Neuberg, Donna; Amsterdam, Adam; Roberts, Thomas M.

    2008-01-01

    There is an interesting overlap of function in a wide range of organisms between genes that modulate the stress responses and those that regulate aging phenotypes and, in some cases, lifespan. We have therefore screened mutagenized zebrafish embryos for the altered expression of a stress biomarker, senescence-associated β-galactosidase (SA-β-gal) in our current study. We validated the use of embryonic SA-β-gal production as a screening tool by analyzing a collection of retrovirus-insertional mutants. From a pool of 306 such mutants, we identified 11 candidates that showed higher embryonic SA-β-gal activity, two of which were selected for further study. One of these mutants is null for a homologue of Drosophila spinster, a gene known to regulate lifespan in flies, whereas the other harbors a mutation in a homologue of the human telomeric repeat binding factor 2 (terf2) gene, which plays roles in telomere protection and telomere-length regulation. Although the homozygous spinster and terf2 mutants are embryonic lethal, heterozygous adult fish are viable and show an accelerated appearance of aging symptoms including lipofuscin accumulation, which is another biomarker, and shorter lifespan. We next used the same SA-β-gal assay to screen chemically mutagenized zebrafish, each of which was heterozygous for lesions in multiple genes, under the sensitizing conditions of oxidative stress. We obtained eight additional mutants from this screen that, when bred to homozygosity, showed enhanced SA-β-gal activity even in the absence of stress, and further displayed embryonic neural and muscular degenerative phenotypes. Adult fish that are heterozygous for these mutations also showed the premature expression of aging biomarkers and the accelerated onset of aging phenotypes. Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and

  5. Hemoglobin adducts from acrylonitrile and ethylene oxide in cigarette smokers: effects of glutathione S-transferase T1-null and M1-null genotypes.

    PubMed

    Fennell, T R; MacNeela, J P; Morris, R W; Watson, M; Thompson, C L; Bell, D A

    2000-07-01

    Acrylonitrile (ACN) is used to manufacture plastics and fibers. It is carcinogenic in rats and is found in cigarette smoke. Ethylene oxide (EO) is a metabolite of ethylene, also found in cigarette smoke, and is carcinogenic in rodents. Both ACN and EO undergo conjugation with glutathione. The objectives of this study were to examine the relationship between cigarette smoking and hemoglobin adducts derived from ACN and EO and to investigate whether null genotypes for glutathione transferase (GSTM1 and GSTT1) alter the internal dose of these agents. The hemoglobin adducts N-(2-cyanoethyl)valine (CEVal), which is formed from ACN, and N-(2-hydroxyethyl)valine (HEVal), which is formed from EO, and GST genotypes were determined in blood samples obtained from 16 nonsmokers and 32 smokers (one to two packs/day). Smoking information was obtained by questionnaire, and plasma cotinine levels were determined by immunoassay. Glutathione transferase null genotypes (GSTM1 and GSTT1) were determined by PCR. Both CEVal and HEVal levels increased with increased cigarette smoking dose (both self-reported and cotinine-based). CEVal and HEVal levels were also correlated. GSTM1 and GSTT1 genotypes had little effect on CEVal concentrations. GSTM1 null genotypes had no significant impact on HEVal. However, HEVal levels were significantly elevated in GSTT1-null individuals when normalized to smoking status or cotinine levels. The ratio of HEVal:CEVal was also elevated in GSTT1-null smokers (1.50 +/- 0.57 versus 0.88 +/- 0.24; P = 0.0002). The lack of a functional GSTT1 is estimated to increase the internal dose of EO derived from cigarette smoke by 50-70%. PMID:10919741

  6. Modifiers of mutant huntingtin aggregation

    PubMed Central

    Teuling, Eva; Bourgonje, Annika; Veenje, Sven; Thijssen, Karen; de Boer, Jelle; van der Velde, Joeri; Swertz, Morris; Nollen, Ellen

    2011-01-01

    Protein aggregation is a common hallmark of a number of age-related neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and polyglutamine-expansion disorders such as Huntington’s disease, but how aggregation-prone proteins lead to pathology is not known. Using a genome-wide RNAi screen in a C. elegans-model for polyglutamine aggregation, we previously identified 186 genes that suppress aggregation. Using an RNAi screen for human orthologs of these genes, we here present 26 human genes that suppress aggregation of mutant huntingtin in a human cell line. Among these are genes that have not been previously linked to mutant huntingtin aggregation. They include those encoding eukaryotic translation initiation, elongation and translation factors, and genes that have been previously associated with other neurodegenerative diseases, like the ATP-ase family gene 3-like 2 (AFG3L2) and ubiquitin-like modifier activating enzyme 1 (UBA1). Unravelling the role of these genes will broaden our understanding of the pathogenesis of Huntington’s disease. PMID:21915392

  7. Hepatic Effects of a Methionine-Choline-Deficient Diet in Hepatocyte RXRα-null Mice

    PubMed Central

    Gyamfi, Maxwell Afari; Tanaka, Yuji; He, Lin; Klaassen, Curtis D.; Wan, Yu-Jui Yvonne

    2009-01-01

    Retinoid X receptor-α (RXRα) is an obligate partner for several nuclear hormone receptors that regulate important physiological processes in the liver. In this study the impact of hepatocyte RXRα deficiency on methionine and choline deficient (MCD) diet-induced steatosis, oxidative stress, inflammation, and hepatic transporters gene expression were examined. The mRNA of sterol regulatory element-binding protein (SREBP)-regulated genes, important for lipid synthesis, were not altered in wild type (WT) mice, but were increased 2.0- to 5.4-fold in hepatocyte RXRα-null (H-RXRα-null) mice fed a MCD diet for 14 days. Furthermore, hepatic mRNAs and proteins essential for fatty acid β-oxidation were not altered in WT mice, but were decreased in the MCD diet-fed H-RXRα-null mice, resulting in increased hepatic free fatty acid levels. Cyp2e1 enzyme activity and lipid peroxide levels were induced only in MCD-fed WT mice. In contrast, hepatic mRNA levels of pro-inflammatory factors were increased only in H-RXRα-null mice fed the MCD diet. Hepatic uptake transporters Oatp1a1 and Oatp1b2 mRNA levels were decreased in WT mice fed the MCD diet, whereas the efflux transporter Mrp4 was increased. However, in the H-RXRα-null mice, the MCD diet only moderately decreased Oatp1a1 and induced both Oatp1a4 and Mrp4 gene expression. Whereas the MCD diet increased serum bile acid levels and alkaline phosphatase activity in both WT and H-RXRα-null mice, serum ALT levels were induced (2.9-fold) only in the H-RXRα-null mice. In conclusion, these data suggest a critical role for RXRα in hepatic fatty acid homeostasis and protection against MCD-induced hepatocyte injury. PMID:18952117

  8. Behavioural signs of chronic back pain in the SPARC-null mouse

    PubMed Central

    Millecamps, Magali; Tajerian, Maral; Sage, E. Helene; Stone, Laura S

    2010-01-01

    Study Design SPARC-null mice were examined for behavioural signs of chronic low back and/or radicular pain. Objective To assess SPARC-null mice as a rodent model of chronic low back and/or radicular pain due to degenerative disc disease. Summary of Background Data Degeneration of intervertebral discs is a major cause of chronic low back and radicular pain in humans. Inactivation of the SPARC (Secreted Protein, Acidic and Rich in Cysteine, also known as osteonectin and BM-40) gene in mice results in premature intervertebral disc degeneration. The impact of disc degeneration on behavioural measures of chronic pain has not been evaluated in this model. Methods Cohorts of young and old (3 and 6–12 months, respectively) SPARC-null and wild-type control mice were screened for behavioural indices of low back and/or radiating pain. Sensitivity to mechanical, cold and heat stimuli, locomotor impairment, and movement-evoked hypersensitivity were determined. Animals were challenged with three analgesic agents with different mechanisms: morphine, dexamethasone, and gabapentin. Results SPARC-null mice showed signs of movement-evoked discomfort as early as 3 months of age. Hypersensitivity to cold stimuli on both the lower back and hindpaws developed with increasing age. SPARC-null mice had normal sensitivity to tactile and heat stimuli, and locomotor skills were not impaired. The hypersensitivity to cold was reversed by morphine, but not by dexamethasone or gabapentin. Conclusion SPARC-null mice display behavioural signs consistent with chronic low back and radicular pain that we attribute to intervertebral disc degeneration. We predict that the SPARC-null mouse is a useful model of chronic back pain due to degenerative disc disease. PMID:20714283

  9. Nonlinear Alfvén wave dynamics at a 2D magnetic null point: ponderomotive force

    NASA Astrophysics Data System (ADS)

    Thurgood, J. O.; McLaughlin, J. A.

    2013-07-01

    Context. In the linear, β = 0 MHD regime, the transient properties of magnetohydrodynamic (MHD) waves in the vicinity of 2D null points are well known. The waves are decoupled and accumulate at predictable parts of the magnetic topology: fast waves accumulate at the null point; whereas Alfvén waves cannot cross the separatricies. However, in nonlinear MHD mode conversion can occur at regions of inhomogeneous Alfvén speed, suggesting that the decoupled nature of waves may not extend to the nonlinear regime. Aims: We investigate the behaviour of low-amplitude Alfvén waves about a 2D magnetic null point in nonlinear, β = 0 MHD. Methods: We numerically simulate the introduction of low-amplitude Alfvén waves into the vicinity of a magnetic null point using the nonlinear LARE2D code. Results: Unlike in the linear regime, we find that the Alfvén wave sustains cospatial daughter disturbances, manifest in the transverse and longitudinal fluid velocity, owing to the action of nonlinear magnetic pressure gradients (viz. the ponderomotive force). These disturbances are dependent on the Alfvén wave and do not interact with the medium to excite magnetoacoustic waves, although the transverse daughter becomes focused at the null point. Additionally, an independently propagating fast magnetoacoustic wave is generated during the early stages, which transports some of the initial Alfvén wave energy towards the null point. Subsequently, despite undergoing dispersion and phase-mixing due to gradients in the Alfvén-speed profile (∇cA ≠ 0) there is no further nonlinear generation of fast waves. Conclusions: We find that Alfvén waves at 2D cold null points behave largely as in the linear regime, however they sustain transverse and longitudinal disturbances - effects absent in the linear regime - due to nonlinear magnetic pressure gradients.

  10. Effects of Local Heart Irradiation in a Glutathione S-Transferase Alpha 4-Null Mouse Model

    PubMed Central

    Boerma, Marjan; Singh, Preeti; Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Singh, Sharda P.

    2015-01-01

    Glutathione S-transferase alpha 4 (GSTA4-4) is one of the enzymes responsible for the removal of 4-hydroxynonenal (4-HNE), an electrophilic product of lipid peroxidation in cellular membranes during oxidative stress. 4-HNE is a direct activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor with many target genes encoding antioxidant and anti-electrophile enzymes. We have previously shown that Gsta4-null mice on a 129/Sv background exhibited increased activity of Nrf2 in the heart. Here we examined the sensitivity of this Gsta4-null mouse model towards cardiac function and structure loss due to local heart irradiation. Male Gsta4-null and wild-type mice were exposed to a single X-ray dose of 18 Gy to the heart. Six months after irradiation, immunohistochemical staining for respiratory complexes 2 and 5 indicated that radiation exposure had caused most pronounced alterations in mitochondrial morphology in Gsta4-null mice. On the other hand, wild-type mice showed a decline in cardiac function and an increase in plasma levels of troponin-I, while no such changes were observed in Gsta4-null mice. Radiation-induced Nrf2-target gene expression only in Gsta4-null mice. In conclusion, although loss of GSTA4-4 led to enhanced susceptibility of cardiac mitochondria to radiation-induced loss of morphology, cardiac function was preserved in Gsta4-null mice. We propose that this protection against cardiac function loss may occur, at least in part, by upregulation of the Nrf2 pathway. PMID:26010708

  11. Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

    PubMed

    Sengle, Gerhard; Carlberg, Valerie; Tufa, Sara F; Charbonneau, Noe L; Smaldone, Silvia; Carlson, Eric J; Ramirez, Francesco; Keene, Douglas R; Sakai, Lynn Y

    2015-06-01

    Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background) are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that fibrillin-2 can

  12. Hepatic effects of a methionine-choline-deficient diet in hepatocyte RXR{alpha}-null mice

    SciTech Connect

    Gyamfi, Maxwell Afari; Tanaka, Yuji; He Lin; Klaassen, Curtis D.; Wan, Y.-J.Y.

    2009-01-15

    Retinoid X receptor-{alpha} (RXR{alpha}) is an obligate partner for several nuclear hormone receptors that regulate important physiological processes in the liver. In this study the impact of hepatocyte RXR{alpha} deficiency on methionine and choline deficient (MCD) diet-induced steatosis, oxidative stress, inflammation, and hepatic transporters gene expression were examined. The mRNA of sterol regulatory element-binding protein (SREBP)-regulated genes, important for lipid synthesis, were not altered in wild type (WT) mice, but were increased 2.0- to 5.4-fold in hepatocyte RXR{alpha}-null (H-RXR{alpha}-null) mice fed a MCD diet for 14 days. Furthermore, hepatic mRNAs and proteins essential for fatty acid {beta}-oxidation were not altered in WT mice, but were decreased in the MCD diet-fed H-RXR{alpha}-null mice, resulting in increased hepatic free fatty acid levels. Cyp2e1 enzyme activity and lipid peroxide levels were induced only in MCD-fed WT mice. In contrast, hepatic mRNA levels of pro-inflammatory factors were increased only in H-RXR{alpha}-null mice fed the MCD diet. Hepatic uptake transporters Oatp1a1 and Oatp1b2 mRNA levels were decreased in WT mice fed the MCD diet, whereas the efflux transporter Mrp4 was increased. However, in the H-RXR{alpha}-null mice, the MCD diet only moderately decreased Oatp1a1 and induced both Oatp1a4 and Mrp4 gene expression. Whereas the MCD diet increased serum bile acid levels and alkaline phosphatase activity in both WT and H-RXR{alpha}-null mice, serum ALT levels were induced (2.9-fold) only in the H-RXR{alpha}-null mice. In conclusion, these data suggest a critical role for RXR{alpha} in hepatic fatty acid homeostasis and protection against MCD-induced hepatocyte injury.

  13. Partial rescue of epithelial phenotype in integrin beta4 null mice by a keratin-5 promoter driven human integrin beta4 transgene.

    PubMed

    van der Neut, R; Cachaço, A S; Thorsteinsdóttir, S; Janssen, H; Prins, D; Bulthuis, J; van der Valk, M; Calafat, J; Sonnenberg, A

    1999-11-01

    Integrin beta4 null mice exhibit extensive epidermal detachment, reminiscent of the human skin blistering disease junctional epidermolysis bullosa associated with pyloric atresia. Hemidesmosomes, the stable adhesion structures of squamous epithelia, are not formed in the absence of alpha6beta4. Null mutant mice die shortly after birth, but apart from their striking epithelial phenotype, no obvious developmental defects have been observed. To elucidate the cause of death in these mice, we generated transgenic mice with a heterologous construct consisting of the squamous epithelial-specific keratin-5 promoter and a human integrin beta4 subunit cDNA. The transgene was not expressed in the presence of endogenous beta4, probably as a result of competition for a limited pool of alpha6 subunits. In a beta4 null background, however, the transgene was expressed, and its expression pattern followed that of squamous epithelial-specific keratins. These rescued pups appeared healthy and ultrastructural analysis revealed that the interspecies heterodimer alpha6(mouse)/beta4(human) was sufficient to trigger the assembly of hemidesmosomes. After a variable period of up to 48 hours after birth these animals began to exhibit haemorrhages at the plantar and palmar areas. We observed the formation of small blisters and found that the transgene was not detectably expressed in this region, which is devoid of hair follicles. The rescued neonates became increasingly cyanotic and died soon after the onset of this phenomenon. We performed a developmental study of the expression of beta4 in the complete respiratory tract, but we found no correlation between the spatiotemporal distribution of beta4 and the onset of the respiratory insufficiency. It became clear, however, that there was a gradual detachment of squamous epithelia in the oral and nasal cavities which led to obstruction of the respiratory tract, suggesting that in beta4 null and rescued mice, neonatal death was a direct

  14. Allele Specific p53 Mutant Reactivation

    PubMed Central

    Yu, Xin; Vazquez, Alexei; Levine, Arnold J.; Carpizo, Darren R.

    2012-01-01

    Summary Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development. PMID:22624712

  15. Natural selection for the Duffy-null allele in the recently admixed people of Madagascar.

    PubMed

    Hodgson, Jason A; Pickrell, Joseph K; Pearson, Laurel N; Quillen, Ellen E; Prista, António; Rocha, Jorge; Soodyall, Himla; Shriver, Mark D; Perry, George H

    2014-08-22

    While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa. PMID:24990677

  16. A Null Space Control of Two Wheels Driven Mobile Manipulator Using Passivity Theory

    NASA Astrophysics Data System (ADS)

    Shibata, Tsuyoshi; Murakami, Toshiyuki

    This paper describes a control strategy of null space motion of a two wheels driven mobile manipulator. Recently, robot is utilized in various industrial fields and it is preferable for the robot manipulator to have multiple degrees of freedom motion. Several studies of kinematics for null space motion have been proposed. However stability analysis of null space motion is not enough. Furthermore, these approaches apply to stable systems, but they do not apply unstable systems. Then, in this research, base of manipulator equips with two wheels driven mobile robot. This robot is called two wheels driven mobile manipulator, which becomes unstable system. In the proposed approach, a control design of null space uses passivity based stabilizing. A proposed controller is decided so that closed-loop system of robot dynamics satisfies passivity. This is passivity based control. Then, control strategy is that stabilizing of the robot system applies to work space observer based approach and null space control while keeping end-effector position. The validity of the proposed approach is verified by simulations and experiments of two wheels driven mobile manipulator.

  17. Teleparallelism as a universal connection on null hypersurfaces in general relativity

    NASA Technical Reports Server (NTRS)

    Mazur, P. O.; Sokolowski, L. M.

    1986-01-01

    It is shown that a close relationship between the inner geometry of a null hypersurface N3 and the Newman-Penrose (NP) (1962, 1963) spin coefficient formalism exists. Projecting the null complex NP tetrad onto N3, two triads of basis vectors in N3 are obtained. The inner geometry of N3 is based on the assumption that these vectors are parallelly transported along the surface; this gives rise to the teleparallel connection as a metric nonsymmetric affine connection. The gauge freedom for the choice of the basis triads is given by the isotropy subgroup of the local Lorentz group leaving invariant the direction of the null generators of N3, and teleparallelism is determined by the equivalence class of the basis triads with respect to the global gauge group. Nine of the twelve NP coefficients are identified as the triad components of the torsion and the second fundamental form of N3. The resulting generalized Gauss-Codazzi equations are identical to nine of the NP equations, i.e., to the half of the Ricci identities. This result gives a geometrical meaning to the entire formalism. Finally a general proof of Penrose's theorem that the shear of the null generators of N3 is the only initial null datum for a gravitational field on N3 is presented.

  18. Stimulus-specific defect in the phagocytic pathways of annexin 1 null macrophages

    PubMed Central

    Yona, Simon; Buckingham, Julia C; Perretti, Mauro; Flower, Roderick J

    2004-01-01

    The role of the glucocorticoid-regulated protein annexin 1 during the process of phagocytosis has been studied using annexin 1 null peritoneal macrophages. Wild type and annexin 1 null macrophages were incubated with several distinct phagocytic targets. No differences were observed in rate or the maximal response with respect to IgG complexes or opsonised zymosan phagocytosis, as assessed by monitoring the production of reactive oxygen species. When annexin 1 null macrophages were incubated with non-opsonised zymosan particles, they exhibited impaired generation of reactive oxygen species, which was linked to a defect in binding of cells to the particles, as determined with fluorescent zymosan. This phenomenon was further confirmed by electron microscopy analysis, where annexin 1 null macrophages internalised fewer non-opsonised zymosan particles. Specific alterations in macrophage plasma membrane markers were observed in the annexin 1 null cells. Whereas no differences in dectin-1 and FcγR II/III expression were measured between the two genotypes, decreased membrane CD11b and F4/80 levels were measured selectively in macrophages lacking annexin 1. These cells also responded with an enhanced release of PGE2 and COX-2 protein expression following addition of the soluble stimulants, LPS and heat-activated IgG. In conclusion, these results suggest that participation of endogenous annexin 1 during zymosan phagocytosis is critical and that this protein plays a tonic inhibitory role during macrophage activation. PMID:15197108

  19. Protection from oxidative and electrophilic stress in the Gsta4-null mouse heart

    PubMed Central

    Beneš, Helen; Vuong, Mai K.; Boerma, Marjan; McElhanon, Kevin E.; Siegel, Eric R.; Singh, Sharda P.

    2013-01-01

    4-hydroxynonenal (4-HNE) mediates many pathological effects of oxidative and electrophilic stress and signals to activate cytoprotective gene expression regulated by NF-E2-related factor 2 (Nrf2). By exhibiting very high levels of 4-HNE-conjugating activity, the murine glutathione transferase alpha 4 (GSTA4-4) helps regulate cellular 4-HNE levels. To examine the role of 4-HNE in vivo, we disrupted the murine Gsta4 gene. Gsta4-null mice exhibited no cardiac phenotype under normal conditions and no difference in cardiac 4-HNE level as compared to wild-type (WT) mice. We hypothesized that the Nrf2 pathway might contribute an important compensatory mechanism to remove excess cardiac 4-HNE in Gsta4-null mice. Cardiac nuclear extracts from Gsta4-null mice exhibited significantly higher Nrf2 binding to antioxidant-response elements (AREs). We also observed responses in critical Nrf2 target gene products: elevated Sod2, Cat, and Akr1b7 mRNA levels and significant increases in both cardiac anti-oxidant and anti-electrophile enzyme activities. Gsta4-null mice were less sensitive and maintained normal cardiac function following chronic doxorubicin (DOX) treatment, known to increase cardiac 4-HNE levels. Hence, in the absence of GSTA4-4 to modulate both physiological and pathological 4-HNE levels, the adaptive Nrf2 pathway may be primed to contribute to a preconditioned cardiac phenotype in the Gsta4-null mouse. PMID:23690225

  20. Natural selection for the Duffy-null allele in the recently admixed people of Madagascar

    PubMed Central

    Hodgson, Jason A.; Pickrell, Joseph K.; Pearson, Laurel N.; Quillen, Ellen E.; Prista, António; Rocha, Jorge; Soodyall, Himla; Shriver, Mark D.; Perry, George H.

    2014-01-01

    While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa. PMID:24990677

  1. Current singularities at quasi-separatrix layers and three-dimensional magnetic nulls

    SciTech Connect

    Craig, I. J. D.; Effenberger, Frederic

    2014-11-10

    The open problem of how singular current structures form in line-tied, three-dimensional magnetic fields is addressed. A Lagrangian magneto-frictional relaxation method is employed to model the field evolution toward the final near-singular state. Our starting point is an exact force-free solution of the governing magnetohydrodynamic equations that is sufficiently general to allow for topological features like magnetic nulls to be inside or outside the computational domain, depending on a simple set of parameters. Quasi-separatrix layers (QSLs) are present in these structures and, together with the magnetic nulls, they significantly influence the accumulation of current. It is shown that perturbations affecting the lateral boundaries of the configuration lead not only to collapse around the magnetic null but also to significant QSL currents. Our results show that once a magnetic null is present, the developing currents are always attracted to that specific location and show a much stronger scaling with resolution than the currents that form along the QSL. In particular, the null-point scalings can be consistent with models of 'fast' reconnection. The QSL currents also appear to be unbounded but give rise to weaker singularities, independent of the perturbation amplitude.

  2. Association of the GSTM1 null polymorphism with breast cancer in a Mexican population.

    PubMed

    Soto-Quintana, O; Zúñiga-González, G M; Ramírez-Patiño, R; Ramos-Silva, A; Figuera, L E; Carrillo-Moreno, D I; Gutiérrez-Hurtado, I A; Puebla-Pérez, A M; Sánchez-Llamas, B; Gallegos-Arreola, M P

    2015-01-01

    The glutathione S transferase (GST) family plays an important role in the processing of carcinogens. Data on the null GSTM1 genotype has revealed associations with cancer, and has been suggested to affect carcinogen metabolism and to contribute to tumor promotion in the mammary gland. We examined the role of the null GSTM1 genotype by comparing the genotypes of 276 healthy Mexican women with those of 558 Mexican women with breast cancer (BC). The genotype frequencies observed in the controls and patients with BC were 38 and 45% for the null GSTM1 genotype, respectively. The obtained odds ratio (OR) was 1.36, with a 95% confidence interval (95%CI) of 1.02-1.8, P = 0.04. The protective association was also evident upon analysis of the distributions of the null GSTM1 genotype in patients with positive chemotherapy response who had high plasma levels of glucose (OR 0.56, 95%CI = 0.33-0.94, P = 0.03). This study suggested that the null GSTM1 genotype is associated with BC susceptibility in the Mexican population analyzed. PMID:26535619

  3. Spontaneous Skin Ulceration and Defective T Cell Function in CD18 Null Mice

    PubMed Central

    Scharffetter-Kochanek, Karin; Lu, Huifang; Norman, Keith; van Nood, Nicole; Munoz, Flor; Grabbe, Stephan; McArthur, Mark; Lorenzo, Isabel; Kaplan, Sheldon; Ley, Klaus; Wayne Smith, C.; Montgomery, Charles A.; Rich, Susan; Beaudet, Arthur L.

    1998-01-01

    A null mutation was prepared in the mouse for CD18, the β2 subunit of leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with extensive facial and submandibular erosions. The phenotype includes elevated neutrophil counts, increased immunoglobulin levels, lymphadenopathy, splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney. Very few neutrophils were found in spontaneously occurring skin lesions or with an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell proliferation was found in the CD18 null mice when T cell receptors were stimulated either by staphylococcal enterotoxin A or by major histocompatibility complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T cell responses than previously documented. The null mice are useful for delineating the functions of CD18 in vivo. PMID:9653089

  4. Spontaneous skin ulceration and defective T cell function in CD18 null mice.

    PubMed

    Scharffetter-Kochanek, K; Lu, H; Norman, K; van Nood, N; Munoz, F; Grabbe, S; McArthur, M; Lorenzo, I; Kaplan, S; Ley, K; Smith, C W; Montgomery, C A; Rich, S; Beaudet, A L

    1998-07-01

    A null mutation was prepared in the mouse for CD18, the beta2 subunit of leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with extensive facial and submandibular erosions. The phenotype includes elevated neutrophil counts, increased immunoglobulin levels, lymphadenopathy, splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney. Very few neutrophils were found in spontaneously occurring skin lesions or with an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell proliferation was found in the CD18 null mice when T cell receptors were stimulated either by staphylococcal enterotoxin A or by major histocompatibility complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T cell responses than previously documented. The null mice are useful for delineating the functions of CD18 in vivo. PMID:9653089

  5. Null mutations of the Dictyostelium cyclic nucleotide phosphodiesterase gene block chemotactic cell movement in developing aggregates.

    PubMed

    Sucgang, R; Weijer, C J; Siegert, F; Franke, J; Kessin, R H

    1997-12-01

    Extracellular cAMP is a critical messenger in the multicellular development of the cellular slime mold Dictyostelium discoideum. The levels of cAMP are controlled by a cyclic nucleotide phosphodiesterase (PDE) that is secreted by the cells. The PDE gene (pdsA) is controlled by three promoters that permit expression during vegetative growth, during aggregation, and in prestalk cells of the older structures. Targeted disruption of the gene aborts development, and complementation with a modified pdsA restores development. Two distinct promoters must be used for full complementation, and an inhibitory domain of the PDE must be removed. We took advantage of newly isolated PDE-null cells and the natural chimerism of the organism to ask whether the absence of PDE affected individual cell behavior. PDE-null cells aggregated with isogenic wild-type cells in chimeric mixtures, but could not move in a coordinated manner in mounds. The wild-type cells move inward toward the center of the mound, leaving many of the PDE-null cells at the periphery of the aggregate. During the later stages of development, PDE-null cells in the chimera segregate to regions which correspond to the prestalk region and the rear of the slug. Participation in the prespore/spore population returns with the restoration of a modified pdsA to the null cells. PMID:9405107

  6. First-Order Adaptive Azimuthal Null-Steering for the Suppression of Two Directional Interferers

    NASA Astrophysics Data System (ADS)

    Derkx, René M. M.

    2010-12-01

    An azimuth steerable first-order superdirectional microphone response can be constructed by a linear combination of three eigenbeams: a monopole and two orthogonal dipoles. Although the response of a (rotation symmetric) first-order response can only exhibit a single null, we will look at a slice through this beampattern lying in the azimuthal plane. In this way, we can define maximally two nulls in the azimuthal plane which are symmetric with respect to the main-lobe axis. By placing these two nulls on maximally two directional sources to be rejected and compensating for the drop in level for the desired direction, we can effectively reject these directional sources without attenuating the desired source. We present an adaptive null-steering scheme for adjusting the beampattern so as to obtain this suppression of the two directional interferers automatically. Closed-form expressions for this optimal null-steering are derived, enabling the computation of the azimuthal angles of the interferers. It is shown that the proposed technique has a good directivity index when the angular difference between the desired source and each directional interferer is at least 90 degrees.

  7. High Contrast Vacuum Nuller Testbed (VNT) Contrast, Performance and Null Control

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-01-01

    Herein we report on our contrast assessment and the development, sensing and control of the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraphy (VNC) for exoplanet detection and characterization. Tbe VNC is one of the few approaches that works with filled, segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be flown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center has an established effort to develop VNC technologies, and an incremental sequence of testbeds to advance this approach and its critical technologies. We discuss the development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 10(exp 8), 10(exp 9) and ideally 10(exp 10) at an inner working angle of 2*lambda/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the laboratory results, optical configuration, critical technologies and the null sensing and control approach.

  8. Vacuum Nuller Testbed (VNT) Performance, Characterization and Null Control: Progress Report

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.; Noecker, M. Charley; Kendrick, Stephen; Helmbrecht, Michael

    2011-01-01

    Herein we report on the development. sensing and control and our first results with the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraph (VNC) for exoplanet coronagraphy. The VNC is one of the few approaches that works with filled. segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be Hown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies. and has developed an incremental sequence of VNC testbeds to advance this approach and the enabling technologies associated with it. We discuss the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). Tbe VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 10(sup 8), 10(sup 9) and ideally 10(sup 10) at an inner working angle of 2*lambda/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the initial laboratory results, the optical configuration, critical technologies and the null sensing and control approach.

  9. Design and fabrication of CGH for aspheric surface testing and its experimental comparison with null lens

    NASA Astrophysics Data System (ADS)

    Li, Fazhi; Zhao, Jingli; Li, Ruigang; Zhang, Binzhi; Zheng, Ligong; Zhang, Xuejun

    2010-10-01

    Computer-generated hologram (CGH) is an effective way to compensate wavefront in null test of aspheric surfaces and freeform surfaces. Our strategies of CGH design and fabrication for optical testing are presented, and an experiment demonstrating the compensation results of CGH and null lens is also reported. In order to design complex CGH, software was developed, with which we can design a CGH including three sections: main section for compensating wavefront in null test, alignment section for adjusting the relative position between CGH and interferometer, and fiducial section for projecting fiducial marks around the optics under test. The design result is represented in GDS II format file which could drive a laser-direct-writer-machine to fabricate a photomask. Then, a 1:1 replication process is applied to duplicate the patterns from photomask to a parallel optical substrate whose surface is error better than λ/60 rms. Finally, an off-axis aspheric surface was tested with CGH and null lens respectively. The test result with CGH (0.019λrms) is almost the same as the result with null lens (0.020λ rms). This experiment also demonstrated that fiducial marks projected by CGH can be used to guide the alignment of the optics and measurement of its off-axis distance.

  10. Targeting the Ataxia Telangiectasia Mutated-null phenotype in chronic lymphocytic leukemia with pro-oxidants

    PubMed Central

    Agathanggelou, Angelo; Weston, Victoria J.; Perry, Tracey; Davies, Nicholas J.; Skowronska, Anna; Payne, Daniel T.; Fossey, John S.; Oldreive, Ceri E.; Wei, Wenbin; Pratt, Guy; Parry, Helen; Oscier, David; Coles, Steve J.; Hole, Paul S.; Darley, Richard L.; McMahon, Michael; Hayes, John D.; Moss, Paul; Stewart, Grant S.; Taylor, A. Malcolm R.; Stankovic, Tatjana

    2015-01-01

    Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting. We found that in comparison to Ataxia Telangiectasia Mutated-wild type chronic lymphocytic leukemia, pro-oxidant treatment of Ataxia Telangiectasia Mutated-null cells led to reduced binding of NF-E2 p45-related factor-2 to antioxidant response elements and thus decreased expression of target genes. Furthermore, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia cells contained lower levels of antioxidants and elevated mitochondrial reactive oxygen species. Consequently, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia, but not tumors with 11q deletion or TP53 mutations, exhibited differentially increased sensitivity to pro-oxidants both in vitro and in vivo. We found that cell death was mediated by a p53- and caspase-independent mechanism associated with apoptosis inducing factor activity. Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia. PMID:25840602

  11. Current Structure and Nonideal Behavior at Magnetic Null Points in the Turbulent Magnetosheath

    NASA Technical Reports Server (NTRS)

    Wendel, D. E.; Adrian, M. L.

    2013-01-01

    The Poincaré index indicates that the Cluster spacecraft tetrahedron entraps a number of 3-D magnetic nulls during an encounter with the turbulent magnetosheath. Previous researchers have found evidence for reconnection at one of the many filamentary current layers observed by Cluster in this region. We find that many of the entrained nulls are also associated with strong currents. We dissect the current structure of a pair of spiral nulls that may be topologically connected. At both nulls, we find a strong current along the spine, accompanied by a somewhat more modest current perpendicular to the spine that tilts the fan toward the axis of the spine. The current along the fan is comparable to the that along the spine. At least one of the nulls manifests a rotational flow pattern in the fan plane that is consistent with torsional spine reconnection as predicted by theory. These results emphasize the importance of examining the magnetic topology in interpreting the nature of currents and reconnection in 3-D turbulence.

  12. Targeting FoxM1 effectively retards p53-null lymphoma and sarcoma

    PubMed Central

    Wang, Zebin; Zheng, Yu; Park, Hyun Jung; Li, Jing; Carr, Janai R.; Chen, Yi-ju; Kiefer, Megan M.; Kopanja, Dragana; Bagchi, Srilata; Tyner, Angela L.; Raychaudhuri, Pradip

    2013-01-01

    The forkhead box transcription factor FOXM1 is considered to be a promising target for cancer therapy. However, the significance of FOXM1 in tumors harboring mutation in p53, which is very common, is unclear. In this study, we investigated the efficacy of FoxM1-targeting in spontaneous p53-null tumors using genetic ablation as well as using a peptide-inhibitor of FOXM1. We show that conditional deletion of FoxM1 inhibits growth of the p53 null thymic lymphoma and sarcoma cells. In addition, deletion of FoxM1 induces apoptotic cell death of the p53 null tumors, accompanied by reduced expression of the FOXM1 target genes Survivin and Bmi1. An ARF-derived peptide that inhibits the activity of FOXM1, by targeting it to the nucleolus, also induces apoptosis in the p53 null sarcoma and lymphoma, leading to a strong inhibition of their metastatic colonization. Together, our observations suggest that FOXM1 is critical for survival and growth of the p53-null lymphoma and sarcoma, and provide proof-of-principle that FOXM1 is an effective therapeutic target for sarcoma and lymphoma carrying loss of function mutation in p53. PMID:23427295

  13. The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype.

    PubMed

    Kudryashova, Elena; Struyk, Arie; Mokhonova, Ekaterina; Cannon, Stephen C; Spencer, Melissa J

    2011-10-15

    Mutations in tripartite motif protein 32 (TRIM32) are responsible for several hereditary disorders that include limb girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathy (STM) and Bardet Biedl syndrome. Most LGMD2H mutations in TRIM32 are clustered in the NHL β-propeller domain at the C-terminus and are predicted to interfere with homodimerization. To get insight into TRIM32's role in the pathogenesis of LGMD2H and to create an accurate model of disease, we have generated a knock-in mouse (T32KI) carrying the c.1465G > A (p.D489N) mutation in murine Trim32 corresponding to the human LGMD2H/STM pathogenic mutation c.1459G > A (p.D487N). Our data indicate that T32KI mice have both a myopathic and a neurogenic phenotype, very similar to the one described in the Trim32-null mice that we created previously. Analysis of Trim32 gene expression in T32KI mice revealed normal mRNA levels, but a severe reduction in mutant TRIM32 (D489N) at the protein level. Our results suggest that the D489N pathogenic mutation destabilizes the protein, leading to its degradation, and results in the same mild myopathic and neurogenic phenotype as that found in Trim32-null mice. Thus, one potential mechanism of LGMD2H might be destabilization of mutated TRIM32 protein leading to a null phenotype. PMID:21775502

  14. Abnormal lignin in a loblolly pine mutant

    SciTech Connect

    Ralph, J.; MacKay, J.J.; Hatfield, R.D.

    1997-07-11

    Novel lignin is formed in a mutant loblolly pine (Pinus taeda L.) severely depleted in cinnamyl alcohol dehydrogenase (E.C. 1.1.1.195), which converts coniferaldehyde to coniferyl alcohol, the primary lignin precursor in pines. Dihydroconiferyl alcohol, a monomer not normally associated with the lignin biosynthetic pathway, is the major component of the mutant`s lignin, accounting for {approximately}30 percent (versus {approximately}3 percent in normal pine) of the units. The level of aldehydes, including new 2-methoxybenzaldehydes, is also increased. The mutant pines grew normally indicating that, even within a species, extensive variations in lignin composition need not disrupt the essential functions of lignin.

  15. Identifying representative drug resistant mutants of HIV

    PubMed Central

    2015-01-01

    Background Drug resistance is one of the most important causes for failure of anti-AIDS treatment. During therapy, multiple mutations accumulate in the HIV genome, eventually rendering the drugs ineffective in blocking replication of the mutant virus. The huge number of possible mutants precludes experimental analysis to explore the molecular mechanisms of resistance and develop improved antiviral drugs. Results In order to solve this problem, we have developed a new algorithm to reveal the most representative mutants from the whole drug resistant mutant database based on our newly proposed unified protein sequence and 3D structure encoding method. Mean shift clustering and multiple regression analysis were applied on genotype-resistance data for mutants of HIV protease and reverse transcriptase. This approach successfully chooses less than 100 mutants with the highest resistance to each drug out of about 10K in the whole database. When considering high level resistance to multiple drugs, the numbers reduce to one or two representative mutants. Conclusion This approach for predicting the most representative mutants for each drug has major importance for experimental verification since the results provide a small number of representative sequences, which will be amenable for in vitro testing and characterization of the expressed mutant proteins. PMID:26678327

  16. Transcription-dependent DNA transactions in the mitochondrial genome of a yeast hypersuppressive petite mutant.

    PubMed

    Van Dyck, E; Clayton, D A

    1998-05-01

    Mitochondrial DNA (mtDNA) of Saccharomyces cerevisiae contains highly conserved sequences, called rep/ori, that are associated with several aspects of its metabolism. These rep/ori sequences confer the transmission advantage exhibited by a class of deletion mutants called hypersuppressive petite mutants. In addition, because they share features with the mitochondrial leading-strand DNA replication origin of mammals, rep/ori sequences have also been proposed to participate in mtDNA replication initiation. Like the mammalian origins, where transcription is used as a priming mechanism for DNA synthesis, yeast rep/ori sequences contain an active promoter. Although transcription is required for maintenance of wild-type mtDNA in yeast, the role of the rep/ori promoter as a cis-acting element involved in the replication of wild-type mtDNA is unclear, since mitochondrial deletion mutants need neither transcription nor a rep/ori sequence to maintain their genome. Similarly, transcription from the rep/ori promoter does not seem to be necessary for biased inheritance of mtDNA. As a step to elucidate the function of the rep/ori promoter, we have attempted to detect transcription-dependent DNA transactions in the mtDNA of a hypersuppressive petite mutant. We have examined the mtDNA of the well-characterized petite mutant a-1/1R/Z1, whose repeat unit shelters the rep/ori sequence ori1, in strains carrying either wild-type or null alleles of the nuclear genes encoding the mitochondrial transcription apparatus. Complex DNA transactions were detected that take place around GC-cluster C, an evolutionarily conserved GC-rich sequence block immediately downstream from the rep/ori promoter. These transactions are strictly dependent upon mitochondrial transcription. PMID:9566917

  17. On Bäcklund transformation and vortex filament equation for pseudo null curves in Minkowski 3-space

    NASA Astrophysics Data System (ADS)

    Grbović, Milica; Nešović, Emilija

    2016-04-01

    In this paper, we introduce Bäcklund transformation of a pseudo null curve in Minkowski 3-space as a transformation mapping a pseudo null helix to another pseudo null helix congruent to the given one. We also give the sufficient conditions for a transformation between two pseudo null curves in the Minkowski 3-space such that these curves have equal constant torsions. By using the Da Rios vortex filament equation, based on localized induction approximation (LIA), we derive the vortex filament equation for a pseudo null curve and prove that the evolution equation for the torsion is the viscous Burger’s equation. As an application, we show that pseudo null curves and their Frenet frames generate solutions of the Da Rios vortex filament equation.

  18. Anti-optic-null medium: Achieving the optic-null medium effect by enclosing an air region with relatively low-anisotropy media

    NASA Astrophysics Data System (ADS)

    Sun, Fei; Liu, Yichao; He, Sailing

    2016-07-01

    A so-called anti-optic-null medium (anti-ONM), which can be utilized to cancel the optic-null medium (ONM) and create many novel optical illusions, is introduced and designed by transformation optics (TO). Optical separation illusions can be achieved with an anti-ONM. With the help of the anti-ONM, we can achieve the same optical illusions where ONM is required via a shelled structure filled with low anisotropic medium, which is easier to realize for some novel optical devices designed by TO and optical surface transformation. The special function of the anti-ONM will lead to a new way to design optical devices or simplify the material requirements. Overlapping illusions, and wave-front reshapers are designed to demonstrate the function of the proposed method.

  19. Arabidopsis KINETOCHORE NULL2 Is an Upstream Component for Centromeric Histone H3 Variant cenH3 Deposition at Centromeres[W

    PubMed Central

    Lermontova, Inna; Kuhlmann, Markus; Friedel, Swetlana; Rutten, Twan; Heckmann, Stefan; Sandmann, Michael; Demidov, Dmitri; Schubert, Veit; Schubert, Ingo

    2013-01-01

    The centromeric histone H3 variant cenH3 is an essential centromeric protein required for assembly, maintenance, and proper function of kinetochores during mitosis and meiosis. We identified a KINETOCHORE NULL2 (KNL2) homolog in Arabidopsis thaliana and uncovered features of its role in cenH3 loading at centromeres. We show that Arabidopsis KNL2 colocalizes with cenH3 and is associated with centromeres during all stages of the mitotic cell cycle, except from metaphase to mid-anaphase. KNL2 is regulated by the proteasome degradation pathway. The KNL2 promoter is mainly active in meristematic tissues, similar to the cenH3 promoter. A knockout mutant for KNL2 shows a reduced level of cenH3 expression and reduced amount of cenH3 protein at chromocenters of meristematic nuclei, anaphase bridges during mitosis, micronuclei in pollen tetrads, and 30% seed abortion. Moreover, knl2 mutant plants display reduced expression of suppressor of variegation 3-9 homologs2, 4, and 9 and reduced DNA methylation, suggesting an impact of KNL2 on the epigenetic environment for centromere maintenance. PMID:24014547

  20. Investigation of the extraordinary null reconstruction phenomenon in polarization volume hologram.

    PubMed

    Wang, J; Kang, G; Wu, A; Liu, Y; Zang, J; Li, P; Tan, X; Shimura, T; Kuroda, K

    2016-01-25

    Polarization holography is the superposition of differently polarized beams. Due to its ability to record the polarization states, some extraordinary optical phenomena were found in the polarization holography. For example, the recently reported null-reconstruction phenomenon in polarization volume hologram is odd for the conventional holography which only records the amplitude and phase. In this paper, we perform a thorough investigation of the null reconstruction of polarization hologram recorded by orthogonal circularly polarized waves. To explore the mechanism behind this phenomenon, an interferometry was built to measure the phase difference between the same polarized components within the reconstructed wave. The phase difference of π was secured in our experiment, indicating a destructive interfering effect, which nicely explains the extraordinary null reconstruction observed in the polarization hologram. PMID:26832542

  1. Impact of criticism of null-hypothesis significance testing on statistical reporting practices in conservation biology.

    PubMed

    Fidler, Fiona; Burgman, Mark A; Cumming, Geoff; Buttrose, Robert; Thomason, Neil

    2006-10-01

    Over the last decade, criticisms of null-hypothesis significance testing have grown dramatically, and several alternative practices, such as confidence intervals, information theoretic, and Bayesian methods, have been advocated. Have these calls for change had an impact on the statistical reporting practices in conservation biology? In 2000 and 2001, 92% of sampled articles in Conservation Biology and Biological Conservation reported results of null-hypothesis tests. In 2005 this figure dropped to 78%. There were corresponding increases in the use of confidence intervals, information theoretic, and Bayesian techniques. Of those articles reporting null-hypothesis testing--which still easily constitute the majority--very few report statistical power (8%) and many misinterpret statistical nonsignificance as evidence for no effect (63%). Overall, results of our survey show some improvements in statistical practice, but further efforts are clearly required to move the discipline toward improved practices. PMID:17002771

  2. High performance testbed for four-beam infrared interferometric nulling and exoplanet detection.

    PubMed

    Martin, Stefan; Booth, Andrew; Liewer, Kurt; Raouf, Nasrat; Loya, Frank; Tang, Hong

    2012-06-10

    Technology development for a space-based infrared nulling interferometer capable of earthlike exoplanet detection and characterization started in earnest in the last 10 years. At the Jet Propulsion Laboratory, the planet detection testbed was developed to demonstrate the principal components of the beam combiner train for a high performance four-beam nulling interferometer. Early in the development of the testbed, the importance of "instability noise" for nulling interferometer sensitivity was recognized, and the four-beam testbed would produce this noise, allowing investigation of methods for mitigating this noise source. The testbed contains the required features of a four-beam combiner for a space interferometer and performs at a level matching that needed for the space mission. This paper describes in detail the design, functions, and controls of the testbed. PMID:22695670

  3. TPF Planet Detection Testbed: demonstrating deep, stable nulling and planet detection

    NASA Technical Reports Server (NTRS)

    Martin, Stefan

    2005-01-01

    The design of a testbed being built at the Jet Propulsion Laboratory is described. Simulatiung a dual chopped Bracewell interferometer, the testbed comprises a four beam star and planet source and nulling beam combiner. Since achieving a stable null is of great concern the testbed has many control systems designed to achieve stability of alignment and optical path difference over long periods of time. Comparisons between the testbed and the flight system are drawn and key performance parameters are discussed. The interaction between designs for phaseplate systems that achromatically invert the electric field of one of each pair of the incoming beams to achieve the null and the choice of fringe tracking schemes is also discussed.

  4. Minimum Variance Distortionless Response Beamformer with Enhanced Nulling Level Control via Dynamic Mutated Artificial Immune System

    PubMed Central

    Kiong, Tiong Sieh; Salem, S. Balasem; Paw, Johnny Koh Siaw; Sankar, K. Prajindra

    2014-01-01

    In smart antenna applications, the adaptive beamforming technique is used to cancel interfering signals (placing nulls) and produce or steer a strong beam toward the target signal according to the calculated weight vectors. Minimum variance distortionless response (MVDR) beamforming is capable of determining the weight vectors for beam steering; however, its nulling level on the interference sources remains unsatisfactory. Beamforming can be considered as an optimization problem, such that optimal weight vector should be obtained through computation. Hence, in this paper, a new dynamic mutated artificial immune system (DM-AIS) is proposed to enhance MVDR beamforming for controlling the null steering of interference and increase the signal to interference noise ratio (SINR) for wanted signals. PMID:25003136

  5. Partial Müllerian Duct Retention in Smad4 Conditional Mutant Male Mice

    PubMed Central

    Petit, Fabrice G.; Deng, Chuxia; Jamin, Soazik P.

    2016-01-01

    Müllerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-β) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Müllerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Müllerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Müllerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor α. As previously described in a β-catenin conditional mutant mouse model, β-catenin contributes to Müllerian duct regression. In our mutant male embryos, it appears that β-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/β-catenin signalling leading to the partial persistence of Müllerian duct. PMID:27194944

  6. Biofilm formation ability of Salmonella enterica serovar Typhimurium acrAB mutants.

    PubMed

    Schlisselberg, Dov B; Kler, Edna; Kisluk, Guy; Shachar, Dina; Yaron, Sima

    2015-10-01

    Recent studies offer contradictory findings about the role of multidrug efflux pumps in bacterial biofilm development. Thus, the aim of this study was to investigate the involvement of the AcrAB efflux pump in biofilm formation by investigating the ability of AcrB and AcrAB null mutants of Salmonella enterica serovar Typhimurium to produce biofilms. Three models were used to compare the ability of S. Typhimurium wild-type and its mutants to form biofilms: formation of biofilm on polystyrene surfaces; production of biofilm (mat model) on the air/liquid interface; and expression of curli and cellulose on Congo red-supplemented agar plates. All three investigated genotypes formed biofilms with similar characteristics. However, upon exposure to chloramphenicol, formation of biofilms on solid surfaces as well as the production of curli were either reduced or were delayed more significantly in both mutants, whilst there was no visible effect on pellicle formation. It can be concluded that when no selective pressure is applied, S. Typhimurium is able to produce biofilms even when the AcrAB efflux pumps are inactivated, implying that the use of efflux pump inhibitors to prevent biofilm formation is not a general solution and that combined treatments might be more efficient. Other factors that affect the ability to produce biofilms depending on efflux pump activity are yet to be identified. PMID:26260191

  7. Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function in chromatin regulation

    PubMed Central

    Biagioli, Marta; Ferrari, Francesco; Mendenhall, Eric M.; Zhang, Yijing; Erdin, Serkan; Vijayvargia, Ravi; Vallabh, Sonia M.; Solomos, Nicole; Manavalan, Poornima; Ragavendran, Ashok; Ozsolak, Fatih; Lee, Jong Min; Talkowski, Michael E.; Gusella, James F.; Macdonald, Marcy E.; Park, Peter J.; Seong, Ihn Sik

    2015-01-01

    The CAG repeat expansion in the Huntington's disease gene HTT extends a polyglutamine tract in mutant huntingtin that enhances its ability to facilitate polycomb repressive complex 2 (PRC2). To gain insight into this dominant gain of function, we mapped histone modifications genome-wide across an isogenic panel of mouse embryonic stem cell (ESC) and neuronal progenitor cell (NPC) lines, comparing the effects of Htt null and different size Htt CAG mutations. We found that Htt is required in ESC for the proper deposition of histone H3K27me3 at a subset of ‘bivalent’ loci but in NPC it is needed at ‘bivalent’ loci for both the proper maintenance and the appropriate removal of this mark. In contrast, Htt CAG size, though changing histone H3K27me3, is prominently associated with altered histone H3K4me3 at ‘active’ loci. The sets of ESC and NPC genes with altered histone marks delineated by the lack of huntingtin or the presence of mutant huntingtin, though distinct, are enriched in similar pathways with apoptosis specifically highlighted for the CAG mutation. Thus, the manner by which huntingtin function facilitates PRC2 may afford mutant huntingtin with multiple opportunities to impinge upon the broader machinery that orchestrates developmentally appropriate chromatin status. PMID:25574027

  8. TBX6 Null Variants and a Common Hypomorphic Allele in Congenital Scoliosis

    PubMed Central

    Wu, N.; Ming, X.; Xiao, J.; Wu, Z.; Chen, X.; Shinawi, M.; Shen, Y.; Yu, G.; Liu, J.; Xie, H.; Gucev, Z.S.; Liu, S.; Yang, N.; Al-Kateb, H.; Chen, J.; Zhang, Jian; Hauser, N.; Zhang, T.; Tasic, V.; Liu, P.; Su, X.; Pan, X.; Liu, C.; Wang, L.; Shen, Joseph; Shen, Jianxiong; Chen, Y.; Zhang, T.; Zhang, Jianguo; Choy, K.W.; Wang, Jun; Wang, Q.; Li, S.; Zhou, W.; Guo, J.; Wang, Y.; Zhang, C.; Zhao, H.; An, Y.; Zhao, Y.; Wang, Jiucun; Liu, Z.; Zuo, Y.; Tian, Y.; Weng, X.; Sutton, V.R.; Wang, H.; Ming, Y.; Kulkarni, S.; Zhong, T.P.; Giampietro, P.F.; Dunwoodie, S.L.; Cheung, S.W.; Zhang, X.; Jin, L.; Lupski, J.R.; Qiu, G.; Zhang, F.

    2015-01-01

    BACKGROUND Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. METHODS We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions. RESULTS We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. CONCLUSIONS Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. PMID:25564734

  9. APOL1 Null Alleles from a Rural Village in India Do Not Correlate with Glomerulosclerosis

    PubMed Central

    Johnstone, Duncan B.; Shegokar, Vijay; Nihalani, Deepak; Rathore, Yogendra Singh; Mallik, Leena; Ashish; Zare, Vasant; Ikizler, H. Omer; Powar, Rajaram; Holzman, Lawrence B.

    2012-01-01

    Background Among African-Americans, genome wide association revealed a strong correlation between the G1 and G2 alleles of APOL1 (apolipoproteinL1, also called trypanolytic factor) and kidney diseases including focal and segmental glomerulosclerosis, HIV-associated nephropathy and hypertensive nephrosclerosis. In the prevailing hypothesis, heterozygous APOL1 G1 and G2 alleles increase resistance against Trypanosoma that cause African sleeping sickness, resulting in positive selection of these alleles, but when homozygous the G1 and G2 alleles predispose to glomerulosclerosis. While efforts are underway to screen patients for G1 and G2 alleles and to better understand “APOL1 glomerulopathy,” no data prove that these APOL1 sequence variants cause glomerulosclerosis. G1 and G2 correlate best with glomerulosclerosis as recessive alleles, which suggests a loss of function mutation for which proof of causality is commonly tested with homozygous null alleles. This test cannot be performed in rodents as the APOL gene cluster evolved only in primates. However, there is a homozygous APOL1 null human being who lives in a village in rural India. This individual and his family offer a unique opportunity to test causality between APOL1 null alleles and glomerulosclerosis. Methods and Findings We obtained clinical data, blood and urine from this APOL1 null patient and 50 related villagers. Based on measurements of blood pressure, BUN, creatinine, albuminuria, genotyping and immunoblotting, this APOL1 null individual does not have glomerulosclerosis, nor do his relatives who carry APOL1 null alleles. Conclusions This small study cannot provide definitive conclusions but the absence of glomerulosclerosis in this unique population is consistent with the possibility that African-American glomerulosclerosis is caused, not by loss of APOL1 function, but by other mechanisms including a subtle gain of function or by the “genetic hitchhiking” of deleterious mutations in a gene

  10. Stimulation of Sigma-1 Receptor Ameliorates Depressive-like Behaviors in CaMKIV Null Mice.

    PubMed

    Moriguchi, Shigeki; Sakagami, Hiroyuki; Yabuki, Yasushi; Sasaki, Yuzuru; Izumi, Hisanao; Zhang, Chen; Han, Feng; Fukunaga, Kohji

    2015-12-01

    Sigma-1 receptor (Sig-1R) is a molecular chaperone regulating calcium efflux from the neuronal endoplasmic reticulum to the mitochondria. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) null mice exhibit depressive-like behaviors and impaired neurogenesis as assessed by bromodeoxyuridine (BrdU) incorporation into newborn cells of the hippocampal dentate gyrus (DG). Here, we demonstrate that chronic stimulation of Sig-1R by treatment with the agonist SA4503 or the SSRI fluvoxamine for 14 days improves depressive-like behaviors in CaMKIV null mice. By contrast, treatment with paroxetine, which lacks affinity for Sig-1R, did not alter these behaviors. Reduced numbers of BrdU-positive cells and decreased brain-derived neurotrophic factor (BDNF) mRNA expression and protein kinase B (Akt; Ser-473) phosphorylation seen in the DG of CaMKIV null mice were significantly rescued by chronic Sig-1R stimulation. Interestingly, reduced ATP production observed in the DG of CaMKIV null mice was improved by chronic Sig-1R stimulation. Such stimulation also improved hippocampal long-term potentiation (LTP) induction and maintenance, which are impaired in the DG of CaMKIV null mice. LTP rescue was closely associated with both increases in calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and GluA1 (Ser-831) phosphorylation. Taken together, Sig-1R stimulation by SA4503 or fluvoxamine treatment increased hippocampal neurogenesis, which is closely associated with amelioration of depressive-like behaviors in CaMKIV null mice. PMID:25316382

  11. A genetic algorithmic approach to antenna null-steering using a cluster computer.

    NASA Astrophysics Data System (ADS)

    Recine, Greg; Cui, Hong-Liang

    2001-06-01

    We apply a genetic algorithm (GA) to the problem of electronically steering the maximums and nulls of an antenna array to desired positions (null toward enemy listener/jammer, max toward friendly listener/transmitter). The antenna pattern itself is computed using NEC2 which is called by the main GA program. Since a GA naturally lends itself to parallelization, this simulation was applied to our new twin 64-node cluster computers (Gemini). Design issues and uses of the Gemini cluster in our group are also discussed.

  12. Physical optics model of side lobe nulling by discs on a parabolic reflector

    NASA Astrophysics Data System (ADS)

    Trapp, D. A.

    1985-12-01

    By mounting small disc reflectors that are moveable relative to the inner reflector surface of a parabolic dish antenna, nulls can be generated in the side lobe region of the power radiation pattern with minimal distortion effects to the main beam. A physical optics model of this antenna system is developed to investigate in a simplified direct manner the phenomena of phase nulling caused by disc movement. Array theory using isotropic radiators is used to sample the aperture distribution to approximate the far field electric field of the dish. A physical optics approximation for scattering off a flat metal disc is used for discs and feed blockage effects.

  13. Extending the scanning angle of a phased array antenna by using a null-space medium.

    PubMed

    Sun, Fei; He, Sailing

    2014-01-01

    By introducing a columnar null-space region as the reference space, we design a radome that can extend the scanning angle of a phased array antenna (PAA) by a predetermined relationship (e.g. a linear relationship between the incident angle and steered output angle can be achieved). After some approximation, we only need two homogeneous materials to construct the proposed radome layer by layer. This kind of medium is called a null-space medium, which has been studied and fabricated for realizing hyper-lenses and some other devices. Numerical simulations verify the performance of our radome. PMID:25355198

  14. Extending the scanning angle of a phased array antenna by using a null-space medium

    NASA Astrophysics Data System (ADS)

    Sun, Fei; He, Sailing

    2014-10-01

    By introducing a columnar null-space region as the reference space, we design a radome that can extend the scanning angle of a phased array antenna (PAA) by a predetermined relationship (e.g. a linear relationship between the incident angle and steered output angle can be achieved). After some approximation, we only need two homogeneous materials to construct the proposed radome layer by layer. This kind of medium is called a null-space medium, which has been studied and fabricated for realizing hyper-lenses and some other devices. Numerical simulations verify the performance of our radome.

  15. Extending the scanning angle of a phased array antenna by using a null-space medium

    PubMed Central

    Sun, Fei; He, Sailing

    2014-01-01

    By introducing a columnar null-space region as the reference space, we design a radome that can extend the scanning angle of a phased array antenna (PAA) by a predetermined relationship (e.g. a linear relationship between the incident angle and steered output angle can be achieved). After some approximation, we only need two homogeneous materials to construct the proposed radome layer by layer. This kind of medium is called a null-space medium, which has been studied and fabricated for realizing hyper-lenses and some other devices. Numerical simulations verify the performance of our radome. PMID:25355198

  16. Organic anion transporting polypeptide 1a1 null mice are sensitive to cholestatic liver injury.

    PubMed

    Zhang, Youcai; Csanaky, Iván L; Cheng, Xingguo; Lehman-McKeeman, Lois D; Klaassen, Curtis D

    2012-06-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis. PMID:22461449

  17. Null tests for oblate spheroids. [aspheric surfaces in reflecting optical system designs

    NASA Technical Reports Server (NTRS)

    Rodgers, J. M.; Parks, R. E.

    1984-01-01

    In most real cases requiring simple null optics, the optical path difference cannot be reduced to zero but can be kept at a fractional wavelength level so that interferometric data reduction can be used to account for the residual error. In other cases, computer-generated holograms may be used to obtain apparently straight fringes when the desired surface is obtained. Two examples, one involving an f/2.5 concave oblate spheroid and the other a Paul-Baker secondary, are examined. It is shown that although the null tests are not generally perfect, the residual error is small and the tests are simple.

  18. The Null method applied to GNSS three-carrier phase ambiguity resolution

    NASA Astrophysics Data System (ADS)

    Fernández-Plazaola, U.; Martín-Guerrero, T. M.; Entrambasaguas-Muñoz, J. T.; Martín-Neira, M.

    2004-09-01

    The Null method is a technique to fix the ambiguity in L1 phase measurements of the global positioning system (GPS). The method is adapted to new global navigation satellite systems (GNSS) which offer phase measurements at three frequencies. In order to validate the efficiency of the adapted method, results obtained using a software simulator and an emulator are presented. The results are then compared to those obtained with the least-squares ambiguity decorrelation adjustment (LAMBDA) method. Good performance of the Null method in new GNSS systems is shown.

  19. Design approaches and parameters for magnetically levitated transport systems. [Null flux suspension (Maglev)

    SciTech Connect

    Danby, G.T.; Powell, J.R.

    1988-01-01

    Mechanically levitated transport system approaches are assessed with regard to thrust power needs, track cost, suspension stability, and safety. The null flux suspension appears as the favored approach, having the least thrust power requirements, highest stability, and lowest amount of track material. Various null flux configurations are described together with their operating parameters. The Linear Synchronous Motor (LSM) propulsion system is also described for propelling the suspended vehicles. Cryogenics and superconductivity aspects are discussed and the effect of high T/sub c/ superconductors evaluated. 13 refs., 16 figs., 2 tabs.

  20. Wound Healing Characteristics of ICAM-1 Null Mice Devoid of All Isoforms of ICAM-1

    PubMed Central

    Gay, Andre N.; Mushin, Oren P.; Lazar, David A.; Naik-Mathuria, Bindi J.; Yu, Ling; Gobin, Andre; Smith, C. Wayne; Olutoye, Oluyinka O.

    2011-01-01

    Background Intercellular Adhesion Molecule-1 (ICAM-1) permits leukocyte-endothelial adhesion and transmigration during inflammation. Membrane-bound ICAM-1 knockout mice have been used to understand this molecule’s role in wound-healing, but expressed spliced isoforms of ICAM-1 may have impacted results. We aimed to characterize wound-healing in an ICAM-1 null model devoid of all ICAM-1 isoforms. Methods Full-thickness 8-mm wounds were created on C57/BL6 wild-type (n=24) and ICAM-1 null (n=24) mice. Wound area was calculated using daily photographs. Histologic samples were harvested on post-operative Days 1,3,7, and 14. Wound margins were evaluated for mRNA expression of 13 inflammatory cytokines. A separate group of wild-type and ICAM-1 null mice (n=24) received full-thickness incisions with tensiometry measured at Day 14. Separately, complete blood counts were measured in unwounded wild-type (n=4) and ICAM-1 null mice (n=4). Results Wound-closure was significantly delayed in ICAM-1 null mice through Day 7 by gross and histologic measurement. mRNA expression of VEGF-A was increased in ICAM-1 null mice on Day 3, although no increase in VEGF-A was observed in the wound bed by immunohistochemistry. ICAM-1 null wounds demonstrated higher stiffness upon Day 14 tensiometry compared to the wild-type (1880 ± 926 kPa vs. 478 ± 117 kPa;p<0.01), and had higher counts of white blood cells (10,009 vs. 5,720 cells/microliter,p<0.05), neutrophils (2,130 vs. 630 cells/microliter,p<0.01), and lymphocytes (7,130 vs. 4,740 cells/microliter, p<0.05). Conclusions ICAM-1 null mice demonstrate delayed wound-healing and decreased wound elasticity compared to wild-type controls. This lag, however, was less than observed in earlier membrane-bound ICAM-1 knockouts, suggesting that other ICAM-1 isoforms may promote delayed wound-healing. PMID:21872884

  1. Petrology of the Cangas de Onis and nulles regolith breccias Implications for parent body history

    NASA Technical Reports Server (NTRS)

    Williams, C. V.; Rubin, A. E.; Keil, K.; San Miguel, A.

    1985-01-01

    The present study of the Cangas de Onis and Nulles H chondrite regolith breccias indicates that the minerals in the matrices and equilibrated clasts have essentially the same compositional distributions, so that much of the material in the castic matrix would have to have been derived from the impact comminution of clats. The apparently exclusive occurrence of H6 clasts in Cangas de Onis, and H4 clasts in Nulles, suggests that, at the locations where these breccias formed, the regolith predominantly consisted of H6 and H4 material, respectively.

  2. Petrology of the Cangas de Onis and nulles regolith breccias Implications for parent body history

    NASA Astrophysics Data System (ADS)

    Williams, C. V.; Rubin, A. E.; Keil, K.; San Miguel, A.

    1985-06-01

    Cangas de Onis and Nulles are H chondrite regolith breccias from northern Spain. Uniform mineral compositions in both Cangas de Onis and Nulles indicate that their matrices consist almost entirely of comminuted equilibrated clasts. If these meteorites are representative samples of the regoliths in which they resided, the regoliths were compositionally homogeneous at the time of breccia consolidation. Zoned taenites within the clastic matrix of Cangas de Onis scatter widely on composition-dimension plots, indicating that these taenites cooled at different rates (about 1 - 1000 K/m.y.) at various depths (1 - 150 km). This suggests that the H chondrite parent body was disrupted and reassembled.

  3. Brucella abortus Cyclic β-1,2-Glucan Mutants Have Reduced Virulence in Mice and Are Defective in Intracellular Replication in HeLa Cells

    PubMed Central

    Briones, Gabriel; Iñón de Iannino, Nora; Roset, Mara; Vigliocco, Ana; Paulo, Patricia Silva; Ugalde, Rodolfo A.

    2001-01-01

    Null cyclic β-1,2-glucan synthetase mutants (cgs mutants) were obtained from Brucella abortus virulent strain 2308 and from B. abortus attenuated vaccinal strain S19. Both mutants show greater sensitivity to surfactants like deoxycholic acid, sodium dodecyl sulfate, and Zwittergent than the parental strains, suggesting cell surface alterations. Although not to the same extent, both mutants display reduced virulence in mice and defective intracellular multiplication in HeLa cells. The B. abortus S19 cgs mutant was completely cleared from the spleens of mice after 4 weeks, while the 2308 mutant showed a 1.5-log reduction of the number of brucellae isolated from the spleens after 12 weeks. These results suggest that cyclic β-1,2-glucan plays an important role in the residual virulence of the attenuated B. abortus S19 strain. Although the cgs mutant was cleared from the spleens earlier than the wild-type parental strain (B. abortus S19) and produced less inflammatory response, its ability to confer protection against the virulent strain B. abortus 2308 was fully retained. Equivalent levels of induction of spleen gamma interferon mRNA and anti-lipopolysaccharide (LPS) of immunoglobulin G2a (IgG2a) subtype antibodies were observed in mice injected with B. abortus S19 or the cgs mutant. However, the titer of anti-LPS antibodies of the IgG1 subtype induced by the cgs mutant was lower than that observed with the parental S19 strain, thus suggesting that the cgs mutant induces a relatively exclusive Th1 response. PMID:11401996

  4. The heparan sulphate deficient Hspg2 exon 3 null mouse displays reduced deposition of TGF-β1 in skin compared to C57BL/6 wild type mice.

    PubMed

    Shu, Cindy; Smith, Susan M; Melrose, James

    2016-06-01

    This was an observational study where we examined the role of perlecan HS on the deposition of TGF-β1 in C57BL/6 and Hspg2(∆3-/∆3-) perlecan exon 3 null mouse skin. Despite its obvious importance in skin repair and tissue homeostasis no definitive studies have immunolocalised TGF-β1 in skin in WT or Hspg2(∆3-/∆3-) perlecan exon 3 null mice. Vertical parasagittal murine dorsal skin from 3, 6 and 12 week old C57BL/6 and Hspg2(∆3-/∆3-) mice were fixed in neutral buffered formalin, paraffin embedded and 4 μm sections stained with Mayers haematoxylin and eosin (H & E). TGF-β1 was immunolocalised using a rabbit polyclonal antibody, heat retrieval and the Envision NovaRED detection system. Immunolocalisation of TGF-β1 differed markedly in C57BL/6 and Hspg2(∆3-/∆3-) mouse skin, ablation of exon 3 of Hspg2 resulted in a very severe reduction in the deposition of TGF-β1 in skin 3-12 weeks postnatally. The reduced deposition of TGF-β1 observed in the present study would be expected to impact detrimentally on the remodelling and healing capacity of skin in mutant mice compounding on the poor wound-healing properties already reported for perlecan exon 3 null mice due to an inability to signal with FGF-2 and promote angiogenic repair processes. TGF-β1 also has cell mediated effects in tissue homeostasis and matrix stabilisation a reduction in TGF-β1 deposition would therefore be expected to detrimentally impact on skin homeostasis in the perlecan mutant mice. PMID:27098652

  5. Regulation of Mutant p53 Protein Expression

    PubMed Central

    Vijayakumaran, Reshma; Tan, Kah Hin; Miranda, Panimaya Jeffreena; Haupt, Sue; Haupt, Ygal

    2015-01-01

    For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type (wt) counterpart. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. While wt p53 returns to basal level following recovery from stress, mutant p53 remains stable. In part, this can be explained in mutant p53-expressing cells by the lack of an auto-regulatory loop with Mdm2 and other negative regulators, which are pivotal for wt p53 regulation. Further, additional protective mechanisms are acquired by mutant p53, largely mediated by the co-chaperones and their paralogs, the stress-induced heat shock proteins. Consequently, mutant p53 is accumulated in cancer cells in response to chronic stress and this accumulation is critical for its oncogenic gain of functions (GOF). Building on the extensive knowledge regarding wt p53, the regulation of mutant p53 is unraveling. In this review, we describe the current understanding on the major levels at which mutant p53 is regulated. These include the regulation of p53 protein levels by microRNA and by enzymes controlling p53 proteasomal degradation. PMID:26734569

  6. Uncaging Mutants: Moving From Menageries to Menages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The thousands of mutants of maize are a remarkable resource for study of plant physiology, phylogeny, cell biology, biochemistry, development, and molecular biology. Mutants are most often applied in research studies as "members of collections" rather than as select families of members relevant to ...

  7. Nebulin binding impedes mutant desmin filament assembly

    PubMed Central

    Baker, Laura K.; Gillis, David C.; Sharma, Sarika; Ambrus, Andy; Herrmann, Harald; Conover, Gloria M.

    2013-01-01

    Desmin intermediate filaments (DIFs) form an intricate meshwork that organizes myofibers within striated muscle cells. The mechanisms that regulate the association of desmin to sarcomeres and their role in desminopathy are incompletely understood. Here we compare the effect nebulin binding has on the assembly kinetics of desmin and three desminopathy-causing mutant desmin variants carrying mutations in the head, rod, or tail domains of desmin (S46F, E245D, and T453I). These mutants were chosen because the mutated residues are located within the nebulin-binding regions of desmin. We discovered that, although nebulin M160–164 bound to both desmin tetrameric complexes and mature filaments, all three mutants exhibited significantly delayed filament assembly kinetics when bound to nebulin. Correspondingly, all three mutants displayed enhanced binding affinities and capacities for nebulin relative to wild-type desmin. Electron micrographs showed that nebulin associates with elongated normal and mutant DIFs assembled in vitro. Moreover, we measured significantly delayed dynamics for the mutant desmin E245D relative to wild-type desmin in fluorescence recovery after photobleaching in live-cell imaging experiments. We propose a mechanism by which mutant desmin slows desmin remodeling in myocytes by retaining nebulin near the Z-discs. On the basis of these data, we suggest that for some filament-forming desmin mutants, the molecular etiology of desminopathy results from subtle deficiencies in their association with nebulin, a major actin-binding filament protein of striated muscle. PMID:23615443

  8. Mutants of thermotaxis in Dictyostelium discoideum

    SciTech Connect

    Schneider, M.J.; Fontana, D.R.; Poff, K.L.

    1982-08-01

    Amoebae of Dictyostelium discoideum, strain HL50 were mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine, cloned, allowed to form pseudoplasmodia and screened for aberrant positive and negative thermotaxis. Three types of mutants were found. Mutant HO428 exhibits only positive thermotaxis over the entire temperature range (no negative thermotaxis). HO596 and HO813 exhibit weakened positive thermotaxis and normal negative thermotaxis. The weakened positive thermotactic response results in a shift toward warmer temperatures in the transition temperature from negative to positive thermotaxis. Mutant HO209 exhibits weakened positive and negative thermotactic responses and has a transition temperature similar to the 'wild type' (HL50).The two types of mutants represented by HO428, HO596 and HO813 support the model that positive and negative thermotaxis have separate pathways for temperature sensing. The type of mutants which contains HO209 suggests that those two pathways converge at some point before the response.

  9. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome

    PubMed Central

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both −/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress. PMID:24769161

  10. Electric Current Filamentation at a Non-potential Magnetic Null-point Due to Pressure Perturbation

    NASA Astrophysics Data System (ADS)

    Jelínek, P.; Karlický, M.; Murawski, K.

    2015-10-01

    An increase of electric current densities due to filamentation is an important process in any flare. We show that the pressure perturbation, followed by an entropy wave, triggers such a filamentation in the non-potential magnetic null-point. In the two-dimensional (2D), non-potential magnetic null-point, we generate the entropy wave by a negative or positive pressure pulse that is launched initially. Then, we study its evolution under the influence of the gravity field. We solve the full set of 2D time dependent, ideal magnetohydrodynamic equations numerically, making use of the FLASH code. The negative pulse leads to an entropy wave with a plasma density greater than in the ambient atmosphere and thus this wave falls down in the solar atmosphere, attracted by the gravity force. In the case of the positive pressure pulse, the plasma becomes evacuated and the entropy wave propagates upward. However, in both cases, owing to the Rayleigh-Taylor instability, the electric current in a non-potential magnetic null-point is rapidly filamented and at some locations the electric current density is strongly enhanced in comparison to its initial value. Using numerical simulations, we find that entropy waves initiated either by positive or negative pulses result in an increase of electric current densities close to the magnetic null-point and thus the energy accumulated here can be released as nanoflares or even flares.

  11. What Are Null Hypotheses? The Reasoning Linking Scientific and Statistical Hypothesis Testing

    ERIC Educational Resources Information Center

    Lawson, Anton E.

    2008-01-01

    We should dispense with use of the confusing term "null hypothesis" in educational research reports. To explain why the term should be dropped, the nature of, and relationship between, scientific and statistical hypothesis testing is clarified by explication of (a) the scientific reasoning used by Gregor Mendel in testing specific…

  12. An Argument Framework for the Application of Null Hypothesis Statistical Testing in Support of Research

    ERIC Educational Resources Information Center

    LeMire, Steven D.

    2010-01-01

    This paper proposes an argument framework for the teaching of null hypothesis statistical testing and its application in support of research. Elements of the Toulmin (1958) model of argument are used to illustrate the use of p values and Type I and Type II error rates in support of claims about statistical parameters and subject matter research…

  13. A study of the performance of a nulling interferometer testbed preparatory to the Darwin mission

    NASA Astrophysics Data System (ADS)

    Gabor, Pavel

    2009-09-01

    Preparations for a future interferometric flagship space mission (Darwin, TPF-I) are under way in order to study Earth-like extrasolar planets in the habitable zones of their parent stars, and more particularly to estimate the proportion of such exoplanets with atmospheric compositions suggesting the presence of biotic photosynthesis. Nulling interferometry operating in the spectral band between 6 and 18 μm may allow distinguishing the emissions of the exoplanet from those of its star and the ambient diffuse sources. The thesis summarises the experimental work performed on the SYNAPSE test bed at the Institut d'Astrophysique Spatiale in Orsay. The bench was tested in the K band, from 2.0 to 2.5 μm, as well as with a laser at 3.39 μm. The results confirm the trend observed by other research groups, viz., the performance is better in monochromatic light than in broadband (nulling ratios of 1E-5 monochromatic, and 3E-4 broad band). Extensive experimental study of this phe nomenon is described. In addition to these efforts aiming at a better grasp of nulling interferometry as such, we tested an Achromatic Phase Shifter prototype (a key element in broadband nulling) based on the through-focus principle. We developed a technique of optical path difference stabilisation, where interferometrically combined flux is measured while dithering the optical path difference. We reached stability levels comparable to those required for the future space mission.

  14. Interpretation of Chinese Overt and Null Embedded Arguments by English-Speaking Learners

    ERIC Educational Resources Information Center

    Zhao, Lucy Xia

    2012-01-01

    It has been proposed that external interfaces are vulnerable to residue optionality, whereas pure syntax and internal interfaces are acquirable in second language (L2) acquisition (Sorace, 2005, 2011; Sorace and Filiaci, 2006). The proposal was tested in this article through the interpretation of overt and null embedded arguments in L2 Chinese…

  15. Numerical Study of the Gravitational and Electromagnetic Waves on the Null Cone

    NASA Astrophysics Data System (ADS)

    Babiuc, Maria

    2015-04-01

    The numerical calculation of the Einstein-Maxwell equations in a characteristic framework has not been done numerically before and is expected to shed new light on nonlinear phenomena like null memory. The main objective of this study is the analytical and numerical modeling of the of gravitational and electromagnetic radiation in a fully general relativistic framework, as it propagates on the null cone to null infinity, with no simplifications due to assumed symmetries. Moreover, the global interaction between the gravitational and electromagnetic radiation will be closely monitored, in order to reveal the electromagnetic radiation memory induced by the gravitational field. The numerical approach used, called the ``Cauchy-characteristic extraction'' method, is the most precise method for the computation of gravitational waveforms at infinite distance from a world-tube that encloses the source. The analytical and numerical models presented here will be implemented in the PittNull code, and the experience gained will be disseminated, in order to facilitate new standalone characteristic codes.This will lead to more insight on the interaction between gravitational and electromagnetic fields, and even point to new effects.

  16. Path Length Control in a Nulling Coronagraph with a MEMS Deformable Mirror and a Calibration Interferometer

    NASA Technical Reports Server (NTRS)

    Rao, Shanti R.; Wallacea, J. Kent; Samuele, Rocco; Chakrabarti, Supriya; Cook, Timothy; Hicks, Brian; Jung, Paul; Lane, Benjamin; Levine, B. Martin; Mendillo, Chris; Schmidtlin, Edouard; Shao, Mike; Stewart, Jason B.

    2008-01-01

    We report progress on a nulling coronagraph intended for direct imaging of extrasolar planets. White light is suppressed in an interferometer, and phase errors are measured by a second interferometer. A 1020-pixel MEMS deformable mirror in the first interferometer adjusts the path length across the pupil. A feedback control system reduces deflections of the deformable mirror to order of 1 nm rms.

  17. A Range-Null Hypothesis Approach for Testing DIF under the Rasch Model

    ERIC Educational Resources Information Center

    Wells, Craig S.; Cohen, Allan S.; Patton, Jeffrey

    2009-01-01

    A primary concern with testing differential item functioning (DIF) using a traditional point-null hypothesis is that a statistically significant result does not imply that the magnitude of DIF is of practical interest. Similarly, for a given sample size, a non-significant result does not allow the researcher to conclude the item is free of DIF. To…

  18. 2D Grushin-type equations: Minimal time and null controllable data

    NASA Astrophysics Data System (ADS)

    Beauchard, Karine; Miller, Luc; Morancey, Morgan

    2015-12-01

    We study internal null controllability for degenerate parabolic equations of Grushin-type Gγ = ∂xx2 +| x | 2 γ ∂yy2 (γ > 0), in the rectangle (x, y) ∈ Ω = (- 1, 1) × (0, 1). Previous works proved that null controllability holds for weak degeneracies (γ small), and fails for strong degeneracies (γ large). Moreover, in the transition regime and with strip shaped control domains, a positive minimal time is required. In this paper, we work with controls acting on two strips, symmetric with respect to the degeneracy. We give the explicit value of the minimal time and we characterize some initial data that can be steered to zero in time T (when the system is not null controllable): their regularity depends on the control domain and the time T. We also prove that, with a control that acts on one strip, touching the degeneracy line { x = 0 }, then Grushin-type equations are null controllable in any time T > 0 and for any degeneracy γ > 0. Our approach is based on a precise study of the observability property for the one-dimensional heat equations satisfied by the Fourier coefficients in variable y. This precise study is done, through a transmutation process, on the resulting one-dimensional wave equations, by lateral propagation of energy method.

  19. Experimental progress in deep and broadband infrared nulling for TPF-I

    NASA Technical Reports Server (NTRS)

    Wallace, J. Kent; Bartos, Randall; Gappinger, Robert; Loya, Frank; Moser, Steve; Negron, John

    2005-01-01

    Our activities are focused upon the experimental demonstration of deep nulling in the mid-IR over a wide bandpass. Specifically, our near-term goal is demonstrating a contrast of 10^-6 at 10 um with a 25% spectral bandwidth.

  20. Parallel-propagated frame along null geodesics in higher-dimensional black hole spacetimes

    SciTech Connect

    Kubiznak, David; Frolov, Valeri P.; Connell, Patrick; Krtous, Pavel

    2009-01-15

    In [arXiv:0803.3259] the equations describing the parallel transport of orthonormal frames along timelike (spacelike) geodesics in a spacetime admitting a nondegenerate principal conformal Killing-Yano 2-form h were solved. The construction employed is based on studying the Darboux subspaces of the 2-form F obtained as a projection of h along the geodesic trajectory. In this paper we demonstrate that, although slightly modified, a similar construction is possible also in the case of null geodesics. In particular, we explicitly construct the parallel-transported frames along null geodesics in D=4, 5, 6 Kerr-NUT-(A)dS spacetimes. We further discuss the parallel transport along principal null directions in these spacetimes. Such directions coincide with the eigenvectors of the principal conformal Killing-Yano tensor. Finally, we show how to obtain a parallel-transported frame along null geodesics in the background of the 4D Plebanski-Demianski metric which admits only a conformal generalization of the Killing-Yano tensor.

  1. A Communication Researchers' Guide to Null Hypothesis Significance Testing and Alternatives

    ERIC Educational Resources Information Center

    Levine, Timothy R.; Weber, Rene; Park, Hee Sun; Hullett, Craig R.

    2008-01-01

    This paper offers a practical guide to use null hypotheses significance testing and its alternatives. The focus is on improving the quality of statistical inference in quantitative communication research. More consistent reporting of descriptive statistics, estimates of effect size, confidence intervals around effect sizes, and increasing the…

  2. High Contrast Vacuum Nuller Testbed (VNT) Contrast, Performance and Null Control

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-01-01

    Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal planeregion extending from 14 D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. TheVNC is a hybrid interferometriccoronagraphic approach for exoplanet science. It operates with high Lyot stopefficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential futureNASA flight telescopes. NASAGoddard Space Flight Center (GSFC) has a well-established effort to develop the VNCand its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and itsenabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry tounprecedented levels. The VNC is based on a modified Mach-Zehnder nulling interferometer, with a W configurationto accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters.We give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, criticaltechnologies and null sensing and control.

  3. Stable deep nulling in polychromatic unpolarized light with multiaxial beam combination.

    PubMed

    Buisset, Christophe; Rejeaunier, Xavier; Rabbia, Yves; Barillot, Marc

    2007-11-10

    In the context of the space-based nulling mission ESA-Darwin, Thales Alenia Space has developed a nulling breadboard for the European Space Agency (ESA): the multiaperture imaging interferometer (MAII) to demonstrate deep and stable nulling and to investigate various subsystems of the ESA-Darwin interferometer. Recently, we have extended our investigations to the multiaxial beam combination. This combination scheme presents many advantages: simplicity, compactness, and a high coupling efficiency for a three-beam combination. The near-infrared (lambda approximately 1.55 microm) MAII breadboard has been upgraded to the multiaxial beam combination. Polarization and stability issues have been thoroughly investigated. We report on the recent results we have obtained with the multiaxial configuration of MAII in unpolarized light with a relative spectral bandwidth of 5%: nulling ratios of mean value N=1.7 x 10(-5), stable over 1 h with a standard deviation sigma( N )=5.7 x 10(-7). These results indicate that the multiaxial beam combination has the potential to meet Darwin requirements. PMID:17994130

  4. Irxl1 mutant mice show reduced tendon differentiation and no patterning defects in musculoskeletal system development.

    PubMed

    Kimura, Wataru; Machii, Masashi; Xue, XiaoDong; Sultana, Nishat; Hikosaka, Keisuke; Sharkar, Mohammad T K; Uezato, Tadayoshi; Matsuda, Masashi; Koseki, Haruhiko; Miura, Naoyuki

    2011-01-01

    Irxl1 (Iroquois-related homeobox like-1) is a newly identified three amino-acid loop extension (TALE) homeobox gene, which is expressed in various mesoderm-derived tissues, particularly in the progenitors of the musculoskeletal system. To analyze the roles of Irxl1 during embryonic development, we generated mice carrying a null allele of Irxl1. Mice homozygous for the targeted allele were viable, fertile, and showed reduced tendon differentiation. Skeletal morphology and skeletal muscle weight in Irxl1-knockout mice appeared normal. Expression patterns of several marker genes for cartilage, tendon, and muscle progenitors in homozygous mutant embryos were unchanged. These results suggest that Irxl1 is required for the tendon differentiation but dispensable for the patterning of the musculoskeletal system in development. PMID:21254332

  5. Drosophila calmodulin mutants with specific defects in the musculature or in the nervous system.

    PubMed Central

    Wang, Bo; Sullivan, Kathleen M C; Beckingham, Kathy

    2003-01-01

    We have studied lethal mutations in the single calmodulin gene (Cam) of Drosophila to gain insight into the in vivo functions of this important calcium sensor. As a result of maternal calmodulin (CaM) in the mature egg, lethality is delayed until the postembryonic stages. Prior to death in the first larval instar, Cam nulls show a striking behavioral abnormality (spontaneous backward movement) whereas a mutation, Cam7, that results in a single amino acid change (V91G) produces a very different phenotype: short indented pupal cases and pupal death with head eversion defects. We show here that the null behavioral phenotype originates in the nervous system and involves a CaM function that requires calcium binding to all four sites of the protein. Further, backward movement can be induced in hypomorphic mutants by exposure to high light levels. In contrast, the V91G mutation specifically affects the musculature and causes abnormal calcium release in response to depolarization of the muscles. Genetic interaction studies suggest that failed regulation of the muscle calcium release channel, the ryanodine receptor, is the major defect underlying the Cam7 phenotype. PMID:14668380

  6. Systematic screening of glycosylation- and trafficking-associated gene knockouts in Saccharomyces cerevisiae identifies mutants with improved heterologous exocellulase activity and host secretion

    PubMed Central

    2013-01-01

    Background As a strong fermentator, Saccharomyces cerevisiae has the potential to be an excellent host for ethanol production by consolidated bioprocessing. For this purpose, it is necessary to transform cellulose genes into the yeast genome because it contains no cellulose genes. However, heterologous protein expression in S. cerevisiae often suffers from hyper-glycosylation and/or poor secretion. Thus, there is a need to genetically engineer the yeast to reduce its glycosylation strength and to increase its secretion ability. Results Saccharomyces cerevisiae gene-knockout strains were screened for improved extracellular activity of a recombinant exocellulase (PCX) from the cellulose digesting fungus Phanerochaete chrysosporium. Knockout mutants of 47 glycosylation-related genes and 10 protein-trafficking-related genes were transformed with a PCX expression construct and screened for extracellular cellulase activity. Twelve of the screened mutants were found to have a more than 2-fold increase in extracellular PCX activity in comparison with the wild type. The extracellular PCX activities in the glycosylation-related mnn10 and pmt5 null mutants were, respectively, 6 and 4 times higher than that of the wild type; and the extracellular PCX activities in 9 protein-trafficking-related mutants, especially in the chc1, clc1 and vps21 null mutants, were at least 1.5 times higher than the parental strains. Site-directed mutagenesis studies further revealed that the degree of N-glycosylation also plays an important role in heterologous cellulase activity in S. cerevisiae. Conclusions Systematic screening of knockout mutants of glycosylation- and protein trafficking-associated genes in S. cerevisiae revealed that: (1) blocking Golgi-to-endosome transport may force S. cerevisiae to export cellulases; and (2) both over- and under-glycosylation may alter the enzyme activity of cellulases. This systematic gene-knockout screening approach may serve as a convenient means for

  7. Incomplete flagellar structures in Escherichia coli mutants.

    PubMed Central

    Suzuki, T; Komeda, Y

    1981-01-01

    Escherichia coli mutants with defects in 29 flagellar genes identified so far were examined by electron microscopy for possession of incomplete flagellar structures in membrane-associated fractions. The results are discussed in consideration of the known transcriptional interaction of flagellar genes. Hook-basal body structures were detected in flaD, flaS, flaT, flbC, and hag mutants. The flaE mutant had a polyhook-basal body structure. An intact basal body appeared in flaK mutants. Putative precursors of the basal body were detected in mutants with defects in flaM, flaU, flaV, and flaY. No structures homologous to the flagellar basal body or its parts were detected in mutants with defects in flaA, flaB, flaC, flaG, flaH, flaI, flaL, flaN, flaO, flaP, flaQ, flaR, flaW, flaX, flbA, flbB, and flbD. One flaZ mutant had an incomplete flagellar basal body structure and another formed no significant structure, suggesting that flaZ is responsible for both basal body assembly and the transcription of the hag gene. Images PMID:7007337

  8. Kasugamycin-dependent mutants of Escherichia coli.

    PubMed Central

    Dabbs, E R

    1978-01-01

    Kasugamycin-dependent mutants have been isolated from Escherichia coli B. They were obtained through mutagenesis with ethyl methane sulfonate or nitrosoguanidine in conjunction with an antibiotic underlay technique. In the case of nitrosoguanidine, dependent mutants were obtained at a frequency of about 3% of survivors growing up in the selection. In the case of ethyl methane sulfonate, the corresponding value was 1%. Nineteen mutants showing a kasugamycin-dependent phenotype were studied. In terms of response to various temperatures and antibiotic concentrations, they were very heterogeneous, although most fell into two general classes. Genetic analysis indicated that in at least some cases, the kasugamycin-dependent phenotype was the product of two mutations. Two-dimensional gel electropherograms revealed alterations in the ribosomal proteins of seven mutants. One mutant had an alteration in protein S13, and one had an alteration in protein L14. Three showed changes in protein S9. Each of two mutants had changes in two proteins, S18 and L11. Three of these mutants additionally had protein S18 occurring in a partly altered, partly unaltered form. Images PMID:363701

  9. Exome sequencing identified null mutations in LOXL3 associated with early-onset high myopia

    PubMed Central

    Li, Jiali; Gao, Bei; Xiao, Xueshan; Li, Shiqiang; Jia, Xiaoyun; Sun, Wenmin; Guo, Xiangming

    2016-01-01

    Purpose To identify null mutations in novel genes associated with early-onset high myopia using whole exome sequencing. Methods Null mutations, including homozygous and compound heterozygous truncations, were selected from whole exome sequencing data for 298 probands with early-onset high myopia. These data were compared with those of 507 probands with other forms of eye diseases. Null mutations specific to early-onset high myopia were considered potential candidates. Candidate mutations were confirmed with Sanger sequencing and were subsequently evaluated in available family members and 480 healthy controls. Results A homozygous frameshift mutation (c.39dup; p.L14Afs*21) and a compound heterozygous frameshift mutation (c.39dup; p.L14Afs*21 and c.594delG; p.Q199Kfs*35) in LOXL3 were separately identified in two of the 298 probands with early-onset high myopia. These mutations were confirmed with Sanger sequencing and were not detected in 1,974 alleles of the controls from the same region (507 individuals with other conditions and 480 healthy control individuals). These two probands were singleton cases, and their parents had only heterozygous mutations. A homozygous missense mutation in LOXL3 was recently reported in a consanguineous family with Stickler syndrome. Conclusions Our results suggest that null mutations in LOXL3 are likely associated with autosomal recessive early-onset high myopia. LOXL3 is a potential candidate gene for high myopia, but this possibility should be confirmed in additional studies. LOXL3 null mutations in human beings are not lethal, providing a phenotype contrary to that in mice. PMID:26957899

  10. SOLAR CYCLE VARIATIONS OF CORONAL NULL POINTS: IMPLICATIONS FOR THE MAGNETIC BREAKOUT MODEL OF CORONAL MASS EJECTIONS

    SciTech Connect

    Cook, G. R.; Mackay, D. H.; Nandy, Dibyendu E-mail: duncan@mcs.st-and.ac.u

    2009-10-20

    In this paper, we investigate the solar cycle variation of coronal null points and magnetic breakout configurations in spherical geometry, using a combination of magnetic flux transport and potential field source surface models. Within the simulations, a total of 2843 coronal null points and breakout configurations are found over two solar cycles. It is found that the number of coronal nulls present at any time varies cyclically throughout the solar cycle, in phase with the flux emergence rate. At cycle maximum, peak values of 15-17 coronal nulls per day are found. No significant variation in the number of nulls is found from the rising to the declining phase. This indicates that the magnetic breakout model is applicable throughout both phases of the solar cycle. In addition, it is shown that when the simulations are used to construct synoptic data sets, such as those produced by Kitt Peak, the number of coronal nulls drops by a factor of 1/6. The vast majority of the coronal nulls are found to lie above the active latitudes and are the result of the complex nature of the underlying active region fields. Only 8% of the coronal nulls are found to be connected to the global dipole. Another interesting feature is that 18% of coronal nulls are found to lie above the equator due to cross-equatorial interactions between bipoles lying in the northern and southern hemispheres. As the majority of coronal nulls form above active latitudes, their average radial extent is found to be in the low corona below 1.25 R {sub sun} (175, 000 km above the photosphere). Through considering the underlying photospheric flux, it is found that 71% of coronal nulls are produced though quadrupolar flux distributions resulting from bipoles in the same hemisphere interacting. When the number of coronal nulls present in each rotation is compared to the number of bipoles emerging, a wide scatter is found. The ratio of coronal nulls to emerging bipoles is found to be approximately 1/3. Overall

  11. Swimming activity in dystonia musculorum mutant mice.

    PubMed

    Lalonde, R; Joyal, C C; Cote, C

    1993-07-01

    Dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar fibers, were evaluated in a visible platform swim test. It was found that dt mutants were slower to reach the platform than normal mice. However, the number of quadrants traversed was not higher in dt mutants. It is concluded that spinocerebellar fibers to the vermis are important in limb control during swimming but not in visuo-motor guidance (navigational skills) of the animal towards a visible goal, at least in regard to the quadrant measure. It is not excluded that a measure tracing their path may find a mild deviation from the goal. PMID:8327590

  12. Novel Mutants Define Genes Required for the Expression of Human Histocompatibility Leukocyte Antigen DM: Evidence for Loci on Human Chromosome 6p

    PubMed Central

    Fling, Steven P.; Rak, Jennifer; Muczynski, Kimberly A.; Arp, Benjamin; Pious, Donald

    1997-01-01

    We and others have shown that the products of the HLA-DM locus are required for the intracellular assembly of major histocompatibility complex class II molecules with cognate peptides for antigen presentation. HLA-DM heterodimers mediate the dissociation of invariant chain (Ii)-derived class II–associated Ii peptides (CLIP) from class II molecules and facilitate the loading of class II molecules with antigenic peptides. Here we describe novel APC mutants with defects in the formation of class II–peptide complexes. These mutants express class II molecules which are conformationally altered, and an aberrantly high percentage of these class II molecules are associated with Ii-derived CLIP. This phenotype resembles that of DM null mutants. However, we show that the defects in two of these new mutants do not map to the DM locus. Nevertheless, our evidence suggests that the antigen processing defective phenotype in these mutants results from deficient DM expression. These mutants thus appear to define genes in which mutations have differential effects on the expression of conventional class II molecules and DM molecules. Our data are most consistent with these factors mapping to human chromosome 6p. Previous data have suggested that the expression of DM and class II genes are coordinately regulated. The results reported here suggest that DM and class II can also be differentially regulated, and that this differential regulation has significant effects on class II–restricted antigen processing. PMID:9348304

  13. Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

    PubMed

    Lauer, Peter; Metzner, Hubert J; Zettlmeissl, Gerd; Li, Meng; Smith, Austin G; Lathe, Richard; Dickneite, Gerhard

    2002-12-01

    Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies. PMID:12529747

  14. A Novel DNA-Binding Protein Bound to the Mitochondrial Inner Membrane Restores the Null Mutation of Mitochondrial Histone Abf2p in Saccharomyces cerevisiae

    PubMed Central

    Cho, Jae Hyoung; Ha, Sang Jin; Kao, Ling Rong; Megraw, Timothy L.; Chae, Chi-Bom

    1998-01-01

    The yeast mitochondrial HMG-box protein, Abf2p, is essential for maintenance of the mitochondrial genome. To better understand the role of Abf2p in the maintenance of the mitochondrial chromosome, we have isolated a multicopy suppressor (YHM2) of the temperature-sensitive defect associated with an abf2 null mutation. The function of Yhm2p was characterized at the molecular level. Yhm2p has 314 amino acid residues, and the deduced amino acid sequence is similar to that of a family of mitochondrial carrier proteins. Yhm2p is localized in the mitochondrial inner membrane and is also associated with mitochondrial DNA in vivo. Yhm2p exhibits general DNA-binding activity in vitro. Thus, Yhm2p appears to be novel in that it is a membrane-bound DNA-binding protein. A sequence that is similar to the HMG DNA-binding domain is important for the DNA-binding activity of Yhm2p, and a mutation in this region abolishes the ability of YHM2 to suppress the temperature-sensitive defect of respiration of the abf2 null mutant. Disruption of YHM2 causes a significant growth defect in the presence of nonfermentable carbon sources such as glycerol and ethanol, and the cells have defects in respiration as determined by 2,3,5,-triphenyltetrazolium chloride staining. Yhm2p may function as a member of the protein machinery for the mitochondrial inner membrane attachment site of mitochondrial DNA during replication and segregation of mitochondrial genomes. PMID:9742088

  15. An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment.

    PubMed

    Rubio, Silvia; Larson, Tony R; Gonzalez-Guzman, Miguel; Alejandro, Santiago; Graham, Ian A; Serrano, Ramón; Rodriguez, Pedro L

    2006-03-01

    Once the plant coenzyme A (CoA) biosynthetic pathway has been elucidated by comparative genomics, it is feasible to analyze the physiological relevance of CoA biosynthesis in plant life. To this end, we have identified and characterized Arabidopsis (Arabidopsis thaliana) T-DNA knockout mutants of two CoA biosynthetic genes, HAL3A and HAL3B. The HAL3A gene encodes a 4'-phosphopantothenoyl-cysteine decarboxilase that generates 4'-phosphopantetheine. A second gene, HAL3B, whose gene product is 86% identical to that of HAL3A, is present in the Arabidopsis genome. HAL3A appears to have a predominant role over HAL3B according to their respective mRNA expression levels. The hal3a-1, hal3a-2, and hal3b mutants were viable and showed a similar growth rate as that in wild-type plants; in contrast, a hal3a-1 hal3b double mutant was embryo lethal. Unexpectedly, seedlings that were null for HAL3A and heterozygous for HAL3B (aaBb genotype) displayed a sucrose (Suc)-dependent phenotype for seedling establishment, which is in common with mutants defective in beta-oxidation. This phenotype was genetically complemented in aaBB siblings of the progeny and chemically complemented by pantethine. In contrast, seedling establishment of Aabb plants was not Suc dependent, proving a predominant role of HAL3A over HAL3B at this stage. Total fatty acid and acyl-CoA measurements of 5-d-old aaBb seedlings in medium lacking Suc revealed stalled storage lipid catabolism and impaired CoA biosynthesis; in particular, acetyl-CoA levels were reduced by approximately 80%. Taken together, these results provide in vivo evidence for the function of HAL3A and HAL3B, and they point out the critical role of CoA biosynthesis during early postgerminative growth. PMID:16415216

  16. SCS1, a multicopy suppressor of hsp60-ts mutant alleles, does not encode a mitochondrially targeted protein.

    PubMed Central

    Shu, Y; Hallberg, R L

    1995-01-01

    We identified and isolated a Saccharomyces cerevisiae gene which, when overexpressed, suppressed the temperature-sensitive phenotype of cells expressing a mutant allele of the gene encoding the mitochondrial chaperonin, Hsp60. This gene, SCS1 (suppressor of chaperonin sixty-1), encodes a 757-amino-acid protein of as yet unknown function which, nonetheless, has human, rice, and Caenorhabditis elegans homologs with high degrees (ca. 60%) of amino acid sequence identity. SCS1 is not an essential gene, but SCS1-null strains do not grow above 37 degrees C and show some growth-related defects at 30 degrees C as well. This gene is expressed at both 30 and 38 degrees C, producing little or no differences in mRNA levels at these two temperatures. Overexpression of SCS1 could not complement an HSP60-null allele, indicating that suppression was not due to the bypassing of Hsp60 activity. Of 10 other hsp60-ts alleles tested, five could also be suppressed by SCS1 overexpression. There were no common mutant phenotypes of the strains expressing these alleles that give any clue as to why they were suppressible while others were not. An epitope (influenza virus hemagglutinin)-tagged form of SCS1 in single copy complemented an SCS1-null allele. The Scs1-hemagglutinin protein was found to be at comparable levels and in similar multiply modified forms in cells growing at both 30 and 38 degrees C. Surprisingly, when localized either by cell fractionation procedures or by immunocytochemistry, these proteins were found not in mitochondria but in the cytosol. The overexpression of SCS1 had significant effects on the cellular levels of mRNAs encoding the proteins Cpn10 and Mgel, two other mitochondrial protein cochaperones, but not on mRNAs encoding a number of other mitochondrial or cytosolic proteins analyzed. The implications of these findings are discussed. PMID:7565713

  17. Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson's Disease Patients

    PubMed Central

    Swart, Chrisna; van der Westhuizen, Francois; van Dyk, Hayley; van der Merwe, Lize; van der Merwe, Celia; Loos, Ben; Carr, Jonathan; Kinnear, Craig; Bardien, Soraya

    2016-01-01

    Mutations in the parkin gene are the most common cause of early-onset Parkinson's disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models with parkin null mutations are particularly valuable for investigating the mitochondrial functions of parkin. However, published results reporting on patient-derived parkin-mutant fibroblasts have been inconsistent. This study aimed to functionally compare parkin-mutant fibroblasts from PD patients with wild-type control fibroblasts using a variety of assays to gain a better understanding of the role of mitochondrial dysfunction in PD. To this end, dermal fibroblasts were obtained from three PD patients with homozygous whole exon deletions in parkin and three unaffected controls. Assays of mitochondrial respiration, mitochondrial network integrity, mitochondrial membrane potential, and cell growth were performed as informative markers of mitochondrial function. Surprisingly, it was found that mitochondrial respiratory rates were markedly higher in the parkin-mutant fibroblasts compared to control fibroblasts (p = 0.0093), while exhibiting more fragmented mitochondrial networks (p = 0.0304). Moreover, cell growth of the parkin-mutant fibroblasts was significantly higher than that of controls (p = 0.0001). These unanticipated findings are suggestive of a compensatory mechanism to preserve mitochondrial function and quality control in the absence of parkin in fibroblasts, which warrants further investigation. PMID:27034887

  18. Cytochrome d but not cytochrome o rescues the toluidine blue growth sensitivity of arc mutants of Escherichia coli.

    PubMed

    Alvarez, Adrian F; Malpica, Roxana; Contreras, Martha; Escamilla, Edgardo; Georgellis, Dimitris

    2010-01-01

    The Arc (anoxic redox control) two-component signal transduction system, consisting of the ArcB sensor kinase and the ArcA response regulator, allows adaptive responses of Escherichia coli to changes of O(2) availability. The arcA gene was previously known as the dye gene because null mutants were growth sensitive to the photosensitizer redox dyes toluidine blue and methylene blue, a phenotype whose molecular basis still remains elusive. In this study we report that the toluidine blue O (TBO) effect on the arc mutants is light independent and observed only during aerobic growth conditions. Moreover, 16 suppressor mutants with restored growth were generated and analyzed. Thirteen of those possessed insertion elements upstream of the cydAB operon, rendering its expression ArcA independent. Also, it was found that, in contrast to cythocrome d, cythocrome o was not able to confer toluidine blue resistance to arc mutants, thereby representing an intriguing difference between the two terminal oxidases. Finally, a mechanism for TBO sensitivity and resistance is discussed. PMID:19897650

  19. Post-translational regulation and nuclear entry of TIMELESS and PERIOD are affected in new timeless mutant

    PubMed Central

    Hara, Taichi; Koh, Kyunghee; Combs, David J.; Sehgal, Amita

    2011-01-01

    The molecular circadian clock consists of a feedback loop in which canonical clock proteins negatively regulate transcription of their own genes. Timed nuclear entry of these proteins is critical, but regulation of this event is poorly understood. In Drosophila melanogaster, the idea that nuclear entry of PERIOD (PER) is controlled by its partner protein, TIMELESS (TIM), has been challenged by several studies. We identify here a novel mutation in the tim gene that eliminates behavioral rhythms while allowing robust expression of TIM and PER. Mutant TIM can bind to and stabilize PER. However, neither protein is expressed cyclically, and phosphorylation of both is reduced. In addition, TIM and PER are localized in the cytoplasm at all times of day and mutant TIM attenuates transcriptional feedback by PER in cultured cells, suggesting that it holds PER in the cytoplasm. In fact, much of the reduced phosphorylation of PER in the new tim mutant appears to result from the cytoplasmic localization of PER. Interestingly, mutating a threonine near the original mutation produces similar phenotypes, raising the possibility that defective phosphorylation is the basis of TIM dysfunction in the novel tim mutant. We also show that a stable form of PER is cytoplasmic in tim-null flies. These studies establish an essential role of TIM in the timed nuclear entry of PER. PMID:21734289

  20. Characterization of pullulanase (PUL)-deficient mutants of rice (Oryza sativa L.) and the function of PUL on starch biosynthesis in the developing rice endosperm.

    PubMed

    Fujita, Naoko; Toyosawa, Yoshiko; Utsumi, Yoshinori; Higuchi, Toshiyuki; Hanashiro, Isao; Ikegami, Akira; Akuzawa, Sayuri; Yoshida, Mayumi; Mori, Akiko; Inomata, Kotaro; Itoh, Rumiko; Miyao, Akio; Hirochika, Hirohiko; Satoh, Hikaru; Nakamura, Yasunori

    2009-01-01

    Rice (Oryza sativa) allelic sugary1 (sug1) mutants defective in isoamylase 1 (ISA1) accumulate varying levels of starch and phytoglycogen in their endosperm, and the activity of a pullulanase-type of a debranching enzyme (PUL) was found to correlate closely with the severity of the sug1 phenotype. Thus, three PUL-deficient mutants were generated to investigate the function of PUL in starch biosynthesis. The reduction of PUL activity had no pleiotropic effects on the other enzymes involved in starch biosynthesis. The short chains (DP < or = 13) of amylopectin in PUL mutants were increased compared with that of the wild type, but the extent of the changes was much smaller than that of sug1 mutants. The alpha-glucan composition [amylose, amylopectin, water-soluble polysaccharide (WSP)] and the structure of the starch components (amylose and amylopectin) of the PUL mutants were essentially the same, although the average chain length of the B(2-3) chains of amylopectin in the PUL mutant was approximately 3 residues longer than that of the wild type. The double mutants between the PUL-null and mild sug1 mutants still retained starch in the outer layer of endosperm tissue, while the amounts of WSP and short chains (DP < or = 7) of amylopectin were higher than those of the sug1 mutant; this indicates that the PUL function partially overlaps with that of ISA1 and its deficiency has a much smaller effect on the synthesis of amylopectin than ISA1 deficiency and the variation of the sug1 phenotype is not significantly dependent on the PUL activities. PMID:19190097

  1. Phosphoglucomutase Mutants of Escherichia coli K-12

    PubMed Central

    Adhya, Sankar; Schwartz, Maxime

    1971-01-01

    Bacteria with strongly depressed phosphoglucomutase (EC 2.7.5.1) activity are found among the mutants of Escherichia coli which, when grown on maltose, accumulate sufficient amylose to be detectable by iodine staining. These pgm mutants grow poorly on galactose but also accumulate amylose on this carbon source. Growth on lactose does not produce high amylose but, instead, results in the induction of the enzymes of maltose metabolism, presumably by accumulation of maltose. These facts suggest that the catabolism of glucose-1-phosphate is strongly depressed in pgm mutants, although not completely abolished. Anabolism of glucose-1-phosphate is also strongly depressed, since amino acid- or glucose-grown pgm mutants are sensitive to phage C21, indicating a deficiency in the biosynthesis of uridine diphosphoglucose or uridine diphosphogalactose, or both. All pgm mutations isolated map at about 16 min on the genetic map, between purE and the gal operon. PMID:4942754

  2. Cooperative Interaction Within RNA Virus Mutant Spectra.

    PubMed

    Shirogane, Yuta; Watanabe, Shumpei; Yanagi, Yusuke

    2016-01-01

    RNA viruses usually consist of mutant spectra because of high error rates of viral RNA polymerases. Growth competition occurs among different viral variants, and the fittest clones predominate under given conditions. Individual variants, however, may not be entirely independent of each other, and internal interactions within mutant spectra can occur. Examples of cooperative and interfering interactions that exert enhancing and suppressing effects on replication of the wild-type virus, respectively, have been described, but their underlying mechanisms have not been well defined. It was recently found that the cooperation between wild-type and variant measles virus genomes produces a new phenotype through the heterooligomer formation of a viral protein. This observation provides a molecular mechanism underlying cooperative interactions within mutant spectra. Careful attention to individual sequences, in addition to consensus sequences, may disclose further examples of internal interactions within mutant spectra. PMID:26162566

  3. Mutant p53: one name, many proteins

    PubMed Central

    Freed-Pastor, William A.; Prives, Carol

    2012-01-01

    There is now strong evidence that mutation not only abrogates p53 tumor-suppressive functions, but in some instances can also endow mutant proteins with novel activities. Such neomorphic p53 proteins are capable of dramatically altering tumor cell behavior, primarily through their interactions with other cellular proteins and regulation of cancer cell transcriptional programs. Different missense mutations in p53 may confer unique activities and thereby offer insight into the mutagenic events that drive tumor progression. Here we review mechanisms by which mutant p53 exerts its cellular effects, with a particular focus on the burgeoning mutant p53 transcriptome, and discuss the biological and clinical consequences of mutant p53 gain of function. PMID:22713868

  4. A mutant allele of BARA/LIN-9 rescues the cdk4 {sup -/-} phenotype by releasing the repression on E2F-regulated genes

    SciTech Connect

    Sandoval, Raudel; Xue Jiaping; Tian Xinyong; Barrett, Kelly; Pilkinton, Mark; Ucker, David S.; Raychaudhuri, Pradip; Kineman, Rhonda D.; Luque, Raul M.; Baida, Gleb; Zou, Xianghong; Kiyokawa, Hiroaki; Valli, V.E.; Cook, James L.; Colamonici, Oscar R. . E-mail: ocolamon@uic.edu

    2006-08-01

    It has been proposed that C. elegans LIN-9 functions downstream of CDK4 in a pathway that regulates cell proliferation. Here, we report that mammalian BARA/LIN-9 is a predominantly nuclear protein that inhibits cell proliferation. More importantly, we demonstrate that BARA/LIN-9 also acts downstream of cyclin D/CDK4 in mammalian cells since (i) its antiproliferative effect is partially blocked by coexpression of cyclin D1, and (ii) a mutant form that lacks the first 84 amino acids rescues several phenotypic alterations observed in mice null for cdk4. Interestingly, mutation of BARA/LIN-9 restores the expression of E2F target genes in CDK4 null MEFs, indicating that the wild-type protein plays a role in the expression of genes required for the G1/S transition.

  5. Study of Cyclin Proteolysis in Anaphase-Promoting Complex (APC) Mutant Cells Reveals the Requirement for APC Function in the Final Steps of the Fission Yeast Septation Initiation Network

    PubMed Central

    Chang, Louise; Morrell, Jennifer L.; Feoktistova, Anna; Gould, Kathleen L.

    2001-01-01

    Cytokinesis in eukaryotic cells requires the inactivation of mitotic cyclin-dependent kinase complexes. An apparent exception to this relationship is found in Schizosaccharomyces pombe mutants with mutations of the anaphase-promoting complex (APC). These conditional lethal mutants arrest with unsegregated chromosomes because they cannot degrade the securin, Cut2p. Although failing at nuclear division, these mutants septate and divide. Since septation requires Cdc2p inactivation in wild-type S. pombe, it has been suggested that Cdc2p inactivation occurs in these mutants by a mechanism independent of cyclin degradation. In contrast to this prediction, we show that Cdc2p kinase activity fluctuates in APC cut mutants due to Cdc13/cyclin B destruction. In APC-null mutants, however, septation and cutting do not occur and Cdc13p is stable. We conclude that APC cut mutants are hypomorphic with respect to Cdc13p degradation. Indeed, overproduction of nondestructible Cdc13p prevents septation in APC cut mutants and the normal reorganization of septation initiation network components during anaphase. PMID:11533255

  6. Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice

    PubMed Central

    Roundtree, Harrison M.; Simeone, Timothy A.; Johnson, Chaz; Matthews, Stephanie A.; Samson, Kaeli K.; Simeone, Kristina A.

    2016-01-01

    Study Objective: Comorbid sleep disorders occur in approximately one-third of people with epilepsy. Seizures and sleep disorders have an interdependent relationship where the occurrence of one can exacerbate the other. Orexin, a wake-promoting neuropeptide, is associated with sleep disorder symptoms. Here, we tested the hypothesis that orexin dysregulation plays a role in the comorbid sleep disorder symptoms in the Kcna1-null mouse model of temporal lobe epilepsy. Methods: Rest-activity was assessed using infrared beam actigraphy. Sleep architecture and seizures were assessed using continuous video-electroencephalography-electromyography recordings in Kcna1-null mice treated with vehicle or the dual orexin receptor antagonist, almorexant (100 mg/kg, intraperitoneally). Orexin levels in the lateral hypothalamus/perifornical region (LH/P) and hypothalamic pathology were assessed with immunohistochemistry and oxygen polarography. Results: Kcna1-null mice have increased latency to rapid eye movement (REM) sleep onset, sleep fragmentation, and number of wake epochs. The numbers of REM and non-REM (NREM) sleep epochs are significantly reduced in Kcna1-null mice. Severe seizures propagate to the wake-promoting LH/P where injury is apparent (indicated by astrogliosis, blood-brain barrier permeability, and impaired mitochondrial function). The number of orexin-positive neurons is increased in the LH/P compared to wild-type LH/P. Treatment with a dual orexin receptor antagonist significantly increases the number and duration of NREM sleep epochs and reduces the latency to REM sleep onset. Further, almorexant treatment reduces the incidence of severe seizures and overall seizure burden. Interestingly, we report a significant positive correlation between latency to REM onset and seizure burden in Kcna1-null mice. Conclusion: Dual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in

  7. Arabidopsis mutants with a reduced seed dormancy.

    PubMed Central

    Léon-Kloosterziel, K M; van de Bunt, G A; Zeevaart, J A; Koornneef, M

    1996-01-01

    The development of seed dormancy is an aspect of seed maturation, the last stage of seed development. To isolate mutants of Arabidopsis thaliana that are affected in this process, we selected directly for the absence of dormancy among freshly harvested M2 seeds. The screen yielded two mutants exhibiting a reduced dormancy, rdo1 and rdo2, that are specifically affected in dormancy determined by the embryo. The rdo1 and rdo2 mutants show normal levels of abscisic acid and the same sensitivity to abscisic acid, ethylene, auxin, and cytokinin as the wild type. The rdo2 mutant but not the rdo1 mutant has a reduced sensitivity to the gibberellin biosynthesis inhibitor tetcyclacis. Double-mutant analysis suggested that the RDO1 and RDO2 genes are involved in separate pathways leading to the development of dormancy. We assume that the RDO2 gene controls a step in the induction of dormancy that is most likely induced by abscisic acid and is expressed as an increase of the gibberellin requirement for germination. PMID:8587986

  8. Caloric restriction restores the chronological life span of the Goa1 null mutant of Candida albicans in spite of high cell levels of ROS.

    PubMed

    Chen, Hui; Calderone, Richard; Sun, Nuo; Wang, Yun; Li, Dongmei

    2012-12-01

    The Candida albicans Goa1p is required for mitochondrial functions. In a strain lacking GOA1 (GOA31), respiration, mitochondrial membrane potential, complex I (CI) activity of the electron transport chain, and ATP synthesis are significantly decreased. A shortened chronological life span (CLS) of GOA31 occurs in 2% glucose that is associated with an increase in cell reactive oxidant species (ROS) and apoptosis. We now show that caloric restriction (CR) in media containing 0.5% glucose instead of 2% glucose-SC extends the CLS to the level of parental and gene-reconstituted strains. Paradoxically, ROS levels in GOA31 far exceed those of control strains in 0.5% glucose and, as a consequence, increased lipid peroxidation occurs even though CLS is restored. Microarray analysis was used to characterize transcriptional changes during CR in GOA31. We found that CR shifts cells of all strains to a non-glucose carbon metabolism (β-oxidation). Our model of ROS formation in GOA31 follows the paradigm that the generation of oxygen radicals from β-oxidation of cell lipids via FADH(2) (CII) and NADH (CI) creates an unfavorable cellular FADH(2)/NADH ratio that causes a transient overload in CII activity resulting in excess free cell radicals. In GOA31 the CI and peroxisomal dysfunctions increase the levels of ROS compared to control strains. Recovery from high levels of ROS may be associated with an increase in iron and sugar transporters, as well as an anti-stress response that includes the SOD1 and GPX1. Thus, CR creates a favorable growth environment, but cells of GOA31 must overcome a high but transient ROS production. PMID:23063955

  9. Overexpression of the Coq8 Kinase in Saccharomyces cerevisiae coq Null Mutants Allows for Accumulation of Diagnostic Intermediates of the Coenzyme Q6 Biosynthetic Pathway*

    PubMed Central

    Xie, Letian X.; Ozeir, Mohammad; Tang, Jeniffer Y.; Chen, Jia Y.; Jaquinod, Sylvie-Kieffer; Fontecave, Marc; Clarke, Catherine F.; Pierrel, Fabien

    2012-01-01

    Most of the Coq proteins involved in coenzyme Q (ubiquinone or Q) biosynthesis are interdependent within a multiprotein complex in the yeast Saccharomyces cerevisiae. Lack of only one Coq polypeptide, as in Δcoq strains, results in the degradation of several Coq proteins. Consequently, Δcoq strains accumulate the same early intermediate of the Q6 biosynthetic pathway; this intermediate is therefore not informative about the deficient biosynthetic step in a particular Δcoq strain. In this work, we report that the overexpression of the protein Coq8 in Δcoq strains restores steady state levels of the unstable Coq proteins. Coq8 has been proposed to be a kinase, and we provide evidence that the kinase activity is essential for the stabilizing effect of Coq8 in the Δcoq strains. This stabilization results in the accumulation of several novel Q6 biosynthetic intermediates. These Q intermediates identify chemical steps impaired in cells lacking Coq4 and Coq9 polypeptides, for which no function has been established to date. Several of the new intermediates contain a C4-amine and provide information on the deamination reaction that takes place when para-aminobenzoic acid is used as a ring precursor of Q6. Finally, we used synthetic analogues of 4-hydroxybenzoic acid to bypass deficient biosynthetic steps, and we show here that 2,4-dihydroxybenzoic acid is able to restore Q6 biosynthesis and respiratory growth in a Δcoq7 strain overexpressing Coq8. The overexpression of Coq8 and the use of 4-hydroxybenzoic acid analogues represent innovative tools to elucidate the Q biosynthetic pathway. PMID:22593570

  10. Partial suppression of the respiratory defect of qrs1/her2 glutamyl-tRNA amidotransferase mutants by overexpression of the mitochondrial pentatricopeptide Msc6p.

    PubMed

    Moda, Bruno S; Ferreira-Júnior, José Ribamar; Barros, Mario H

    2016-08-01

    Recently, a large body of evidences indicates the existence in the mitochondrial matrix of foci that contain different proteins involved in mitochondrial RNA metabolism. Some of these proteins have a pentatricopeptide repeat motif that constitutes their RNA-binding structures. Here we report that MSC6, a mitochondrial pentatricopeptide protein of unknown function, is a multi copy suppressor of mutations in QRS1/HER2 a component of the trimeric complex that catalyzes the transamidation of glutamyl-tRNAQ to glutaminyl-tRNAQ. This is an essential step in mitochondrial translation because of the lack of a specific mitochondrial aminoacyl glutaminyl-tRNA synthetase. MSC6 over-expression did not abolish translation of an aberrant variant form of Cox2p detected in QRS1/HER2 mutants, arguing against a suppression mechanism that bypasses Qrs1p function. A slight decrement of the mitochondrial translation capacity as well as diminished growth on respiratory carbon sources media for respiratory activity was observed in the msc6 null mutant. Additionally, the msc6 null mutant did not display any impairment in RNA transcription, processing or turnover. We concluded that Msc6p is a mitochondrial matrix protein and further studies are required to indicate the specific function of Msc6p in mitochondrial translation. PMID:26780366

  11. Pseudo-constitutivity of nitrate-responsive genes in nitrate reductase mutants

    PubMed Central

    Schinko, Thorsten; Gallmetzer, Andreas; Amillis, Sotiris; Strauss, Joseph

    2013-01-01

    In fungi, transcriptional activation of genes involved in NO3- assimilation requires the presence of an inducer (nitrate or nitrite) and low intracellular concentrations of the pathway products ammonium or glutamine. In Aspergillus nidulans, the two transcription factors NirA and AreA act synergistically to mediate nitrate/nitrite induction and nitrogen metabolite derepression, respectively. In all studied fungi and in plants, mutants lacking nitrate reductase (NR) activity express nitrate-metabolizing enzymes constitutively without the addition of inducer molecules. Based on their work in A. nidulans, Cove and Pateman proposed an “autoregulation control” model for the synthesis of nitrate metabolizing enzymes in which the functional nitrate reductase molecule would act as co-repressor in the absence and as co-inducer in the presence of nitrate. However, NR mutants could simply show “pseudo-constitutivity” due to induction by nitrate which accumulates over time in NR-deficient strains. Here we examined this possibility using strains which lack flavohemoglobins (fhbs), and are thus unable to generate nitrate internally, in combination with nitrate transporter mutations (nrtA, nrtB) and a GFP-labeled NirA protein. Using different combinations of genotypes we demonstrate that nitrate transporters are functional also in NR null mutants and show that the constitutive phenotype of NR mutants is not due to nitrate accumulation from intracellular sources but depends on the activity of nitrate transporters. However, these transporters are not required for nitrate signaling because addition of external nitrate (10 mM) leads to standard induction of nitrate assimilatory genes in the nitrate transporter double mutants. We finally show that NR does not regulate NirA localization and activity, and thus the autoregulation model, in which NR would act as a co-repressor of NirA in the absence of nitrate, is unlikely to be correct. Results from this study instead suggest

  12. Cystatin A, a Potential Common Link for Mutant Myocilin Causative Glaucoma

    PubMed Central

    Kennedy, K. David; AnithaChristy, S. A.; Buie, LaKisha K.; Borrás, Teresa

    2012-01-01

    Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in the trabecular meshwork tissue of the eye, where it was discovered. Mutations in MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC mutation varies, but all of them cause elevated intraocular pressure (IOP). In cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine protease. This proteolytic process is inhibited by MYOC mutants. In this study, we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and overexpressed them in human trabecular meshwork cells. We analyzed expression profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as controls. Analysis of trabecular meshwork relevant mechanisms showed that the unfolded protein response (UPR) was the most affected. Search for individual candidate genes revealed that genes that have been historically connected to trabecular meshwork physiology and pathology were altered by the MYOC mutants. Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all mutants and not by the wild-type. Subsequent functional analysis of the selected gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary trabecular meshwork cells while an inactive mutated CSTA was not. These findings provide a new molecular understanding of the mechanisms of MYOC-causative glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker and drug for the treatment of MYOC-induced glaucoma. PMID:22615763

  13. Incidence and origin of [open quotes]Null[close quotes] alleles in the (AC)n microsatellite markers

    SciTech Connect

    Callen, D.F.,; Thompson, A.D.; Shen, Y.; Phillips, H.A.; Richards, R.I.; Mulley, J.C.; Sutherland, G.R. )

    1993-05-01

    Twenty-three (AC)n repeat markers from chromosome 16 were typed in the parents of the 40 CEPH (Centre d'Etude du Polymorphisme Humain) families. Where parents were informative, the entire families were then typed. There were seven markers in which null alleles were demonstrated, as recognized by the apparent noninheritance, by a sib, of a parental allele. Four of these markers showed a null allele in a single sibship, while in the other three at least 30% of the CEPH sibships were shown to have a null allele segregating. One null allele was sequenced and shown to be the result of an 8-bp deletion occurring within the priming sequence for PCR amplification of the (AC)n repeats. In gene mapping or in application to diagnosis, the presence of a segregating null allele will not corrupt the linkage data but could result in loss of information. In isolated instances a segregating null allele may be interpreted as nonpaternity. The presence of a null allele may generate misleading data when individuals are haplotyped to determine the presence of linkage disequilibrium with a disease gene. 10 refs., 2 figs., 1 tab.

  14. Bursty, Broadband Electromagnetic Waves Associated with Three-Dimensional Nulls Observed in Turbulent Magnetosheath Reconnection

    NASA Technical Reports Server (NTRS)

    Adrian, Mark L.; Wendel, D. E.

    2012-01-01

    We investigate observations of intense bursts of electromagnetic wave energy in association with the thin current layers of turbulent magnetosheath reconnection. These observed emissions - typically detected in the layers immediately outside of the current layer proper - form two distinct types: (i) broadband emissions that extend continuously to lOs of Hertz; and (ii) structured bursts of emitted energy that occur above 80-Hz, often displaying features reminiscent of absorption bands and are observed near the local minima in the magnetic field. We present detailed analyses of these intense bursts of electromagnetic energy and quantify their proximity to X-IO-nulls and magnetic spine connected null pairs, as well as their correlation - if any - to the amount of magnetic energy converted by the process of magnetic reconnection.

  15. Hidden symmetries, null geodesics, and photon capture in the Sen black hole

    SciTech Connect

    Hioki, Kenta; Miyamoto, Umpei

    2008-08-15

    Important classes of null geodesics and hidden symmetries in the Sen black hole are investigated. First, we obtain the principal null geodesics and circular photon orbits. Then, an irreducible rank-two Killing tensor and a conformal Killing tensor are derived, which represent the hidden symmetries. Analyzing the properties of Killing tensors, we clarify why the Hamilton-Jacobi and wave equations are separable in this spacetime. We also investigate the gravitational capture of photons by the Sen black hole and compare the result with those by the various charged/rotating black holes and naked singularities in the Kerr-Newman family. For these black holes and naked singularities, we show the capture regions in a two dimensional impact parameter space (or equivalently the 'shadows' observed at infinity) to form a variety of shapes such as the disk, circle, dot, arc, and their combinations.

  16. DAMA confronts null searches in the effective theory of dark matter-nucleon interactions

    NASA Astrophysics Data System (ADS)

    Catena, Riccardo; Ibarra, Alejandro; Wild, Sebastian

    2016-05-01

    We examine the dark matter interpretation of the modulation signal reported by the DAMA experiment from the perspective of effective field theories displaying Galilean invariance. We consider the most general effective coupling leading to the elastic scattering of a dark matter particle with spin 0 or 1/2 off a nucleon, and we analyze the compatibility of the DAMA signal with the null results from other direct detection experiments, as well as with the non-observation of a high energy neutrino flux in the direction of the Sun from dark matter annihilation. To this end, we develop a novel semi-analytical approach for comparing experimental results in the high-dimensional parameter space of the non-relativistic effective theory. Assuming the standard halo model, we find a strong tension between the dark matter interpretation of the DAMA modulation signal and the null result experiments. We also list possible ways-out of this conclusion.

  17. Measurement of the refractive index of transparent materials using null polarimetry near Brewster's angle

    NASA Astrophysics Data System (ADS)

    Nee, Soe-Mie F.

    1998-10-01

    The nondestructive measurement of refractive index of transmissive materials using null polarimetry is simple, accurate and does not require much on sample preparation. In null polarimetry, the ellipsometric parameter (psi) for reflection from a sample is measured. (psi) for transparent material is defined by tan (psi) equals rp/rs where rp and rs are coefficients of reflection for the p- and s-polarization respectively. By choosing the angle of incidence (Theta) near the Brewster angle, refractive index can be computed from (Theta) and (psi) directly. The only requirement on the sample is that no back surface reflection is allowed to mess up the front surface reflection. Precision in the refractive index is about 0.0004. Spectra of refractive index for quartz are measured and compared with the spectra quoted from existing Handbooks.

  18. Boosting the Power of the Sequence Kernel Association Test by Properly Estimating Its Null Distribution.

    PubMed

    Wang, Kai

    2016-07-01

    The sequence kernel association test (SKAT) is probably the most popular statistical test used in rare-variant association studies. Its null distribution involves unknown parameters that need to be estimated. The current estimation method has a valid type I error rate, but the power is compromised given that all subjects are used for estimation. I have developed an estimation method that uses only control subjects. Named SKAT+, this method uses the same test statistic as SKAT but differs in the way the null distribution is estimated. Extensive simulation studies and applications to data from the Genetic Analysis Workshop 17 and the Ocular Hypertension Treatment Study demonstrated that SKAT+ has superior power over SKAT while maintaining control over the type I error rate. This method is applicable to extensions of SKAT in the literature. PMID:27292111

  19. Double Force Compensation Method to Enhance the Performance of a Null Balance Force Sensor

    NASA Astrophysics Data System (ADS)

    Choi, In-Mook; Choi, Dong-June; Kim, Soo Hyun

    2002-06-01

    Microforce measurement is becoming more essential as precision industries such as biomedicine, precision chemistry, semiconductor manufacturing, and so forth develop. A null balance method has been introduced in order to improve on force measurement performances involving a loadcell. The null-balance type force sensor is analyzed and designed for the improvement of measurement performances. The measurement range and the resolution are dependent on the force generation capacity and the various error sources. These characteristics are estimated and verified according to the mechanical sensitivity and the force compensation sensitivity. Two different coil systems are designed and tested experimentally. Double force compensation is proposed in order to obtain a large range and high resolution. The measurement range of the large coil system and the resolution of the small one are fully realized by the double compensation method. After manufacturing, a range over 300 gf and resolution under ± 0.1 mgf were obtained by the double compensation method.

  20. Towards a stable and absolute atmospheric carbon dioxide instrument using spectroscopic null method

    NASA Astrophysics Data System (ADS)

    Xiang, B.; Nelson, D. D.; McManus, J. B.; Zahniser, M. S.; Wofsy, S. C.

    2013-07-01

    We present a novel spectral method to measure atmospheric carbon dioxide (CO2) with high precision and stability without resorting to calibration tanks during long-term operation. This spectral null method improves precision by reducing spectral proportional noise associated with laser emission instabilities. We employ sealed quartz cells with known CO2 column densities to serve as the permanent internal references in the null method, which improve the instrument's stability and accuracy. A prototype instrument - ABsolute Carbon dioxide (ABC) is developed using this new approach. The instrument has a one-second precision of 0.02 ppm, which averages down to 0.007 ppm within one minute. Long-term stability of within 0.1 ppm is achieved without any calibrations for over a one-month period. These results have the potential for eliminating the need for calibration cylinders for high accuracy field measurements of carbon dioxide.

  1. Towards a stable and absolute atmospheric carbon dioxide instrument using spectroscopic null method

    NASA Astrophysics Data System (ADS)

    Xiang, B.; Nelson, D. D.; McManus, J. B.; Zahniser, M. S.; Wofsy, S. C.

    2013-02-01

    We present a novel spectral method to measure atmospheric carbon dioxide (CO2) with high precision and stability without resorting to calibration tanks during long-term operation. This spectral null method improves precision by reducing spectral proportional noise associated with laser emission instabilities. We employ sealed quartz cells with known CO2 column densities to serve as the permanent internal references in the null method, which improve the instrument's stability and accuracy. A prototype instrument - ABsolute Carbon dioxide (ABC) is developed using this new approach. The instrument has one-second precision of 0.02 ppm, which averages down to 0.007 ppm within one minute. Long-term stability of within 0.1 ppm is achieved without any calibrations for over a one-month period. These results have the potential for eliminating the need for calibration cylinders for high accuracy field measurements of carbon dioxide.

  2. Commissioning the LBTI for use as a nulling interferometer and coherent imager

    NASA Astrophysics Data System (ADS)

    Hinz, Phil; Bailey, Vanessa P.; Defrère, D.; Downey, E.; Esposito, Simone; Hill, J.; Hoffmann, William F.; Leisenring, J.; Montoya, Manny; McMahon, T.; Puglisi, A.; Skemer, A.; Skrutskie, M.; Vaitheeswaran, Vidhya; Vaz, Amali

    2014-07-01

    The Large Binocular Telescope Interferometer (LBTI) is a strategically important instrument for exploiting the use of the LBT as a 22.7 m telescope. The LBTI has two science cameras (covering the 1.5-5 μm and 8-13 μm atmospheric windows), and a number of observing modes that allow it to carry out a wide range of high-spatial resolution observations. Some simple modes, such as AO imaging, are in routine use. We report here on testing and commissioning of the system for its more ambitious goals as a nulling interferometer and coherent imager. The LBTI will carry out key surveys to Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) and an LBTI Exozodi-Exoplanet Common Hunt (LEECH). The current nulling and coherent imaging performance is described.

  3. Common-path lateral-shearing nulling interferometry with a Savart plate for exoplanet detection.

    PubMed

    Murakami, Naoshi; Baba, Naoshi

    2010-09-15

    We propose a common-path lateral-shearing nulling interferometer for direct detection of exoplanets. A Savart plate is placed between crossed polarizers to produce a lateral shear and realize fully achromatic and highly stable nulling interference for starlight. We construct a double-shearing interferometer using two Savart plates for implementing orthogonal x and y shears. A laboratory demonstration is carried out using a broadband light source with a bandwidth of Δλ/λ(0)=0.33 (Δλ=0.2 μm and λ(0)=0.6 μm). As a result, achieved extinction levels are 4 × 10(-4) at peak and 4 × 10(-7) at 10λ(0)/D(L) (D(L) is the diameter of a Lyot stop). PMID:20847759

  4. Performance of the Cophasing System of Persee, a Dynamic Nulling Demonstrator

    NASA Astrophysics Data System (ADS)

    Houairi, K.; Cassaing, F.; Duigou, J. M. L.; Amans, J. P.; Barillo, M.; Coudé du Foresto, V.; Hénault, F.; Jacquinod, S.; Lozi, J.; Montri, J.; Ollivier, M.; Reess, J. M.; Sorrente, B.

    2010-10-01

    Spectral characterization of exoplanets can be made by nulling interferometers. In this context, several projects have been proposed such as DARWIN/TPF-I, FKSI, PEGASE, and ALADDIN. To stabilize the beams with the required nanometric accuracy, a cophasing system is required, made of a piston/tip/tilt actuator on each arm and a piston/tip-tilt sensor. The demonstration of the feasibility of such a cophasing system is a central issue. In this goal, a laboratory breadboard named PERSEE is under integration at Observatoire de Paris-Meudon. This paper describes the current status of PERSEE. We show that a cophasing at a subnanometric level has been reached, which allowed us to reach a monochromatic null depth of N=6.2×10-5 ± 6.3×10-6.

  5. Calculation of motion induced eddy current forces in null flux coils

    SciTech Connect

    Davey, K.; Morris, T.; Shaaf, J.; Rote, D.

    1995-11-01

    Time dependent motion induced eddy current forces can be quite difficult to compute. The movement of null flux coils between magnets is approached using a coupled boundary element-circuit approach to compute the forces on the structure. The technique involves treating the magnets as a separate circuit whose current is dictated by the product of the magnet thickness and the working coercivity. The mutual inductance between the windows of the moving null flux coil and the stationary equivalent magnet coil hold the key for predicting lift, guidance, and drag forces on the coil. The rate of change of these inductances with respect to position determines the forces and currents. A steady state approximation to these forces is derived in addition to a numerical simulation when the steady state assumption is invalid. The results compare favorably to laboratory results from a 4 ft. diameter experimental test wheel.

  6. Computer modeling and experimental verification of figure-eight-shaped null-flux coil suspension system

    SciTech Connect

    He, J.L.; Mulcahey, T.M.; Rote, D.M.; Kelly, T.

    1994-12-01

    This report discusses the computer modeling and experimental verification of the magnetic forces associated with a figure-eight-shaped null-flux coil suspension system. A set of computer codes called COILGDWY, were developed on the basis of the dynamic circuit model and verified by means of a laboratory model. The experimental verification was conducted with a rotating PVC drum, the surface of which held various types of figure-eight-shaped null-flux coils that interacted with a stationary permanent magnet. The transient and dynamic magnetic forces between the stationary magnet and the rotating conducting coils were measured and compared with results obtained from the computer model. Good agreement between the experimental results and computer simulations was obtained. The computer model can also be used to calculate magnetic forces in a large-scale magnetic-levitation system.

  7. Magnetic damping forces in figure-eight-shaped null-flux coil suspension systems

    SciTech Connect

    He, Jianliang; Coffey, H.

    1997-08-01

    This paper discusses magnetic damping forces in figure-eight-shaped null-flux coil suspension systems, focusing on the Holloman maglev rocket system. The paper also discusses simulating the damping plate, which is attached to the superconducting magnet by two short-circuited loop coils in the guideway. Closed-form formulas for the magnetic damping coefficient as functions of heave-and-sway displacements are derived by using a dynamic circuit model. These formulas are useful for dynamic stability studies.

  8. Dual null formalism for the collapse of fluids in a cosmological background

    NASA Astrophysics Data System (ADS)

    Maciel, Alan; Le Delliou, Morgan; Mimoso, José P.

    2015-10-01

    In this work we revisit the definition of matter trapping surfaces (MTS) and show how it can be expressed in the so-called dual null formalism developed for trapping horizons (TH). With the aim of unifying both approaches, we construct a 2 +2 threading from the 1 +3 flow in spherical symmetry and thus isolate one preferred spatial direction that allows straightforward translation into a dual null subbasis and deduction of the geometric apparatus that follows. We express the MTS conditions in terms of 2-expansion of the flow, then in purely geometric form of the dual null expansions. The Raychadhuri equations that describe both MTS and TH are written and interpreted using a generalized Tolman-Oppenheimer-Volkov functional. Further using the Misner-Sharp mass and its perfect fluid definition, we relate the spatial 2-expansion to the fluid pressure, density, and acceleration. The Raychaudhuri equations also allow us to define the MTS dynamic condition with first order differentials so the MTS conditions are now shown to be all first order differentials. This unified formalism allows one to realize that the MTS can exist only in normal regions, and so it can exist only between black hole horizons and cosmological horizons. Finally we obtain a relation yielding the sign, on a TH, of the nonvanishing null expansion that determines the nature of the TH from fluid content and flow characteristics. The 2 +2 unified formalism here investigated thus proves a powerful tool to reveal, in the future extensions, more of the very rich and subtle relations between MTS and TH.

  9. Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo

    PubMed Central

    2012-01-01

    Background Neuroglobin is considered to be a novel important pharmacological target in combating stroke and neurodegenerative disorders, although the mechanism by which this protection is accomplished remains an enigma. We hypothesized that if neuroglobin is directly involved in neuroprotection, then permanent cerebral ischemia would lead to larger infarct volumes in neuroglobin-null mice than in wild-type mice. Methods Using neuroglobin-null mice, we estimated the infarct volume 24 hours after permanent middle cerebral artery occlusion using Cavalieri’s Principle, and compared the infarct volume in neuroglobin-null and wild-type mice. Neuroglobin antibody staining was used to examine neuroglobin expression in the infarct area of wild-type mice. Results Infarct volumes 24 hours after permanent middle cerebral artery occlusion were significantly smaller in neuroglobin-null mice than in wild-types (p < 0.01). Neuroglobin immunostaining of the penumbra area revealed no visible up-regulation of neuroglobin protein in ischemic wild-type mice when compared to uninjured wild-type mice. In uninjured wild-type mice, neuroglobin protein was seen throughout cortical layer II and sparsely in layer V. In contrast, no neuroglobin-immunoreactive neurons were observed in the aforementioned layers of the ischemia injured cortical area, or in the surrounding penumbra of ischemic wild-type mice. This suggests no selective sparing of neuroglobin expressing neurons in ischemia. Conclusions Neuroglobin-deficiency resulted in reduced tissue infarction, suggesting that, at least at endogenous expression levels, neuroglobin in itself is non-protective against ischemic injury. PMID:22901501

  10. What is too much variation? The null hypothesis in small-area analysis.

    PubMed Central

    Diehr, P; Cain, K; Connell, F; Volinn, E

    1990-01-01

    A small-area analysis (SAA) in health services research often calculates surgery rates for several small areas, compares the largest rate to the smallest, notes that the difference is large, and attempts to explain this discrepancy as a function of service availability, physician practice styles, or other factors. SAAs are often difficult to interpret because there is little theoretical basis for determining how much variation would be expected under the null hypothesis that all of the small areas have similar underlying surgery rates and that the observed variation is due to chance. We developed a computer program to simulate the distribution of several commonly used descriptive statistics under the null hypothesis, and used it to examine the variability in rates among the counties of the state of Washington. The expected variability when the null hypothesis is true is surprisingly large, and becomes worse for procedures with low incidence, for smaller populations, when there is variability among the populations of the counties, and when readmissions are possible. The characteristics of four descriptive statistics were studied and compared. None was uniformly good, but the chi-square statistic had better performance than the others. When we reanalyzed five journal articles that presented sufficient data, the results were usually statistically significant. Since SAA research today is tending to deal with low-incidence events, smaller populations, and measures where readmissions are possible, more research is needed on the distribution of small-area statistics under the null hypothesis. New standards are proposed for the presentation of SAA results. PMID:2312306

  11. Altered astrocyte morphology and vascular development in dystrophin-Dp71-null mice.

    PubMed

    Giocanti-Auregan, Audrey; Vacca, Ophélie; Bénard, Romain; Cao, Sijia; Siqueiros, Lourdes; Montañez, Cecilia; Paques, Michel; Sahel, José-Alain; Sennlaub, Florian; Guillonneau, Xavier; Rendon, Alvaro; Tadayoni, Ramin

    2016-05-01

    Understanding retinal vascular development is crucial because many retinal vascular diseases such as diabetic retinopathy (in adults) or retinopathy of prematurity (in children) are among the leading causes of blindness. Given the localization of the protein Dp71 around the retinal vessels in adult mice and its role in maintaining retinal homeostasis, the aim of this study was to determine if Dp71 was involved in astrocyte and vascular development regulation. An experimental study in mouse retinas was conducted. Using a dual immunolabeling with antibodies to Dp71 and anti-GFAP for astrocytes on retinal sections and isolated astrocytes, it was found that Dp71 was expressed in wild-type (WT) mouse astrocytes from early developmental stages to adult stage. In Dp71-null mice, a reduction in GFAP-immunopositive astrocytes was observed as early as postnatal day 6 (P6) compared with WT mice. Using real-time PCR, it was showed that Dp71 mRNA was stable between P1 and P6, in parallel with post-natal vascular development. Regarding morphology in Dp71-null and WT mice, a significant decrease in overall astrocyte process number in Dp71-null retinas at P6 to adult age was found. Using fluorescence-conjugated isolectin Griffonia simplicifolia on whole mount retinas, subsequent delay of developing vascular network at the same age in Dp71-null mice was found. An evidence that the Dystrophin Dp71, a membrane-associated cytoskeletal protein and one of the smaller Duchenne muscular dystrophy gene products, regulates astrocyte morphology and density and is associated with subsequent normal blood vessel development was provided. GLIA 2016;64:716-729. PMID:26711882

  12. Shuttle mutagenesis of Neisseria gonorrhoeae: pilin null mutations lower DNA transformation competence.

    PubMed Central

    Seifert, H S; Ajioka, R S; Paruchuri, D; Heffron, F; So, M

    1990-01-01

    The method of shuttle mutagenesis has been extended to Neisseria gonorrhoeae. We have constructed a defective mini-Tn3 derivative that encodes chloramphenicol resistance in both N. gonorrhoeae and Escherichia coli and selected for mutations in the chloramphenicol resistance gene that express higher levels of antibiotic resistance in N. gonorrhoeae. Isogenic N. gonorrhoeae strains that differ only in pilin expression were constructed and used to test the effect of pilin null mutations on DNA transformation competence. PMID:2152910

  13. Gene Coexpression Analyses Differentiate Networks Associated with Diverse Cancers Harboring TP53 Missense or Null Mutations

    PubMed Central

    Oros Klein, Kathleen; Oualkacha, Karim; Lafond, Marie-Hélène; Bhatnagar, Sahir; Tonin, Patricia N.; Greenwood, Celia M. T.

    2016-01-01

    In a variety of solid cancers, missense mutations in the well-established TP53 tumor suppressor gene may lead to the presence of a partially-functioning protein molecule, whereas mutations affecting the protein encoding reading frame, often referred to as null mutations, result in the absence of p53 protein. Both types of mutations have been observed in the same cancer type. As the resulting tumor biology may be quite different between these two groups, we used RNA-sequencing data from The Cancer Genome Atlas (TCGA) from four different cancers with poor prognosis, namely ovarian, breast, lung and skin cancers, to compare the patterns of coexpression of genes in tumors grouped according to their TP53 missense or null mutation status. We used Weighted Gene Coexpression Network analysis (WGCNA) and a new test statistic built on differences between groups in the measures of gene connectivity. For each cancer, our analysis identified a set of genes showing differential coexpression patterns between the TP53 missense- and null mutation-carrying groups that was robust to the choice of the tuning parameter in WGCNA. After comparing these sets of genes across the four cancers, one gene (KIR3DL2) consistently showed differential coexpression patterns between the null and missense groups. KIR3DL2 is known to play an important role in regulating the immune response, which is consistent with our observation that this gene's strongly-correlated partners implicated many immune-related pathways. Examining mutation-type-related changes in correlations between sets of genes may provide new insight into tumor biology. PMID:27536319

  14. First results of nulling interferometry with the Multiple-Mirror Telescope

    NASA Astrophysics Data System (ADS)

    Hinz, Philip M.; Angel, J. Roger P.; Hoffmann, William F.; McCarthy, Donald W.; McGuire, Patrick C.; Cheselka, Matt; Hora, Joseph L.; Woolf, Neville J.

    1998-07-01

    We have successfully used nulling interferometry at 10 micrometers wavelength to interferometrically suppress a star's radiation. This technique was first proposed by Bracewell 20 years ago to image extra-solar planets and is now the basis for proposed space-borne instruments to search for Earth- like extra-solar planets and their spectroscopic signatures of habitability and life. In our experiment, the beams from two 1.8 m telescopes of the multiple mirror telescope were brought into registration at a semi-transparent beamsplitter, and the images made coincident on an IR array detector capable of taking rapid short exposure images. The atmospheric fluctuations caused the phase difference between the beams to fluctuate, changing the total flux of the star seen in the image plane. When the atmosphere caused the wavefronts to be exactly out of phase the entire stellar Airy pattern disappeared. For the unresolved star (alpha) Tauri the cancellation was such that a companion only 0.2 arcsec from the star and 25 times fainter would appear equal in intensity to the nulled star. The residual flux was spread into a wide halo suggesting the cause of this flux was imperfect cancellation of the aberrated wavefronts. To increase the precision of nulling beyond this first step several sources of error need to be addressed. We discuss the control of errors due to amplitude, polarization, chromatic differences, stellar leak, and sampling time. Improvements such as active phase tracking, adaptive optics, and cooled optics will increase the achievable gain of nulling interferometry and allow it to be used on fainter objects.

  15. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice

    PubMed Central

    Zhao, Yang; Dai, Xiao-yan; Zhou, Zhou; Zhao, Ge-xin; Wang, Xian; Xu, Ming-jiang

    2016-01-01

    Aim: Recent evidence suggests that the essential amino acid leucine may be involved in systemic cholesterol metabolism. In this study, we investigated the effects of leucine supplementation on the development of atherosclerosis in apoE null mice. Methods: ApoE null mice were fed with chow supplemented with leucine (1.5% w/v) in drinking water for 8 week. Aortic atherosclerotic lesions were examined using Oil Red O staining. Plasma lipoprotein-cholesterol levels were measured with fast protein liquid chromatography. Hepatic gene expression was detected using real-time PCR and Western blot analyses. Results: Leucine supplementation resulted in 57.6% reduction of aortic atherosclerotic lesion area in apoE null mice, accompanied by 41.2% decrease of serum LDL-C levels and 40.2% increase of serum HDL-C levels. The body weight, food intake and blood glucose level were not affected by leucine supplementation. Furthermore, leucine supplementation increased the expression of Abcg5 and Abcg8 (that were involved in hepatic cholesterol efflux) by 1.28- and 0.86-fold, respectively, and significantly increased their protein levels. Leucine supplementation also increased the expression of Srebf1, Scd1 and Pgc1b (that were involved in hepatic triglyceride metabolism) by 3.73-, 1.35- and 1.71-fold, respectively. Consequently, leucine supplementation resulted in 51.77% reduction of liver cholesterol content and 2.2-fold increase of liver triglyceride content. Additionally, leucine supplementation did not affect the serum levels of IL-6, IFN-γ, TNF-α, IL-10 and IL-12, but markedly decreased the serum level of MCP-1. Conclusion: Leucine supplementation effectively attenuates atherosclerosis in apoE null mice by improving the plasma lipid profile and reducing systemic inflammation. PMID:26687933

  16. Null Trajectories and Bending of Light in Charged Black Holes with Quintessence

    NASA Astrophysics Data System (ADS)

    Fernando, Sharmanthie; Meadows, Scott; Reis, Kevon

    2015-10-01

    We have studied null geodesics of the charged black hole surrounded by quintessence. Quintessence is a candidate for dark energy and is represented by a scalar field. Here, we have done a detailed study of the photon trajectories. The exact solutions for the trajectories are obtained in terms of the Jacobi-elliptic integrals for all possible energy and angular momentum of the photons. We have also studied the bending angle using the Rindler and Ishak method.

  17. The first mecp2-null zebrafish model shows altered motor behaviors

    PubMed Central

    Pietri, Thomas; Roman, Angel-Carlos; Guyon, Nicolas; Romano, Sebastián A.; Washbourne, Philip; Moens, Cecilia B.; de Polavieja, Gonzalo G.; Sumbre, Germán

    2013-01-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder and one of the most common causes of mental retardation in affected girls. Other symptoms include a rapid regression of motor and cognitive skills after an apparently early normal development. Sporadic mutations in the transcription factor MECP2 has been shown to be present in more than 90% of the patients and several models of MeCP2-deficient mice have been created to understand the role of this gene. These models have pointed toward alterations in the maintenance of the central nervous system rather than its development, in line with the late onset of the disease in humans. However, the exact functions of MeCP2 remain difficult to delineate and the animal models have yielded contradictory results. Here, we present the first mecp2-null allele mutation zebrafish model. Surprisingly and in contrast to MeCP2-null mouse models, mecp2-null zebrafish are viable and fertile. They present nonetheless clear behavioral alterations during their early development, including spontaneous and sensory-evoked motor anomalies, as well as defective thigmotaxis. PMID:23874272

  18. [Development of new soybean germplasm with null lipoxygenase and Kunitz trypsin inhibitor genes].

    PubMed

    Han, Fen-Xia; Ding, An-Lin; Sun, Jun-Ming; Li, Gui-Ying

    2005-04-01

    Soybean is one of the most important sources of plant protein for human. Soybean protein is a kind of high-quality protein composed of balanced amino acids, which contains all kinds of amino acids, especially 8 amino acids necessary for human. But it also contains some components that are not good for human and affect food quality, such as lipoxygenase (Lox) and trypsin inhibitor (Ti). Those are important anti-nutritious factors. Nutritional value and processing quality of soybean can be improved by means of development of new variety with null Lox and Ti. In this paper, new soybean germplasms that pyramided multiple genes of high quality, null lipoxygenase and trypsin inhibitor genes (Ix1, Ix2, Ix3 and ti) were developed by means of cross and biochemical marker-assisted selection of progenies for null lipoxygenase and trypsin inhibitor genes using known Lox and Ti markers (protein markers). Female parents were soybean varieties Ludou 4, Zhongpin 661, Yudou 8,91D15, wei8640 popularized in Huanghuaihai Plain. Male parents were varieties introduced from US, trypsin-inhibitor (Ti)-deficient varieties P. I. L83-4387 and near isogenic lines of varieties Century for lipoxygenase (Lox)-deficient genes, Century-2 (Ix2), Century-2.3 (Ix2Ix3) and Century-1.3 (Ix1 Ix3). These new germplasms will promote soybean breeding for improved quality production,and utilization. PMID:16011034

  19. Impaired spare respiratory capacity in cortical synaptosomes from Sod2 null mice

    PubMed Central

    Flynn, James M.; Choi, Sung W.; Day, Nicholas U.; Gerencser, Akos A.; Hubbard, Alan; Melov, Simon

    2011-01-01

    Pre-synaptic nerve terminals require high levels of ATP for the maintenance of synaptic function. Failure of synaptic mitochondria to generate adequate ATP has been implicated as a causative event preceding loss of synaptic networks in neurodegenerative disease. Endogenous oxidative stress has often been postulated as an etiological basis for this pathology, but has been difficult to test in vivo. Inactivation of the superoxide dismutase gene (Sod2) encoding the chief defense enzyme against mitochondrial superoxide radicals results in neonatal lethality. However, intervention with an SOD mimetic extends the lifespan of this model, and uncovers a neurodegenerative phenotype providing a unique model for the examination of in vivo oxidative stress. We present here studies on synaptic termini isolated from the frontal cortex of Sod2 null mice demonstrating impaired bioenergetic function as a result of mitochondrial oxidative stress. Cortical synaptosomes from Sod2 null mice demonstrate a severe decline in mitochondrial spare respiratory capacity to physiological demand induced by mitochondrial respiratory chain uncoupling with FCCP or plasma membrane depolarization induced by 4-aminopyridine treatment. However, Sod2 null animals compensate for impaired oxidative metabolism in part by Pasteur effect allowing for normal neurotransmitter release at the synapse, setting up a potentially detrimental energetic paradigm. The results of this study demonstrate that high throughput respirometry is a facile method for analyzing specific regions of the brain in transgenic models, and can uncover bioenergetic deficits in subcellular regions due to endogenous oxidative stress. PMID:21215798

  20. Problems in the application of a null lens for precise measurements of aspheric mirrors.

    PubMed

    Chkhalo, N I; Malyshev, I V; Pestov, A E; Polkovnikov, V N; Salashchenko, N N; Toropov, M N; Soloviev, A A

    2016-01-20

    Problems in the application of a null lens for surface shape measurements of aspherical mirrors are discussed using the example of manufacturing an aspherical concave mirror for the beyond extreme ultraviolet nanolithographer. A method for allowing measurement of the surface shape of a sample under study and the aberration of a null lens simultaneously, and for evaluating measurement accuracy, is described. Using this method, we made a mirror with an aspheric surface of the 6th order (i.e., the maximum deviation from the best-fit sphere is 6.6 μm) with the parameters of the deviations from the designed surface PV=5.3  nm and RMS=0.8  nm. An approximation of the surface shape was carried out using Zernike polynomials {Z(n)(m)(r,φ),m+n≤36}. The physical limitations of this technique are analyzed. It is shown that for aspheric measurements to an Angstrom accuracy, one needs to have a null lens with errors of less than 1 nm. For accurate measurements, it is necessary to establish compliance with the coordinates on the sample and on the interferogram. PMID:26835938

  1. Marker assisted accelerated introgression of null allele of kunitz trypsin inhibitor in soybean

    PubMed Central

    Kumar, Vineet; Rani, Anita; Rawal, Reena; Mourya, Vaishali

    2015-01-01

    Development of kunitz trypsin inhibitor (KTI)-free soybean is crucial for soy-food industry as the heat inactivation employed to inactivate the anti-nutritional factor in regular soybean incurs extra cost and affects protein solubility. In the presented work, a null allele of KTI from PI542044 was introgressed into cultivar ‘JS97-52’ (recurrent parent) through marker assisted backcrossing. Foreground selection in BC1F2, BC2F2 and BC3F2 was carried out using the null allele-specific marker in tandem with SSR marker Satt228, tightly linked with a trypsin inhibitor Ti locus. Background selection in null allele-carrying plants through 106 polymorphic SSR markers across the genome led to the identification of 9 KTI-free lines exhibiting 98.6% average recurrent parent genome content (RPGC) after three backcrosses, which otherwise had required 5–6 backcrosses through conventional method. Introgressed lines (ILs) were free from KTI and yielded at par with recurrent parent. Reduction of 68.8–83.5% in trypsin inhibitor content (TIC) in ILs compared to the recurrent parent (‘JS97-52’) was attributed to the elimination of KTI. PMID:26719748

  2. Null Stream Approach for finding Sky Position of Pulsar Timing Array sources

    NASA Astrophysics Data System (ADS)

    Hazboun, Jeffrey; Larson, Shane

    2016-03-01

    A null stream is constructed from the timing residuals of three pulsars by noting that the same source polarization amplitudes appear in the data stream from each pulsar. Null stream mapping of gravitational wave sources has been described for LIGO and LISA, relying on the correlated gravitational wave signals between detectors. For a collection of pulsars observing the same source, the gravitational wave signal is common to all pulsars in the array, but modified by geometric factors related to the relative position of the source on the sky. Linear combinations of a set of individual pulsar data streams can be shown to be a two-parameter family (the two sky position angles of the source) that can be minimized to determine the location of the source on the sky. Overlaying a number of null streams allows for an even stronger localization of the gravitational waves source. This presents a large advantage in a PTA where there are more independent signals than interferometric detectors. We show how multiple sub-arrays of pulsars affect the pointing accuracy. Additionally, a simple noise model is used to demonstrate how the presence of noise will change the character of the spectrum, suppressing features related to the gravitational wave signal.

  3. Torsional magnetic reconnection at three dimensional null points: A phenomenological study

    SciTech Connect

    Wyper, Peter; Jain, Rekha

    2010-09-15

    Magnetic reconnection around three dimensional (3D) magnetic null points is the natural progression from X-point reconnection in two dimensions. In 3D the separator field lines of the X-point are replaced with the spine line and fan plane (the field lines which asymptotically approach or recede from the null). In this work analytical models are developed for the newly classified torsional spine and torsional fan reconnection regimes by solving the steady state, kinematic, resistive magnetohydrodynamic equations. Reconnection is localized to around the null through the use of a localized field perturbation leading to a localized current while a constant resistivity is assumed. For the torsional spine case current is found to localize around the spine leading to a spiraling slippage of the field around the spine and out along the fan. For the torsional fan case current is found to be localized to the fan plane leading again to a spiraling slippage of the field. In each case no flux is transported across either the spine or the fan. An intermediate twist is then introduced and a link is established between the two regimes. We find that for a general twist plasma flows associated with both torsional spine and fan appear in distinct regions. As such we suggest that the ''pure'' flows of each are extreme cases.

  4. Designing null phase screens to test a fast plano-convex aspheric lens

    NASA Astrophysics Data System (ADS)

    DelOlmo-Márquez, Jesús; Castán-Ricaño, Diana; Avendaño-Alejo, Maximino; Díaz-Uribe, Rufino

    2015-08-01

    We have obtained a formula to represent the wavefront produced by a plano-convex aspheric lens with symmetry of revolution considering a plane wavefront propagating parallel to the optical axis and impinging on the refracting surface, it is called a zero-distance phase front, being it the first wavefront to be out of the optical system. Using a concept of differential geometry called parallel curves it is possible to obtain an analytic formula to represent the wavefront propagated at arbitrary distances through the optical axis. In order to evaluate qualitatively a plano-convex aspheric lens, we have modified slightly an interferometer Tywman-Green as follow: In the reference beam we use a plane mirror and the beam of test we have used a spatial light modulator (SLM) to compensate the phase produced by the lens under test. It will be called a null phase interferometer. The main idea is to recombine both wavefronts in order to get a null interferogram, otherwise we will associate the patterns of the interferogram to deformations of the lens under test. The null phase screens are formed with concentric circumferences assuming different gray levels printed on SLM.

  5. Auto-nulling system design of ultraviolet enhanced electrically calibrated pyroelectric radiometer

    NASA Astrophysics Data System (ADS)

    Hu, Qi; Gu, Lingjuan; Li, Wen; Zhuang, Songlin

    2006-02-01

    Electrically calibrated pyroelectric radiometer (ECPR) is a kind of electrical substitution radiometer (ESR) with high precision in optical power measurement. Its electrically calibrated pyroelectric detector (ECP) has been a widely used instrument in measuring optical power at relatively low levels over a broad wavelength range. The Precise automatic electrical pulse is used to heat the detecting surface which has the gold-black absorber material, and the electrical signal is accurately equal to the generated electrical signal of the modulated optical signal illuminated on the same detecting surface. This paper presents the principle of the electrical-optical equivalence and the auto-nulling circuit. The auto-nulling circuit is a kind of servo-loop circuits which could adjust the magnitude of the current pulses to reach the null condition at the output of the synchronous rectifier circuit. At this point, the optical power is equal to the electrical power, so the absolute value of the optical illumination can be determined by measuring the electrical power.

  6. Human TSC2-null fibroblast-like cells induce hair follicle neogenesis and hamartoma morphogenesis.

    PubMed

    Li, Shaowei; Thangapazham, Rajesh L; Wang, Ji-An; Rajesh, Sangeetha; Kao, Tzu-Cheg; Sperling, Leonard; Moss, Joel; Darling, Thomas N

    2011-01-01

    Hamartomas are composed of cells native to an organ but abnormal in number, arrangement or maturity. In the tuberous sclerosis complex (TSC), hamartomas develop in multiple organs because of mutations in TSC1 or TSC2. Here we show that TSC2-null fibroblast-like cells grown from human TSC skin hamartomas induced normal human keratinocytes to form hair follicles and stimulated hamartomatous changes. Follicles were complete with sebaceous glands, hair shafts and inner and outer root sheaths. TSC2-null cells surrounding the hair bulb expressed markers of the dermal sheath and dermal papilla. Tumour xenografts recapitulated characteristics of TSC skin hamartomas with increased mammalian target of the rapamycin complex 1 (mTORC1) activity, angiogenesis, mononuclear phagocytes and epidermal proliferation. Treatment with an mTORC1 inhibitor normalized these parameters and reduced the number of tumour cells. These studies indicate that TSC2-null cells are the inciting cells for TSC skin hamartomas, and suggest that studies on hamartomas will provide insights into tissue morphogenesis and regeneration. PMID:21407201

  7. Internal structure of an optical null Ronchi grating test for a plano-parabolic lens.

    PubMed

    Ortega-Vidals, Paula; Juárez-Reyes, Salvador Alejandro; Silva-Ortigoza, Gilberto; Cabrera-Rosas, Omar de J

    2016-01-01

    In this work we use geometrical optics and the caustic touching theorem, introduced by Berry, to describe the internal structure of the null Ronchi grating for a plano-parabolic lens illuminated by a point light source placed on the optical axis. The aim of this work is to explain the role of the caustic region in the process of morphology change between image and object in computing the null Ronchi grating. To this end, we obtain the analytic expression of the null Ronchi grating, and after that we deeply study the change in morphology between a single straight fringe image at the Ronchigram and the multiple curve rulings that can generate it (one open and one closed). We analyze exactly how multiple rulings generate the same straight image fringe, or how an entire ruling collapses into a single point image. For this analysis, we take different observation planes at different positions with respect to the caustic region. Finally, we characterize this topological change as one of two possible kinds depending on the relative position between the observation plane and the caustic region. PMID:26831584

  8. Tooth development in a model reptile: functional and null generation teeth in the gecko Paroedura picta

    PubMed Central

    Zahradnicek, Oldrich; Horacek, Ivan; Tucker, Abigail S

    2012-01-01

    This paper describes tooth development in a basal squamate, Paroedura picta. Due to its reproductive strategy, mode of development and position within the reptiles, this gecko represents an excellent model organism for the study of reptile development. Here we document the dental pattern and development of non-functional (null generation) and functional generations of teeth during embryonic development. Tooth development is followed from initiation to cytodifferentiation and ankylosis, as the tooth germs develop from bud, through cap to bell stages. The fate of the single generation of non-functional (null generation) teeth is shown to be variable, with some teeth being expelled from the oral cavity, while others are incorporated into the functional bone and teeth, or are absorbed. Fate appears to depend on the initiation site within the oral cavity, with the first null generation teeth forming before formation of the dental lamina. We show evidence for a stratum intermedium layer in the enamel epithelium of functional teeth and show that the bicuspid shape of the teeth is created by asymmetrical deposition of enamel, and not by folding of the inner dental epithelium as observed in mammals. PMID:22780101

  9. Asymptotic symmetries of Rindler space at the horizon and null infinity

    SciTech Connect

    Chung, Hyeyoun

    2010-08-15

    We investigate the asymptotic symmetries of Rindler space at null infinity and at the event horizon using both systematic and ad hoc methods. We find that the approaches that yield infinite-dimensional asymptotic symmetry algebras in the case of anti-de Sitter and flat spaces only give a finite-dimensional algebra for Rindler space at null infinity. We calculate the charges corresponding to these symmetries and confirm that they are finite, conserved, and integrable, and that the algebra of charges gives a representation of the asymptotic symmetry algebra. We also use relaxed boundary conditions to find infinite-dimensional asymptotic symmetry algebras for Rindler space at null infinity and at the event horizon. We compute the charges corresponding to these symmetries and confirm that they are finite and integrable. We also determine sufficient conditions for the charges to be conserved on-shell, and for the charge algebra to give a representation of the asymptotic symmetry algebra. In all cases, we find that the central extension of the charge algebra is trivial.

  10. Instrumental stability requirements for exoplanet detection with a nulling interferometer: variability noise as a central issue.

    PubMed

    Chazelas, Bruno; Brachet, Frank; Bordé, Pascal; Mennesson, Bertrand; Ollivier, Marc; Absil, Olivier; Labèque, Alain; Valette, Claude; Léger, Alain

    2006-02-10

    We revisit the nulling interferometer performances that are needed for direct detection and the spectroscopic analysis of exoplanets, e.g., with the DARWIN [European Space Agency-SCI 12 (2000)] or TPF-I [JPL Publ. 05-5, (2005)] missions. Two types of requirement are found, one concerning the mean value of the instrumental nulling function (nl(lambda)) and another regarding its stability. The stress is usually put on the former. It is stringent at short wavelengths but somewhat relaxed at longer wavelengths. The latter, which we call the variability noise condition, does not usually receive enough attention. It is required regardless of telescope size and stellar distance. The results from three nulling experiments performed in laboratories around the world are reported and compared with the requirements. All three exhibit 1/f noise that is incompatible with the performances required by the mission. As pointed out by Lay [Appl. Opt. 43, 6100-6123 (2004)], this stability problem is not fully solved by modulation techniques. Adequate solutions must be found that are likely to include servo systems using the stellar signal itself as a reference and internal metrology with high stability. PMID:16512542

  11. Altered Ca2+ homeostasis in the skeletal muscle of DJ – 1 null mice

    PubMed Central

    Shtifman, Alexander; Zhong, Nan; Lopez, Jose R.; Shen, Jie; Xu, Jin

    2009-01-01

    Loss-of-function mutations in DJ – 1 are associated with early-onset of Parkinson’s disease. Although DJ – 1 is ubiquitously expressed, the functional pathways affected by it remain unresolved. Here we demonstrate an involvement of DJ – 1 in the regulation of Ca2+ homeostasis in mouse skeletal muscle. Using enzymatically dissociated flexor digitorum brevis muscle fibers from wild-type (wt) and DJ – 1 null mice, we examined the effects of DJ – 1 protein on resting, cytoplasmic [Ca2+] ([Ca2+]i) and depolarization-evoked Ca2+ release in the mouse skeletal muscle. The loss of DJ – 1 resulted in a more than two-fold increase in resting [Ca2+]i. While there was no alteration in the resting membrane potential, there was a significant decrease in depolarization-evoked Ca2+ release from the sarcoplasmic reticulum in the DJ – 1 null muscle cells. Consistent with the role of DJ – 1 in oxidative stress regulation and mitochondrial functional maintenance, treatments of DJ – 1 null muscle cells with resveratrol, a mitochondrial activator, or glutathione, a potent antioxidant, reversed the effects of the loss of DJ – 1 on Ca2+ homeostasis. These results provide evidence of DJ – 1’s association with Ca2+ regulatory pathways in mouse skeletal muscle, and suggest the potential benefit of resveratrol to functionally compensate for the loss of DJ – 1. PMID:19683835

  12. Simulations of 3D Magnetic Merging: Resistive Scalings for Null Point and QSL Reconnection

    NASA Astrophysics Data System (ADS)

    Effenberger, Frederic; Craig, I. J. D.

    2016-01-01

    Starting from an exact, steady-state, force-free solution of the magnetohydrodynamic (MHD) equations, we investigate how resistive current layers are induced by perturbing line-tied three-dimensional magnetic equilibria. This is achieved by the superposition of a weak perturbation field in the domain, in contrast to studies where the boundary is driven by slow motions, like those present in photospheric active regions. Our aim is to quantify how the current structures are altered by the contribution of so-called quasi-separatrix layers (QSLs) as the null point is shifted outside the computational domain. Previous studies based on magneto-frictional relaxation have indicated that despite the severe field line gradients of the QSL, the presence of a null is vital in maintaining fast reconnection. Here, we explore this notion using highly resolved simulations of the full MHD evolution. We show that for the null-point configuration, the resistive scaling of the peak current density is close to J˜η^{-1}, while the scaling is much weaker, i.e. J˜η^{-0.4}, when only the QSL connectivity gradients provide a site for the current accumulation.

  13. Kelvin-Helmholtz instability in a current-vortex sheet at a 3D magnetic null

    SciTech Connect

    Wyper, P. F.; Pontin, D. I.

    2013-03-15

    We report here, for the first time, an observed instability of a Kelvin-Helmholtz nature occurring in a fully three-dimensional (3D) current-vortex sheet at the fan plane of a 3D magnetic null point. The current-vortex layer forms self-consistently in response to foot point driving around the spine lines of the null. The layer first becomes unstable at an intermediate distance from the null point, with the instability being characterized by a rippling of the fan surface and a filamentation of the current density and vorticity in the shear layer. Owing to the 3D geometry of the shear layer, a branching of the current filaments and vortices is observed. The instability results in a mixing of plasma between the two topologically distinct regions of magnetic flux on either side of the fan separatrix surface, as flux is reconnected across this surface. We make a preliminary investigation of the scaling of the system with the dissipation parameters. Our results indicate that the fan plane separatrix surface is an ideal candidate for the formation of current-vortex sheets in complex magnetic fields and, therefore, the enhanced heating and connectivity change associated with the instabilities of such layers.

  14. Multi-transmitter multi-receiver null coupled systems forinductive detection and characterization of metallic objects

    SciTech Connect

    Smith, J. Torquil; Morrison, H. Frank; Doolittle, Lawrence R.; Tseng, Hung-Wen

    2005-10-17

    Equivalent dipole polarizabilities are a succinct way tosummarize the inductive response of an isolated conductive body atdistances greater than the scale of the body. Their estimation requiresmeasurement of secondary magnetic fields due to currents induced in thebody by time varying magnetic fields in at least three linearlyindependent (e.g., orthogonal) directions. Secondary fields due to anobject are typically orders of magnitude smaller than the primaryinducing fields near the primary field sources (transmitters). Receivercoils may be oriented orthogonal to primary fields from one or twotransmitters, nulling their response to those fields, but simultaneouslynulling to fields of additional transmitters is problematic. Iftransmitter coils are constructed symmetrically with respect to inversionin a point, their magnetic fields are symmetric with respect to thatpoint. If receiver coils are operated in pairs symmetric with respect toinversion in the same point, then their differenced output is insensitiveto the primary fields of any symmetrically constructed transmitters,allowing nulling to three (or more) transmitters. With a sufficientnumber of receivers pairs, object equivalent dipole polarizabilities canbe estimated in situ from measurements at a single instrument sitting,eliminating effects of inaccurate instrument location on polarizabilityestimates. The method is illustrated with data from a multi-transmittermulti-receiver system with primary field nulling through differencedreceiver pairs, interpreted in terms of principal equivalent dipolepolarizabilities as a function of time.

  15. Persee: a nulling demonstrator with real-time correction of external disturbances

    NASA Astrophysics Data System (ADS)

    Cassaing, F.; Le Duigou, J. M.; Amans, J. P.; Barillot, M.; Buey, T.; Henault, F.; Houairi, K.; Jacquinod, S.; Laporte, P.; Marcotto, A.; Pirson, L.; Reess, J. M.; Sorrente, B.; Rousset, G.; Coudé du Foresto, V.; Ollivier, M.

    2008-07-01

    Nulling interferometry is one of the most promising methods to study habitable extrasolar systems. Several projects, such as Darwin, TPF, Pegase, FKSI or Aladdin, are currently considered and supported by R&D programs. One of the main issues of nulling interferometry is the feasibility of a stable polychromatic null despite the presence of significant disturbances, induced by vibrations, atmospheric turbulence on the ground or satellite drift for spaceborne missions. To reduce cost and complexity of the whole system, it is necessary to optimize not only the control loop performance at platform and payload levels, but also their interaction. In this goal, it was decided in 2006 to build a laboratory demonstrator named Persee. Persee is mostly funded by CNES and built by a consortium including CNES, IAS, LESIA, OCA, ONERA and TAS. After a definition phase in 2006, the implementation of the sub-systems has now begun and the integration near Paris by GIS-PHASE (LESIA, ONERA and GEPI) is planned in 2009. This paper details the main objectives of PERSEE, describes the definition of the bench, presents the current status and reports results obtained with the first sub-systems.

  16. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity

    PubMed Central

    Joyce, Peter I.; Mcgoldrick, Philip; Saccon, Rachele A.; Weber, William; Fratta, Pietro; West, Steven J.; Zhu, Ning; Carter, Sarah; Phatak, Vinaya; Stewart, Michelle; Simon, Michelle; Kumar, Saumya; Heise, Ines; Bros-Facer, Virginie; Dick, James; Corrochano, Silvia; Stanford, Macdonnell J.; Luong, Tu Vinh; Nolan, Patrick M.; Meyer, Timothy; Brandner, Sebastian; Bennett, David L.H.; Ozdinler, P. Hande; Greensmith, Linda; Fisher, Elizabeth M.C.; Acevedo-Arozena, Abraham

    2015-01-01

    Transgenic mouse models expressing mutant superoxide dismutase 1 (SOD1) have been critical in furthering our understanding of amyotrophic lateral sclerosis (ALS). However, such models generally overexpress the mutant protein, which may give rise to phenotypes not directly relevant to the disorder. Here, we have analysed a novel mouse model that has a point mutation in the endogenous mouse Sod1 gene; this mutation is identical to a pathological change in human familial ALS (fALS) which results in a D83G change in SOD1 protein. Homozgous Sod1D83G/D83G mice develop progressive degeneration of lower (LMN) and upper motor neurons, likely due to the same unknown toxic gain of function as occurs in human fALS cases, but intriguingly LMN cell death appears to stop in early adulthood and the mice do not become paralyzed. The D83 residue coordinates zinc binding, and the D83G mutation results in loss of dismutase activity and SOD1 protein instability. As a result, Sod1D83G/D83G mice also phenocopy the distal axonopathy and hepatocellular carcinoma found in Sod1 null mice (Sod1−/−). These unique mice allow us to further our understanding of ALS by separating the central motor neuron body degeneration and the peripheral effects from a fALS mutation expressed at endogenous levels. PMID:25468678

  17. Staphylococcus aureus formyl-methionyl transferase mutants demonstrate reduced virulence factor production and pathogenicity.

    PubMed

    Lewandowski, Thomas; Huang, Jianzhong; Fan, Frank; Rogers, Shannon; Gentry, Daniel; Holland, Reannon; Demarsh, Peter; Aubart, Kelly; Zalacain, Magdalena

    2013-07-01

    Inhibitors of peptide deformylase (PDF) represent a new class of antibacterial agents with a novel mechanism of action. Mutations that inactivate formyl methionyl transferase (FMT), the enzyme that formylates initiator methionyl-tRNA, lead to an alternative initiation of protein synthesis that does not require deformylation and are the predominant cause of resistance to PDF inhibitors in Staphylococcus aureus. Here, we report that loss-of-function mutations in FMT impart pleiotropic effects that include a reduced growth rate, a nonhemolytic phenotype, and a drastic reduction in production of multiple extracellular proteins, including key virulence factors, such as α-hemolysin and Panton-Valentine leukocidin (PVL), that have been associated with S. aureus pathogenicity. Consequently, S. aureus FMT mutants are greatly attenuated in neutropenic and nonneutropenic murine pyelonephritis infection models and show very high survival rates compared with wild-type S. aureus. These newly discovered effects on extracellular virulence factor production demonstrate that FMT-null mutants have a more severe fitness cost than previously anticipated, leading to a substantial loss of pathogenicity and a restricted ability to produce an invasive infection. PMID:23571548

  18. Staphylococcus aureus Formyl-Methionyl Transferase Mutants Demonstrate Reduced Virulence Factor Production and Pathogenicity

    PubMed Central

    Lewandowski, Thomas; Huang, Jianzhong; Fan, Frank; Rogers, Shannon; Gentry, Daniel; Holland, Reannon; DeMarsh, Peter; Zalacain, Magdalena

    2013-01-01

    Inhibitors of peptide deformylase (PDF) represent a new class of antibacterial agents with a novel mechanism of action. Mutations that inactivate formyl methionyl transferase (FMT), the enzyme that formylates initiator methionyl-tRNA, lead to an alternative initiation of protein synthesis that does not require deformylation and are the predominant cause of resistance to PDF inhibitors in Staphylococcus aureus. Here, we report that loss-of-function mutations in FMT impart pleiotropic effects that include a reduced growth rate, a nonhemolytic phenotype, and a drastic reduction in production of multiple extracellular proteins, including key virulence factors, such as α-hemolysin and Panton-Valentine leukocidin (PVL), that have been associated with S. aureus pathogenicity. Consequently, S. aureus FMT mutants are greatly attenuated in neutropenic and nonneutropenic murine pyelonephritis infection models and show very high survival rates compared with wild-type S. aureus. These newly discovered effects on extracellular virulence factor production demonstrate that FMT-null mutants have a more severe fitness cost than previously anticipated, leading to a substantial loss of pathogenicity and a restricted ability to produce an invasive infection. PMID:23571548

  19. Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency.

    PubMed

    Takeda, Hiromasa; Takigawa, Nagio; Ohashi, Kadoaki; Minami, Daisuke; Kataoka, Itaru; Ichihara, Eiki; Ochi, Nobuaki; Tanimoto, Mitsune; Kiura, Katsuyuki

    2013-02-15

    The effectiveness of vandetanib, an agent that targets RET, VEGFR and EGFR signaling, against EGFR-mutant lung cancer cells with PTEN loss was investigated. Two EGFR mutant non-small cell lung cancer (NSCLC) cell lines, PC-9 (PTEN wild type) and NCI-H1650 (PTEN null), were used. We transfected an intact PTEN gene into H1650 cells and knocked down PTEN expression in PC-9 cells using shRNA. The effectiveness of gefitinib and vandetanib was assessed using a xenograft model. While PC-9 cells were more resistant to vandetanib than gefitinib, H1650 cells were more sensitive to vandetanib than gefitinib. Both gefitinib and vandetanib suppressed the activation of EGFR and MAPK in H1650 cells, although phosphorylated AKT levels were not affected. In an H1650 cell xenograft model, vandetanib was also more effective than gefitinib. Although PTEN-transfected H1650 cells did not show restoration of sensitivity to gefitinib in vitro, the xenograft tumors responded to gefitinib and vandetanib. Knockdown of PTEN in PC-9 cells caused resistance to gefitinib. In conclusion, vandetanib might be effective in NSCLC with EGFR mutations that lack PTEN expression. The contribution of PTEN absence to vandetanib activity in NSCLC cells harboring EGFR mutations should be further examined. PMID:23274758

  20. Identification of novel attenuated Salmonella Enteritidis mutants.

    PubMed

    Chang, Jason; Pang, Ervinna; He, Haiqi; Kwang, Jimmy

    2008-06-01

    Salmonella Enteritidis is a major food-borne pathogen that causes nontyphoidal diarrhoea in humans. Infection of adult egg-laying hens usually results in symptomless carriage but in young chicks it may cause paratyphoid disease. It is not known whether S. Enteritidis requires genes additional to known virulence genes for systemic infection of young chickens. A transposon insertion library was created using S. Enteritidis 10/02, which yielded 1246 mutants. Of 384 mutants screened in chickens for attenuation (30.8% of insertion library), 12 (3.1%) had a 50% lethal dose at least 100 times that of the parental strain. Sequencing revealed insertions in genes involved in the biosynthesis of lipopolysaccharide, cell membrane, ATP biosynthesis, transcriptional regulation of virulence and the yhbC gene, which has an unknown function. Evaluation of in vitro virulence characteristics of a Delta yhbC mutant revealed that its ability to invade HeLa cells and survive within a chicken macrophage cell line (HD11) was significantly reduced. It was also less resistant to reactive oxygen and nitrogen intermediates and had a retarded growth rate. Chickens challenged with the Delta yhbC mutant cleared the organism from the liver and spleen 1 week faster than the parental strain and were able to develop specific serum IgG antibodies against the Delta yhbC mutant. PMID:18355292

  1. Inositol-Requiring Mutants of SACCHAROMYCES CEREVISIAE

    PubMed Central

    Culbertson, Michael R.; Henry, Susan A.

    1975-01-01

    Fifty-two inositol-requiring mutants of Saccharomyces cerevisiae were isolated following mutagenesis with ethyl methanesulfonate. Complementation and tetrad analysis revealed ten major complementation classes, representing ten independently segregating loci (designated ino1 through ino10) which recombined freely with their respective centromeres. Members of any given complementation class segregated as alleles of a single locus. Thirteen complementation subclasses were identified among thirty-six mutants which behaved as alleles of the ino1 locus. The complementation map for these mutants was circular.—Dramatic cell viability losses indicative of unbalanced growth were observed in liquid cultures of representative mutants under conditions of inositol starvation. Investigation of the timing, kinetics, and extent of cell death revealed that losses in cell viability in the range of 2-4 log orders could be prevented by the addition of inositol to the medium or by disruption of protein synthesis with cycloheximide. Mutants defective in nine of the ten loci identified in this study displayed these unusual characteristics. The results suggest an important physiological role for inositol that may be related to its cellular localization and function in membrane phospholipids. The possibility is discussed that inositol deficiency initiates the process of unbalanced growth leading to cell death through the loss of normal assembly, function, or integrity of biomembranes.—Part of this work has been reported in preliminary form (Culbertson and Henry 1974). PMID:1093935

  2. Escherichia coli mutants deficient in deoxyuridine triphosphatase.

    PubMed Central

    Hochhauser, S J; Weiss, B

    1978-01-01

    Mutants deficient in deoxyuridine triphosphatase (dUTPase) were identified by enzyme assays of randomly chosen heavily mutagenized clones. Five mutants of independent origin were obtained. One mutant produced a thermolabile enzyme, and it was presumed to have a mutation in the structural gene for dUTPase, designated dut. The most deficient mutant had the following associated phenotypes: less than 1% of parental dUTPase activity, prolonged generation time, increased sensitivity to 5'-fluorodeoxyuridine, increased rate of spontaneous mutation, increased rate of recombination (hyper-Rec), an inhibition of growth in the presence of 2 mM uracil, and a decreased ability to support the growth of phage P1 (but not T4 or lambda). This mutation also appeared to be incompatible with pyrE mutations. A revertant selected by its faster growth had regained dUTPase activity and lost its hyper-Rec phenotype. Many of the properties of the dut mutants are compatible with their presumed increased incorporation of uracil into DNA and the subsequent transient breakage of the DNA by excision repair. PMID:148458

  3. Phanerochaete mutants with enhanced ligninolytic activity

    SciTech Connect

    Kakar, S.N.; Perez, A.; Gonzales, J.

    1993-06-01

    In addition to lignin, the white rot fungus Phanerochaete chrysosporium has the ability to degrade a wide spectrum of recalcitrant organopollutants in soils and aqueous media. Although some of the organic compounds are degraded under nonligninolytic conditions, most are degraded under ligninolytic conditions with the involvement of the extracellular enzymes, lignin peroxidases, and manganese-dependent peroxidases, which are produced as secondary metabolites triggered by conditions of nutrient starvation (e.g., nitrogen limitation). The fungus and its enzymes can thus provide alternative technologies for bioremediation, biopulping, biobleaching, and other industrial applications. The efficiency and effectiveness of the fungus can be enhanced by increasing production and secretion of the important enzymes in large quantities and as primary metabolites under enriched conditions. One way this can be achieved is through isolation of mutants that are deregulated or are hyperproducers or supersecretors of key enzymes under enriched conditions. Through ultraviolet-light and gamma-rays mutagenesis we have isolated a variety of mutants, some of which produce key enzymes of the ligninolytic system under high-nitrogen growth conditions. One of the mutants produced 272 units (U) of lignin peroxidases enzyme activity per liter after nine days under high nitrogen. The mutant and the parent strains produced up to 54 U/L and 62 U/L, respectively, of the enzyme activity under low-nitrogen growth conditions during this period. In some experiments the mutant showed 281 U/L of enzyme activity under high nitrogen after 17 days.

  4. Vitamin E Status and Metabolism in Adult and Aged Aryl Hydrocarbon Receptor Null Mice

    PubMed Central

    Traber, Maret G.; Mustacich, Debbie J.; Sullivan, Laura C.; Leonard, Scott W.; Ahern-Rindell, Amelia; Kerkvliet, Nancy

    2009-01-01

    The aryl hydrocarbon receptor (AhR) is involved in regulation of mechanisms for detoxification of xenobiotics, as well as vitamin A metabolism. Vitamin E is a fat-soluble nutrient whose metabolism is initialized via the cytochrome P450 system. Thus, AhR absence could alter hepatic regulation of α-tocopherol metabolism. To test this hypothesis, we assessed vitamin E status in adult (2–5 m) and old (21–22 m), wildtype and AhR-null mice. Plasma α-tocopherol concentrations in AhR null mice (2.3 ± 1.2 μmol/L, n= 19) were lower than those of wildtype mice (3.2 ± 1.2, n=17, P=0.0131); those in old mice (3.2 ± 1.2, n= 20) were higher than those of adults (2.2 ± 1.0, n=16, p=0.0075). Hepatic α-tocopherol concentrations were not different between genotypes, but were nearly double in old (32 ± 8 nmol/g, n=20) as compared with adult mice (17 ± 2, n=16, p<0.0001). Hepatic Cyp3a concentrations in AhR-null mice were greater than those in wildtypes (p=0.0011). Genotype (p=0.0047), sex (p<0.0001) and age (p<0.0001) were significant modifiers of liver α-tocopherol metabolite (α-CEHC) concentrations. In general, Cyp3a concentrations correlated with hepatic α-tocopherol (r= 0.3957, p<0.05) and α-CEHC (r=0.4260, p<0.05) concentrations. Since there were no significant genotype differences in the hepatic α- or γ-tocopherol concentrations, AhR null mice did not have dramatically altered vitamin E metabolism. Since they did have higher hepatic α-CEHC concentrations, these data suggest metabolism was up-regulated in the AhR null mice in order to maintain the hepatic tocopherol concentrations similar to those of wildtypes. PMID:20153623

  5. Optomechanical design of near-null subaperture test system based on counter-rotating CGH plates

    NASA Astrophysics Data System (ADS)

    Li, Yepeng; Chen, Shanyong; Song, Bing; Li, Shengyi

    2014-09-01

    In off-axis subapertures of most convex aspheres, astigmatism and coma dominate the aberrations with approximately quadratic and linear increase as the off-axis distance increases. A pair of counter-rotating computer generated hologram (CGH) plates is proposed to generate variable amount of Zernike terms Z4 and Z6, correcting most of the astigmatism and coma for subapertures located at different positions on surfaces of various aspheric shapes. The residual subaperture aberrations are then reduced within the vertical range of measurement of the interferometer, which enables near-null test of aspheres flexibly. The alignment tolerances for the near-null optics are given with optomechanical analysis. Accordingly a novel design for mounting and aligning the CGH plates is proposed which employs three concentric rigid rings. The CGH plate is mounted in the inner ring which is supported by two couples of ball-end screws in connection with the middle ring. The CGH plate along with the inner ring is hence able to be translated in X-axis and tipped by adjusting the screws. Similarly the middle ring is able to be translated in Y-axis and tilted by another two couples of screws orthogonally arranged and connected to the outer ring. This design is featured by the large center-through hole, compact size and capability of four degrees-of-freedom alignment (lateral shift and tip-tilt). It reduces the height measured in the direction of optical axis as much as possible, which is particularly advantageous for near-null test of convex aspheres. The CGH mounts are then mounted on a pair of center-through tables realizing counter-rotation. Alignment of the interferometer, the CGHs, the tables and the test surface is also discussed with a reasonable layout of the whole test system. The interferometer and the near-null optics are translated by a three-axis stage while the test mirror is rotated and tilted by two rotary tables. Experimental results are finally given to show the near-null

  6. Multi-Segment Radius Measurement Using an Absolute Distance Meter Through a Null Assembly

    NASA Technical Reports Server (NTRS)

    Merle, Cormic; Wick, Eric; Hayden, Joseph

    2011-01-01

    This system was one of the test methods considered for measuring the radius of curvature of one or more of the 18 segmented mirrors that form the 6.5 m diameter primary mirror (PM) of the James Webb Space Telescope (JWST). The assembled telescope will be tested at cryogenic temperatures in a 17-m diameter by 27-m high vacuum chamber at the Johnson Space Center. This system uses a Leica Absolute Distance Meter (ADM), at a wavelength of 780 nm, combined with beam-steering and beam-shaping optics to make a differential distance measurement between a ring mirror on the reflective null assembly and individual PM segments. The ADM is located inside the same Pressure-Tight Enclosure (PTE) that houses the test interferometer. The PTE maintains the ADM and interferometer at ambient temperature and pressure so that they are not directly exposed to the telescope s harsh cryogenic and vacuum environment. This system takes advantage of the existing achromatic objective and reflective null assembly used by the test interferometer to direct four ADM beamlets to four PM segments through an optical path that is coincident with the interferometer beam. A mask, positioned on a linear slide, contains an array of 1.25 mm diameter circular subapertures that map to each of the 18 PM segments as well as six positions around the ring mirror. A down-collimated 4 mm ADM beam simultaneously covers 4 adjacent PM segment beamlets and one ring mirror beamlet. The radius, or spacing, of all 18 segments can be measured with the addition of two orthogonally-oriented scanning pentaprisms used to steer the ADM beam to any one of six different sub-aperture configurations at the plane of the ring mirror. The interferometer beam, at a wavelength of 687 nm, and the ADM beamlets, at a wavelength of 780 nm, pass through the objective and null so that the rays are normally incident on the parabolic PM surface. After reflecting off the PM, both the ADM and interferometer beams return to their respective

  7. Structure of mutant human oncogene protein determined

    SciTech Connect

    Baum, R.

    1989-01-16

    The protein encoded by a mutant human oncogene differs only slightly in structure from the native protein that initiates normal cell division, a finding that may complicate efforts to develop inhibitors of the mutant protein. Previously, the x-ray structure of the protein encoded by the normal c-Ha-ras gene, a protein believed to signal cells to start or stop dividing through its interaction with guanosine triphosphate (GTP), was reported. The structure of the protein encoded by a transforming c-Ha-ras oncogene, in which a valine codon replaces the normal glycine codon at position 12 in the gene, has now been determined. The differences in the structures of the mutant and normal proteins are located primarily in a loop that interacts with the /beta/-phosphate of a bound guanosine diphosphate (GDP) molecule.

  8. Amphid defective mutant of Caenorhabditis elegans.

    PubMed

    De Riso, L; Ristoratore, F; Sebastiano, M; Bazzicalupo, P

    1994-01-01

    Studies are reported on a chemoreception mutant which arose in a mutator strain. The mutant sensory neurons do not stain with fluoresceine isothiocyanate (Dyf phenotype), hence the name, dyf-1, given to the gene it identifies. The gene maps on LGI, 0.4 map units from dpy-5 on the unc-11 side. The response of mutant worms to various repellents has been studied and shown to be partially altered. Other chemoreception based behaviors are less affected. The cilia of the sensory neurons of the amphid are shorter than normal and the primary defect may be in the capacity of the sheath cells to secrete the matrix material that fills the space between cilia in the amphid channel. Progress toward the molecular cloning of the gene is also reported. Relevant results from other laboratories are briefly reviewed. PMID:7896139

  9. High Persister Mutants in Mycobacterium tuberculosis.

    PubMed

    Torrey, Heather L; Keren, Iris; Via, Laura E; Lee, Jong Seok; Lewis, Kim

    2016-01-01

    Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection. PMID:27176494

  10. High Persister Mutants in Mycobacterium tuberculosis

    PubMed Central

    Torrey, Heather L.; Keren, Iris; Via, Laura E.; Lee, Jong Seok; Lewis, Kim

    2016-01-01

    Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection. PMID:27176494

  11. TOMATOMA: a novel tomato mutant database distributing Micro-Tom mutant collections.

    PubMed

    Saito, Takeshi; Ariizumi, Tohru; Okabe, Yoshihiro; Asamizu, Erika; Hiwasa-Tanase, Kyoko; Fukuda, Naoya; Mizoguchi, Tsuyoshi; Yamazaki, Yukiko; Aoki, Koh; Ezura, Hiroshi

    2011-02-01

    The tomato is an excellent model for studies of plants bearing berry-type fruits and for experimental studies of the Solanaceae family of plants due to its conserved genetic organization. In this study, a comprehensive mutant tomato population was generated in the background of Micro-Tom, a dwarf, rapid-growth variety. In this and previous studies, a family including 8,598 and 6,422 M(2) mutagenized lines was produced by ethylmethane sulfonate (EMS) mutagenesis and γ-ray irradiation, and this study developed and investigated these M(2) plants for alteration of visible phenotypes. A total of 9,183 independent M(2) families comprising 91,830 M(2) plants were inspected for phenotypic alteration, and 1,048 individual mutants were isolated. Subsequently, the observed mutant phenotypes were classified into 15 major categories and 48 subcategories. Overall, 1,819 phenotypic categories were found in 1,048 mutants. Of these mutants, 549 were pleiotropic, whereas 499 were non-pleiotropic. Multiple different mutant alleles per locus were found in the mutant libraries, suggesting that the mutagenized populations were nearly saturated. Additionally, genetic analysis of backcrosses indicated the successful inheritance of the mutations in BC(1)F(2) populations, confirming the reproducibility in the morphological phenotyping of the M(2) plants. To integrate and manage the visible phenotypes of mutants and other associated data, we developed the in silico database TOMATOMA, a relational system interfacing modules between mutant line names and phenotypic categories. TOMATOMA is a freely accessible database, and these mutant recourses are available through the TOMATOMA (http://tomatoma.nbrp.jp/index.jsp). PMID:21258066

  12. TOMATOMA: A Novel Tomato Mutant Database Distributing Micro-Tom Mutant Collections

    PubMed Central

    Saito, Takeshi; Ariizumi, Tohru; Okabe, Yoshihiro; Asamizu, Erika; Hiwasa-Tanase, Kyoko; Fukuda, Naoya; Mizoguchi, Tsuyoshi; Yamazaki, Yukiko; Aoki, Koh; Ezura, Hiroshi

    2011-01-01

    The tomato is an excellent model for studies of plants bearing berry-type fruits and for experimental studies of the Solanaceae family of plants due to its conserved genetic organization. In this study, a comprehensive mutant tomato population was generated in the background of Micro-Tom, a dwarf, rapid-growth variety. In this and previous studies, a family including 8,598 and 6,422 M2 mutagenized lines was produced by ethylmethane sulfonate (EMS) mutagenesis and γ-ray irradiation, and this study developed and investigated these M2 plants for alteration of visible phenotypes. A total of 9,183 independent M2 families comprising 91,830 M2 plants were inspected for phenotypic alteration, and 1,048 individual mutants were isolated. Subsequently, the observed mutant phenotypes were classified into 15 major categories and 48 subcategories. Overall, 1,819 phenotypic categories were found in 1,048 mutants. Of these mutants, 549 were pleiotropic, whereas 499 were non-pleiotropic. Multiple different mutant alleles per locus were found in the mutant libraries, suggesting that the mutagenized populations were nearly saturated. Additionally, genetic analysis of backcrosses indicated the successful inheritance of the mutations in BC1F2 populations, confirming the reproducibility in the morphological phenotyping of the M2 plants. To integrate and manage the visible phenotypes of mutants and other associated data, we developed the in silico database TOMATOMA, a relational system interfacing modules between mutant line names and phenotypic categories. TOMATOMA is a freely accessible database, and these mutant recourses are available through the TOMATOMA (http://tomatoma.nbrp.jp/index.jsp). PMID:21258066

  13. The Fourier-Kelvin Stellar Interferometer (FKSI) Nulling Testbed II: Closed-loop Path Length Metrology And Control Subsystem

    NASA Technical Reports Server (NTRS)

    Frey, B. J.; Barry, R. K.; Danchi, W. C.; Hyde, T. T.; Lee, K. Y.; Martino, A. J.; Zuray, M. S.

    2006-01-01

    The Fourier-Kelvin Stellar Interferometer (FKSI) is a mission concept for an imaging and nulling interferometer in the near to mid-infrared spectral region (3-8 microns), and will be a scientific and technological pathfinder for upcoming missions including TPF-I/DARWIN, SPECS, and SPIRIT. At NASA's Goddard Space Flight Center, we have constructed a symmetric Mach-Zehnder nulling testbed to demonstrate techniques and algorithms that can be used to establish and maintain the 10(exp 4) null depth that will be required for such a mission. Among the challenges inherent in such a system is the ability to acquire and track the null fringe to the desired depth for timescales on the order of hours in a laboratory environment. In addition, it is desirable to achieve this stability without using conventional dithering techniques. We describe recent testbed metrology and control system developments necessary to achieve these goals and present our preliminary results.

  14. Escherichia coli mutants deficient in exonuclease VII.

    PubMed Central

    Chase, J W; Richardson, C C

    1977-01-01

    Mutants of Escherichia coli having reduced levels of exonuclease VII activity have been isolated by a mass screening procedure. Nine mutants, five of which are known to be of independent origin, were obtained and designated xse. The defects in these strains lie at two or more loci. One of these loci, xseA, lies in the interval between purG and purC; it is 93 to 97% co-transducible with guaA. The order of the genes in this region is purG-xseA guaA,B-purC. The available data do not allow xseA to be ordered with respect to guaA,B. Exonuclease VII purified from E. coli KLC3 xseA3 is more heat labile than exonuclease VII purified from the parent, E. coli PA610 xse+. Therefore, xseA is the structural gene for exonuclease VII. Mutants with defects in the xseA gene show increased sensitivity to nalidixic acid and have an abnormally high frequency of recombination (hyper-Rec phenotype) as measured by the procedure of Konrad and Lehlman (1974). The hyper-Rec character of xseA strains is approximately one-half that of the polAex1 mutant defective in the 5' leads to 3' hydrolytic activity of deoxyribonucleic acid polymerase I. The double mutant, polAex1 xseA7, is twice as hyper-Rec as the polAex1 mutant alone. The xseA- strains are slightly more sensitive to ultraviolet irradiation than the parent strain. Bacteriophages T7, fd, and lambdared grow normally in xseA- strains. Images PMID:320198

  15. Neurospora crassa mutants deficient in asparagine synthetase.

    PubMed Central

    MacPhee, K G; Nelson, R E; Schuster, S M

    1983-01-01

    Neurospora crassa mutants deficient in asparagine synthetase were selected by using the procedure of inositol-less death. Complementation tests among the 100 mutants isolated suggested that their alterations were genetically allelic. Recombination analysis with strain S1007t, an asparagine auxotroph, indicated that the mutations were located near or within the asn gene on linkage group V. In vitro assays with a heterokaryon indicated that the mutation was dominant. Thermal instability of cell extracts from temperature-sensitive strains in an in vitro asparagine synthetase assay determined that the mutations were in the structural gene(s) for asparagine synthetase. PMID:6137480

  16. Evolutionary Mutant Models for Human Disease

    PubMed Central

    Albertson, R. Craig; Cresko, William; Detrich, H. William; Postlethwait, John H.

    2010-01-01

    Although induced mutations in traditional laboratory animals have been valuable as models for human diseases, they have some important limitations. Here we propose a complementary approach to discover genes and mechanisms that might contribute to human disorders: the analysis of evolutionary mutant models whose adaptive phenotypes mimic maladaptive human diseases. If the type and mode of action of mutations favored by natural selection in wild populations are similar to those that contribute to human diseases, then studies in evolutionary mutant models have the potential to identify novel genetic factors and gene-by-environment interactions that affect human health and underlie human disease. PMID:19108930

  17. Testing of the Mirrors for the Constellation-X Spectroscopy X-ray Telescope with a Refractive Null

    NASA Technical Reports Server (NTRS)

    Lehan, John; Hadimichael, T.; Skocik, C.

    2007-01-01

    We present an introduction to the use of a refractive null lens for testing grazing incidence x-ray mirrors for the Constellation-X mission. The singular role of mirror mounting in glass shell mirror metrology is also touched upon. We compare results achieved to date with mission requirements along with some of the unique properties of the null lens. Additionally, uses beyond mirror metrology are briefly discussed.

  18. Lanthionine ketimine ethyl ester partially rescues neurodevelopmental defects in unc-33 (DPYSL2/CRMP2) mutants.

    PubMed

    Hubbard, Caleb; Benda, Erica; Hardin, Tyler; Baxter, Taylor; St John, Elizabeth; O'Brien, Sean; Hensley, Kenneth; Holgado, Andrea M

    2013-09-01

    Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite with potent neurotrophic activity. Proteomics indicate that LK interacts with collapsin response mediator protein-2 (CRMP2/DPYSL2/UNC-33), a brain-enriched protein that was shown to regulate cytoskeletal remodeling, neuronal morphology, and synaptic function. To elucidate further the molecular interplay and biological action of LK and UNC-33, we began examining the nervous system of Caenorhabditis elegans nematodes in which both LK concentrations and UNC-33 protein were manipulated. To this end, a cell-permeable LK-ester (LKE) was administered to developing C. elegans engineered to express yellow fluorescent protein (YFP) in cholinergic neurons (strain RM3128) or green fluorescent protein (GFP) in GABAergic neurons (strain CZ1200), and neural morphology was assessed. Fluorescent imaging analyses show that LKE exposure to wild-type animals induced neural commissure outgrowth, crossing over, and bundling in both neurites from GABAergic and cholinergic motor neurons. Additionally, when unc-33(e204) hypomorph mutant nematodes (D389N substitution mutants) were exposed to LKE, both the neuroanatomical defects of incomplete dorsoventral neural commissures and the ventral nerve cord gaps were partially rescued. In contrast, LKE did not rescue ventral nerve cord gaps found in unc-33(mn407) null mutant. Together these data suggest possible functions for LK as a regulator of neuritic elongation, corroborate roles for UNC-33/CRMP2 in the mechanism of LKE activity, and suggest the potential of LKE as a therapeutic molecule for neurological diseases involving CRMP2 dysfunction. PMID:23825043

  19. Precocious metamorphosis in the juvenile hormone-deficient mutant of the silkworm, Bombyx mori.

    PubMed

    Daimon, Takaaki; Kozaki, Toshinori; Niwa, Ryusuke; Kobayashi, Isao; Furuta, Kenjiro; Namiki, Toshiki; Uchino, Keiro; Banno, Yutaka; Katsuma, Susumu; Tamura, Toshiki; Mita, Kazuei; Sezutsu, Hideki; Nakayama, Masayoshi; Itoyama, Kyo; Shimada, Toru; Shinoda, Tetsuro

    2012-01-01

    Insect molting and metamorphosis are intricately governed by two hormones, ecdysteroids and juvenile hormones (JHs). JHs prevent precocious metamorphosis and allow the larva to undergo multiple rounds of molting until it attains the proper size for metamorphosis. In the silkworm, Bombyx mori, several "moltinism" mutations have been identified that exhibit variations in the number of larval molts; however, none of them have been characterized molecularly. Here we report the identification and characterization of the gene responsible for the dimolting (mod) mutant that undergoes precocious metamorphosis with fewer larval-larval molts. We show that the mod mutation results in complete loss of JHs in the larval hemolymph and that the mutant phenotype can be rescued by topical application of a JH analog. We performed positional cloning of mod and found a null mutation in the cytochrome P450 gene CYP15C1 in the mod allele. We also demonstrated that CYP15C1 is specifically expressed in the corpus allatum, an endocrine organ that synthesizes and secretes JHs. Furthermore, a biochemical experiment showed that CYP15C1 epoxidizes farnesoic acid to JH acid in a highly stereospecific manner. Precocious metamorphosis of mod larvae was rescued when the wild-type allele of CYP15C1 was expressed in transgenic mod larvae using the GAL4/UAS system. Our data therefore reveal that CYP15C1 is the gene responsible for the mod mutation and is essential for JH biosynthesis. Remarkably, precocious larval-pupal transition in mod larvae does not occur in the first or second instar, suggesting that authentic epoxidized JHs are not essential in very young larvae of B. mori. Our identification of a JH-deficient mutant in this model insect will lead to a greater understanding of the molecular basis of the hormonal control of development and metamorphosis. PMID:22412378

  20. Maize mutants lacking chloroplast FtsY exhibit pleiotropic defects in the biogenesis of thylakoid membranes.

    PubMed

    Asakura, Yukari; Hirohashi, Toshiya; Kikuchi, Shingo; Belcher, Susan; Osborne, Erin; Yano, Satoshi; Terashima, Ichiro; Barkan, Alice; Nakai, Masato

    2004-01-01

    A chloroplast signal recognition particle (SRP) that is related to the SRP involved in secretion in bacteria and eukaryotic cells is used for the insertion of light-harvesting chlorophyll proteins (LHCPs) into the thylakoid membranes. A conserved component of the SRP mechanism is a membrane-bound SRP receptor, denoted FtsY in bacteria. Plant genomes encode FtsY homologs that are targeted to the chloroplast (cpFtsY). To investigate the in vivo roles of cpFtsY, we characterized maize cpFtsY and maize mutants having a Mu transposon insertion in the corresponding gene (chloroplast SRP receptor1, or csr1). Maize cpFtsY accumulates to much higher levels in leaf tissue than in roots and stems. Interestingly, it is present at similar levels in etiolated and green leaf tissue and was found to bind the prolamellar bodies of etioplasts. A null cpFtsY mutant, csr1-1, showed a substantial loss of leaf chlorophyll, whereas a "leaky" allele, csr1-3, conditioned a more moderate chlorophyll deficiency. Both alleles caused the loss of various LHCPs and the thylakoid-bound photosynthetic enzyme complexes and were seedling lethal. By contrast, levels of the membrane-bound components of the thylakoid protein transport machineries were not altered. The thylakoid membranes in csr1-1 chloroplasts were unstacked and reduced in abundance, but the prolamellar bodies in mutant etioplasts appeared normal. These results demonstrate the essentiality of cpFtsY for the biogenesis not only of the LHCPs but also for the assembly of the other membrane-bound components of the photosynthetic apparatus. PMID:14688289