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Sample records for cells lumican null

  1. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

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    Hongshan Liu

    Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

  2. Lumican reduces tumor growth via induction of fas-mediated endothelial cell apoptosis.

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    Williams, Kent E; Fulford, Logan A; Albig, Allan R

    2010-11-18

    Matrikines are important components of tumor microenvironments that integrate communication between extracellular matricies and membrane-bound receptors thereby regulating cellular behaviors. One such matrikine that is differentially expressed in cancer microenvironments is the extracellular matrix protein lumican; however its precise role in cancer remains ambiguous. To study the effects of lumican on cancer cells, we created lumican-overexpressing cell lines from murine fibrosarcoma (MCA102) and pancreatic adenocarcinoma (Pan02) cells. Lumican overexpression in Pan02 cells increased invasiveness, decreased soft agar colony size, and increased proliferation. Conversely in MCA102 cells, lumican decreased invasiveness, increased soft agar colony size, but did not influence proliferation. In contrast to these pleiotropic in vitro results, lumican overexpression within the in vivo tumor microenvironment produced uniformly smaller tumors. Importantly, reduced tumor size was correlated with reduced vascular density. Consistent with lumican's proposed anti-angiogenic activity, lumican increased endothelial cell apoptosis. Importantly, lumican was previously shown to influence Fas expression and our results show that lumican enhanced Fas mediated endothelial cell apoptosis although we were unable to detect any difference in Fas or Fas ligand expression between lumican-overexpressing and control cells. Interestingly, lumican had no effect on MCA102 apoptosis, suggesting that the observed reduction in tumor size is specifically due to endothelial cell apoptosis rather than a direct effect on the cancerous cells themselves. Therefore, this study is the first to demonstrate a causal relationship between tumor reduction and lumican's effect on angiogenesis as opposed to an effect on the cancerous cells themselves.

  3. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint

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    K. Okamoto

    2015-02-01

    Full Text Available Several epidemiological studies have reported that temporomandibular disorders (TMDs are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular joint (TMJ is made up of connective tissue with an extracellular matrix (ECM composed of collagen and proteoglycan. One proteoglycan family, comprised of small leucine-rich repeat proteoglycans (SLRPs, was found to be involved in collagen fibril formation and interaction. In recent years, the participation of SLRPs such as lumican and fibromodulin in the internal derangement of TMJ has been suggested. Although these SLRPs may contribute to the restoration of the synovium, their effect is still unclear. The purpose of this study was to investigate the effect of DHEA, a sex hormone, on the expression of lumican and fibromodulin in human temporomandibular specimens and in cultured human TMJ fibroblast-like synovial cells in the presence or absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta. In the in vivo study, both normal and osteoarthritic (OA human temporomandibular synovial tissues were immunohistochemically examined. In the in vitro study, five fibroblast-like synoviocyte (FLS cell lines were established from human TMJ synovial tissue of patients with osteoarthritis. The subcultured cells were then incubated for 3, 6, 12 or 24 h with/without IL-1beta (1 ng/mL in the presence or absence of DHEA (10 μM. The gene expression of lumican and fibromodulin was examined using the real-time polymerase chain reaction (PCR and their protein expression was examined using immunofluorescent staining. We demonstrated that the expression of lumican

  4. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint.

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    Okamoto, K; Kiga, N; Shinohara, Y; Tojyo, I; Fujita, S

    2015-02-23

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular joint (TMJ) is made up of connective tissue with an extracellular matrix (ECM) composed of collagen and proteoglycan. One proteoglycan family, comprised of small leucine-rich repeat proteoglycans (SLRPs), was found to be involved in collagen fibril formation and interaction. In recent years, the participation of SLRPs such as lumican and fibromodulin in the internal derangement of TMJ has been suggested. Although these SLRPs may contribute to the restoration of the synovium, their effect is still unclear. The purpose of this study was to investigate the effect of DHEA, a sex hormone, on the expression of lumican and fibromodulin in human temporomandibular specimens and in cultured human TMJ fibroblast-like synovial cells in the presence or absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). In the in vivo study, both normal and osteoarthritic (OA) human temporomandibular synovial tissues were immunohistochemically examined. In the in vitro study, five fibroblast-like synoviocyte (FLS) cell lines were established from human TMJ synovial tissue of patients with osteoarthritis. The subcultured cells were then incubated for 3, 6, 12 or 24 h with/without IL-1beta (1 ng/mL) in the presence or absence of DHEA (10 μM). The gene expression of lumican and fibromodulin was examined using the real-time polymerase chain reaction (PCR) and their protein expression was examined using immunofluorescent staining. We demonstrated that the expression of lumican significantly

  5. TNF-α-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation.

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    Pilling, Darrell; Vakil, Varsha; Cox, Nehemiah; Gomer, Richard H

    2015-09-22

    In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis.

  6. Expression of lumican related to CD34 and VEGF in the articular disc of the human temporomandibular joint.

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    N. Kiga

    2010-07-01

    Full Text Available Lumican belongs to the small leucine-rich repeat proteoglycan (SLRP gene family and has been reported to exist in the cornea, intervertebral disc and tendon. Lumican plays a significant role in the assembly and regulation of collagen fibres. The human temporomandibular joint (TMJ disc is made up of fibrocartilage with an extracellular matrix (ECM composed of collagen and proteoglycans. The existence and behaviour of lumican have not been studied in the human TMJ disc. Therefore, we used immunohistochemical methods to detect lumican, CD34 and vascular endothelial growth factor (VEGF and histochemical staining with toluidine blue in 13 human TMJ specimens (10 surgically removed and 3 obtained from autopsy. In both normal and deformed discs we observed staining with toluidine blue. We found that the area of metachromasia inside the deformed disc was uneven and expression of lumican was strong in the areas negative for metachromasia. Staining of VEGF and CD34 inside the deformed disc was seen. We confirmed the expression of lumican in the human TMJ disc and showed that a large number of fibroblastlike cells existed in the area of strong lumican expression. These new findings about the behaviour of lumican suggest that it may play a key role in the generation of a new collagen network by fibroblast-like cells.

  7. Causal cells: spacetime polytopes with null hyperfaces

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    Neiman, Yasha

    2012-01-01

    We consider polyhedra and 4-polytopes in Minkowski spacetime - in particular, null polyhedra with zero volume, and 4-polytopes that have such polyhedra as their hyperfaces. We present the basic properties of several classes of null-faced 4-polytopes: 4-simplices, "tetrahedral diamonds" and 4-parallelotopes. We propose a "most regular" representative of each class. The most-regular parallelotope is of particular interest: its edges, faces and hyperfaces are all congruent, and it features both null hyperplanes and null segments. A tiling of spacetime with copies of this polytope can be viewed alternatively as a lattice with null edges, such that each point is at the intersection of four lightrays in a tetrahedral pattern. We speculate on the relevance of this construct for discretizations of curved spacetime and for quantum gravity.

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

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

    2016-05-15

    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.

  9. Pituitary null cell adenoma in a domestic llama (Lama glama).

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    Chalkley, M D; Kiupel, M; Draper, A C E

    2014-07-01

    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama.

  10. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

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    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities.

  11. Stem cell expansion during carcinogenesis in stem cell-depleted conditional telomeric repeat factor 2 null mutant mice.

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    Bojovic, B; Ho, H-Y; Wu, J; Crowe, D L

    2013-10-24

    To examine the role of telomeric repeat-binding factor 2 (TRF2) in epithelial tumorigenesis, we characterized conditional loss of TRF2 expression in the basal layer of mouse epidermis. These mice exhibit some characteristics of dyskeratosis congenita, a human stem cell depletion syndrome caused by telomere dysfunction. The epidermis in conditional TRF2 null mice exhibited DNA damage response and apoptosis, which correlated with stem cell depletion. The stem cell population in conditional TRF2 null epidermis exhibited shorter telomeres than those in control mice. Squamous cell carcinomas induced in conditional TRF2 null mice developed with increased latency and slower growth due to reduced numbers of proliferating cells as the result of increased apoptosis. TRF2 null epidermal stem cells were found in both primary and metastatic tumors. Despite the low-grade phenotype of the conditional TRF2 null primary tumors, the number of metastatic lesions was similar to control cancers. Basal cells from TRF2 null tumors demonstrated extreme telomere shortening and dramatically increased numbers of telomeric signals by fluorescence in situ hybridization due to increased genomic instability and aneuploidy in these cancers. DNA damage response signals were detected at telomeres in TRF2 null tumor cells from these mice. The increased genomic instability in these tumors correlated with eightfold expansion of the transformed stem cell population compared with that in control cancers. We concluded that genomic instability resulting from loss of TRF2 expression provides biological advantages to the cancer stem cell population.

  12. A Transmit Beamforming and Nulling Approach with Distributed Scheduling to Improve Cell Edge Throughput

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    Wendy C. Wong

    2010-01-01

    Full Text Available We propose a transmit scheme for WiMAX systems, where multiple base stations (BSs employ downlink transmit beamforming and nulling for interference mitigation, with minimal coordination amongst BSs. This scheme improves system throughput and robustness, by increasing cell edge and overall cell throughputs by 68% and 19%, respectively, and by delivering improvement for mobile speed up to 60 km/h. First, cell edge users suffering from severe interferences are identified. Next, the RRM unit allocates resource to serving cell edge users only. BSs will schedule to serve their cell edge users independently using the allocated resources by the RRM. A special uplink sounding region is designed for BSs to learn the interference environment and form proper beams and nulls. The nulls formed towards users served by other BSs reduced interference from a BS towards these users and is the basic building block of our algorithm.

  13. Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics.

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    Pieper, J; Johansson, S; Snir, O; Linton, L; Rieck, M; Buckner, J H; Winqvist, O; van Vollenhoven, R; Malmström, V

    2014-02-01

    Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population.

  14. Absence of C-type virus production in human leukemic B cell, T cell and null cell lines.

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    Ogura,Hajime

    1978-06-01

    Full Text Available Electron microscope observation of cultured human leukemic B cell, T cell and null cell lines and reverse transcriptase assay of the culture supernatants were all negative for the presence of C-type virus. Bat cell line, which propagates primate C-type viruses well, was cocultivated with the human leukemic cell lines, in the hope of amplification of virus if present. Three weeks after mixed culture, the culture supernatants were again examined for reverse transcriptase activity and the cells were tested for syncytia formation by cocultivation with rat XC, human KC and RSb cell lines. All these tests, except for the positive control using a simian sarcoma virus, were negative, suggesting that no C-type was produced from these human leukemic cell lines.

  15. Statins in lymphangioleiomyomatosis. Simvastatin and atorvastatin induce differential effects on tuberous sclerosis complex 2-null cell growth and signaling.

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    Atochina-Vasserman, Elena N; Goncharov, Dmitry A; Volgina, Alla V; Milavec, Megan; James, Melane L; Krymskaya, Vera P

    2013-11-01

    Mutations of the tumor suppressor genes tuberous sclerosis complex (TSC)1 and TSC2 cause pulmonary lymphangioleiomyomatosis (LAM) and tuberous sclerosis (TS). Current rapamycin-based therapies for TS and LAM have a predominantly cytostatic effect, and disease progression resumes with therapy cessation. Evidence of RhoA GTPase activation in LAM-derived and human TSC2-null cells suggests that 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor statins can be used as potential adjuvant agents. The goal of this study was to determine which statin (simvastatin or atorvastatin) is more effective in suppressing TSC2-null cell growth and signaling. Simvastatin, but not atorvastatin, showed a concentration-dependent (0.5-10 μM) inhibitory effect on mouse TSC2-null and human LAM-derived cell growth. Treatment with 10 μM simvastatin induced dramatic disruption of TSC2-null cell monolayer and cell rounding; in contrast, few changes were observed in cells treated with the same concentration of atorvastatin. Combined treatment of rapamycin with simvastatin but not with atorvastatin showed a synergistic growth-inhibitory effect on TSC2-null cells. Simvastatin, but not atorvastatin, inhibited the activity of prosurvival serine-threonine kinase Akt and induced marked up-regulation of cleaved caspase-3, a marker of cell apoptosis. Simvastatin, but not atorvastatin, also induced concentration-dependent inhibition of p42/p44 Erk and mTORC1. Thus, our data show growth-inhibitory and proapoptotic effects of simvastatin on TSC2-null cells compared with atorvastatin. These findings have translational significance for combinatorial therapeutic strategies of simvastatin to inhibit TSC2-null cell survival in TS and LAM.

  16. Isolation and characterization of calcium sensing receptor null cells: a highly malignant and drug resistant phenotype of colon cancer.

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    Singh, Navneet; Liu, Guangming; Chakrabarty, Subhas

    2013-05-01

    The expression of calcium sensing receptor (CaSR) in the human colonic crypt epithelium is linked to cellular differentiation while its lack of expression is associated with undifferentiated and invasive colon carcinoma. Human colon carcinoma cell lines contain small subpopulations (10-20%) that do not express CaSR (termed CaSR null cells). Here, we report on the isolation, propagation, maintenance and characterization of CaSR null cells from the CBS and HCT116 human colon carcinoma cell lines. CaSR null cells grew as three-dimensional non-adherent spherical clusters with increased propensity for anchorage independent growth, cellular proliferation and invasion of matrigels. CaSR null cells were highly resistant to fluorouracil and expressed abundant amount of thymidylate synthase and survivin. Molecular profiling by real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blots showed a high level of expression of the previously reported cancer stem cell markers CD133, CD44 and Nanog in CaSR null cells. A significant increase in the expression of epithelial-mesenchymal transitional molecules and transcription factors was also observed. These include N-cadherin, β-catenin, vimentin, fibronectin, Snail1, Snail2, Twist and FOXC2. The expression of the tumor suppressive E-cadherin and miR145, on the other hand, was greatly reduced while expression of the oncogenic microRNAs: miR21, miR135a and miR135b was significantly up-regulated. CaSR null cells possess a myriad of cellular and molecular features that drive and sustain the malignant phenotype. We conclude that CaSR null constitutes a highly malignant and drug resistant phenotype of colon cancer.

  17. Induction of CaSR expression circumvents the molecular features of malignant CaSR null colon cancer cells.

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    Singh, Navneet; Chakrabarty, Subhas

    2013-11-15

    We recently reported on the isolation and characterization of calcium sensing receptor (CaSR) null human colon cancer cells (Singh et al., Int J Cancer 2013; 132: 1996-2005). CaSR null cells possess a myriad of molecular features that are linked to a highly malignant and drug resistant phenotype of colon cancer. The CaSR null phenotype can be maintained in defined human embryonic stem cell culture medium. We now show that the CaSR null cells can be induced to differentiate in conventional culture medium, regained the expression of CaSR with a concurrent reversal of the cellular and molecular features associated with the null phenotype. These features include cellular morphology, expression of colon cancer stem cell markers, expression of survivin and thymidylate synthase and sensitivity to fluorouracil. Other features include the expression of epithelial mesenchymal transition linked molecules and transcription factors, oncogenic miRNAs and tumor suppressive molecule and miRNA. With the exception of cancer stem cell markers, the reversal of molecular features, upon the induction of CaSR expression, is directly linked to the expression and function of CaSR because blocking CaSR induction by shRNA circumvented such reversal. We further report that methylation and demethylation of the CaSR gene promoter underlie CaSR expression. Due to the malignant nature of the CaSR null cells, inclusion of the CaSR null phenotype in disease management may improve on the mortality of this disease. Because CaSR is a robust promoter of differentiation and mediates its action through diverse mechanisms and pathways, inactivation of CaSR may serve as a new paradigm in colon carcinogenesis.

  18. Heterotransplantation of human leukemic B-cell, T-cell and null-cell lines in hamsters.

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    Hiraki,Shunkichi

    1979-02-01

    Full Text Available Human leukemic B-cell (BALL-1, T-cell (TALL-1 and null-cell (NALL-1 lines have been established from three patients with acute lymphoblastic leukemia (ALL. To study the heterotransplantability and in vivo growth characteristics, attempts were made to transplant these ALL cell lines into newborn Syrian hamsters treated with rabbit anti-hamster thymocyte serum. Intraperitoneal implantation of 1.8-3.5 x 10(7 cells gave rise to invasive tumors in all recipients after 15 to 41 days. In addition to a common in vivo feature of mesenteric and retroperitoneal tumors, BALL-1 line was characterized by infiltration of the skin, massive ascites and bone marrow invasion. TALL-1 cells infiltrated various organs including the lymph nodes, liver, gallbladder, spleen, bone marrow, central nervous system and eyes. NALL-1 line grew slowly, producing the least tumors, although there were distant metastases in the lungs. Tumor cells were detected in the blood of 2 of 3 BALL-1-bearing hamsters and in the blood of 4 of 5 TALL-1-bearing hamsters. Thus, these three ALL cell lines were found to exhibit a characteristic biological behavior in hamsters, which might be related to the different cell lineage.

  19. Naphthoquinone Derivative PPE8 Induces Endoplasmic Reticulum Stress in p53 Null H1299 Cells

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    Jin-Cherng Lien

    2015-01-01

    Full Text Available Endoplasmic reticulum (ER plays a key role in synthesizing secretory proteins and sensing signal function in eukaryotic cells. Responding to calcium disturbance, oxidation state change, or pharmacological agents, ER transmembrane protein, inositol-regulating enzyme 1 (IRE1, senses the stress and triggers downstream signals. Glucose-regulated protein 78 (GRP78 dissociates from IRE1 to assist protein folding and guard against cell death. In prolonged ER stress, IRE1 recruits and activates apoptosis signal-regulating kinase 1 (ASK1 as well as downstream JNK for cell death. Naphthoquinones are widespread natural phenolic compounds. Vitamin K3, a derivative of naphthoquinone, inhibits variant tumor cell growth via oxygen uptake and oxygen stress. We synthesized a novel naphthoquinone derivative PPE8 and evaluated capacity to induce ER stress in p53 null H1299 and p53 wild-type A549 cells. In H1299 cells, PPE8 induced ER enlargement, GRP78 expression, and transient IER1 activation. Activated IRE1 recruited ASK1 for downstream JNK phosphorylation. IRE1 knockdown by siRNA attenuated PPE8-induced JNK phosphorylation and cytotoxicity. Prolonged JNK phosphorylation may be involved in PPE8-induced cytotoxicity. Such results did not arise in A549 cells, but p53 knockdown by siRNA restored PPE8-induced GRP78 expression and JNK phosphorylation. We offer a novel compound to induce ER stress and cytotoxicity in p53-deficient cancer cells, presenting an opportunity for treatment.

  20. c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets

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    Bush, Andrew; Mateyak, Maria; Dugan, Kerri; Obaya, Alvaro; Adachi, Susumu; Sedivy, John; Cole, Michael

    1998-01-01

    We report here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion of c-myc. Two noteworthy exceptions are the gene cad, which has reduced log phase expression and serum induction in c-myc null cells, and the growth arrest gene gadd45, which is derepressed by c-myc knockout. Thus, cad and gadd45 are the only proposed targets of c-Myc that may contribute to the dramatic slow growth phenotype of c-myc null cells. Our results demonstrate that a loss-of-function approach is critical for the evaluation of potential c-Myc target genes. PMID:9869632

  1. Identification of a subtype-specific ENC1 gene related to invasiveness in human pituitary null cell adenoma and oncocytomas.

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    Feng, Jie; Hong, Lichuan; Wu, Yonggang; Li, Chuzhong; Wan, Hong; Li, Guilin; Sun, Yilin; Yu, Shenyuan; Chittiboina, Prashant; Montgomery, Blake; Zhuang, Zhengping; Zhang, Yazhuo

    2014-09-01

    Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Surgery is a treatment option, but unlike the case for functional pituitary adenomas, there are almost no drug treatments available for NFPAs. Markers of invasiveness are needed to guide therapeutic decision-making and identify potential adjuvant drugs. Owing to the highly heterogeneous nature of NFPAs, little is known regarding the subtype-specific gene expression profiles associated with invasiveness. To identify important biomarkers of invasiveness, we selected 23 null cell adenomas and 20 oncocytomas. These tumors were classified as invasive or non-invasive adenomas based on magnetic resonance imaging, pathology slides and surgical findings. Firstly, we observed that there were significant differences in expression between invasive (n = 3) and non-invasive (n = 4) adenomas by gene expression microarray. A total of 1,188 genes were differentially expressed in the invasive and non-invasive adenomas. Among these 1,188 genes, 578 were upregulated and 610 were downregulated in invasive adenomas. Secondly, the expression of ENC1, which displayed the significant alterations, was further confirmed by qRT-PCR and Western blot analysis in all 43 tumor samples and three normal pituitary glands. Low levels of ENC1 were found in tumor samples, while high levels were detected in normal pituitary glands. Interestingly, the ENC1 expression level was low in invasive null cell adenomas compared with non-invasive adenomas, but this relationship was not observed in invasive oncocytomas. Immunohistochemistry also demonstrated that the staining of ENC1 was different between invasive and non-invasive null cell adenomas. In addition, bioinformatics studies, including gene ontology and protein interaction analyses, were also performed to better understand the critical role of ENC1 in the development and progression of null cell adenomas and oncocytomas. Consequently, ENC1 may be an important biomarker for null cell

  2. Impaired Lymphocytes Development and Xenotransplantation of Gastrointestinal Tumor Cells in Prkdc-Null SCID Zebrafish Model

    Directory of Open Access Journals (Sweden)

    In Hye Jung

    2016-08-01

    Full Text Available Severe combined immunodeficiency (SCID mice have widely been used as hosts for human tumor cell xenograft study. This animal model, however, is labor intensive. As zebrafish is largely emerging as a promising model system for studying human diseases including cancer, developing efficient immunocompromised strains for tumor xenograft study are also demanded in zebrafish. Here, we have created the Prkdc-null SCID zebrafish model which provides the stable immune-deficient background required for xenotransplantation of tumor cell. In this study, the two transcription activator-like effector nucleases that specifically target the exon3 of the zebrafish Prkdc gene were used to induce a frame shift mutation, causing a complete knockout of the gene function. The SCID zebrafish showed susceptibility to spontaneous infection, a well-known phenotype found in the SCID mutation. Further characterization revealed that the SCID zebrafish contained no functional T and B lymphocytes which reflected the phenotypes identified in the mice SCID model. Intraperitoneal injection of human cancer cells into the adult SCID zebrafish clearly showed tumor cell growth forming into a solid mass. Our present data show the suitability of using the SCID zebrafish strain for xenotransplantation experiments, and in vivo monitoring of the tumor cell growth in the zebrafish demonstrates use of the animal model as a new platform of tumor xenograft study.

  3. Null surfaces of null curves on 3-null cone

    Science.gov (United States)

    Sun, Jianguo; Pei, Donghe

    2014-03-01

    The null surfaces of null curves on 3-null cone have the applications in the studying of horizon types. Via the pseudo-scalar product and Frenet equations, the differential geometry of null curves on 3-null cone is obtained. In the local sense, the curvature describes the contact of submanifolds with pseudo-spheres. We introduce the geometric properties of the curvatures and show the singularities of null surfaces, which are constructed over the null curves.

  4. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma

    DEFF Research Database (Denmark)

    Zhang, Qian; Raghunath, Puthryaveett N; Xue, Liquan

    2002-01-01

    Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector...... known STATs was consistently tyrosine phosphorylated in these cell lines. In addition, malignant cells in tissue sections from all (10 of 10) ALK+ TCL patients expressed tyrosine-phosphorylated STAT3. Transfection of BaF3 cells with NPM/ALK resulted in tyrosine phosphorylation of STAT3. Furthermore...

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

    Science.gov (United States)

    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.

  6. Metabolic reprogramming for producing energy and reducing power in fumarate hydratase null cells from hereditary leiomyomatosis renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Youfeng Yang

    Full Text Available Fumarate hydratase (FH-deficient kidney cancer undergoes metabolic remodeling, with changes in mitochondrial respiration, glucose, and glutamine metabolism. These changes represent multiple biochemical adaptations in glucose and fatty acid metabolism that supports malignant proliferation. However, the metabolic linkages between altered mitochondrial function, nucleotide biosynthesis and NADPH production required for proliferation and survival have not been elucidated. To characterize the alterations in glycolysis, the Krebs cycle and the pentose phosphate pathways (PPP that either generate NADPH (oxidative or do not (non-oxidative, we utilized [U-(13C]-glucose, [U-(13C,(15N]-glutamine, and [1,2- (13C2]-glucose tracers with mass spectrometry and NMR detection to track these pathways, and measured the oxygen consumption rate (OCR and extracellular acidification rate (ECAR of growing cell lines. This metabolic reprogramming in the FH null cells was compared to cells in which FH has been restored. The FH null cells showed a substantial metabolic reorganization of their intracellular metabolic fluxes to fulfill their high ATP demand, as observed by a high rate of glucose uptake, increased glucose turnover via glycolysis, high production of glucose-derived lactate, and low entry of glucose carbon into the Krebs cycle. Despite the truncation of the Krebs cycle associated with inactivation of fumarate hydratase, there was a small but persistent level of mitochondrial respiration, which was coupled to ATP production from oxidation of glutamine-derived α-ketoglutarate through to fumarate. [1,2- (13C2]-glucose tracer experiments demonstrated that the oxidative branch of PPP initiated by glucose-6-phosphate dehydrogenase activity is preferentially utilized for ribose production (56-66% that produces increased amounts of ribose necessary for growth and NADPH. Increased NADPH is required to drive reductive carboxylation of α-ketoglutarate and fatty acid

  7. Metabolic reprogramming for producing energy and reducing power in fumarate hydratase null cells from hereditary leiomyomatosis renal cell carcinoma.

    Science.gov (United States)

    Yang, Youfeng; Lane, Andrew N; Ricketts, Christopher J; Sourbier, Carole; Wei, Ming-Hui; Shuch, Brian; Pike, Lisa; Wu, Min; Rouault, Tracey A; Boros, Laszlo G; Fan, Teresa W-M; Linehan, W Marston

    2013-01-01

    Fumarate hydratase (FH)-deficient kidney cancer undergoes metabolic remodeling, with changes in mitochondrial respiration, glucose, and glutamine metabolism. These changes represent multiple biochemical adaptations in glucose and fatty acid metabolism that supports malignant proliferation. However, the metabolic linkages between altered mitochondrial function, nucleotide biosynthesis and NADPH production required for proliferation and survival have not been elucidated. To characterize the alterations in glycolysis, the Krebs cycle and the pentose phosphate pathways (PPP) that either generate NADPH (oxidative) or do not (non-oxidative), we utilized [U-(13)C]-glucose, [U-(13)C,(15)N]-glutamine, and [1,2- (13)C2]-glucose tracers with mass spectrometry and NMR detection to track these pathways, and measured the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of growing cell lines. This metabolic reprogramming in the FH null cells was compared to cells in which FH has been restored. The FH null cells showed a substantial metabolic reorganization of their intracellular metabolic fluxes to fulfill their high ATP demand, as observed by a high rate of glucose uptake, increased glucose turnover via glycolysis, high production of glucose-derived lactate, and low entry of glucose carbon into the Krebs cycle. Despite the truncation of the Krebs cycle associated with inactivation of fumarate hydratase, there was a small but persistent level of mitochondrial respiration, which was coupled to ATP production from oxidation of glutamine-derived α-ketoglutarate through to fumarate. [1,2- (13)C2]-glucose tracer experiments demonstrated that the oxidative branch of PPP initiated by glucose-6-phosphate dehydrogenase activity is preferentially utilized for ribose production (56-66%) that produces increased amounts of ribose necessary for growth and NADPH. Increased NADPH is required to drive reductive carboxylation of α-ketoglutarate and fatty acid synthesis

  8. Berberine Induces Apoptosis in p53-Null Leukemia Cells by Down-Regulating XIAP at the Post-Transcriptional Level

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2013-11-01

    Full Text Available Background: Berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. However, the underlying molecular mechanisms of berberine induced p53-independent apoptosis remain unclear. Methods: The p53-null leukemia cell line EU-4 cells were exposed to berberine. Then the cell viability and apoptosis were determined. Western blot and PCR were employed to detect the expression of apoptosis related protein, XIAP and MDM2. Small interfering RNA (siRNA was applied to knock down endogenous expression of MDM2 and XIAP. Results: Berberine induced p53-independent, XIAP-mediated apoptotic cell death in p53-null leukemia cells. Treatment with berberine resulted in suppression of XIAP protein in a dose- and time- dependent manner. Berberine induced down-regulation of XIAP protein involving inhibition of MDM2 expression and a proteasome-dependent pathway. Moreover, inhibition of XIAP by berberine or siRNA increased the sensitivity of leukemia cells to doxorubicin-induced apoptosis. Conclusion: Our findings characterize the molecular mechanisms of berberine-induced caspase activation and subsequent apoptosis, and berberine may be a novel candidate inducer of apoptosis in leukemia cells, which normally lack p53 expression.

  9. Association between HLA-DRB1, HLA-DRQB1 alleles, and CD4(+)CD28(null) T cells in a Chinese population with coronary heart disease.

    Science.gov (United States)

    Sun, Wenjie; Cui, Ying; Zhen, Lihui; Huang, Lijuan

    2011-03-01

    CD4(+)CD28(null) T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome. However, the triggers of expansion of these cells are unclear. Susceptibility to coronary heart disease (CHD) is strongly associated with alleles of human leukocyte antigen (HLA), but it is not equally strong in different human populations. The objective of the study was to investigate association between CD4(+)CD28(null) T cells and HLA-DRB1 alleles. The HLA alleles were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) method, in a group of CHD patients and control subjects from the same area. The number of CD4(+)CD28(null) T cells was measured using the flow cytometry technique. The HLA-DRB1*01 (RR = 4.705, P Chinese population, and increased numbers of CD4(+)CD28(null) T cells were found in association with HLA-DRB1*04 (17.1%) and DRB*01 (12.9%), while decreased numbers of CD4(+)CD28(null) T cells were present in subjects with DRB1*15 (0.8%). CHD in Chinese population is strongly associated with HLA-DRB1*01 and DRB1*04 haplotypes, and formation of CD4(+)CD28(null) T cells was related to HLA-DRB1*01, DRB1*04, and DRB1*15 alleles.

  10. Cytomegalovirus-Associated CD4(+) CD28(null) Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction.

    Science.gov (United States)

    Shabir, S; Smith, H; Kaul, B; Pachnio, A; Jham, S; Kuravi, S; Ball, S; Chand, S; Moss, P; Harper, L; Borrows, R

    2016-04-01

    Emerging data suggest that expansion of a circulating population of atypical, cytotoxic CD4(+) T cells lacking costimulatory CD28 (CD4(+) CD28(null) cells) is associated with latent cytomegalovirus (CMV) infection. The purpose of the current study was to increase the understanding of the relevance of these cells in 100 unselected kidney transplant recipients followed prospectively for a median of 54 months. Multicolor flow cytometry of peripheral blood mononuclear cells before transplantation and serially posttransplantation was undertaken. CD4(+) CD28(null) cells were found predominantly in CMV-seropositive patients and expanded in the posttransplantation period. These cells were predominantly effector-memory phenotype and expressed markers of endothelial homing (CX3CR1) and cytotoxicity (NKG2D and perforin). Isolated CD4(+) CD27(-) CD28(null) cells proliferated in response to peripheral blood mononuclear cells previously exposed to CMV-derived (but not HLA-derived) antigens and following such priming incubation with glomerular endothelium resulted in signs of endothelial damage and apoptosis (release of fractalkine and von Willebrand factor; increased caspase 3 expression). This effect was mitigated by NKG2D-blocking antibody. Increased CD4(+) CD28(null) cell frequencies were associated with delayed graft function and lower estimated glomerular filtration rate at end follow-up. This study suggests an important role for this atypical cytotoxic CD4(+) CD28(null) cell subset in kidney transplantation and points to strategies that may minimize the impact on clinical outcomes.

  11. Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. II. A hybridoma secreting antibody against an antigen expressed by human B and null lymphocytes.

    Science.gov (United States)

    Beckman, I G; Bradley, J; Brooks, D A; Kupa, A; McNamara, P J; Thomas, M E; Zola, H

    1980-06-01

    A hybridoma (FMC4) has been derived which secretes antibody showing selective reaction with human B lymphocytes, monocytes and some null lymphocytes. Few, if any, T lymphocytes in normal blood are stained, although stimulation of lymphocytes with PHA leads to an increase in the proportion of cells reacting with the hybridoma antibody. The antibody reacts with B and null lymphoblastoid cell lines but not with T cell lines. B chronic lymphocytic leukaemia (CLL) cells but not T-CLLs are stained and null-type acute lymphoblastic leukaemia (ALL) cells but not T-type ALL also react. Normal blood myeloid cells do not react with FMC4 supernatant whilst some myeloid leukaemias do. The expression of the antigen reacting with FMC4 supernatant suggests that FMC4 may secrete an antibody against the human equivalent of the Ia antigen.

  12. Physapubescin selectively induces apoptosis in VHL-null renal cell carcinoma cells through down-regulation of HIF-2α and inhibits tumor growth

    Science.gov (United States)

    Chen, Lixia; Xia, Guiyang; Qiu, Feng; Wu, Chunli; Denmon, Andria P.; Zi, Xiaolin

    2016-01-01

    We have purified physapubescin, a predominant steroidal lactone, from medicinal plant Physalis pubescens L., commonly named as “hairy groundcherry” in English and “Deng-Long-Cao” in Chinese. Von Hippel-Lindau (VHL)-null 786-O, RCC4 and A498 Renal Cell Carcinoma (RCC) cell lines expressing high levels of Hypoxia Inducible Factor (HIF)-2α are more sensitive to physapubescin-mediated apoptosis and growth inhibitory effect than VHL wild-type Caki-2 and ACHN RCC cell lines. Restoration of VHL in RCC4 cells attenuated the growth inhibitory effect of physapubescin. Physapubescin decreases the expression of HIF-2α and increases the expression of CCAAT/enhancer-binding protein homologus protein (CHOP), which leads to up-regulation of death receptor 5 (DR5), activation of caspase-8 and -3, cleavage of poly (ADP-Ribose) polymerase (PARP) and apoptosis. Under hypoxia conditions, the apoptotic and growth inhibitory effects of physapubescin are further enhanced. Additionally, physapubescin synergizes with TNF-related apoptosis-inducing ligand (TRAIL) for markedly enhanced induction of apoptosis in VHL-null 786-O cells but not in VHL wild-type Caki-2 cells. Physapubescin significantly inhibited in vivo angiogenesis in the 786-O xenograft. Physapubescin as a novel agent for elimination of VHL-null RCC cells via apoptosis is warranted for further investigation. PMID:27581364

  13. Circulating CD4(+)CD28null T Cells May Increase the Risk of an Atherosclerotic Vascular Event Shortly after Kidney Transplantation.

    Science.gov (United States)

    Betjes, Michiel G H; Weimar, Willem; Litjens, Nicolle H R

    2013-01-01

    Proinflammatory CD4(+) T cells without the costimulatory molecule CD28 (CD4(+)CD28null T cells) are expanded in patients with end-stage renal disease (ESRD) and associated with atherosclerotic vascular events (AVE). In a prospective study, the number of circulating CD4(+)CD28null T cells was established in 295 ESRD patients prior to receiving a kidney allograft. Within the first year after transplantation, an AVE occurred in 20 patients. Univariate analysis showed that besides a history of cardiovascular disease (CVDpos, HR 8.1, P AVE. In a multivariate analysis, only CVDpos remained a significant risk factor with a significant and positive interaction between the terms CVDpos and the % of CD4(+)CD28null T cells (HR 1.05, 95% CI 1.03-1.11, P AVE was 13% in the lowest tertile compared to 25% in the highest tertile of % of CD4(+)CD28null T cells. In conclusion, the presence of circulating CD4(+)CD28null T cells is associated with an increased risk for a cardiovascular event shortly after kidney transplantation.

  14. Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution

    Directory of Open Access Journals (Sweden)

    Sercarz Eli E

    2011-07-01

    Full Text Available Abstract Background Non Obese Diabetic mice lacking B cells (NOD.Igμnull mice do not develop diabetes despite their susceptible background. Upon reconstitution of B cells using a chimera approach, animals start developing diabetes at 20 weeks of age. Methods We have used the spectratyping technique to follow the T cell receptor (TCR V beta repertoire of NOD.Igμnull mice following B cell reconstitution. This technique provides an unbiased approach to understand the kinetics of TCR expansion. We have also analyzed the TCR repertoire of reconstituted animals receiving cyclophosphamide treatment and following tissue transplants to identify common aggressive clonotypes. Results We found that B cell reconstitution of NOD.Igμnull mice induces a polyclonal TCR repertoire in the pancreas 10 weeks later, gradually diversifying to encompass most BV families. Interestingly, these clonotypic BV expansions are mainly confined to the pancreas and are absent from pancreatic lymph nodes or spleens. Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution reorganized the predominant TCR repertoires by removing potential regulatory clonotypes (BV1, BV8 and BV11 and increasing the frequency of others (BV4, BV5S2, BV9, BV16-20. These same clonotypes are more frequently present in neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted diabetic NOD.Igμnull mice, suggesting their higher invasiveness. Phenotypic analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell reconstituted animals show a predominance of CD19+ B cells with a B:T lymphocyte ratio of 4:1. In contrast, in other lymphoid organs (pancreatic lymph nodes and spleens analyzed by FACS, the B:T ratio was 1:1. Lymphocytes infiltrating the pancreas secrete large amounts of IL-6 and are of Th1 phenotype after CD3-CD28 stimulation in vitro. Conclusions Diabetes in NOD.Igμnull mice appears to be caused by a polyclonal repertoire of T cell

  15. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Coric, Vesna M; Simic, Tatjana P; Pekmezovic, Tatjana D; Basta-Jovanovic, Gordana M; Savic Radojevic, Ana R; Radojevic-Skodric, Sanja M; Matic, Marija G; Dragicevic, Dejan P; Radic, Tanja M; Bogdanovic, Ljiljana M; Dzamic, Zoran M; Pljesa-Ercegovac, Marija S

    2016-01-01

    The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and pnull, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC.

  16. In vitro generated Rh(null) red cells recapitulate the in vivo deficiency: a model for rare blood group phenotypes and erythroid membrane disorders.

    Science.gov (United States)

    Cambot, Marie; Mazurier, Christelle; Canoui-Poitrine, Florence; Hebert, Nicolas; Picot, Julien; Clay, Denis; Picard, Véronique; Ripoche, Pierre; Douay, Luc; Dubart-Kupperschmitt, Anne; Cartron, Jean-Pierre

    2013-05-01

    Lentiviral modification combined with ex vivo erythroid differentiation was used to stably inhibit RhAG expression, a critical component of the Rh(rhesus) membrane complex defective in the Rh(null) syndrome. The cultured red cells generated recapitulate the major alterations of native Rh(null) cells regarding antigen expression, membrane deformability, and gas transport function, providing the proof of principle for their use as model of Rh(null) syndrome and to investigate Rh complex biogenesis in human primary erythroid cells. Using this model, we were able to reveal for the first time that RhAG extinction alone is sufficient to explain ICAM-4 and CD47 loss observed on native Rh(null) RBCs. Together with the effects of RhAG forced expression in Rh(null) progenitors, this strongly strengthens the hypothesis that RhAG is critical to Rh complex formation. The strategy is also promising for diagnosis purpose in order to overcome the supply from rare blood donors and is applicable to other erythroid defects and rare phenotypes, providing models to dissect membrane biogenesis of multicomplex proteins in erythroid cells, with potential clinical applications in transfusion medicine.

  17. Long-term passage of Vif-null HIV-1 in CD4(+) T cells expressing sub-lethal levels of APOBEC proteins fails to develop APOBEC resistance.

    Science.gov (United States)

    Miyagi, Eri; Kao, Sandra; Fumitaka, Miyoshi; Buckler-White, Alicia; Plishka, Ron; Strebel, Klaus

    2017-04-01

    APOBEC3G (A3G) is a cytidine deaminase with potent antiviral activity that is antagonized by Vif. A3G is expressed in a cell type-specific manner and some semi-permissive cells, including A3.01, express A3G but fail to block replication of Vif-null HIV-1. Here we explored the semi-permissive nature of A3.01 cells and found it to be defined exclusively by the levels of A3G. Indeed, minor changes in A3G levels rendered A3.01 cells either fully permissive or non-permissive for Vif-null HIV-1. Our data indicate that A3.01 cells express sub-lethal levels of catalytically active A3G that affects Vif-null HIV-1 at the proviral level but does not completely block virus replication due to purifying selection. Attempts to use the selective pressure exerted by such sub-lethal levels of A3G to select for APOBEC-resistant Vif-null virus capable of replicating in H9 cells failed despite passaging virus for five months, demonstrating that Vif is a critical viral accessory protein.

  18. Heat Shock Proteins 60 and 70 Specific Proinflammatory and Cytotoxic Response of CD4+CD28null Cells in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ashok K. Yadav

    2013-01-01

    Full Text Available Background. CD4+CD28null T cells are expanded in peripheral blood of patients with chronic kidney disease and associated with subclinical atherosclerosis. However, triggers for the oligoclonal expansion and activation of these cells are not clear. Methods. We investigated twenty-five stage V-IV chronic kidney disease (CKD patients and eight healthy subjects (HC. Peripheral mononuclear cells were isolated and incubated with heat shock protein- (HSP 60 and 70. CD4+CD28null and CD4+CD28+ cells were sorted by flowcytometry and antigen specific response was assessed by the mRNA and protein expression of interferon (IFN-γ, perforin, and granzyme B using qRT-PCR and Elispot. Results. The basal mRNA expression of IFN-γ, perforin, and granzyme B in CD4+CD28null cells was higher in subjects with CKD compared to that in HC (P<0.0001. Subjects with CKD also showed expression of IFN-γ, perforin, and granzyme B in the CD4+CD28+ subset, but this was much weaker than that seen in the CD4+CD28null population (P<0.0001. We did not note the expression of these molecules at mRNA or protein level in either subset of CD4 cells in HC. After incubation with HSP60 and HSP70, CD4+CD28null cells showed increased expression at mRNA (P<0.001 and protein level (P<0.001. CD4+CD28+ cells also showed a weak increase in expression. No antigen-specific response was noted in HC. Conclusion. These data show that CD4+CD28null cells in subjects with CKD react with HSP60 and HSP70 by upregulating the expression of IFN-γ, perforin and granzyme B. Increased circulating level of HSP60 and HSP70 might play a role in initiation and/or progression of atherosclerosis in CKD subjects through perturbation of CD4+CD28null cells.

  19. Doxycycline inhibits matrix metalloproteinase-2 secretion from TSC2-null mouse embryonic fibroblasts and lymphangioleiomyomatosis cells

    NARCIS (Netherlands)

    Moir, L M; Ng, H Y; Poniris, M H; Santa, T; Burgess, J K; Oliver, B G G; Krymskaya, V P; Black, J L

    2011-01-01

    BACKGROUND AND PURPOSE: Lymphangioleiomyomatosis (LAM) is characterized by the abnormal growth of smooth muscle-like cells (LAM cells) and cystic destruction of the lung parenchyma. LAM cell-derived matrix metalloproteinases (MMPs) are thought to play a prominent role in the tissue destruction. The

  20. A role for TGFbeta1 in langerhans cell biology. Further characterization of the epidermal Langerhans cell defect in TGFbeta1 null mice.

    OpenAIRE

    Borkowski, T A; Letterio, J J; Mackall, C. L.; Saitoh, A; Wang, X. J.; Roop, D R; Gress, R. E.; Udey, M C

    1997-01-01

    Previous studies of TGFbeta1 null (-/-) mice indicated that the epidermis was devoid of Langerhans cells (LC) and that the LC deficiency was not secondary to the inflammation that is the dominant feature of the -/- phenotype (Borkowski, T.A., J.J. Letterio, A.G. Farr, and M.C. Udey. 1996. J. Exp. Med. 184:2417-2422). Herein, we demonstrate that dendritic cells could be expanded from the bone marrow of -/- mice and littermate controls. Bone marrow from -/- mice also gave rise to LC after trans...

  1. Argonaute-2-null embryonic stem cells are retarded in self-renewal and differentiation

    Indian Academy of Sciences (India)

    P Chandra Shekar; Adnan Naim; D Partha Sarathi; Satish Kumar

    2011-09-01

    RNA interference (RNAi) pathways regulate self-renewal and differentiation of embryonic stem (ES) cells. Argonaute 2 (Ago2) is a vital component of RNA-induced silencing complex (RISC) and the only Ago protein with slicer activity. We generated Ago2-deficient ES cells by conditional gene targeting. Ago2-deficient ES cells are defective in the small-RNA-mediated gene silencing and are significantly compromised in biogenesis of mature microRNA. The self-renewal rate of Ago2-deficient ES cells is affected due to failure of silencing of Cdkn1a by ES-cell-specific microRNAs (miRNA) in the absence of Ago2. Interestingly, unlike Dicer- and Dgcr8-deficient ES cells, they differentiate to all three germ layers both in vivo and in vitro. However, early differentiation of Ago2-deficient ES cells is delayed by 2–4 days as indicated by persistence of higher levels of self-renewal/ pluripotency markers during differentiation. Further, appearance of morphological and differentiation markers is also delayed during the differentiation. In this study we show that Ago2 is essential for normal self-renewal and differentiation. Also, our data suggest that self-renewal and differentiation of ES cells are regulated by both siRNA and miRNA pathways.

  2. Loss of Sparc in p53-null Astrocytes Promotes Macrophage Activation and Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival.

    Science.gov (United States)

    Thomas, Stacey L; Schultz, Chad R; Mouzon, Ezekiell; Golembieski, William A; El Naili, Reima; Radakrishnan, Archanna; Lemke, Nancy; Poisson, Laila M; Gutiérrez, Jorge A; Cottingham, Sandra; Rempel, Sandra A

    2015-07-01

    Both the induction of SPARC expression and the loss of the p53 tumor suppressor gene are changes that occur early in glioma development. Both SPARC and p53 regulate glioma cell survival by inverse effects on apoptotic signaling. Therefore, during glioma formation, the upregulation of SPARC may cooperate with the loss of p53 to enhance cell survival. This study determined whether the loss of Sparc in astrocytes that are null for p53 would result in reduced cell survival and tumor formation and increased tumor immunogenicity in an in vivo xenograft brain tumor model. In vitro, the loss of Sparc in p53-null astrocytes resulted in an increase in cell proliferation, but a loss of tumorigenicity. At 7 days after intracranial implantation, Sparc-null tumors had decreased tumor cell survival, proliferation and reduced tumor size. The loss of Sparc promoted microglia/macrophage activation and phagocytosis of tumor cells. Our results indicate that the loss of p53 by deletion/mutation in the early stages of glioma formation may cooperate with the induction of SPARC to potentiate cancer cell survival and escape from immune surveillance.

  3. Partial Restoration of CFTR Function in cftr-Null Mice following Targeted Cell Replacement Therapy.

    Science.gov (United States)

    Duchesneau, Pascal; Besla, Rickvinder; Derouet, Mathieu F; Guo, Li; Karoubi, Golnaz; Silberberg, Amanda; Wong, Amy P; Waddell, Thomas K

    2017-03-01

    Cystic fibrosis (CF) is a fatal recessive genetic disorder caused by a mutation in the gene encoding CF transmembrane conductance regulator (CFTR) protein. Alteration in CFTR leads to thick airway mucus and bacterial infection. Cell therapy has been proposed for CFTR restoration, but efficacy has been limited by low engraftment levels. In our previous studies, we have shown that using a pre-conditioning regimen in combination with optimization of cell number and time of delivery, we could obtain greater bone marrow cell (BMC) retention in the lung. Here, we found that optimized delivery of wild-type (WT) BMC contributed to apical CFTR expression in airway epithelium and restoration of select ceramide species and fatty acids in CFTR(-/-) mice. Importantly, WT BMC delivery delayed Pseudomonas aeruginosa lung infection and increased survival of CFTR(-/-) recipients. Only WT BMCs had a beneficial effect beyond 6 months, suggesting a dual mechanism of BMC benefit: a non-specific effect early after cell delivery, possibly due to the recruitment of macrophages and neutrophils, and a late beneficial effect dependent on long-term CFTR expression. Taken together, our results suggest that BMC can improve overall lung function and may have potential therapeutic benefit for the treatment of CF.

  4. Investigation of the in vitro therapeutic efficacy of nilotinib in immortalized human NF2-null vestibular schwannoma cells.

    Directory of Open Access Journals (Sweden)

    Nesrin Sabha

    Full Text Available Vestibular schwannomas (VS are a common posterior fossa brain tumor, and though benign can cause significant morbidity, particularly loss of hearing, tinnitus, vertigo and facial paralysis. The current treatment options for VS include microsurgical resection, stereotactic radiosurgery or close surveillance monitoring, with each treatment option carrying associated complications and morbidities. Most importantly, none of these options can definitively reverse hearing loss or tinnitus. Identification of a novel medical therapy, through the use of targeted molecular inhibition, is therefore a highly desirable treatment strategy that may minimize complications arising from both tumor and treatment and more importantly be suitable for patients whose options are limited with respect to surgical or radiosurgical interventions. In this study we chose to examine the effect of Nilotinib on VS. Nilotinib (Tasigna® is a second-generation receptor tyrosine kinase (RTK inhibitor with a target profile similar to that of imatinib (Gleevec®, but increased potency, decreased toxicity and greater cellular and tissue penetration. Nilotinib targets not only the BCR-ABL oncoprotein, but also platelet-derived growth factor (PDGF receptor signalling. In this preclinical study, the human NF2-null schwannoma cell line HEI-193 subjected to nilotinib inhibition demonstrated decreased viability, proliferation and anchorage-independent growth, and increased apoptosis. A daily dose of nilotinib for 5 days inhibited HEI-I93 proliferation at a clinically-relevant concentration in a dose-dependent manner (IC(50 3-5 µmol/L in PDGF-stimulated cells. These anti-tumorigenic effects of nilotinib were correlated to inhibited activation of PDGFR-α and PDGFR-β and major downstream signalling pathways. These experiments support a therapeutic potential for Nilotinib in VS.

  5. Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice.

    Science.gov (United States)

    Ochsner, Scott A; Russell, Darryl L; Day, Anthony J; Breyer, Richard M; Richards, Joanne S

    2003-03-01

    Ovulation, the release of fertilizable oocytes from mature follicles, involves tissue remodeling and increased prostaglandin (PG) signaling. Cyclooxygenase (COX)-2 is the rate-limiting enzyme during PG synthesis. Female mice null for either COX-2 or the PGE(2) receptor EP2 are infertile, show decreased ovulation, and exhibit abnormal cumulus expansion. Cumulus expansion is the production of a complex extracellular matrix surrounding the cumulus-oocyte complex (COC). Matrix components consist of hyaluronan, proteoglycans, and proteins with hyaluronan binding domains. One such hyaluronan binding protein is TNFalpha-stimulated gene 6 (TSG-6). By various methods, we show induction of TSG-6 and hyaluronan synthase-2 mRNA in ovaries of mice treated with pregnant mare serum gonadotropin and human chorionic gonadotropin. By in situ hybridization, we show that both genes are expressed in periantral mural granulosa cells and cumulus cells of the mouse ovary. Notably, RT-PCR and in situ hybridization show that TSG-6 mRNA but not hyaluronan synthase-2 mRNA expression is selectively reduced in cumulus cells of COX-2 and EP2 null mice. Western analysis further confirms that TSG-6 protein is reduced in isolated COCs but remains covalently associated with inter alpha-trypsin inhibitor in COX-2 null mice. These observations identify TSG-6 as a target of PG action and show that its production in ovulatory follicles is associated with proper formation of the cumulus-derived extracellular matrix.

  6. Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null cell lines.

    Directory of Open Access Journals (Sweden)

    Elisabeth Silden

    Full Text Available The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1, Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(PH quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level.

  7. Geometry of null hypersurfaces

    CERN Document Server

    Jezierski, J

    2004-01-01

    We review some basic natural geometric objects on null hypersurfaces. Gauss-Codazzi constraints are given in terms of the analog of canonical ADM momentum which is a well defined tensor density on the null surface. Bondi cones are analyzed with the help of this object.

  8. Oxazolone and ethanol induce colitis in non-obese diabetic-severe combined immunodeficiency interleukin-2Rγnull mice engrafted with human peripheral blood mononuclear cells

    Science.gov (United States)

    Nolte, T; Zadeh-Khorasani, M; Safarov, O; Rueff, F; Gülberg, V; Herbach, N; Wollenberg, A; Mueller, T; Siebeck, M; Wolf, E; Gropp, R

    2013-01-01

    Oxazolone-induced colitis in mice has become a recognized model to study the efficacy of therapeutics targeting the immunological response underlying the development of inflammatory bowel disease. However, this model cannot be used when therapeutics designed to address human targets do not interact with the respective murine counterpart. In this study, we examined the induction of oxazolone mediated colitis in non-obese diabetic-severe combined immunodeficiency interleukin-2Rγnull (NOD-SCID IL2Rγnull) mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from ulcerative colitis (UC), atopic dermatitis (AD) and healthy volunteers. NOD-SCID IL2Rγ null mice were engrafted with hPBMC followed by challenge with oxazolone or ethanol vehicle. Mice developed the same symptoms as observed previously in immunocompetent mice. The clinical activity score increased and the colon architecture was characterized by the development of oedema, fibrosis, crypt loss and dense infiltration of predominantly T cells into the lamina propria. Fluorescence activated cell sorter (FACS) analysis of lymphocytes in the colon identified natural killer (NK) T cells as a major constituent. In contrast to studies with immunocompetent mice, we observed the same phenotype in the group challenged with ethanol vehicle. The phenotype was most pronounced in mice engrafted with PBMC derived from a patient suffering from UC, suggesting that the immunological history of the donors predisposes the engrafted mice to react to ethanol. The model described here has the potential to study the efficacy of therapeutics targeting human lymphocytes in a model which is more reflective of the human disease. In addition, it might be developed to elucidate molecular mechanisms underlying the disease. PMID:23574330

  9. Verified Null-Move Pruning

    CERN Document Server

    David-Tabibi, Omid

    2008-01-01

    In this article we review standard null-move pruning and introduce our extended version of it, which we call verified null-move pruning. In verified null-move pruning, whenever the shallow null-move search indicates a fail-high, instead of cutting off the search from the current node, the search is continued with reduced depth. Our experiments with verified null-move pruning show that on average, it constructs a smaller search tree with greater tactical strength in comparison to standard null-move pruning. Moreover, unlike standard null-move pruning, which fails badly in zugzwang positions, verified null-move pruning manages to detect most zugzwangs and in such cases conducts a re-search to obtain the correct result. In addition, verified null-move pruning is very easy to implement, and any standard null-move pruning program can use verified null-move pruning by modifying only a few lines of code.

  10. Transplantation of human spleen into immunodeficient NOD/SCID IL2Rγ(null) mice generates humanized mice that improve functional B cell development.

    Science.gov (United States)

    Chung, Yun Shin; Son, Jin Kyung; Choi, Bongkum; Park, Jae Berm; Chang, Jun; Kim, Sung Joo

    2015-12-01

    We previously generated humanized TB34N mice that received human fetal thymus (T), bone tissue (B) and fetal liver-derived (FL)-CD34(+) cells (34) in immunodeficient, NOD/SCID IL2Rγ(null) (N) mice. Although humanized TB34N mice had excellent hematopoiesis, here, we sought to further improve this model by additional transplantation of human spleen tissue (S) as a secondary hematopoietic tissue (TBS34N). The human spleen grafts were enlarged and differentiated into a similar morphology of adult humans, including follicular lymphoid structures with T- and B-cells. The TBS34N mice mimicked mature human immune system (HIS): mature T- and B-cells and follicular dendritic cells; activated germinal center B-cells expressing CD71, BR3(+) cells, memory B-cells and activation-induced cytidine deaminase(+) B-cells; CD138(+) plasma cells were enriched in the mouse spleen. HBsAg-specific hIgG antibodies were secreted into the sera of all TBS34N mice upon immunization with HBsAg. Taken together, the humanized TBS34N mice improved mature HIS and achieved adaptive antibody responses.

  11. Bak compensated for Bax in p53-null cells to release cytochrome c for the initiation of mitochondrial signaling during Withanolide D-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Susmita Mondal

    Full Text Available The goal of cancer chemotherapy to induce multi-directional apoptosis as targeting a single pathway is unable to decrease all the downstream effect arises from crosstalk. Present study reports that Withanolide D (WithaD, a steroidal lactone isolated from Withania somnifera, induced cellular apoptosis in which mitochondria and p53 were intricately involved. In MOLT-3 and HCT116p53+/+ cells, WithaD induced crosstalk between intrinsic and extrinsic signaling through Bid, whereas in K562 and HCT116p53-/- cells, only intrinsic pathway was activated where Bid remain unaltered. WithaD showed pronounced activation of p53 in cancer cells. Moreover, lowered apoptogenic effect of HCT116p53-/- over HCT116p53+/+ established a strong correlation between WithaD-mediated apoptosis and p53. WithaD induced Bax and Bak upregulation in HCT116p53+/+, whereas increase only Bak expression in HCT116p53-/- cells, which was coordinated with augmented p53 expression. p53 inhibition substantially reduced Bax level and failed to inhibit Bak upregulation in HCT116p53+/+ cells confirming p53-dependent Bax and p53-independent Bak activation. Additionally, in HCT116p53+/+ cells, combined loss of Bax and Bak (HCT116Bax-Bak- reduced WithaD-induced apoptosis and completely blocked cytochrome c release whereas single loss of Bax or Bak (HCT116Bax-Bak+/HCT116Bax+Bak- was only marginally effective after WithaD treatment. In HCT116p53-/- cells, though Bax translocation to mitochondria was abrogated, Bak oligomerization helped the cells to release cytochrome c even before the disruption of mitochondrial membrane potential. WithaD also showed in vitro growth-inhibitory activity against an array of p53 wild type and null cancer cells and K562 xenograft in vivo. Taken together, WithaD elicited apoptosis in malignant cells through Bax/Bak dependent pathway in p53-wild type cells, whereas Bak compensated against loss of Bax in p53-null cells.

  12. Magnetic Null Points in Kinetic Simulations of Space Plasmas

    Science.gov (United States)

    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.

  13. Null twisted geometries

    CERN Document Server

    Speziale, Simone

    2013-01-01

    We define and investigate a quantisation of null hypersurfaces in the context of loop quantum gravity on a fixed graph. The main tool we use is the parametrisation of the theory in terms of twistors, which has already proved useful in discussing the interpretation of spin networks as the quantization of twisted geometries. The classical formalism can be extended in a natural way to null hypersurfaces, with the Euclidean polyhedra replaced by null polyhedra with space-like faces, and SU(2) by the little group ISO(2). The main difference is that the simplicity constraints present in the formalims are all first class, and the symplectic reduction selects only the helicity subgroup of the little group. As a consequence, information on the shapes of the polyhedra is lost, and the result is a much simpler, abelian geometric picture. It can be described by an Euclidean singular structure on the 2-dimensional space-like surface defined by a foliation of space-time by null hypersurfaces. This geometric structure is na...

  14. Expression of Lumican and Parkin in hepatocellular carcinoma and its significance%肝细胞癌中Lumican和Parkin的表达及意义

    Institute of Scientific and Technical Information of China (English)

    徐迈宇; 陈钢; 陈峰; 陈雷; 金肖丹

    2012-01-01

    Objective To investigate the expression and significance of Lumican protein and Parkin protein in hepalocellular carcinoma,and to study their correlation. Methods The expressions of Lumican protein and Parkin protein in 62 cases of HCC and 62 cases of para-carcinoma liver tissues were analyzed by immunohistochemistry method. Results ( 1 ) The expression negative rate of Lumican protein(35. 5% ) and Parkin protein (32. 3% ) in hepatocellular carcinoma was significantly higher than that in the para-carcinoma liver tissues( P <0. 05). (2)Lumican expression had no correlation with gender,tumor size, AFP level,HBsAg and cirrhosis, but had correlation with Edmondson grade and thrombus in the portal vein( P <0. 05). (3) Parkin expression had no correlation with gender, tumor size,cirrhosis and HbsAg,but had correlation with Edmondson grade, AFP level, and thrombus in the portal vein(P< 0. 05). (4)The expression of Lumican protein was positively associated with Parkin( r =0. 450,P <0. 05). Conclusion Lumican and Parkin may play an important role in the development and progression of liver cancer and may be a new target for cancer therapy.%目的 探讨肝细胞癌组织中Lumican蛋白及Parkin蛋白的表达及意义,并分析两者的相关性.方法 应用免疫组织化学S-P法检测62例肝癌患者癌组织及62例癌旁组织中Lumican及Parkin蛋白的表达并分析其与临床病理因素之间的关系.结果 (1)肝癌组织中Lumican、Parkin的阳性表达率分别为35.5%、32.3%,与癌旁组织的阳性表达率比较(66.1%、72.6%),差异具有统计学意义(P<0.05);(2) Lumican蛋白的表达与Edmondson分级及是否伴有门静脉癌栓相关(P<0.05),而与性别、肿瘤大小、HBsAg、肝硬化和AFP无关(P >0.05);(3) Parkin蛋白的表达与患者肝癌Edmondson分级、AFP水平、是否伴有门静脉癌栓相关(P<0.05),而与性别、肿瘤大小、HBsAg和肝硬化无关(P>0.05);(4)Lumican与Parkin呈正相关(r=0.450

  15. Jagged1 upregulation in prostate epithelial cells promotes formation of reactive stroma in the Pten null mouse model for prostate cancer

    Science.gov (United States)

    Su, Qingtai; Zhang, Boyu; Zhang, Li; Dang, Truong; Rowley, David; Ittmann, Michael; Xin, Li

    2016-01-01

    The role of Notch signaling in prostate cancer has not been defined definitively. Several large scale tissue microarray studies revealed that the expression of some Notch signaling components including the Jagged1 ligand are upregulated in advanced human prostate cancer specimens. Jagged1 expressed by tumor cells may activate Notch signaling in both adjacent tumor cells and cells in tumor microenvironment. However, it remains undetermined whether increased Jagged1 expression reflects a cause for or a consequence of tumor progression in vivo. To address this question, we generated a novel R26-LSL-JAG1 mouse model that enables spatiotemporal Jagged1 expression. Prostate specific upregulation of Jagged1 neither interferes with prostate epithelial homeostasis nor significantly accelerates tumor initiation or progression in the prostate-specific Pten deletion mouse model for prostate cancer. However, Jagged1 upregulation results in increased inflammatory foci in tumors and incidence of intracystic adenocarcinoma. In addition, Jagged1 overexpression upregulates Tgfβ signaling in prostate stromal cells and promotes progression of a reactive stromal microenvironment in the Pten null prostate cancer model. Collectively, Jagged1 overexpression does not significantly accelerate prostate cancer initiation and progression in the context of loss-of-function of Pten, but alters tumor histopathology and microenvironment. Our study also highlights an understudied role of Notch signaling in regulating prostatic stromal homeostasis. PMID:27345403

  16. Rescue of motor coordination by Purkinje cell-targeted restoration of Kv3.3 channels in Kcnc3-null mice requires Kcnc1.

    Science.gov (United States)

    Hurlock, Edward C; Bose, Mitali; Pierce, Ganon; Joho, Rolf H

    2009-12-16

    The role of cerebellar Kv3.1 and Kv3.3 channels in motor coordination was examined with an emphasis on the deep cerebellar nuclei (DCN). Kv3 channel subunits encoded by Kcnc genes are distinguished by rapid activation and deactivation kinetics that support high-frequency, narrow action potential firing. Previously we reported that increased lateral deviation while ambulating and slips while traversing a narrow beam of ataxic Kcnc3-null mice were corrected by restoration of Kv3.3 channels specifically to Purkinje cells, whereas Kcnc3-mutant mice additionally lacking one Kcnc1 allele were partially rescued. Here, we report mice lacking all Kcnc1 and Kcnc3 alleles exhibit no such rescue. For Purkinje cell output to reach the rest of the brain it must be conveyed by neurons of the DCN or vestibular nuclei. As Kcnc1, but not Kcnc3, alleles are lost, mutant mice exhibit increasing gait ataxia accompanied by spike broadening and deceleration in DCN neurons, suggesting the facet of coordination rescued by Purkinje-cell-restricted Kv3.3 restoration in mice lacking just Kcnc3 is hypermetria, while gait ataxia emerges when additionally Kcnc1 alleles are lost. Thus, fast repolarization in Purkinje cells appears important for normal movement velocity, whereas DCN neurons are a prime candidate locus where fast repolarization is necessary for normal gait patterning.

  17. Rescue of Motor Coordination by Purkinje Cell-Targeted Restoration of Kv3.3 Channels in Kcnc3-Null Mice Requires Kcnc1

    Science.gov (United States)

    Hurlock, Edward C.; Bose, Mitali; Pierce, Ganon

    2009-01-01

    The role of cerebellar Kv3.1 and Kv3.3 channels in motor coordination was examined with an emphasis on the deep cerebellar nuclei (DCN). Kv3 channel subunits encoded by Kcnc genes are distinguished by rapid activation and deactivation kinetics that support high-frequency, narrow action potential firing. Previously we reported that increased lateral deviation while ambulating and slips while traversing a narrow beam of ataxic Kcnc3-null mice were corrected by restoration of Kv3.3 channels specifically to Purkinje cells, whereas Kcnc3-mutant mice additionally lacking one Kcnc1 allele were partially rescued. Here, we report mice lacking all Kcnc1 and Kcnc3 alleles exhibit no such rescue. For Purkinje cell output to reach the rest of the brain it must be conveyed by neurons of the DCN or vestibular nuclei. As Kcnc1, but not Kcnc3, alleles are lost, mutant mice exhibit increasing gait ataxia accompanied by spike broadening and deceleration in DCN neurons, suggesting the facet of coordination rescued by Purkinje-cell-restricted Kv3.3 restoration in mice lacking just Kcnc3 is hypermetria, while gait ataxia emerges when additionally Kcnc1 alleles are lost. Thus, fast repolarization in Purkinje cells appears important for normal movement velocity, whereas DCN neurons are a prime candidate locus where fast repolarization is necessary for normal gait patterning. PMID:20016089

  18. Carbon-ion beam irradiation kills X-ray-resistant p53-null cancer cells by inducing mitotic catastrophe.

    Directory of Open Access Journals (Sweden)

    Napapat Amornwichet

    Full Text Available BACKGROUND AND PURPOSE: To understand the mechanisms involved in the strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies. MATERIALS AND METHODS: DNA damage responses after carbon-ion beam or X-ray irradiation in isogenic HCT116 colorectal cancer cell lines with and without TP53 (p53+/+ and p53-/-, respectively were analyzed as follows: cell survival by clonogenic assay, cell death modes by morphologic observation of DAPI-stained nuclei, DNA double-strand breaks (DSBs by immunostaining of phosphorylated H2AX (γH2AX, and cell cycle by flow cytometry and immunostaining of Ser10-phosphorylated histone H3. RESULTS: The p53-/- cells were more resistant than the p53+/+ cells to X-ray irradiation, while the sensitivities of the p53+/+ and p53-/- cells to carbon-ion beam irradiation were comparable. X-ray and carbon-ion beam irradiations predominantly induced apoptosis of the p53+/+ cells but not the p53-/- cells. In the p53-/- cells, carbon-ion beam irradiation, but not X-ray irradiation, markedly induced mitotic catastrophe that was associated with premature mitotic entry with harboring long-retained DSBs at 24 h post-irradiation. CONCLUSIONS: Efficient induction of mitotic catastrophe in apoptosis-resistant p53-deficient cells implies a strong cancer cell-killing effect of carbon-ion beam irradiation that is independent of the p53 status, suggesting its biological advantage over X-ray treatment.

  19. Visible Nulling Coronagraph

    Science.gov (United States)

    Shao, M.; Samuel, R.; Wallace, K.; Levine, B.

    2007-06-01

    To date, nulling coronography has achieved the deepest level of starlight suppression than any other coronagraphic technique. The terms starlight suppression and contrast are often used interchangeably and incorrectly. At 3.5 lambda/D the airy function sidelobes has dropped to 0.001 of the stellar flux. Starlight suppression of 1e-7 will then produce a speckle pattern with a contrast of 1e-10. This paper describes three topics in nulling coronagraphs. The first is starlight suppression of 1.1e-7 in laser light, the level of star light suppression needed for 1e-10 contrast. A similar experiment in broadband (16%) white light has demonstrated ~1.2e-6 suppression. Both experiments were starlight suppression using a single mode optical fiber. Starlight suppression to 1e-6~1e-7 requires wavefront measurements with sub-angstrom level accuracy. This is most easily done with a wavefront sensor that works with light after the coronagraph rather than the bright starlight in front of the coronagraph. Our nulling coronagraph uses a post coronagraphic interferometer to perform two functions, 1) measure the wavefront and provide an correction/error signal for the deformable mirror, and 2) post coronagraph PSF subtraction. We show that the post coronagraph interferometer has very significant SNR advantages over other post coronagraph approaches such as speckle nulling. A secondary function of the post coronagraphic wavefront sensor is that since it measures the amplitude and phase of the wavefront of the starlight after exiting the coronagraph, that amp*exp(i*phi) can be used to estimate the residual speckle pattern for subsequent PSF subtraction. By measuring the PSF at the same time as we're measuring the science image, the stability requirements can be relaxed by many orders of magnitude. (over rotating the telescope around the line of sight for example). The post coronagraph interferometer is being used in three projects, the PICTURE project (coronagraph behind a 60 cm

  20. Noscapine Induced Apoptosis via Downregulation of Survivin in Human Neuroblastoma Cells Having Wild Type or Null p53

    OpenAIRE

    Shiwang Li; Jing He; Shuai Li; Guoqing Cao; Shaotao Tang; Qiangsong Tong; Joshi, Harish C.

    2012-01-01

    Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. Noscapine, a nontoxic natural compound, can trigger apoptosis in many cancer types. We now show that p53 is dispensable for Noscapine-induced cell death in neuroblastoma cell lines, proapoptotic response to this promising chemopreventive agent is mediated by suppression of survivin protein exp...

  1. Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1.

    Science.gov (United States)

    Islam, Abul B M M K; Dave, Mandar; Amin, Sonia; Jensen, Roderick V; Amin, Ashok R

    2016-04-01

    The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2(-/-) or COX-1(-/-) mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2(-/-)>COX-1(-/-)>WT+IL-1β. COX-1(-/-) or COX-2(-/-) cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive "anti-inflammatory, proinflammatory, and redox-activated" signature in the protein-protein interactome map was observed in COX-2(-/-) cells. The augmented COX-1 mRNA (in COX-2(-/-) cells) was associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1α, thromboxane B2 (TXB2), and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2(-/-) cells generated an "eicosanoid storm". The genomic characteristics of COX-2(-/-) is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1(-/-) and COX-2(-/-) cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  2. Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1

    Directory of Open Access Journals (Sweden)

    Abul B.M.M.K. Islam

    2016-04-01

    Full Text Available The constitutively-expressed cyclooxygenase 1 (COX-1 and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA to prostaglandins (PGs. However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT mice and COX-2-/- or COX-1-/- mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-/- > COX-1-/- > WT + IL-1β. COX-1-/- or COX-2-/- cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive “anti-inflammatory, proinflammatory, and redox-activated” signature in the protein–protein interactome map was observed in COX-2-/- cells. The augmented COX-1 mRNA (in COX-2-/- cells was associated with the upregulation of mRNAs for glutathione S-transferase (GST, superoxide dismutase (SOD, NAD(PH dehydrogenase quinone 1 (NQO1, aryl hydrocarbon receptor (AhR, peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4, PGF1α, thromboxane B2 (TXB2, and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an “eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  3. Noscapine induced apoptosis via downregulation of survivin in human neuroblastoma cells having wild type or null p53.

    Directory of Open Access Journals (Sweden)

    Shiwang Li

    Full Text Available Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. Noscapine, a nontoxic natural compound, can trigger apoptosis in many cancer types. We now show that p53 is dispensable for Noscapine-induced cell death in neuroblastoma cell lines, proapoptotic response to this promising chemopreventive agent is mediated by suppression of survivin protein expression. The Noscapine treatment increased levels of total and Ser(15-phosphorylated p53 protein in SK-SY5Y cells, but the proapoptotic response to this agent was maintained even after knockdown of the p53 protein level. Exposure of SK-SY5Y and LA1-5S cells to Noscapine resulted in a marked decrease in protein and mRNA level of survivin as early as 12 hours after treatment. Ectopic expression of survivin conferred statistically significant protection against Noscapine-mediated cytoplasmic histone-associated apoptotic DNA fragmentation. Also, the Noscapine-induced apoptosis was modestly but statistically significantly augmented by RNA interference of survivin in both cell lines. Furthermore, Noscapine-induced apoptotic cell death was associated with activation of caspase-3 and cleavage of PARP. In conclusion, the present study provides novel insight into the molecular circuitry of Noscapine-induced apoptosis to indicate suppression of survivin expression as a critical mediator of this process.

  4. Noscapine induced apoptosis via downregulation of survivin in human neuroblastoma cells having wild type or null p53.

    Science.gov (United States)

    Li, Shiwang; He, Jing; Li, Shuai; Cao, Guoqing; Tang, Shaotao; Tong, Qiangsong; Joshi, Harish C

    2012-01-01

    Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. Noscapine, a nontoxic natural compound, can trigger apoptosis in many cancer types. We now show that p53 is dispensable for Noscapine-induced cell death in neuroblastoma cell lines, proapoptotic response to this promising chemopreventive agent is mediated by suppression of survivin protein expression. The Noscapine treatment increased levels of total and Ser(15)-phosphorylated p53 protein in SK-SY5Y cells, but the proapoptotic response to this agent was maintained even after knockdown of the p53 protein level. Exposure of SK-SY5Y and LA1-5S cells to Noscapine resulted in a marked decrease in protein and mRNA level of survivin as early as 12 hours after treatment. Ectopic expression of survivin conferred statistically significant protection against Noscapine-mediated cytoplasmic histone-associated apoptotic DNA fragmentation. Also, the Noscapine-induced apoptosis was modestly but statistically significantly augmented by RNA interference of survivin in both cell lines. Furthermore, Noscapine-induced apoptotic cell death was associated with activation of caspase-3 and cleavage of PARP. In conclusion, the present study provides novel insight into the molecular circuitry of Noscapine-induced apoptosis to indicate suppression of survivin expression as a critical mediator of this process.

  5. Stable and null current hysteresis perovskite solar cells based nitrogen doped graphene oxide nanoribbons hole transport layer

    Science.gov (United States)

    Kim, Jeongmo; Mat Teridi, Mohd Asri; Mohd Yusoff, Abd. Rashid Bin; Jang, Jin

    2016-06-01

    Perovskite solar cells are becoming one of the leading technologies to reduce our dependency on traditional power sources. However, the frequently used component poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) has several shortcomings, such as an easily corroded indium-tin-oxide (ITO) interface at elevated temperatures and induced electrical inhomogeneity. Herein, we propose solution-processed nitrogen-doped graphene oxide nanoribbons (NGONRs) as a hole transport layer (HTL) in perovskite solar cells, replacing the conducting polymer PEDOT:PSS. The conversion efficiency of NGONR-based perovskite solar cells has outperformed a control device constructed using PEDOT:PSS. Moreover, our proposed NGONR-based devices also demonstrate a negligible current hysteresis along with improved stability. This work provides an effective route for substituting PEDOT:PSS as the effective HTL.

  6. Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains

    Energy Technology Data Exchange (ETDEWEB)

    Willing, M.C.; Deschenes, S.P.; Roberts, E.J. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1996-10-01

    Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type I. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type I. 42 refs., 6 figs., 1 tab.

  7. Radiant Temperature Nulling Radiometer

    Science.gov (United States)

    2002-01-01

    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. The underlying principle of nulling and self-calibration is the same as that of a typical microwave radiometer, but because of differences between the characteristics of signals in the infrared and microwave spectral regions, the principle must be implemented in a different way. A detailed description of the instrument including an infrared photodetector equipped with focusing input optics [e.g., lens(es) and/or mirrors] and an input LWIR band-pass filter is presented.

  8. Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγnull mice treated with alogliptin

    Directory of Open Access Journals (Sweden)

    Jurczyk A

    2013-12-01

    Full Text Available Agata Jurczyk,1 Philip diIorio,1 Dean Brostowin,1 Linda Leehy,1 Chaoxing Yang,1 Fumihiko Urano,2 David M Harlan,3 Leonard D Shultz,4 Dale L Greiner,1 Rita Bortell1 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 2Department of Medicine, Washington University School of Medicine, St Louis, MO, 3Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 4The Jackson Laboratory, Bar Harbor, ME, USA Purpose: Dipeptidyl-peptidase-4 (DPP-4 inhibitors are known to increase insulin secretion and beta cell proliferation in rodents. To investigate the effects on human beta cells in vivo, we utilize immunodeficient mice transplanted with human islets. The study goal was to determine the efficacy of alogliptin, a DPP-4 inhibitor, to enhance human beta cell function and proliferation in an in vivo context using diabetic immunodeficient mice engrafted with human pancreatic islets. Methods: Streptozotocin-induced diabetic NOD-scid IL2rγnull (NSG mice were transplanted with adult human islets in three separate trials. Transplanted mice were treated daily by gavage with alogliptin (30 mg/kg/day or vehicle control. Islet graft function was compared using glucose tolerance tests and non-fasting plasma levels of human insulin and C-peptide; beta cell proliferation was determined by bromodeoxyuridine (BrdU incorporation. Results: Glucose tolerance tests were significantly improved by alogliptin treatment for mice transplanted with islets from two of the three human islet donors. Islet-engrafted mice treated with alogliptin also had significantly higher plasma levels of human insulin and C-peptide compared to vehicle controls. The percentage of insulin+BrdU+ cells in human islet grafts from alogliptin-treated mice was approximately 10-fold more than from vehicle control mice, consistent with a significant increase in human beta cell proliferation. Conclusion: Human islet-engrafted immunodeficient mice

  9. Gravitational action with null boundaries

    CERN Document Server

    Lehner, Luis; Poisson, Eric; Sorkin, Rafael D

    2016-01-01

    We present a complete discussion of the boundary term in the action functional of general relativity when the boundary includes null segments in addition to the more usual timelike and spacelike segments. We confirm that ambiguities appear in the contribution from a null segment, because it depends on an arbitrary choice of parametrization for the generators. We also show that similar ambiguities appear in the contribution from a codimension-two surface at which a null segment is joined to another (spacelike, timelike, or null) segment. The parametrization ambiguity can be tamed by insisting that the null generators be affinely parametrized; this forces each null contribution to the boundary action to vanish, but leaves intact the fredom to rescale the affine parameter by a constant factor on each generator. Once a choice of parametrization is made, the ambiguity in the joint contributions can be eliminated by formulating well-motivated rules that ensure the additivity of the gravitational action. Enforcing t...

  10. Active site cysteine-null glyceraldehyde-3-phosphate dehydrogenase (GAPDH) rescues nitric oxide-induced cell death.

    Science.gov (United States)

    Kubo, Takeya; Nakajima, Hidemitsu; Nakatsuji, Masatoshi; Itakura, Masanori; Kaneshige, Akihiro; Azuma, Yasu-Taka; Inui, Takashi; Takeuchi, Tadayoshi

    2016-02-29

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a homotetrameric enzyme involved in a key step of glycolysis, also has a role in mediating cell death under nitrosative stress. Our previous reports suggest that nitric oxide-induced intramolecular disulfide-bonding GAPDH aggregation, which occurs through oxidation of the active site cysteine (Cys-152), participates in a mechanism to account for nitric oxide-induced death signaling in some neurodegenerative/neuropsychiatric disorders. Here, we demonstrate a rescue strategy for nitric oxide-induced cell death accompanied by GAPDH aggregation in a mutant with a substitution of Cys-152 to alanine (C152A-GAPDH). Pre-incubation of purified wild-type GAPDH with C152A-GAPDH under exposure to nitric oxide inhibited wild-type GAPDH aggregation in a concentration-dependent manner in vitro. Several lines of structural analysis revealed that C152A-GAPDH extensively interfered with nitric oxide-induced GAPDH-amyloidogenesis. Overexpression of doxycycline-inducible C152A-GAPDH in SH-SY5Y neuroblastoma significantly rescued nitric oxide-induced death, concomitant with the decreased formation of GAPDH aggregates. Further, both co-immunoprecipitation assays and simulation models revealed a heterotetramer composed of one dimer each of wild-type GAPDH and C152A-GAPDH. These results suggest that the C152A-GAPDH mutant acts as a dominant-negative molecule against GAPDH aggregation via the formation of this GAPDH heterotetramer. This study may contribute to a new therapeutic approach utilizing C152A-GAPDH against brain damage in nitrosative stress-related disorders.

  11. Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. III. A marker defining a subpopulation of lymphocytes which cuts across the normal T-B-null classification.

    Science.gov (United States)

    Zola, H; Beckman, I G; Bradley, J; Brooks, D A; Kupa, A; McNamara, P J; Smart, I J; Thomas, M E

    1980-06-01

    A somatic cell hybrid line which secreted antibody reacting selectively with a proportion of the white cells in human blood was prepared. The hybridoma appeared to be monoclonal, and the antibody secreted stained 67% of the lymphocyte population in blood. It reacted less well with granulocytes and monocytes. The lymphocytes stained comprised 80% of the T cells and 50% of the B cells. The antibody showed no recognizable pattern in its reactivity with cell lines and leukaemic cells, although B cells tended to react less well than T cells, null cells, or myeloid leukaemic cells. The expression of the antigenic determinant is discussed in relation to the classification of leucocytes. This determinant and certain other markers exhibited differential expression on closely related cells, and yet were shared by more distantly related cells.

  12. Accumulation of xenotransplanted canine bone marrow cells in NOD/SCID/γc(null) mice with acute hepatitis induced by CCl4.

    Science.gov (United States)

    Kato, Takashi; Hisasue, Masaharu; Segawa, Kazuhito; Fujimoto, Ayumi; Makiishi, Eri; Neo, Sakurako; Yasuno, Kyohei; Kobayashi, Ryosuke; Tsuchiya, Ryo

    2013-07-31

    Bone marrow cell infusion (BMI) has recently been suggested as an effective therapy for refractory liver disease; however, the efficiency of BMI using canine bone marrow cells (cBMCs) has not been reported. We evaluated the accumulation potential of cBMCs in a mouse model of acute liver failure. Acute hepatitis was induced by carbon tetrachloride (CCl4) treatment in NOD/SCID/γc(null)(NOG) mice and wild-type (WT) C57BL mice, and the characteristics of liver dysfunction and the degree of hepatic injury and regeneration were compared between the two mouse models. Next, female CCl4-treated NOG mice were xenotransplanted with male PKH26-labeled cBMCs, and the potential of cBMCs to accumulate in injured liver tissue compartments was examined. Fluorescence microscopy was performed to histologically detect the infused cBMCs, and DNA polymerase chain reaction was performed for detection of the male Y chromosome (SRY gene) in the recipient female NOG mice. The number of PKH26-positive cBMCs transplanted in the liver tissue gradually increased in the NOG mice. The infused cBMCs were located in the necrotic area of the liver at an early stage after transplantation, and most had accumulated a week after transplantation. However, the therapeutic efficacy of the xenotransplantation remained unclear, because no significant differences were observed concerning the extent liver injury and regeneration between the cBMC-transplanted and saline control mice. These results suggest that cBMCs will specifically accumulate in injured liver tissue and that BMC transplantation may have the potential to repair liver deficiency.

  13. Wnt-responsive cancer stem cells are located close to distorted blood vessels and not in hypoxic regions in a p53-null mouse model of human breast cancer.

    Science.gov (United States)

    Vadakkan, Tegy J; Landua, John D; Bu, Wen; Wei, Wei; Li, Fuhai; Wong, Stephen T C; Dickinson, Mary E; Rosen, Jeffrey M; Lewis, Michael T; Zhang, Mei

    2014-07-01

    Cancer stem cells (CSCs, or tumor-initiating cells) may be responsible for tumor formation in many types of cancer, including breast cancer. Using high-resolution imaging techniques, we analyzed the relationship between a Wnt-responsive, CSC-enriched population and the tumor vasculature using p53-null mouse mammary tumors transduced with a lentiviral Wnt signaling reporter. Consistent with their localization in the normal mammary gland, Wnt-responsive cells in tumors were enriched in the basal/myoepithelial population and generally located in close proximity to blood vessels. The Wnt-responsive CSCs did not colocalize with the hypoxia-inducible factor 1α-positive cells in these p53-null basal-like tumors. Average vessel diameter and vessel tortuosity were increased in p53-null mouse tumors, as well as in a human tumor xenograft as compared with the normal mammary gland. The combined strategy of monitoring the fluorescently labeled CSCs and vasculature using high-resolution imaging techniques provides a unique opportunity to study the CSC and its surrounding vasculature.

  14. Ex vivo expanded human regulatory T cells delay islet allograft rejection via inhibiting islet-derived monocyte chemoattractant protein-1 production in CD34+ stem cells-reconstituted NOD-scid IL2rγnull mice.

    Directory of Open Access Journals (Sweden)

    Fang Xiao

    Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune disease caused by immune-mediated destruction of insulin-secreting β cells of the pancreas. Near complete dependence on exogenous insulin makes T1DM very difficult to control, with the result that patients are exposed to high blood glucose and risk of diabetic complications and/or intermittent low blood glucose that can cause unconsciousness, fits and even death. Allograft transplantation of pancreatic islets restores normoglycemia with a low risk of surgical complications. However, although successful immediately after transplantation, islets are progressively lost, with most of the patients requiring exogenous insulin within 2 years post-transplant. Therefore, there is an urgent requirement for the development of new strategies to prevent islet rejection. In this study, we explored the importance of human regulatory T cells in the control of islets allograft rejection. We developed a pre-clinical model of human islet transplantation by reconstituting NOD-scid IL2rγnull mice with cord blood-derived human CD34+ stem cells and demonstrated that although the engrafted human immune system mediated the rejection of human islets, their survival was significantly prolonged following adoptive transfer of ex vivo expanded human Tregs. Mechanistically, Tregs inhibited the infiltration of innate immune cells and CD4+ T cells into the graft by down-regulating the islet graft-derived monocyte chemoattractant protein-1. Our findings might contribute to the development of clinical strategies for Treg therapy to control human islet rejection. We also show for the first time that CD34+ cells-reconstituted NOD-scid IL2rγnull mouse model could be beneficial for investigating human innate immunity in vivo.

  15. MAGNETIC NULL POINTS IN KINETIC SIMULATIONS OF SPACE PLASMAS

    Energy Technology Data Exchange (ETDEWEB)

    Olshevsky, Vyacheslav; Innocenti, Maria Elena; Cazzola, Emanuele; Lapenta, Giovanni [Centre for Mathematical Plasma Astrophysics (CmPA), KU Leuven (Belgium); Deca, Jan [Laboratory for Atmospheric and Space Physics (LASP), University of Colorado Boulder, Boulder, CO (United States); Divin, Andrey [St. Petersburg State University, St. Petersburg (Russian Federation); Peng, Ivy Bo; Markidis, Stefano, E-mail: sya@mao.kiev.ua [High Performance Computing and Visualization (HPCViz), KTH Royal Institute of Technology, Stockholm (Sweden)

    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.

  16. Energy dissipation in magnetic null points at kinetic scales

    CERN Document Server

    Olshevsky, Vyacheslav; Eriksson, Elin; Markidis, Stefano; Lapenta, Giovanni

    2015-01-01

    We use kinetic particle-in-cell and magnetohydrodynamic simulations supported by an observational dataset to investigate magnetic reconnection in clusters of null points in space plasma. The magnetic configuration under investigation is driven by fast adiabatic flux rope compression that dissipates almost half of the initial magnetic field energy. In this phase powerful currents are excited producing secondary instabilities, and the system is brought into a state of `intermittent turbulence' within a few ion gyro-periods. Reconnection events are distributed all over the simulation domain and energy dissipation is rather volume-filling. Numerous spiral null points interconnected via their spines form null lines embedded into magnetic flux ropes; null point pairs demonstrate the signatures of torsional spine reconnection. However, energy dissipation mainly happens in the shear layers formed by adjacent flux ropes with oppositely directed currents. In these regions radial null pairs are spontaneously emerging an...

  17. ENERGY DISSIPATION IN MAGNETIC NULL POINTS AT KINETIC SCALES

    Energy Technology Data Exchange (ETDEWEB)

    Olshevsky, Vyacheslav; Lapenta, Giovanni [Centre for Mathematical Plasma Astrophysics (CmPA), KU Leuven (Belgium); Divin, Andrey [Department of Physics, St. Petersburg State University (Russian Federation); Eriksson, Elin [Swedish Institute of Space Physics, Uppsala Division, Uppsala (Sweden); Markidis, Stefano, E-mail: sya@mao.kiev.ua [High Performance Computing and Visualization (HPCViz), KTH Royal Institute of Technology, Stockholm (Sweden)

    2015-07-10

    We use kinetic particle-in-cell and MHD simulations supported by an observational data set to investigate magnetic reconnection in clusters of null points in space plasma. The magnetic configuration under investigation is driven by fast adiabatic flux rope compression that dissipates almost half of the initial magnetic field energy. In this phase powerful currents are excited producing secondary instabilities, and the system is brought into a state of “intermittent turbulence” within a few ion gyro-periods. Reconnection events are distributed all over the simulation domain and energy dissipation is rather volume-filling. Numerous spiral null points interconnected via their spines form null lines embedded into magnetic flux ropes; null point pairs demonstrate the signatures of torsional spine reconnection. However, energy dissipation mainly happens in the shear layers formed by adjacent flux ropes with oppositely directed currents. In these regions radial null pairs are spontaneously emerging and vanishing, associated with electron streams and small-scale current sheets. The number of spiral nulls in the simulation outweighs the number of radial nulls by a factor of 5–10, in accordance with Cluster observations in the Earth's magnetosheath. Twisted magnetic fields with embedded spiral null points might indicate the regions of major energy dissipation for future space missions such as the Magnetospheric Multiscale Mission.

  18. Energy Dissipation in Magnetic Null Points at Kinetic Scales

    Science.gov (United States)

    Olshevsky, Vyacheslav; Divin, Andrey; Eriksson, Elin; Markidis, Stefano; Lapenta, Giovanni

    2015-07-01

    We use kinetic particle-in-cell and MHD simulations supported by an observational data set to investigate magnetic reconnection in clusters of null points in space plasma. The magnetic configuration under investigation is driven by fast adiabatic flux rope compression that dissipates almost half of the initial magnetic field energy. In this phase powerful currents are excited producing secondary instabilities, and the system is brought into a state of “intermittent turbulence” within a few ion gyro-periods. Reconnection events are distributed all over the simulation domain and energy dissipation is rather volume-filling. Numerous spiral null points interconnected via their spines form null lines embedded into magnetic flux ropes; null point pairs demonstrate the signatures of torsional spine reconnection. However, energy dissipation mainly happens in the shear layers formed by adjacent flux ropes with oppositely directed currents. In these regions radial null pairs are spontaneously emerging and vanishing, associated with electron streams and small-scale current sheets. The number of spiral nulls in the simulation outweighs the number of radial nulls by a factor of 5-10, in accordance with Cluster observations in the Earth's magnetosheath. Twisted magnetic fields with embedded spiral null points might indicate the regions of major energy dissipation for future space missions such as the Magnetospheric Multiscale Mission.

  19. Magnetic null points in kinetic simulations of space plasmas

    CERN Document Server

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

    2015-01-01

    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 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 lunar magnetic ano...

  20. On the randomness of pulsar nulls

    Science.gov (United States)

    Redman, Stephen L.; Rankin, Joanna M.

    2009-05-01

    Pulsar nulling is not always a random process; most pulsars, in fact, null non-randomly. The Wald-Wolfowitz statistical runs test is a simple diagnostic that pulsar astronomers can use to identify pulsars that have non-random nulls. It is not clear at this point how the dichotomy in pulsar nulling randomness is related to the underlying nulling phenomenon, but its nature suggests that there are at least two distinct reasons that pulsars null.

  1. The HLA-G*0105N null allele induces cell surface expression of HLA-E molecule and promotes CD94/NKG2A-mediated recognition in JAR choriocarcinoma cell line.

    Science.gov (United States)

    Sala, Frédéric G; Del Moral, Pierre-Marie; Pizzato, Nathalie; Legrand-Abravanel, Florence; Le Bouteiller, Philippe; Lenfant, Françoise

    2004-12-01

    HLA-G is a non-classical HLA class Ib molecule primarily expressed in trophoblast cells, and is thought to play a key role in the induction of materno-fetal tolerance during pregnancy. In addition, the HLA-G gene provides a suitable leader sequence peptide capable of binding to HLA-E. However, the existence of placentas homozygous for the HLA-G*0105N null allele suggests that HLA-G1 might not be essential for fetal survival. To investigate whether expression of the HLA-G*0105N allele supports HLA-E cell surface expression, we transfected the HLA-G*0105N gene into JAR trophoblast cells. Flow cytometry analysis showed that HLA-G*0105N-transfected cells express surface HLA-E to a similar extent as the unmutated HLA-G gene, whereas HLA-G1 cell surface expression was undetectable. Using the NKL cell line in a standard (51)Cr release assay, the HLA-E molecules were found to inhibit natural killer lysis, through a mechanism partially dependent on CD94/NKG2A-mediated recognition.

  2. NULL Convention Floating Point Multiplier

    OpenAIRE

    Anitha Juliette Albert; Seshasayanan Ramachandran

    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 p...

  3. Gravitational action with null boundaries

    Science.gov (United States)

    Lehner, Luis; Myers, Robert C.; Poisson, Eric; Sorkin, Rafael D.

    2016-10-01

    We present a complete discussion of the boundary term in the action functional of general relativity when the boundary includes null segments in addition to the more usual timelike and spacelike segments. We confirm that ambiguities appear in the contribution from a null segment, because it depends on an arbitrary choice of parametrization for the generators. We also show that similar ambiguities appear in the contribution from a codimension-two surface at which a null segment is joined to another (spacelike, timelike, or null) segment. The parametrization ambiguity can be tamed by insisting that the null generators be affinely parametrized; this forces each null contribution to the boundary action to vanish, but leaves intact the fredom to rescale the affine parameter by a constant factor on each generator. Once a choice of parametrization is made, the ambiguity in the joint contributions can be eliminated by formulating well-motivated rules that ensure the additivity of the gravitational action. Enforcing these rules, we calculate the time rate of change of the action when it is evaluated for a so-called "Wheeler-DeWitt patch" of a black hole in asymptotically anti de Sitter space. We recover a number of results cited in the literature, obtained with a less complete analysis.

  4. Magnetic null points in kinetic simulations of space plasmas

    OpenAIRE

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

    2015-01-01

    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 n...

  5. Phase-Occultation Nulling Coronagraphy

    CERN Document Server

    Lyon, Richard G; Clampin, Mark; Petrone, Peter

    2015-01-01

    The search for life via characterization of earth-like planets in the habitable zone is one of the key scientific objectives in Astronomy. We describe a new phase-occulting (PO) interferometric nulling coronagraphy (NC) approach. The PO-NC approach employs beamwalk and freeform optical surfaces internal to the interferometer cavity to introduce a radially dependent plate scale difference between each interferometer arm (optical path) that nulls the central star at high contrast while transmitting the off-axis field. The design is readily implemented on segmented-mirror telescope architectures, utilizing a single nulling interferometer to achieve high throughput, a small inner working angle (IWA), sixth-order or higher starlight suppression, and full off-axis discovery space, a combination of features that other coronagraph designs generally must trade. Unlike previous NC approaches, the PO-NC approach does not require pupil shearing; this increases throughput and renders it less sensitive to on-axis common-mo...

  6. NULL Convention Floating Point Multiplier

    Directory of Open Access Journals (Sweden)

    Anitha Juliette Albert

    2015-01-01

    Full Text Available 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.

  7. NULL convention floating point multiplier.

    Science.gov (United States)

    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.

  8. Fracture characterisation using geoelectric null-arrays

    Science.gov (United States)

    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.

  9. Null eikonal helices and Null eikonal slant helices in the 4-dimensional Lorentzian manifold

    OpenAIRE

    Zıplar, Evren

    2014-01-01

    In this paper, we define the notion of eikonal helix and eikonal slant helix for null curves in the 4-dimensional Lorentzian manifold M 1 4 and give a characterization for the null curve to be the null eikonal helix. Moreover, we indicate an important relation between the null eikonal helix and null eikonal slant helix and find the axis of the null eikonal helix. We obtain some relationships between the curvatures of these curves.

  10. Parasitic interference in nulling interferometry

    CERN Document Server

    Matter, Alexis; Danchi, William C; Lopez, Bruno; Absil, Olivier

    2013-01-01

    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 pertubations 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 ...

  11. Balloon Exoplanet Nulling Interferometer (BENI)

    Science.gov (United States)

    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.

  12. Areas and volumes for null cones

    CERN Document Server

    Grant, James D E

    2010-01-01

    Motivated by recent work of Choquet-Bruhat, Chrusciel, and Martin-Garcia, we prove monotonicity properties and comparison results for the area of slices of the null cone of a point in a Lorentzian manifold. We also prove volume comparison results for subsets of the null cone analogous to the Bishop-Gromov relative volume monotonicity theorem and Guenther's volume comparison theorem. We briefly discuss how these estimates may be used to control the null second fundamental form of slices of the null cone in Ricci-flat Lorentzian four-manifolds with null curvature bounded above.

  13. An analysis of radio pulsar nulling statistics

    Science.gov (United States)

    Biggs, James D.

    1992-01-01

    Survival analysis methods are used to seek correlations between the fraction of null pulsars and other pulsar characteristics for an ensemble of 72 radio pulsars. The strongest correlation is found between the null fraction and the pulse period, suggesting that nulling is a manifestation of a faltering emission mechanism. Correlations are also found between the fraction of null pulses and other parameters that have a strong dependence on the pulse period. The results presented here suggest that nulling is broad-band and may ultimately be explained in terms of polar cap models of pulsar emission.

  14. Islet-specific CTL cloned from a type 1 diabetes patient cause beta-cell destruction after engraftment into HLA-A2 transgenic NOD/scid/IL2RG null mice.

    Directory of Open Access Journals (Sweden)

    Wendy W J Unger

    Full Text Available Despite increasing evidence that autoreactive CD8 T-cells are involved in both the initiation of type 1 diabetes (T1D and the destruction of beta-cells, direct evidence for their destructive role in-vivo is lacking. To address a destructive role for autoreactive CD8 T-cells in human disease, we assessed the pathogenicity of a CD8 T-cell clone derived from a T1D donor and specific for an HLA-A2-restricted epitope of islet-specific glucose-6-phosphatase catalytic-subunit related protein (IGRP. HLA-A2/IGRP tetramer staining revealed a higher frequency of IGRP-specific CD8 T-cells in the peripheral blood of recent onset human individuals than of healthy donors. IGRP(265-273-specific CD8 T-cells that were cloned from the peripheral blood of a recent onset T1D individual were shown to secrete IFNγ and Granzyme B after antigen-specific activation and lyse HLA-A2-expressing murine islets in-vitro. Lytic capacity was also demonstrated in-vivo by specific killing of peptide-pulsed target cells. Using the HLA-A2 NOD-scid IL2rγ(null mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced a destructive insulitis. Together, this is the first evidence that human HLA-restricted autoreactive CD8 T-cells target HLA-expressing beta-cells in-vivo, demonstrating the translational value of humanized mice to study mechanisms of disease and therapeutic intervention strategies.

  15. Null Similar Curves with Variable Transformations in Minkowski 3-space

    OpenAIRE

    Önder, Mehmet

    2012-01-01

    In this study, we define a family of null curves in Minkowski 3-space and called null similar curves. We obtain some properties of these special curves. We show that two null curves are null similar curves if and only if these curves form a null Bertrand pair. Moreover, we obtain that the family of null geodesics and null helices form the families of null similar curves with variable transformation.

  16. Human immune system development and survival of non-obese diabetic (NOD)-scid IL2rγ(null) (NSG) mice engrafted with human thymus and autologous haematopoietic stem cells.

    Science.gov (United States)

    Covassin, L; Jangalwe, S; Jouvet, N; Laning, J; Burzenski, L; Shultz, L D; Brehm, M A

    2013-12-01

    Immunodeficient mice bearing targeted mutations in the IL2rg gene and engrafted with human immune systems are effective tools for the study of human haematopoiesis, immunity, infectious disease and transplantation biology. The most robust human immune model is generated by implantation of human fetal thymic and liver tissues in irradiated recipients followed by intravenous injection of autologous fetal liver haematopoietic stem cells [often referred to as the BLT (bone marrow, liver, thymus) model]. To evaluate the non-obese diabetic (NOD)-scid IL2rγ(null) (NSG)-BLT model, we have assessed various engraftment parameters and how these parameters influence the longevity of NSG-BLT mice. We observed that irradiation and subrenal capsule implantation of thymus/liver fragments was optimal for generating human immune systems. However, after 4 months, a high number of NSG-BLT mice develop a fatal graft-versus-host disease (GVHD)-like syndrome, which correlates with the activation of human T cells and increased levels of human immunoglobulin (Ig). Onset of GVHD was not delayed in NSG mice lacking murine major histocompatibility complex (MHC) classes I or II and was not associated with a loss of human regulatory T cells or absence of intrathymic cells of mouse origin (mouse CD45(+) ). Our findings demonstrate that NSG-BLT mice develop robust human immune systems, but that the experimental window for these mice may be limited by the development of GVHD-like pathological changes.

  17. Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase

    NARCIS (Netherlands)

    Ng, Ho Yin; Oliver, Brian Gregory George; Burgess, Janette Kay; Krymskaya, Vera P.; Black, Judith Lee; Moir, Lyn M.

    2015-01-01

    Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify

  18. On the Penrose inequality along null hypersurfaces

    CERN Document Server

    Mars, Marc

    2015-01-01

    The null Penrose inequality, i.e. the Penrose inequality in terms of the Bondi energy, is studied by introducing a funtional on surfaces and studying its properties along a null hypersurface $\\Omega$ 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 Asymptotic 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 and Bergqvist. By exploiting further properties of the functional along general geodesic foliations, we introduce an approach to the null Penrose inequality called Renormalized Area Method and find a set of two conditions which implies the validity of the null Penrose inequality. One of the conditions involves a limit at infinity and the other a condition on the spacetime curvature along the flow. We investigate the...

  19. Co-transplantation of human fetal thymus, bone and CD34(+) cells into young adult immunodeficient NOD/SCID IL2Rγ(null) mice optimizes humanized mice that mount adaptive antibody responses.

    Science.gov (United States)

    Chung, Yun Shin; Son, Jin Kyung; Choi, Bongkum; Joo, Sung-Yeon; Lee, Yong-Soo; Park, Jae Berm; Moon, Hana; Kim, Tae Jin; Kim, Se Ho; Hong, Seokmann; Chang, Jun; Kang, Myung-Soo; Kim, Sung Joo

    2015-04-01

    Both the thymus (T) and bone (B) are necessary hematopoietic niches in adult humans. We previously showed that co-transplantation of human fetal T and B tissues into neonatal immunodeficient NOD/SCID IL2Rγ(null) (NSG, N) mice facilitated hematopoiesis. However, transplantation into neonatal mice resulted in high frequency of early death, making it unrealistic for repetitive experiments. In this study, young adult N mice were pre-engrafted with T and B, T alone, B alone or no tissues. The animals were irradiated and injected with autologous fetal liver (FL)-derived CD34(+) cells (34). The resultant mice were TB34N, T34N, B34N and 34N, respectively, and challenged with T cell dependent antigens (Ags). The humanized TB34N mice showed best performance of these mouse models in many aspects resembling the adult human Ag-experienced spleen. The TB34N mice exhibited better hematopoietic reconstitution; balanced development of T- and B-cell, and common progenitor cells; follicular lymphoid structures with a functional germinal center (GC) enriched with follicular dendritic cells (FDCs) and plasma cells (PCs); secretion of hIgG in the sera in response to Ags at comparable levels to those of human; derivations of hIgG mAb-secreting hybridoma clones. Collectively, the humanized TB34N mice could develop an adaptive immunity that was capable of producing Ag-specific hIgG at a significant level via class switching. This unprecedented TB34N platform in humanized mice would be useful in dissecting human immunity, for generating human Abs and clinical applications.

  20. No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

    Directory of Open Access Journals (Sweden)

    Ohlemiller Kevin K

    2010-07-01

    Full Text Available Abstract Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.

  1. The Importance of Proving the Null

    Science.gov (United States)

    Gallistel, C. R.

    2009-01-01

    Null hypotheses are simple, precise, and theoretically important. Conventional statistical analysis cannot support them; Bayesian analysis can. The challenge in a Bayesian analysis is to formulate a suitably vague alternative, because the vaguer the alternative is (the more it spreads out the unit mass of prior probability), the more the null is…

  2. Collapsing spherical null shells in general relativity

    Directory of Open Access Journals (Sweden)

    S Khakshournia

    2011-03-01

    Full Text Available In this work, the gravitational collapse of a spherically symmetric null shell with the flat interior and a charged Vaidya exterior spacetimes is studied. There is no gravitational impulsive wave present on the null hypersurface which is shear-free and contracting. It follows that there is a critical radius at which the shell bounces and starts expanding.

  3. Caloric restriction restores the chronological life span of the Goa1 null mutant of Candida albicans in spite of high cell levels of ROS.

    Science.gov (United States)

    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.

  4. Magnetic Nulls in the Earth's Magnetotail

    Science.gov (United States)

    Eriksson, Elin; Vaivads, Andris; Khotyaintsev, Yuri; Markidis, Stefano; André, Mats; Fu, Huishan; Karlsson, Tomas

    2015-04-01

    Regions with vanishing magnetic field, also referred to as magnetic nulls, are of high interest in plasma physics. Near magnetic nulls particles become unmagnetized and can by interacting with electric fields be accelerated up to high energies. Magnetic nulls have been observed and studied before using different methods for a few events. Here we present a statistical study of magnetic nulls in the Earth's magnetotail. In addition we study the role of magnetic field disturbances on the magnetic null identification. We study the magnetic nulls using full resolution data from all of the Cluster satellites when their maximum separation is less than one ion inertial length (approximately 1000 km). This is only fulfilled in 2003 when the maximum spacecraft separation is approximately 250 km. The magnetic nulls are not found using the more common method of Poincaré index. Instead we create a box surrounding the tetrahedron defined by the positions of the spacecrafts. If the positions of the magnetic nulls, using Taylor expansion, are within this box, they are saved for further analysis. All together 23 time intervals are found using this method and two error constraints. We find most of the nulls in the magnetotail current sheet, but a few of them are found at the magnetopause. We identify magnetic null types and currents associated with them. We present a detailed analysis of one example from August 6, 2003 00:45:40:00 UT - 00:45:41:05 UT when the satellites are in the magnetotail. Based on a linear magnetic field model created using parameters taken from the real data, we demonstrate the effect of magnetic field disturbance on the magnetic null identification. We show that magnetic disturbances of large enough amplitude can lead to a change in the magnetic null type, consistent with the data example. Therefore we suggest that for magnetic null type identification an additional constraint based on magnetic field disturbance amplitude have to be introduced. The obtained

  5. IRAN: interferometric remapped array nulling

    Science.gov (United States)

    Aristidi, Eric; Vakili, Farrokh; Abe, Lyu; Belu, Adrian; Lopez, Bruno; Lanteri, Henri; Schutz, A.; Menut, Jean-Luc

    2004-10-01

    This paper describes a method of beam-combination in the so-called hypertelescope imaging technique recently introduced by Labeyrie in optical interferometry. The method we propose is an alternative to the Michelson pupil reconfiguration that suffers from the loss of the classical object-image convolution relation. From elementary theory of Fourier optics we demonstrate that this problem can be solved by observing in a combined pupil plane instead of an image plane. The point-source intensity distribution (PSID) of this interferometric "image" tends towards a psuedo Airy disc (similar to that of a giant monolithic telescope) for a sufficiently large number of telescopes. Our method is applicable to snap-shot imaging of extended sources with a field comparable to the Airy pattern of single telescopes operated in a co-phased multi-aperture interferometric array. It thus allows to apply conveniently pupil plane coronagraphy. Our technique called Interferometric Remapped Array Nulling (IRAN) is particularly suitable for high dynamic imaging of extra-solar planetary companions, circumstellar nebulosities or extra-galactic objects where long baseline interferometry would closely probe the central regions of AGNs for instance.

  6. Energy dissipation in magnetic null points at kinetic scales

    OpenAIRE

    Olshevsky, Vyacheslav; Divin, Andrey; Eriksson, Elin; Markidis, Stefano; Lapenta, Giovanni

    2015-01-01

    We use kinetic particle-in-cell and MHD simulations supported by an observational data set to investigate magnetic reconnection in clusters of null points in space plasma. The magnetic configuration under investigation is driven by fast adiabatic flux rope compression that dissipates almost half of the initial magnetic field energy. In this phase powerful currents are excited producing secondary instabilities, and the system is brought into a state of "intermittent turbulence" within a few io...

  7. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

    Science.gov (United States)

    Chen, Jane Q; Mori, Hidetoshi; Cardiff, Robert D; Trott, Josephine F; Hovey, Russell C; Hubbard, Neil E; Engelberg, Jesse A; Tepper, Clifford G; Willis, Brandon J; Khan, Imran H; Ravindran, Resmi K; Chan, Szeman R; Schreiber, Robert D; Borowsky, Alexander D

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.

  8. High-contrast Nulling Interferometry Techniques Project

    Data.gov (United States)

    National Aeronautics and Space Administration — "We are developing rotating-baseline nulling-interferometry techniques and algorithms on the single-aperture Hale and Keck telescopes at near-infrared wavelengths,...

  9. Scientists Find a Magnetic Null in Nature

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ An international team has found the first in situ evidence for the existance of a null point in the central area of magnetic reconnection. The discovery was reported in the July issue of Nature Physics.

  10. Latex allergy and filaggrin null mutations

    DEFF Research Database (Denmark)

    Carlsen, Berit C; Meldgaard, Michael; Hamann, Dathan

    2011-01-01

    Objectives Natural rubber latex (NRL) contains over 200 proteins of which 13 have been identified as allergens and the cause of type I latex allergy. Health care workers share a high occupational risk for developing latex allergy. Filaggrin null mutations increase the risk of type I sensitizations...... to aeroallergens and it is possible that filaggrin null mutations also increase the risk of latex allergy. The aim of this paper was to examine the association between filaggrin null mutations and type I latex allergy. Methods Twenty latex allergic and 24 non-latex allergic dentists and dental assistants......, occupationally exposed to latex, were genotyped for filaggrin null mutations R501X and 2282del4. Latex allergy was determined by a positive reaction or a historical positive reaction to a skin prick test with NRL. Results 41 individuals were successfully genotyped. Three individuals were filaggrin mutation...

  11. New null screen design for corneal topography

    Science.gov (United States)

    Campos-García, Manuel; Estrada-Molina, Amilcar; Díaz-Uribe, Rufino

    2011-09-01

    In this work we report the design of a null screen for corneal topography. Here we assume that the corneal surface is an ellipsoid with a diameter of 12 mm and a curvature radius of 7.8 mm. 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 spots (similar to ellipses) drawn on it in such a way that its image, which is formed by reflection on the test surface, becomes an exact radial array of circular spots if the surface is perfect. Additionally, we performed a numerical simulation introducing Gaussian random errors in the coordinates of the centroids of the spots on the image plane, and in the coordinates of the sources (spots on the null-screen) in order to obtain the conical null-screen that reduces the error in the evaluation of the topography.

  12. Characterization of Null Geodesics on Kerr Spacetimes

    CERN Document Server

    Paganini, Claudio F; Oancea, Marius A

    2016-01-01

    We consider null geodesics in the domain of outer communication of a sub-extremal Kerr spacetime. We show, that most fundamental properties of null geodesics can be represented in one plot. In particular one can see immediately that the ergoregion and trapping are separated in phase space. Furthermore we show that from the point of view of any timelike observer outside of a black hole, trapping can be understood as a smooth set of spacelike directions on the observers' celestial sphere.

  13. Null-sissemakse - eraisikule riskantne / Tõnu Tramm

    Index Scriptorium Estoniae

    Tramm, Tõnu, 1968-

    2005-01-01

    Ilmunud ka: Delovõje Vedomosti 20. apr. lk. 26. Hansaliising ja Ühisliising käivitasid kampaania, mille käigus pakutakse uusi kuni 250 000 krooni maksvaid autosid null-sissemaksega. Kommenteerib ASi SEB Ühisliising arendusdirektor Ove Muuk. Tabel: Null-sissemaksega auto tuleb kallim. Lisad: Kuidas saavutada võimalikult väike kuumakse?; Kuidas maksta võimalikult vähe intressi? Vt. samas: Argo Rebane: Liisingufirmast saab parema hinna

  14. Null vectors of the $WBC_2$ algebra

    CERN Document Server

    Bajnok, Z

    1994-01-01

    Using the fusion principle of Bauer et al. we give explicit expressions for some null vectors in the highest weight representations of the \\bc algebra in two different forms. These null vectors are the generalization of the Virasoro ones described by Benoit and Saint-Aubin and analogues of the $W_3$ ones constructed by Bowcock and Watts. We find connection between quantum Toda models and the fusion method.

  15. Faddeev Null Plane Model of Proton

    CERN Document Server

    D'Araújo, W R B; Frederico, T

    1998-01-01

    The proton is formulated as a relativistic system of three constituent quarks interacting via a zero-range two-body force in the null-plane. The covariance of the null-plane Faddeev-like equation under kinematical front-form boosts is discussed. A simplified three-boson model of the nucleon wave-function is obtained numerically. The proton electric form-factor reproduces the experimental data for low momentum transfers and qualitatively describes the asymptotic region.

  16. Phase-only nulling for transmit antenna

    Science.gov (United States)

    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.

  17. Rac-null leukocytes are associated with increased inflammation-mediated alveolar bone loss.

    Science.gov (United States)

    Sima, Corneliu; Gastfreund, Shoshi; Sun, Chunxiang; Glogauer, Michael

    2014-02-01

    Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such as decreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis.

  18. The Emergence, Motion, and Disappearance of Magnetic Null Points

    OpenAIRE

    Murphy, Nicholas; Parnell, Clare; Haynes, Andrew; Pontin, David

    2013-01-01

    Magnetic reconnection frequently occurs at and around magnetic null points. We derive exact expressions for the motion of a magnetic null point in a smoothly varying magnetic field. We define xn as the position of a null, U = dxn/dt as the null's velocity, and M as the Jacobian matrix of the magnetic field at the null. By evaluating the derivative of the magnetic field following the motion of the null, we find the null velocity to be U = -M-1 ∂B/∂t with all quantities evaluated ...

  19. Null structure groups in eleven dimensions

    CERN Document Server

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

    2004-01-01

    We classify all the structure groups which arise as subgroups of the isotropy group, $(Spin(7)\\ltimes\\mathbb{R}^8)\\times\\mathbb{R}$, of a single null Killing spinor in eleven dimensions. We construct the spaces of spinors fixed by these groups. We determine the conditions under which structure subgroups of the maximal null strucuture group $(Spin(7)\\ltimes\\mathbb{R}^8)\\times\\mathbb{R}$ may also be embedded in SU(5), and hence the conditions under which supersymmetric spacetime admits only null, or both timelike and null, Killing spinors. This concludes, for spacetimes admitting at least one null Killing spinor, the first, purely algebraic, phase of the refined G-structure classification of supersymmetric spacetimes in eleven dimensions, the objective of which is the derivation of the general local bosonic solution of the Killing spinor equation of eleven dimensional supergravity. Finally, we discuss how the second phase of the classification, involving the direct analysis of the Killing spinor equation, may b...

  20. Two Roads to the Null Energy Condition

    CERN Document Server

    Parikh, Maulik

    2015-01-01

    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 simply 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.

  1. Null Points in Three-Dimensional Kinetic Simulations of Magnetic Reconnection

    Science.gov (United States)

    Deca, J.; Olshevsky, V.; Divin, A. V.; Innocenti, M. E.; Cazzola, E.; Peng, B.; Markidis, S.; Ormvråk, M.; Lapenta, G.

    2015-12-01

    Kinetic particle-in-cell simulations are the primary tool for studying magnetic reconnection in space plasmas. Magnetic null points are believed to be the preferred locations in space where magnetic reconnection is luckily to happen, and are in the focus of interest of space missions such as Cluster and MMS. Simulations of magnetic reconnection in various configurations performed with the implicit particle-in-cell code iPic3D revealed that nulls are ubiquitious in these models. We apply the Poincare index technique to locate and identify the topological characteristics of the magnetic null points in different three-dimensional simulations. We investigate the relevance of magnetic nulls to energy dissipation, turbulence and plasma instabilities. In particular, we found out that magnetic nulls of spiral type associated with magnetic islands and flux ropes play more important role in the energy release than the radial nulls. This finding is in accordance with some recent MHD simulations and in situ observations of Cluster spacecraft.

  2. Magnetized Emergent Universe with Null Radiation Flow

    Science.gov (United States)

    Singh, J. K.; Rani, Sarita

    2016-01-01

    In this paper, we study the Bianchi type-I cosmological model in a different basic form incorporating with null radiation flow with the perfect fluid in the presence as well as absence of a source free magnetic field. A set of new exact solutions of Einstein field equations are obtained in both the cases. We observe that the emergent universe model with null radiation flow approaches to de-sitter universe at late time obeying the same rate of expansion in presence and absence of the magnetic field.

  3. Null Geodesics in Brane World Scenarios

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-Feng; ZHANG Yuan-Zhong

    2004-01-01

    We study the null bulk geodesic motion in the brane world in which the bulk metric has an un-stabilized extra spatial dimension. We find that the null bulk geodesic motion as observed on the 3-brane with Z2 symmetry would be a timelike geodesic motion even though there exists an extra non-gravitational force in contrast with the case of the stabilized extra spatial dimension. In other words the presence of the extra non-gravitational force would not violate thc Z2 symmetry.

  4. MPD in Telomerase Null Mice

    Science.gov (United States)

    2007-09-01

    telomere dysfunctional mice will further fuel the genomic instability generated from progressive Figure 5 5FU treated telomere dysfunction bone...marrow has increased megakaryocytic colonies. Equal number of bone marrow cells from the 5FU treated mice of the various indicated cohorts are...We treated the cohorts of the G4 mTerc mutant mice with telomere dysfunction and normal G0 controls with 5FU at (50mg/kg body weight) once every

  5. The Emergence, Motion, and Disappearance of Magnetic Null Points

    Science.gov (United States)

    Murphy, Nicholas; Parnell, Clare; Haynes, Andrew; Pontin, David

    2013-10-01

    Magnetic reconnection frequently occurs at and around magnetic null points. We derive exact expressions for the motion of a magnetic null point in a smoothly varying magnetic field. We define xn as the position of a null, U = dxn/dt as the null's velocity, and M as the Jacobian matrix of the magnetic field at the null. By evaluating the derivative of the magnetic field following the motion of the null, we find the null velocity to be U = -M-1 ∂B/∂t with all quantities evaluated at the null point. For resistive MHD, this reduces to U =V (xn) - ηM-1∇2B. This expression indicates that any difference between the plasma flow velocity at the null and the velocity of the null itself is due to resistive diffusion of the magnetic field. Null points must diffuse in and out of existence. Null-null pairs first appear (or disappear) as a single degenerate null with singular M, and then instantaneously move apart (together) infinitely fast. An expression describing the motion of separators cannot depend solely on local parameters and must include information on connectivity changes due to reconnection along the entire field line.

  6. The Null Hypothesis as the Research Hypothesis.

    Science.gov (United States)

    Myers, Barbara E.; Pohlmann, John T.

    A procedure was developed within hypothesis-testing logic that allows researchers to support a hypothesis that has traditionally been the statistical or null hypothesis. Four activities involved in attainment of this goal were discussed: (1) development of statistical logic needed to define the sampling distribution associated with the hypothesis…

  7. Polarization nulling interferometry for exoplanet detection

    NARCIS (Netherlands)

    Spronck, J.; Pereira, S.F.; Braat, J.J.M.

    2006-01-01

    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, th

  8. Infinite Blueshift of Charged Null Particles

    OpenAIRE

    Mann, R. B.; Sajko, W. N.

    1994-01-01

    We demonstrate that charged null particles can be infinitely blue\\-shifted in a Kerr-Newman spacetime. The surface of infinite blueshift can be outside of the ergosphere in a Kerr-Newman spacetime, and outside of the outer event horizon for a Reissner-Nordstrom spacetime. Implications for extensions of the standard model which incorporate charged neutrinos are discussed.

  9. Effect of Interleukin-1beta and Dehydroepiandrosterone on the Expression of Lumican and Fibromodulin in Fibroblast-Like Synovial Cells of the Human Temporomandibular Joint

    OpenAIRE

    Okamoto, K; Kiga, N.; Shinohara, Y.; Tojyo, I.; Fujita, S.

    2015-01-01

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular jo...

  10. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint

    OpenAIRE

    Okamoto, K; Kiga, N.; Shinohara, Y.; Tojyo, I.; Fujita, S.

    2015-01-01

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular jo...

  11. Gravitational collapse of a cylindrical null shell in vacuum

    Directory of Open Access Journals (Sweden)

    S. Khakshournia

    2008-03-01

    Full Text Available   Barrabès-Israel null shell formalism is used to study the gravitational collapse of a thin cylindrical null shell in vacuum. In general the lightlike matter shell whose history coincides with a null hypersurface is characterized by a surface energy density. In addition, a gravitational impulsive wave is present on this null hypersurface whose generators admit both the shear and expansion. In the case of imposing the cylindrical flatness the surface energy-momentum tensor of the matter shell on the null hypersurface vanishes and the null hyper- surface is just the history of the gravitational wave .

  12. Depressed adrenomedullin in the embryonic transforming growth factor-beta1 null mouse becomes elevated postnatally.

    Science.gov (United States)

    Bodegas, Elena; Martínez, Alfredo; Ozbun, Laurent L; Garayoa, Mercedes; Letterio, John J; Montuenga, Luis M; Jakowlew, Sonia B

    2004-02-01

    Transforming growth factor-beta (TGF-beta) and adrenomedullin are multifunctional regulatory proteins which are expressed in developing embryonic and adult tissues. Because of their colocalization, TGF-beta1 and adrenomedullin may be able to coordinately act to influence development and differentiation. In order to learn more about the biology of adrenomedullin in the absence of the effects of TGF-beta1 in vivo, we examined adrenomedullin in the TGF-beta1 null mouse. A generally lower amount of adrenomedullin was detected by immunohistochemical staining analysis in multiple tissues from embryonic TGF-beta1 null mice compared to wildtype animals, including the heart, lung, brain, liver, and kidney, among others. In contrast, immunohistochemical staining for adrenomedullin was more intense in tissues of the postnatal TGF-beta1 null mouse compared to the wildtype mouse. These observations were confirmed by quantitative real time RT-PCR for adrenomedullin in both embryos and postnatal animals, as well as in cultured mouse embryo fibroblasts from TGF-beta1 null and wildtype mice. In addition, when cultured mouse embryo fibroblasts were treated with a neutralizing monoclonal antibody against TGF-beta1, the levels of adrenomedullin expression were statistically reduced compared to untreated cells. Our data show that expression of adrenomedullin is reduced in tissues of the developing embryonic TGF-beta1 null mouse compared to the wildtype mouse, but increases during postnatal development in TGF-beta1 null mice. The elevated expression of adrenomedullin which occurs postnatally in the TGF-beta1 null mouse may be a cause or a consequence of the multifocal wasting syndrome which is characteristic of postnatal TGF-beta1 null mice.

  13. Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice.

    Science.gov (United States)

    Martineau, Corine; Martin-Falstrault, Louise; Brissette, Louise; Moreau, Robert

    2014-08-01

    A positive correlation between plasma levels of HDL and bone mass has been reported by epidemiological studies. As scavenger receptor class B, type I (SR-BI), the gene product of Scarb1, is known to regulate HDL metabolism, we recently characterized bone metabolism in Scarb1-null mice. These mice display high femoral bone mass associated with enhanced bone formation. As gender differences have been reported in HDL metabolism and SR-BI function, we investigated gender-specific bone alterations in Scarb1-null mice by microtomography and histology. We found 16% greater relative bone volume and 39% higher bone formation rate in the vertebrae from 2-month-old Scarb1-null females. No such alteration was seen in males, indicating gender- and region-specific differences in skeletal phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma levels, were increased in both Scarb1-null genders, the latter being concurrent to impaired corticosterone response to fasting. Plasma levels of estradiol did not differ between null and WT females, suggesting that the estrogen metabolism alteration is not relevant to the higher vertebral bone mass in female Scarb1-null mice. Constitutively, high plasma levels of leptin along with 2.5-fold increase in its expression in white adipose tissue were measured in female Scarb1-null mice only. In vitro exposure of bone marrow stromal cells to ACTH and leptin promoted osteoblast differentiation as evidenced by increased gene expression of osterix and collagen type I alpha. Our results suggest that hyperleptinemia may account for the gender-specific high bone mass seen in the vertebrae of female Scarb1-null mice.

  14. The atherogenic Scarb1 null mouse model shows a high bone mass phenotype.

    Science.gov (United States)

    Martineau, Corine; Martin-Falstrault, Louise; Brissette, Louise; Moreau, Robert

    2014-01-01

    Scavenger receptor class B, type I (SR-BI), the Scarb1 gene product, is a receptor associated with cholesteryl ester uptake from high-density lipoproteins (HDL), which drives cholesterol movement from peripheral tissues toward the liver for excretion, and, consequently, Scarb1 null mice are prone to atherosclerosis. Because studies have linked atherosclerosis incidence with osteoporosis, we characterized the bone metabolism in these mice. Bone morphometry was assessed through microcomputed tomography and histology. Marrow stromal cells (MSCs) were used to characterize influence of endogenous SR-BI in cell functions. Total and HDL-associated cholesterol in null mice were increased by 32-60%, correlating with its role in lipoprotein metabolism. Distal metaphyses from 2- and 4-mo-old null mice showed correspondingly 46 and 37% higher bone volume fraction associated with a higher number of trabeculae. Histomorphometric analyses in 2-mo-old null male mice revealed 1.42-fold greater osteoblast surface, 1.37-fold higher percent mineralizing surface, and 1.69-fold enhanced bone formation rate. In vitro assays for MSCs from null mice revealed 37% higher proliferation rate, 48% more alkaline phosphatase activity, 70% greater mineralization potential and a 2-fold osterix (Sp7) expression, yet a 0.5-fold decrease in caveolin-1 (Cav1) expression. Selective uptake levels of HDL-associated cholesteryl oleate and estradiol were similar between MSC from wild-type and Scarb1 null mice, suggesting that its contribution to this process is not its main role in these cells. However, Scarb1 knockout stunted the HDL-dependent regulation of Cav1 genic expression. Scarb1 null mice are not prone to osteoporosis but show higher bone mass associated with enhanced bone formation.

  15. Molecular identification of rare FY*Null and FY*X alleles in Caucasian thalassemic family from Sardinia.

    Science.gov (United States)

    Manfroi, Silvia; Scarcello, Antonio; Pagliaro, Pasqualepaolo

    2015-10-01

    Molecular genetic studies on Duffy blood group antigens have identified mutations underlying rare FY*Null and FY*X alleles. FY*Null has a high frequency in Blacks, especially from sub-Saharan Africa, while its frequency is not defined in Caucasians. FY*X allele, associated with Fy(a-b+w) phenotype, has a frequency of 2-3.5% in Caucasian people while it is absent in Blacks. During the project of extensive blood group genotyping in patients affected by hemoglobinopathies, we identified FY*X/FY*Null and FY*A/FY*Null genotypes in a Caucasian thalassemic family from Sardinia. We speculate on the frequency of FY*X and FY*Null alleles in Caucasian and Black people; further, we focused on the association of FY*X allele with weak Fyb antigen expression on red blood cells and its identification performing high sensitivity serological typing methods or genotyping.

  16. Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Lao, Ye; Maximov, Anton;

    2008-01-01

    secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance...

  17. MAPK signaling pathways and HDAC3 activity are disrupted during emerin-null myogenic progenitor differentiation.

    Science.gov (United States)

    Collins, Carol M; Ellis, Joseph; Holaska, James M

    2017-02-10

    Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD). Emerin is an integral inner nuclear membrane protein and a component of the nuclear lamina. EDMD is characterized by skeletal muscle wasting, cardiac conduction defects and tendon contractures. The failure to regenerate skeletal muscle is predicted to contribute to the skeletal muscle pathology of EDMD. We hypothesize muscle regeneration defects are caused by impaired muscle stem cell differentiation. Myogenic progenitors derived from emerin-null mice were used to confirm their impaired differentiation and analyze selected myogenic molecular pathways. Emerin-null progenitors were delayed in their cell cycle exit, had decreased myosin heavy chain (MyHC) expression and formed fewer myotubes. Emerin binds to and activates histone deacetylase 3 (HDAC3). Here we show theophylline, an HDAC3-specific activator, improved myotube formation in emerin-null cells. Addition of the HDAC3-specific inhibitor RGFP966 blocked myotube formation and MyHC expression in wildtype and emerin-null myogenic progenitors, but did not affect cell cycle exit. Downregulation of emerin was previously shown to affect the p38 and ERK MAPK pathways in C2C12 myoblast differentiation. Using a pure population of myogenic progenitors completely lacking emerin expression we show these pathways are also disrupted. ERK inhibition improved MyHC expression in emerin-null cells, but failed to rescue myotube formation or cell cycle exit. p38 MAPK inhibition prevented differentiation in both wildtype and emerin-null progenitors. These results show each of these molecular pathways specifically regulate particular stages of myogenic differentiation in an emerin-dependent manner. Thus, pharmacological targeting of multiple pathways acting at specific differentiation stages may be a better therapeutic approach in the future to rescue muscle regeneration in vivo.

  18. Statistics and accuracy of magnetic null identification in multispacecraft data

    Science.gov (United States)

    Eriksson, E.; Vaivads, A.; Khotyaintsev, Yu. V.; Khotyayintsev, V. M.; André, M.

    2015-09-01

    Complex magnetic topologies are ubiquitous in astrophysical plasmas. Analyzing magnetic nulls, regions of vanishing magnetic field, is one way to characterize 3-D magnetic topologies. Magnetic nulls are believed to be important in 3-D reconnection and turbulence. In the vicinity of a null, plasma particles become unmagnetized and can be accelerated to high energies by electric fields. We present the first statistical study of the occurrence of magnetic nulls and their types in the Earth's nightside magnetosphere. We are able to identify the nulls both in the tail and in the magnetopause current sheets. On average, we find one null for every few current sheet crossings. We show that the type identification of magnetic nulls may be sensitive to local fluctuations in the magnetic field. We develop and demonstrate a method to estimate the reliability of the magnetic null type identification.

  19. Statistics and accuracy of magnetic null identification in multispacecraft data

    OpenAIRE

    Eriksson, Elin; Vaivads, Andris; Khotyaintsev, Yuri V.; Khotyayintsev, V. M.; Andre, Mats

    2015-01-01

    Complex magnetic topologies are ubiquitous in astrophysical plasmas. Analyzing magnetic nulls, regions of vanishing magnetic field, is one way to characterize 3-D magnetic topologies. Magnetic nulls are believed to be important in 3-D reconnection and turbulence. In the vicinity of a null, plasma particles become unmagnetized and can be accelerated to high energies by electric fields. We present the first statistical study of the occurrence of magnetic nulls and their types in the Earth's nig...

  20. Generation of hematopoietic humanized mice in the newborn BALB/c-Rag2null Il2rγnull mouse model: a multivariable optimization approach.

    Science.gov (United States)

    Lang, Julie; Weiss, Nicholas; Freed, Brian M; Torres, Raul M; Pelanda, Roberta

    2011-07-01

    Hematopoietic humanized mice generated via transplantation of human hematopoietic stem cells (hHSCs) into immunodeficient mice are a valuable tool for studying development and function of the human immune system. This study was performed to generate a protocol that improves development and quality of humanized mice in the BALB/c-Rag2(null)Il2rγ(null) strain, testing route of injection, in vitro culture and freezing of hHSCs, types of cytokines in the culture, and co-injection of lineage-depleted CD34(-) cells. Specific hHSC culturing conditions and the addition of support cells were found to increase the frequency, and human hematopoietic chimerism, of humanized mice. The optimized protocol resulted in BALB/c-Rag2(null)Il2rγ(null) humanized mice displaying more consistent human hematopoietic and lymphoid engraftment. Thus, hematopoietic humanized mice generated on a BALB/c immunodeficient background represent a useful model to study the human immune system.

  1. A Conformal Extension Theorem based on Null Conformal Geodesics

    CERN Document Server

    Lübbe, Christian

    2008-01-01

    In this article we describe the formulation of null geodesics as null conformal geodesics and their description in the tractor formalism. A conformal extension theorem through an isotropic singularity is proven by requiring the boundedness of the tractor curvature and its derivatives to sufficient order along a congruence of null conformal geodesic. This article extends earlier work by Tod and Luebbe.

  2. Null controllability and the algebraic Riccati equation in Banach Spaces

    NARCIS (Netherlands)

    Van Neerven, J.M.A.M.

    2005-01-01

    By a recent result of Priola and Zabczyk, a null controllable linear system [y'(t) = Ay(t) + Bu(t)] in a Hilbert space E is null controllable with vanishing energy if and only if it is null controllable and the only positive self-adjoint solution of the associated algebraic Riccati equation [XA + A*

  3. Morphological Uniformity and the Null Subject Parameter in Adult SLA.

    Science.gov (United States)

    Davies, William D.

    1996-01-01

    Focuses on the application of the Null Subject Parameter. Data reveals that some second-language learners exhibit knowledge that English is morphologically nonuniform yet still accept English null subject sentences. Findings disprove the Morphological Uniformity Hypothesis, indicating that any reformulation of the Null Subject Parameter must…

  4. Blob dynamics in TORPEX poloidal null configurations

    Science.gov (United States)

    Shanahan, B. W.; Dudson, B. D.

    2016-12-01

    3D blob dynamics are simulated in X-point magnetic configurations in the TORPEX device via a non-field-aligned coordinate system, using an isothermal model which evolves density, vorticity, parallel velocity and parallel current density. By modifying the parallel gradient operator to include perpendicular perturbations from poloidal field coils, numerical singularities associated with field aligned coordinates are avoided. A comparison with a previously developed analytical model (Avino 2016 Phys. Rev. Lett. 116 105001) is performed and an agreement is found with minimal modification. Experimental comparison determines that the null region can cause an acceleration of filaments due to increasing connection length, but this acceleration is small relative to other effects, which we quantify. Experimental measurements (Avino 2016 Phys. Rev. Lett. 116 105001) are reproduced, and the dominant acceleration mechanism is identified as that of a developing dipole in a moving background. Contributions from increasing connection length close to the null point are a small correction.

  5. Collapse and bounce of null fluids

    CERN Document Server

    Creelman, Bradley

    2016-01-01

    Exact solutions describing the spherical collapse of null fluids can contain regions which violate the energy conditions. Physically the violations occur when the infalling matter continues to move inwards even when non-gravitational repulsive forces become stronger than gravity. In 1991 Ori proposed a resolution for these violations: spacetime surgery should be used to replace the energy condition violating region with an outgoing solution. The matter bounces. We revisit and implement this proposal for the more general Husain null fluids. We find that: 1) generically there is a thin shell discontinuity along the junction surface between ingoing and outgoing solutions, 2) there are special cases where the shell vanishes and 3) these conclusions also apply to charged Vaidya (the original paper argued that there were no shells at the junctions). Along the way we note an apparent error in the standard classification of energy condition violations for Type II stress-energy tensors.

  6. Compressional plasma flows near magnetic null points

    Energy Technology Data Exchange (ETDEWEB)

    Bulanov, S.V.; Ol' shanetskii, M.A.

    1985-06-01

    Self-similar solutions of the MHD equations describing time-varying plasma flows near magnetic null points are analyzed. Various classes of particular solutions are constructed. Special attention is paid to compressional flows which involve the development of sharp maxima. The stability of the self-similar solutions is studied. Solutions describing the motion of a vortex in MHD are constructed. The possibility of producing current sheets in nonuniform magnetic configurations is demonstrated.

  7. Collapse and bounce of null fluids

    OpenAIRE

    Creelman, Bradley; Booth, Ivan

    2016-01-01

    Exact solutions describing the spherical collapse of null fluids can contain regions which violate the energy conditions. Physically the violations occur when the infalling matter continues to move inwards even when non-gravitational repulsive forces become stronger than gravity. In 1991 Ori proposed a resolution for these violations: spacetime surgery should be used to replace the energy condition violating region with an outgoing solution. The matter bounces. We revisit and implement this p...

  8. PHASE CLOSURE NULLING: THEORY AND PRACTICE

    Directory of Open Access Journals (Sweden)

    A. Chelli

    2009-01-01

    Full Text Available We provide a complete theory of the phase closure of a binary system in which a small, feeble, and unresolved companion acts as a perturbing parameter on the spatial frequency spectrum of a dominant, bright, resolved source. We demonstrate that the in uence of the companion can be measured with precision by measuring the phase closure of the system near the nulls of the primary visibility function. In these regions of phase closure nulling, frequency intervals always exist where the phase closure signature of the companion is larger than any systematic error and can thus be measured. We show that this technique allows retrieval of many astrophysically relevant properties of faint and close companions such as ux, position, and in favorable cases, spectrum. As a proof of concept, using the AMBER/VLTI instrument with 3 auxiliary telescopes of 1.8 m and only 15 minutes of on-sky integration, we detected the ve magnitudes fainter companion of HD 59717 at only 3.5 stellar radii distance from the primary. This is one of the highest contrast detected by interferometry between a companion and its parent star. We conclude by a rapid study of the potentialities of phase closure nulling observations with current interferometers and explore the requirements for a new type of dedicated instrument.

  9. A note on inextensible flows of partially and pseudo null curves in E_1^4

    OpenAIRE

    Yuzbasi, Zuhal Kucukarslan; Bektas, Mehmet

    2013-01-01

    In this paper, we study inextensible flows of partially null and pseudo null curves in E_1^4. We give neccessary and sufficent conditions for inextensible flows of partially null and pseudo null curves in E_1^4

  10. System and Method for Null-Lens Wavefront Sensing

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. Null Object模式研究%Research on Null Object Pattern

    Institute of Scientific and Technical Information of China (English)

    吴清寿

    2013-01-01

    在许多面向对象的程序设计语言中,对象引用可能为空.在调用任何方法之前这些引用需要被检测以确保它们不为空.频繁的检测会引起代码的重复和系统的不稳定.Null Object模式能够用来解决这一问题.本文阐述了Null Object模式及其实现方式,针对空目标的单一实例化策略,给出了改进措施.Null Object模式对去除重复检测和减少空引用异常有较明显的效果.

  13. Magnetic nulls in three-dimensional kinetic simulations of space plasmas

    Science.gov (United States)

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

    2016-04-01

    We present a survey of magnetic nulls and associated energy dissipation in different three-dimensional kinetic particle-in-cell simulations of space plasmas. The configurations under study include: a traditional Harris current sheet and current sheets with asymmetric density distribution, dipolar and quadrupolar planetary magnetospheres, lunar magnetic anomalies, and decaying turbulence. Nulls are detected in the simulation snapshots by the topological degree method. In all runs except the quadrupolar magnetospere the dominating majority of nulls are of spiral topological type. When supported by strong currents, these nulls indicate the regions of strong energy dissipation. Dissipation, often accompanied by the changes in magnetic topology, is caused by plasma instabilities in the current channels or on their interfaces. Radial nulls show less activity, they can be created or destroyed in pairs, via topological bifurcations. Although such events demonstrate energy release, they are rather rare and short-living. An important implication of our study to observations is that magnetic topology should not be considered independently of other plasma properties such as currents.

  14. Magnetic reconnection in turbulent space plasmas: null-points or pinches?

    Science.gov (United States)

    Olshevsky, Vyacheslav; Lapenta, Giovanni; Markidis, Stefano; Divin, Andrey

    2014-05-01

    We report particle-in-cell simulations of magnetic reconnection in the configuration containing both null-points and pinches. All indicators suggest that secondary magnetic reconnection driven by kinking of the pinches plays a dominant role in the energetics of the system. While there is no substantial energy dissipation in the vicinity of X-type null-points. Such reconnection results in tremendous release of magnetic energy, generation of suprathermal particles and waves. Similar scenario may take place in turbulent space plasmas, where current channels and twisted magnetic fields are detected.

  15. Kinetic simulations of magnetic reconnection in three-dimensional null-points.

    Science.gov (United States)

    Olshevsky, Vyacheslav; Lapenta, Giovanni; Divin, Andrey; Markidis, Stefano

    2015-04-01

    We report kinetic particle-in-cell simulations of an essentially three-dimensional magnetized plasma configuration. Initially the evolution is governed by large-scale fluid modes excited by the pressure imbalance. At this phase current channels (pinches) are created along the sequences of spiral null-points. After ten ion gyroperiods the relaxation is over, and about half of magnetic energy is converted to ion currents, particle heating, and generation of suprathermal particles. At the next phase the evolution is dominated by volumetric magnetic reconnection, mainly associated with spiral null-points (pinches); non-spiral nulls don't play important role in the energy release. Such reconection is a possible mechanism of magnetic energy dissipation in turbulent space plasmas where currents and twisted field lines are ubiquitous.

  16. Energetics of kinetic reconnection in a three-dimensional null points cluster

    CERN Document Server

    Olshevsky, Vyacheslav; Markidis, Stefano

    2015-01-01

    We performed three-dimensional Particle-in-Cell simulations of magnetic reconnection with multiple magnetic null points. Magnetic field energy conversion into kinetic energy was about five times higher than in traditional Harris sheet configuration. More than 85% of initial magnetic field energy was transferred to particle energy during 25 reversed ion cyclofrequencies. Magnetic reconnection in the cluster of null points evolved in three phases. During the first phase, ion beams were excited, that then gave part of their energy back to magnetic field in the second phase. In the third phase, magnetic reconnection occurs in many small patches around the current channels formed along the stripes of low magnetic field. Magnetic reconnection in null points presents essentially three-dimensional features, with no two dimensional symmetries or current sheets.

  17. Energetics of kinetic reconnection in a three-dimensional null-point cluster.

    Science.gov (United States)

    Olshevsky, V; Lapenta, G; Markidis, S

    2013-07-26

    We perform three-dimensional particle-in-cell simulations of magnetic reconnection with multiple magnetic null points. Magnetic field energy conversion into kinetic energy is about five times higher than in traditional Harris sheet configuration. More than 85% of initial magnetic field energy is transferred to particle energy during 25 reversed ion cyclofrequencies. Magnetic reconnection in the cluster of null points evolves in three phases. During the first phase, ion beams are excited, then give part of their energy back to the magnetic field in the second phase. In the third phase, magnetic reconnection occurs in many small patches around the current channels formed along the stripes of a low magnetic field. Magnetic reconnection in null points essentially presents three-dimensional features, with no two-dimensional symmetries or current sheets.

  18. Reconnection experiments with 3D magnetic nulls

    Science.gov (United States)

    Vrublevskis, A.; Egedal, J.; Le, A.; Montag, P.

    2011-10-01

    Three-dimensional effects have been crucial in explaining experiments at the Versatile Toroidal Facility (VTF) even in nominal axisymmetric plasmas with a non-vanishing toroidal field. In general, depending on the topological and geometric structure of the magnetic field, a rich collection of magnetic reconnection scenarios is possible in three dimensions. The new adjustable set of coils in VTF allows exploring reconnection in 2D and 3D geometries including configurations with magnetic null points. We present results of a numerical and experimental investigation of magnetic field topologies attainable in VTF. This work was supported by NSF CAREER Award 0844620.

  19. Stimulation of Sigma-1 Receptor Ameliorates Depressive-like Behaviors in CaMKIV Null Mice.

    Science.gov (United States)

    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.

  20. Recent developments with the visible nulling coronagraph

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Bolcar, Matthew R.; Clampin, Mark; Petrone, Peter; Helmbrecht, Michael A.; Howard, Joseph M.; Miller, Ian J.

    2016-08-01

    A wide array of general astrophysics studies including detecting and characterizing habitable exoplanets could be enabled by a future large segmented telescope with sensitivity in the UV, optical, and infrared bands. When paired with a starshade or coronagraph, such an observatory could enable direct imaging and detailed spectroscopic observations of nearby Earth-like habitable zone planets. Over the past several years, a laboratory-based Visible Nulling Coronagraph (VNC) has evolved to reach requisite contrasts over a 1 nm bandwidth at narrow source angle separation using a segmented deformable mirror in one arm of a Mach-Zehnder layout. More recent efforts targeted broadband performance following the addition of two sets of half-wave Fresnel rhomb achromatic phase shifters (APS) with the goal of reaching 10-9 contrast, at a separation of 2λ/D, using a 40 nm (6%) bandwidth single mode fiber source. Here we present updates on the VNC broadband nulling effort, including approaches to addressing system contrast limitations.

  1. Generation and characterization of UL21-null herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Yoshifumi eMuto

    2012-11-01

    Full Text Available UL21 of herpes simplex virus type 1 (HSV-1 is an accessory gene that encodes a component of the tegument. Homologs of this protein have been identified in the alpha, beta, and gamma herpesvirus subfamilies, although their functions are unclear. To clarify the functions of UL21, we generated a UL21-null HSV-1 mutant. Growth analysis showed that the synthesis of infectious UL21-null HSV-1 in glial cells was delayed and that the overall yield was low. The plaque sizes of the UL21-null mutant were smaller than those of wild-type HSV-1. We identified several candidate UL21-interacting proteins, including intermediate filaments, by yeast two-hybrid screening. The distribution of glial fibrillary acidic protein (GFAP, which is the main component of intermediate filaments, was altered in UL21-null mutant-infected glial cells compared to wild-type virus-infected cells. These results will help clarify the function of UL21 and broaden our understanding of the life cycle of HSV.

  2. On the null origin of the ambitwistor string

    Science.gov (United States)

    Casali, Eduardo; Tourkine, Piotr

    2016-11-01

    In this paper we present the null string origin of the ambitwistor string. Classically, the null string is the tensionless limit of string theory, and so too is the ambitwistor string. Both have as constraint algebra the Galilean Conformal Algebra in two dimensions. But something interesting happens in the quantum theory since there is an ambiguity in quantizing the null string. We show that, given a particular choice of quantization scheme and a particular gauge, the null string coincides with the ambitwistor string both classically and quantum mechanically. We also show that the same holds for the spinning versions of the null string and ambitwistor string. With these results we clarify the relationship between the ambitwistor string, the null string, the usual string and the Hohm-Siegel-Zwiebach theory.

  3. Jet phenomena above null points of the coronal magnetic field

    Science.gov (United States)

    Filippov, B.; Koutchmy, S.; Golub, L.

    2009-12-01

    Short-lived plasma jets of various scales, from giant X-ray jets more than 300 Mm in extent to numerous small jets with sizes typical of macrospicules, are the phenomena observed in the solar corona in extreme ultraviolet and X-ray emission. Small jets are particularly prominent in polar coronal holes. They are close neighbors of tiny bright loops and coincide in time with their sudden brightening and increase in size. The geometric shape of the jets and their location suggest that they arise near singular null points of the coronal magnetic field. These points appear in coronal holes due to the emergence of small bipolar or unipolar magnetic structures within large-scale unipolar cells. Polar jets show a distinct vertical plasma motion in a coronal hole that introduces significant momentum and mass into the solar wind flow. Investigating the dynamics of polar jets can elucidate certain details in the problem of fast solar wind acceleration.

  4. Particle acceleration near magnetic nulls using MMS data

    Science.gov (United States)

    Eriksson, Elin; Vaivads, Andris; Khotyaintsev, Yuri; Graham, Daniel; Markidis, Stefano; Peng, Ivy Bo; André, Mats; Burch, James; Lindqvist, Per-Arne; Ergun, Robert; Torbert, Roy; Magnes, Werner; Russell, Christopher; Giles, Barbara; Pollock, Craig

    2016-04-01

    Regions with vanishing magnetic field, also referred to as magnetic nulls, are of high interest in plasma physics. Near magnetic nulls particles become unmagnetized and can by interacting with electric fields be accelerated up to high energies. Magnetic nulls have been observed and studied before using using Cluster data with different methods. Magnetic nulls found by Cluster have been obtained with spacecraft separation comparable to ion scales and particle instrumentation is not sufficient to resolve in detail physical processes of particle acceleration around the null. Now we use the MMS (Magnetospheric Multiscale) data to study these processes in detail. The MMS separation is well below the ion scale and data from particle instruments has sufficient resolution during burst mode to resolve these processes for our events. We study nulls in detail during phase 1a of the MMS mission. Burst data during this phase are mainly from the magnetopause, but some intervals cover the magnetosheath, bowshock, and solar wind. We particularly focus on magnetic nulls associated with strong currents, which can potentially be associated with the electron diffusion region of magnetic reconnection. There we also expect particle acceleration to occur. A preliminary study has already identified several nulls of high interest in the burst data. We present a detailed study of these nulls.

  5. Improving accuracy in the MPM method using a null space filter

    Science.gov (United States)

    Gritton, Chris; Berzins, Martin

    2017-01-01

    The material point method (MPM) has been very successful in providing solutions to many challenging problems involving large deformations. Nevertheless there are some important issues that remain to be resolved with regard to its analysis. One key challenge applies to both MPM and particle-in-cell (PIC) methods and arises from the difference between the number of particles and the number of the nodal grid points to which the particles are mapped. This difference between the number of particles and the number of grid points gives rise to a non-trivial null space of the linear operator that maps particle values onto nodal grid point values. In other words, there are non-zero particle values that when mapped to the grid point nodes result in a zero value there. Moreover, when the nodal values at the grid points are mapped back to particles, part of those particle values may be in that same null space. Given positive mapping weights from particles to nodes such null space values are oscillatory in nature. While this problem has been observed almost since the beginning of PIC methods there are still elements of it that are problematical today as well as methods that transcend it. The null space may be viewed as being connected to the ringing instability identified by Brackbill for PIC methods. It will be shown that it is possible to remove these null space values from the solution using a null space filter. This filter improves the accuracy of the MPM methods using an approach that is based upon a local singular value decomposition (SVD) calculation. This local SVD approach is compared against the global SVD approach previously considered by the authors and to a recent MPM method by Zhang and colleagues.

  6. Dynamics of a probe null string in the gravitational field of a closed null string radially collapsing in the plane

    Science.gov (United States)

    Lelyakov, A. P.; Karpenko, A. S.

    2017-01-01

    We consider the dynamics of a probe null string in the gravitational field of a closed ( "thick") null string radially collapsing in a plane. Analysis of the obtained solutions suggests that there might exist several properties of a null-string gas interesting from the cosmological standpoint, such as acceleration of expansion or contraction, a granular structure of the gas, the emergence of stable polarized states, and a domain structure.

  7. Averaged Null Energy Condition from Causality

    CERN Document Server

    Hartman, Thomas; Tajdini, Amirhossein

    2016-01-01

    Unitary, Lorentz-invariant quantum field theories in flat spacetime obey microcausality: commutators vanish at spacelike separation. For interacting theories in more than two dimensions, we show that this implies that the averaged null energy, $\\int du T_{uu}$, must be positive. This non-local operator appears in the operator product expansion of local operators in the lightcone limit, and therefore contributes to $n$-point functions. We derive a sum rule that isolates this contribution and is manifestly positive. The argument also applies to certain higher spin operators other than the stress tensor, generating an infinite family of new constraints of the form $\\int du X_{uuu\\cdots u} \\geq 0$. These lead to new inequalities for the coupling constants of spinning operators in conformal field theory, which include as special cases (but are generally stronger than) the existing constraints from the lightcone bootstrap, deep inelastic scattering, conformal collider methods, and relative entropy. We also comment ...

  8. Null fluid collapse in brane world models

    CERN Document Server

    Harko, Tiberiu

    2013-01-01

    The brane world description of our universe entails a large extra dimension and a fundamental scale of gravity that may be lower than the Planck scale by several orders of magnitude. An interesting consequence of this scenario occurs in the nature of spherically-symmetric vacuum solutions to the brane gravitational field equations, which often have properties quite distinct from the standard black hole solutions of general relativity. In this paper, the spherically-symmetric collapse on the brane world of four types of null fluid, governed by the barotropic, polytropic, strange quark "bag" model and Hagedorn equations of state, is investigated. In each case, we solve the approximate gravitational field equations, obtained in the high density limit, determine the equation which governs the formation of apparent horizons and investigate the conditions for the formation of naked singularities. Though, naively, one would expect the increased effective energy density on the brane to favor the formation of black ho...

  9. Wormholes minimally violating the null energy condition

    CERN Document Server

    Bouhmadi-Lopez, Mariam; Martin-Moruno, Prado

    2014-01-01

    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 "the little sibling of the big rip", 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 analyze 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 generalisation of the eq...

  10. Reconnection experiments including 3D magnetic nulls

    Science.gov (United States)

    Le, A.; Egedal, J.; Vrublevskis, A.

    2010-11-01

    A rich collection of magnetic reconnection scenarios is possible in three dimensions depending on the topological and geometric structure of the magnetic field [1]. In recent experiments at the Versatile Toroidal Facility (VTF) three-dimensional effects were essential even in nearly axisymmetric plasmas with a non-vanishing toroidal field [2]. To explore reconnection in 3D geometries including magnetic null points, a new adjustable set of coils will be installed in the vacuum chamber of VTF. The range of vacuum magnetic field topologies attainable in VTF will be explored numerically. Plasma reconnection experiments will be run in these configurations, and measurements will be presented if available. [4pt] [1] CE Parnell, et al., (2009) ``Three-Dimensional Magnetic Reconnection, in Magnetic Coupling between the Interior and the Atmosphere of the Sun,'' eds. S.S. Hasan and R.J. Rutten, Springer-Verlag, Heidelberg, Berlin. [0ex] [2] Katz, N. et al., (2010) Phys. Rev. Lett. 104, 255004.

  11. DARWIN nulling interferometer breadboard II: design and manufacturing

    NARCIS (Netherlands)

    Vink, H.J.P.; Doelman, N.J.; Flatscher, R.; Sodnik, Z.

    2003-01-01

    Nulling interferometry is a direct method to detect earth-like planets. To determine whether a planet is earth-like spectrometry can be performed which requires a broadband optical input signal from the planet. Nulling interferometry should decrease the broadband (λ ≈ 6-18μm) star signal by about a

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

    Science.gov (United States)

    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. Einstein equations in the null quasi-spherical gauge

    CERN Document Server

    Bartnik, R A

    1997-01-01

    The structure of the full Einstein equations in a coordinate gauge based on expanding null hypersurfaces foliated by metric 2-spheres is explored. The simple form of the resulting equations has many applications -- in the present paper we describe the structure of timelike boundary conditions; the matching problem across null hypersurfaces; and the propagation of gravitational shocks.

  14. A new dynamic null model for phylogenetic community structure

    NARCIS (Netherlands)

    Pigot, Alex L; Etienne, Rampal S

    2015-01-01

    Phylogenies are increasingly applied to identify the mechanisms structuring ecological communities but progress has been hindered by a reliance on statistical null models that ignore the historical process of community assembly. Here, we address this, and develop a dynamic null model of assembly by

  15. Gravity Degrees of Freedom on a Null Surface

    CERN Document Server

    Hopfmüller, Florian

    2016-01-01

    A canonical analysis for general relativity is performed on a null surface without fixing the diffeomorphism gauge, and the canonical pairs of configuration and momentum variables are derived. Next to the well-known spin-2 pair, also spin-1 and spin-0 pairs are identified. The boundary action for a null boundary segment of spacetime is obtained, including terms on codimension two corners.

  16. Logarithmic corrections to gravitational entropy and the null energy condition

    Science.gov (United States)

    Parikh, Maulik; Svesko, Andrew

    2016-10-01

    Using a relation between the thermodynamics of local horizons and the null energy condition, we consider the effects of quantum corrections to the gravitational entropy. In particular, we find that the geometric form of the null energy condition is not affected by the inclusion of logarithmic corrections to the Bekenstein-Hawking entropy.

  17. Logarithmic corrections to gravitational entropy and the null energy condition

    Directory of Open Access Journals (Sweden)

    Maulik Parikh

    2016-10-01

    Full Text Available Using a relation between the thermodynamics of local horizons and the null energy condition, we consider the effects of quantum corrections to the gravitational entropy. In particular, we find that the geometric form of the null energy condition is not affected by the inclusion of logarithmic corrections to the Bekenstein–Hawking entropy.

  18. Exact null controllability of degenerate evolution equations with scalar control

    Energy Technology Data Exchange (ETDEWEB)

    Fedorov, Vladimir E; Shklyar, Benzion

    2012-12-31

    Necessary and sufficient conditions for the exact null controllability of a degenerate linear evolution equation with scalar control are obtained. These general results are used to examine the exact null controllability of the Dzektser equation in the theory of seepage. Bibliography: 13 titles.

  19. Collagen VI deficiency reduces muscle pathology, but does not improve muscle function, in the γ-sarcoglycan-null mouse.

    Science.gov (United States)

    de Greef, Jessica C; Hamlyn, Rebecca; Jensen, Braden S; O'Campo Landa, Raul; Levy, Jennifer R; Kobuke, Kazuhiro; Campbell, Kevin P

    2016-04-01

    Muscular dystrophy is characterized by progressive skeletal muscle weakness and dystrophic muscle exhibits degeneration and regeneration of muscle cells, inflammation and fibrosis. Skeletal muscle fibrosis is an excessive deposition of components of the extracellular matrix including an accumulation of Collagen VI. We hypothesized that a reduction of Collagen VI in a muscular dystrophy model that presents with fibrosis would result in reduced muscle pathology and improved muscle function. To test this hypothesis, we crossed γ-sarcoglycan-null mice, a model of limb-girdle muscular dystrophy type 2C, with a Col6a2-deficient mouse model. We found that the resulting γ-sarcoglycan-null/Col6a2Δex5 mice indeed exhibit reduced muscle pathology compared with γ-sarcoglycan-null mice. Specifically, fewer muscle fibers are degenerating, fiber size varies less, Evans blue dye uptake is reduced and serum creatine kinase levels are lower. Surprisingly, in spite of this reduction in muscle pathology, muscle function is not significantly improved. In fact, grip strength and maximum isometric tetanic force are even lower in γ-sarcoglycan-null/Col6a2Δex5 mice than in γ-sarcoglycan-null mice. In conclusion, our results reveal that Collagen VI-mediated fibrosis contributes to skeletal muscle pathology in γ-sarcoglycan-null mice. Importantly, however, our data also demonstrate that a reduction in skeletal muscle pathology does not necessarily lead to an improvement of skeletal muscle function, and this should be considered in future translational studies.

  20. Null hypersurfaces in generalized Robertson-Walker spacetimes

    Science.gov (United States)

    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.

  1. Estimating Relatedness in the Presence of Null Alleles.

    Science.gov (United States)

    Huang, Kang; Ritland, Kermit; Dunn, Derek W; Qi, Xiaoguang; Guo, Songtao; Li, Baoguo

    2016-01-01

    Studies of genetics and ecology often require estimates of relatedness coefficients based on genetic marker data. However, with the presence of null alleles, an observed genotype can represent one of several possible true genotypes. This results in biased estimates of relatedness. As the numbers of marker loci are often limited, loci with null alleles cannot be abandoned without substantial loss of statistical power. Here, we show how loci with null alleles can be incorporated into six estimators of relatedness (two novel). We evaluate the performance of various estimators before and after correction for null alleles. If the frequency of a null allele is 0.5, the potency of estimation is too low and such a locus should be excluded. We make available a software package entitled PolyRelatedness v1.6, which enables researchers to optimize these estimators to best fit a particular data set.

  2. Reconnection experiments with 3D magnetic nulls in different topologies

    Science.gov (United States)

    Vrublevskis, A.; Egedal, J.; Le, A.

    2012-10-01

    Magnetic reconnection has been predominantly investigated in two dimensions. However, depending on the topology and geometry of the magnetic field, a rich collection of magnetic reconnection scenarios is possible in 3D including reconnection at magnetic nulls. At the Versatile Toroidal Facility (VTF) we have implemented a new magnetic geometry with a pair of 3D null points in the background toroidal field. We form a flux rope along the background field and observe it to rapidly restructure and rewire as the nulls develop. We can adjust the topology of the configuration from one where a field line connects the nulls to one where the nulls are no longer linked. A suit of diagnostics will be deployed and results presented for how the topology affects the dynamics of the flux rope.

  3. Sidelobe Suppression with Null Steering by Independent Weight Control

    Directory of Open Access Journals (Sweden)

    Zafar-Ullah Khan

    2015-01-01

    Full Text Available A uniform linear array of n antenna elements can steer up to n-1 nulls. In situations where less than n-1 nulls are required to be steered, the existing algorithms have no criterion to utilize the remaining weights for sidelobe suppression. This work combines sidelobe suppression capability with null steering by independent weight control. For this purpose, the array factor is transformed as the product of two polynomials. One of the polynomials is used for null steering by independent weight control, while the second one is for sidelobe suppression whose coefficients or weights are determined by using convex optimization. Finally, a new structure is proposed to incorporate the product of two polynomials such that sidelobe suppression weights are decoupled from those of null steering weights. Simulation results validate the effectiveness of the proposed scheme.

  4. Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord

    Directory of Open Access Journals (Sweden)

    Kucharova Karolina

    2011-11-01

    Full Text Available Abstract Background Multiple sclerosis (MS is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination. Methods Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR. Results The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype. Conclusions Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result

  5. Reversing hypomyelination in BACE1-null mice with Akt-DD overexpression.

    Science.gov (United States)

    Hu, Xiangyou; Schlanger, Rita; He, Wanxia; Macklin, Wendy B; Yan, Riqiang

    2013-05-01

    β-Site amyloid precursor protein convertase enzyme 1 (BACE1), a type I transmembrane aspartyl protease required to cleave amyloid precursor protein for releasing a toxic amyloid peptide, also cleaves type I and type III neuregulin-1 (Nrg-1). BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination if injured. In BACE1-null mice, the abolished cleavage of neuregulin-1 by BACE1 is speculated to cause reduced myelin sheath thickness in both the central nervous system and peripheral nervous system because reduced cleavage of Nrg-1 correlates with reduced Akt phosphorylation, a downstream signaling molecule of the Nrg-1/ErbB pathway. Here we tested specifically whether increasing Akt activity alone in oligodendrocytes would be sufficient to reverse the hypomyelination phenotype in BACE1-null mice. BACE1-null mice were bred with transgenic mice expressing constitutively active Akt (Akt-DD; mutations with D(308)T and D(473)S) in oligodendrocytes. Relative to littermate BACE1-null controls, BACE1(-/-)/Akt-DD mice exhibited enhanced expression of myelin basic protein and promoter of proteolipid protein. The elevated expression of myelin proteins correlated with a thicker myelin sheath in optic nerves; comparison of quantified g ratios with statistic significance was used to confirm this reversion. However, it appeared that myelin sheath thickness in the sciatic nerves was not increased in BACE1(-/-)/Akt-DD mice, as the g ratio was not significantly different from the control. Hence, increased Akt activity in BACE1-null myelinating cells only compensates for the loss of BACE1 activity in the central nervous system, which is consistent with the observation that overexpression of Akt-DD in Schwann cells did not induce hypermyelination. Our results suggest that signaling activity other than Akt may also contribute to proper myelination in peripheral nerves.

  6. Intimal hyperplasia in loop-injured carotid arteries is attenuated in transglutaminase 2-null mice.

    Science.gov (United States)

    Min, Seung-Kee; Min, Sang-Il; Jeong, Eui Man; Cho, Sung-Yup; Ha, Jongwon; Kim, Sang Joon; Kim, In-Gyu

    2014-03-01

    Arterial restenosis frequently develops after open or endovascular surgery due to intimal hyperplasia. Since tissue transglutaminase (TG2) is known to involve in fibrosis, wound healing, and extracellular matrix remodeling, we examined the role of TG2 in the process of intimal hyperplasia using TG2-null mice. The neointimal formation was compared between TG2-null and wild-type (C57BL/6) mice by two different injury models; carotid ligation and carotid loop injury. In ligation model, there was no difference in intimal thickness between two groups. In loop injury model, intimal hyperplasia developed in both groups and the intimal/medial area ratio was significantly reduced in TG2-null mice (P = 0.007). TG2 was intensely stained in neointimal cells in 2 weeks. In situ activity of TG2 in the injured arteries steadily increased until 4 weeks compared to uninjured arteries. Taken together, intimal hyperplasia was significantly reduced in TG2-null mice, indicating that TG2 has an important role in the development of intimal hyperplasia. This suggests that TG2 may be a novel target to prevent the arterial restenosis after vascular surgery.

  7. Null Models for Everyone: A Two-Step Approach to Teaching Null Model Analysis of Biological Community Structure

    Science.gov (United States)

    McCabe, Declan J.; Knight, Evelyn J.

    2016-01-01

    Since being introduced by Connor and Simberloff in response to Diamond's assembly rules, null model analysis has been a controversial tool in community ecology. Despite being commonly used in the primary literature, null model analysis has not featured prominently in general textbooks. Complexity of approaches along with difficulty in interpreting…

  8. A null model for Pearson coexpression networks.

    Science.gov (United States)

    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.

  9. 'Null method' determination of drug biophase concentration.

    Science.gov (United States)

    Tallarida, Ronald J; Lamarre, Neil; Raffa, Robert B

    2012-03-01

    PK/PD modeling is enhanced by improvements in the accuracy of its metrics. For PK/PD modeling of drugs and biologics that interact with enzymes or receptors, the equilibrium constant of the interaction can provide critical insight. Methodologies such as radioliogand binding and isolated tissue preparations can provide estimates of the equilibrium constants (as the dissociation constant, K value) for drugs and endogenous ligands that interact with specific enzymes and receptors. However, an impediment to further precision for PK/PD modeling is that it remains a problem to convert the concentration of drug in bulk solution (A) into an estimate of receptor occupation, since A is not necessarily the concentration (C) of drug in the biophase that yields fractional binding from the law of mass action, viz., C/(C + K). In most experimental studies A is much larger than K, so the use of administered instead of biophase concentration gives fractional occupancies very close to unity. We here provide a simple way to obtain an estimate of the factor that converts the total drug concentration into the biophase concentration in isolated tissue preparation. Our approach is an extension of the now classic 'null method' introduced and applied by Furchgott to determination of drug-receptor dissociation constants.

  10. A null model for Pearson coexpression networks.

    Directory of Open Access Journals (Sweden)

    Andrea Gobbi

    Full Text Available 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.

  11. The Curious Case of Null Warped Space

    CERN Document Server

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

    2010-01-01

    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 th...

  12. Null fluid collapse in brane world models

    Science.gov (United States)

    Harko, Tiberiu; Lake, Matthew J.

    2014-03-01

    The brane world description of our Universe entails a large extra dimension and a fundamental scale of gravity that may be lower than the Planck scale by several orders of magnitude. An interesting consequence of this scenario occurs in the nature of spherically symmetric vacuum solutions to the brane gravitational field equations, which often have properties quite distinct from the standard black hole solutions of general relativity. In this paper, the spherically symmetric collapse on the brane world of four types of null fluid, governed by the barotropic, polytropic, strange quark "bag" model and Hagedorn equations of state, is investigated. In each case, we solve the approximate gravitational field equations, obtained in the high-density limit, determine the equation which governs the formation of apparent horizons and investigate the conditions for the formation of naked singularities. Though, naively, one would expect the increased effective energy density on the brane to favor the formation of black holes over naked singularities, we find that, for the types of fluid considered, this is not the case. However, the black hole solutions differ substantially from their general-relativistic counterparts and brane world corrections often play a role analogous to charge in general relativity. As an astrophysical application of this work, the possibility that energy emission from a Hagedorn fluid collapsing to form a naked singularity may be a source of GRBs in the brane world is also considered.

  13. Increased Engraftment of Human Short Term Repopulating Hematopoietic Cells in NOD/SCID/IL2rγnull Mice by Lentiviral Expression of NUP98-HOXA10HD.

    Science.gov (United States)

    Abraham, Allistair; Kim, Yoon-Sang; Zhao, Huifen; Humphries, Keith; Persons, Derek A

    2016-01-01

    Techniques to expand human hematopoietic stem cells ex-vivo could be beneficial to the fields of clinical hematopoietic stem cell transplantation and gene therapy targeted at hematopoietic stem cells. NUP98-HOXA10HD is a relatively newly discovered fusion gene that in mouse transplant experiments has been shown to increase numbers of hematopoietic stem cells. We evaluated whether this fusion gene could be used to expand engrafting human primitive CD34+ cells in an immunodeficient mouse model. Gene transfer was achieved using a lentiviral based vector. The engraftment of mobilized peripheral blood human CD34+ cells grown in culture for one week after gene transfer was evaluated 3-4 months after transplant and found to be 2-3 fold higher in the NUP98-HOXA10HD groups as compared to controls. These data suggest an expansive effect at least at the short term human repopulating cell level. Further evaluation in long term repopulating models and investment in a NUP98-HOXA10HD protein seems worthy of consideration. Additionally, the results here provide strong impetus to utilize NUP98-HOXA10HD as a tool to search for underlying genes and pathways involved in hematopoietic stem cell expansion that can be enhanced and have an even more potent expansive effect.

  14. Increased Engraftment of Human Short Term Repopulating Hematopoietic Cells in NOD/SCID/IL2rγnull Mice by Lentiviral Expression of NUP98-HOXA10HD.

    Directory of Open Access Journals (Sweden)

    Allistair Abraham

    Full Text Available Techniques to expand human hematopoietic stem cells ex-vivo could be beneficial to the fields of clinical hematopoietic stem cell transplantation and gene therapy targeted at hematopoietic stem cells. NUP98-HOXA10HD is a relatively newly discovered fusion gene that in mouse transplant experiments has been shown to increase numbers of hematopoietic stem cells. We evaluated whether this fusion gene could be used to expand engrafting human primitive CD34+ cells in an immunodeficient mouse model. Gene transfer was achieved using a lentiviral based vector. The engraftment of mobilized peripheral blood human CD34+ cells grown in culture for one week after gene transfer was evaluated 3-4 months after transplant and found to be 2-3 fold higher in the NUP98-HOXA10HD groups as compared to controls. These data suggest an expansive effect at least at the short term human repopulating cell level. Further evaluation in long term repopulating models and investment in a NUP98-HOXA10HD protein seems worthy of consideration. Additionally, the results here provide strong impetus to utilize NUP98-HOXA10HD as a tool to search for underlying genes and pathways involved in hematopoietic stem cell expansion that can be enhanced and have an even more potent expansive effect.

  15. Visualization of the human CD4{sup +} T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/γc{sup null} (NOG) mice by retrogenic expression of the human TCR gene

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Takeshi, E-mail: takeshi-takahashi@ciea.or.jp; Katano, Ikumi; Ito, Ryoji; Ito, Mamoru

    2015-01-02

    Highlights: • β-Lactoglobulin (BLG) specific TCR genes were introduced to human HSC by retrovirus. • Human HSC with BLG-specific TCR were transplanted into NOG-HLA-DR4 I-A{sup −/−} mice. • BLG-specific TCR induced positive selection of thymocytes. • BLG-specific TCR positive CD4{sup +} T cells mediated immune responses in humanized mice. - Abstract: The development of severe immunodeficient mouse strains containing various human genes, including cytokines or HLA, has enabled the reconstitution of functional human immune systems after transplantation of human hematopoietic stem cells (HSC). Accumulating evidence has suggested that HLA-restricted antigen-specific human T-cell responses can be generated in these humanized mice. To directly monitor immune responses of human CD4{sup +} T cells, we introduced β-lactoglobulin (BLG)-specific T cell receptor (TCR) genes derived from CD4{sup +} T-cell clones of cow-milk allergy patients into HSCs, and subsequently transplanted them into NOG-HLA-DR4 transgenic/I-Aβ deficient mice (NOG-DR4/I-A{sup o}). In the thymus, thymocytes with BLG-specific TCR preferentially differentiated into CD4{sup +}CD8{sup −} single-positive cells. Adoptive transfer of mature CD4{sup +} T cells expressing the TCR into recipient NOG-DR4/I-A{sup o} mice demonstrated that human CD4{sup +} T cells proliferated in response to antigenic stimulation and produced IFN-γ in vivo, suggesting that functional T-cell reactions (especially Th1-skewed responses) were induced in humanized mice.

  16. Null fields in the outer Jovian magnetosphere: Ulysses observations

    Science.gov (United States)

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

    1994-01-01

    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.

  17. The Density of Coronal Null Points from Hinode and MDI

    CERN Document Server

    Longcope, Dana; DeForest, Craig

    2009-01-01

    Magnetic null points can be located numerically in a potential field extrapolation or their average density can be estimated from the Fourier spectrum of a magnetogram. We use both methods to compute the null point density from a quiet Sun magnetogram made with Hinode's NFI and from magnetograms from SOHO's MDI in both its high-resolution and low-resolution modes. All estimates of the super-chromospheric column density (z>1.5 Mm) agree with one another and with the previous measurements: 0.003 null points per square Mm of solar surface.

  18. A Null Space Approach for Solving Nonlinear Complementarity Problems

    Institute of Scientific and Technical Information of China (English)

    Pu-yan Nie

    2006-01-01

    In this work, null space techniques are employed to tackle nonlinear complementarity problems(NCPs). NCP conditions are transform into a nonlinear programming problem, which is handled by null space algorithms. The NCP conditions are divided into two groups. Some equalities and inequalities in an NCP are treated as constraints. While other equalities and inequalities in an NCP are to be regarded as objective function.Two groups are all updated in every step. Null space approaches are extended to nonlinear complementarity problems. Two different solvers are employed for an NCP in an algorithm.

  19. The Importance of Phase in Nulling Interferometry and a Three Telescope Closure-Phase Nulling Interferometer Concept

    OpenAIRE

    Danchi, W. C.; Rajagopal, J.; Kuchner, M.; Richardson, J; Deming, D.

    2006-01-01

    We discuss the theory of the Bracewell nulling interferometer and explicitly demonstrate that the phase of the "white light" null fringe is the same as the phase of the bright output from an ordinary stellar interferometer. As a consequence a "closure phase" exists for a nulling interferometer with three or more telescopes. We calculate the phase offset as a function of baseline length for an Earth-like planet around the Sun at 10 pc, with a contrast ratio of $10^{-6}$ at 10 $\\mu$m. The magni...

  20. Dynamics of a Spherical Null Shell within the Distributional Formalism

    OpenAIRE

    Khakshournia, Samad; Mansouri, Reza

    2004-01-01

    Dynamics of a null thin shell immersed in a generic spherically symmetric spacetime is obtained within the distributional formalism. It has been shown that the distributional formalism leads to the same result as in the conventional formalism.

  1. Uniform Consistency for Nonparametric Estimators in Null Recurrent Time Series

    DEFF Research Database (Denmark)

    Gao, Jiti; Kanaya, Shin; Li, Degui;

    2015-01-01

    This paper establishes uniform consistency results for nonparametric kernel density and regression estimators when time series regressors concerned are nonstationary null recurrent Markov chains. Under suitable regularity conditions, we derive uniform convergence rates of the estimators. Our...

  2. A new dynamic null model for phylogenetic community structure.

    Science.gov (United States)

    Pigot, Alex L; Etienne, Rampal S

    2015-02-01

    Phylogenies are increasingly applied to identify the mechanisms structuring ecological communities but progress has been hindered by a reliance on statistical null models that ignore the historical process of community assembly. Here, we address this, and develop a dynamic null model of assembly by allopatric speciation, colonisation and local extinction. Incorporating these processes fundamentally alters the structure of communities expected due to chance, with speciation leading to phylogenetic overdispersion compared to a classical statistical null model assuming equal probabilities of community membership. Applying this method to bird and primate communities in South America we show that patterns of phylogenetic overdispersion - often attributed to negative biotic interactions - are instead consistent with a species neutral model of allopatric speciation, colonisation and local extinction. Our findings provide a new null expectation for phylogenetic community patterns and highlight the importance of explicitly accounting for the dynamic history of assembly when testing the mechanisms governing community structure.

  3. Waves and null congruences in a draining bathtub

    CERN Document Server

    Dempsey, David

    2016-01-01

    We study wave propagation in a draining bathtub: a fluid-mechanical black hole analogue in which perturbations are governed by a Klein-Gordon equation on an effective Lorentzian geometry. Like the Kerr spacetime, the draining bathtub geometry possesses an (effective) horizon, an ergosphere and null circular orbits. We propose that a `pulse' disturbance may be used to map out the light-cone of the effective geometry. First, we apply the eikonal approximation to elucidate the link between wavefronts, null geodesic congruences and the Raychaudhuri equation. Next, we solve the wave equation numerically in the time domain using the method of lines. Starting with Gaussian initial data, we demonstrate that a pulse will propagate along a null congruence and thus trace out the light-cone of the effective geometry. Our numerical results reveal features, such as wavefront intersections, frame-dragging, winding and interference effects, that are closely associated with the presence of null circular orbits and the ergosph...

  4. Overt and Null Subject Pronouns in Jordanian Arabic

    Directory of Open Access Journals (Sweden)

    Islam M. Al-Momani

    2015-08-01

    Full Text Available The paper aims at examining the role that morphology plays in allowing and/or motivating sentences in Jordanian Arabic (hereafter JA to be formed with or without subject pronouns. It also aims at giving a comprehensive and descriptive presentation of the distribution of overt and null subject pronouns in JA, and tries to determine to what extent there is optionality in its system. Keywords: null subject pronouns, overt subjects, pro-drop languages, verbal inflectional morphology

  5. Shear-free Null Quasi-Spherical Spacetimes

    CERN Document Server

    Bartnik, R A

    1997-01-01

    The residual gauge freedom within the null quasi-spherical coordinate condition is studied, for spacetimes admitting an {\\em expanding, shear-free} null foliation. The freedom consists of a boost and rotation at each coordinate sphere, corresponding to a specification of inertial frame at each sphere. Explicit formulae involving arbitrary functions of two variables are obtained for the accelerated Minkowski, Schwarzschild, and Robinson-Trautman spacetimes. These examples will be useful as test metrics in numerical relativity.

  6. The geometry of D=11 null killing spinors

    Energy Technology Data Exchange (ETDEWEB)

    Gauntlett, Jerome P.; Gutowski, Jan B. E-mail: gutowski@maths.ox.ac.uk; Stathis Pakis

    2003-12-01

    We determine the necessary and sufficient conditions on the metric and the four-form for the most general bosonic supersymmetric configurations of D=11 supergravity which admit a null Killing spinor i.e. a Killing spinor which can be used to construct a null Killing vector. This class covers all supersymmetric time-dependent configurations and completes the classification of the most general supersymmetric configurations initiated in hep-th/0212008. (author)

  7. The Geometry of D=11 Null Killing Spinors

    CERN Document Server

    Gauntlett, J P; Pakis, S

    2003-01-01

    We determine the necessary and sufficient conditions on the metric and the four-form for the most general bosonic supersymmetric configurations of D=11 supergravity which admit a null Killing spinor i.e. a Killing spinor which can be used to construct a null Killing vector. This class covers all supersymmetric time-dependent configurations and completes the classification of the most general supersymmetric configurations initiated in hep-th/0212008.

  8. Magnetoacoustic shock formation near a magnetic null point

    OpenAIRE

    Gruszecki, M. (Marcin); Vasheghani Farahani, Soheil; Nakariakov, V. M.; Arber, T. D.

    2011-01-01

    We investigate the interaction of nonlinear fast magnetoacoustic waves with a magnetic null point in connection with the triggering of solar flares. \\ud \\ud Methods. We model the propagation of fast, initially axisymmetric waves towards a two-dimensional isothermal magnetic null point in terms of ideal magnetohydrodynamic equations. The numerical simulations are carried out with the Lagrangian remap code Lare2D. \\ud \\ud Results. Dynamics of initially axisymmetric fast pulses of small amplitud...

  9. Development of New Sputter System by Magnetic Null Plasma

    OpenAIRE

    敦田, 悟; 楊, 鍾煥; 川尻, 晋平; 成, 烈[ブン; 本田, 親久; 大坪, 昌久

    2004-01-01

    Abstract ###A new type of plasma system based on the magnetic neutral loop discharge (NLD) concept ###has been developed for sputter application. This system is characterized by plasma production ###around the multi null magnetic field on the electrode surface, where a capacitive RF electric ###field is applied. From the experimental results and numerical analysis of electron behavior in ###this system, we found that electrons around the magnetic null region on the target surface ###moved in ...

  10. Designing asynchronous circuits using NULL convention logic (NCL)

    CERN Document Server

    Smith, Scott

    2009-01-01

    Designing Asynchronous Circuits using NULL Convention Logic (NCL) begins with an introduction to asynchronous (clockless) logic in general, and then focuses on delay-insensitive asynchronous logic design using the NCL paradigm. The book details design of input-complete and observable dual-rail and quad-rail combinational circuits, and then discusses implementation of sequential circuits, which require datapath feedback. Next, throughput optimization techniques are presented, including pipelining, embedding registration, early completion, and NULL cycle reduction. Subsequently, low-power design

  11. Using Multivalued Logic in Relational Database Containing Null Value

    Institute of Scientific and Technical Information of China (English)

    马宗民; YanLi

    1996-01-01

    In this paper,several kinds of multivalued logic for relational database and their developing process are presented on the basis of null value's semantics.A new 5 valued logic is led into relational database containing null value.The feasibility and necessity of using 5 valued logic are expounded.Comparative calculation and logical calculation under 5 valued logic are defined at the end of the paper.

  12. Null controllability of a cascade system of Schrodinger equations

    Directory of Open Access Journals (Sweden)

    Marcos Lopez-Garcia

    2016-03-01

    Full Text Available This article presents a control problem for a cascade system of two linear N-dimensional Schrodinger equations. We address the problem of null controllability by means of a control supported in a region not satisfying the classical geometrical control condition. The proof is based on the application of a Carleman estimate with degenerate weights to each one of the equations and a careful analysis of the system in order to prove null controllability with only one control force.

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

    Science.gov (United States)

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

    2016-07-26

    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.

  14. Reconnection Experiments with Flux Ropes near 3D Magnetic Nulls

    Science.gov (United States)

    Vrublevskis, A.; Egedal, J.; Le, A.

    2012-12-01

    Magnetic reconnection has been predominantly investigated in two dimensions. However, depending on the topology and geometry of the magnetic field, a rich collection of magnetic reconnection scenarios is possible in 3D including reconnection at magnetic nulls. Nulls have been reported in the solar corona [1] and in Earth's magnetosphere [2], yet there are a limited number of laboratory observations. At the Versatile Toroidal Facility (VTF) we have implemented a new magnetic geometry with a pair of 3D null points in the background toroidal field. We form a flux rope along the background field and observe it to rapidly restructure and rewire as the nulls develop. We can adjust the topology of the configuration from one where a field line connects the nulls to one where the nulls are no longer linked. A suit of diagnostics will be deployed and results presented for the dynamics of the flux rope. [1] Fletcher et al., Astrophys. J. 554, 451(2001) [2] Xiao et al., Nat. Phys. 2, 478 (2006)

  15. Autism phenotypes in ZnT3 null mice: Involvement of zinc dyshomeostasis, MMP-9 activation and BDNF upregulation.

    Science.gov (United States)

    Yoo, Min Heui; Kim, Tae-Youn; Yoon, Young Hee; Koh, Jae-Young

    2016-06-29

    To investigate the role of synaptic zinc in the ASD pathogenesis, we examined zinc transporter 3 (ZnT3) null mice. At 4-5 weeks of age, male but not female ZnT3 null mice exhibited autistic-like behaviors. Cortical volume and neurite density were significantly greater in male ZnT3 null mice than in WT mice. In male ZnT3 null mice, consistent with enhanced neurotrophic stimuli, the level of BDNF as well as activity of MMP-9 was increased. Consistent with known roles for MMPs in BDNF upregulation, 2.5-week treatment with minocycline, an MMP inhibitor, significantly attenuated BDNF levels as well as megalencephaly and autistic-like behaviors. Although the ZnT3 null state removed synaptic zinc, it rather increased free zinc in the cytosol of brain cells, which appeared to increase MMP-9 activity and BDNF levels. The present results suggest that zinc dyshomeostasis during the critical period of brain development may be a possible contributing mechanism for ASD.

  16. Classical and alternative activation and metalloproteinase expression occurs in foam cell macrophages in male and female ApoE null mice in the absence of T- and B-lymphocytes

    Directory of Open Access Journals (Sweden)

    Elaine Mo Hayes

    2014-10-01

    Full Text Available Background: Rupture of advanced atherosclerotic plaques accounts for most life-threatening myocardial infarctions. Classical (M1 and alternative (M2 macrophage activation could promote atherosclerotic plaque progression and rupture by increasing production of proteases, including matrix metalloproteinases (MMPs. Lymphocyte-derived cytokines may be essential for generating M1 and M2 phenotypes in plaques, although this has not been rigorously tested until now.Methods and Results: We validated the expression of M1 markers (iNOS and COX-2 and M2 markers (arginase-1, Ym-1 and CD206 and then measured MMP mRNA levels in mouse macrophages during classical and alternative activation in vitro. We then compared mRNA expression of these genes ex vivo in foam cells from subcutaneous granulomas in fat-fed immune-competent ApoE knockout and immune-compromised ApoE/Rag-1 double knockout mice, which lack all T and B cells. Furthermore, we performed immunohistochemistry in subcutaneous granulomas and in aortic root and brachiocephalic artery atherosclerotic plaques to measure the extent of M1/M2 marker and MMP protein expression in vivo. Classical activation of mouse macrophages with bacterial lipopolysaccharide in vitro increased MMPs-13, -14 and -25 but decreased MMP-19 and TIMP-2 mRNA expressions. Alternative activation with IL-4 increased MMP-19 expression. Foam cells in subcutaneous granulomas expressed all M1/M2 markers and MMPs at ex vivo mRNA and in vivo protein levels, irrespective of Rag-1 genotype. There were also similar percentages of foam cell macrophages carrying M1/M2 markers and MMPs in atherosclerotic plaques from ApoE knockout and ApoE/Rag-1 double knockout mice. Conclusions: Classical and alternative activation leads to distinct MMP expression patterns in mouse macrophages in vitro. M1 and M2 polarization in vivo occurs in the absence of T and B lymphocytes in either granuloma or plaque foam cell macrophages.

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

    CERN Document Server

    Murphy, Nicholas A; Haynes, Andrew L

    2015-01-01

    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 vector 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 conv...

  18. Three-dimensional magnetic reconnection through a moving magnetic null

    Directory of Open Access Journals (Sweden)

    V. S. Lukin

    2011-11-01

    Full Text Available A computational study of three-dimensional magnetic reconnection between two flux ropes through a moving reconnection site is presented. The configuration is considered in the context of two interacting spheromaks constrained by a perfectly conducting cylindrical boundary and oriented to form a single magnetic field null at its center. The initial magnetic field configuration is embedded into a uniform thermal plasma and is unstable to tilting. As the spheromaks tilt, their magnetic fields begin to reconnect at the null, subsequently displacing both the null and the reconnection site. The motion of the reconnection region and the magnetic null are shown to be correlated, with stronger correlation and faster reconnection observed in plasmas with lower thermal to magnetic pressure ratio. It is also shown that ion inertial effects allow for yet faster reconnection, but do not qualitatively change the dynamics of the process. Implications of the coupling between moving magnetic nulls and reconnection sites, as well as of possible mechanisms for fast reconnection through a moving reconnection region, are discussed. The simulations are conducted using both single-fluid and Hall MHD plasma models within the HiFi multi-fluid modeling framework.

  19. Three-dimensional magnetic reconnection through a moving magnetic null

    Science.gov (United States)

    Lukin, V. S.; Linton, M. G.

    2011-11-01

    A computational study of three-dimensional magnetic reconnection between two flux ropes through a moving reconnection site is presented. The configuration is considered in the context of two interacting spheromaks constrained by a perfectly conducting cylindrical boundary and oriented to form a single magnetic field null at its center. The initial magnetic field configuration is embedded into a uniform thermal plasma and is unstable to tilting. As the spheromaks tilt, their magnetic fields begin to reconnect at the null, subsequently displacing both the null and the reconnection site. The motion of the reconnection region and the magnetic null are shown to be correlated, with stronger correlation and faster reconnection observed in plasmas with lower thermal to magnetic pressure ratio. It is also shown that ion inertial effects allow for yet faster reconnection, but do not qualitatively change the dynamics of the process. Implications of the coupling between moving magnetic nulls and reconnection sites, as well as of possible mechanisms for fast reconnection through a moving reconnection region, are discussed. The simulations are conducted using both single-fluid and Hall MHD plasma models within the HiFi multi-fluid modeling framework.

  20. Long-term Observations of Three Nulling Pulsars

    CERN Document Server

    Young, N J; Stappers, B W; Lyne, A G; Kramer, M

    2015-01-01

    We present an analysis of approximately 200 hours of observations of the pulsars J1634$-$5107, J1717$-$4054 and J1853$+$0505, taken over the course of 14.7 yr. We show that all of these objects exhibit long term nulls and radio-emitting phases (i.e. minutes to many hours), as well as considerable nulling fractions (NFs) in the range $\\sim67\\,\\% - 90\\,\\%$. PSR J1717$-$4054 is also found to exhibit short timescale nulls ($1 - 40~P$) and burst phases ($\\lesssim 200~P$) during its radio-emitting phases. This behaviour acts to modulate the NF, and therefore the detection rate of the source, over timescales of minutes. Furthermore, PSR J1853$+$0505 is shown to exhibit a weak emission state, in addition to its strong and null states, after sufficient pulse integration. This further indicates that nulls may often only represent transitions to weaker emission states which are below the sensitivity thresholds of particular observing systems. In addition, we detected a peak-to-peak variation of $33\\pm1\\,\\%$ in the spin-...

  1. Visible Nulling Coronagraphy Testbed Development for Exoplanet Detection

    Science.gov (United States)

    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.

  2. The causal topology of neutral 4-manifolds with null boundary

    CERN Document Server

    Georgiou, Nikos

    2016-01-01

    This paper considers aspects of 4-manifold topology from the point of view of a neutral metric, a point of view we call neutral causal topology. In particular, we construct and investigate neutral 4-manifolds with null boundary that arise from canonical 3- and 4-dimensional settings. A null hypersurface is foliated by its normal and, in the neutral case, inherits a pair of totally null planes at each point. This paper focuses on this structure in a number of classical settings The first construction is the conformal compactification of flat neutral 4-space into the 4-ball. The null foliation on the boundary in this case is the Hopf fibration on the 3-sphere and the totally null planes in the boundary are integrable. The metric on the 4-ball is a conformally flat, scalar-flat, positive Ricci curvature neutral metric. The second constructions are subsets of the 4-dimensional space of oriented geodesics in a 3-dimensional space-form, equipped with its canonical neutral metric. We consider all oriented geodesics ...

  3. Phenotypic characteristics of aged CD4(+) CD28(null) T lymphocytes are determined by changes in the whole-genome DNA methylation pattern.

    Science.gov (United States)

    Suarez-Álvarez, Beatriz; Rodríguez, Ramón M; Schlangen, Karin; Raneros, Aroa Baragaño; Márquez-Kisinousky, Leonardo; Fernández, Agustín F; Díaz-Corte, Carmen; Aransay, Ana M; López-Larrea, Carlos

    2017-04-01

    Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4(+) lymphocytes (CD28(null) T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28(null) T cells and its CD28(+) counterpart. A comparative analysis revealed that 296 genes are differentially methylated between the two cell subsets. A total of 160 genes associated with cytotoxicity (e.g. GRZB, TYROBP, and RUNX3) and cytokine/chemokine signaling (e.g. CX3CR1, CD27, and IL-1R) are demethylated in CD28(null) T cells, while 136 de novo-methylated genes matched defects in the TCR signaling pathway (e.g. ITK, TXK, CD3G, and LCK). TCR-landscape analysis confirmed that CD28(null) T cells have an oligo/monoclonal expansion over the polyclonal background of CD28(+) T cells, but feature a Vβ family repertoire specific to each individual. We reported that CD28(null) T cells show a preactivation state characterized by a higher level of expression of inflammasome-related genes that leads to the release of IL-1β when activated. Overall, our results demonstrate that CD28(null) T cells have a unique DNA methylation landscape, which is associated with differences in gene expression, contributing to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could suggest novel therapeutic strategies to prevent the accumulation and activation of these cells during aging.

  4. Phase closure nulling: results from the 2009 campaign

    Science.gov (United States)

    Duvert, Gilles; Malbet, Fabien; Chelli, Alain; Millan-Gabet, Rafael; Monnier, John D.; Schaefer, Gail H.

    2010-07-01

    We present here a new observational technique, Phase Closure Nulling (PCN), which has the potential to obtain very high contrast detection and spectroscopy of faint companions to bright stars. PCN consists in measuring closure phases of fully resolved objects with a baseline triplet where one of the baselines crosses a null of the object visibility function. For scenes dominated by the presence of a stellar disk, the correlated flux of the star around nulls is essentially canceled out, and in these regions the signature of fainter, unresolved, scene object(s) dominates the imaginary part of the visibility in particular the closure phase. We present here the basics of the PCN method, the initial proof-of-concept observation, the envisioned science cases and report about the first observing campaign made on VLTI/AMBER and CHARA/MIRC using this technique.

  5. Phase Closure Nulling: results from the 2009 campaign

    CERN Document Server

    Duvert, Gilles; Chelli, Alain; Millan-Gabet, Rafael; Monnier, John D; Schaefer, Gail H

    2010-01-01

    We present here a new observational technique, Phase Closure Nulling (PCN), which has the potential to obtain very high contrast detection and spectroscopy of faint companions to bright stars. PCN consists in measuring closure phases of fully resolved objects with a baseline triplet where one of the baselines crosses a null of the object visibility function. For scenes dominated by the presence of a stellar disk, the correlated flux of the star around nulls is essentially canceled out, and in these regions the signature of fainter, unresolved, scene object(s) dominates the imaginary part of the visibility in particular the closure phase. We present here the basics of the PCN method, the initial proof-of-concept observation, the envisioned science cases and report about the first observing campaign made on VLTI/AMBER and CHARA/MIRC using this technique.

  6. Characterizing the Properties of Coronal Magnetic Null Points

    Science.gov (United States)

    Barnes, Graham; DeRosa, Marc; Wagner, Eric

    2015-08-01

    The topology of the coronal magnetic field plays a role in a wide range of phenomena, from Coronal Mass Ejections (CMEs) through heating of the corona. One fundamental topological feature is the null point, where the magnetic field vanishes. These points are natural sites of magnetic reconnection, and hence the release of energy stored in the magnetic field. We present preliminary results of a study using data from the Helioseismic and Magnetic Imager aboard NASA's Solar Dynamics Observatory to characterize the properties and evolution of null points in a Potential Field Source Surface model of the coronal field. The main properties considered are the lifetime of the null points, their distribution with height, and how they form and subsequently vanish.This work is supported by NASA/LWS Grant NNX14AD45G, and by NSF/SHINE grant 1357018.

  7. Neutral evolution: A null model for language dynamics

    CERN Document Server

    Blythe, R A

    2011-01-01

    We review the task of aligning simple models for language dynamics with relevant empirical data, motivated by the fact that this is rarely attempted in practice despite an abundance of abstract models. We propose that one way to meet this challenge is through the careful construction of null models. We argue in particular that rejection of a null model must have important consequences for theories about language dynamics if modelling is truly to be worthwhile. Our main claim is that the stochastic process of neutral evolution (also known as genetic drift or random copying) is a viable null model for language dynamics. We survey empirical evidence in favour and against neutral evolution as a mechanism behind historical language changes, highlighting the theoretical implications in each case.

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

    CERN Document Server

    Chakraborty, Sumanta

    2015-01-01

    The emergent gravity paradigm interprets gravitational field equations as a 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 Ts 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 extremises 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 arXiv 1506.03814 to a...

  9. Interpreting null findings from trials of alcohol brief interventions.

    Science.gov (United States)

    Heather, Nick

    2014-01-01

    The effectiveness of alcohol brief intervention (ABI) has been established by a succession of meta-analyses but, because the effects of ABI are small, null findings from randomized controlled trials are often reported and can sometimes lead to skepticism regarding the benefits of ABI in routine practice. This article first explains why null findings are likely to occur under null hypothesis significance testing (NHST) due to the phenomenon known as "the dance of the p-values." A number of misconceptions about null findings are then described, using as an example the way in which the results of the primary care arm of a recent cluster-randomized trial of ABI in England (the SIPS project) have been misunderstood. These misinterpretations include the fallacy of "proving the null hypothesis" that lack of a significant difference between the means of sample groups can be taken as evidence of no difference between their population means, and the possible effects of this and related misunderstandings of the SIPS findings are examined. The mistaken inference that reductions in alcohol consumption seen in control groups from baseline to follow-up are evidence of real effects of control group procedures is then discussed and other possible reasons for such reductions, including regression to the mean, research participation effects, historical trends, and assessment reactivity, are described. From the standpoint of scientific progress, the chief problem about null findings under the conventional NHST approach is that it is not possible to distinguish "evidence of absence" from "absence of evidence." By contrast, under a Bayesian approach, such a distinction is possible and it is explained how this approach could classify ABIs in particular settings or among particular populations as either truly ineffective or as of unknown effectiveness, thus accelerating progress in the field of ABI research.

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

    Science.gov (United States)

    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. Reduced urea flux across the blood-testis barrier and early maturation in the male reproductive system in UT-B-null mice.

    Science.gov (United States)

    Guo, Lirong; Zhao, Dan; Song, Yuanlin; Meng, Yan; Zhao, Huashan; Zhao, Xuejian; Yang, Baoxue

    2007-07-01

    A urea-selective urine-concentrating defect was found in transgenic mice deficient in urea transporter (UT)-B. To determine the role of facilitated urea transport in extrarenal organs expressing UT-B, we studied the kinetics of [(14)C]urea distribution in UT-B-null mice versus wild-type mice. After renal blood flow was disrupted, [(14)C]urea distribution was selectively reduced in testis in UT-B-null mice. Under basal conditions, total testis urea content was 335.4 +/- 43.8 microg in UT-B-null mice versus 196.3 +/- 18.2 microg in wild-type mice (P UT-B-null mice (6.6 +/- 0.8 mg/g body wt) was significantly greater than in wild-type mice (4.2 +/- 0.8 mg/g body wt). Elongated spermatids were observed earlier in UT-B-null mice compared with wild type mice on day 24 versus day 32, respectively. First breeding ages in UT-B knockout males (48 +/- 3 days) were also significantly earlier than that in wild-type males (56 +/- 2 days). In competing mating tests with wild-type males and UT-B-null males, all pups carried UT-B-targeted genes, which indicates that all pups were produced from breeding of UT-B-null males. Experiments of the expression of follicle-stimulating hormone receptor (FSHR) and androgen binding protein (ABP) indicated that the development of Sertoli cells was also earlier in UT-B-null mice than that in wild-type mice. These results suggest that UT-B plays an important role in eliminating urea produced by Sertoli cells and that UT-B deletion causes both urea accumulation in the testis and early maturation of the male reproductive system. The UT-B knockout mouse may be a useful experimental model to define the molecular mechanisms of early puberty.

  12. Magnetic Reconnection at a Three-dimensional Solar Null Point

    DEFF Research Database (Denmark)

    Frederiksen, Jacob Trier; Baumann, Gisela; Galsgaard, Klaus

    2012-01-01

    -like). The MHD simulations start out from a potential magnetic field containing a null-point, obtained from a SOHO magnetogram extrapolation approximately 8 hours before a C-class flare was observed. The magnetic field is stressed with a boundary motion pattern similar to the horizontal motions observed by SOHO......Using a specific solar null point reconnection case studied by Masson et al (2009; ApJ 700, 559) we investigate the dependence of the reconnection rate on boundary driving speed, numerical resolution, type of resistivity (constant or numerical), and assumed stratification (constant density or solar...

  13. On nulls of perturbed Fredholm operators and degenerate homoclinic bifurcations

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    It is known that small perturbations of a Fredholm operator L have nulls of dimension not larger than dirnN(L). In this paper for any given positive integer κ≤ dimN(L)we prove that there is a perturbation of L which has an exactlyκ-dimensional null. Actually,our proof gives a construction of the perturbation. We further apply our result to concrete examples of differential equations with degenerate homoclinic orbits, showing how many independent homoclinic orbits can be bifurcated from a perturbation.

  14. Cartan's Equivalence Method and Null coframes in General Relativity

    CERN Document Server

    Gallo, E; Kozameh, C; Gallo, Emanuel; Iriondo, Mirta; Kozameh, Carlos

    2004-01-01

    Using Cartan's equivalence method for point transformations we obtain from first principles the conformal geometry associated with third order ODEs and a special class of PDEs in two dimensions. We explicitly construct the null tetrads of a family of Lorentzian metrics, the conformal group in three and four dimensions and the so called normal metric connection. A special feature of this connection is that the non vanishing components of its torsion depend on one relative invariant, the (generalized) W\\"unschmann Invariant. We show that the above mentioned construction naturally contains the Null Surface Formulation of General Relativity.

  15. Strength of the null singularity inside black holes

    CERN Document Server

    Burko, L M

    1999-01-01

    We study analytically the Cauchy horizon singularity inside spherically-symmetric charged black holes, coupled to a spherical self-gravitating, minimally-coupled, massless scalar field. We show that all causal geodesics terminate at the Cauchy horizon at a null singularity, which is weak according to the Tipler classification. The singularity is also deformationally-weak in the sense of Ori. Our results are valid at arbitrary points along the null singularity, in particular at late retarded times, when non-linear effects are crucial.

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

    Science.gov (United States)

    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.

  17. Pubertal and adult windows of susceptibility to a high animal fat diet in Trp53-null mammary tumorigenesis.

    Science.gov (United States)

    Zhu, Yirong; Aupperlee, Mark D; Zhao, Yong; Tan, Ying Siow; Kirk, Erin L; Sun, Xuezheng; Troester, Melissa A; Schwartz, Richard C; Haslam, Sandra Z

    2016-12-13

    Premenopausal breast cancer is associated with increased animal fat consumption among normal weight, but not overweight women (Farvid et al., 2014). Our previous findings in obesity-resistant BALB/c mice similarly showed promotion of carcinogen-induced mammary tumorigenesis by a diet high in saturated animal fat (HFD). This effect was specific to pubertal versus adult HFD. This study identifies the effects of HFD during puberty versus adulthood in Trp53-null transplant BALB/c mice and investigates its mechanism of enhancing tumorigenesis. Either pubertal or adult HFD is sufficient to increase incidence of Trp53-null mammary tumors. Puberty-restricted HFD exposure promoted tumor cell proliferation, increased angiogenesis, and increased recruitment of total and M2 macrophages in epithelial tumors. Adult-restricted exposure to HFD similarly increased proliferation, angiogenesis, recruitment of total and M2 macrophages, and additionally reduced apoptosis. Adult HFD also increased incidence of spindle cell carcinomas resembling claudin-low breast cancer, and thus adult HFD in the Trp53-null transplantation system may be a useful model for human claudin low breast cancer. Importantly, these results on Trp53-null and our prior studies on DMBA-induced mammary tumorigenesis demonstrate a pubertal window of susceptibility to the promotional effects of HFD, indicating the potential of early life dietary intervention to reduce breast cancer risk.

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

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Nicholas A., E-mail: namurphy@cfa.harvard.edu [Harvard-Smithsonian Center for Astrophysics, Cambridge, Massachusetts 02138 (United States); Parnell, Clare E.; Haynes, Andrew L. [School of Mathematics and Statistics, University of St Andrews, North Haugh, St Andrews, Fife KY16 9SS (United Kingdom)

    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.

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

    Science.gov (United States)

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

    2015-10-01

    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.

  20. Averaged null energy condition and quantum inequalities in curved spacetime

    CERN Document Server

    Kontou, Eleni-Alexandra

    2015-01-01

    The Averaged Null Energy Condition (ANEC) states that the integral along a complete null geodesic of the projection of the stress-energy tensor onto the tangent vector to the geodesic cannot be negative. ANEC can be used to rule out spacetimes with exotic phenomena, such as closed timelike curves, superluminal travel and wormholes. We prove that ANEC is obeyed by a minimally-coupled, free quantum scalar field on any achronal null geodesic (not two points can be connected with a timelike curve) surrounded by a tubular neighborhood whose curvature is produced by a classical source. To prove ANEC we use a null-projected quantum inequality, which provides constraints on how negative the weighted average of the renormalized stress-energy tensor of a quantum field can be. Starting with a general result of Fewster and Smith, we first derive a timelike projected quantum inequality for a minimally-coupled scalar field on flat spacetime with a background potential. Using that result we proceed to find the bound of a qu...

  1. Effectiveness of Null Signal Sky Localization in Pulsar Timing Arrays

    Science.gov (United States)

    Shafiq Hazboun, Jeffrey

    2017-01-01

    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. 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. Taking the product of a number of null streams allows for an even stronger localization of the gravitational wave's source; a large advantage in a PTA where there are more independent signals than other gravitational wave detectors. While a null stream contains the same information as any other data stream with the same number of pulsars, the statistics of a product of noisy signals is inherently different than for a sum of those same signals.A comparison of how null signal searches compare to other techniques for sky localization of PTA sources will be discussed, as well as an assessment of the types of searches for which the method may be useful.

  2. Null Lens Assembly for X-Ray Mirror Segments

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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…

  4. Overt and Null Subject Pronouns in Jordanian Arabic

    Science.gov (United States)

    Al-Momani, Islam M.

    2015-01-01

    The paper aims at examining the role that morphology plays in allowing and/or motivating sentences in Jordanian Arabic (hereafter JA) to be formed with or without subject pronouns. It also aims at giving a comprehensive and descriptive presentation of the distribution of overt and null subject pronouns in JA, and tries to determine to what extent…

  5. Null controllability for a fourth order parabolic equation

    Institute of Scientific and Technical Information of China (English)

    YU Hang

    2009-01-01

    In the paper,the null interior controllability for a fourth order parabolic equation is obtained.The method Is based on Lebeau-Rabbiano inequality which is a quantitative unique continuation property for the sum of eigenfunctions of the Laplacian.

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

    Science.gov (United States)

    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…

  7. Maxwell Fields and Shear-Free Null Geodesic Congruences

    CERN Document Server

    Newman, E

    2004-01-01

    We study and report on the class of vacuum Maxwell fields in Minkowski space that possess a non-degenerate, diverging, principle null vector field (null eigenvector field of the Maxwell tensor) that is tangent to a shear-free null geodesics congruence. These congruences can be either surface forming (the tangent vectors proportional to gradients) or not, i.e., the twisting congruences. In the non-twisting case, the associated Maxwell fields are precisely the Lienard-Wiechert fields, i.e., those Maxwell fields arising from an electric monopole moving on an arbitrary worldline. The null geodesic congruence is given by the generators of the light-cones with apex on the world-line. The twisting case is much richer, more interesting and far more complicated. In a twisting subcase, where our main interests lie, it can be given the following strange interpretation. If we allow the real Minkowski space to be complexified so that the real Minkowski coordinates x^a take complex values, i.e., x^a => z^a=x^a+iy^a with co...

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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.

  10. Dispersion in nulling interferometry for exoplanet detection: experimental validation

    NARCIS (Netherlands)

    Spronck, J.F.P.; Los, J.W.N.; Pereira, S.F.

    2009-01-01

    It is well known that dispersion affects the performance of a wide-band nulling interferometer, since it induces wavelength-dependent phase differences between the arms of the interferometer. This property is used to create achromatic phase shift by combining several dielectric plates. In this paper

  11. Progress in broadband infrared nulling technology for TPF

    Science.gov (United States)

    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.

  12. MHD oscillations and waves near a magnetic null line

    Energy Technology Data Exchange (ETDEWEB)

    Bulanov, S.V.; Syrovatskii, S.I.

    1980-11-01

    An informative picture is drawn of the propagation of Alfven and magnetosonic waves in a two-dimensional magnetic field with a hyperbolic null point in the approximation of a cold plasma. The magnetosonic waves asymptotically transform into cylindrical waves. The wave amplitude increases toward the null point. A distortion of the plasma boundary produces excitation of noncylindrical magnetosonic waves. If the frequency of these waves is below the critical value, they will not penetrate into the plasma. Dissipation leads to a reflection of magnetosonic waves near the null line. Any arbitrarily slight dissipation leads to the appearance of a discrete spectrum of weakly damped Alfven oscillations. Oscillations of this type also occur in adiabatic confinement systems in which the magnetic field has null points. The nonlinear distortion of magnetosonic waves which leads to wave breaking and to the appearance of weak shock waves is studied. The amplitude of the magnetic field perturbations in a shock wave propagating toward the center asymptotically approaches a constant value.

  13. Magnetoacoustic shock formation near a magnetic null point

    Science.gov (United States)

    Gruszecki, M.; Vasheghani Farahani, S.; Nakariakov, , V. M.; Arber, T. D.

    2011-07-01

    Aims: We investigate the interaction of nonlinear fast magnetoacoustic waves with a magnetic null point in connection with the triggering of solar flares. Methods: We model the propagation of fast, initially axisymmetric waves towards a two-dimensional isothermal magnetic null point in terms of ideal magnetohydrodynamic equations. The numerical simulations are carried out with the Lagrangian remap code Lare2D. Results: Dynamics of initially axisymmetric fast pulses of small amplitude is found to be consistent with a linear analytical solution proposed earlier. The increase in the amplitude leads to the nonlinear acceleration of the compression pulse and deceleration of the rarefaction pulse and hence the distortion of the wave front. The pulse experiences nonlinear steepening in the radial direction either on the leading or the back slopes for the compression and rarefaction pulses, respectively. This effect is most pronounced in the directions perpendicular to the field. Hence, the nonlinear evolution of the fast pulse depends on the polar angle. The nonlinear steepening generates the sharp spikes of the electric current density. As in the uniform medium, the position of the shock formation also depends on the initial width of the pulse. Only sufficiently smooth and low-amplitude initial pulses can reach the vicinity of the null point, create there current density spikes, and initiate magnetic reconnection by seeding anomalous electrical resistivity. Steeper and higher amplitude initial pulses overturn at larger distance from the null point, and cannot trigger reconnection.

  14. Design of a polarization nulling interferometer for exoplanet detection

    NARCIS (Netherlands)

    Spronck, J.; Vosteen, L.L.A.; Pereira, S.F.; Braat, J.J.M.

    2007-01-01

    We present the design of a new testbed experiment to demonstrate nulling interferometry using polarization properties. This three-beam set-up is perfectly symmetric with respect to the number of reflections and transmissions and should therefore allow a high rejection ratio in a wide spectral band.

  15. Nulling interferometry for exoplanet detection using polarization properties

    NARCIS (Netherlands)

    Spronck, J.; Pereira, S.F.; Braat, J.J.M.

    2006-01-01

    We present a new type of nulling interferometer that makes use of polarization properties to have on-axis destructive interference. The proposed design, which only involves commercial components and no achromatic device, is also suitable for internal modulation. This type of interferometer should en

  16. Compensation and optimization of dispersion in nulling interferometry

    NARCIS (Netherlands)

    Spronck, J.F.P.; Los, J.W.N.; Pereira, S.F.

    2008-01-01

    The optical properties of materials are wavelength-dependent. This property, called dispersion, affects the performance of a wide-band nulling interferometer by inducing wavelength-dependent phase differences between the arms of the interferometer. In this paper, we analyze the influence of dispersi

  17. Waves and null congruences in a draining bathtub

    Science.gov (United States)

    Dempsey, David; Dolan, Sam R.

    2016-04-01

    We study wave propagation in a draining bathtub: a black hole analogue in fluid mechanics whose perturbations are governed by a Klein-Gordon equation on an effective Lorentzian geometry. Like the Kerr spacetime, the draining bathtub geometry possesses an (effective) horizon, an ergosphere and null circular orbits. We propose here that a ‘pulse’ disturbance may be used to map out the light-cone of the effective geometry. First, we apply the eikonal approximation to elucidate the link between wavefronts, null geodesic congruences and the Raychaudhuri equation. Next, we solve the wave equation numerically in the time domain using the method of lines. Starting with Gaussian initial data, we demonstrate that a pulse will propagate along a null congruence and thus trace out the light-cone of the effective geometry. Our new results reveal features, such as wavefront intersections, frame-dragging, winding and interference effects, that are closely associated with the presence of null circular orbits and the ergosphere.

  18. Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice

    DEFF Research Database (Denmark)

    Larsen, Peter Hjørringgaard; DaSilva, Angelika G.; Conant, Kathrine;

    2006-01-01

    The matrix metalloproteinases (MMPs) are implicated in several activities within the nervous system. Although many functions of abnormally elevated MMPs are undesirable, the discrete expression of particular MMP members can have beneficial roles. We previously found that MMP-9 expressed locally a......-9 and -12, to be upregulated during the period of myelin formation. These MMPs partake in myelinogenesis because myelination in the corpus callosum of MMP-9 and/or MMP-12 null mice was deficient from postnatal days 7 to 14 compared with that of wild-type mice. The deficient myelination...... was correlated with fewer mature oligodendrocytes, but similar precursor cell numbers, in MMP null animals compared with wild type. Because an important growth factor for oligodendrocyte maturation is insulin-like growth factor-1 (IGF-1), we addressed whether this was involved in the deficient myelination in MMP...... null mice. Indeed, the addition of IGF-1 normalized the lack of maturation of oligodendrocytes that occurred in cultures from MMP-12 null mice. Furthermore, we determined that IGF binding protein 6 (IGFBP-6), which sequesters IGF-1, was a substrate for MMP processing. Finally, we found IGFBP-6 levels...

  19. Atrial tachyarrhythmia in Rgs5-null mice.

    Directory of Open Access Journals (Sweden)

    Mu Qin

    Full Text Available AIMS: The aim of this study was to elucidate the effects of regulator of G-protein signaling 5 (Rgs5, a negative regulator of G protein-mediated signaling, on atrial repolarization and tachyarrhythmia (ATA in mice. METHODS AND RESULTS: In present study, the incidence of ATA were increased in Rgs5(-/- Langendorff-perfused mouse hearts during program electrical stimulation (PES (46.7%, 7 of 15 and burst pacing (26.7%, 4 of 15 compared with wild-type (WT mice (PES: 7.1%,1 of 14; burst:7.1%,1 of 14 (P30 s but none of them observed in WT mice. Atrial prolonged repolarization was observed in Rgs5(-/- hearts including widened P wave in surface ECG recording, increased action potential duration (APD and atrial effective refractory periods (AERP, all of them showed significant difference with WT mice (P<0.05. At the cellular level, whole-cell patch clamp recorded markedly decreased densities of repolarizing K(+ currents including I(Kur (at +60 mV: 14.0±2.2 pF/pA and I(to (at +60 mV: 16.7±1.3 pA/pF in Rgs5(-/- atrial cardiomyocytes, compared to those of WT mice (at +60 mV I(to: 20.4±2.0 pA/pF; I(kur: 17.9±2.0 pF/pA (P<0.05. CONCLUSION: These results suggest that Rgs5 is an important regulator of arrhythmogenesis in the mouse atrium and that the enhanced susceptibility to atrial tachyarrhythmias in Rgs5(-/- mice may contribute to abnormalities of atrial repolarization.

  20. Proof of a Null Penrose Conjecture using a new Quasi-local Mass

    CERN Document Server

    Roesch, Henri

    2016-01-01

    We define an explicit quasi-local mass functional which is non-decreasing along all foliations (satisfying a convexity assumption) of null cones. We use this new functional to prove the null Penrose conjecture under fairly generic conditions.

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

    Science.gov (United States)

    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.

  2. Biological and genetic properties of the p53 null preneoplastic mammary epithelium

    Science.gov (United States)

    Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

    2002-01-01

    The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

  3. Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

    Science.gov (United States)

    Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

    2016-01-01

    Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

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

    Science.gov (United States)

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

    2011-02-01

    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.

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

    Science.gov (United States)

    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.

  6. Null fluids: A new viewpoint of Galilean fluids

    Science.gov (United States)

    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.

  7. Averaged null energy condition in Loop Quantum Cosmology

    CERN Document Server

    Li, Li-Fang

    2008-01-01

    Wormhole and time machine are very interesting objects in general relativity. However, they need exotic matters which are impossible in classical level to support them. But if we introduce the quantum effects of gravity into the stress-energy tensor, these peculiar objects can be constructed self-consistently. Fortunately, loop quantum cosmology (LQC) has the potential to serve as a bridge connecting the classical theory and quantum gravity. Therefore it provides a simple way for the study of quantum effect in the semiclassical case. As is well known, loop quantum cosmology is very successful to deal with the behavior of early universe. In the early stage, if taken the quantum effect into consideration, inflation is natural because of the violation of every kind of local energy conditions. Similar to the inflationary universe, the violation of the averaged null energy condition is the necessary condition for the traversable wormholes. In this paper, we investigate the averaged null energy condition in LQC in ...

  8. Defocusing of null rays in infinite derivative gravity

    Science.gov (United States)

    Conroy, Aindriú; Koshelev, Alexey S.; Mazumdar, Anupam

    2017-01-01

    Einstein's General theory of relativity permits spacetime singularities, where null geodesic congruences focus in the presence of matter, which satisfies an appropriate energy condition. In this paper, we provide a minimal defocusing condition for null congruences without assuming any ansatz-dependent background solution. The two important criteria are: (1) an additional scalar degree of freedom, besides the massless graviton must be introduced into the spacetime; and (2) an infinite derivative theory of gravity is required in order to avoid tachyons or ghosts in the graviton propagator. In this regard, our analysis strengthens earlier arguments for constructing non-singular bouncing cosmologies within an infinite derivative theory of gravity, without assuming any ansatz to solve the full equations of motion.

  9. Analysis of nulling phase functions suitable to image plane coronagraphy

    CERN Document Server

    Henault, Francois; Verinaud, Christophe

    2016-01-01

    Coronagraphy is a very efficient technique for identifying and characterizing extra-solar planets orbiting in the habitable zone of their parent star, especially when used in a space environment. An important family of coronagraphs is based on phase plates located at an intermediate image plane of the optical system, that spread the starlight outside the "Lyot" exit pupil plane of the instrument. In this communication we present a set of candidate phase functions generating a central null at the Lyot plane, and study how it propagates to the image plane of the coronagraph. These functions include linear azimuthal phase ramps (the well-known optical vortex), azimuthally cosine-modulated phase profiles, and circular phase gratings. Numerical simulations of the expected null depth, inner working angle, sensitivity to pointing errors, effect of central obscuration located at the pupil or image planes, and effective throughput including image mask and Lyot stop transmissions are presented and discussed. The prelim...

  10. Null Fluids - A New Viewpoint of Galilean Fluids

    CERN Document Server

    Banerjee, Nabamita; Jain, Akash

    2015-01-01

    This article is a detailed version of our short letter `On equilibrium partition function for non-relativistic fluid' [arXiv:1505.05677] extended to include an anomalous $U(1)$ symmetry. We construct a relativistic system, which we call 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 Poincare 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 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.

  11. Averaged-null-energy condition for electromagnetism in Minkowski spacetime

    Energy Technology Data Exchange (ETDEWEB)

    Folacci, A. (Universite de Corse, Faculte des Sciences, Boite Postale 52, 20250 Corti (France))

    1992-09-15

    We show, on four-dimensional Minkowski spacetime, that {l angle}{psi}{vert bar}{ital T}{sub {mu}{nu}}{vert bar}{psi}{r angle}, the renormalized expectation value in a general quantum state {vert bar}{psi}{r angle} of the stress-energy tensor for electromagnetism, satisfies the averaged-null-energy condition, i.e., that {integral}{ital d}{lambda}{l angle}{psi}{vert bar}{ital T}{sub {mu}{nu}}{vert bar}{psi}{r angle}{ital t}{sup {mu}}{ital t{nu}}{ge}0 where this integral is along complete null geodesics with an affine parameter {lambda} and tangent vector {ital t}{sup {mu}}.

  12. Magnetic Reconnection at a Three-dimensional Solar Null Point

    Science.gov (United States)

    Frederiksen, J. T.; Baumann, G.; Galsgaard, K.; Haugbølle, T.; Nordlund, Å.

    2012-04-01

    Using a specific solar null point reconnection case studied by Masson et al (2009; ApJ 700, 559) we investigate the dependence of the reconnection rate on boundary driving speed, numerical resolution, type of resistivity (constant or numerical), and assumed stratification (constant density or solar-like). The MHD simulations start out from a potential magnetic field containing a null-point, obtained from a SOHO magnetogram extrapolation approximately 8 hours before a C-class flare was observed. The magnetic field is stressed with a boundary motion pattern similar to the horizontal motions observed by SOHO during the period preceding the flare. The general behavior is nearly independent of driving speed and numerical resolution, and is also very similar in stratified and unstratified models, provided only that the boundary motions are slow enough.

  13. MHD Mode Conversion around a 2D Magnetic Null Point

    CERN Document Server

    McDougall, A M D; 10.1063/1.3099224

    2009-01-01

    Mode conversion occurs when a wave passes through a region where the sound and Alfven speeds are equal. At this point there is a resonance, which allows some of the incident wave to be converted into a different mode. We study this phenomenon in the vicinity of a two-dimensional, coronal null point. As a wave approaches the null it passes from low- to high-beta plasma, allowing conversion to take place. We simulate this numerically by sending in a slow magnetoacoustic wave from the upper boundary; as this passes through the conversion layer a fast wave can clearly be seen propagating ahead. Numerical simulations combined with an analytical WKB investigation allow us to determine and track both the incident and converted waves throughout the domain.

  14. Nonparametric Regression Estimation for Multivariate Null Recurrent Processes

    Directory of Open Access Journals (Sweden)

    Biqing Cai

    2015-04-01

    Full Text Available This paper discusses nonparametric kernel regression with the regressor being a \\(d\\-dimensional \\(\\beta\\-null recurrent process in presence of conditional heteroscedasticity. We show that the mean function estimator is consistent with convergence rate \\(\\sqrt{n(Th^{d}}\\, where \\(n(T\\ is the number of regenerations for a \\(\\beta\\-null recurrent process and the limiting distribution (with proper normalization is normal. Furthermore, we show that the two-step estimator for the volatility function is consistent. The finite sample performance of the estimate is quite reasonable when the leave-one-out cross validation method is used for bandwidth selection. We apply the proposed method to study the relationship of Federal funds rate with 3-month and 5-year T-bill rates and discover the existence of nonlinearity of the relationship. Furthermore, the in-sample and out-of-sample performance of the nonparametric model is far better than the linear model.

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

    Science.gov (United States)

    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.

  16. Do electromagnetic waves always propagate along null geodesics?

    CERN Document Server

    Asenjo, Felipe A

    2016-01-01

    We find exact solutions to Maxwell equations written in terms of four-vector potentials in non--rotating, as well as in G\\"odel and Kerr spacetimes. Exact electromagnetic waves solutions are written on given gravitational field backgrounds where they evolve. We find that in non--rotating spherical symmetric spacetimes, electromagnetic plane waves travel along null geodesics. However, electromagnetic plane waves on G\\"odel and Kerr spacetimes do not exhibit that behavior.

  17. Null controllability for a parabolic-elliptic coupled system

    CERN Document Server

    Fernández-Cara, E; de Menezes, S B

    2012-01-01

    In this paper, we prove the null controllability of some parabolic-elliptic systems. The control is distributed, locally supported in space and appears only in one PDE. The arguments rely on fixed-point reformulation and suitable Carleman estimates for the solutions to the adjoint system. Under appropriate assumptions, we also prove that the solution can be obtained as the asymptotic limit of some similar parabolic systems.

  18. Null-Tetradic treatment of the Relativistic Dynamics (II)

    Science.gov (United States)

    Gottlieb, I.; Maftei, Gh.

    The authors apply the Null-tetradic formalism as was given in the book by Kramer, Stephani, Herlt, Mac-Callum, Exact Solutions (1980) to some of the chapters of General Relativity which were not examined in the book above and such a way make a connection with another classic book in General Relativity: that of Landau and Lifchitz, Theorie des champs, Ed. Mir, Moscou (1989).

  19. Three-dimensional magnetic reconnection through a moving magnetic null

    OpenAIRE

    Lukin, V. S.; Linton, M. G.

    2011-01-01

    A computational study of three-dimensional magnetic reconnection between two flux ropes through a moving reconnection site is presented. The configuration is considered in the context of two interacting spheromaks constrained by a perfectly conducting cylindrical boundary and oriented to form a single magnetic field null at its center. The initial magnetic field configuration is embedded into a uniform thermal plasma and is unstable to tilting. As the sphe...

  20. Three-dimensional magnetic reconnection through a moving magnetic null

    OpenAIRE

    Lukin, V. S.; Linton, M. G.

    2011-01-01

    A computational study of three-dimensional magnetic reconnection between two flux ropes through a moving reconnection site is presented. The configuration is considered in the context of two interacting spheromaks constrained by a perfectly conducting cylindrical boundary and oriented to form a single magnetic field null at its center. The initial magnetic field configuration is embedded into a uniform thermal plasma and is unstable to tilting. As the spheromaks tilt, their magnetic fi...

  1. (abstract) Ulysses Observations of Magnetic Nulls in the Solar Wind

    Science.gov (United States)

    Winterhalter, D.; Murphy, N.; Tsurutani, B. T.; Smith, E. J.; Balogh, A.; Erdos, G.

    1993-01-01

    High time resolution magnetic field measurements (1 vector/s) at radial distances out to 5.3 AU and heliographic latitudes from 0(deg) to > 35(deg) S reveal the presence of solitary pulses lasting tens of seconds in which the field magnitude approaches or reaches zero. The properties of these nulls, their spatial distribution and relation to solar wind structures and to similar-apppearing interplanetary and magnetospheric impulses will be discussed.

  2. Nulling interferometry for exoplanet detection using polarization properties

    OpenAIRE

    Spronck, J.; Pereira, S.F.; Braat, J.J.M.

    2006-01-01

    We present a new type of nulling interferometer that makes use of polarization properties to have on-axis destructive interference. The proposed design, which only involves commercial components and no achromatic device, is also suitable for internal modulation. This type of interferometer should enable a high rejection ratio in a theoretically unlimited spectral band. We implemented that concept on a two-beam white-light interferometer and we present here the first experimental results

  3. Fresnel rhombs as achromatic phase shifters for infrared nulling interferometry

    OpenAIRE

    Mawet, D.; Hanot, Charles; Lenaers, C.; Riaud, Pierre; Defrere, Denis; Vandormael; Loicq, Jerôme; Fleury, K.; Plesseria, Jean-Yves; Surdej, Jean; Habraken, Serge

    2007-01-01

    We propose a new family of achromatic phase shifters for infrared nulling interferometry. These key optical components can be seen as optimized Fresnel rhombs, using the total internal reflection phenomenon, modulated or not. The total internal reflection indeed comes with a phase shift between the polarization components of the incident light. We propose a solution to implement this vectorial phase shift between interferometer arms to provide the destructive interference process needed to di...

  4. The Steinhaus property and Haar-null sets

    CERN Document Server

    Dodos, Pandelis

    2010-01-01

    It is shown that if $G$ is an uncountable Polish group and $A\\subseteq G$ is a universally measurable set such that $A^{-1}A$ is meager, then the set $T_l(A)=\\{\\mu\\in P(G): \\mu(gA)=0 \\text{for all} g\\in G\\}$ is co-meager. In particular, if $A$ is analytic and not left Haar-null, then $1\\in\\mathrm{Int}(A^{-1}AA^{-1}A)$.

  5. Null controllability for linear parabolic cascade systems with interior degeneracy

    Directory of Open Access Journals (Sweden)

    Idriss Boutaayamou

    2016-11-01

    Full Text Available We study the null controllability problem for linear degenerate parabolic systems with one control force through Carleman estimates for the associated adjoint problem. The novelty of this article is that for the first time it is considered a problem with an interior degeneracy and a control set that only requires to contain an interval lying on one side of the degeneracy points. The obtained result improves and complements a number of earlier works. As a consequence, observability inequalities are established.

  6. 4-dimensional spacetimes from 2-dimensional conformal null data

    Science.gov (United States)

    Goswami, Rituparno; Ellis, George F. R.

    2017-03-01

    In this paper we investigate whether the holographic principle proposed in string theory has a classical counterpart in general relativity theory. We show that there is a partial correspondence: at least in the case of vacuum Petrov type D spacetimes that admit a non-trivial Killing tensor, which encompass all the astrophysical black hole spacetimes, there exists a one-to-one correspondence between gravity in bulk and a 2-dimensional classical conformal scalar field on a null boundary.

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

    Science.gov (United States)

    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.

  8. Retarded Fields of Null Particles and the Memory Effect

    CERN Document Server

    Tolish, Alexander

    2014-01-01

    We consider the retarded solution to the scalar, electromagnetic, and linearized gravitational field equations in Minkowski spacetime, with source given by a particle moving on a null geodesic. In the scalar case and in the Lorenz gauge in the electromagnetic and gravitational cases, the retarded integral over the infinite past of the source does not converge as a distribution, so we cut off the null source suitably at a finite time $t_0$ and then consider two different limits: (i) the limit as the observation point goes to null infinity at fixed $t_0$, from which the ``$1/r$'' part of the fields can be extracted and (ii) the limit $t_0 \\to - \\infty$ at fixed ``observation point.'' The limit (i) gives rise to a ``velocity kick'' on distant test particles in the scalar and electromagnetic cases, and it gives rise to a ``memory effect'' (i.e., a permanent change in relative separation of two test particles) in the linearized gravitational case, in agreement with previous analyses. Although the second limit does...

  9. Evaluating thermoregulation in reptiles: an appropriate null model.

    Science.gov (United States)

    Christian, Keith A; Tracy, Christopher R; Tracy, C Richard

    2006-09-01

    Established indexes of thermoregulation in ectotherms compare body temperatures of real animals with a null distribution of operative temperatures from a physical or mathematical model with the same size, shape, and color as the actual animal but without mass. These indexes, however, do not account for thermal inertia or the effects of inertia when animals move through thermally heterogeneous environments. Some recent models have incorporated body mass, to account for thermal inertia and the physiological control of warming and cooling rates seen in most reptiles, and other models have incorporated movement through the environment, but none includes all pertinent variables explaining body temperature. We present a new technique for calculating the distribution of body temperatures available to ectotherms that have thermal inertia, random movements, and different rates of warming and cooling. The approach uses a biophysical model of heat exchange in ectotherms and a model of random interaction with thermal environments over the course of a day to create a null distribution of body temperatures that can be used with conventional thermoregulation indexes. This new technique provides an unbiased method for evaluating thermoregulation in large ectotherms that store heat while moving through complex environments, but it can also generate null models for ectotherms of all sizes.

  10. Zero emission city. Preliminary study; Null-Emissions-Stadt. Sondierungsstudie

    Energy Technology Data Exchange (ETDEWEB)

    Diefenbach, N.; Enseling, A.; Werner, P.; Flade, A.; Greiff, R.; Hennings, D.; Muehlich, E.; Wullkopf, U.; Sturm, P.; Kieslich, W.; Born, R.; Grossklos, M.; Hatteh, R.; Mueller, K.; Ratschow, A.; Valouch-Fornoff, C.

    2002-10-01

    The idea of a 'zero emission city' is investigated by the Institut Wohnen und Umwelt on behalf of the Federal Minister of Education and Research. After describing the current situation and defining the key parameters of a 'zero emission city', settlement structures, power supply, production processes and transportation are analyzed and linked with the communal action level to obtain a framework for research, activities and actions. The study ends with recommendations for a research programme 'zero emission city'. (orig.) [German] Die von den Staedten der Industrielaender ausgehenden Emissionen stellen im Hinblick auf die globalen Belastungen wie z.B. Treibhauseffekt, Ozonabbau und Versauerung das Hauptproblem dar. Aus diesem Grunde bietet es sich an, den Gedanken der 'Null-Emissions-Stadt', der Vision einer moeglichst emissionsfreien Stadt, aufzugreifen und auf seine Tragfaehigkeit fuer innovative Handlungsmodelle forschungsstrategisch zu ueberpruefen. Das Bundesministerium fuer Bildung und Forschung hat das Institut Wohnen und Umwelt beauftragt, in einer Sondierungsstudie dieser Fragestellung nachzugehen. Nach der Festlegung der Ausgangsbedingungen und Eckpunkte der Vision 'Null-Emissions-Stadt' und der Analyse der vier Handlungsfelder Siedlungsstrukturen, Energieversorgung, Produktionsprozesse (Kreislaufwirtschaft) und Verkehr werden diese aufgegriffen und mit der kommunalen Handlungsebene verknuepft und zu einem Forschungs-, Handlungs- und moeglichen Aktionsrahmen zusammengefuegt. Die Studie schliesst mit Hinweisen fuer die Gestaltung eines Forschungsprogramms 'Null-Emissions-Stadt'. (orig.)

  11. Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice

    Directory of Open Access Journals (Sweden)

    Barbara Ghinassi

    2011-01-01

    Full Text Available Ex vivo expanded erythroblasts (EBs may serve as advanced transfusion products provided that lodgment occurs in the macrophage-niche of the marrow permitting maturation. EBs expanded from adult and cord blood expressed the receptors (CXCR4, VLA-4, and P-selectin ligand 1 necessary for interaction with macrophages. However, 4-days following transfusion to intact NOD/SCID/IL2Rγnull mice, CD235apos EBs were observed inside CD235aneg splenic cells suggesting that they underwent phagocytosis. When splenectomized and intact NOD/SCID/IL2Rγnull mice were transfused using retrovirally labeled human EBs, human cells were visualized by bioluminescence imaging only in splenectomized animals. Four days after injection, human CD235apos cells were detected in marrow and liver of splenectomized mice but only in spleen of controls. Human CD235apos erythrocytes in blood remained low in all cases. These studies establish splenectomized NOD/SCID/IL2Rγnull mice as a suitable model for tracking and quantification of human EBs in vivo.

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

    Energy Technology Data Exchange (ETDEWEB)

    Parattu, Krishnamohan; Chakraborty, Sumanta; Padmanabhan, T. [IUCAA, Post Bag 4, Pune (India)

    2016-03-15

    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. (orig.)

  13. Variational Principle for Gravity with Null and Non-null boundaries: A Unified Boundary Counter-term

    CERN Document Server

    Parattu, Krishnamohan; Padmanabhan, T

    2016-01-01

    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.

  14. Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice

    Directory of Open Access Journals (Sweden)

    Han Renzhi

    2011-12-01

    Full Text Available Abstract Background Mutations in the genes coding for either dystrophin or dysferlin cause distinct forms of muscular dystrophy. Dystrophin links the cytoskeleton to the sarcolemma through direct interaction with β-dystroglycan. This link extends to the extracellular matrix by β-dystroglycan's interaction with α-dystroglycan, which binds extracellular matrix proteins, including laminin α2, agrin and perlecan, that possess laminin globular domains. The absence of dystrophin disrupts this link, leading to compromised muscle sarcolemmal integrity. Dysferlin, on the other hand, plays an important role in the Ca2+-dependent membrane repair of damaged sarcolemma in skeletal muscle. Because dysferlin and dystrophin play different roles in maintaining muscle cell integrity, we hypothesized that disrupting sarcolemmal integrity with dystrophin deficiency would exacerbate the pathology in dysferlin-null mice and allow further characterization of the role of dysferlin in skeletal muscle. Methods To test our hypothesis, we generated dystrophin/dysferlin double-knockout (DKO mice by breeding mdx mice with dysferlin-null mice and analyzed the effects of a combined deficiency of dysferlin and dystrophin on muscle pathology and sarcolemmal integrity. Results The DKO mice exhibited more severe muscle pathology than either mdx mice or dysferlin-null mice, and, importantly, the onset of the muscle pathology occurred much earlier than it did in dysferlin-deficient mice. The DKO mice showed muscle pathology of various skeletal muscles, including the mandible muscles, as well as a greater number of regenerating muscle fibers, higher serum creatine kinase levels and elevated Evans blue dye uptake into skeletal muscles. Lengthening contractions caused similar force deficits, regardless of dysferlin expression. However, the rate of force recovery within 45 minutes following lengthening contractions was hampered in DKO muscles compared to mdx muscles or dysferlin-null

  15. Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice.

    Science.gov (United States)

    Aaker, Joshua D; Elbaz, Benayahu; Wu, Yuwen; Looney, Timothy J; Zhang, Li; Lahn, Bruce T; Popko, Brian

    2016-10-01

    The transcriptional program that controls oligodendrocyte maturation and central nervous system (CNS) myelination has not been fully characterized. In this study, we use high-throughput RNA sequencing to analyze how the loss of a key transcription factor, zinc finger protein 191 (ZFP191), results in oligodendrocyte development abnormalities and CNS hypomyelination. Using a previously described mutant mouse that is deficient in ZFP191 protein expression (Zfp191(null)), we demonstrate that key transcripts are reduced in the whole brain as well as within oligodendrocyte lineage cells cultured in vitro To determine whether the loss of myelin seen in Zfp191(null) mice contributes indirectly to these perturbations, we also examined the transcriptome of a well-characterized mouse model of hypomyelination, in which the myelin structural protein myelin basic protein (MBP) is deficient. Interestingly, Mbp(shi) (shiverer) mice had far fewer transcripts perturbed with the loss of myelin alone. This study demonstrates that the loss of ZFP191 disrupts expression of genes involved in oligodendrocyte maturation and myelination, largely independent from the loss of myelin. Nevertheless, hypomyelination in both mouse mutants results in the perturbation of lipid synthesis pathways, suggesting that oligodendrocytes have a feedback system that allows them to regulate myelin lipid synthesis depending on their myelinating state. The data presented are of potential clinical relevance as the human orthologs of the Zfp191 and MBP genes reside on a region of Chromosome 18 that is deleted in childhood leukodystrophies.

  16. Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi Mice

    Directory of Open Access Journals (Sweden)

    Joshua D. Aaker

    2016-09-01

    Full Text Available The transcriptional program that controls oligodendrocyte maturation and central nervous system (CNS myelination has not been fully characterized. In this study, we use high-throughput RNA sequencing to analyze how the loss of a key transcription factor, zinc finger protein 191 (ZFP191, results in oligodendrocyte development abnormalities and CNS hypomyelination. Using a previously described mutant mouse that is deficient in ZFP191 protein expression (Zfp191null, we demonstrate that key transcripts are reduced in the whole brain as well as within oligodendrocyte lineage cells cultured in vitro. To determine whether the loss of myelin seen in Zfp191null mice contributes indirectly to these perturbations, we also examined the transcriptome of a well-characterized mouse model of hypomyelination, in which the myelin structural protein myelin basic protein (MBP is deficient. Interestingly, Mbpshi (shiverer mice had far fewer transcripts perturbed with the loss of myelin alone. This study demonstrates that the loss of ZFP191 disrupts expression of genes involved in oligodendrocyte maturation and myelination, largely independent from the loss of myelin. Nevertheless, hypomyelination in both mouse mutants results in the perturbation of lipid synthesis pathways, suggesting that oligodendrocytes have a feedback system that allows them to regulate myelin lipid synthesis depending on their myelinating state. The data presented are of potential clinical relevance as the human orthologs of the Zfp191 and MBP genes reside on a region of Chromosome 18 that is deleted in childhood leukodystrophies.

  17. Increased angiogenic response in aortic explants of collagen XVIII/endostatin-null mice.

    Science.gov (United States)

    Li, Qing; Olsen, Bjorn R

    2004-08-01

    Endostatin, a proteolytic fragment of basement membrane-associated collagen XVIII, has been shown to be a potent angiogenesis inhibitor both in vivo and in vitro when given at high concentrations. The precise molecular mechanisms by which it functions and whether or not it plays a role in physiological regulation of angiogenesis are not clear. In mice with targeted null alleles of Col18a1, there appears to be no major abnormality in vascular patterns or capillary density in most organs. Furthermore, the growth of experimental tumors is not increased. However, a detailed analysis of induced angiogenesis in these mice has not been performed. Therefore, we compared the angiogenic responses induced by in vitro culture of aortic explants from collagen XVIII/endostatin-null mice (ko) to wild-type (wt) littermates. We found a twofold increase in microvessel outgrowth in explants from ko mice, relative to wt explants. This increased angiogenesis was reduced to the wt level by the addition of low levels (0.1 microg/ml) of recombinant mouse or human endostatin during the culture period. To address cellular/molecular mechanisms underlying this difference in angiogenic response between ko and wt mice, we isolated endothelial cells from both strains and compared their biological behavior. Proliferation assays showed no difference between the two types of endothelial cells. In contrast, adhesion assays showed a striking difference in their ability to adhere to fibronectin suggesting that collagen XVIII/endostatin may regulate interactions between endothelial cells and underlying basement membrane-associated components, including fibronectin, such that in the absence of collagen XVIII/endostatin, endothelial cells are more adhesive to fibronectin. In the aortic explant assay, characterized by dynamic processes of microvessel elongation and regression, this may result in stabilization of newly formed vessels, reduced regression, and a net increase in microvessel outgrowth in

  18. MicroRNA Dysregulation in Liver and Pancreas of CMP-Neu5Ac Hydroxylase Null Mice Disrupts Insulin/PI3K-AKT Signaling

    Directory of Open Access Journals (Sweden)

    Deug-Nam Kwon

    2014-01-01

    Full Text Available CMP-Neu5Ac hydroxylase (Cmah-null mice fed with a high-fat diet develop fasting hyperglycemia, glucose intolerance, and pancreatic β-cell dysfunction and ultimately develop characteristics of type 2 diabetes. The precise metabolic role of the Cmah gene remains poorly understood. This study was designed to investigate the molecular mechanisms through which microRNAs (miRNAs regulate type 2 diabetes. Expression profiles of miRNAs in Cmah-null mouse livers were compared to those of control mouse livers. Liver miFinder miRNA PCR arrays (n=6 showed that eight miRNA genes were differentially expressed between the two groups. Compared with controls, seven miRNAs were upregulated and one miRNA was downregulated in Cmah-null mice. Specifically, miR-155-5p, miR-425-5p, miR-15a-5p, miR-503-5p, miR-16-5p, miR-29a-3p, and miR-29b-3p were significantly upregulated in the liver and pancreas of Cmah-null mice. These target miRNAs are closely associated with dysregulation of insulin/PI3K-AKT signaling, suggesting that the Cmah-null mice could be a useful model for studying diabetes.

  19. Brn3c null mutant mice show long-term, incomplete retention of some afferent inner ear innervation

    Directory of Open Access Journals (Sweden)

    Pirvola Ulla

    2003-01-01

    Full Text Available Abstract Background Ears of Brn3c null mutants develop immature hair cells, identifiable only by certain molecular markers, and undergo apoptosis in neonates. This partial development of hair cells could lead to enough neurotrophin expression to sustain sensory neurons through embryonic development. We have therefore investigated in these mutants the patterns of innervation and of expression of known neurotrophins. Results At birth there is a limited expression of BDNF and NT-3 in the mutant sensory epithelia and DiI tracing shows no specific reduction of afferents or efferents that resembles neurotrophin null mutations. At postnatal day 7/8 (P7/8, innervation is severely reduced both qualitatively and quantitatively. 1% of myosin VIIa-positive immature hair cells are present in the mutant cochlea, concentrated in the base. Around 20% of immature hair cells exist in the mutant vestibular sensory epithelia. Despite more severe loss of hair cells (1% compared to 20%, the cochlea retains many more sensory neurons (46% compared to 15% than vestibular epithelia. Even 6 months old mutant mice have some fibers to all vestibular sensory epithelia and many more to the cochlear apex which lacks MyoVIIa positive hair cells. Topologically organized central cochlea projections exist at least until P8, suggesting that functional hair cells are not required to establish such projections. Conclusion The limited expression of neurotrophins in the cochlea of Brn3c null mice suffices to support many sensory neurons, particularly in the cochlea, until birth. The molecular nature of the long term survival of apical spiral neurons remains unclear.

  20. Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip

    Directory of Open Access Journals (Sweden)

    Jongeun Lee

    2013-05-01

    Keratin 8 and 18 (K8/K18 are major intermediate filament proteins of liver hepatocytes. They provide mechanical and nonmechanical stability, thereby protecting cells from stress. Hence, K8-null mice are highly sensitive to Fas-mediated liver cell apoptosis. However, the role of c-Flip protein in K8-null related susceptibility to liver injury is controversial. Here we analyzed c-Flip protein expression in various K8 or K18 null/mutant transgenic livers and show that they are similar in all analyzed transgenic livers and that previously reported c-Flip protein changes are due to antibody cross-reaction with mouse K18. Furthermore, analysis of various apoptosis- or cell survival-related proteins demonstrated that inhibition of phosphorylation of NF-κB and various stress activated protein kinases (SAPKs, such as p38 MAPK, p44/42 MAPK and JNK1/2, is related to the higher sensitivity of K8-null hepatocytes whose nuclear NF-κB is rapidly depleted through Fas-mediated apoptosis. Notably, we found that NF-κB and the studied protein kinases are associated with the K8/K18 complex and are released upon phosphorylation. Therefore, interaction of keratins with cell survival-related protein kinases and transcription factors is another important factor for hepatocyte survival.

  1. The glutathione-S-transferase mu 1 (GSTM1) null genotype and increased neutrophil response to low-level ozone (0.06 ppm).

    Science.gov (United States)

    Background: Exposure of healthy young adults to 03 modulates immune cell biology in the airways and causes a significant increase in neutrophilic inflammation which can vary considerably in magnitude across individuals. The GSTM1null genotype modulates Oj-induced inflammation, bu...

  2. The association between null mutations in the filaggrin gene and contact sensitization to nickel and other chemicals in the general population

    DEFF Research Database (Denmark)

    Thyssen, J P; Johansen, J D; Linneberg, A;

    2010-01-01

    It was recently shown that filaggrin gene (FLG) null mutations are positively associated with nickel sensitization. We have hypothesized that histidine-rich filaggrin proteins in the epidermis chelate nickel ions and prevent their skin penetration and exposure to Langerhans cells. Furthermore, we...

  3. Vacuum Nuller Testbed Performance, Characterization and Null Control

    Science.gov (United States)

    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.

  4. Why is the null HBT result at RHIC so interesting?

    CERN Document Server

    Gyulassy, M

    2003-01-01

    Pion interferometry (HBT of A+A) data have posed a thorn in the theoretical interpretation of AA collisions at RHIC (sq root s = 130 AGeV). How can R sub o sub u sub t approx R sub s sub i sub d sub e approx R sub l sub o sub n sub g and remain so between AGS and RHIC? Where is the QGP Stall? Can elephants hide along the x sub 0 sup + dimension? We rummage old hydrodynamic scenarios and uncover some previously ignored NULL solutions. (author)

  5. Conformal symmetry wormholes and the null energy condition

    CERN Document Server

    Kuhfittig, Peter K F

    2016-01-01

    In this paper we seek a relationship between the assumption of conformal symmetry and the exotic matter needed to hold a wormhole open. By starting with a Morris-Thorne wormhole having a constant energy density, it is shown that the conformal factor provides the extra degree of freedom sufficient to account for the exotic matter. The same holds for Morris-Thorne wormholes in a noncommutative-geometry setting. Applied to thin shells, there would exist a radius that results in a wormhole with positive surface density and negative surface pressure and which violates the null energy condition on the thin shell.

  6. An Efficient Null Model for Conformational Fluctuations in Proteins

    DEFF Research Database (Denmark)

    Harder, Tim Philipp; Borg, Mikael; Bottaro, Sandro

    2012-01-01

    limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide...... bridges. The choice of the restraints themselves is heuristic, but the resulting probabilistic model is well-defined and rigorous. Conceptually, TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information...

  7. Midinfrared broadband achromatic astronomical beam combiner for nulling interferometry.

    Science.gov (United States)

    Hsiao, Hsien-kai; Winick, Kim A; Monnier, John D

    2010-12-10

    Integrated optic beam combiners offer many advantages over conventional bulk optic implementations for astronomical imaging. To our knowledge, integrated optic beam combiners have only been demonstrated at operating wavelengths below 4 μm. Operation in the midinfrared wavelength region, however, is highly desirable. In this paper, a theoretical design technique based on three coupled waveguides is developed to achieve fully achromatic, broadband, polarization-insensitive, lossless beam combining. This design may make it possible to achieve the very deep broadband nulls needed for exoplanet searching.

  8. Scale anomalies imply violation of the averaged null energy condition

    CERN Document Server

    Visser, M

    1994-01-01

    Considerable interest has recently been expressed regarding the issue of whether or not quantum field theory on a fixed but curved background spacetime satisfies the averaged null energy condition (ANEC). A comment by Wald and Yurtsever [Phys. Rev. D43, 403 (1991)] indicates that in general the answer is no. In this note I explore this issue in more detail, and succeed in characterizing a broad class of spacetimes in which the ANEC is guaranteed to be violated. Finally, I add some comments regarding ANEC violation in Schwarzschild spacetime.

  9. DBI Genesis: An Improved Violation of the Null Energy Condition

    CERN Document Server

    Hinterbichler, Kurt; Khoury, Justin; Miller, Godfrey E J

    2013-01-01

    We show that the DBI conformal galileons, derived from the world-volume theory of a 3-brane moving in an AdS bulk, admit a background, stable under quantum corrections, which violates the Null Energy Condition (NEC). The perturbations around this background are stable and propagate subluminally. Unlike other known examples of NEC violation, such as ghost condensation and conformal galileons, this theory also admits a stable, Poincare-invariant vacuum, with a Lorentz-invariant S-matrix satisfying standard analyticity conditions. Like conformal galileons, perturbations around deformations of the Poincare invariant vacuum propagate superluminally.

  10. A Visualization of Null Geodesics for the Bonnor Massive Dipole

    CERN Document Server

    Oliva-Mercado, Guillermo Andree; Cordero-García, Iván; Frutos-Alfaro, Francisco

    2015-01-01

    In this work we simulate null geodesics for the Bonnor massive dipole metric by implementing a symbolic-numerical algorithm in Sage and Python. This program is also capable of visualizing in 3D, in principle, the geodesics for any given metric. Geodesics are launched from a common point, collectively forming a cone of light beams, simulating a solid-angle section of a point source in front of a massive object with a magnetic field. Parallel light beams also were considered, and their bending due to the curvature of the space-time was simulated.

  11. Analysis of nulling phase functions suitable to image plane coronagraphy

    Science.gov (United States)

    Hénault, François; Carlotti, Alexis; Vérinaud, Christophe

    2016-07-01

    Coronagraphy is a very efficient technique for identifying and characterizing extra-solar planets orbiting in the habitable zone of their parent star, especially in a space environment. An important family of coronagraphs is actually based on phase plates located at an intermediate image plane of the optical system, and spreading the starlight outside the "Lyot" exit pupil plane of the instrument. In this commutation we present a set of candidate phase functions generating a central null at the Lyot plane, and study how it propagates to the image plane of the coronagraph. These functions include linear azimuthal phase ramps (the well-known optical vortex), azimuthally cosine-modulated phase profiles, and circular phase gratings. Nnumerical simulations of the expected null depth, inner working angle, sensitivity to pointing errors, effect of central obscuration located at the pupil or image planes, and effective throughput including image mask and Lyot stop transmissions are presented and discussed. The preliminary conclusion is that azimuthal cosine functions appear as an interesting alternative to the classical optical vortex of integer topological charge.

  12. Holographic Description of Negative Null Energy in Squeezed Vacuum States

    CERN Document Server

    Lee, Da-Shin

    2016-01-01

    Using the AdS/CFT duality, we study the expectation value of stress tensor in squeezed vacuum states of $2+1$-dimensional quantum critical theories with a general dynamical scaling $z$. The holographic dual theory is the theory of gravity in 3+1-dimensional Lifshitz backgrounds. We then adopt a consistent approach to obtain the boundary stress tensor from bulk construction, which satisfies the trace Ward identity associated with Lifshitz scaling symmetry. The scheme for holographic dual of squeezed vacuum states is found to be the gravity theory in the geometry perturbed by gravitational wave. For small squeezing parameters, the expectation value of stress tensor in squeezed vacuum states is obtained for both strongly coupled quantum critical fields and free relativistic fields. We find that, in both cases with $z=1$, the stress tensor satisfies the averaged null energy condition and is consistent with the quantum interest conjecture. In particular, the negative lower bound on null-contracted stress tensor, w...

  13. Null Zig-Zag Wilson Loops in N=4 SYM

    CERN Document Server

    Xie, Zhifeng

    2009-01-01

    In planar ${\\cal N}=4$ supersymmetric Yang-Mills theory we have studied supersymmetric Wilson loops composed of a large number of light-like segments, i.e., null zig-zags. These contours oscillate around smooth underlying spacelike paths. At one-loop in perturbation theory we have compared the finite part of the expectation value of null zig-zags to the finite part of the expectation value of non-scalar-coupled Wilson loops whose contours are the underlying smooth spacelike paths. In arXiv:0710.1060 [hep-th] it was argued that these quantities are equal for the case of a rectangular Wilson loop. Here we present a modest extension of this result to zig-zags of circular shape and zig-zags following non-parallel, disconnected line segments and show analytically that the one-loop finite part is indeed that given by the smooth spacelike Wilson loop without coupling to scalars which the zig-zag contour approximates. We make some comments regarding the generalization to arbitrary shapes.

  14. Null Zig-Zag Wilson Loops in {N}=4 Sym

    Science.gov (United States)

    Xie, Zhifeng

    In planar {N}=4 supersymmetric Yang-Mills theory we have studied one kind of (locally) BPS Wilson loops composed of a large number of light-like segments, i.e. null zig-zags. These contours oscillate around smooth underlying spacelike paths. At one-loop in perturbation theory, we have compared the finite part of the expectation value of null zig-zags to the finite part of the expectation value of non-scalar-coupled Wilson loops whose contours are the underlying smooth spacelike paths. In arXiv:0710.1060 [hep-th] it was argued that these quantities are equal for the case of a rectangular Wilson loop. Here we present a modest extension of this result to zig-zags of circular shape and zig-zags following non-parallel, disconnected line segments and show analytically that the one-loop finite part is indeed that given by the smooth spacelike Wilson loop without coupling to scalars which the zig-zag contour approximates. We make some comments regarding the generalization to arbitrary shapes.

  15. Principal components null space analysis for image and video classification.

    Science.gov (United States)

    Vaswani, Namrata; Chellappa, Rama

    2006-07-01

    We present a new classification algorithm, principal component null space analysis (PCNSA), which is designed for classification problems like object recognition where different classes have unequal and nonwhite noise covariance matrices. PCNSA first obtains a principal components subspace (PCA space) for the entire data. In this PCA space, it finds for each class "i," an Mi-dimensional subspace along which the class' intraclass variance is the smallest. We call this subspace an approximate null space (ANS) since the lowest variance is usually "much smaller" than the highest. A query is classified into class "i" if its distance from the class' mean in the class' ANS is a minimum. We derive upper bounds on classification error probability of PCNSA and use these expressions to compare classification performance of PCNSA with that of subspace linear discriminant analysis (SLDA). We propose a practical modification of PCNSA called progressive-PCNSA that also detects "new" (untrained classes). Finally, we provide an experimental comparison of PCNSA and progressive PCNSA with SLDA and PCA and also with other classification algorithms-linear SVMs, kernel PCA, kernel discriminant analysis, and kernel SLDA, for object recognition and face recognition under large pose/expression variation. We also show applications of PCNSA to two classification problems in video--an action retrieval problem and abnormal activity detection.

  16. Does horizon entropy satisfy a Quantum Null Energy Conjecture?

    CERN Document Server

    Fu, Zicao

    2016-01-01

    A modern version of the idea that the area of event horizons gives $4G$ times an entropy is the Hubeny-Rangamani Causal Holographic Information (CHI) proposal for holographic field theories. Given a region $R$ of a holographic QFTs, CHI computes $A/4G$ on a certain cut of an event horizon in the gravitational dual. The result is naturally interpreted as a coarse-grained entropy. CHI is known to be finitely greater than the fine-grained Hubeny-Rangamani-Takayanagi (HRT) entropy when $\\partial R$ lies on a Killing horizon of the QFT spacetime, and in this context satisfies other non-trivial properties expected of an entropy. Here we present evidence that it also satisfies the quantum null energy condition (QNEC), which bounds the second derivative of the entropy of a quantum field theory on one side of a non-expanding null surface by the flux of stress-energy across the surface. In particular, we show CHI to satisfy the QNEC in 1+1 holographic CFTs when evaluated in states dual to conical defects in AdS$_3$. Th...

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

    Science.gov (United States)

    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.

  18. Research on Null Verb Be in Chinese Based on Minimalist Program Theory

    Institute of Scientific and Technical Information of China (English)

    郭璐

    2013-01-01

    In this paper,based on the null categories and VP-shell light verb inthe Minimalist Program of Chomsky,the author proposed the concept of null verb be in Chinese and then studied the text of Moonlight over the Lotus Pondwritten by Zhuziqing to validate this assumption. The results indicate that null verb be could explain the classification of verbs and adjectives in Chinese as well as some other grammatical phenomena within the framework of Minimalist Program.

  19. Differential expression of pancreatic protein andchemosensing receptor mRNAs in NKCC1-null intestine

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    AIM To investigate the intestinal functions of the NKCC1Na+-K+-2Cl cotransporter (SLC12a2 gene), differentialmRNA expression changes in NKCC1-null intestine wereanalyzed.METHODS: Microarray analysis of mRNA from intestinesof adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed toidentify patterns of differential gene expression changes.Differential expression patterns were further examinedby Gene Ontology analysis using the online Gorillaprogram, and expression changes of selected genes wereverified using northern blot analysis and quantitativereal time-polymerase chain reaction. Histological stainingand immunofluorescence were performed to identify celltypes in which upregulated pancreatic digestive enzymeswere expressed.RESULTS: Genes typically associated with pancreaticfunction were upregulated. These included lipase,amylase, elastase, and serine proteases indicative ofpancreatic exocrine function, as well as insulin andregenerating islet genes, representative of endocrinefunction. Northern blot analysis and immunohistochemistryshowed that differential expression of exocrinepancreas mRNAs was specific to the duodenum andlocalized to a subset of goblet cells. In addition, a majorpattern of changes involving differential expression ofolfactory receptors that function in chemical sensing, aswell as other chemosensing G-protein coupled receptors,was observed. These changes in chemosensory receptorexpression may be related to the failure of intestinalfunction and dependency on parenteral nutritionobserved in humans with SLC12a2 mutations.CONCLUSION: The results suggest that loss of NKCC1affects not only secretion, but also goblet cell functionand chemosensing of intestinal contents via G-proteincoupled chemosensory receptors.

  20. A TRUST REGION ALGORITHM WITH NULL SPACE TECHNIQUE FOR EQUALITY CONSTRAINED OPTIMIZATION

    Institute of Scientific and Technical Information of China (English)

    TONG Xiaojiao; LI Donghui

    2004-01-01

    This paper presents a trust region algorithm with null space technique fornonlinear equality constrained optimizationConsidering in the null space methods that,the convergent rate of range space step is faster than the null space step for the most cases,the proposed algorithm computes null steps more often than range space stepMoreover,the new algorithm is based on the reduced Hessian SQP methodGlobal convergence ofthe proposed algorithm is provedThe effectiveness of the method is demonstrated bysome numerical examples.

  1. Null quadrature domains and a free boundary problem for the Laplacian

    CERN Document Server

    Karp, Lavi

    2010-01-01

    Null quadrature domains are unbounded domains in $\\R^n$ ($n \\geq 2$) with external gravitational force zero in some generalized sense. In this paper we prove a quadratic growth estimate of the Schwarz potential of a null quadrature domain and conclude by a theorem of Caffarelli, Karp and Shahgolian that any null quadrature domain is the complement of a convex set with analytic boundary. Using this result we prove that a null quadrature domain with a non-zero upper Lebesgue density at infinity is half-space.

  2. Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Kelsen, Jesper;

    2012-01-01

    , 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 

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

    Science.gov (United States)

    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.

  4. Evolution of clustered magnetic nulls in a turbulent-like reconnection region in the magnetotail

    Science.gov (United States)

    Guo, Ruilong; Pu, Zuyin; Fu, Suiyan; Xie, Lun; Dunlop, Malcolm; Bogdanova, Yulia V.; He, Jiansen; Wang, Xin; Yao, Zhonghua

    2016-07-01

    Magnetic null points and flux ropes play important roles in the three-dimensional process of magnetic reconnection. In this study, a cluster of null points are reconstructed in the reconnection region in the magnetotail by applying a fitting-reconstruction method to measurements from the Cluster mission. The number of reconstructed null points varies rapidly, presenting a turbulent-like evolution of the magnetic structure. The electron density and the flux of the accelerated electrons were enhanced in this turbulent-like region. During this unstable reconnection process, a B-As-B null structure was formed, showing flux rope features and resembling a secondary island in the observation.

  5. How to Find Magnetic Nulls and Reconstruct Field Topology with MMS Data?

    Science.gov (United States)

    Fu, H.; Vaivads, A.; Khotyaintsev, Y. V.; Olshevsky, V.; Andre, M.; Cao, J.; Huang, S.; Retino, A.; Lapenta, G.

    2015-12-01

    In this study, we apply a new method—the first-order Taylor expansion (FOTE)—to find magnetic nulls and reconstruct 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 FOTE method can find a null both inside and outside the tetrahedron and also deduce its drift velocity. In addition, the FOTE method can (1) avoid limitations of the 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) reconstruct the magnetic field topology. We quantitively test the accuracy of FOTE in positioning magnetic nulls and reconstructing field topology, by using the data from 3D kinetic simulations. The influences of SC separation (0.05~1 di) and null-SC distance (0~1 di) on the accuracy are both considered. We find that: (1) for an isolated null, the method is accurate when the SC separation is smaller than 1 di, and the null-SC distance is smaller than 0.25~0.5 di; (2) for a null pair, the accuracy is same as in the isolated-null situation, except at the separator line, where the field is nonlinear. We define a parameter in terms of the eigenvalues of the null to quantify the quality of our method—the smaller this parameter the better the results. Comparing to the previously used one, this parameter is more relevant for null identification. Using the new method, we reconstruct 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. We therefore suggest using this method to find magnetic nulls and reconstruct field topology with four-point measurements, particularly from Cluster and

  6. Lung mechanics in the TIMP3 null mouse and its response to mechanical ventilation.

    Science.gov (United States)

    Martin, Erica L; Truscott, Emily A; Bailey, Timothy C; Leco, Kevin J; McCaig, Lynda A; Lewis, James F; Veldhuizen, Ruud A W

    2007-03-01

    Tissue inhibitor of metalloproteinase-3 (TIMP3) null mice develop emphysema-like airspace enlargement due to an enzymatic imbalance. This study investigates how these abnormalities alter lung mechanics and the response to 2 different mechanical ventilation strategies. Phenotypically, TIMP3 null mice had increased compliance, and decreased resistance, tissue damping, and tissue elastance over wild-type controls. Decreased compliance and increased resistance were observed following the injurious ventilation strategy; however, the TIMP3 null response to both ventilation strategies was similar to wild-type mice. In conclusion, TIMP3 null mice have significant alterations in lung mechanics; however, this does not affect their response to ventilation.

  7. Effects of osmolality on PLP-null myelin structure: Implications re axon damage

    OpenAIRE

    Rosenbluth, Jack; Schiff, Rolf; Lam, Pokman

    2008-01-01

    In order to test the adhesiveness of PLP-null compact myelin lamellae we soaked aldehyde-fixed CNS specimens from PLP-null and control mice overnight in distilled water, in Ringer’s solution or in Ringer’s solution with added 1M sucrose. Subsequent examination of the tissue by EM showed that both PLP-null and control white matter soaked in Ringer remained largely compact. After the distilled water soak, control myelin was virtually unchanged, but PLP-null myelin showed some decompaction, i.e....

  8. Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.

    Directory of Open Access Journals (Sweden)

    Niwa Ali

    Full Text Available The occurrence of Graft-versus-Host Disease (GvHD is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice" are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null, notably the NOD-scid IL-2Rγ(null (NSG and BALB/c-Rag2(null IL-2Rγ(null (BRG mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+ compartment and higher engraftment levels of CD3(+ T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM phenotype and high levels of cutaneous lymphocyte antigen (CLA expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM-cell driven GvHD.

  9. Null-stream pointing with pulsar timing arrays

    CERN Document Server

    Hazboun, Jeffrey S

    2016-01-01

    Locating sources on the sky is one of the largest challenges in gravitational wave astronomy, owing to the omni-directional nature of gravitational wave detection techniques, and the often intrinsically weak signals being observed. Ground-based detectors can address the pointing problem by observing with a network of detectors, effectively triangulating signal locations by observing the arrival times across the network. Space-based detectors will observe long-lived sources that persist while the detector moves relative to their location on the sky, using Doppler shifts of the signal to locate the sky position. While these methods improve the pointing capability of a detector or network, the angular resolution is still coarse compared to the standards one expects from electromagnetic astronomy. Another technique that can be used for sky localization is null-stream pointing. In the case where multiple independent data streams exist, a single astrophysical source of gravitational waves will appear in each of the...

  10. Linearized gravitational waves near space-like and null infinity

    CERN Document Server

    Beyer, Florian; Frauendiener, Jörg; Whale, Ben

    2013-01-01

    Linear perturbations on Minkowski space are used to probe numerically the remote region of an asymptotically flat space-time close to spatial infinity. The study is undertaken within the framework of Friedrich's conformal field equations and the corresponding conformal representation of spatial infinity as a cylinder. The system under consideration is the (linear) zero-rest-mass equation for a spin-2 field. The spherical symmetry of the underlying background is used to decompose the field into separate non-interacting multipoles. It is demonstrated that it is possible to reach null-infinity from initial data on an asymptotically Euclidean hyper-surface and that the physically important radiation field can be extracted accurately on $\\scri^+$.

  11. From Satisfying to Violating the Null Energy Condition

    CERN Document Server

    Elder, Benjamin; Khoury, Justin

    2013-01-01

    We construct a theory which admits a time-dependent solution smoothly interpolating between a null energy condition (NEC)-satisfying phase at early times and a NEC-violating phase at late times. We first review earlier attempts to violate the NEC and an argument of Rubakov, presented in 1305.2614, which forbids the existence of such interpolating solutions in a single-field dilation-invariant theory. We then construct a theory which, in addition to possessing a Poincar\\'e-invariant vacuum, does admit such a solution. For a wide range of parameters, perturbations around this solution are at all times stable, comfortably subluminal and weakly-coupled. The theory requires us to explicitly break dilation-invariance, so it is unlikely that the theory is fully stable under quantum corrections, but we argue that the existence of a healthy interpolating solution is quantum-mechanically robust.

  12. An Operator Product Expansion for Polygonal null Wilson Loops

    CERN Document Server

    Alday, Luis F; Maldacena, Juan; Sever, Amit; Vieira, Pedro

    2010-01-01

    We consider polygonal Wilson loops with null edges in conformal gauge theories. We derive an OPE-like expansion when several successive lines of the polygon are becoming aligned. The limit corresponds to a collinear, or multicollinear, limit and we explain the systematics of all the subleading corrections, going beyond the leading terms that were previously considered. These subleading corrections are governed by excitations of high spin operators, or excitations of a flux tube that goes between two Wilson lines. The discussion is valid for any conformal gauge theory, for any coupling and in any dimension. For N=4 super Yang Mills we check this expansion at strong coupling and at two loops at weak coupling . We also make predictions for the remainder function at higher loops. In the process, we also derived a new version for the TBA integral equations that determine the strong coupling answer and present the area as the associated Yang-Yang functional.

  13. A new interferometer architecture combining nulling with phase closure measurements

    CERN Document Server

    Lacour, S; Monnier, J D; Kotani, T; Gauchet, L; Labeye, P

    2013-01-01

    Imaging the direct light signal from a faint exoplanet against the overwhelming glare of its host star presents one of the fundamental challenges to modern astronomical instrumentation. Achieving sufficient signal-to-noise for detection by direct imaging is limited by three basic physical processes: aberration of the wavefronts (both instrumental and atmospheric), photon noise, and detector noise. In this paper, we advance a novel optical setup which synthesizes the advantages of two different techniques: nulling interferometry to mitigate photon noise, and closure phase to combat optical aberrations. Our design, which employs technology from integrated optics and photonics, is intended to combine the advantageous aspects of both a coronagraph and a non-redundant interferometer. We show that such an instrument would allow readout noise limited detection of exoplanets, even in the presence of residual co-phasing errors. As a result, this concept would be ideal for space interferometry and for ground based obse...

  14. On the Null Trajectories in Conformal Weyl Gravity

    CERN Document Server

    Villanueva, J R

    2013-01-01

    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.

  15. Power spectrum nulls due to non-standard inflationary evolution

    CERN Document Server

    Goswami, Gaurav

    2010-01-01

    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 wavenumber. Near this wavenumber, 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.

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

    Science.gov (United States)

    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.

  17. Null Geodesics in a Magnetically Charged Stringy Black Hole Spacetime

    CERN Document Server

    Kuniyal, Ravi Shankar; Nandan, Hemwati; Purohit, K D

    2015-01-01

    We study the geodesic motion of massless test particles in the background of a magnetic charged black hole spacetime in four dimensions in dilaton-Maxwell gravity. The behaviour of effective potential in view of the different values of black hole parameters is analysed in the equatorial plane. The possible orbits for null geodesics are also discussed in detail in view of the different values of the impact parameter. We have also calculated the frequency shift of photons in this spacetime. The results obtained are then compared with those for the electrically charged stringy black hole spacetime and the Schwarzschild black hole spacetime. It is observed that there exists no stable circular orbit outside the event horizon for massless test particles.

  18. Fresnel rhombs as achromatic phase shifters for infrared nulling interferometry

    Science.gov (United States)

    Mawet, D.; Hanot, C.; Lenaers, C.; Riaud, P.; Defrère, D.; Vandormael, D.; Loicq, J.; Fleury, K.; Plesseria, J. Y.; Surdej, J.; Habraken, S.

    2007-09-01

    We propose a new family of achromatic phase shifters for infrared nulling interferometry. These key optical components can be seen as optimized Fresnel rhombs, using the total internal reflection phenomenon, modulated or not. The total internal reflection indeed comes with a phase shift between the polarization components of the incident light. We propose a solution to implement this vectorial phase shift between interferometer arms to provide the destructive interference process needed to disentangle highly contrasted objects from one another. We also show that, modulating the index transition at the total internal reflection interface allows compensating for the intrinsic material dispersion in order to make the subsequent phase shift achromatic over especially broad bands. The modulation can be induced by a thin film of a well-chosen material or a subwavelength grating whose structural parameters are thoroughly optimized. We present results from theoretical simulations! together with preliminary fabrication outcomes and measurements for a prototype in Zinc Selenide.

  19. Solar Particle Acceleration at Reconnecting 3D Null Points

    CERN Document Server

    Stanier, Adam J; Dalla, Silvia

    2012-01-01

    Context: The strong electric fields associated with magnetic reconnection in solar flares are a plausible mechanism to accelerate populations of high energy, non-thermal particles. One such reconnection scenario occurs at a 3D magnetic null point, where global plasma flows give rise to strong currents in the spine axis or fan plane. Aims: To understand the mechanism of charged particle energy gain in both the external drift region and the diffusion region associated with 3D magnetic reconnection. In doing so we evaluate the efficiency of resistive spine and fan models for particle acceleration, and find possible observables for each. Method: We use a full orbit test particle approach to study proton trajectories within electromagnetic fields that are exact solutions to the steady and incompressible magnetohydrodynamic equations. We study single particle trajectories and find energy spectra from many particle simulations. The scaling properties of the accelerated particles with respect to field and plasma para...

  20. Causal Space-Times on a Null Lattice

    CERN Document Server

    Schaden, Martin

    2015-01-01

    I investigate a model of quantum gravity based on the first order Hilbert Palatini action with cosmological constant, discretized on a causal null-lattice with SL(2,C) structure group. The description is coordinate invariant and foliates in a causal and physically transparent manner. Lattice variables and observables are constructed. Conditions for a lattice configuration to describe a triangulated causal manifold are derived and encoded by a topological lattice theory. An equivariant BRST-construction is used to partially localize the SL(2,C) structure group of this model to the compact SU(2) of local spatial rotations. The latter in turn is completely localized using the spinors of this formulation. The integration measure of this completely localized model is derived from the SL(2,C)-invariant integration measure and is expressed in terms of SL(2,C)-invariant variables. An invariant regularization of the lattice integration measure that suppresses configurations with small local four-volumes is proposed. N...

  1. Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene

    Directory of Open Access Journals (Sweden)

    Lionel Anath C

    2011-03-01

    Full Text Available Abstract Background Copy number variations (CNVs can contribute to variable degrees of fitness and/or disease predisposition. Recent studies show that at least 1% of any given genome is copy number variable when compared to the human reference sequence assembly. Homozygous deletions (or CNV nulls that are found in the normal population are of particular interest because they may serve to define non-essential genes in human biology. Results In a genomic screen investigating CNV in Autism Spectrum Disorders (ASDs we detected a heterozygous deletion on chromosome 10p12.1, spanning the Patched-domain containing 3 (PTCHD3 gene, at a frequency of ~1.4% (6/427. This finding seemed interesting, given recent discoveries on the role of another Patched-domain containing gene (PTCHD1 in ASD. Screening of another 177 ASD probands yielded two additional heterozygous deletions bringing the frequency to 1.3% (8/604. The deletion was found at a frequency of ~0.73% (27/3,695 in combined control population from North America and Northern Europe predominately of European ancestry. Screening of the human genome diversity panel (HGDP-CEPH covering worldwide populations yielded deletions in 7/1,043 unrelated individuals and those detected were confined to individuals of European/Mediterranean/Middle Eastern ancestry. Breakpoint mapping yielded an identical 102,624 bp deletion in all cases and controls tested, suggesting a common ancestral event. Interestingly, this CNV occurs at a break of synteny between humans and mouse. Considering all data, however, no significant association of these rare PTCHD3 deletions with ASD was observed. Notwithstanding, our RNA expression studies detected PTCHD3 in several tissues, and a novel shorter isoform for PTCHD3 was characterized. Expression in transfected COS-7 cells showed PTCHD3 isoforms colocalize with calnexin in the endoplasmic reticulum. The presence of a patched (Ptc domain suggested a role for PTCHD3 in various biological

  2. Dinucleotide controlled null models for comparative RNA gene prediction

    Directory of Open Access Journals (Sweden)

    Gesell Tanja

    2008-05-01

    Full Text Available Abstract 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

  3. Does horizon entropy satisfy a quantum null energy conjecture?

    Science.gov (United States)

    Fu, Zicao; Marolf, Donald

    2016-12-01

    A modern version of the idea that the area of event horizons gives 4G times an entropy is the Hubeny-Rangamani causal holographic information (CHI) proposal for holographic field theories. Given a region R of a holographic QFTs, CHI computes A/4G on a certain cut of an event horizon in the gravitational dual. The result is naturally interpreted as a coarse-grained entropy for the QFT. CHI is known to be finitely greater than the fine-grained Hubeny-Rangamani-Takayanagi (HRT) entropy when \\partial R lies on a Killing horizon of the QFT spacetime, and in this context satisfies other non-trivial properties expected of an entropy. Here we present evidence that it also satisfies the quantum null energy condition (QNEC), which bounds the second derivative of the entropy of a quantum field theory on one side of a non-expanding null surface by the flux of stress-energy across the surface. In particular, we show CHI to satisfy the QNEC in 1  +  1 holographic CFTs when evaluated in states dual to conical defects in AdS3. This surprising result further supports the idea that CHI defines a useful notion of coarse-grained holographic entropy, and suggests unprecedented bounds on the rate at which bulk horizon generators emerge from a caustic. To supplement our motivation, we include an appendix deriving a corresponding coarse-grained generalized second law for 1  +  1 holographic CFTs perturbatively coupled to dilaton gravity.

  4. Cadmium modulates adipocyte functions in metallothionein-null mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya, E-mail: suzukis@ph.bunri-u.ac.jp

    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.

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

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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

  7. Renal NHE expression and activity in neonatal NHE3- and NHE8-null mice.

    Science.gov (United States)

    Pirojsakul, Kwanchai; Gattineni, Jyothsna; Dwarakanath, Vangipuram; Baum, Michel

    2015-01-01

    Na(+)/H(+) exchanger (NHE)3 is the predominant NHE on the brush-border membrane of the proximal tubule in adult animals. NHE8 has been localized to the brush-border membrane of proximal tubules and is more highly expressed in neonates than in adult animals. However, the relative role of NHE8 in neonatal renal acidification is unclear. The present study examined if there was a compensatory increase in NHE3 in NHE8-null neonatal mice and whether there was a compensatory increase in NHE8 in NHE3-null neonatal mice. In addition, we examined whether wild-type, NHE3-null, and NHE8-null mice had an increase in NHE activity in response to metabolic acidosis. We found that at baseline, there was comparable renal NHE3 mRNA, total protein, and brush-border membrane protein abundance as in neonatal control and NHE8-null mice. There was comparable renal NHE8 mRNA, total protein, and brush-border membrane protein abundance in NHE3-null neonatal and control mice. Both NHE3- and NHE8-null mice had a comparable but lower rate of NHE activity than control mice. We next imposed metabolic acidosis in wild-type, NHE3-null, and NHE8-null mice. Acidemic NHE8-null mice had an increase in brush-border membrane vesicle NHE3 protein abundance and NHE activity compared with vehicle-treated mice. Likewise, NHE3-null mice had an increase in NHE8 brush-border membrane protein abundance and NHE activity in response to metabolic acidosis. In conclusion, both NHE3 and NHE8 likely play a role in neonatal acidification.

  8. Effects on hippocampus of lifelong absence of glucocorticoids in the pro-opiomelanocortin null mutant mouse reveal complex relationship between glucocorticoids and hippocampal structure and function.

    Science.gov (United States)

    Ostwald, Dirk; Karpac, Jason; Hochgeschwender, Ute

    2006-01-01

    In humans changes in serum cortisol levels have been observed with aging, stress, and with affective disorders such as major depression and post-traumatic stress disorder. Corticosteroids are known to influence hippocampal structure and function; specifically, plasma corticosteroid levels have been inversely correlated with hippocampal cell proliferation, cell death, and impaired memory function. The relationship between corticosteroids and structure and function of the hippocampus has been studied in experimental systems in adult animals by increasing or decreasing corticosterone levels through pharmacological supplementation and through surgical removal of the adrenal gland. Here, we utilized the genetically engineered pro-opiomelanocortin (POMC) null mutant mouse, which because of the lack of all POMC peptides has no corticosterone from birth throughout life. The effect of this lifelong absence of corticosterone on the dentate gyrus of the hippocampus is a decrease in granule cell density, which correlated with a decrease in cell proliferation but not an increase in cell degeneration. Fine morphology of granule cells was unaltered. Analyses of gene expression revealed no changes in POMC null mutant vs wild-type hippocampus with respect to levels of expression of corticoid receptor genes or genes known to be regulated by corticosterone. Spatial learning as tested by the Morris water maze was not altered in the POMC null mutant mouse. Taken together with findings from other studies of the effects of altered levels of corticosteroids on the hippocampus, our results argue for a complex homeostasis in which disturbances of any one factor can offset the system in varying ways.

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

    Science.gov (United States)

    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.…

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

    Science.gov (United States)

    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.

  11. Toward quantifying uncertainty in travel time tomography using the null-space shuttle

    NARCIS (Netherlands)

    Wit, R.W.L. de; Trampert, J.; van der Hilst, R.D.

    2012-01-01

    The solution of large linear tomographic inverse problems is fundamentally non-unique. We suggest to explore the non-uniqueness explicitly by examining the null-space of the forward operator. We show that with the null-space shuttle it is possible to assess robustness in tomographic models, and we i

  12. Null controllability of the viscous Camassa–Holm equation with moving control

    Indian Academy of Sciences (India)

    Peng Gao

    2016-02-01

    In this paper, we study the null controllability of the viscous Camassa–Holm equation on the one-dimensional torus. By using a moving distributed control, we obtain that the system is null controllable for a given data with certain regularity.

  13. The role of amplitude, phase, polarization and their interconnection in nulling interferometry

    NARCIS (Netherlands)

    Spronck, J.F.P.

    2008-01-01

    Nulling interferometry is a promising technique to directly detect Earth-like exoplanets. Unfortunately, it is extremely challenging to build a nulling interferometer and to meet the requirements needed for Earth-like planet detection. In this, thesis, we analyze the role of amplitude, phase and pol

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

    NARCIS (Netherlands)

    Spronck, J.; Pereira, S.F.; Braat, J.J.M.

    2006-01-01

    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

  15. The effect of the longitudinal polarization component in multi-axial nulling interferometry for exoplanet detection

    NARCIS (Netherlands)

    Spronck, J.F.P.; Pereira, S.F.

    2009-01-01

    We show a fundamental limitation of multi-axial beam combiners in nulling interferometry. The longitudinal electric field induced by the focusing optics can drastically limit the performance of such a nulling interferometer. We further analyze the filtering capabilities of a single-mode optical fibe

  16. Learning How to License Null Noun-Class Prefixes in Sesotho

    Science.gov (United States)

    Demuth, Katherine; Machobane, Malillo; Moloi, Francina

    2009-01-01

    Noun-class prefixes are obligatory in most Bantu languages. However, the Sotho languages (Sesotho, Setswana, Sepedi) permit a subset of prefixes to be realized as null at the intersection of "unmarked" phonological, syntactic, and discourse conditions. This raises the question of how and when the licensing of null prefixes is learned. Using…

  17. Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse.

    Science.gov (United States)

    Gibertini, Sara; Zanotti, Simona; Savadori, Paolo; Curcio, Maurizio; Saredi, Simona; Salerno, Franco; Andreetta, Francesca; Bernasconi, Pia; Mantegazza, Renato; Mora, Marina

    2014-05-01

    The Sgcb-null mouse, with knocked-down β-sarcoglycan, develops severe muscular dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse, lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD). Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in limb muscles. To characterize ECM protein deposition and the progression of muscle fibrosis, we evaluated protein and transcript levels of collagens I, III and VI, decorin, and TGF-β1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26, and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks in both quadriceps and diaphragm, and included conspicuous deposition of extracellular matrix components. Histopathological features of Sgcb-null mouse muscles were similar to those of age-matched mdx muscles at all ages examined, but, in the Sgcb-null mouse, the extent of connective tissue deposition was generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of all three collagen isoforms increased steadily, while, in the mdx, they remained stable. We also found that, at 12 weeks, macrophages were significantly more numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx quadriceps (but not in highly inflamed regions), while, in the diaphragm, macrophages did not differ significantly between the two models, in either region. Osteopontin mRNA was also significantly greater at 12 weeks in laser-dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx quadriceps. TGF-β1 was present in areas of degeneration-regeneration, but levels were highly variable and in general did not differ significantly between the two models and controls. The roles of the various subtypes of macrophages in muscle repair and fibrosis in the two models require further study. The Sgcb-null mouse, which develops early fibrosis

  18. null Faults, null Images

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Through the study of faults and their effects, much can be learned about the size and recurrence intervals of earthquakes. Faults also teach us about crustal...

  19. A 3+1 perspective on null hypersurfaces and isolated horizons

    CERN Document Server

    Gourgoulhon, E

    2006-01-01

    The isolated horizon formalism recently introduced by Ashtekar et al. aims at providing a quasi-local concept of a black hole in equilibrium in an otherwise possibly dynamical spacetime. In this formalism, a hierarchy of geometrical structures is constructed on a null hypersurface. On the other side, the 3+1 formulation of general relativity provides a powerful setting for studying the spacetime dynamics, in particular gravitational radiation from black hole systems. We revisit the kinematics and dynamics of null hypersurfaces by making use of the 3+1 slicing. In particular, the additional structures induced on null hypersurfaces by the 3+1 slicing of spacetime permit a natural extension to the full spacetime of geometrical quantities defined on the null hypersurface. This 4-dimensional point of view facilitates the link between the null and spatial geometries. We proceed by reformulating the isolated horizon structure in this framework. We also reformulate previous works, such as Damour's black hole mechanic...

  20. PSF and field of view characteristics of imaging and nulling interferometers

    Science.gov (United States)

    Hénault, François

    2010-07-01

    In this communication are presented some complements to a recent paper entitled "Simple Fourier optics formalism for high angular resolution systems and nulling interferometry" [1], dealing with imaging and nulling capacities of a few types of multi-aperture optical systems. Herein the characteristics of such systems in terms of Point Spread Function (PSF) and Field of View (FoV) are derived from simple analytical expressions that are further evaluated numerically for various configurations. We consider successively the general cases of Fizeau and Michelson interferometers, and those of a monolithic pupil, nulling telescope, of a nulling, Sheared-Pupil Telescope (SPT), and of a sparse aperture, Axially Combined Interferometer (ACI). The analytical formalism also allows establishing the exact Object-Image relationships applicable to nulling PSTs or ACIs that are planned for future space missions searching for habitable extra-solar planets.

  1. PSF and field of view characteristics of imaging and nulling interferometers

    CERN Document Server

    Hénault, François

    2010-01-01

    In this communication are presented some complements to a recent paper entitled "Simple Fourier optics formalism for high angular resolution systems and nulling interferometry", dealing with imaging and nulling capacities of a few types of multi-aperture optical systems. Herein the characteristics of such systems in terms of Point Spread Function (PSF) and Field of View (FoV) are derived from simple analytical expressions that are further evaluated numerically for various configurations. We consider successively the general cases of Fizeau and Michelson interferometers, and those of a monolithic pupil, nulling telescope, of a nulling, Sheared-Pupil Telescope (SPT), and of a sparse aperture, Axially Combined Interferometer (ACI). The analytical formalism also allows establishing the exact Object-Image relationships applicable to nulling PSTs or ACIs that are planned for future space missions searching for habitable extra-solar planets.

  2. Current Structure and Non-Ideal Behavior at Magnetic Null Points in the Turbulent Magnetosheath

    Science.gov (United States)

    Wendel, D. E.; Adrian, M. L.

    2012-12-01

    The Poincaré index indicates the Cluster spacecraft tetrahedron entraps a number of 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 modest current perpendicular to the spine that tilts the axis of the spine toward the fan plane. At least one of the nulls manifests a non-ideal 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 three-dimensional turbulence.

  3. Current sheet formation and non-ideal behaviour at three-dimensional magnetic null points

    CERN Document Server

    Pontin, D I; Galsgaard, K

    2007-01-01

    The nature of the evolution of the magnetic field, and of current sheet formation, at three-dimensional (3D) magnetic null points is investigated. A kinematic example is presented which demonstrates that there is no possible choice of boundary conditions which renders the evolution of the field ideal at the null, when the ratios of the null eigenvalues are time-dependent. Resistive MHD simulations are described which demonstrate that this evolution is generic. A 3D null is subjected to boundary driving by shearing motions, and it is shown that a current sheet localised at the null is formed. The qualitative and quantitative properties of the current sheet are discussed. Accompanying the sheet development is the growth of a localised parallel electric field, one of the signatures of magnetic reconnection. Finally, the relevance of the results to a recent theory of turbulent reconnection are discussed.

  4. Continuous development of current sheets near and away from magnetic nulls

    Science.gov (United States)

    Kumar, Sanjay; Bhattacharyya, R.

    2016-04-01

    The presented computations compare the strength of current sheets which develop near and away from the magnetic nulls. To ensure the spontaneous generation of current sheets, the computations are performed congruently with Parker's magnetostatic theorem. The simulations evince current sheets near two dimensional and three dimensional magnetic nulls as well as away from them. An important finding of this work is in the demonstration of comparative scaling of peak current density with numerical resolution, for these different types of current sheets. The results document current sheets near two dimensional magnetic nulls to have larger strength while exhibiting a stronger scaling than the current sheets close to three dimensional magnetic nulls or away from any magnetic null. The comparative scaling points to a scenario where the magnetic topology near a developing current sheet is important for energetics of the subsequent reconnection.

  5. Blind Null-space Tracking for MIMO Underlay Cognitive Radio Networks

    CERN Document Server

    Manolakos, Alexandros; Goldsmith, Andrea J

    2012-01-01

    Blind Null Space Learning (BNSL) has recently been proposed for fast and accurate learning of the null-space associated with the channel matrix between a secondary transmitter and a primary receiver. In this paper we propose a channel tracking enhancement of the algorithm, namely the Blind Null Space Tracking (BNST) algorithm that allows transmission of information to the Secondary Receiver (SR) while simultaneously learning the null-space of the time-varying target channel. Specifically, the enhanced algorithm initially performs a BNSL sweep in order to acquire the null space. Then, it performs modified Jacobi rotations such that the induced interference to the primary receiver is kept lower than a given threshold $P_{Th}$ with probability $p$ while information is transmitted to the SR simultaneously. We present simulation results indicating that the proposed approach has strictly better performance over the BNSL algorithm for channels with independent Rayleigh fading with a small Doppler frequency.

  6. Computer generated hologram null test of a freeform optical surface with rectangular aperture

    Science.gov (United States)

    Su, Ping; Ma, Jianshe; Tan, Qiaofeng; Kang, Guoguo; Liu, Yi; Jin, Guofan

    2012-02-01

    In null computed generated hologram (CGH) test of optical elements, fitting method is needed in null CGH design to generate continuous phase function from the ray-traced discrete phase data. The null CGH for freeform testing usually has a deformed aperture and a high order phase function, because of the aberrations introduced by freeform wavefront propagation. With traditional Zernike polynomial fitting method, selection of an orthogonal basis set and choosing number of terms are needed before fitting. Zernike polynomial fitting method is not suitable in null CGH design for freeform testing; a novel CGH design method with cubic B-spline interpolation is developed. For a freeform surface with 18×18 mm2 rectangular aperture and 630 μm peak-to-valley undulation, the null CGH with a curved rectangular aperture is designed by using the method proposed. Simulation and experimental results proved the feasibility of the novel CGH design method.

  7. Gibberellins are involved in effect of near-null magnetic field on Arabidopsis flowering.

    Science.gov (United States)

    Xu, Chunxiao; Yu, Yang; Zhang, Yuxia; Li, Yue; Wei, Shufeng

    2017-01-01

    We previously found that flowering of Arabidopsis was suppressed by near-null magnetic field, which was related to the modification of cryptochrome. To disclose the physiological mechanism of this effect, we detected gibberellin (GA) levels and expressions of GA biosynthetic and signaling genes in wild type Arabidopsis plants and cryptochrome double mutant, cry1/cry2, grown in near-null magnetic field. We found that levels of GA4 , GA9 , GA34 , and GA51 in wild type plants in near-null magnetic field were significantly decreased compared with local geomagnetic field controls. However, GA levels in cry1/cry2 mutants in near-null magnetic field were similar to controls. Expressions of three GA20-oxidase (GA20ox) genes (GA20ox1, GA20ox2, and GA20ox3) and four GA3-oxidase (GA3ox) genes (GA3ox1, GA3ox2, GA3ox3, and GA3ox4) in wild type plants in near-null magnetic field were significantly reduced compared with controls, while expressions of GA20ox4, GA20ox5, GA2-oxidase (GA2ox) genes, and GA signaling-related genes in wild type plants in near-null magnetic field were not significantly different from controls. In contrast, expressions of all the detected GA biosynthetic and signaling genes in cry1/cry2 mutants were not affected by near-null magnetic field. Moreover, transcriptions of flowering-related genes, LFY and SOC1, in wild type plants were downregulated by near-null magnetic field, while they were not affected by near-null magnetic field in cry1/cry2 mutants. Our results suggest that the effect of near-null magnetic field on Arabidopsis flowering is GA-related, which is caused by cryptochrome-involved suppression of GA biosynthesis. Bioelectromagnetics. 38:1-10, 2017. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. Electric currents in the solar atmosphere in the presence of magnetic null points

    Science.gov (United States)

    Carlo Santos, Jean; Büchner, Jörg; Otto, Antonius

    So far the role of magnetic null points in 3D reconnection was investigated mainly for the close vicinity of the null, with perturbations being applied at the nearby boundaries. In the solar atmosphere, however, electric currents are generated due to perturbations originating at the photosphere, far a way from coronal 3D nulls. We investigate the consequences of photospheric motion for the development of electric cur-rents in a coronal magnetic field configuration containing a null, located far away from the boundaries, and the influence of topological structures on their spatial distribution. We use a 3D resistive MHD code to investigate the consequences of photospheric plasma motion for the generation of currents in a coronal magnetic field containing a null. The plasma is consid-ered fully compressible and is initially in hydrostatic equilibrium. The initial magnetic field is current free (potential). Initially the photospheric plasma motion creates a magnetic field perturbation that propagates to the corona along the field lines at the local Alfvén speed. The shear Alfvenic wave pertur-e bation corresponds to a propagating current. The currents are mainly parallel to the magnetic field. The perturbations starting close to the foot points of the field lines that connect to the null eventually reach the vicinity of the null. Since the local Alfvén speed decreases as we approach the magnetic null point, the perturbations of the magnetic field never reach the null. Meanwhile, strong currents develop around the null point where the perturbations reach the intersection of two separatrices. On those regions, when there is an appropriate perturbation, a shear of the magnetic field is created in a length scale much smaller than the characteristic length scale of the system, generating a strong current channel.

  11. Irx3 and Bmp2 Regulate Mouse Mesenchymal Cell Chondrogenic Differentiation in Both a Sox9-Dependent and -Independent Manner.

    Science.gov (United States)

    Tamamura, Yoshihiro; Katsube, Kenichi; Mera, Hisashi; Itokazu, Maki; Wakitani, Shigeyuki

    2017-01-06

    Sox9, a master regulator of cartilage development, controls the cell fate decision to differentiate from mesenchymal to chondrogenic cells. In addition, Sox9 regulates the proliferation and differentiation of chondrocytes, as well as the production of cartilage-specific proteoglycans. The existence of Sox9-independent mechanisms in cartilage development remains to be determined. Here, we attempted to identify genes involved in such putative mechanisms via microarray analysis using a mouse chondrogenic cell line, N1511. We first focused on transcription factors that exhibited upregulated expression following Bmp2 treatment, which was not altered by subsequent treatment with Sox9 siRNA. Among these, we selected positive regulators for chondrogenesis and identified Iroquois-related homeobox 3 (Irx3) as one of the candidate genes. Irx3 expression gradually increased with chondrocyte terminal differentiation in a reciprocal manner to Sox9 expression, and promoted the chondrogenic differentiation of mesenchymal cells upon Bmp2 treatment. Furthermore, Irx3 partially rescued impaired chondrogenesis by upregulating the expression of epiphycan and lumican under reduced Sox9 expression. Finally, Irx3 was shown to act in concert with Bmp2 signaling to activate the p38 MAPK pathway, which in turn stimulated Sox9 expression, as well as the expression of epiphycan and lumican in a Sox9-independent manner. These results indicate that Irx3 represents a novel chondrogenic factor of mesenchymal cells, acts synergistically with Bmp2-mediated signaling, and regulates chondrogenesis independent of the transcriptional machinery associated with Sox9-mediated regulation. This article is protected by copyright. All rights reserved.

  12. Strong subadditivity, null energy condition and charged black holes

    Energy Technology Data Exchange (ETDEWEB)

    Caceres, Elena [Facultad de Ciencias, Universidad de Colima,Bernal Diaz del Castillo 340, Colima (Mexico); Theory Group, Department of Physics, The University of Texas,Austin, TX 78712 (United States); Kundu, Arnab [Theory Group, Department of Physics, The University of Texas,Austin, TX 78712 (United States); Pedraza, Juan F.; Tangarife, Walter [Theory Group, Department of Physics, The University of Texas,Austin, TX 78712 (United States); Texas Cosmology Center, The University of Texas,Austin, TX 78712 (United States)

    2014-01-16

    Using the Hubeny-Rangamani-Takayanagi (HRT) conjectured formula for entanglement entropy in the context of the AdS/CFT correspondence with time-dependent backgrounds, we investigate the relation between the bulk null energy condition (NEC) of the stress-energy tensor with the strong sub-additivity (SSA) property of entanglement entropy in the boundary theory. In a background that interpolates between an AdS to an AdS-Reissner-Nordstrom-type geometry, we find that generically there always exists a critical surface beyond which the violation of NEC would naively occur. However, the extremal area surfaces that determine the entanglement entropy for the boundary theory, can penetrate into this forbidden region only for certain choices for the mass and the charge functions in the background. This penetration is then perceived as the violation of SSA in the boundary theory. We also find that this happens only when the critical surface lies above the apparent horizon, but not otherwise. We conjecture that SSA, which is thus non-trivially related to NEC, also characterizes the entire time-evolution process along which the dual field theory may thermalize.

  13. Strong Subadditivity, Null Energy Condition and Charged Black Holes

    CERN Document Server

    Caceres, Elena; Pedraza, Juan F; Tangarife, Walter

    2014-01-01

    Using the Hubeny-Rangamani-Takayanagi (HRT) conjectured formula for entanglement entropy in the context of the AdS/CFT correspondence with time-dependent backgrounds, we investigate the relation between the bulk null energy condition (NEC) of the stress-energy tensor with the strong sub-additivity (SSA) property of entanglement entropy in the boundary theory. In a background that interpolates between an AdS to an AdS-Reissner-Nordstrom-type geometry, we find that generically there always exists a critical surface beyond which the violation of NEC would naively occur. However, the extremal area surfaces that determine the entanglement entropy for the boundary theory, can penetrate into this forbidden region only for certain choices for the mass and the charge functions in the background. This penetration is then perceived as the violation of SSA in the boundary theory. We also find that this happens only when the critical surface lies above the apparent horizon, but not otherwise. We conjecture that SSA, which...

  14. Muscular dystrophy in PTFR/cavin-1 null mice

    Science.gov (United States)

    Ding, Shi-Ying; Pilch, Paul F.

    2017-01-01

    ice and humans lacking the caveolae component polymerase I transcription release factor (PTRF, also known as cavin-1) exhibit lipo- and muscular dystrophy. Here we describe the molecular features underlying the muscle phenotype for PTRF/cavin-1 null mice. These animals had a decreased ability to exercise, and exhibited muscle hypertrophy with increased muscle fiber size and muscle mass due, in part, to constitutive activation of the Akt pathway. Their muscles were fibrotic and exhibited impaired membrane integrity accompanied by an apparent compensatory activation of the dystrophin-glycoprotein complex along with elevated expression of proteins involved in muscle repair function. Ptrf deletion also caused decreased mitochondrial function, oxygen consumption, and altered myofiber composition. Thus, in addition to compromised adipocyte-related physiology, the absence of PTRF/cavin-1 in mice caused a unique form of muscular dystrophy with a phenotype similar or identical to that seen in humans lacking this protein. Further understanding of this muscular dystrophy model will provide information relevant to the human situation and guidance for potential therapies.

  15. A null relationship between media multitasking and well-being.

    Directory of Open Access Journals (Sweden)

    Shui-I Shih

    Full Text Available 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.

  16. Null Method’ Determination of Drug Biophase Concentration

    Science.gov (United States)

    Tallarida, Ronald J.; Lamarre, Neil

    2014-01-01

    PK/PD modeling is enhanced by improvements in the accuracy of its metrics. For PK/PD modeling of drugs and biologics that interact with enzymes or receptors, the equilibrium constant of the interaction can provide critical insight. Methodologies such as radioliogand binding and isolated tissue preparations can provide estimates of the equilibrium constants (as the dissociation constant, K value) for drugs and endogenous ligands that interact with specific enzymes and receptors. However, an impediment to further precision for PK/PD modeling is that it remains a problem to convert the concentration of drug in bulk solution (A) into an estimate of receptor occupation, since A is not necessarily the concentration (C) of drug in the biophase that yields fractional binding from the law of mass action, viz., C/(C + K). In most experimental studies A is much larger than K, so the use of administered instead of biophase concentration gives fractional occupancies very close to unity. We here provide a simple way to obtain an estimate of the factor that converts the total drug concentration into the biophase concentration in isolated tissue preparation. Our approach is an extension of the now classic ‘null method’ introduced and applied by Furchgott to determination of drug-receptor dissociation constants. PMID:22037914

  17. Charged particle motion near a linear magnetic null

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.; Cary, J.R.

    1983-08-01

    Charged particle motion near the null of a two-dimensional magnetic field is studied. Specifically, the magnetic field is given by the vector potential A = zpsi/sub 0/((y/a)/sup 2/+(epsilonx/a)/sup 2/), in which psi/sub 0/,a, and epsilon are constants with epsilon parameterizing the ellipticity of the flux surfaces. Conservation of canonical z momentum p/sub z/ reduces the number of nontrivial degrees of freedom to two. Scaling reduces the number of parameters in the system to two, epsilon and sigma (the sign of p/sub z/ ). Analytical and numerical methods are used to study the nature of orbits. The results are expressed conveniently in terms of epsilon and Qequivalent(2mE)/sup 1/2//p/sub z/. When epsilon is unity, the additional symmetry implies integrability. When epsilon is less than unity (the case epsilon>1 is trivially related) three regimes are found: (1) For Vertical BarQVertical Bar>>1 particle orbits are regular, (2) for epsilon/sup 3/2/< or approx. =Vertical BarQVertical Bar< or approx. =1 most particle orbits are stochastic, and (3) for Vertical BarQVertical Bar<

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

    Science.gov (United States)

    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.

  19. Magnetic flipping: Reconnection in three-dimensions without null points

    Energy Technology Data Exchange (ETDEWEB)

    Priest, E.R.; Forbes, T.G. (Univ. of New Hampshire, Durham (United States))

    1992-02-01

    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 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.

  20. Metric-based Hamiltonians, null boundaries, and isolated horizons

    CERN Document Server

    Booth, I S

    2001-01-01

    We extend the quasilocal (metric-based) Hamiltonian formulation of general relativity so that it may be used to study regions of spacetime with null boundaries. In particular we use this generalized Brown-York formalism to study the physics of isolated horizons. We show that the first law of isolated horizon mechanics follows directly from the first variation of the Hamiltonian. This variation is not restricted to the phase space of solutions to the equations of motion but is instead through the space of all (off-shell) spacetimes that contain isolated horizons. We find two-surface integrals evaluated on the horizons that are consistent with the Hamiltonian and which define the energy and angular momentum of these objects. These are closely related to the corresponding Komar integrals and for Kerr-Newman spacetime are equal to the corresponding ADM/Bondi quantities. Thus, the energy of an isolated horizon calculated by this method is in agreement with that recently calculated by Ashtekar and collaborators but...

  1. Aspects of QCD current algebra on a null plane

    Science.gov (United States)

    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.

  2. Suppression of Arabidopsis flowering by near-null magnetic field is affected by light.

    Science.gov (United States)

    Xu, Chunxiao; Li, Yue; Yu, Yang; Zhang, Yuxia; Wei, Shufeng

    2015-09-01

    We previously reported that a near-null magnetic field suppressed Arabidopsis flowering in white light, which might be related to the function modification of cryptochrome (CRY). To further demonstrate that the effect of near-null magnetic field on Arabidopsis flowering is associated with CRY, Arabidopsis wild type and CRY mutant plants were grown in the near-null magnetic field under blue or red light with different light cycle and photosynthetic photon flux density. We found that Arabidopsis flowering was significantly suppressed by near-null magnetic field in blue light with lower intensity (10 µmol/m(2) /s) and shorter cycle (12 h period: 6 h light/6 h dark). However, flowering time of CRY1/CRY2 mutants did not show any difference between plants grown in near-null magnetic field and in local geomagnetic field under detected light conditions. In red light, no significant difference was shown in Arabidopsis flowering between plants in near-null magnetic field and local geomagnetic field under detected light cycles and intensities. These results suggest that changes of blue light cycle and intensity alter the effect of near-null magnetic field on Arabidopsis flowering, which is mediated by CRY.

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

    Science.gov (United States)

    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. Assessment of the association between GSTM1 null genotype and risk of type 2 diabetes.

    Science.gov (United States)

    Yi, Ran; Liu, Bin; Dong, Qi

    2013-06-01

    Many studies have investigated the association between Glutathione S-Transferase M1 (GSTM1) null genotype and risk of diabetes mellitus, but the impact of GSTM1 null genotype on diabetes mellitus is unclear owing to the obvious inconsistence among those studies. This study aimed to quantify the strength of association between GSTM1 null genotype and risk of diabetes mellitus. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTM1 null genotype and risk of diabetes mellitus. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by type of diabetes and ethnicity. 10 case-control studies with 7, 054 subjects were included into this meta-analysis. Meta-analysis of total 10 studies showed GSTM1 null genotype was associated increased risk of diabetes mellitus (OR = 1.59, 95 % CI 1.14-2.22, P = 0.007). Subgroup analyses by type of diabetes mellitus suggested GSTM1 null genotype was associated increased risk of type 2 diabetes (OR = 1.90, 95 % CI 1.37-2.64, P null genotype and increased risk of type 2 diabetes. The cumulative meta-analyses showed a trend of obvious association between GSTM1 null genotype and risk of type 2 diabetes as information accumulated. No evidence of publication bias was observed. Thus, evidence from current meta-analysis suggests an association between GSTM1 null genotype and risk of type 2 diabetes.

  5. Reliability assessment of null allele detection: inconsistencies between and within different methods.

    Science.gov (United States)

    Dąbrowski, M J; Pilot, M; Kruczyk, M; Żmihorski, M; Umer, H M; Gliwicz, J

    2014-03-01

    Microsatellite loci are widely used in population genetic studies, but the presence of null alleles may lead to biased results. Here, we assessed five methods that indirectly detect null alleles and found large inconsistencies among them. Our analysis was based on 20 microsatellite loci genotyped in a natural population of Microtus oeconomus sampled during 8 years, together with 1200 simulated populations without null alleles, but experiencing bottlenecks of varying duration and intensity, and 120 simulated populations with known null alleles. In the natural population, 29% of positive results were consistent between the methods in pairwise comparisons, and in the simulated data set, this proportion was 14%. The positive results were also inconsistent between different years in the natural population. In the null-allele-free simulated data set, the number of false positives increased with increased bottleneck intensity and duration. We also found a low concordance in null allele detection between the original simulated populations and their 20% random subsets. In the populations simulated to include null alleles, between 22% and 42% of true null alleles remained undetected, which highlighted that detection errors are not restricted to false positives. None of the evaluated methods clearly outperformed the others when both false-positive and false-negative rates were considered. Accepting only the positive results consistent between at least two methods should considerably reduce the false-positive rate, but this approach may increase the false-negative rate. Our study demonstrates the need for novel null allele detection methods that could be reliably applied to natural populations.

  6. Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases.

    Science.gov (United States)

    Sabolić Pipinić, I; Varnai, V M; Turk, R; Breljak, D; Kezić, S; Macan, J

    2013-06-01

    Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing north-south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.

  7. Resistance to acetaminophen-induced hepatotoxicity in glutathione S-transferase Mu 1-null mice.

    Science.gov (United States)

    Arakawa, Shingo; Maejima, Takanori; Fujimoto, Kazunori; Yamaguchi, Takashi; Yagi, Masae; Sugiura, Tomomi; Atsumi, Ryo; Yamazoe, Yasushi

    2012-01-01

    We investigated the role of glutathione S-transferases Mu 1 (GSTM1) in acetaminophen (APAP)-induced hepatotoxicity using Gstm1-null mice. A single oral administration of APAP resulted in a marked increase in plasma alanine aminotransferase accompanied by hepatocyte necrosis 24 hr after administration in wild-type mice, but its magnitude was unexpectedly attenuated in Gstm1-null mice. Therefore, it is suggested that Gstm1-null mice are resistant to APAP-induced hepatotoxicity. To examine the mechanism of this resistance in Gstm1-null mice, we measured phosphorylation of c-jun N-terminal kinase (JNK), which mediates the signal of APAP-induced hepatocyte necrosis, by Western blot analysis 2 and 6 hr after APAP administration. A marked increase in phosphorylated JNK was observed in wild-type mice, but the increase was markedly suppressed in Gstm1-null mice. Therefore, it is suggested that suppressed phosphorylation of JNK may be a main mechanism of the resistance to APAP-induced hepatotoxicity in Gstm1-null mice, although other possibilities of the mechanism cannot be eliminated. Additionally, phosphorylation of glycogen synthase kinase-3β and mitogen-activated protein kinase kinase 4, which are upstream kinases of JNK in APAP-induced hepatotoxicity, were also suppressed in Gstm1-null mice. A decrease in liver total glutathione 2 hr after APAP administration, which is an indicator for exposure to N-acetyl-p-benzoquinoneimine, the reactive metabolite of APAP, were similar in wild-type and Gstm1-null mice. In conclusion, Gstm1-null mice are considered to be resistant to APAP-induced hepatotoxicity perhaps by the suppression of JNK phosphorylation. This study indicates the novel role of GSTM1 as a factor mediating the cellular signal for APAP-induced hepatotoxicity.

  8. Magnetoacoustic Waves in a Stratified Atmosphere with a Magnetic Null Point

    Science.gov (United States)

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

    2017-03-01

    We perform nonlinear MHD simulations to study the propagation of magnetoacoustic waves from the photosphere to the low corona. We focus on a 2D system with a gravitationally stratified atmosphere and three photospheric concentrations of magnetic flux that produce a magnetic null point with a magnetic dome topology. We find that a single wavepacket introduced at the lower boundary splits into multiple secondary wavepackets. A portion of the packet refracts toward the null owing to the varying Alfvén speed. Waves incident on the equipartition contour surrounding the null, where the sound and Alfvén speeds coincide, partially transmit, reflect, and mode-convert between branches of the local dispersion relation. Approximately 15.5% of the wavepacket’s initial energy (E input) converges on the null, mostly as a fast magnetoacoustic wave. Conversion is very efficient: 70% of the energy incident on the null is converted to slow modes propagating away from the null, 7% leaves as a fast wave, and the remaining 23% (0.036E input) is locally dissipated. The acoustic energy leaving the null is strongly concentrated along field lines near each of the null’s four separatrices. The portion of the wavepacket that refracts toward the null, and the amount of current accumulation, depends on the vertical and horizontal wavenumbers and the centroid position of the wavepacket as it crosses the photosphere. Regions that refract toward or away from the null do not simply coincide with regions of open versus closed magnetic field or regions of particular field orientation. We also model wavepacket propagation using a WKB method and find that it agrees qualitatively, though not quantitatively, with the results of the numerical simulation.

  9. Observation of Magnetic Reconnection at a 3D Null Point Associated with a Solar Eruption

    Science.gov (United States)

    Sun, J. Q.; Zhang, J.; Yang, K.; Cheng, X.; Ding, M. D.

    2016-10-01

    Magnetic null has long been recognized as a special structure serving as a preferential site for magnetic reconnection (MR). However, the direct observational study of MR at null-points is largely lacking. Here, we show the observations of MR around a magnetic null associated with an eruption that resulted in an M1.7 flare and a coronal mass ejection. The Geostationary Operational Environmental Satellites X-ray profile of the flare exhibited two peaks at ∼02:23 UT and ∼02:40 UT on 2012 November 8, respectively. Based on the imaging observations, we find that the first and also primary X-ray peak was originated from MR in the current sheet (CS) underneath the erupting magnetic flux rope (MFR). On the other hand, the second and also weaker X-ray peak was caused by MR around a null point located above the pre-eruption MFR. The interaction of the null point and the erupting MFR can be described as a two-step process. During the first step, the erupting and fast expanding MFR passed through the null point, resulting in a significant displacement of the magnetic field surrounding the null. During the second step, the displaced magnetic field started to move back, resulting in a converging inflow and subsequently the MR around the null. The null-point reconnection is a different process from the current sheet reconnection in this flare; the latter is the cause of the main peak of the flare, while the former is the cause of the secondary peak of the flare and the conspicuous high-lying cusp structure.

  10. 'True' null allele detection in microsatellite loci: a comparison of methods, assessment of difficulties and survey of possible improvements.

    Science.gov (United States)

    Dąbrowski, M J; Bornelöv, S; Kruczyk, M; Baltzer, N; Komorowski, J

    2015-05-01

    Null alleles are alleles that for various reasons fail to amplify in a PCR assay. The presence of null alleles in microsatellite data is known to bias the genetic parameter estimates. Thus, efficient detection of null alleles is crucial, but the methods available for indirect null allele detection return inconsistent results. Here, our aim was to compare different methods for null allele detection, to explain their respective performance and to provide improvements. We applied several approaches to identify the 'true' null alleles based on the predictions made by five different methods, used either individually or in combination. First, we introduced simulated 'true' null alleles into 240 population data sets and applied the methods to measure their success in detecting the simulated null alleles. The single best-performing method was ML-NullFreq_frequency. Furthermore, we applied different noise reduction approaches to improve the results. For instance, by combining the results of several methods, we obtained more reliable results than using a single one. Rule-based classification was applied to identify population properties linked to the false discovery rate. Rules obtained from the classifier described which population genetic estimates and loci characteristics were linked to the success of each method. We have shown that by simulating 'true' null alleles into a population data set, we may define a null allele frequency threshold, related to a desired true or false discovery rate. Moreover, using such simulated data sets, the expected null allele homozygote frequency may be estimated independently of the equilibrium state of the population.

  11. Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing

    Science.gov (United States)

    Edelman, Theresa L. B.; McCulloch, Katherine A.; Barr, Angela; Frøkjær-Jensen, Christian; Jorgensen, Erik M.; Rougvie, Ann E.

    2016-01-01

    The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing. PMID:27729432

  12. Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing.

    Science.gov (United States)

    Edelman, Theresa L B; McCulloch, Katherine A; Barr, Angela; Frøkjær-Jensen, Christian; Jorgensen, Erik M; Rougvie, Ann E

    2016-12-07

    The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

  13. Neil2-null Mice Accumulate Oxidized DNA Bases in the Transcriptionally Active Sequences of the Genome and Are Susceptible to Innate Inflammation* ♦

    Science.gov (United States)

    Chakraborty, Anirban; Wakamiya, Maki; Venkova-Canova, Tatiana; Pandita, Raj K.; Aguilera-Aguirre, Leopoldo; Sarker, Altaf H.; Singh, Dharmendra Kumar; Hosoki, Koa; Wood, Thomas G.; Sharma, Gulshan; Cardenas, Victor; Sarkar, Partha S.; Sur, Sanjiv; Pandita, Tej K.; Boldogh, Istvan; Hazra, Tapas K.

    2015-01-01

    Why mammalian cells possess multiple DNA glycosylases (DGs) with overlapping substrate ranges for repairing oxidatively damaged bases via the base excision repair (BER) pathway is a long-standing question. To determine the biological role of these DGs, null animal models have been generated. Here, we report the generation and characterization of mice lacking Neil2 (Nei-like 2). As in mice deficient in each of the other four oxidized base-specific DGs (OGG1, NTH1, NEIL1, and NEIL3), Neil2-null mice show no overt phenotype. However, middle-aged to old Neil2-null mice show the accumulation of oxidative genomic damage, mostly in the transcribed regions. Immuno-pulldown analysis from wild-type (WT) mouse tissue showed the association of NEIL2 with RNA polymerase II, along with Cockayne syndrome group B protein, TFIIH, and other BER proteins. Chromatin immunoprecipitation analysis from mouse tissue showed co-occupancy of NEIL2 and RNA polymerase II only on the transcribed genes, consistent with our earlier in vitro findings on NEIL2's role in transcription-coupled BER. This study provides the first in vivo evidence of genomic region-specific repair in mammals. Furthermore, telomere loss and genomic instability were observed at a higher frequency in embryonic fibroblasts from Neil2-null mice than from the WT. Moreover, Neil2-null mice are much more responsive to inflammatory agents than WT mice. Taken together, our results underscore the importance of NEIL2 in protecting mammals from the development of various pathologies that are linked to genomic instability and/or inflammation. NEIL2 is thus likely to play an important role in long term genomic maintenance, particularly in long-lived mammals such as humans. PMID:26245904

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

    Science.gov (United States)

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

    2015-03-01

    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 enhance TP53

  15. Simple computation of null-geodesics, with applications to vortex boundary detection

    Science.gov (United States)

    Serra, Mattia; Haller, George

    2016-11-01

    Recent results show that boundaries of coherent vortices (elliptic coherent structures) can be computed as closed null-geodesics of appropriate Lorentzian metrics defined on the physical domain of the underlying fluid. Here we derive a new method for computing null-geodesics of general Lorentzian metrics, founded on the geometry of geodesic flows. We also derive the correct set of initial conditions for the computation of closed null-geodesics, based on simple topological properties of planar closed curves. This makes the computation of coherent vortex boundaries fully automated, simpler and more accurate compared to the existing procedure. As an illustration, we compute objective coherent vortex boundaries in Oceanic and Atmospheric Flows.

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

    Science.gov (United States)

    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.

  17. Direction finding of GPS receiver interference based on the nulling weights

    Science.gov (United States)

    Wang, Jing; Amin, Moeness

    2007-04-01

    Most military applications of GPS require performing both jammer nulling and localization. While nulling can be achieved using adaptive gradient techniques applied to the input sampled data, high resolution direction of arrival estimation can precede using subspace and eigenstructure methods applied to the estimate of the covariance matrix. In this paper, we extract the jammer direction of arrival (DOA) information directly from the adaptive weights, in which case we assume interference nulling precedes interference localization. This high resolution DOA estimation approach based on available beamforming weight values leads to simplified receiver structure and allows a choice of IF or baseband processing as well as flexibility for analog, digital or mixed mode implementations.

  18. Tangential and sagittal curvature from the normals computed by the null screen method in corneal topography

    Science.gov (United States)

    Estrada-Molina, Amilcar; Díaz-Uribe, Rufino

    2011-08-01

    A new method for computing the tangential and sagittal curvatures from the normals to a cornea is proposed. The normals are obtained through a Null Screen method from the coordinates of the drops shaped spots at the null screen, the coordinates on a reference approximating surface and the centroids on the image plane. This method assumes that the cornea has rotational symmetry and our derivations will be carried out in the meridional plane that contains the symmetry axis. Experimental results are shown for a calibration spherical surface, using cylindrical null screens with radial point arrays.

  19. Parathyroid hormone administration improves bone marrow microenvironment and partially rescues haematopoietic defects in Bmi1-null mice.

    Directory of Open Access Journals (Sweden)

    Ruinan Lu

    Full Text Available The epigenetic regulator Bmi1 is key in haematopoietic stem cells, and its inactivation leads to defects in haematopoiesis. Parathyroid hormone (PTH, an important modulator of bone homeostasis, also regulates haematopoiesis, so we asked whether PTH administration improves bone marrow microenvironment and rescues the haematopoietic defects in Bmi1-null mice. The mice were treated with PTH1-34 (containing the first 34 residues of mature PTH, an anabolic drug currently used for treating osteoporosis, and compared with the vehicle-treated Bmi1-/- and wild-type littermates in terms of skeletal and haematopoietic phenotypes. We found that the administration significantly increased all parameters related to osteoblastic bone formation and significantly reduced the adipocyte number and PPARγ expression. The bone marrow cellularity, numbers of haematopoietic progenitors and stem cells in the femur, and numbers of lymphocytes and other white blood cells in the peripheral blood all increased significantly when compared to vehicle-treated Bmi1-/- mice. Moreover, the number of Jagged1-positive cells and percentage of Notch intracellular domain-positive bone marrow cells and protein expression levels of Jagged1 and NICD in bone tissue were also increased in Bmi1-/- mice upon PTH1-34 administration,whereas the up-regulation of PTH on both Notch1 and Jagged1 gene expression was blocked by the Notch inhibitor DAPT administration. These results thus indicate that PTH administration activates the notch pathway and partially rescues haematopoietic defects in Bmi1-null mice, further suggesting that haematopoietic defects in the animals are not only a result of reduced self-renewal of haematopoietic stem cells but also due to impaired bone marrow microenvironment.

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

    Directory of Open Access Journals (Sweden)

    Lucie Aumailley

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  2. Retina restored and brain abnormalities ameliorated by single-copy knock-in of human NR2E1 in null mice.

    Science.gov (United States)

    Schmouth, J-F; Banks, K G; Mathelier, A; Gregory-Evans, C Y; Castellarin, M; Holt, R A; Gregory-Evans, K; Wasserman, W W; Simpson, E M

    2012-04-01

    Nr2e1 encodes a stem cell fate determinant of the mouse forebrain and retina. Abnormal regulation of this gene results in retinal, brain, and behavioral abnormalities in mice. However, little is known about the functionality of human NR2E1. We investigated this functionality using a novel knock-in humanized-mouse strain carrying a single-copy bacterial artificial chromosome (BAC). We also documented, for the first time, the expression pattern of the human BAC, using an NR2E1-lacZ reporter strain. Unexpectedly, cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1. These results correlated with an absence of NR2E1-lacZ reporter expression in the dorsal pallium of embryos and proliferative cells of adult brains. Surprisingly, retinal histology and electroretinograms demonstrated complete correction of the retina-null phenotype. These results correlated with appropriate expression of the NR2E1-lacZ reporter in developing and adult retina. We conclude that the human BAC contained all the elements allowing correction of the mouse-null phenotype in the retina, while missing key regulatory regions important for proper spatiotemporal brain expression. This is the first time a separation of regulatory mechanisms governing NR2E1 has been demonstrated. Furthermore, candidate genomic regions controlling expression in proliferating cells during neurogenesis were identified.

  3. General principles of describing second- and higher-order null points of a potential magnetic field in 3D

    Science.gov (United States)

    Lukashenko, A. T.; Veselovsky, I. S.

    2015-12-01

    General principles of describing secondand higher-order null points of a potential magnetic field are formulated. The potential near a second-order null of the general form can be specified by a linear combination of four basic functions, the list of which is presented. Near secondand higher-order null points, field line equations often cannot be integrated analytically; however, in some cases, it is possible to present a qualitative description of the geometry of null vicinities with consideration of the behavior of field lines near rays outgoing from null, at which the field is radial or equals zero.

  4. In vivo assay of human NK-dependent ADCC using NOD/SCID/gammac(null) (NOG) mice.

    Science.gov (United States)

    Shiokawa, Miho; Takahashi, Takeshi; Murakami, Akihiro; Kita, Shoichi; Ito, Mamoru; Sugamura, Kazuo; Ishii, Naoto

    2010-09-03

    Monoclonal antibodies are essential to the success of molecularly targeted therapies. Recently, numerous therapeutic antibodies have been developed for various diseases, including cancer and autoimmune diseases. Experimental systems to effectively evaluate these candidate antibodies are urgently needed. One of the mechanisms used by antibodies to kill tumor cells is antibody-dependent cellular cytotoxicity (ADCC), in which natural killer cells (NK) are the main mediator. The capacity to induce ADCC has conventionally been assessed in the human-mouse xeno-graft model, in which human peripheral blood mononuclear cells (PBMC), containing NK cells along with antibodies, are administered to tumor-bearing immunodeficient mice. However, contamination from other cellular populations often affects tumor growth, making it difficult to evaluate the antibody's effect. In this study, we established a new NK-dependent ADCC assay model using a supra-immunodeficient strain of mice, NOD/SCID/gammac(null) (NOG). Our model system simply consisted of three elements: isolated human NK cells, a Burkitt's lymphoma cell line (Daudi), and an anti-CD20 antibody (Rituximab). In this experimental setting, human NK cells from healthy donors retained their killing activity and suppressed the growth of Daudi cells in NOG mice when they were administered along with Rituximab. This system, therefore, is useful for evaluating the in vivo function of human NK cells.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Entropy of a generic null surface from its associated Virasoro algebra

    Science.gov (United States)

    Chakraborty, Sumanta; Bhattacharya, Sourav; Padmanabhan, T.

    2016-12-01

    Null surfaces act as one-way membranes, blocking information from those observers who do not cross them (e.g., in the black hole and the Rindler spacetimes) and these observers associate an entropy (and temperature) with the null surface. The black hole entropy can be computed from the central charge of an appropriately defined, local, Virasoro algebra on the horizon. We show that one can extend these ideas to a general class of null surfaces, all of which possess a Virasoro algebra and a central charge, leading to an entropy density (i.e., per unit area) which is just (1 / 4). All the previously known results of associating entropy with horizons arise as special cases of this very general property of null surfaces demonstrated here and we believe this work represents the derivation of the entropy-area law in the most general context. The implications are discussed.

  7. The Determining Method about the Conflict between the Null Constraints and the Set of Functional Dependencies

    Institute of Scientific and Technical Information of China (English)

    刘惟一

    1989-01-01

    In this paper the conflict between the null constraints and the set of functional dependencies is defined.Some rules for determining the conflicts and a method for processing the conflicts are obtained.

  8. Proper Accelerations of Time-Like Curves near a Null Geodesic

    Institute of Scientific and Technical Information of China (English)

    田贵花; 赵峥

    2003-01-01

    It is well known that when given a null geodesic γ0(λ) with a point r in (p, q) conjugate to p along γ0(λ), there will be a variation of γ0(λ) which can give a time-like curve from p to q. Here we prove that the time-like curves coming from the above-mentioned variation (with the second derivative β2 ≠ 0) have a proper acceleration A = √AaAa which approaches infinity as the time-like curve approaches the null geodesic. Because the curve obtained from variation of the null geodesic must be everywhere time-like, we also discuss the constraint of the vector field Za on the null geodesic γ0(λ) cannot be zero.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ryutov, D. D.; Umansky, M. V. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States)

    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.

  10. Current Singularities at Quasi-Separatrix Layers and Three-Dimensional Magnetic Nulls

    CERN Document Server

    Craig, I J D

    2014-01-01

    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 towards the final near-singular state. Our starting point is an exact force-free solution of the governing magnetohydrodynamic (MHD) equations which 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 wit...

  11. Magnetic reconnection at 3D null points: effect of magnetic field asymmetry

    CERN Document Server

    Al-Hachami, A K

    2009-01-01

    The aim of this paper is to investigate the properties of magnetic reconnection at a 3D null point, with respect to their dependence on the symmetry of the magnetic field around the null. In particular we examine the rate of flux transport across the null point with symmetric/asymmetric diffusion regions, as well as how the current sheet forms in time, and its properties. Mathematical modelling and finite difference resistive MHD simulations are used. It is found that the basic structure of the mode of magnetic reconnection considered is unaffected by varying the magnetic field symmetry, that is, the plasma flow is found cross both the spine and fan of the null. However, the peak intensity and dimensions of the current sheet are dependent on the symmetry/ asymmetry of the field lines. As a result, the reconnection rate is also found to be strongly dependent on the field asymmetry.

  12. Octet Magnetic Moments with Null Instantons and Semibosonized Nambu-Jona-Lasinio Model

    CERN Document Server

    Bukina, E N

    1999-01-01

    It is shown that the difference between the magnetic moment results in the quark model with null instantons and semibosonized Nambu-Jona-Lasinio model lies in the description of the magnetic moment of the $ \\Lambda$-hyperon.

  13. Vlasov fluid stability of a 2-D plasma with a linear magnetic field null

    Energy Technology Data Exchange (ETDEWEB)

    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 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.

  14. Vectorial analysis of polarization issues in multi-axial nulling interferometers for exoplanet detection

    NARCIS (Netherlands)

    Spronck, J.; Pereira, S.F.; Braat, J.J.M.

    2007-01-01

    We show the theoretical limitations of a multi-axial nulling interferometer with respect to longitudinal polarization. We furthermore analyze the filtering capabilities of a single-mode fiber in this case.

  15. Possible Solution to Publication Bias Through Bayesian Statistics, Including Proper Null Hypothesis Testing

    NARCIS (Netherlands)

    Konijn, Elly A.; van de Schoot, Rens; Winter, Sonja D.; Ferguson, Christopher J.

    2015-01-01

    The present paper argues that an important cause of publication bias resides in traditional frequentist statistics forcing binary decisions. An alternative approach through Bayesian statistics provides various degrees of support for any hypothesis allowing balanced decisions and proper null hypothes

  16. Current sheets at three-dimensional magnetic nulls: Effect of compressibility

    Science.gov (United States)

    Pontin, D. I.; Bhattacharjee, A.; Galsgaard, K.

    2007-05-01

    The nature of current sheet formation in the vicinity of three-dimensional (3D) magnetic null points is investigated. The particular focus is upon the effect of the compressibility of the plasma on the qualitative and quantitative properties of the current sheet. An initially potential 3D null is subjected to shearing perturbations, as in a previous paper [Pontin et al., Phys. Plasmas 14, 052106 (2007)]. It is found that as the incompressible limit is approached, the collapse of the null point is suppressed and an approximately planar current sheet aligned to the fan plane is present instead. This is the case regardless of whether the spine or fan of the null is sheared. Both the peak current and peak reconnection rate are reduced. The results have a bearing on previous analytical solutions for steady-state reconnection in incompressible plasmas, implying that fan current sheet solutions are dynamically accessible, while spine current sheet solutions are not.

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

    CERN Document Server

    Cai, Rong-Gen; Yang, Tao

    2015-01-01

    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 $d_L(z)$. Combining the independent observations of $H(z)$ and $d_L(z)$, we use the model-independent smoothing technique, Gaussian processes, to reconstruct them and determine the cosmic curvature $\\Omega_K^{(0)}$ in the null test relation. The null test is totally geometrical and without assuming any cosmological model. We show that the cosmic curvature $\\Omega_K^{(0)}=0$ is consistent with current observational data sets, falling within the $1\\sigma$ limit. To demonstrate the effect on the precision of the null test, we produce a series of simulated data of the models with different $\\Omega_K^{(0)}$. Future observations in better quality can provide a greater improvement to constrain or refute the flat universe with $\\Omega_K^{(0)}=0$.

  18. Structures of magnetic null points in reconnection diffusion region: Cluster observations

    Institute of Scientific and Technical Information of China (English)

    HU YunHui; R.NAKAMURA; W.BAUMJOHANN; H.R'EME; C.M.CARR; DENG XiaoHua; ZHOU Meng; TANG RongXin; ZHAO Hui; FU Song; SU ZhiWen; WANG JingFang; YUAN ZhiGang

    2008-01-01

    Magnetic reconnection is a very important and fundamental plasma process in transferring energy from magnetic field into plasma. Previous theory, numerical simulations and observations mostly concen-trate on 2-dimensional (2D) model; however, magnetic reconnection is a 3-dimensional (3D) nonlinear process in nature. The properties of reconnection in 3D and its associated singular structure have not been resolved completely. Here we investigate the structures and characteristics of null points inside the reconnection diffusion region by introducing the discretized Poincaré index through Gauss integral and using magnetic field data with high resolution from the four satellites of Cluster mission. We esti-mate the velocity and trajectory of null points by calculating its position in different times, and compare and discuss the observations with different reconnection models with null points based on character-istics of electric current around null points.

  19. Null Controllability for Some Systems of Two Backward Stochastic Heat Equations with One Control Force

    Institute of Scientific and Technical Information of China (English)

    Hongheng LI; Qi L(U)

    2012-01-01

    The authors establish the null controllability for some systems coupled by two backward stochastic heat equations.The desired controllability result is obtained by means of proving a suitable observability estimate for the dual system of the controlled system.

  20. Magnetohydrodynamics dynamical relaxation of coronal magnetic fields. IV. 3D tilted nulls

    Science.gov (United States)

    Fuentes-Fernández, J.; Parnell, C. E.

    2013-06-01

    Context. There are various types of reconnection that may take place at 3D magnetic null points. Each different reconnection scenario must be associated with a particular type of current layer. Aims: A range of current layers may form because the topology of 3D nulls permits currents to form by either twisting the field about the spine of the null or by folding the fan and spine into each other. Additionally, the initial geometry of the field can lead to variations in the currents that are accumulated. Here, we study current accumulations in so-called 3D "tilted" nulls formed by a folding of the spine and fan. A non-zero component of current parallel to the fan is required such that the null's fan plane and spine are not perpendicular. Our aims are to provide valid magnetohydrostatic equilibria and to describe the current accumulations in various cases involving finite plasma pressure. Methods: To create our equilibrium current structures we use a full, non-resistive, magnetohydrodynamic (MHD) code so that no reconnection is allowed. A series of experiments are performed in which a perturbed 3D tilted null relaxes towards an equilibrium via real, viscous damping forces. Changes to the initial plasma pressure and to magnetic parameters are investigated systematically. Results: An initially tilted fan is associated with a non-zero Lorentz force that drives the fan and spine to collapse towards each other, in a similar manner to the collapse of a 2D X-point. In the final equilibrium state for an initially radial null with only the current perpendicular to the spine, the current concentrates along the tilt axis of the fan and in a layer about the null point with a sharp peak at the null itself. The continued growth of this peak indicates that the system is in an asymptotic regime involving an infinite time singularity at the null. When the initial tilt disturbance (current perpendicular to the spine) is combined with a spiral-type disturbance (current parallel to the

  1. On the Domain of the Triangle on the Spaces of Null, Convergent, and Bounded Sequences

    Directory of Open Access Journals (Sweden)

    Naim L. Braha

    2013-01-01

    Full Text Available We introduce the spaces of -null, -convergent, and -bounded sequences. We examine some topological properties of the spaces and give some inclusion relations concerning these sequence spaces. Furthermore, we compute -, -, and -duals of these spaces. Finally, we characterize some classes of matrix transformations from the spaces of -bounded and -convergent sequences to the spaces of bounded, almost convergent, almost null, and convergent sequences and present a Steinhaus type theorem.

  2. Cardiac Characterization of sgca-Null Mice Using High Resolution Echocardiography.

    Science.gov (United States)

    Fayssoil, Abdallah; Renault, Gilles; Guerchet, Nicolas; Marchiol-Fournigault, Carmen; Fougerousse, Françoise; Richard, Isabelle

    2013-01-01

    Limb-girdle muscular dystrophy 2D (LGMD2D) is an inherited myogenic disorder belonging to the group of muscular dystrophies. Sgca-null mouse is a knock-out model of LGMD2D. Little is known about cardiac phenotype characterization in this model at different ages. We conducted a prospective study to characterize cardiac sgca-null mice phenotype using high resolution Doppler echocardiography at different ages. Conventional echocardiography was performed on anesthetised mice using a Vevo 770 (Visualsonics) with 30 MHz cardiac probe. Wild Type (WT) and sgca-null mice were scanned at 13, 15 and 17 months. From M-mode, we measured interventricular septal (IVS) wall thickness, posterior wall (PW) thickness, and end-left ventricular diameter in systolic and diastolic. From the above parameters, we calculated left ventricular (LV) shortening fraction (SF), LV ejection fraction (EF) and LV mass. At age 13 months, PW diastolic thickness was increased in sgca-null mice (0.89±0.14 mm vs 0.73±0.2 mm; P=0.020) and LV mass was higher in sgca-null mice (LV mass 205.2 mg vs 143 mg; P=0.001). We found also dilation of the LV (LVEDD: 4.84 mm vs 4.29 mm; P=0.019) in sgca-null mice. At age 15 months, dilation of the LV (LVEDD: 4.86 mm vs 4 mm; P=0.05) with an increase of the LV mass (165.7 mg vs 127.12; P=0.03) are found in sgca-null mice. At age 17 months, we found a decrease of the PW thickening (17% vs 30%; P=0.036). This work provides echocardiographic insights for the assessment of pharmaceutical therapies in sgca-null mice.

  3. A NOVEL NULLING ALGORITHM IN THE SUBARRAY OF A LARGE ARRAY

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhou Yinqing; Xu Huaping

    2006-01-01

    Forming nulls in the radiation pattern of an antenna is to suppress the interference from certain directions or to cancel desired signals. This letter presents an effective method based on the Gram-Schmidt orthogonal algorithm for forming nulls in the subarray of a large array. The theory and realizing methods are discussed, and the corresponding formulas are derived in details. The simulation results are given to demonstrate the feasibility, the availability and the quick-convergence of the presented method.

  4. Some magnetic null lines of astrophysical interest. II. [in magnetic Ap stars

    Science.gov (United States)

    Adelman, S. J.

    1974-01-01

    A list of magnetic null lines from selected spectroscopic analyses is presented for possible use in detailed studies of magnetic Ap stars. The presented data represent an extension of the magnetic null lines whose usefulness Shore and Adelman (1974) have recently demonstrated for the study of the overall physical conditions prevailing in the atmospheres of peculiar A stars and for testing the consequences of the mechanism of selective elemental diffusion.

  5. Kahel korral järjest null häält / Maarius Suviste

    Index Scriptorium Estoniae

    Suviste, Maarius, 1966-

    2005-01-01

    Kohalike omavalitsuste volikogude valimistel ei saanud ühtegi häält 233 kandidaati. Oma kandideerimise põhjusi selgitavad juba teist korda valimistel null häält saanud Viljandi tisler Kaljo Jürman, Põlvamaa mahetalunik Liisi Kutkina ja Ida-Virumaa pensionär Vaike Zaitseva. Lisatud statistilised andmed null häält saanud kandidaatide kohta maakondade ja erakondade kaupa

  6. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

    Science.gov (United States)

    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  7. PSF and field of view characteristics of imaging and nulling interferometers

    OpenAIRE

    Hénault, François

    2010-01-01

    In this communication are presented some complements to a recent paper entitled "Simple Fourier optics formalism for high angular resolution systems and nulling interferometry", dealing with imaging and nulling capacities of a few types of multi-aperture optical systems. Herein the characteristics of such systems in terms of Point Spread Function (PSF) and Field of View (FoV) are derived from simple analytical expressions that are further evaluated numerically for various configurations. We c...

  8. Hamiltonian analysis of the double null 2+2 decomposition of Ashtekar variables

    CERN Document Server

    d'Inverno, R A; Vickers, J A

    2006-01-01

    We derive a canonical analysis of a double null 2+2 Hamiltonian description of General Relativity in terms of complex 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.

  9. Computer model simulation of null-flux magnetic suspension and guidance

    Energy Technology Data Exchange (ETDEWEB)

    He, Jianliang; Rote, D.M.

    1992-06-01

    This paper discusses the magnetic force computations in a null-flux suspension system using dynamic circuit theory. A computer simulation model that can be used to compute magnetic forces and predict the system performance is developed on the basis of dynamic circuit theory. Numerical examples are presented to demonstrate the application of the model. The performance of the null-flux suspension system is simulated and discussed. 8 refs.

  10. Computer model simulation of null-flux magnetic suspension and guidance

    Energy Technology Data Exchange (ETDEWEB)

    He, Jianliang; Rote, D.M.

    1992-01-01

    This paper discusses the magnetic force computations in a null-flux suspension system using dynamic circuit theory. A computer simulation model that can be used to compute magnetic forces and predict the system performance is developed on the basis of dynamic circuit theory. Numerical examples are presented to demonstrate the application of the model. The performance of the null-flux suspension system is simulated and discussed. 8 refs.

  11. Current accumulation at an asymmetric 3D null point caused by generic shearing motions

    Science.gov (United States)

    Galsgaard, K.; Pontin, D. I.

    2011-10-01

    Context. Here we investigate the dynamical evolution of the reconnection process at an initially linear 3D null point that is stressed by a localised shear motion across the spine axis. The difference to previous investigations is that the fan plane is not rotationally symmetric and this allows for different behaviours depending on the alignment of the fan plane relative to the imposed driver direction. Aims: The aim is to show how the current accumulation and the associated reconnection process at the non-axisymmetric null depends on the relative orientation between the driver imposed stress across the spine axis of the null and the main eigenvector direction in the fan plane. Methods: The time evolution of the 3D null point is investigated solving the 3D non-ideal MHD equations numerically in a Cartesian box. The magnetic field is frozen to the boundaries and the boundary velocity is only non-zero where the imposed driving for stressing the system is applied. Results: The current accumulation is found to be along the direction of the fan eigenvector associated with the smallest eigenvalue until the direction of the driver is almost parallel to this eigenvector. When the driving velocity is parallel to the weak eigenvector and has an impulsive temporal profile the null only has a weak collapse forming only a weak current layer. However, when the null point is stressed continuously boundary effects dominates the current accumulation. Conclusions: There is a clear relation between the orientation of the current concentration and the direction of the fan eigenvector corresponding to the small eigenvalue. This shows that the structure of the magnetic field is the most important in determining where current is going to accumulate when a single 3D null point is perturbed by a simple shear motion across the spine axis. As the angle between the driving direction and the strong eigenvector direction increases, the current that accumulates at the null becomes progressively

  12. Increased susceptibility of Nrf2-null mice to 1-bromopropane-induced hepatotoxicity.

    Science.gov (United States)

    Liu, Fang; Ichihara, Sahoko; Valentine, William M; Itoh, Ken; Yamamoto, Masayuki; Sheik Mohideen, Sahabudeen; Kitoh, Junzoh; Ichihara, Gaku

    2010-06-01

    1-Bromopropane (1-BP) was introduced as an alternative to ozone-depleting solvents. However, it was found to exhibit neurotoxicity, reproductive toxicity, and hepatotoxicity in rodents and neurotoxicity in human. However, the mechanisms underlying the toxicities of 1-BP remain elusive. The present study investigated the role of oxidative stress in 1-BP-induced hepatotoxicity using nuclear factor erythroid 2-related factor 2 (Nrf2)-null mice. Groups of 24 male Nrf2-null mice and 24 male wild-type (WT) C57BL/6J mice were each divided into three groups of eight and exposed to 1-BP at 0, 100, or 300 ppm for 8 h/day for 28 days by inhalation. Liver histopathology showed significantly larger area of necrosis in Nrf2-null mice relative to WT mice at the same exposure level. Nrf2-null mice also had greater malondialdehyde (MDA) levels, higher ratio of oxidized glutathione/reduced form of glutathione, and lower total glutathione content. The constitutive level and the increase in ratio per exposure level of glutathione S-transferase (GST) activity were lower in the liver of Nrf2-null mice than WT mice. Exposure to 1-BP at 300 ppm increased the messenger RNA levels of heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GcLm), glutamate-cysteine synthetase (GcLc), glutathione reductase, and NAD(P)H: quinone oxidoreductase 1 (NQO1) in WT mice but not in Nrf2-null mice except for GST Yc2. Nrf2-null mice were more susceptible to 1-BP-induced hepatotoxicity. That oxidative stress plays a role in 1-BP hepatotoxicity is deduced from the low expression levels and activities of antioxidant enzymes and high MDA levels in Nrf2-null mice.

  13. Power Analysis and Experimental Study of the Fiber Null Coupler with an Acousto-optic Device

    Institute of Scientific and Technical Information of China (English)

    WU Lei; ZHENG Yuan; QI Jiang; PU Hongtu; CHEN Shuqiang

    2002-01-01

    A single-mode fiber acousto-optic (AO) switch based on a null coupler at wavelength of 1.55 μm is reported.According to the coupled mode theory,power distribution of the null coupler with the acoustic-wave is formulated for general case.Excess loss of 0.1 dB and the schematic graph of throughput and coupled power are obtained experimentally.

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

    Science.gov (United States)

    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.

  15. Observation of Magnetic reconnection at a 3D null point associated with a solar eruption

    CERN Document Server

    Sun, J Q; Yang, K; Cheng, X; Ding, M D

    2016-01-01

    Magnetic null has long been recognized as a special structure serving as a preferential site for magnetic reconnection (MR). However, the direct observational study of MR at null-points is largely lacking. Here, we show the observations of MR around a magnetic null associated with an eruption that resulted in an M1.7 flare and a coronal mass ejection. The GOES X- ray profile of the flare exhibited two peaks at 02:23 UT and 02:40 UT on 2012 November 8, respectively. Based on the imaging observations, we find that the first and also primary X- ray peak was originated from MR in the current sheet underneath the erupting magnetic flux rope (MFR). On the other hand, the second and also weaker X-ray peak was caused by MR around a null-point located above the pre-eruption MFR. The interaction of the null-point and the erupting MFR can be described as a two-step process. During the first step, the erupting and fast expanding MFR passed through the null-point, resulting in a significant displacement of the magnetic fi...

  16. Dynamical Relaxation of Coronal Magnetic Fields. III. 3D Spiral Nulls

    CERN Document Server

    Fuentes-Fernandez, Jorge

    2012-01-01

    Context: The majority of studies on stressed 3D magnetic null points consider magnetic reconnection driven by an external perturbation, but the formation of a genuine current sheet equilibrium remains poorly understood. This problem has been considered more extensively in two-dimensions, but lacks a generalization into 3D fields. Aims: 3D magnetic nulls are more complex than 2D nulls and the field can take a greater range of magnetic geometries local to the null. Here, we focus on one type and consider the dynamical non-resistive relaxation of 3D spiral nulls with initial spine-aligned current. We aim to provide a valid magnetohydrostatic equilibrium, and describe the electric current accumulations in various cases, involving a finite plasma pressure. Methods: A full MHD code is used, with the resistivity set to zero so that reconnection is not allowed, to run a series of experiments in which a perturbed spiral 3D null point is allowed to relax towards an equilibrium, via real, viscous damping forces. Changes...

  17. Review article: MHD wave propagation near coronal null points of magnetic fields

    CERN Document Server

    McLaughlin, J A; De Moortel, I; 10.1007/s11214-010-9654-y

    2010-01-01

    We present a comprehensive review of MHD wave behaviour in the neighbourhood of coronal null points: locations where the magnetic field, and hence the local Alfven speed, is zero. The behaviour of all three MHD wave modes, i.e. the Alfven wave and the fast and slow magnetoacoustic waves, has been investigated in the neighbourhood of 2D, 2.5D and (to a certain extent) 3D magnetic null points, for a variety of assumptions, configurations and geometries. In general, it is found that the fast magnetoacoustic wave behaviour is dictated by the Alfven-speed profile. In a $\\beta=0$ plasma, the fast wave is focused towards the null point by a refraction effect and all the wave energy, and thus current density, accumulates close to the null point. Thus, null points will be locations for preferential heating by fast waves. Independently, the Alfven wave is found to propagate along magnetic fieldlines and is confined to the fieldlines it is generated on. As the wave approaches the null point, it spreads out due to the di...

  18. Proton acceleration in three-dimensional non-null magnetic reconnection

    Science.gov (United States)

    Akbari, Z.; Hosseinpour, M.; Mohammadi, M. A.

    2016-10-01

    In a three-dimensional non-null magnetic reconnection, the process of magnetic reconnection takes place in the absence of a null point where the magnetic field vanishes. By randomly injecting a population of 10 000 protons, the trajectory and energy distribution of accelerated protons are investigated in the presence of magnetic and electric fields of a particular model of non-null magnetic reconnection with the typical parameters for the solar corona. The results show that protons are accelerated along the magnetic field lines away from the non-null point only at azimuthal angles where the magnitude of the electric field is strongest and therefore particles obtain kinetic energies of the order of thousands of MeV and even higher. Moreover, the energy distribution of the population depends strongly on the amplitude of the electric and magnetic fields. Comparison shows that a non-null magnetic reconnection is more efficient in accelerating protons to very high GeV energies than a null-point reconnection.

  19. Why are flare ribbons associated with the spines of magnetic null points generically elongated?

    CERN Document Server

    Pontin, D I; Demoulin, P

    2016-01-01

    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, that can be analysed using the `squashing factor', $Q$. In this paper we make a detailed analysis of 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/fan in the direction in which $|{\\bf B}|$ increases most slowly. In particular, this demonstrates that the extend...

  20. Electron acceleration by whistler-mode waves around the magnetic null during 3D reconnection

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Fuliang [School of Physics and Electronic Sciences, Changsha University of Science and Technology, Changsha, 410004 (China); Zong Qiugang; Pu Zuyin; He Jiansen; Wang Yongfu [School of Earth and Space Sciences, Peking University, Beijing 100871 (China); Su Zhenpeng; Zheng Huinan [CAS Key Laboratory for Basic Plasma Physics, School of Earth and Space Sciences, University of Science and Technology of China, Hefei (China); Cao Jinbin, E-mail: qgzong@pku.edu.c [State Key Laboratory of Space Weather, PO Box 8701, Beijing 100080 (China)

    2010-05-15

    The magnetic field configuration around a magnetic null pair and its associated electron behavior during 3D magnetic reconnection have recently been reported from in situ observations. Electrons are suggested to be temporarily trapped in the central reconnection region as indicated by an electron density peak observed near the magnetic null (He J-S et al 2008 Geophys. Res. Lett. 35 L14104). It is highly interesting that energetic electron beams of a few kiloelectronvolts are found to be related to the magnetic null structure. However, the acceleration mechanism is still not fully understood. In this paper, we show that strong whistler-mode electromagnetic waves are indeed found around the magnetic null. Further we propose a new electron acceleration scenario of trapped electrons near the magnetic null points driven by the whistler-mode waves, which is confirmed by numerical results. It is demonstrated that whistler waves can enhance the phase space density (PSD) of electrons for energies of approx2 keV by a factor of 100 at lower pitch angles very rapidly, typically within 2 s. The accelerated electrons may escape from the loss cone of the magnetic cusp mirrors around the magnetic null, leading to the observed energetic beams. (brief communication)

  1. Magnetoacoustic Waves in a Stratified Atmosphere with a Magnetic Null Point

    CERN Document Server

    Tarr, Lucas A; Leake, James

    2016-01-01

    We perform nonlinear MHD simulations to study the propagation of magnetoacoustic waves from the photosphere to the low corona. We focus on a 2D system with a gravitationally stratified atmosphere and three photospheric concentrations of magnetic flux that give rise to a magnetic null point with a magnetic dome topology. We find that a single wavepacket introduced at the lower boundary splits into multiple secondary wavepackets. A portion of the packet refracts towards the null due to the varying Alfv\\'en speed. Waves incident on the equipartition contour surrounding the null, where the sound and Alfv\\'en speeds coincide, partially transmit, reflect, and mode convert between branches of the local dispersion relation. Approximately $15.5\\%$ of the wavepacket's initial energy ($E_{input}$) converges on the null, mostly as a fast magnetoacoustic wave. Conversion is very efficient: $70\\%$ of the energy incident on the null is converted to slow modes propagating away from the null, $7\\%$ leaves as a fast wave, and ...

  2. Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer.

    Science.gov (United States)

    Komiya, T; Coxon, A; Park, Y; Chen, W-D; Zajac-Kaye, M; Meltzer, P; Karpova, T; Kaye, F J

    2010-03-18

    Activation of Crtc1 (also known as Mect1/Torc1) by a t(11;19) chromosomal rearrangement underlies the etiology of malignant salivary gland tumors. As LKB1 is a target for mutational inactivation in lung cancer and was recently shown to regulate hepatic Crtc2/CREB transcriptional activity in mice, we now present evidence suggesting disruption of an LKB1/Crtc pathway in cancer. Although Crtc1 is preferentially expressed in adult brain tissues, we observed elevated levels of steady-state Crtc1 in thoracic tumors. In addition, we show that somatic loss of LKB1 is associated with underphosphorylation of endogenous Crtc1, enhanced Crtc1 nuclear localization and enhanced expression of the Crtc prototypic target gene, NR4A2/Nurr1. Inhibition of NR4A2 was associated with growth suppression of LKB1 null tumors, but showed little effect on LKB1-wildtype cells. These data strengthen the role of dysregulated Crtc as a bona fide cancer gene, present a new element to the complex LKB1 tumorigenic axis, and suggest that Crtc genes may be aberrantly activated in a wider range of common adult malignancies.

  3. Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice

    Science.gov (United States)

    Picard, Brigitte; Kammoun, Malek; Gagaoua, Mohammed; Barboiron, Christiane; Meunier, Bruno; Chambon, Christophe; Cassar-Malek, Isabelle

    2016-01-01

    Hsp27—encoded by HspB1—is a member of the small heat shock proteins (sHsp, 12–43 kDa (kilodalton)) family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse. Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1-null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1), contraction (TnnT3), energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1) and the Hsp proteins family (HspA9). These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps.

  4. Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype.

    Science.gov (United States)

    Storry, Jill R; Jöud, Magnus; Christophersen, Mikael Kronborg; Thuresson, Britt; Åkerström, Bo; Sojka, Birgitta Nilsson; Nilsson, Björn; Olsson, Martin L

    2013-05-01

    The Vel antigen is present on red blood cells (RBCs) from all humans except rare Vel-negative individuals who can form antibodies to Vel in response to transfusion or pregnancy. These antibodies may cause severe hemolytic reactions in blood recipients. We combined SNP profiling and transcriptional network modeling to link the Vel-negative phenotype to SMIM1, located in a 97-kb haplotype block on chromosome 1p36. This gene encodes a previously undiscovered, evolutionarily conserved transmembrane protein expressed on RBCs. Notably, 35 of 35 Vel-negative individuals were homozygous for a frameshift deletion of 17 bp in exon 3. Functional studies using antibodies raised against SMIM1 peptides confirmed a null phenotype in RBC membranes, and SMIM1 overexpression induced Vel expression. Genotype screening estimated that ~1 of 17 Swedish blood donors is a heterozygous deletion carrier and ~1 of 1,200 is a homozygous deletion knockout and enabled identification of Vel-negative donors. Our results establish SMIM1 as a new erythroid gene and Vel as a new blood group system.

  5. Joint dysfunction and functional decline in middle age myostatin null mice.

    Science.gov (United States)

    Guo, Wen; Miller, Andrew D; Pencina, Karol; Wong, Siu; Lee, Amanda; Yee, Michael; Toraldo, Gianluca; Jasuja, Ravi; Bhasin, Shalender

    2016-02-01

    Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway.

  6. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

    Directory of Open Access Journals (Sweden)

    Sara N. Koenig

    2015-03-01

    Full Text Available Thoracic aortic aneurysms (TAA are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/−; Nos3−/− mice. Echocardiographic analysis of Notch1+/−; Nos3−/− mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/−; Nos3−/− mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  7. Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a penetrating brain injury

    Directory of Open Access Journals (Sweden)

    Krady J Kyle

    2006-06-01

    Full Text Available Abstract The cytokines IL-1α and IL-1β are induced rapidly after insults to the CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-1R1 has been regarded as essential for a normal astroglial and microglial/macrophage response. To determine whether abrogating signaling through the IL-1R1 will alter the cardinal astrocytic responses to injury, we analyzed molecules characteristic of activated astrocytes in response to a penetrating stab wound in wild type mice and mice with a targeted deletion of IL-1R1. Here we show that after a stab wound injury, glial fibrillary acidic protein (GFAP induction on a per cell basis is delayed in the IL-1R1-null mice compared to wild type counterparts. However, the induction of chondroitin sulfate proteoglycans, tenascin, S-100B as well as glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are independent of IL-1RI signaling. Cumulatively, our studies on gliosis in the IL-1R1-null mice indicate that abrogating IL-1R1 signaling delays some responses of astroglial activation; however, many of the important neuroprotective adaptations of astrocytes to brain trauma are preserved. These data recommend the continued development of therapeutics to abrogate IL-1R1 signaling to treat traumatic brain injuries. However, astroglial scar related proteins were induced irrespective of blocking IL-1R1 signaling and thus, other therapeutic strategies will be required to inhibit glial scarring.

  8. A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice.

    Science.gov (United States)

    Tanimoto, Keiji; Kanafusa, Sumiyo; Ushiki, Aki; Matsuzaki, Hitomi; Ishida, Junji; Sugiyama, Fumihiro; Fukamizu, Akiyoshi

    2014-10-01

    Renin is predominantly expressed in juxtaglomerular cells in the kidney and regulates blood pressure homeostasis. To examine possible in vivo functions of a mouse distal enhancer (mdE), we generated transgenic mice (TgM) carrying either wild-type or mdE-deficient renin BACs (bacterial artificial chromosome), integrated at the identical chromosomal site. In the kidneys of the TgM, the mdE contributed 80% to basal renin promoter activity. To test for possible physiological roles for the mdE, renin BAC transgenes were used to rescue the hypotensive renin-null mice. Interestingly, renal renin expression in the Tg(BAC):renin-null compound mice was indistinguishable between the wild-type and mutant BAC carriers. Surprisingly, however, the plasma renin activity and angiotensin I concentration in the mdE compound mutant mice were significantly lower than the same parameters in the control mice, and the mutants were consistently hypotensive, demonstrating that blood pressure homeostasis is regulated through transcriptional cis elements controlling renin activity.

  9. Kharon1 null mutants of Leishmania mexicana are avirulent in mice and exhibit a cytokinesis defect within macrophages.

    Directory of Open Access Journals (Sweden)

    Khoa D Tran

    Full Text Available 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.

  10. Carrageenan-Induced Colonic Inflammation Is Reduced in Bcl10 Null Mice and Increased in IL-10-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Sumit Bhattacharyya

    2013-01-01

    Full Text Available The common food additive carrageenan is a known activator of inflammation in mammalian tissues and stimulates both the canonical and noncanonical pathways of NF-κB activation. Exposure to low concentrations of carrageenan (10 μg/mL in the water supply has produced glucose intolerance, insulin resistance, and impaired insulin signaling in C57BL/6 mice. B-cell leukemia/lymphoma 10 (Bcl10 is a mediator of inflammatory signals from Toll-like receptor (TLR 4 in myeloid and epithelial cells. Since the TLR4 signaling pathway is activated in diabetes and by carrageenan, we addressed systemic and intestinal inflammatory responses following carrageenan exposure in Bcl10 wild type, heterozygous, and null mice. Fecal calprotectin and circulating keratinocyte chemokine (KC, nuclear RelA and RelB, phospho(Thr559-NF-κB-inducing kinase (NIK, and phospho(Ser36-IκBα in the colonic epithelial cells were significantly less (P<0.001 in the carrageenan-treated Bcl10 null mice than in controls. IL-10-deficient mice exposed to carrageenan in a germ-free environment showed an increase in activation of the canonical pathway of NF-κB (RelA activation, but without increase in RelB or phospho-Bcl10, and exogenous IL-10 inhibited only the canonical pathway of NF-κB activation in cultured colonic cells. These findings demonstrate a Bcl10 requirement for maximum development of carrageenan-induced inflammation and lack of complete suppression by IL-10 of carrageenan-induced inflammation.

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

    Directory of Open Access Journals (Sweden)

    Gerhard Sengle

    2015-06-01

    Full Text Available 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

  12. Attainment of brown adipocyte features in white adipocytes of hormone-sensitive lipase null mice.

    Directory of Open Access Journals (Sweden)

    Kristoffer Ström

    Full Text Available BACKGROUND: Hormone-sensitive lipase (HSL is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: Following a high-fat diet (HFD regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissue of HSL null mice was characterized by reduced mass and reduced protein expression of PPARgamma, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the differentiation state of the adipocyte. The protein expression of uncoupling protein-1 (UCP-1, the highly specific marker of brown adipocytes, was increased 7-fold in white adipose tissue of HSL null mice compared to wildtype littermates. Transmission electron microscopy revealed an increase in the size of mitochondria of white adipocytes of HSL null mice. The mRNA expression of pRb and RIP140 was decreased in isolated white adipocytes, while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to wildtype littermates. Basal oxygen consumption was increased almost 3-fold in white adipose tissue of HSL null mice and was accompanied by increased uncoupling activity. CONCLUSIONS: These data suggest that HSL is involved in the determination of white versus brown adipocytes during adipocyte differentiation The exact mechanism(s underlying this novel role of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal expression levels of pRb and RIP140, which both promote differentiation into the white, rather than the brown

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

    Science.gov (United States)

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

    2015-06-01

    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.

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

    Science.gov (United States)

    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

  15. Influence of choice of null network on small-world parameters of structural correlation networks.

    Science.gov (United States)

    Hosseini, S M Hadi; Kesler, Shelli R

    2013-01-01

    In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures.

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

    Science.gov (United States)

    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.

  17. Particle Transport along Magnetic Null Lines as Sputter or Antihydrogen Source

    Science.gov (United States)

    Lane, R. A.; Ordonez, C. A.

    Particle transport along null magnetic lines is investigated using classical trajectory Monte Carlo simulations and described as a traveling wave and through diffusion equations. A magnetic null line is defined as a one-dimensional region where the magnetic field magnitude is zero. This region may take any shape in three-dimensional space. The field used in the simulations is generated by two infinite wires of negligible thickness carrying identical current and separated by a small distance. Thus, an infinite magnetic null line exists directly between the wires. The particle trajectories are simulated by solving the equations of motion for each simulated particle of a mono- energetic set. Each is considered individually, with all trajectories starting from the same position along the null line. Each trajectory is simulated until it reaches a specified distance from the initial point or a maximum time elapses. The simulation is repeated using a full set for multiple endpoints and maximum times for ten different amounts of current in the wires. Each current value is selected so that no particles can travel more than seven times the distance between the wires from the null line. The fraction of particles that reach the endpoint in a given time is calculated and used to describe particle transport parallel to the null line. The results are given in normalized, dimensionless units and their possible applications as an antihydrogen source and use in ultra-high purity sputter are discussed. The results are used to find the conditions necessary to obtain a steady and uniform particle flux suitable for ultra-high purity sputter, assuming that plasma is generated near the null line.

  18. 3D Alfvén wave behaviour about proper and improper magnetic null points

    Science.gov (United States)

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

    2013-10-01

    Context. Magnetohydrodynamic (MHD) waves and magnetic null points are both prevalent in many astrophysical plasmas, including the solar atmosphere. Interaction between waves and null points has been implicated as a possible mechanism for localised heating events. Aims: Here we investigate the transient behaviour of the Alfvén wave about fully 3D proper and improper magnetic null points. Methods: We introduce an Alfvén wave into the vicinity of both proper and improper null points by numerically solving the ideal, β = 0 MHD equations using the LARE3D code. A magnetic fieldline and flux-based coordinate system permits the isolation of resulting wave modes and the analysis of their interaction. Results: We find that the Alfvén wave propagates throughout the region and accumulates near the fan-plane, causing current build up. For different values of null point eccentricity, the qualitative behaviour changes only by the imposition of anisotropic pulse dilation, owing to the differing rates at which fieldlines diverge from the spine. For all eccentricities, we find that the fast and Alfvén waves are linearly decoupled. During the driving phase, an independently propagating fast wave is nonlinearly generated owing to the ponderomotive force. Subsequently, no further excitation of fast waves occurs. Conclusions: We find that the key aspects of the theory of Alfvén waves about 2D null points extends intuitively to the fully 3D case; i.e. the wave propagates along fieldlines and thus accumulates at predictable parts of the topology. We also highlight that unlike in the 2D case, in 3D Alfvén-wave pulses are always toroidal, and thus any aspects of 2D Alfvén-wave-null models that are pulse-geometry specific must be reconsidered in 3D.

  19. Review Article: MHD Wave Propagation Near Coronal Null Points of Magnetic Fields

    Science.gov (United States)

    McLaughlin, J. A.; Hood, A. W.; de Moortel, I.

    2011-07-01

    We present a comprehensive review of MHD wave behaviour in the neighbourhood of coronal null points: locations where the magnetic field, and hence the local Alfvén speed, is zero. The behaviour of all three MHD wave modes, i.e. the Alfvén wave and the fast and slow magnetoacoustic waves, has been investigated in the neighbourhood of 2D, 2.5D and (to a certain extent) 3D magnetic null points, for a variety of assumptions, configurations and geometries. In general, it is found that the fast magnetoacoustic wave behaviour is dictated by the Alfvén-speed profile. In a β=0 plasma, the fast wave is focused towards the null point by a refraction effect and all the wave energy, and thus current density, accumulates close to the null point. Thus, null points will be locations for preferential heating by fast waves. Independently, the Alfvén wave is found to propagate along magnetic fieldlines and is confined to the fieldlines it is generated on. As the wave approaches the null point, it spreads out due to the diverging fieldlines. Eventually, the Alfvén wave accumulates along the separatrices (in 2D) or along the spine or fan-plane (in 3D). Hence, Alfvén wave energy will be preferentially dissipated at these locations. It is clear that the magnetic field plays a fundamental role in the propagation and properties of MHD waves in the neighbourhood of coronal null points. This topic is a fundamental plasma process and results so far have also lead to critical insights into reconnection, mode-coupling, quasi-periodic pulsations and phase-mixing.

  20. Magnetohydrodynamics dynamical relaxation of coronal magnetic fields. III. 3D spiral nulls

    Science.gov (United States)

    Fuentes-Fernández, J.; Parnell, C. E.

    2012-08-01

    Context. The majority of studies on stressed 3D magnetic null points consider magnetic reconnection driven by an external perturbation, but the formation of a genuine current sheet equilibrium remains poorly understood. This problem has been considered more extensively in two dimensions, but lacks a generalization into 3D fields. Aims: 3D magnetic nulls are more complex than 2D nulls and the field can take a greater range of magnetic geometries local to the null. Here, we focus on one type and consider the dynamical non-resistive relaxation of 3D spiral nulls with initial spine-aligned current. We aim to provide a valid magnetohydrostatic equilibrium, and describe the electric current accumulations in various cases, involving a finite plasma pressure. Methods: A full MHD code was used, with the resistivity set to zero so that reconnection is not allowed, to run a series of experiments in which a perturbed spiral 3D null point was allowed to relax towards an equilibrium via real, viscous damping forces. Changes to the initial plasma pressure and other magnetic parameters were systematically investigated. Results: For the axisymmetric case, the evolution of the field and the plasma is such that it concentrates the current density into two cone-shaped regions along the spine, thus concentrating the twist of the magnetic field around the spine, leaving a radial configuration in the fan plane. The plasma pressure redistributes to maintain the current density accumulations. However, it is found that changes in the initial plasma pressure do not significantly modify the final state. In the cases where the initial magnetic field is not axisymmetric, an infinite-time singularity of current perpendicular to the fan is found at the location of the null.

  1. A Toxoplasma MORN1 null mutant undergoes repeated divisions but is defective in basal assembly, apicoplast division and cytokinesis.

    Directory of Open Access Journals (Sweden)

    Alexander Lorestani

    Full Text Available The membrane occupation and recognition nexus protein 1 (MORN1 is highly conserved among apicomplexan parasites and is associated with several structures that have a role in cell division. Here we dissected the role of MORN1 using the relatively simple budding process of Toxoplasma gondii as a model. Ablation of MORN1 in a conditional null mutant resulted in pronounced defects suggesting a central role for MORN1 in apicoplast segregation and in daughter cell budding. Lack of MORN1 resulted in double-headed parasites. These Janus-headed parasites form two complete apical complexes but fail to assemble a basal complex. Moreover, these parasites were capable of undergoing several more budding rounds resulting in the formation of up to 16-headed parasites conjoined at the basal end. Despite this segregation defect, the mother's cytoskeleton was completely disassembled in every budding round. Overall this argues that successful completion of the budding is not required for cell cycle progression. None of the known basal complex components, including a set of recently identified inner membrane complex (IMC proteins, localized correctly in these multi-headed parasites. These data suggest that MORN1 is essential for assembly of the basal complex, and that lack of the basal complex abolishes the contractile capacity assigned to the basal complex late in daughter formation. Consistent with this hypothesis we observe that MORN1 mutants fail to efficiently constrict and divide the apicoplast. We used the null background provided by the mutant to dissect the function of subdomains of the MORN1 protein. This demonstrated that deletion of a single MORN domain already prevented the function of MORN1 whereas a critical role for the short linker between MORN domains 6 and 7 was identified. In conclusion, MORN1 is required for basal complex assembly and loss of MORN1 results in defects in apicoplast division and daughter segregation.

  2. Current Structure and Nonideal Behavior at Magnetic Null Points in the Turbulent Magnetosheath

    Science.gov (United States)

    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.

  3. Susceptibility to hepatocellular carcinoma associated with null genotypes of GSTM1 and GSTT1

    Institute of Scientific and Technical Information of China (English)

    Jian Chao Bian; Fu Min Shen; Li Shen; Tian Ru Wang; Xiao Hong Wang; Gong Chao Chen; Jin Bing Wang

    2000-01-01

    ALM In order to study the association between the null genotypes of GSTM1 and GSTT1 and the genetic susceptibility to hepatocellular carcinoma (HCC). METHODS The genotypes of GSTM1 and GSTT1 of 63 cases of HCC and 88 controls were detected with the multiple PCR technique. RESULTS The frequency of GSTM1 null genotype was 57.1% among the cases, and 42.0% among the controls, the difference being statistically significant (x2 = 3.35, P = 0.067),but X2 value approaching the significance level.The odds ratio was 1.84 (95% Cl=0.91 - 3.37).The frequency of GSTT1 non-null genotype was 87.3% among the cases and 62.5% among the controls, the difference being statistically significant (X2=11.42, P=0.0007274). The odds ratio was 4.13 (95% Cl = 1.64 - 10.70).According to the cross analysis, the GSTT1 nonnull genotype was more closely associated with HCC than GSTM1 null genotype, and these two factors play an approximate addlitive interaction in the occurrence of HCC. CONCLUSION The persons with GSTM1 nullgenotype and GSTT1 non-null genotype have the increased risk to HCC.

  4. Vacuum Nuller Testbed (VNT) Performance, Characterization and Null Control: Progress Report

    Science.gov (United States)

    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.

  5. Time asymmetric spacetimes near null and spatial infinity: I. Expansions of developments of conformally flat data

    Science.gov (United States)

    Valiente Kroon, Juan Antonio

    2004-12-01

    The conformal Einstein equations and the representation of spatial infinity as a cylinder introduced by Friedrich are used to analyse the behaviour of the gravitational field near null and spatial infinity for the development of data which are asymptotically Euclidean, conformally flat and time asymmetric. Our analysis allows for initial data whose second fundamental form is more general than the one given by the standard Bowen York ansatz. The conformal Einstein equations imply, upon evaluation on the cylinder at spatial infinity, a hierarchy of transport equations which can be used to calculate asymptotic expansions for the gravitational field in a recursive way. It is found that the solutions to these transport equations develop logarithmic divergences at the critical sets where null infinity meets spatial infinity. Associated with these, there is a series of quantities expressible in terms of the initial data (obstructions), which if zero, preclude the appearance of some of the logarithmic divergences. The obstructions are, in general, time asymmetric. That is, the obstructions at the intersection of future null infinity with spatial infinity are in general different from those obtained at the intersection of past null infinity with spatial infinity. The latter allows for the possibility of having spacetimes where future and past null infinity have different degrees of smoothness. Finally, it is shown that if both sets of obstructions vanish up to a certain order, then the initial data have to be asymptotically Schwarzschildean in a certain sense.

  6. Spacetime characterizations of Λ-vacuum metrics with a null Killing 2-form

    Science.gov (United States)

    Mars, Marc; Senovilla, José M. M.

    2016-10-01

    An exhaustive list of four-dimensional Λ-vacuum spacetimes admitting a Killing vector ξ whose self-dual Killing two-form {{ F }}μ ν is null is obtained assuming that the self-dual Weyl tensor is proportional to the tensor product of {{ F }}μ ν by itself. Our analysis complements previous results (Mars 1999 Class Quantum Grav. 16 2507-23 Mars and Senovilla 2015 Ann. H. Poincaré 16 1509-50) concerning the case with non-null {{ F }}μ ν . We analyze both cases with Λ vanishing or not. In the latter case we prove that {{Λ }}\\lt 0 must hold necessarily, and we find a characterization of the Einstein spacetimes conformal to pp-waves. In the former case we obtain spacetime characterizations of vacuum plane waves and of the stationary vacuum Brinkmann spacetimes. At the light of the full set of results, old and new, we reformulate the case with non-null {{ F }}μ ν and {{Λ }}=0. We finally present a table collecting the results for both null, and non-null, {{ F }}μ ν .

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

    Science.gov (United States)

    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.

  8. Mid-infrared laser light nulling experiment using single-mode conductive waveguides

    CERN Document Server

    Labadie, L; Maurand, R; Labeye, P; Kern, P; Arezki, B; Broquin, J -E

    2007-01-01

    Aims: In the context of space interferometry missions devoted to the search of exo-Earths, this paper investigates the capabilities of new single mode conductive waveguides at providing modal filtering in an infrared and monochromatic nulling experiment; Methods: A Michelson laser interferometer with a co-axial beam combination scheme at 10.6 microns is used. After introducing a Pi phase shift using a translating mirror, dynamic and static measurements of the nulling ratio are performed in the two cases where modal filtering is implemented and suppressed. No additional active control of the wavefront errors is involved. Results: We achieve on average a statistical nulling ratio of 2.5e-4 with a 1-sigma upper limit of 6e-4, while a best null of 5.6e-5 is obtained in static mode. At the moment, the impact of external vibrations limits our ability to maintain the null to 10 to 20 seconds.; Conclusions: A positive effect of SM conductive waveguide on modal filtering has been observed in this study. Further improv...

  9. Current structure and nonideal behavior at magnetic null points in the turbulent magnetosheath

    Science.gov (United States)

    Wendel, D. E.; Adrian, M. L.

    2013-04-01

    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.

  10. Steady state reconnection at a single 3D magnetic null point

    Science.gov (United States)

    Galsgaard, K.; Pontin, D. I.

    2011-05-01

    Aims: We systematically stress a rotationally symmetric 3D magnetic null point by advecting the opposite footpoints of the spine axis in opposite directions. This stress eventually concentrates in the vicinity of the null point, thereby forming a local current sheet through which magnetic reconnection takes place. The aim is to look for a steady state evolution of the current sheet dynamics, which may provide scaling relations for various characteristic parameters of the system. Methods: The evolution is followed by solving numerically the non-ideal MHD equations in a Cartesian domain. The null point is embedded in an initially constant density and temperature plasma. Results: It is shown that a quasi-steady reconnection process can be set up at a 3D null by continuous shear driving. It appears that a true steady state is unlikely to be realised because the current layer tends to grow until it is restricted by the geometry of the computational domain and the imposed driving profile. However, ratios between characteristic quantities clearly settle after some time to stable values, so that the evolution is quasi-steady. The experiments show a number of scaling relations, but they do not provide a clear consensus for extending to lower magnetic resistivity or faster driving velocities. More investigations are needed to fully clarify the properties of current sheets at magnetic null points.

  11. Current amplification and magnetic reconnection at a 3D null point. I - Physical characteristics

    CERN Document Server

    Pontin, D I

    2007-01-01

    The behaviour of magnetic perturbations of an initially potential three-dimensional equilibrium magnetic null point are investigated. The basic components which constitute a typical disturbance are taken to be rotations and shears, in line with previous work. The spine and fan of the null point (the field lines which asymptotically approach or recede from the null) are subjected to such rotational and shear perturbations, using three-dimensional magnetohydrodynamic simulations. It is found that rotations of the fan plane and about the spine lead to current sheets which are spatially diffuse in at least one direction, and form in the locations of the spine and fan. However, shearing perturbations lead to 3D-localised current sheets focused at the null point itself. In addition, rotations are associated with a growth of current parallel to the spine, driving rotational flows and a type of rotational reconnection. Shears, on the other hand, cause a current through the null which is parallel to the fan plane, and...

  12. Influence of frame-dragging on magnetic null points near rotating black holes

    Science.gov (United States)

    Karas, V.; Kopáček, O.; Kunneriath, D.

    2012-02-01

    Understanding the mechanisms of particle acceleration from the vicinity of black holes poses a challenge. Electromagnetic effects are thought to be a prime suspect, but details still need an explanation. To this end, we study a three-dimensional structure of oblique magnetic fields near a rotating black hole in vacuum. It has been proposed that such a setup can lead to efficient acceleration when plasma is injected near a magnetic null point. We focus our attention especially on the magnetic field in the immediate neighborhood of the magnetic null point, which was previously shown to occur in the equatorial plane. By employing the line integral convolution method, we visualize the magnetic field lines and explore the electric lines rising out of the equatorial plane. We show the magnetic field structure near the boundary of ergosphere, depending on the spin of the black hole. Electric field develops a non-vanishing component passing through the magnetic null point and ensuring efficient acceleration of charged particles from this particular location near the horizon. We also examine the effect of translatory boost on the field lines. Similarly to the frame-dragging by rotation, the linear motion carries field lines along with the black hole. The position of the magnetic null point recedes from the black hole horizon as the spin parameter increases. For the extreme value of a = 1, the null point can occur outside the ergosphere.

  13. Current Singularities at Quasi-separatrix Layers and Three-dimensional Magnetic Nulls

    Science.gov (United States)

    Craig, I. J. D.; Effenberger, Frederic

    2014-11-01

    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.

  14. 3D Alfven wave behaviour around proper and improper magnetic null points

    CERN Document Server

    Thurgood, J O

    2013-01-01

    Context: MHD waves and magnetic null points are both prevalent in many astrophysical plasmas, including the solar atmosphere. Interaction between waves and null points has been implicated as a possible mechanism for localised heating events. Aims: Here we investigate the transient behaviour of the Alfven wave about fully 3D proper and improper 3D magnetic null points. Previously, the behaviour of fast magnetoacoustic waves at null points in 3D, cold MHD was considered by Thurgood & McLaughlin (Astronomy & Astrophysics, 2012, 545, A9). Methods: We introduce an Alfven wave into the vicinity of both proper and improper null points by numerically solving the ideal, $\\beta=0$ MHD equations using the LARE3D code. A magnetic fieldline and flux-based coordinate system permits the isolation of resulting wave-modes and the analysis of their interaction. Results: We find that the Alfven wave propagates throughout the region and accumulates near the fan-plane, causing current build up. For different values of nul...

  15. The double-null map - equilibrium, safety factor on magnetic axis, and perturbation from map parameter

    Science.gov (United States)

    Barnes, Daniel; Braxton-Gravin, Asiha; Jenkins, Jade; Ali, Halima; Punjabi, Alkesh

    2013-10-01

    The double-null map is the simplest symplectic map that has the generic magnetic topology of double-null divertor tokamaks. The generating function of the double-null map is given by S (x , y) = x2 /2 +y2 /2-y4/4. The equilibrium magnetic surfaces of the double-null map are calculated from the generating function. 0 1/4 gives open surfaces. The scaling of safety factor on the magnetic axis, q0, with map parameter k is calculated. The scaling of root mean square deviation of energy on the q95 surface with map parameter k is calculated and taken as the estimate of magnetic asymmetry to represent the magnetic perturbation. The results of this work will be reported. These results are used to calculate heteroclinic tangles of the separatrix of double-null map. This work is supported by grants DE-FG02-01ER54624, DE-FG02-04ER54793, and DE-FG02-07ER54937.

  16. Feasibility of a self-nulling beam combiner using no external phase inverter

    Science.gov (United States)

    Bloemhof, E. E.

    2005-08-01

    Space-based nulling interferometers will play a major role in the search for exoplanets, as both NASA and ESA plan missions for the near future. Current architectures produce the requisite broadband π phase shift in one arm of each nulling telescope pair by means of a system of "field flip" optics that may involve one of a number of sophisticated technologies (periscope, phase plates, through-focus, or other). The two beams, of equal intensity but conjugate phase, are then combined, perhaps in a modified Mach-Zehnder (MMZ) or similar beam combiner of high configurational symmetry. A novel approach has recently been proposed, however, in which the achromatic π phase shift is supplied by two applications of the innate π/2 phase shift between transmitted and reflected beams in a beam splitter. This simply requires using the traditionally bright output port of the MMZ as a nulled port; adaptive nulling can be used to ease the tolerances on matching the moduli of reflection and transmission coefficients. The rather substantial systems benefit that accrues is that the external phase shifting ("field flipping") optics may be entirely eliminated. Here, I discuss the feasibility of this "self-nulling" beam combiner scheme.

  17. On Bäcklund transformation and vortex filament equation for pseudo null curves in Minkowski 3-space

    Science.gov (United States)

    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. On geometry of congruences of null strings in 4-dimensional complex and real pseudo-Riemannian spaces

    CERN Document Server

    Chudecki, Adam

    2016-01-01

    4-dimensional spaces equipped with 2-dimensional (complex holomorphic or real smooth) completely integrable distributions are considered. The integral manifolds of such distributions are totally null and totally geodesics 2-dimensional surfaces which are called the null strings. Properties of congruences (foliations) of such 2-surfaces are studied. Relation between properties of congruences of null strings and Petrov-Penrose type of SD Weyl spinor and algebraic types of traceless Ricci tensor is analyzed.

  19. Üheksa nulli : null null null null null null null... / Anthony de Kowalsky

    Index Scriptorium Estoniae

    Kowalsky, Anthony de

    2008-01-01

    Lühiarvustus 18.- 20. 07. Põlvamaal Intsikurmu laululaval etendunud vabaõhulavastusele "Üheksa nulliga Eesti". Stsenaariumi on kirjutanud Kadri Pettai, Aapo Ilves, Olavi Ruitlane ja Veiko Märka. Lavastanud Reeda Toots

  20. Anti-optic-null medium: Achieving the optic-null medium effect by enclosing an air region with relatively low-anisotropy media

    Science.gov (United States)

    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.

  1. Shear Nulling after PSF Gaussianisation: moment-based weak lensing measurements with subpercent noise bias

    CERN Document Server

    Herbonnet, Ricardo; Kuijken, Konrad

    2016-01-01

    Current optical imaging surveys for cosmology are covering large areas of sky. To exploit the statistical power of these surveys for weak lensing measurements requires shape measurement methods with subpercent systematic errors. We introduce a new weak lensing shear measurement algorithm, Shear Nulling after PSF Gaussianisation (SNAPG), designed to avoid the noise biases that affect most other methods. SNAPG operates on images that have been convolved with a kernel that renders the Point Spread Function (PSF) a circular Gaussian, and uses weighted second moments of the sources. The response of such second moments to a shear of the pre-seeing galaxy image can be predicted analytically, allowing us to construct a shear nulling scheme that finds the shear parameters for which the observed galaxies are consistent with an unsheared, isotropically oriented population of sources. The inverse of this nulling shear is then an estimate of the gravitational lensing shear. We identify the uncertainty of the estimated cen...

  2. Maxwell, Yang-Mills, Weyl and eikonal fields defined by any null shear-free congruence

    Science.gov (United States)

    Kassandrov, Vladimir V.; Rizcallah, Joseph A.

    We show that (specifically scaled) equations of shear-free null geodesic congruences on the Minkowski space-time possess intrinsic self-dual, restricted gauge and algebraic structures. The complex eikonal, Weyl 2-spinor, SL(2, ℂ) Yang-Mills and complex Maxwell fields, the latter produced by integer-valued electric charges (“elementary” for the Kerr-like congruences), can all be explicitly associated with any shear-free null geodesic congruence. Using twistor variables, we derive the general solution of the equations of the shear-free null geodesic congruence (as a modification of the Kerr theorem) and analyze the corresponding “particle-like” field distributions, with bounded singularities of the associated physical fields. These can be obtained in a straightforward algebraic way and exhibit nontrivial collective dynamics simulating physical interactions.

  3. A New Method of Identifying 3D Null Points in Solar Vector Magnetic Fields

    Institute of Scientific and Technical Information of China (English)

    Hui Zhao; Jing-Xiu Wang; Jun Zhang; Chi-Jie Xiao

    2005-01-01

    Employing the Poincaré index of isolated null-points in a vector field,we worked out a mathematical method of searching for 3D null-points in coronal magnetic fields. After introducing the relevant differential topology, we test the method by using the analytical model of Brown & Priest. The location of nullpoint identified by our method coincides precisely with the analytical solution.Finally we apply the method to the 3D coronal magnetic fields reconstructed from an observed MDI magnetogram of a super-active region (NOAA 10488). We find that the 3D null-point seems to be a key element in the magnetic topology associated with flare occurrence.

  4. Null reconstruction of orthogonal circular polarization hologram with large recording angle.

    Science.gov (United States)

    Wu, An'an; Kang, Guoguo; Zang, Jinliang; Liu, Ying; Tan, Xiaodi; Shimura, Tsutomu; Kuroda, Kazuo

    2015-04-01

    We report on the null reconstruction of polarization volume hologram recorded by orthogonal circularly polarized waves with a large cross angle. Based on the recently developed tensor theory for polarization holography, the disappearance of the reconstruction was analytically verified, where a nice agreement was found between the experimental and theoretical results. When the polarization and intensity hologram attain a balance, not only the null reconstruction but also the faithful reconstruction can be realized by the illumination of the orthogonal reference wave and original reference wave. As a consequence of the hologram recorded without paraxial approximation, the null reconstruction may lead to important applications, such as a potential enhancement in optical storage capacity for volume holograms.

  5. Investigation of the extraordinary null reconstruction phenomenon in polarization volume hologram.

    Science.gov (United States)

    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.

  6. Phase Retrieval with One or Two Diffraction Patterns by Alternating Projections of the Null Vector

    CERN Document Server

    Chen, Pengwen; Liu, Gi-Ren

    2015-01-01

    Two versions of alternating projection (AP), the parallel alternating projection (PAP) and the serial alternating projection (SAP), are proposed to solve phase retrieval with at most two coded diffraction patterns. The proofs of geometric convergence are given with sharp bounds on the rates of convergence in terms of a spectral gap condition. To compensate for the local nature of convergence, the null vector method is proposed for initialization and proved to produce asymptotically accurate initialization for the Gaussian case. Extensive numerical experiments are performed to show that the null vector method produces more accurate initialization than the spectral vector method and that PAP/SAP converge faster to more accurate solutions than other iterative schemes for non-convex optimization such as the Wirtinger flow. Moreover, SAP converges still faster than PAP. In practice AP and the null vector method together produce globally convergent iterates to the true object.

  7. Quasi-local mass at the null infinity of the Vaidya spacetime

    CERN Document Server

    Chen, Po-Ning; Yau, Shing-Tung

    2016-01-01

    There are two important statements regarding the Trautman-Bondi mass [1,8,5] at null infinity: one is the positivity [7,6], and the other is the Bondi mass loss formula [1], which are both global in nature. The positivity of the quasi-local mass can potentially lead to a local description at null infinity. This is confirmed for the Vaidya spacetime in this note. We study the Wang-Yau quasi-local mass on surfaces of fixed size at the null infinity of the Vaidya spacetime. The optimal embedding equation is solved explicitly and the quasi-local mass is evaluated in terms of the mass aspect function of the Vaidya spacetime.

  8. Probing the X-ray emission of old nulling pulsars with high magnetic fields

    Science.gov (United States)

    Posselt, Bettina

    2013-10-01

    We propose XMM-Newton observations of two nulling radio pulsars with magnetic fields B>10^(13)G. These long-period pulsars have spin-down properties, including characteristic ages, similar to those of the Magnificent Seven which are bright thermal X-ray emitters. Nulling pulsars have been suggested as evolutionary stage where the magnetospheric emission of a pulsar ceases. In contrast, no magnetospheric emission was detected at all at X-ray or radio wavelengths for the Magnificent Seven. The proposed XMM-Newton observations will probe the magneto-thermal NS evolution model as a potential link between the radio pulsar population and the Magnificent Seven. They will also provide for the first time an X-ray characterization of nulling pulsars with large magnetic fields.

  9. Development of electric currents in a magnetic field configuration containing a magnetic null point

    Science.gov (United States)

    Santos, J. C.; Büchner, J.; Otto, A.

    2011-01-01

    Context. In the past the role of magnetic null points in the generation of electric currents was investigated mainly in the close vicinity of the null, with perturbations being applied at nearby boundaries, or for a magnetic null configuration with a dome-shaped fan. In the solar atmosphere, however, electric currents are generated by perturbations originating at the photosphere, far away from coronal 3D nulls, and the occurence of magnetic nulls with a dome-shaped fan is apparently not common. Aims: We investigate the consequences of photospheric motion for the development of electric currents in a coronal magnetic field configuration containing a null, located far away from the boundaries, and the influence of topological structures on the spatial distribution of the currents. Methods: We use a 3D resistive MHD code to investigate the consequences of photospheric plasma motion for the generation of currents in a coronal magnetic field containing a null. The plasma is considered fully compressible and is initially in hydrostatic equilibrium. The initial magnetic field is potential (current free). Results: The photospheric plasma motion causes magnetic field perturbations that propagate to the corona along the field lines at the local Alfvén speed. The Alfvénic wave perturbations correspond to a propagating current directed mainly parallel to the magnetic field. Perpendicular currents connect to return currents to close the current system. The magnetic perturbations eventually reach the vicinity of the null. However, the currents forming in and around the null, near the fan surface or near the spine field lines, are not always the strongest currents developing in the simulation box. In our simulation, the strongest currents develop close to the bottom boundary, where the plasma is moved, and below the null point, in a region where field line connectivity considerably changes. Conclusions: Our simulation shows that the presence of a magnetic null point does not

  10. Magnetic reconnection and tearing in a 3D current sheet about a solar coronal null

    Science.gov (United States)

    Pontin, David; Wyper, Peter

    2014-06-01

    Three-dimensional magnetic null points are ubiquitous in the solar corona and in any generic mixed-polarity magnetic field. We discuss the nature of flux transfer during reconnection an isolated coronal null point, that occurs across the fan plane when a current sheet forms about the null. We then go on to discuss the breakup of the current sheet via a non-linear tearing-type instability and show that the instability threshold corresponds to a Lundquist number comparable to the 2D case. We also discuss the resulting topology of the magnetic field, which involves a layer in which open and closed magnetic fields are effectively mixed, with implications for particle transport.

  11. Observation of the lower hybrid waves near the three-dimensional null pair

    Institute of Scientific and Technical Information of China (English)

    ZHOU Meng; DENG XiaoHua; FU Song; TANG RongXin; HU YunHui; LI ShiYou; A. VAIVADS; M. ANDRE; LIN Xi; LIN MingHui; ZHOU XiaoMin

    2009-01-01

    Magnetic reconnection is a fundamental process in plasma, which is thought to play important roles both in laboratory and natural plasmas through affecting magnetic topology, heating and accelerating particles. During an event on Oct. 1st, 2001, the Cluster tetrahedron circled around the magnetic re-connection region several times, and Xiao et al. First identified the null pair and found that the spectrum of the null-point oscillation shows the maximum power near the lower-hybrid frequency. In this paper we report the observation of electromagnetic and electrostatic wave enhancements near lower hybrid frequency associated with the reconnection process near the null pair. The lower hybrid waves (LHWs) with quasi-perpendicular propagation were identified and also confirmed by the power law of the spectrum of electric and magnetic fields.

  12. Dichotomies of the set of test measures of a Haar-null set

    CERN Document Server

    Dodos, Pandelis

    2010-01-01

    We prove that if $X$ is a Polish space and $F$ is a face of $P(X)$ with the Baire property, then $F$ is either a meager or a co-meager subset of $P(X)$. As a consequence we show that for every abelian Polish group $X$ and every analytic Haar-null set $A\\subseteq X$, the set of test measures $T(A)$ of $A$ is either meager or co-meager. We characterize the non-locally-compact groups as the ones for which there exists a closed Haar-null set $F\\subseteq X$ with $T(F)$ is meager. Moreover, we answer negatively a question of J. Mycielski by showing that for every non-locally-compact abelian Polish group and every $\\sigma$-compact subgroup $G$ of $X$ there exists a $G$-invariant $F_\\sigma$ subset of $X$ which is neither prevalent nor Haar-null.

  13. Kinematic reconnection at a magnetic null point: spine-aligned current

    Science.gov (United States)

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

    2004-05-01

    Magnetic reconnection at a three-dimensional null point is the natural extension of the familiar two-dimensional X-point reconnection. A model is set up here for reconnection at a spiral null point, by solving the kinematic, steady, resistive magnetohydrodynamic equations in its vicinity. A steady magnetic field is assumed, as well as the existence of a localised diffusion region surrounding the null point. Outside the diffusion region the plasma and magnetic field move ideally. Particular attention is focussed on the way that the magnetic flux changes its connections as a result of the reconnection. The resultant plasma flows are found to be rotational in nature, as is the change in connections of the magnetic field lines.

  14. Observation of the lower hybrid waves near the three-dimensional null pair

    Institute of Scientific and Technical Information of China (English)

    A.; VAIVADS; M.; ANDRE

    2009-01-01

    Magnetic reconnection is a fundamental process in plasma,which is thought to play important roles both in laboratory and natural plasmas through affecting magnetic topology,heating and accelerating particles. During an event on Oct. 1st,2001,the Cluster tetrahedron circled around the magnetic reconnection region several times,and Xiao et al. first identified the null pair and found that the spectrum of the null-point oscillation shows the maximum power near the lower-hybrid frequency. In this paper we report the observation of electromagnetic and electrostatic wave enhancements near lower hybrid frequency associated with the reconnection process near the null pair. The lower hybrid waves(LHWs) with quasi-perpendicular propagation were identified and also confirmed by the power law of the spectrum of electric and magnetic fields.

  15. High performance testbed for four-beam infrared interferometric nulling and exoplanet detection.

    Science.gov (United States)

    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.

  16. Null subjects: a problem for parameter-setting models of language acquisition.

    Science.gov (United States)

    Valian, V

    1990-05-01

    Some languages, like English, require overt surface subjects, while others, like Italian and Spanish, allow "null" subjects. How does the young child determine whether or not her language allows null subjects? Modern parameter-setting theory has proposed a solution, in which the child begins acquisition with the null subject parameter set for either the English-like value or the Italian-like value. Incoming data, or the absence thereof, force a resetting of the parameter if the original value was incorrect. This paper argues that the single-value solution cannot work, no matter which value is chosen as the initial one, because of inherent limitations in the child's parser, and because of the presence of misleading input. An alternative dual-value solution is proposed, in which the child begins acquisition with both values available, and uses theory-confirmation procedures to decide which value is best supported by the available data.

  17. Angular momentum in general relativity: The definition at null infinity includes the spatial definition as a special case

    OpenAIRE

    Rizzi, Anthony

    2001-01-01

    I show that the definition of angular momentum at null infinity given by A. Rizzi, Phys. Rev. Lett. 81, 1150 (1998), reduces to the Arnowitt-Deser-Misner definition at spatial infinity in the appropriate limit. This identification reinforces the gauge condition of the null definition as well as the null definition itself. Insight into the place of the null and spatial definitions is also gained. The methods used in this paper are very useful for understanding far-field problems in general rel...

  18. Magnetic reconnection at 3D null points: effect of magnetic field asymmetry

    Science.gov (United States)

    Al-Hachami, A. K.; Pontin, D. I.

    2010-03-01

    Context. The magnetic field in many astrophysical plasmas, for example in the solar corona, is known to have a highly complex - and clearly three-dimensional - structure. Turbulent plasma motions in high-β regions where field lines are anchored, such as the solar interior, can store large amounts of energy in the magnetic field. This energy can only be released when magnetic reconnection occurs. Reconnection may only occur in locations where huge gradients of the magnetic field develop, and one candidate for such locations are magnetic null points, known to be abundant for example in the solar atmosphere. Reconnection leads to changes in the topology of the magnetic field, and energy being released as heat, kinetic energy and acceleration of particles. Thus reconnection is responsible for many dynamic processes, for instance flares and jets. Aims: The aim of this paper is to investigate the properties of magnetic reconnection at a 3D null point, with respect to their dependence on the symmetry of the magnetic field around the null. In particular we examine the rate of reconnection of magnetic flux at the null point, as well as how the current sheet forms and its properties. Methods: We use mathematical modelling and finite difference resistive MHD simulations. Results: It is found that the basic structure of the mode of magnetic reconnection considered is unaffected by varying the magnetic field symmetry, that is, the plasma flow is found to cross both the spine and fan of the null. However, the peak intensity and dimensions of the current sheet are dependent on the symmetry/asymmetry of the field lines. As a result, the reconnection rate is also found to be strongly dependent on the field asymmetry. Conclusions: The symmetry/asymmetry of the magnetic field in the vicinity of a magnetic null can have a profound effect on the geometry of any associated reconnection region, and the rate at which the reconnection process proceeds.

  19. Distorted Patterns of Dentinogenesis and Eruption in Msx2 Null Mutants: Involvement of Sost/Sclerostin.

    Science.gov (United States)

    Amri, Nawel; Djolé, Stéphane X; Petit, Stéphane; Babajko, Sylvie; Coudert, Amélie E; Castaneda, Beatriz; Simon, Stéphane; Berdal, Ariane

    2016-10-01

    The muscle segment homeogenes Msx1 and Msx2 play a major role in tooth and bone formation. Periodontal osteoclast impairment also occurs in Msx2 null mutant mice, which is restored by overexpression of the receptor activator of NF-κB targeted in osteoclast lineage. Here, we investigated the role of Msx2 in dentinogenesis. Experiments were performed on Msx2(-/-) mice and the MDPC-23 odontoblastic cell line. After Msx2 gene silencing, real-time quantitative RT-PCR data showed significant overexpression of Runx2, Bglap, Dspp, and Alpl. Of three inhibitors of Wnt/β-catenin signaling (Dkk1, SostDc1, and Sost/Sclerostin), only Sost was expressed in postnatal teeth and overexpressed in Msx2(-/-) tooth samples. Initial crown dentin formation-primary dentinogenesis-occurred fairly normally in Msx2(-/-) teeth, albeit with distorted cusp patterns. Later stages of tooth development were characterized by a deviation from secondary toward tertiary dentinogenesis with osteodentin formation and impaired dentin deposition leading to limited root elongation. In Msx2(-/-)/receptor activator of NF-κB-transgenic double mutants, the dentin phenotype, notably in the roots, was rescued and sclerostin levels were normalized. These data suggest that Msx2 may act indirectly on dentinogenesis by controlling osteoclast activity and the signaling network related to eruption, supporting and further extending the concept that Msx2 controls formation of mineralized tissues by inhibition of the Wnt/β-catenin pathway; Sost in dentin and Dkk1 in bone, as previously demonstrated.

  20. Einstein equations in the null quasi-spherical gauge; 3, numerical algorithms

    CERN Document Server

    Bartnik, R A; Bartnik, Robert A.; Norton, Andrew H.

    1999-01-01

    We describe numerical techniques used in the construction of our 4th order evolution for the full Einstein equations, and assess the accuracy of representative solutions. The code is based on a null gauge with a quasi-spherical radial coordinate, and simulates the interaction of a single black hole with gravitational radiation. Techniques used include spherical harmonic representations, convolution spline interpolation and filtering, and an RK4 "method of lines" evolution. For sample initial data of "intermediate" size (gravitational field with 19% of the black hole mass), the code is accurate to 1 part in 10^5, until null time z=55 when the coordinate condition breaks down.