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Sample records for neuronal rictor null

  1. Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.

    Science.gov (United States)

    Kaska, Sophia; Brunk, Rebecca; Bali, Vedrana; Kechner, Megan; Mazei-Robison, Michelle S

    2017-05-01

    While the etiology of depression is not fully understood, increasing evidence from animal models suggests a role for the ventral tegmental area (VTA) in pathogenesis. In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of depression. Utilizing genetic and viral knockout of Rictor (rapamycin-insensitive companion of target of rapamycin), a requisite component of TORC2, we demonstrate that decreasing Rictor-dependent TORC2 signaling in catecholaminergic neurons, or within the VTA specifically, does not alter susceptibility to CSDS. Opiate abuse and mood disorders are often comorbid, and previous data demonstrate a role for VTA TORC2 in mediating opiate reward. Thus, we also investigated its potential role in mediating changes in opiate reward following CSDS. Catecholaminergic deletion of Rictor increases water, sucrose, and morphine intake but not preference in a two-bottle choice assay in stress-naïve mice, and these effects are maintained after stress. VTA-specific knockout of Rictor increases water and sucrose intake after physical CSDS, but does not alter consummatory behavior in the absence of stress. These findings suggest a novel role for TORC2 in mediating stress-induced changes in consummatory behaviors that may contribute to some aspects of mood disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Rictor forms a complex with Cullin-1 to promote SGK1 ubiquitination and destruction

    Science.gov (United States)

    Gao, Daming; Wan, Lixin; Inuzuka, Hiroyuki; Berg, Anders H.; Tseng, Alan; Zhai, Bo; Shaik, Shavali; Bennett, Eric; Tron, Adriana E.; Gasser, Jessica A.; Lau, Alan; Gygi, Steven; Harper, J. Wade; DeCaprio, James A.; Toker, Alex; Wei, Wenyi

    2010-01-01

    Summary The Rictor/mTOR complex (also known as mTORC2) plays a critical role in cellular homeostasis by phosphorylating AGC kinases such as Akt and SGK at their hydrophobic motifs to activate downstream signaling. However, the regulation of mTORC2 and whether it has additional function(s), remains largely unknown. Here we report that Rictor associates with Cullin-1 to form a functional E3 ubiquitin ligase. Rictor, but not Raptor or mTOR alone promotes SGK1 ubiquitination. Loss of Rictor/Cullin-1-mediated ubiquitination leads to increased SGK1 protein levels as detected in Rictor null cells. Moreover, as part of a feedback mechanism, phosphorylation of Rictor at T1135 by multiple AGC kinases disrupts the interaction between Rictor and Cullin-1 to impair SGK1 ubiquitination. These findings indicate that the Rictor/Cullin-1 E3 ligase activity is regulated by a specific signal relay cascade and that misregulation of this mechanism may contribute to the frequent overexpression of SGK1 in various human cancers. PMID:20832730

  3. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

    OpenAIRE

    Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

    2014-01-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing...

  4. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

    Science.gov (United States)

    Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

    2014-01-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis. PMID:24944899

  5. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.

    Science.gov (United States)

    Kocalis, Heidi E; Hagan, Scott L; George, Leena; Turney, Maxine K; Siuta, Michael A; Laryea, Gloria N; Morris, Lindsey C; Muglia, Louis J; Printz, Richard L; Stanwood, Gregg D; Niswender, Kevin D

    2014-07-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.

  6. Nav 1.8-null mice show stimulus-dependent deficits in spinal neuronal activity

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    Wood John N

    2006-02-01

    Full Text Available Abstract Background The voltage gated sodium channel Nav 1.8 has a highly restricted expression pattern to predominantly nociceptive peripheral sensory neurones. Behaviourally Nav 1.8-null mice show an increased acute pain threshold to noxious mechanical pressure and also deficits in inflammatory and visceral, but not neuropathic pain. Here we have made in vivo electrophysiology recordings of dorsal horn neurones in intact anaesthetised Nav 1.8-null mice, in response to a wide range of stimuli to further the understanding of the functional roles of Nav 1.8 in pain transmission from the periphery to the spinal cord. Results Nav 1.8-null mice showed marked deficits in the coding by dorsal horn neurones to mechanical, but not thermal, -evoked responses over the non-noxious and noxious range compared to littermate controls. Additionally, responses evoked to other stimulus modalities were also significantly reduced in Nav 1.8-null mice where the reduction observed to pinch > brush. The occurrence of ongoing spontaneous neuronal activity was significantly less in mice lacking Nav 1.8 compared to control. No difference was observed between groups in the evoked activity to electrical activity of the peripheral receptive field. Conclusion This study demonstrates that deletion of the sodium channel Nav 1.8 results in stimulus-dependent deficits in the dorsal horn neuronal coding to mechanical, but not thermal stimuli applied to the neuronal peripheral receptive field. This implies that Nav 1.8 is either responsible for, or associated with proteins involved in mechanosensation.

  7. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

    KAUST Repository

    Jeong, Suh Young; Crooks, Daniel R.; Wilson-Ollivierre, Hayden; Ghosh, Manik C.; Sougrat, Rachid; Lee, Jaekwon; Cooperman, Sharon; Mitchell, James B.; Beaumont, Carole; Rouault, Tracey A.

    2011-01-01

    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  8. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

    KAUST Repository

    Jeong, Suh Young

    2011-10-07

    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  9. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice.

    Directory of Open Access Journals (Sweden)

    Suh Young Jeong

    Full Text Available Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2, which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  10. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Zheng [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Dadao Bei, Guangzhou 510515 (China); Zhou, Yuning [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Evers, B. Mark [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Wang, Qingding, E-mail: qingding.wang@uky.edu [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Rictor associates with FBXW7 to form an E3 complex. Black-Right-Pointing-Pointer Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. Black-Right-Pointing-Pointer Knockdown of rictor increases protein levels of c-Myc and cylin E. Black-Right-Pointing-Pointer Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Black-Right-Pointing-Pointer Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor-FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  11. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    International Nuclear Information System (INIS)

    Guo, Zheng; Zhou, Yuning; Evers, B. Mark; Wang, Qingding

    2012-01-01

    Highlights: ► Rictor associates with FBXW7 to form an E3 complex. ► Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. ► Knockdown of rictor increases protein levels of c-Myc and cylin E. ► Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. ► Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor–FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  12. Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.

    Directory of Open Access Journals (Sweden)

    Lu Huang

    2017-08-01

    Full Text Available As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2 has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO mice to investigate how Rictor regulates BCR signaling. We found that the key positive and negative BCR signaling molecules, phosphorylated Brutons tyrosine kinase (pBtk and phosphorylated SH2-containing inositol phosphatase (pSHIP, are reduced and enhanced, respectively, in Rictor KO B cells. This suggests that Rictor positively regulates the early events of BCR signaling. We found that the cellular filamentous actin (F-actin is drastically increased in Rictor KO B cells after BCR stimulation through dysregulating the dephosphorylation of ezrin. The high actin-ezrin intensity area restricts the lateral movement of BCRs upon stimulation, consequently reducing BCR clustering and BCR signaling. The reduction in the initiation of BCR signaling caused by actin alteration is associated with a decreased humoral immune response in Rictor KO mice. The inhibition of actin polymerization with latrunculin in Rictor KO B cells rescues the defects of BCR signaling and B cell differentiation. Overall, our study provides a new pathway linking cell metablism to BCR activation, in which Rictor regulates BCR signaling via actin reorganization.

  13. Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and kidney fibrosis.

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    Ren, Jiafa; Li, Jianzhong; Feng, Ye; Shu, Bingyan; Gui, Yuan; Wei, Wei; He, Weichun; Yang, Junwei; Dai, Chunsun

    2017-08-01

    Mammalian target of rapamycin (mTOR) signalling controls many essential cellular functions. However, the role of Rictor/mTOR complex 2 (mTORC2) in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction or ischaemia/reperfusion injury. In bone marrow-derived macrophages (BMMs), deletion of Rictor or blockade of protein kinase Cα inhibited cell migration. Additionally, deletion of Rictor or blockade of Akt abolished interleukin-4-stimulated or transforming growth factor (TGF)-β1-stimulated macrophage M2 polarization. Furthermore, deletion of Rictor downregulated TGF-β1-stimulated upregulation of multiple profibrotic cytokines, including platelet-derived growth factor, vascular endothelial growth factor and connective tissue growth factor, in BMMs. Conditioned medium from TGF-β1-pretreated Rictor -/- macrophages stimulated fibroblast activation less efficiently than that from TGF-β1-pretreated Rictor +/+ macrophages. These results demonstrate that Rictor/mTORC2 signalling can promote macrophage activation and kidney fibrosis. Targeting this signalling pathway in macrophages may shine light on ways to protect against kidney fibrosis in patients with chronic kidney diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival.

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    McDonald, Paul C; Oloumi, Arusha; Mills, Julia; Dobreva, Iveta; Maidan, Mykola; Gray, Virginia; Wederell, Elizabeth D; Bally, Marcel B; Foster, Leonard J; Dedhar, Shoukat

    2008-03-15

    An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors revealed rictor as an ILK-binding protein. This finding was interesting because rictor, originally identified as a regulator of cytoskeletal dynamics, is also a component of mammalian target of rapamycin complex 2 (mTORC2), a complex implicated in Akt phosphorylation. These functions overlap with known ILK functions. Coimmunoprecipitation analyses confirmed this interaction, and ILK and rictor colocalized in membrane ruffles and leading edges of cancer cells. Yeast two-hybrid assays showed a direct interaction between the NH(2)- and COOH-terminal domains of rictor and the ILK kinase domain. Depletion of ILK and rictor in breast and prostate cancer cell lines resulted in inhibition of Akt Ser(473) phosphorylation and induction of apoptosis, whereas, in several cell lines, depletion of mTOR increased Akt phosphorylation. Akt and Ser(473)P-Akt were detected in ILK immunoprecipitates and small interfering RNA-mediated depletion of rictor, but not mTOR, inhibited the amount of Ser(473)P-Akt in the ILK complex. Expression of the NH(2)-terminal (1-398 amino acids) rictor domain also resulted in the inhibition of ILK-associated Akt Ser(473) phosphorylation. These data show that rictor regulates the ability of ILK to promote Akt phosphorylation and cancer cell survival.

  15. Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains.

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    Jian-Qiu Wang

    Full Text Available Nijmegen breakage syndrome (NBS is a chromosomal-instability syndrome. The NBS gene product, NBS1 (p95 or nibrin, is a part of the Mre11-Rad50-NBS1 complex. SIN1 is a component of the mTOR/Rictor/SIN1 complex mediating the activation of Akt. Here we show that NBS1 interacted with mTOR, Rictor, and SIN1. The specific domains of mTOR, Rictor, or SIN1 interacted with the internal domain (a.a. 221-402 of NBS1. Sucrose density gradient showed that NBS1 was located in the same fractions as the mTOR/Rictor/SIN1 complex. Knockdown of NBS1 decreased the levels of phosphorylated Akt and its downstream targets. Ionizing radiation (IR increased the NBS1 levels and activated Akt activity. These results demonstrate that NBS1 interacts with the mTOR/Rictor/SIN1 complex through the a.a. 221-402 domain and contributes to the activation of Akt activity.

  16. Rictor/TORC2 regulates Caenorhabditis elegans fat storage, body size, and development through sgk-1.

    Directory of Open Access Journals (Sweden)

    Kevin T Jones

    2009-03-01

    Full Text Available The target of rapamycin (TOR kinase coordinately regulates fundamental metabolic and cellular processes to support growth, proliferation, survival, and differentiation, and consequently it has been proposed as a therapeutic target for the treatment of cancer, metabolic disease, and aging. The TOR kinase is found in two biochemically and functionally distinct complexes, termed TORC1 and TORC2. Aided by the compound rapamycin, which specifically inhibits TORC1, the role of TORC1 in regulating translation and cellular growth has been extensively studied. The physiological roles of TORC2 have remained largely elusive due to the lack of pharmacological inhibitors and its genetic lethality in mammals. Among potential targets of TORC2, the pro-survival kinase AKT has garnered much attention. Within the context of intact animals, however, the physiological consequences of phosphorylation of AKT by TORC2 remain poorly understood. Here we describe viable loss-of-function mutants in the Caenorhabditis elegans homolog of the TORC2-specific component, Rictor (CeRictor. These mutants display a mild developmental delay and decreased body size, but have increased lipid storage. These functions of CeRictor are not mediated through the regulation of AKT kinases or their major downstream target, the insulin-regulated FOXO transcription factor DAF-16. We found that loss of sgk-1, a homolog of the serum- and glucocorticoid-induced kinase, mimics the developmental, growth, and metabolic phenotypes of CeRictor mutants, while a novel, gain-of-function mutation in sgk-1 suppresses these phenotypes, indicating that SGK-1 is a mediator of CeRictor activity. These findings identify new physiological roles for TORC2, mediated by SGK, in regulation of C. elegans lipid accumulation and growth, and they challenge the notion that AKT is the primary effector of TORC2 function.

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

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    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.

  18. Transmembrane Inhibitor of RICTOR/mTORC2 in Hematopoietic Progenitors

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    Dongjun Lee

    2014-11-01

    Full Text Available Central to cellular proliferative, survival, and metabolic responses is the serine/threonine kinase mTOR, which is activated in many human cancers. mTOR is present in distinct complexes that are either modulated by AKT (mTORC1 or are upstream and regulatory of it (mTORC2. Governance of mTORC2 activity is poorly understood. Here, we report a transmembrane molecule in hematopoietic progenitor cells that physically interacts with and inhibits RICTOR, an essential component of mTORC2. Upstream of mTORC2 (UT2 negatively regulates mTORC2 enzymatic activity, reducing AKTS473, PKCα, and NDRG1 phosphorylation and increasing FOXO transcriptional activity in an mTORC2-dependent manner. Modulating UT2 levels altered animal survival in a T cell acute lymphoid leukemia (T-ALL model that is known to be mTORC2 sensitive. These studies identify an inhibitory component upstream of mTORC2 in hematopoietic cells that can reduce mortality from NOTCH-induced T-ALL. A transmembrane inhibitor of mTORC2 may provide an attractive target to affect this critical cell regulatory pathway.

  19. MicroRNA-let-7a regulates cell autophagy by targeting Rictor in gastric cancer cell lines MGC-803 and SGC-7901.

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    Fan, Hao; Jiang, Mingkun; Li, Bowen; He, Yu; Huang, Chi; Luo, Dakui; Xu, Hao; Yang, Li; Zhou, Jundong

    2018-03-01

    miR-let-7a is the most widely studied miRNA, whose functions have been well-established by scientists in both carcinogenesis and progression of human cancer, including gastric cancer (GC). However, to date there is a lack of information concerning the relationship between miR-let-7a and cellular autophagy. Using western blotting and immunofluorescence, we determined that upregulation of miR-let-7a led to increased cellular autophagic level, whereas miR-let-7a suppression decreased autophagy activity in GC cells. To further elucidate the mechanisms underlying this, we screened potential targets of miR-let-7a using bioinformatics analyses, validated by a series of assays. Our results indicated that Rptor independent companion of mTOR complex 2 (Rictor) was a direct target of miR-let-7a. In addition, rescue experiments in vitro showed that miR-let-7a promoted cellular autophagic level by inhibiting Rictor expression in GC cells. Furthermore, as an upstream executor of Akt-mTOR signaling pathway, we found that Rictor elaborated its effect on autophagy by phosphorylating Akt and mTOR, and this regulatory process could also be mediated by miR-let-7a. Taken together, our results present a novel role for miR-let-7a in GC which modulates autophagy by targeting Rictor, following the regulation of Akt-mTOR signal pathway.

  20. Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor

    DEFF Research Database (Denmark)

    Zhang, Chongben; Cooper, Daniel E; Grevengoed, Trisha J

    2014-01-01

    GPAT3 in mouse hepatocytes, GPAT4 overexpression increased phosphatidic acid (PA), especially di16:0-PA. Conversely, in Gpat4(-/-) hepatocytes, both mTOR/rictor association and mTORC2 activity increased, and the content of PA in Gpat4(-/-) hepatocytes was lower than in controls, with the greatest...

  1. Null cone superspace supergravity

    International Nuclear Information System (INIS)

    Downes-Martin, S.G.

    1980-03-01

    The null cone formalism is used to derive a 2(N-1) parameter family of constraints for O(N) extended superspace supergravity. The invariance groups of these constraints is analysed and is found to be [subgroup U submanifold] contains GL(4,R) for N = 1, the submanifold being eliminated for N > 1. The invariance group defines non-Weyl rotations on the superbein which combine to form Weyl transformations on the supertangent space metric. The invariance of the supergravity Lagrangian under these transformations is discussed. (Auth.)

  2. Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Chien-Min Hung

    2014-07-01

    Full Text Available The in vivo functions of mechanistic target of rapamycin complex 2 (mTORC2 and the signaling mechanisms that control brown adipose tissue (BAT fuel utilization and activity are not well understood. Here, by conditionally deleting Rictor in the Myf5 lineage, we provide in vivo evidence that mTORC2 is dispensable for skeletal muscle development and regeneration but essential for BAT growth. Furthermore, deleting Rictor in Myf5 precursors shifts BAT metabolism to a more oxidative and less lipogenic state and protects mice from obesity and metabolic disease at thermoneutrality. We additionally find that Rictor is required for brown adipocyte differentiation in vitro and that the mechanism specifically requires AKT1 hydrophobic motif phosphorylation but is independent of pan-AKT signaling and is rescued with BMP7. Our findings provide insights into the signaling circuitry that regulates brown adipocytes and could have important implications for developing therapies aimed at increasing energy expenditure as a means to combat human obesity.

  3. Visible Nulling Coronagraph Progress Report

    Science.gov (United States)

    Lyon, R. G.; Clampin, M.; Woodruff, R. A.; Vasudevan, G.; Thompson, P.; Petrone, P.; Madison, T.; Rizzo, M.; Melnick, G.; Tolls, V.

    2010-10-01

    We report on recent laboratory results with the NASA Goddard Space Flight Center Visible Nulling Coronagraph (VNC) testbed. We have achieved focal plane contrasts of 108 and approaching 109 at inner working angles of 2 λ/D and 4 λ/D, respectively. Results were obtained with a broadband source and 40 nm filter centered on 630 nm. A null control breadboard (NCB) was also developed to assess and quantify MEMS based deformable mirror technology (DM), and to develop and assess closed-loop null control algorithms. We have demonstrated closed-loop performance at 27 Hz.

  4. Null lifts and projective dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Cariglia, Marco, E-mail: marco@iceb.ufop.br

    2015-11-15

    We describe natural Hamiltonian systems using projective geometry. The null lift procedure endows the tangent bundle with a projective structure where the null Hamiltonian is identified with a projective conic and induces a Weyl geometry. Projective transformations generate a set of known and new dualities between Hamiltonian systems, as for example the phenomenon of coupling-constant metamorphosis. We conclude outlining how this construction can be extended to the quantum case for Eisenhart–Duval lifts.

  5. Bare Quantum Null Energy Condition.

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    Fu, Zicao; Marolf, Donald

    2018-02-16

    The quantum null energy condition (QNEC) is a conjectured relation between a null version of quantum field theory energy and derivatives of quantum field theory von Neumann entropy. In some cases, divergences cancel between these two terms and the QNEC is intrinsically finite. We study the more general case here where they do not and argue that a QNEC can still hold for bare (unrenormalized) quantities. While the original QNEC applied only to locally stationary null congruences in backgrounds that solve semiclassical theories of quantum gravity, at least in the formal perturbation theory at a small Planck length, the quantum focusing conjecture can be viewed as the special case of our bare QNEC for which the metric is on shell.

  6. Visible nulling coronagraph testbed results

    Science.gov (United States)

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

    2009-08-01

    We report on our recent laboratory results with the NASA/Goddard Space Flight Center (GSFC) Visible Nulling Coronagraph (VNC) testbed. We have experimentally achieved focal plane contrasts of 1 x 108 and approaching 109 at inner working angles of 2 * wavelength/D and 4 * wavelength/D respectively where D is the aperture diameter. The result was obtained using a broadband source with a narrowband spectral filter of width 10 nm centered on 630 nm. To date this is the deepest nulling result with a visible nulling coronagraph yet obtained. Developed also is a Null Control Breadboard (NCB) to assess and quantify MEMS based segmented deformable mirror technology and develop and assess closed-loop null sensing and control algorithm performance from both the pupil and focal planes. We have demonstrated closed-loop control at 27 Hz in the laboratory environment. Efforts are underway to first bring the contrast to > 109 necessary for the direct detection and characterization of jovian (Jupiter-like) and then to > 1010 necessary for terrestrial (Earth-like) exosolar planets. Short term advancements are expected to both broaden the spectral passband from 10 nm to 100 nm and to increase both the long-term stability to > 2 hours and the extent of the null out to a ~ 10 * wavelength / D via the use of MEMS based segmented deformable mirror technology, a coherent fiber bundle, achromatic phase shifters, all in a vacuum chamber at the GSFC VNC facility. Additionally an extreme stability textbook sized compact VNC is under development.

  7. Enhancing mTOR-targeted cancer therapy by preventing mTOR/raptor inhibition-initiated, mTOR/rictor-independent Akt activation

    OpenAIRE

    Wang, Xuerong; Yue, Ping; Kim, Young Ae; Fu, Haian; Khuri, Fadlo R.; Sun, Shi-Yong

    2008-01-01

    It has been shown that mTOR inhibitors activate Akt while inhibiting mTOR signaling. However, the underlying mechanisms and the impact of the Akt activation on mTOR-targeted cancer therapy are unclear. The present work focused on addressing the role of mTOR/rictor in mTOR inhibitor-induced Akt activation and the impact of sustained Akt activation on mTOR-targeted cancer therapy. Thus, we have demonstrated that mTOR inhibitors increase Akt phosphorylation through a mechanism independent of mTO...

  8. Standard and Null Weak Values

    OpenAIRE

    Zilberberg, Oded; Romito, Alessandro; Gefen, Yuval

    2013-01-01

    Weak value (WV) is a quantum mechanical measurement protocol, proposed by Aharonov, Albert, and Vaidman. It consists of a weak measurement, which is weighed in, conditional on the outcome of a later, strong measurement. Here we define another two-step measurement protocol, null weak value (NVW), and point out its advantages as compared to WV. We present two alternative derivations of NWVs and compare them to the corresponding derivations of WVs.

  9. Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans

    NARCIS (Netherlands)

    O’Donnell, Michael P.; Chao, Pin-Hao; Kammenga, Jan E.; Sengupta, Piali

    2018-01-01

    Animals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms

  10. 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…

  11. Conformal symmetry inheritance in null fluid spacetimes

    International Nuclear Information System (INIS)

    Tupper, B O J; Keane, A J; Hall, G S; Coley, A A; Carot, J

    2003-01-01

    We define inheriting conformal Killing vectors for null fluid spacetimes and find the maximum dimension of the associated inheriting Lie algebra. We show that for non-conformally flat null fluid spacetimes, the maximum dimension of the inheriting algebra is seven and for conformally flat null fluid spacetimes the maximum dimension is eight. In addition, it is shown that there are two distinct classes of non-conformally flat generalized plane wave spacetimes which possess the maximum dimension, and one class in the conformally flat case

  12. Null solution of the Yang-Mills equations

    International Nuclear Information System (INIS)

    Tafel, J.

    1986-05-01

    We investigate the correspondence between null solutions of the Yang-Mills equations and shearfree geodesic null congruences. We give an example of a non-Abelian null solution with twisting rays. (orig.)

  13. Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans.

    Directory of Open Access Journals (Sweden)

    Michael P O'Donnell

    2018-02-01

    Full Text Available Animals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms that are not fully understood. The conserved Target of Rapamycin complex 2 (TORC2 controls multiple processes in response to cellular stressors and growth factors. Here we show that TORC2 coordinates larval development and adult behaviors in response to environmental cues and feeding state in the bacterivorous nematode C. elegans. During development, pheromone, bacterial food, and temperature regulate expression of the daf-7 TGF-β and daf-28 insulin-like peptide in sensory neurons to promote a binary decision between reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which together reflect bacterial-diet dependent feeding status, thus providing a mechanism for integration of food signals with external cues in the regulation of neuroendocrine gene expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated foraging behaviors via a PDF-2/PDFR-1 neuropeptide signaling-dependent pathway. We also demonstrate that genetic variation affects food-dependent larval and adult phenotypes, and identify quantitative trait loci (QTL associated with these traits. Together, these results suggest that TORC2 acts as a hub for communication of feeding state information from the gut to the brain, thereby contributing to modulation of neuronal function by internal state.

  14. Null-strut calculus. II. Dynamics

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  15. Null structure groups in eleven dimensions

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  16. On smoothness-asymmetric null infinities

    International Nuclear Information System (INIS)

    Valiente Kroon, Juan Antonio

    2006-01-01

    We discuss the existence of asymptotically Euclidean initial data sets for the vacuum Einstein field equations which would give rise (modulo an existence result for the evolution equations near spatial infinity) to developments with a past and a future null infinity of different smoothness. For simplicity, the analysis is restricted to the class of conformally flat, axially symmetric initial data sets. It is shown how the free parameters in the second fundamental form of the data can be used to satisfy certain obstructions to the smoothness of null infinity. The resulting initial data sets could be interpreted as those of some sort of (nonlinearly) distorted Schwarzschild black hole. Their developments would be that they admit a peeling future null infinity, but at the same time have a polyhomogeneous (non-peeling) past null infinity

  17. 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,...

  18. Null-plane quantization of fermions

    International Nuclear Information System (INIS)

    Mustaki, D.

    1990-01-01

    Massive Dirac fermions are canonically quantized on the null plane using the Dirac-Bergmann algorithm. The procedure is carried out in the framework of quantum electrodynamics as an illustration of a rigorous treatment of interacting fermion fields

  19. On the Penrose inequality along null hypersurfaces

    International Nuclear Information System (INIS)

    Mars, Marc; Soria, Alberto

    2016-01-01

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

  20. Latex allergy and filaggrin null mutations

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... in the cases in this study may not have occurred through direct skin contact but through the respiratory organs via latex proteins that are absorbed in glove powder and aerosolized...

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Null Subjects in European and Brazilian Portuguese

    Directory of Open Access Journals (Sweden)

    Pilar Barbosa

    2005-12-01

    Full Text Available The goals of this paper are twofold: a to provide a structural account of the effects of the informal ‘Avoid Pronoun Principle’, proposed in Chomsky (1981: 65 for the Null Subject Languages (NSLs, and b to compare, in European and Brazilian Portuguese (EP and BP, the distribution of the third person pronouns in its full and null forms, to check whether in written corpora BP incorporates signs of the ongoing loss of the null subject, largely attested in its contemporary spoken language. The strong theoretical claim is that in the Romance non-NSLs the pre-verbal subject is sitting in Spec of IP, while in the Romance NSLs it is Clitic Left-Dislocated (or is extracted by A-bar movement if it belongs to a restricted set of non-referential quantified expressions. The paper provides quantitative evidence that BP is losing the properties associated with the Null Subject Parameter. In its qualitative analysis, it shows that the contrasts between EP and BP are easily accounted for if the two derivations are assumed and if the null subjects in the two varieties are considered to be of a different nature: a pronoun in EP and a pronominal anaphor in BP.

  3. Supersymmetric null-like holographic cosmologies

    International Nuclear Information System (INIS)

    Lin Fengli; Wen Wenyu

    2006-01-01

    We construct a new class of 1/4-BPS time dependent domain-wall solutions with null-like metric and dilaton in type II supergravities, which admit a null-like big bang singularity. Based on the domain-wall/QFT correspondence, these solutions are dual to 1/4-supersymmetric quantum field theories living on a boundary cosmological background with time dependent coupling constant and UV cutoff. In particular we evaluate the holographic c function for the 2-dimensional dual field theory living on the corresponding null-like cosmology. We find that this c function runs in accordance with the c-theorem as the boundary universe evolves, this means that the number of degrees of freedom is divergent at big bang and suggests the possible resolution of big bang singularity

  4. Null-strut calculus. I. Kinematics

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  5. Fine art of computing nulling interferometer maps

    Science.gov (United States)

    Hénault, F.

    2008-07-01

    Spaceborne nulling interferometers are often characterized by means of their nulling ratio, which is defined as the deepest possible extinction of one target star supposed to harbor an extra-solar system. Herein is shown that another parameter, which is the transmitting efficiency of nearby bright fringes, is also of prime importance. More generally, "nulling maps" formed by the whole destructive and constructive fringe pattern projected on-sky, are found to be very sensitive on the design of some subsystems constituting the interferometer. In particular, we consider Spatial Filtering (SF) and Achromatic Phase Shifter (APS) devices, both required achieving planet detection and characterization. Consequences of the SF choice (pinhole or single-mode optical fiber) and APS properties (with or without induced pupil-flip) are discussed, for both monochromatic and polychromatic cases. Examples of numerical simulations are provided for single Bracewell interferometer, Angel cross and X-array configurations, demonstrating noticeable differences in the aspect of resulting nulling maps. It is concluded that both FS and APS designs exhibit variable capacities for serendipitous planet discovery.

  6. Matter sources for a null big bang

    International Nuclear Information System (INIS)

    Bronnikov, K A; Zaslavskii, O B

    2008-01-01

    We consider the properties of stress-energy tensors compatible with a null big bang, i.e., cosmological evolution starting from a Killing horizon rather than a singularity. For Kantowski-Sachs cosmologies, it is shown that if matter satisfies the null energy condition, then (i) regular cosmological evolution can only start from a Killing horizon, (ii) matter is absent at the horizon and (iii) matter can only appear in the cosmological region due to interaction with vacuum. The latter is understood phenomenologically as a fluid whose stress tensor is insensitive to boosts in a particular direction. We also argue that matter is absent in a static region beyond the horizon. All this generalizes the observations recently obtained for a mixture of dust and a vacuum fluid. If, however, we admit the existence of phantom matter, its certain special kinds (with the parameter w ≤ -3) are consistent with a null big bang without interaction with vacuum (or without vacuum fluid at all). Then in the static region there is matter with w ≥ -1/3. Alternatively, the evolution can begin from a horizon in an infinitely remote past, leading to a scenario combining the features of a null big bang and an emergent universe

  7. Instabilities and the null energy condition

    International Nuclear Information System (INIS)

    Buniy, Roman V.; Hsu, Stephen D.H.

    2006-01-01

    We show that violation of the null energy condition implies instability in a broad class of models, including gauge theories with scalar and fermionic matter as well as any perfect fluid. When applied to the dark energy, our results imply that w=p/ρ is unlikely to be less than -1. than -1

  8. Covariant quantum mechanics on a null plane

    International Nuclear Information System (INIS)

    Leutwyler, H.; Stern, J.

    1977-03-01

    Lorentz invariance implies that the null plane wave functions factorize into a kinematical part describing the motion of the system as a whole and an inner wave function that involves the specific dynamical properties of the system - in complete correspondence with the non-relativistic situation. Covariance is equivalent to an angular condition which admits non-trivial solutions

  9. Null vectors in superconformal quantum field theory

    International Nuclear Information System (INIS)

    Huang Chaoshang

    1993-01-01

    The superspace formulation of the N=1 superconformal field theory and superconformal Ward identities are used to give a precise definition of fusion. Using the fusion procedure, superconformally covariant differential equations are derived and consequently a complete and straightforward algorithm for finding null vectors in Verma modules of the Neveu-Schwarz algebra is given. (orig.)

  10. 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 .

  11. Nulling tomography with weak gravitational lensing

    International Nuclear Information System (INIS)

    Huterer, Dragan; White, Martin

    2005-01-01

    We explore several strategies of eliminating (or nulling) the small-scale information in weak lensing convergence power spectrum measurements in order to protect against undesirable effects, for example, the effects of baryonic cooling and pressure forces on the distribution of large-scale structures. We selectively throw out the small-scale information in the convergence power spectrum that is most sensitive to the unwanted bias, while trying to retain most of the sensitivity to cosmological parameters. The strategies are effective in the difficult but realistic situations when we are able to guess the form of the contaminating effect only approximately. However, we also find that the simplest scheme of simply not using information from the largest multipoles works about as well as the proposed techniques in most, although not all, realistic cases. We advocate further exploration of nulling techniques and believe that they will find important applications in the weak lensing data mining

  12. 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...

  13. Null balance type electrostatic generating voltmeters

    International Nuclear Information System (INIS)

    Mahant, A.K.; Sidhu, N.P.S.; Gupta, U.C.

    1977-01-01

    A description is given of a null balance type generating voltmeter for measuring high D.C. voltage upto about 400 kV. The paper discusses the principle of operation, design, calibration and performance of the instrument. Main advantages of the device are: (1) it does not load the high voltage source, (2) no physical connection is required with the H.T. terminal and (3) calibration is independent of the rotor's frequency and amplifier's gain. (author)

  14. Null controllability of the viscous Camassa–Holm equation with ...

    Indian Academy of Sciences (India)

    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. Keywords. Viscous Camassa–Holm equation; null controllability; moving control;.

  15. Clausius entropy for arbitrary bifurcate null surfaces

    International Nuclear Information System (INIS)

    Baccetti, Valentina; Visser, Matt

    2014-01-01

    Jacobson’s thermodynamic derivation of the Einstein equations was originally applied only to local Rindler horizons. But at least some parts of that construction can usefully be extended to give meaningful results for arbitrary bifurcate null surfaces. As presaged in Jacobson’s original article, this more general construction sharply brings into focus the questions: is entropy objectively ‘real’? Or is entropy in some sense subjective and observer-dependent? These innocent questions open a Pandora’s box of often inconclusive debate. A consensus opinion, though certainly not universally held, seems to be that Clausius entropy (thermodynamic entropy, defined via a Clausius relation dS=đQ/T) should be objectively real, but that the ontological status of statistical entropy (Shannon or von Neumann entropy) is much more ambiguous, and much more likely to be observer-dependent. This question is particularly pressing when it comes to understanding Bekenstein entropy (black hole entropy). To perhaps further add to the confusion, we shall argue that even the Clausius entropy can often be observer-dependent. In the current article we shall conclusively demonstrate that one can meaningfully assign a notion of Clausius entropy to arbitrary bifurcate null surfaces—effectively defining a ‘virtual Clausius entropy’ for arbitrary ‘virtual (local) causal horizons’. As an application, we see that we can implement a version of the generalized second law (GSL) for this virtual Clausius entropy. This version of GSL can be related to certain (nonstandard) integral variants of the null energy condition. Because the concepts involved are rather subtle, we take some effort in being careful and explicit in developing our framework. In future work we will apply this construction to generalize Jacobson’s derivation of the Einstein equations. (paper)

  16. Generalized frame of reference with null congruence

    International Nuclear Information System (INIS)

    Ferrarese, G.; Antonelli, R.

    2000-01-01

    The paper derives the main properties of a generalized frame of reference with a null congruence (light flux), by means of adapted non-holonomic techniques; then it studies the geometry of the space-time in terms of non-orthogonal projection: longitudinal and transverse covariant derivatives and corresponding commutation formulae, decomposition of the Riemann and gravitational tensors, lie derivatives of the Ricci rotation coefficients, transverse Bianchi identity. Application to the (absolute and relative) light flux: kinematical characteristics and screen, Sachs theorems etc. are also given

  17. Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice.

    Science.gov (United States)

    Roundtree, Harrison M; Simeone, Timothy A; Johnson, Chaz; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Kristina A

    2016-02-01

    Comorbid sleep disorders occur in approximately one-third of people with epilepsy. Seizures and sleep disorders have an interdependent relationship where the occurrence of one can exacerbate the other. Orexin, a wake-promoting neuropeptide, is associated with sleep disorder symptoms. Here, we tested the hypothesis that orexin dysregulation plays a role in the comorbid sleep disorder symptoms in the Kcna1-null mouse model of temporal lobe epilepsy. Rest-activity was assessed using infrared beam actigraphy. Sleep architecture and seizures were assessed using continuous video-electroencephalography-electromyography recordings in Kcna1-null mice treated with vehicle or the dual orexin receptor antagonist, almorexant (100 mg/kg, intraperitoneally). Orexin levels in the lateral hypothalamus/perifornical region (LH/P) and hypothalamic pathology were assessed with immunohistochemistry and oxygen polarography. Kcna1-null mice have increased latency to rapid eye movement (REM) sleep onset, sleep fragmentation, and number of wake epochs. The numbers of REM and non-REM (NREM) sleep epochs are significantly reduced in Kcna1-null mice. Severe seizures propagate to the wake-promoting LH/P where injury is apparent (indicated by astrogliosis, blood-brain barrier permeability, and impaired mitochondrial function). The number of orexin-positive neurons is increased in the LH/P compared to wild-type LH/P. Treatment with a dual orexin receptor antagonist significantly increases the number and duration of NREM sleep epochs and reduces the latency to REM sleep onset. Further, almorexant treatment reduces the incidence of severe seizures and overall seizure burden. Interestingly, we report a significant positive correlation between latency to REM onset and seizure burden in Kcna1-null mice. Dual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in other epilepsy models. © 2016 Associated

  18. Dall-Null tester for spaceborne applications

    Science.gov (United States)

    Wingler, R. L.

    1984-12-01

    This is a study to design a self correcting primary mirror system for a space telescope. The design is centered around a Dall-Null tester (a Foucault knife-edge tester with compensating lens). An indepth study of the theory of the Foucault test from Foucault's original publications to current work is presented. Also short comings of the diffraction approach are shown. The findings of a simple experiment showed the way to the correct explanation as to the workings of the test. Based on this new explanation, a computer program to find the error in the surface of the mirror from the irradiance pattern provided by the Dall-Null tester was developed. The computer program with a sample run is included in the appendixes A and B. The basic design of an adaptive optic system for a spaceborne application is also presented in the paper. This design has the desired quality of being able to correct the mirror while the telescope is in use. The equations being independent of wavelength allows for the design to be applied to systems working outside of the visible spectrum as well as the systems working in the visible.

  19. Averaged null energy condition from causality

    Science.gov (United States)

    Hartman, Thomas; Kundu, Sandipan; Tajdini, Amirhossein

    2017-07-01

    Unitary, Lorentz-invariant quantum field theories in flat spacetime obey mi-crocausality: commutators vanish at spacelike separation. For interacting theories in more than two dimensions, we show that this implies that the averaged null energy, ∫ duT uu , must be non-negative. 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 ∫ duX uuu··· u ≥ 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 on the relation to the recent derivation of the averaged null energy condition from relative entropy, and suggest a more general connection between causality and information-theoretic inequalities in QFT.

  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. Singular Null Hypersurfaces in General Relativity

    International Nuclear Information System (INIS)

    Dray, T

    2006-01-01

    Null hypersurfaces are a mathematical consequence of the Lorentzian signature of general relativity; singularities in mathematical models usually indicate where the interesting physics takes place. This book discusses what happens when you combine these ideas. Right from the preface, this is a no-nonsense book. There are two principal approaches to singular shells, one distributional and the other 'cut and paste'; both are treated in detail. A working knowledge of GR is assumed, including familiarity with null tetrads, differential forms, and 3 + 1 decompositions. Despite my own reasonably extensive, closely related knowledge, there was material unfamiliar to me already in chapter 3, although I was reunited with some old friends in later chapters. The exposition is crisp, with a minimum of transition from chapter to chapter. In fact, my main criticism is that there is no clear statement of the organization of the book, nor is there an index. Everything is here, and the story is compelling if you know what to look for, although it is less easy to follow the story if you are not already familiar with it. But this is really a book for experts, and the authors certainly qualify, having played a significant role in developing and extending the results they describe. It is also entirely appropriate that the book is dedicated to Werner Israel, who pioneered the thin-shell approach to (non-null) singular surfaces and later championed the use of similar methods for analysing null shells. After an introductory chapter on impulsive signals, the authors show how the Bianchi identities can be used to classify spacetimes with singular null hypersurfaces. This approach, due to the authors, generalizes the framework originally proposed by Penrose. While astrophysical applications are discussed only briefly, the authors point out that detailed physical characteristics of signals from isolated sources can be determined in this manner. In particular, they describe the behaviour of

  2. Global ablation of the mitochondrial calcium uniporter increases glycolysis in cortical neurons subjected to energetic stressors.

    Science.gov (United States)

    Nichols, Matthew; Elustondo, Pia A; Warford, Jordan; Thirumaran, Aruloli; Pavlov, Evgeny V; Robertson, George S

    2017-08-01

    The effects of global mitochondrial calcium (Ca 2+ ) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca 2+ handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca 2+ uptake and Ca 2+ -induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage. Energetic stress enhanced glycolysis and depressed Complex I activity in global MCU null, relative to WT, cortical neurons. HI reduced forebrain NADH levels more in global MCU nulls than WT mice suggesting that increased glycolytic consumption of NADH suppressed Complex I activity. Compared to WT neurons, pyruvate dehydrogenase (PDH) was hyper-phosphorylated in MCU nulls at several sites that lower the supply of substrates for the tricarboxylic acid cycle. Elevation of cytosolic Ca 2+ with glutamate or ionomycin decreased PDH phosphorylation in MCU null neurons suggesting the use of alternative mitochondrial Ca 2+ transport. Under basal conditions, global MCU nulls showed similar increases of Ca 2+ handling genes in the hippocampus as WT mice subjected to HPC. We propose that long-term adaptations, common to HPC, in global MCU nulls compromise resistance to HI brain injury and disrupt HPC.

  3. On the null origin of the ambitwistor string

    Energy Technology Data Exchange (ETDEWEB)

    Casali, Eduardo [Mathematical Institute, University of Oxford,Woodstock Road, Oxford, OX2 6GG (United Kingdom); Tourkine, Piotr [Department of Applied Mathematics and Theoretical Physics,Wilberforce Road, Cambridge, CB3 0WA (United Kingdom)

    2016-11-07

    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.

  4. Technology Advancement of the Visible Nulling Coronagraph

    Science.gov (United States)

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

    2010-01-01

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

  5. [Dilemma of null hypothesis in ecological hypothesis's experiment test.

    Science.gov (United States)

    Li, Ji

    2016-06-01

    Experimental test is one of the major test methods of ecological hypothesis, though there are many arguments due to null hypothesis. Quinn and Dunham (1983) analyzed the hypothesis deduction model from Platt (1964) and thus stated that there is no null hypothesis in ecology that can be strictly tested by experiments. Fisher's falsificationism and Neyman-Pearson (N-P)'s non-decisivity inhibit statistical null hypothesis from being strictly tested. Moreover, since the null hypothesis H 0 (α=1, β=0) and alternative hypothesis H 1 '(α'=1, β'=0) in ecological progresses are diffe-rent from classic physics, the ecological null hypothesis can neither be strictly tested experimentally. These dilemmas of null hypothesis could be relieved via the reduction of P value, careful selection of null hypothesis, non-centralization of non-null hypothesis, and two-tailed test. However, the statistical null hypothesis significance testing (NHST) should not to be equivalent to the causality logistical test in ecological hypothesis. Hence, the findings and conclusions about methodological studies and experimental tests based on NHST are not always logically reliable.

  6. Broadband Active Segmented Aperture and Radial Shear Nulling

    Data.gov (United States)

    National Aeronautics and Space Administration — The Visible Nulling Coronagraph (VNC) is a starlight suppression system for enabling exoplanet detectionand atmospheric measurement. Conceptual space telescope...

  7. MAGNETIC NULL POINTS IN KINETIC SIMULATIONS OF SPACE PLASMAS

    International Nuclear Information System (INIS)

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

    2016-01-01

    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 (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

  8. 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…

  9. Euclidean null controllability of nonlinear infinite delay systems with ...

    African Journals Online (AJOL)

    Sufficient conditions for the Euclidean null controllability of non-linear delay systems with time varying multiple delays in the control and implicit derivative are derived. If the uncontrolled system is uniformly asymptotically stable and if the control system is controllable, then the non-linear infinite delay system is Euclidean null ...

  10. Null infinity and extremal horizons in AdS-CFT

    International Nuclear Information System (INIS)

    Hickling, Andrew; Wiseman, Toby; Lucietti, James

    2015-01-01

    We consider AdS gravity duals to CFT on background spacetimes with a null infinity. Null infinity on the conformal boundary may extend to an extremal horizon in the bulk. For example it does so for Poincaré–AdS, although does not for planar Schwarzschild–AdS. If null infinity does extend into an extremal horizon in the bulk, we show that the bulk near-horizon geometry is determined by the geometry of the boundary null infinity. Hence the ‘infra-red’ geometry of the bulk is fixed by the large scale behaviour of the CFT spacetime. In addition the boundary stress tensor must have a particular decay at null infinity. As an application, we argue that for CFT on asymptotically flat backgrounds, any static bulk dual containing an extremal horizon extending from the boundary null infinity, must have the near-horizon geometry of Poincaré–AdS. We also discuss a class of boundary null infinity that cannot extend to a bulk extremal horizon, although we give evidence that they can extend to an analogous null surface in the bulk which possesses an associated scale-invariant ‘near-geometry’. (paper)

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

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Maulik, E-mail: maulik.parikh@asu.edu; Svesko, Andrew

    2016-10-10

    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.

  12. 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.

  13. A new dynamic null model for phylogenetic community structure

    NARCIS (Netherlands)

    Pigot, Alex L; Etienne, Rampal S

    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

  14. ENERGY DISSIPATION IN MAGNETIC NULL POINTS AT KINETIC SCALES

    International Nuclear Information System (INIS)

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

    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 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

  15. On the Robinson theorem and shearfree geodesic null congruences

    International Nuclear Information System (INIS)

    Tafel, J.

    1985-01-01

    Null electromagnetic fields and shearfree geodesic null congruences in curved and flat spacetimes are studied. We point out some mathematical problems connected with the validity of the Robinson theorem. The problem of finding nonanalytic twisting congruences in the Minkowski space is reduced to the construction of holomorphic functions with specific boundary conditions. (orig.)

  16. An omnibus test for the global null hypothesis.

    Science.gov (United States)

    Futschik, Andreas; Taus, Thomas; Zehetmayer, Sonja

    2018-01-01

    Global hypothesis tests are a useful tool in the context of clinical trials, genetic studies, or meta-analyses, when researchers are not interested in testing individual hypotheses, but in testing whether none of the hypotheses is false. There are several possibilities how to test the global null hypothesis when the individual null hypotheses are independent. If it is assumed that many of the individual null hypotheses are false, combination tests have been recommended to maximize power. If, however, it is assumed that only one or a few null hypotheses are false, global tests based on individual test statistics are more powerful (e.g. Bonferroni or Simes test). However, usually there is no a priori knowledge on the number of false individual null hypotheses. We therefore propose an omnibus test based on cumulative sums of the transformed p-values. We show that this test yields an impressive overall performance. The proposed method is implemented in an R-package called omnibus.

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

    Science.gov (United States)

    Shao, Michael; Levine, B. Martin; Wallace, J. Kent; Liu, Duncan T.; Schmidtlin, Edouard; Serabyn, Eugene; Mennesson, Bertrand; Green, Joseph J.; Aguayo, Francisco; Fregoso, S. Felipe; hide

    2005-01-01

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

  18. Wormholes minimally violating the null energy condition

    Energy Technology Data Exchange (ETDEWEB)

    Bouhmadi-López, Mariam [Departamento de Física, Universidade da Beira Interior, 6200 Covilhã (Portugal); Lobo, Francisco S N; Martín-Moruno, Prado, E-mail: mariam.bouhmadi@ehu.es, E-mail: fslobo@fc.ul.pt, E-mail: pmmoruno@fc.ul.pt [Centro de Astronomia e Astrofísica da Universidade de Lisboa, Campo Grande, Edifício C8, 1749-016 Lisboa (Portugal)

    2014-11-01

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

  19. Bodyweight Assessment of Enamelin Null Mice

    Directory of Open Access Journals (Sweden)

    Albert H.-L. Chan

    2013-01-01

    Full Text Available The Enam null mice appear to be smaller than wild-type mice, which prompted the hypothesis that enamel defects negatively influence nutritional intake and bodyweight gain (BWG. We compared the BWG of Enam−/− and wild-type mice from birth (D0 to Day 42 (D42. Wild-type (WT and Enam−/− (N mice were given either hard chow (HC or soft chow (SC. Four experimental groups were studied: WTHC, WTSC, NHC, and NSC. The mother’s bodyweight (DBW and the average litter bodyweight (ALBW were obtained from D0 to D21. After D21, the pups were separated from the mother and provided the same type of food. Litter bodyweights were measured until D42. ALBW was compared at 7-day intervals using one-way ANOVA, while the influence of DBW on ALBW was analyzed by mixed-model analyses. The ALBW of Enam−/− mice maintained on hard chow (NHC was significantly lower than the two WT groups at D21 and the differences persisted into young adulthood. The ALBW of Enam−/− mice maintained on soft chow (NSC trended lower, but was not significantly different than that of the WT groups. We conclude that genotype, which affects enamel integrity, and food hardness influence bodyweight gain in postnatal and young adult mice.

  20. Tensionless branes and the null string critical dimension

    International Nuclear Information System (INIS)

    Bozhilov, P.

    1998-01-01

    BRST quantization is carried out for a model of p-branes with second class constraints. After extension of the phase space the constraint algebra coincides with the one of null string when p=1. It is shown that in this case one can or cannot obtain critical dimension for the null string, depending on the choice of the operator ordering and corresponding vacuum states. When p>1, operator orderings leading to critical dimension in the p=1 case are not allowed. Admissible orderings give no restrictions on the dimension of the embedding space-time. Finally, a generalization to supersymmetric null branes is proposed

  1. Conditional loss of progranulin in neurons is not sufficient to cause neuronal ceroid lipofuscinosis-like neuropathology in mice.

    Science.gov (United States)

    Petkau, Terri L; Blanco, Jake; Leavitt, Blair R

    2017-10-01

    Progranulin deficiency due to heterozygous null mutations in the GRN gene is a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations cause neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. Progranulin is a secreted glycoprotein expressed in both neurons and microglia, but not astrocytes, in the brain. We generated conditional progranulin-knockout mice that lack progranulin in nestin-expressing cells (Nes-cKO mice), which include most neurons as well as astrocytes. We confirmed near complete knockout of progranulin in neurons in Nes-cKO mice, while microglial progranulin levels remained similar to that of wild-type animals. Overall brain progranulin levels were reduced by about 50% in Nes-cKO, and no Grn was detected in primary Nes-cKO neurons. Nes-cKO mice aged to 12months did not display any increase in lipofuscin deposition, microgliosis, or astrogliosis in the four brain regions examined, though increases were observed for most of these measures in Grn-null animals. We conclude that neuron-specific loss of progranulin is not sufficient to cause similar neuropathological changes to those seen in constitutive Grn-null animals. Our results suggest that increased lipofuscinosis and gliosis in Grn-null animals are not caused by intrinsic progranulin deficiency in neurons, and that microglia-derived progranulin may be sufficient to maintain neuronal health and homeostasis in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Emission and null coordinates: geometrical properties and physical construction

    International Nuclear Information System (INIS)

    Coll, Bartolome; Ferrando, Joan J; Morales-Lladosa, Juan A

    2011-01-01

    A Relativistic Positioning System is defined by four clocks (emitters) broadcasting their proper time. Then, every event reached by the signals is naturally labeled by these four times which are the emission coordinates of this event. The coordinate hypersurfaces of the emission coordinates are the future light cones based on the emitter trajectories. For this reason the emission coordinates have been also named null coordinates or light coordinates. Nevertheless, other coordinate systems used in different relativistic contexts have the own right to be named null or light coordinates. Here we analyze when one can say that a coordinate is a null coordinate and when one can say that a coordinate system is null. Moreover, we examine the physical construction and the geometrical properties of several n ull coordinate systems : the emission and the reception coordinates, the radar coordinates, and the Bondi-Sachs coordinates, among others.

  3. Relative null controllability of linear systems with multiple delays in ...

    African Journals Online (AJOL)

    varying multiple delays in state and control are developed. If the uncontrolled system is uniformly asymptotically stable, and if the linear system is controllable, then the linear system is null controllable. Journal of the Nigerian Association of ...

  4. Null canonical formalism 1, Maxwell field. [Poisson brackets, boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Wodkiewicz, K [Warsaw Univ. (Poland). Inst. Fizyki Teoretycznej

    1975-01-01

    The purpose of this paper is to formulate the canonical formalism on null hypersurfaces for the Maxwell electrodynamics. The set of the Poisson brackets relations for null variables of the Maxwell field is obtained. The asymptotic properties of the theory are investigated. The Poisson bracket relations for the news-functions of the Maxwell field are computed. The Hamiltonian form of the asymptotic Maxwell equations in terms of these news-functions is obtained.

  5. 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.

  6. Sequential weak continuity of null Lagrangians at the boundary

    Czech Academy of Sciences Publication Activity Database

    Kalamajska, A.; Kraemer, S.; Kružík, Martin

    2014-01-01

    Roč. 49, 3/4 (2014), s. 1263-1278 ISSN 0944-2669 R&D Projects: GA ČR GAP201/10/0357 Institutional support: RVO:67985556 Keywords : null Lagrangians * nonhomogeneous nonlinear mappings * sequential weak/in measure continuity Subject RIV: BA - General Mathematics Impact factor: 1.518, year: 2014 http://library.utia.cas.cz/separaty/2013/MTR/kruzik-sequential weak continuity of null lagrangians at the boundary.pdf

  7. On the geometry of null congruences in general relativity

    International Nuclear Information System (INIS)

    Ahsan, Zafar; Malik, N.P.

    1977-01-01

    Some theorems for the null congruences within the framework of general theory of relativity are given. These theorems are important in themselves as they illustrate the geometric meaning of the spin coefficients. The newly developed Geroch-Held-Penrose (GHP) formalism has been used throughout the investigations. The salient features of GHP formalism that are necessary for the present work are given and these techniques are applied to a pair of null congruences C(l) and C(n). (author)

  8. A parameter set for a double-null DEMO reactor

    International Nuclear Information System (INIS)

    Cooke, P.I.H.

    1987-01-01

    The present study is aimed at commenting on the reactor-relevance of the design principles and technology being proposed for NET. The authors propose that a double-null device serve as a basis for a NET-based demonstration reactor. Calculations are carried out to determine the parameter set for reactors based on the double-null NET design, and the results are presented in tabular form. (U.K.)

  9. Vortical null orbits, repulsive barriers, energy confinement in Kerr metric

    Energy Technology Data Exchange (ETDEWEB)

    Calvani, M [Padua Univ. (Italy). Ist. di Astronomia; De Felice, F

    1978-10-01

    The complete analytical description of the null trajectories in the field of a Kerr naked singularity is given. Two peculiar phenomena are described: the existence of repulsive barriers in the r < O world and the existence of null circular bound orbits which surround the singularity in 'shells'. They distribute around the surface at r = m, which is the position of the horizon in the extreme black-hole case; this suggests that a naked singularity 'remembers' the position of the last horizon.

  10. Ambitwistor strings at null infinity and (subleading) soft limits

    International Nuclear Information System (INIS)

    Geyer, Yvonne; Lipstein, Arthur E; Mason, Lionel

    2015-01-01

    The relationship between BMS symmetries at null infinity and Weinberg's soft theorems for gravitons and photons together with their subleading extensions are developed using ambitwistor string theory. Ambitwistor space is the phase space of complex null geodesics in complexified space-time. We show how it can be canonically identified with the cotangent bundle of complexified null infinity. BMS symmetries of null infinity lift to give a Hamiltonian action on ambitwistor space, both in general dimension and in its twistorial four-dimensional representation. General vertex operators arise from Hamiltonians generating diffeomorphisms of ambitwistor space that determine the scattering from past to future null infinity. When a momentum eigenstate goes soft, the diffeomorphism defined by its leading and its subleading part are extended BMS generators realized in the world sheet conformal field theory of the ambitwistor string. More generally, this gives an explicit perturbative correspondence between the scattering of null geodesics and that of the gravitational field via ambitwistor string theory. (paper)

  11. Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias

    Science.gov (United States)

    Hara, Munetsugu; Takahashi, Tomoyuki; Mitsumasu, Chiaki; Igata, Sachiyo; Takano, Makoto; Minami, Tomoko; Yasukawa, Hideo; Okayama, Satoko; Nakamura, Keiichiro; Okabe, Yasunori; Tanaka, Eiichiro; Takemura, Genzou; Kosai, Ken-ichiro; Yamashita, Yushiro; Matsuishi, Toyojiro

    2015-01-01

    Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus, and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure. PMID:26073556

  12. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  13. Resistivity at the field null of the FRC plasma

    International Nuclear Information System (INIS)

    Gerwin, R.A.

    1989-01-01

    In the absence of the major destructive instabilities, the configuration time is ultimately determined by particle and flux containment. If the profiles are ''gentle,'' then the anomalous flux-loss rate depends essentially on the anomalous resistivity at the field null. Conventional electrostatic quasi-linear models of anomalous cross-field resistive diffusivity are based upon the use of rvec E x rvec B drift velocities, and hence break down at the magnetic field null. In this paper, an electromagnetic treatment valid at the field null is developed, based upon the presence of flute-parity perturbations. An expression for anomalous resistivity at the field null in the quasi-linear approximation is derived by averaging in the ignorable direction over the random phases of the perturbations. The expression is valid for arbitrary (non-local) radial shapes of the perturbing modes (for example, the eigenfunctions need not be centered at the field null), and for an arbitrary ratio of real frequency to growth rate. The effective resistivity due to flute perturbations of the MHD type will be considered. 1 ref

  14. Evaluation of null-point detection methods on simulation data

    Science.gov (United States)

    Olshevsky, Vyacheslav; Fu, Huishan; Vaivads, Andris; Khotyaintsev, Yuri; Lapenta, Giovanni; Markidis, Stefano

    2014-05-01

    We model the measurements of artificial spacecraft that resemble the configuration of CLUSTER propagating in the particle-in-cell simulation of turbulent magnetic reconnection. The simulation domain contains multiple isolated X-type null-points, but the majority are O-type null-points. Simulations show that current pinches surrounded by twisted fields, analogous to laboratory pinches, are formed along the sequences of O-type nulls. In the simulation, the magnetic reconnection is mainly driven by the kinking of the pinches, at spatial scales of several ion inertial lentghs. We compute the locations of magnetic null-points and detect their type. When the satellites are separated by the fractions of ion inertial length, as it is for CLUSTER, they are able to locate both the isolated null-points, and the pinches. We apply the method to the real CLUSTER data and speculate how common are pinches in the magnetosphere, and whether they play a dominant role in the dissipation of magnetic energy.

  15. 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

    2010-07-01

    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 108, 109 and 1010 at an inner working angle of 2*λ/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.

  16. Tolerance analysis of null lenses using an end-use system performance criterion

    Science.gov (United States)

    Rodgers, J. Michael

    2000-07-01

    An effective method of assigning tolerances to a null lens is to determine the effects of null-lens fabrication and alignment errors on the end-use system itself, not simply the null lens. This paper describes a method to assign null- lens tolerances based on their effect on any performance parameter of the end-use system.

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

    Science.gov (United States)

    Shaw, Pamela A; Proschan, Michael A

    2013-01-30

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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Science.gov (United States)

    Streiner, David L

    2003-12-01

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

  20. ISCO and Principal Null Congruences in Extremal Kerr Spacetime

    International Nuclear Information System (INIS)

    Pradhan, Parthapratim

    2012-01-01

    The effective potential in universal like coordinates(U, V, θ, φ), which are smooth across the event horizon is derived and investigated the ISCO(Innermost Stable Circular Orbits) explicitly in these coordinates for extremal Kerr spacetime. Extremization of the effective potential for timelike circular orbit shows that the existence of a stable circular geodesics in the extremal spacetime for direct orbit, precisely on the event horizon in terms of the radial coordinate which coincides with the principal null geodesic congruences of the event horizon. These null geodesic congruences mold themselves to the spacetime curvature in such a way that Weyl conformal tensor and its dual are vanished, that is why they are in-fact doubly degenerate principal null congruences.

  1. Phase-space lagrangians for null spinning strings

    International Nuclear Information System (INIS)

    Barcelos-Neto, J.; Ruiz-Altaba, M.; Ramirez, C.

    1990-01-01

    The striking fact that normal-ordered null strings have the same critical dimension as their usual non-zero tension siblings can be understood from the observation that one must, in the tensionless case, keep all the conjugate momenta as independent dynamical variables, thus doubling the number of physical degrees of freedom. The fermionic momenta give rise to a second-class constraint which cannot be solved covariantly, but can be successfully incorporated into the first-class constraint algebra after gauge-fixing. The ghost contributions to the anomaly consist of two b-c (and also two β-γ systems in the supersymmetric case), of the single Virasoro sub(super)algebra for the closed null (spinning) string. In the appropriate gauge, the null (super)string is (super)chiral. (orig.)

  2. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  3. P3-23: Center/Surround Motion Interactions Measured Using a Nulling Procedure

    Directory of Open Access Journals (Sweden)

    Soo Hyun Park

    2012-10-01

    Full Text Available Many direction-selective neurons have a receptive field structure that promotes suppressive interactions between center and surround regions. These interactions sculpt the overall pattern of activity among those neurons and, therefore, presumably impact perceived direction of motion. To test this conjecture, we have assessed the effect of motion signals produced by a moving stimulus on perceived motion within a neighboring region. On each trial a vertical bar (inducer appeared at 8 eccentricity in the upper visual field, moving either leftward or rightward, and a circular shaped random dot kinematogram (test appeared at 4 eccentricity. The test dots moved randomly except when the inducer passed nearby the test, at which time a pulse of coherent motion occurred in one of the two directions within the test. Coherence strength was adjusted by QUEST to maintain equal likelihood (point of subjective equality: PSE of leftward and rightward reports of perceived direction during this motion pulse. The inducer caused a substantial shift in PSE: it was necessary for the test to contain 50% coherent motion in the same direction as that of the inducer to nullify the illusory motion within the test caused by the inducer. The effect of the inducer could also be offset by simultaneously presenting a second inducer moving in the opposite direction. This pattern of results implies substantial suppressive interactions between neighboring moving stimuli, interactions whose strength and direction can be assessed psychophysically using nulling procedures.

  4. 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.

  5. Euclidean null controllability of perturbed infinite delay systems with ...

    African Journals Online (AJOL)

    Euclidean null controllability of perturbed infinite delay systems with limited control. ... Open Access DOWNLOAD FULL TEXT ... The results are established by placing conditions on the perturbation function which guarantee that, if the linear control base system is completely Euclidean controllable, then the perturbed system ...

  6. Euclidean null controllability of linear systems with delays in state ...

    African Journals Online (AJOL)

    Sufficient conditions are developed for the Euclidean controllability of linear systems with delay in state and in control. Namely, if the uncontrolled system is uniformly asymptotically stable and the control equation proper, then the control system is Euclidean null controllable. Journal of the Nigerian Association of ...

  7. Future null infinity of Robertson-Walker spacetimes

    International Nuclear Information System (INIS)

    Moreschi, O.M.

    1988-08-01

    The future null infinity for all non-contracting Robertson-Walker space time is studied systematically. A theorem is proved which establishes the expected relation between the nature of J + and the appearance or absence of cosmic event horizons. (author). 7 refs, 1 tab

  8. The Many Null Distributions of Person Fit Indices.

    Science.gov (United States)

    Molenaar, Ivo W.; Hoijtink, Herbert

    1990-01-01

    Statistical properties of person fit indices are reviewed as indicators of the extent to which a person's score pattern is in agreement with a measurement model. Distribution of a fit index and ability-free fit evaluation are discussed. The null distribution was simulated for a test of 20 items. (SLD)

  9. Spatial and null infinity via advanced and retarded conformal factors

    International Nuclear Information System (INIS)

    Hayward, Sean A.

    2003-01-01

    A new approach to space-time asymptotics is presented, refining Penrose's idea of conformal transformations with infinity represented by the conformal boundary of space-time. It is proposed that the Penrose conformal factor be a product of advanced and retarded conformal factors, which asymptotically relate physical and conformal null coordinates and vanish at future and past null infinity respectively. A refined definition of asymptotic flatness at both spatial and null infinity is given, including that the conformal boundary is locally a light cone, with spatial infinity as the vertex. It is shown how to choose the conformal factors so that this asymptotic light cone is locally a metric light cone. The theory is implemented in the spin-coefficient (or null-tetrad) formalism by a joint transformation of the spin-metric and spin-basis (or metric and tetrad). Asymptotic regularity conditions are proposed, based on the conformal boundary locally being a smoothly embedded metric light cone. These conditions ensure that the Bondi-Sachs energy-flux integrals of ingoing and outgoing gravitational radiation decay at spatial infinity such that the total radiated energy is finite, and that the Bondi-Sachs energy-momentum has a unique limit at spatial infinity, coinciding with the uniquely rendered ADM energy-momentum

  10. Red hair is the null phenotype of MC1R.

    Science.gov (United States)

    Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

    2008-08-01

    The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

  11. On the null distribution of Bayes factors in linear regression

    Science.gov (United States)

    We show that under the null, the 2 log (Bayes factor) is asymptotically distributed as a weighted sum of chi-squared random variables with a shifted mean. This claim holds for Bayesian multi-linear regression with a family of conjugate priors, namely, the normal-inverse-gamma prior, the g-prior, and...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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 sol...

  13. Null point of discrimination in crustacean polarisation vision.

    Science.gov (United States)

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

    2014-07-15

    The polarisation of light is used by many species of cephalopods and crustaceans to discriminate objects or to communicate. Most visual systems with this ability, such as that of the fiddler crab, include receptors with photopigments that are oriented horizontally and vertically relative to the outside world. Photoreceptors in such an orthogonal array are maximally sensitive to polarised light with the same fixed e-vector orientation. Using opponent neural connections, this two-channel system may produce a single value of polarisation contrast and, consequently, it may suffer from null points of discrimination. Stomatopod crustaceans use a different system for polarisation vision, comprising at least four types of polarisation-sensitive photoreceptor arranged at 0, 45, 90 and 135 deg relative to each other, in conjunction with extensive rotational eye movements. This anatomical arrangement should not suffer from equivalent null points of discrimination. To test whether these two systems were vulnerable to null points, we presented the fiddler crab Uca heteropleura and the stomatopod Haptosquilla trispinosa with polarised looming stimuli on a modified LCD monitor. The fiddler crab was less sensitive to differences in the degree of polarised light when the e-vector was at -45 deg than when the e-vector was horizontal. In comparison, stomatopods showed no difference in sensitivity between the two stimulus types. The results suggest that fiddler crabs suffer from a null point of sensitivity, while stomatopods do not. © 2014. Published by The Company of Biologists Ltd.

  14. 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.

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

    Science.gov (United States)

    Bloemhof, Eric E.

    2010-01-01

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

  16. Visible Nulling Coronagraphy for Exo-Planetary Detection and Characterization

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert; Vasudevan, Gopal; Shao, Mike; Levine, Martin; Melnick, Gary; Tolls, Volker; Petrone, Peter; Dogoda, Peter; Duval, Julia; Ge, Jian

    Visible Nulling Coronagraphy (VNC) is the proposed method of detecting and characterizing exo-solar Jovian planets (null depth 10-9) for the proposed NASA's Extrasolar Planetary Imaging Coronagraph (EPIC) Clampin & Lyon 2004 and is an approach under evaluation for NASA's Terrestrial Planet Finder (TPF) mission. The VNC approach uses a single unobscured filled-aperture telescope and splits, via a 50:50 beamsplitter, its re-imaged pupil into two paths within a Mach-Zender interferometer. An achromatic PI phase shift is imposed onto one beam path and the two paths are laterally sheared with respect to each other. The two beams are recombined at a second 50:50 beamsplitter. The net effect is that the on axis (stellar) light is transmitted out of the bright interferometer arm while the off-axis (planetary) light is transmitted out of the nulled interferometer arm. The bright output is used for fine pointing control and coarse wavefront control. The nulled output is relayed to the science camera for science imagery and fine wavefront control. The actual transmission pattern, projected on the sky, follows a θ^2 pattern for a single shear, θ^4 for a double shear, with the spacing of the successive maxima proportional to the inverse of the relative lateral shear. Combinations of shears and spacecraft rolls build up the spatial frequency content of the sky transmission pattern in the same manner as imaging interferometer builds up the spatial frequency content of the image.

  17. Shaping Up the Practice of Null Hypothesis Significance Testing.

    Science.gov (United States)

    Wainer, Howard; Robinson, Daniel H.

    2003-01-01

    Discusses criticisms of null hypothesis significance testing (NHST), suggesting that historical use of NHST was reasonable, and current users should read Sir Ronald Fisher's applied work. Notes that modifications to NHST and interpretations of its outcomes might better suit the needs of modern science. Concludes that NHST is most often useful as…

  18. Relative controllability and null controllability of linear delay systems ...

    African Journals Online (AJOL)

    Necessary and sufficient conditions are established for the relative, absolute controllability and null controllability of the generalized linear delay system and its discrete prototype. The paper presents illuminating examples on previous controllability results by Manitius and Olbrot [7] and carries over the results of Onwuatu [8] ...

  19. A model for electron currents near a field null

    International Nuclear Information System (INIS)

    Stark, R.A.; Miley, G.H.

    1987-01-01

    The fluid approximation is invalid near a field null, since the local electron orbit size and the magnetic scale length are comparable. To model the electron currents in this region we propose a single equation of motion describing the bulk electron dynamics. The equation applies to the plasma within one thermal orbit size of the null. The region is treated as unmagnetized; electrons are accelerated by the inductive electric field and drag on ions; damping is provided by viscosity due to electrons and collisions with ions. Through variational calculations and a particle tracking code for electrons, the size of the terms in the equation of motion have been estimated. The resulting equation of motion combines with Faraday's Law to produce a governing equation which implicitly contains the self inductive field of the electrons. This governing equation predicts that viscosity prevents complete cancellation of the ion current density by the electrons in the null region. Thus electron dynamics near the field null should not prevent the formation and deepening of field reversal using neutral-beam injection

  20. A comment on the null geodesic equations in Schwarzschild geometry

    International Nuclear Information System (INIS)

    Rosa, M.A.F.; Rodrigues Junior, W.A.

    1986-01-01

    An integration of the null geodesic equations in the Schwarzschild geometry, which is valid to first order in GM/Rc 2 is presented. The solution is compared with others published in the literature and their range of validity is analysed. Some misunderstandings are also clarified. (Author) [pt

  1. Maxwell fields and shear-free null geodesic congruences

    International Nuclear Information System (INIS)

    Newman, Ezra T

    2004-01-01

    We study and report on the class of vacuum Maxwell fields in Minkowski space that possess a non-degenerate, diverging, principal 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 being 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 worldline. The twisting case is much richer, more interesting and far more complicated. In a twisting subcase, where our main interests lie, the following strange interpretation can be given. 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 complex metric g η ab dz a dz b , the real vacuum Maxwell equations can be extended into the complex space and rewritten as curl W=i W radical, div W=0 with W=E+iB. This subcase of Maxwell fields can then be extended into the complex space so as to have as source, a complex analytic worldline, i.e., to now become complex Lienard-Wiechart fields. When viewed as real fields on the real Minkowski space (z a = x a ), they possess a real principal null vector that is shear-free but twisting and diverging. The twist is a measure of how far the complex worldline is from the real 'slice'. Most Maxwell fields in this subcase are asymptotically flat with a time-varying set of electric and magnetic moments, all depending on the complex displacements and the complex velocities

  2. A Comparison of Plasma Performance Between Single-Null and Double-Null Configurations During Elming H-Mode

    International Nuclear Information System (INIS)

    Petrie, T.W.; Fenstermacher, M.E.; Allen, S.L.; Carlstrom, T.N.; Gohil, P.; Groebner, R.J.; Greenfield, C.M.; Hyatt, A.W.; Lasnier, C.J.; La Haye, R.J.; Leonard, A.W.; Mahdavi, M.A.; Osborne, T.H.; Porter, G.D.; Rhodes, T.L.; Thomas, D.M.; Watkins, J.G.; West, W.P.; Wolf, N.S.

    1999-01-01

    Tokamak plasma performance generally improves with increased shaping of the plasma cross section, such as higher elongation and higher triangularity. The stronger shaping, especially higher triangularity, leads to changes in the magnetic topology of the divertor. Because there are engineering and divertor physics issues associated with changes in the details of the divertor flux geometry, especially as the configuration transitions from a single-null (SN) divertor to a marginally balanced double-null (DN) divertor, we have undertaken a systematic evaluation of the plasma characteristics as the magnetic geometry is varied, particularly with respect to (1) energy confinement, (2) the response of the plasma to deuterium gas fueling, (3) the operational density range for the ELMing H-mode, and (4) heat flux sharing by the diverters. To quantify the degree of divertor imbalance (or equivalently, to what degree the shape is double-null or single-null), we define a parameter DRSEP. DRSEP is taken as the radial distance between the upper divertor separatrix and the lower divertor separatrix, as determined at the outboard midplane. For example, if DRSEP=O, the configuration is a magnetically balanced DN; if DRSEP = +1.0 cm, the divertor configuration is biased toward the upper divertor. Three examples are shown in Fig. 1. In the following discussions, VB drift is directed toward the lower divertor

  3. Detection of long nulls in PSR B1706-16, a pulsar with large timing irregularities

    Science.gov (United States)

    Naidu, Arun; Joshi, Bhal Chandra; Manoharan, P. K.; Krishnakumar, M. A.

    2018-04-01

    Single pulse observations, characterizing in detail, the nulling behaviour of PSR B1706-16 are being reported for the first time in this paper. Our regular long duration monitoring of this pulsar reveals long nulls of 2-5 h with an overall nulling fraction of 31 ± 2 per cent. The pulsar shows two distinct phases of emission. It is usually in an active phase, characterized by pulsations interspersed with shorter nulls, with a nulling fraction of about 15 per cent, but it also rarely switches to an inactive phase, consisting of long nulls. The nulls in this pulsar are concurrent between 326.5 and 610 MHz. Profile mode changes accompanied by changes in fluctuation properties are seen in this pulsar, which switches from mode A before a null to mode B after the null. The distribution of null durations in this pulsar is bimodal. With its occasional long nulls, PSR B1706-16 joins the small group of intermediate nullers, which lie between the classical nullers and the intermittent pulsars. Similar to other intermediate nullers, PSR B1706-16 shows high timing noise, which could be due to its rare long nulls if one assumes that the slowdown rate during such nulls is different from that during the bursts.

  4. Statistical inferences under the Null hypothesis: Common mistakes and pitfalls in neuroimaging studies.

    Directory of Open Access Journals (Sweden)

    Jean-Michel eHupé

    2015-02-01

    Full Text Available Published studies using functional and structural MRI include many errors in the way data are analyzed and conclusions reported. This was observed when working on a comprehensive review of the neural bases of synesthesia, but these errors are probably endemic to neuroimaging studies. All studies reviewed had based their conclusions using Null Hypothesis Significance Tests (NHST. NHST have yet been criticized since their inception because they are more appropriate for taking decisions related to a Null hypothesis (like in manufacturing than for making inferences about behavioral and neuronal processes. Here I focus on a few key problems of NHST related to brain imaging techniques, and explain why or when we should not rely on significance tests. I also observed that, often, the ill-posed logic of NHST was even not correctly applied, and describe what I identified as common mistakes or at least problematic practices in published papers, in light of what could be considered as the very basics of statistical inference. MRI statistics also involve much more complex issues than standard statistical inference. Analysis pipelines vary a lot between studies, even for those using the same software, and there is no consensus which pipeline is the best. I propose a synthetic view of the logic behind the possible methodological choices, and warn against the usage and interpretation of two statistical methods popular in brain imaging studies, the false discovery rate (FDR procedure and permutation tests. I suggest that current models for the analysis of brain imaging data suffer from serious limitations and call for a revision taking into account the new statistics (confidence intervals logic.

  5. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  6. 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.

  7. Pair of null gravitating shells: III. Algebra of Dirac's observables

    International Nuclear Information System (INIS)

    Kouletsis, I; Hajicek, P

    2002-01-01

    The study of the two-shell system started in 'pair of null gravitating shells I and II' is continued. The pull back of the Liouville form to the constraint surface, which contains complete information about the Poisson brackets of Dirac observables, is computed in the singular double-null Eddington-Finkelstein (DNEF) gauge. The resulting formula shows that the variables conjugate to the Schwarzschild masses of the intershell spacetimes are simple combinations of the values of the DNEF coordinates on these spacetimes at the shells. The formula is valid for any number of in- and outgoing shells. After applying it to the two-shell system, the symplectic form is calculated for each component of the physical phase space; regular coordinates are found, defining it as a symplectic manifold. The symplectic transformation between the initial and final values of observables for the shell-crossing case is given

  8. Local modular Hamiltonians from the quantum null energy condition

    Science.gov (United States)

    Koeller, Jason; Leichenauer, Stefan; Levine, Adam; Shahbazi-Moghaddam, Arvin

    2018-03-01

    The vacuum modular Hamiltonian K of the Rindler wedge in any relativistic quantum field theory is given by the boost generator. Here we investigate the modular Hamiltonian for more general half-spaces which are bounded by an arbitrary smooth cut of a null plane. We derive a formula for the second derivative of the modular Hamiltonian with respect to the coordinates of the cut which schematically reads K''=Tv v . This formula can be integrated twice to obtain a simple expression for the modular Hamiltonian. The result naturally generalizes the standard expression for the Rindler modular Hamiltonian to this larger class of regions. Our primary assumptions are the quantum null energy condition—an inequality between the second derivative of the von Neumann entropy of a region and the stress tensor—and its saturation in the vacuum for these regions. We discuss the validity of these assumptions in free theories and holographic theories to all orders in 1 /N .

  9. Segmented Aperture Interferometric Nulling Testbed (SAINT) II: component systems update

    Science.gov (United States)

    Hicks, Brian A.; Bolcar, Matthew R.; Helmbrecht, Michael A.; Petrone, Peter; Burke, Elliot; Corsetti, James; Dillon, Thomas; Lea, Andrew; Pellicori, Samuel; Sheets, Teresa; Shiri, Ron; Agolli, Jack; DeVries, John; Eberhardt, Andrew; McCabe, Tyler

    2017-09-01

    This work presents updates to the coronagraph and telescope components of the Segmented Aperture Interferometric Nulling Testbed (SAINT). The project pairs an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC) towards demonstrating capabilities for the future space observatories needed to directly detect and characterize a significant sample of Earth-sized worlds around nearby stars in the quest for identifying those which may be habitable and possibly harbor life. Efforts to improve the VNC wavefront control optics and mechanisms towards repeating narrowband results are described. A narrative is provided for the design of new optical components aimed at enabling broadband performance. Initial work with the hardware and software interface for controlling the segmented telescope mirror is also presented.

  10. Lovelock vacua with a recurrent null vector field

    Czech Academy of Sciences Publication Activity Database

    Ortaggio, Marcello

    2018-01-01

    Roč. 97, č. 4 (2018), č. článku 044051. ISSN 2470-0010 R&D Projects: GA ČR GA13-10042S Institutional support: RVO:67985840 Keywords : Lovelock gravity * recurrent null vector field Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals.aps.org/prd/abstract/10.1103/PhysRevD.97.044051

  11. Spherical null geodesics of rotating Kerr black holes

    International Nuclear Information System (INIS)

    Hod, Shahar

    2013-01-01

    The non-equatorial spherical null geodesics of rotating Kerr black holes are studied analytically. Unlike the extensively studied equatorial circular orbits whose radii are known analytically, no closed-form formula exists in the literature for the radii of generic (non-equatorial) spherical geodesics. We provide here an approximate formula for the radii r ph (a/M;cosi) of these spherical null geodesics, where a/M is the dimensionless angular momentum of the black hole and cos i is an effective inclination angle (with respect to the black-hole equatorial plane) of the orbit. It is well-known that the equatorial circular geodesics of the Kerr spacetime (the prograde and the retrograde orbits with cosi=±1) are characterized by a monotonic dependence of their radii r ph (a/M;cosi=±1) on the dimensionless spin-parameter a/M of the black hole. We use here our novel analytical formula to reveal that this well-known property of the equatorial circular geodesics is actually not a generic property of the Kerr spacetime. In particular, we find that counter-rotating spherical null orbits in the range (3√(3)−√(59))/4≲cosi ph (a/M;cosi=const) on the dimensionless rotation-parameter a/M of the black hole. Furthermore, it is shown that spherical photon orbits of rapidly-rotating black holes are characterized by a critical inclination angle, cosi=√(4/7), above which the coordinate radii of the orbits approach the black-hole radius in the extremal limit. We prove that this critical inclination angle signals a transition in the physical properties of the spherical null geodesics: in particular, it separates orbits which are characterized by finite proper distances to the black-hole horizon from orbits which are characterized by infinite proper distances to the horizon.

  12. The quantum null energy condition in curved space

    Science.gov (United States)

    Fu, Zicao; Koeller, Jason; Marolf, Donald

    2017-11-01

    The quantum null energy condition (QNEC) is a conjectured bound on components (Tkk = Tab ka k^b) of the stress tensor along a null vector k a at a point p in terms of a second k-derivative of the von Neumann entropy S on one side of a null congruence N through p generated by k a . The conjecture has been established for super-renormalizeable field theories at points p that lie on a bifurcate Killing horizon with null tangent k a and for large-N holographic theories on flat space. While the Koeller-Leichenauer holographic argument clearly yields an inequality for general ( p, k^a) , more conditions are generally required for this inequality to be a useful QNEC. For d≤slant 3 , for arbitrary backgroud metric we show that the QNEC is naturally finite and independent of renormalization scheme when the expansion θ of N at the point p vanishes. This is consistent with the original QNEC conjecture which required θ and the shear σab to satisfy θ \\vert _p= \\dotθ\\vert p =0 , σab\\vert _p=0 . But for d=4, 5 more conditions than even these are required. In particular, we also require the vanishing of additional derivatives and a dominant energy condition. In the above cases the holographic argument does indeed yield a finite QNEC, though for d≥slant6 we argue these properties to fail even for weakly isolated horizons (where all derivatives of θ, σab vanish) that also satisfy a dominant energy condition. On the positive side, a corrollary to our work is that, when coupled to Einstein-Hilbert gravity, d ≤slant 3 holographic theories at large N satisfy the generalized second law (GSL) of thermodynamics at leading order in Newton’s constant G. This is the first GSL proof which does not require the quantum fields to be perturbations to a Killing horizon.

  13. Null half-supersymmetric solutions in five-dimensional supergravity

    International Nuclear Information System (INIS)

    Grover, Jai; Gutowski, Jan B.; Sabra, Wafic

    2008-01-01

    We classify half-supersymmetric solutions of gauged N = 2, D = 5 supergravity coupled to an arbitrary number of abelian vector multiplets for which all of the Killing spinors generate null Killing vectors. We show that there are four classes of solutions, and in each class we find the metric, scalars and gauge field strengths. When the scalar manifold is symmetric, the solutions correspond to a class of local near horizon geometries recently found by Kunduri and Lucietti.

  14. Yang-Mills theory in null path space

    International Nuclear Information System (INIS)

    Kent, S.L.

    1982-01-01

    A reformulation of classical GL(n,c) Yang-Mills theory is presented. The reformulation is in terms of a single matrix-valued function G on a six-dimensional subspace of the space of paths in Minkowski space, M. This subspace is defined as the null paths beginning at each point, (X/sup a/), of M and ending at future null infinity. A convenient parametrization of these paths is to give the Minkowski coordinates x/sup a/ of the starting point and the (complex) stereographic coordinates (xi, antixi) on S 2 which label the light cone generators of x/sup a/. A path is thus labeled by (x/sup a/,xi, antixi). The function G(x/sup a/,xi, antixi) is defined by the parallel propagation (with a given connection) of n linearly independent fiber vectors from x/sup a/ to null infinity along the (xi, antixi) generator. From knowledge of G(x/sup a/,xi, antixi) the connection one-form γ/sub a/ at the point x/sup a/ can be obtained is shown. Furthermore how the vacuum Yang-Mills equations can be imposed on the G is shown. This results in a rather complicated integro-differential equation for G which involves the characteristic initial data (essentially the radiation field) acting as the driving term. Two simple special cases are immediately obtainable; in the case of self-dual (or anti-self dual) fields the author obtains a simple derivation of the Sparling equation, namely delta G = -GA, while for Abelian (Maxwell) theories obtained the equation delta anti delta log G = -anti delta A-anti delta A, where A and its conjugate anti A are the characteristic free data given on null infinity. The latter equation is equivalent to the vacuum Maxwell equations

  15. Shearfree congruences of null geodesics and Killing tensors

    International Nuclear Information System (INIS)

    Dietz, W.; Ruediger, R.

    1980-01-01

    In this communication, the mutual connections between quantities that are generalizations of the notion of a a Killing vector field are investigated. A classification of these quantities in terms of a complex vector field αsub(a) is given. A common feature of all these quantities is that they imply the existence of a pair of shearfree geodetic null congruences. There are no explicit restrictions posed on the Ricci tensor. (author)

  16. Lovelock vacua with a recurrent null vector field

    Czech Academy of Sciences Publication Activity Database

    Ortaggio, Marcello

    2018-01-01

    Roč. 97, č. 4 (2018), č. článku 044051. ISSN 2470-0010 R&D Projects: GA ČR GA13-10042S Institutional support: RVO:67985840 Keywords : Lovelock gravity * recurrent null vector field Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals. aps .org/prd/abstract/10.1103/PhysRevD.97.044051

  17. In Search of the Null: The NCSA 2003 Presidential Address

    Directory of Open Access Journals (Sweden)

    Beth Davison

    2003-10-01

    Full Text Available Sociologists usually publish articles where the results show statistically significant differences between two groups of people. Results which show the opposite are generally called 'negative findings,' and are not considered publishable. Davison argues that we really ought to be looking for and encouraging the null finding, especially when social inequality and poverty are the issue. In addition, society as a whole should be working to eliminate poverty and inequality

  18. 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.)

  19. The Quantum Focussing Conjecture and Quantum Null Energy Condition

    Science.gov (United States)

    Koeller, Jason

    Evidence has been gathering over the decades that spacetime and gravity are best understood as emergent phenomenon, especially in the context of a unified description of quantum mechanics and gravity. The Quantum Focussing Conjecture (QFC) and Quantum Null Energy Condition (QNEC) are two recently-proposed relationships between entropy and geometry, and energy and entropy, respectively, which further strengthen this idea. In this thesis, we study the QFC and the QNEC. We prove the QNEC in a variety of contexts, including free field theories on Killing horizons, holographic theories on Killing horizons, and in more general curved spacetimes. We also consider the implications of the QFC and QNEC in asymptotically flat space, where they constrain the information content of gravitational radiation arriving at null infinity, and in AdS/CFT, where they are related to other semiclassical inequalities and properties of boundary-anchored extremal area surfaces. It is shown that the assumption of validity and vacuum-state saturation of the QNEC for regions of flat space defined by smooth cuts of null planes implies a local formula for the modular Hamiltonian of these regions. We also demonstrate that the QFC as originally conjectured can be violated in generic theories in d ≥ 5, which led the way to an improved formulation subsequently suggested by Stefan Leichenauer.

  20. 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.)

  1. PERSEE: a nulling interferometer with dynamic correction of external perturbations

    Science.gov (United States)

    Jacquinod, S.; Houairi, K.; Le Duigou, J.-M.; Barillot, M.; Cassaing, F.; Réess, J.-M.; Hénault, F.; Sorrente, B.; Morinaud, G.; Amans, J.-P.; Coudé du Foresto, V.; Ollivier, M.

    2017-11-01

    Nulling interferometry is one of the direct detection methods assessed to find and characterize extrasolar planets and particularly telluric ones. Several projects such as Darwin [1;2], TPF-I [3;4], PEGASE [5;6] or FKSI [7], are currently considered. One of the main issues is the feasibility of a stable polychromatic null despite the presence of significant disturbances, induced by vibrations, atmospheric turbulence on the ground or satellite drift. Satisfying all these requirements is a great challenge and a key issue of these missions. In the context of the PEGASE mission, it was decided (in 2006), to build a laboratory demonstrator named PERSEE. It is the first laboratory setup which couples deep nulling interferometry with a free flying GNC simulator [8]. It is developed by a consortium composed of CNES, IAS, LESIA, OCA, ONERA, and TAS. In this paper, we detail the main objectives, the set-up and the function of the bench. We describe all the subsystems and we focus particularly on two key points of PERSEE: the beam combiner and the Fringe tracker.

  2. Kastor-Traschen black holes, null geodesics and conformal circles

    International Nuclear Information System (INIS)

    Casey, Stephen

    2012-01-01

    The Kastor-Traschen metric is a time-dependent solution of the Einstein-Maxwell equations with positive cosmological constant Λ which can be used to describe an arbitrary number of charged dynamical black holes. In this paper, we consider the null geodesic structure of this solution, in particular, focusing on the projection to the space of orbits of the timelike conformal retraction. It is found that these projected light rays arise as integral curves of a system of third-order ordinary differential equations. This system is not uniquely defined, however, and we use the inherent freedom to construct a new system whose integral curves coincide with the projection of distinguished null curves of Kastor-Traschen arising from a magnetic flow. We discuss our results in the one-centre case and demonstrate a link to conformal circles in the limit Λ → 0. We also show how to construct analytic expressions for the projected null geodesics of this metric by exploiting a well-known diffeomorphism between the K-T metric and extremal Reissner-Nordstrom-de Sitter. We make some remarks about the two-centre solution and demonstrate a link with the one-centre case. (paper)

  3. "Time sweet time": circadian characterization of galectin-1 null mice

    Directory of Open Access Journals (Sweden)

    Rabinovich Gabriel A

    2010-04-01

    Full Text Available Abstract Background Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1 gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1-/- mice. Methods We analyzed wheel-running activity in light-dark conditions, constant darkness, phase responses to light pulses (LP at circadian time 15, and reentrainment to 6 hour shifts in light-dark schedule in wild-type (WT and Lgals1-/- mice. Results We found significant differences in free-running period, which was longer in mutant than in WT mice (24.02 vs 23.57 h, p alpha (14.88 vs. 12.35 circadian h, p Conclusions Given the effect of a null mutation on circadian period and entrainment, we indicate that galectin-1 could be involved in the regulation of murine circadian rhythmicity. This is the first study implicating galectin-1 in the mammalian circadian system.

  4. 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.)

  5. Left cardiac isomerism in the Sonic hedgehog null mouse.

    Science.gov (United States)

    Hildreth, Victoria; Webb, Sandra; Chaudhry, Bill; Peat, Jonathan D; Phillips, Helen M; Brown, Nigel; Anderson, Robert H; Henderson, Deborah J

    2009-06-01

    Sonic hedgehog (Shh) is a secreted morphogen necessary for the production of sidedness in the developing embryo. In this study, we describe the morphology of the atrial chambers and atrioventricular junctions of the Shh null mouse heart. We demonstrate that the essential phenotypic feature is isomerism of the left atrial appendages, in combination with an atrioventricular septal defect and a common atrioventricular junction. These malformations are known to be frequent in humans with left isomerism. To confirm the presence of left isomerism, we show that Pitx2c, a recognized determinant of morphological leftness, is expressed in the Shh null mutants on both the right and left sides of the inflow region, and on both sides of the solitary arterial trunk exiting from the heart. It has been established that derivatives of the second heart field expressing Isl1 are asymmetrically distributed in the developing normal heart. We now show that this population is reduced in the hearts from the Shh null mutants, likely contributing to the defects. To distinguish the consequences of reduced contributions from the second heart field from those of left-right patterning disturbance, we disrupted the movement of second heart field cells into the heart by expressing dominant-negative Rho kinase in the population of cells expressing Isl1. This resulted in absence of the vestibular spine, and presence of atrioventricular septal defects closely resembling those seen in the hearts from the Shh null mutants. The primary atrial septum, however, was well formed, and there was no evidence of isomerism of the atrial appendages, suggesting that these features do not relate to disruption of the contributions made by the second heart field. We demonstrate, therefore, that the Shh null mouse is a model of isomerism of the left atrial appendages, and show that the recognized associated malformations found at the venous pole of the heart in the setting of left isomerism are likely to arise from

  6. Parkin protects dopaminergic neurons from excessive Wnt/β-catenin signaling

    International Nuclear Information System (INIS)

    Rawal, Nina; Corti, Olga; Sacchetti, Paola; Ardilla-Osorio, Hector; Sehat, Bita; Brice, Alexis; Arenas, Ernest

    2009-01-01

    Parkinson's disease (PD) is caused by degeneration of the dopaminergic (DA) neurons of the substantia nigra but the molecular mechanisms underlying the degenerative process remain elusive. Several reports suggest that cell cycle deregulation in post-mitotic neurons could lead to neuronal cell death. We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates β-catenin protein levels in vivo. Stabilization of β-catenin in differentiated primary ventral midbrain neurons results in increased levels of cyclin E and proliferation, followed by increased levels of cleaved PARP and loss of DA neurons. Wnt3a signaling also causes death of post-mitotic DA neurons in parkin null animals, suggesting that both increased stabilization and decreased degradation of β-catenin results in DA cell death. These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and β-catenin-induced cell death.

  7. Apoptosis in spermatogonia irradiated P53 null mice

    International Nuclear Information System (INIS)

    Streit-Bianchi, M.; Hendry, J.H.; Roberts, S.A.; Morris, J.D.; Durgaryan, A.A.

    2007-01-01

    Complete text of publication follows. The exposure of germ cells to ionizing radiations is of concern both from high-dose therapeutic exposures and from low doses causing deleterious trans-generational mutations. P53 protein plays an important role in cellular damage and is expressed in the testis normally during meiosis, its expression being localised to the preleptotene and early/mid pachytene spermatocytes. P53 null mice, heterozygotes possessing a 129 Sv/C57BL6 genetic background and B6D2F1 mice have been irradiated to 1 and 2 Gy single doses. Fractionated exposures of 1+1 Gy at 4 hours interval were also carried out. Apoptosis induction, spermatogonia and spermatocytes survival were assessed by microscope analysis of histological samples at 4 to 96 hours after irradiation in time-course experiments. The same end-points were also assessed at 72 and 96 hours after irradiation to single doses in the region between 20cGy to 2Gy. A dose dependent level of p53 expression was observed at 4 hours after irradiation to 1 and 2 Gy which returned to normal level by 24 hours. Our data support a two process mode of apoptosis with a first wave around 12 hours followed by a second wave at 2-3 days. The first wave apoptosis is substantially reduced in p53 null mice whereas the second wave is reduced in B6D2F1 mice. The initial increase in apoptosis was delayed in some stages of the of germ cells development which were identified by the spermatids shape. Clear correlation exists between apoptosis and survival assessed in stage XI-XII Tubules 72 hours after irradiation. The data are in agreement with other data in literature indicating that irradiated spermatogonia die through apoptosis. The lack of apoptosis observed in p53 null mice results in a very high survival rate of daughter cells assessed later. Theses spermatocytes and the following progenitor cells are likely to carry mutations as most will not die in the smaller second wave of apoptosis observed 3 days after

  8. 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.

  9. Neuronal Glucose Transporter Isoform 3 Deficient Mice Demonstrate Features of Autism Spectrum Disorders

    OpenAIRE

    Zhao, Yuanzi; Fung, Camille; Shin, Don; Shin, Bo-Chul; Thamotharan, Shanthie; Sankar, Raman; Ehninger, Dan; Silva, Alcino; Devaskar, Sherin U.

    2009-01-01

    Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristic...

  10. A visualization of null geodesics for the bonnor massive dipole

    Directory of Open Access Journals (Sweden)

    G. Andree Oliva Mercado

    2015-08-01

    Full Text Available 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. Do electromagnetic waves always propagate along null geodesics?

    International Nuclear Information System (INIS)

    Asenjo, Felipe A; Hojman, Sergio A

    2017-01-01

    We find exact solutions to Maxwell equations written in terms of four-vector potentials in non–rotating, as well as in Gödel and Kerr spacetimes. We show that Maxwell equations can be reduced to two uncoupled second-order differential equations for combinations of the components of the four-vector potential. Exact electromagnetic waves solutions are written on given gravitational field backgrounds where they evolve. We find that in non–rotating spherical symmetric spacetimes, electromagnetic waves travel along null geodesics. However, electromagnetic waves on Gödel and Kerr spacetimes do not exhibit that behavior. (paper)

  12. Two-loop string theory on null compactifications

    International Nuclear Information System (INIS)

    Cove, Henry C.D.; Szabo, Richard J.

    2006-01-01

    We compute the two-loop contributions to the free energy in the null compactification of perturbative string theory at finite temperature. The cases of bosonic, type II and heterotic strings are all treated. The calculation exploits an explicit reductive parametrization of the moduli space of infinite-momentum frame string worldsheets in terms of branched cover instantons. Various arithmetic and physical properties of the instanton sums are described. Applications to symmetric product orbifold conformal field theories and to the matrix string theory conjecture are also briefly discussed

  13. Twisting null geodesic congruences and the Einstein-Maxwell equations

    International Nuclear Information System (INIS)

    Newman, Ezra T; Silva-Ortigoza, Gilberto

    2006-01-01

    In a recent article, we returned to the study of asymptotically flat solutions of the vacuum Einstein equations with a rather unconventional point of view. The essential observation in that work was that from a given asymptotically flat vacuum spacetime with a given Bondi shear, one can find a class of asymptotically shear-free (but, in general, twisting) null geodesic congruences where the class was uniquely given up to the arbitrary choice of a complex analytic 'worldline' in a four-dimensional complex space. By imitating certain terms in the Weyl tensor that are found in the algebraically special type II metrics, this complex worldline could be made unique and given-or assigned-the physical meaning as the complex centre of mass. Equations of motion for this case were found. The purpose of the present work is to extend those results to asymptotically flat solutions of the Einstein-Maxwell equations. Once again, in this case, we get a class of asymptotically shear-free null geodesic congruences depending on a complex worldline in the same four-dimensional complex space. However in this case there will be, in general, two distinct but uniquely chosen worldlines, one of which can be assigned as the complex centre of charge while the other could be called the complex centre of mass. Rather than investigating the situation where there are two distinct complex worldlines, we study instead the special degenerate case where the two worldlines coincide, i.e., where there is a single unique worldline. This mimics the case of algebraically special Einstein-Maxwell fields where the degenerate principle null vector of the Weyl tensor coincides with a Maxwell principle null vector. Again we obtain equations of motion for this worldline-but explicitly found here only in an approximation. Though there are ambiguities in assigning physical meaning to different terms it appears as if reliance on the Kerr and charged Kerr metrics and classical electromagnetic radiation theory helps

  14. The null-event method in computer simulation

    International Nuclear Information System (INIS)

    Lin, S.L.

    1978-01-01

    The simulation of collisions of ions moving under the influence of an external field through a neutral gas to non-zero temperatures is discussed as an example of computer models of processes in which a probe particle undergoes a series of interactions with an ensemble of other particles, such that the frequency and outcome of the events depends on internal properties of the second particles. The introduction of null events removes the need for much complicated algebra, leads to a more efficient simulation and reduces the likelihood of logical error. (Auth.)

  15. Null geodesic deviation II. Conformally flat space--times

    International Nuclear Information System (INIS)

    Peters, P.C.

    1975-01-01

    The equation of geodesic deviation is solved in conformally flat space--time in a covariant manner. The solution is given as an integral equation for general geodesics. The solution is then used to evaluate second derivatives of the world function and derivatives of the parallel propagator, which need to be known in order to find the Green's function for wave equations in curved space--time. A method of null geodesic limits of two-point functions is discussed, and used to find the scalar Green's function as an iterative series

  16. The new null testing method for the special optical window

    Science.gov (United States)

    Huang, Changchun

    2009-07-01

    The high speed, high precision and wide range specifications are requirement for the modern aircraft, which the traditional hemispherical dome can't achieve now, and the novel conformal window instead can enhance the aerodynamic performance of the aircraft obviously. To reduce the aerodynamic drag and radar cross-section, the window geometry is generally aspheric in shape. As a result, the involved fabrication and testing processes are much more challenging than that of conventional optics and must be mastered before these windows and systems can be implemented at an acceptable cost and risk. Metrology is one of the critical areas required to advance the conformal window technology. But as the surface of these conformal windows is not the traditional sphere lens, the measurement method for it is infeasible with the conventional optics measurement processes. This paper we express the development of testing technology for the special conformal windows in brief, and emphatically introduces one available novel testing method- a new null testing, and here based on the theory of compensation methods, The principle of Offner's refractive null lens has been extended to test the transmission wavefront through conformal window optics and provide feedback during surface fabrication. a compensator system for the was designed for the conformal window is given which parameters are 100mm for its aperture and two parabolic surface as conformal window, the final residual wavefront error(RMS) of which is less than 1/20λ(λ=632.8nm).

  17. Randomizing growing networks with a time-respecting null model

    Science.gov (United States)

    Ren, Zhuo-Ming; Mariani, Manuel Sebastian; Zhang, Yi-Cheng; Medo, Matúš

    2018-05-01

    Complex networks are often used to represent systems that are not static but grow with time: People make new friendships, new papers are published and refer to the existing ones, and so forth. To assess the statistical significance of measurements made on such networks, we propose a randomization methodology—a time-respecting null model—that preserves both the network's degree sequence and the time evolution of individual nodes' degree values. By preserving the temporal linking patterns of the analyzed system, the proposed model is able to factor out the effect of the system's temporal patterns on its structure. We apply the model to the citation network of Physical Review scholarly papers and the citation network of US movies. The model reveals that the two data sets are strikingly different with respect to their degree-degree correlations, and we discuss the important implications of this finding on the information provided by paradigmatic node centrality metrics such as indegree and Google's PageRank. The randomization methodology proposed here can be used to assess the significance of any structural property in growing networks, which could bring new insights into the problems where null models play a critical role, such as the detection of communities and network motifs.

  18. Geometry of extended null supersymmetry in M theory

    International Nuclear Information System (INIS)

    Conamhna, Oisin A.P. Mac

    2006-01-01

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

  19. Extrasolar Planetary Imaging Coronagraph (EPIC): visible nulling cornagraph testbed results

    Science.gov (United States)

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

    2008-07-01

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

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

    Science.gov (United States)

    Lyon, Richard G.

    2008-01-01

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

  1. Non-dissipative electromagnetic media with two Lorentz null cones

    International Nuclear Information System (INIS)

    Dahl, Matias F.

    2013-01-01

    We study Maxwell’s equations on a 4-manifold where the electromagnetic medium is modeled by an antisymmetric (2/2 )-tensor with 21 real coefficients. In this setting the Fresnel surface is a fourth-order polynomial surface that describes the dynamical response of the medium in the geometric optics limit. For example, in an isotropic medium the Fresnel surface is a Lorentz null cone. The contribution of this paper is the pointwise description of all electromagnetic medium tensors κ with real coefficients that satisfy the following three conditions: (i)medium κ is invertible, (ii)medium κ is skewon-free, or non-dissipative, (iii)the Fresnel surface of κ is the union of two distinct Lorentz null cones. We show that there are only three classes of media with these properties and give explicit expressions in local coordinates for each class. - Highlights: ► We find two new electromagnetic media classes for which the Fresnel surface decomposes into two light cones. ► In a suitable setting we classify all electromagnetic media where this is the case. ► We find an electromagnetic medium tensor with three different signal speeds in one direction. ► The work is related to [5], which classifies all media with one light cone (in a suitable setting).

  2. Plate with a hole obeys the averaged null energy condition

    International Nuclear Information System (INIS)

    Graham, Noah; Olum, Ken D.

    2005-01-01

    The negative energy density of Casimir systems appears to violate general relativity energy conditions. However, one cannot test the averaged null energy condition (ANEC) using standard calculations for perfectly reflecting plates, because the null geodesic would have to pass through the plates, where the calculation breaks down. To avoid this problem, we compute the contribution to ANEC for a geodesic that passes through a hole in a single plate. We consider both Dirichlet and Neumann boundary conditions in two and three space dimensions. We use a Babinet's principle argument to reduce the problem to a complementary finite disk correction to the perfect mirror result, which we then compute using scattering theory in elliptical and spheroidal coordinates. In the Dirichlet case, we find that the positive correction due to the hole overwhelms the negative contribution of the infinite plate. In the Neumann case, where the infinite plate gives a positive contribution, the hole contribution is smaller in magnitude, so again ANEC is obeyed. These results can be extended to the case of two plates in the limits of large and small hole radii. This system thus provides another example of a situation where ANEC turns out to be obeyed when one might expect it to be violated

  3. Meterwavelength Single-pulse Polarimetric Emission Survey. III. The Phenomenon of Nulling in Pulsars

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Rahul; Mitra, Dipanjan; Melikidze, George I., E-mail: rahulbasu.astro@gmail.com [Janusz Gil Institute of Astronomy, University of Zielona Góra, ul. Szafrana 2, 65–516 Zielona Góra (Poland)

    2017-09-10

    A detailed analysis of nulling was conducted for the pulsars studied in the Meterwavelength Single-pulse Polarimetric Emission Survey. We characterized nulling in 36 pulsars including 17 pulsars where the phenomenon was reported for the first time. The most dominant nulls lasted for a short duration, less than five periods. Longer duration nulls extending to hundreds of periods were also seen in some cases. A careful analysis showed the presence of periodicities in the transition from the null to the burst states in 11 pulsars. In our earlier work, fluctuation spectrum analysis showed multiple periodicities in 6 of these 11 pulsars. We demonstrate that the longer periodicity in each case was associated with nulling. The shorter periodicities usually originate from subpulse drifting. The nulling periodicities were more aligned with the periodic amplitude modulation, indicating a possible common origin for both. The most prevalent nulls last for a single period and can be potentially explained using random variations affecting the plasma processes in the pulsar magnetosphere. On the other hand, longer-duration nulls require changes in the pair-production processes, which need an external triggering mechanism for the changes. The presence of periodic nulling puts an added constraint on the triggering mechanism, which also needs to be periodic.

  4. Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas

    International Nuclear Information System (INIS)

    Chinyengetere, Fadzai; Sekula, David J.; Lu, Yun; Giustini, Andrew J.; Sanglikar, Aarti; Kawakami, Masanori; Ma, Tian; Burkett, Sandra S.; Eisenberg, Burton L.; Wells, Wendy A.; Hoopes, Paul J.; Demicco, Elizabeth G.; Lazar, Alexander J; Torres, Keila E.; Memoli, Vincent; Freemantle, Sarah J.; Dmitrovsky, Ethan

    2015-01-01

    USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. Heterozygous USP18 +/− FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. USP18 −/− FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6–12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly

  5. TorsinA dysfunction causes persistent neuronal nuclear pore defects.

    Science.gov (United States)

    Pappas, Samuel S; Liang, Chun-Chi; Kim, Sumin; Rivera, CheyAnne O; Dauer, William T

    2018-02-01

    A critical challenge to deciphering the pathophysiology of neurodevelopmental disease is identifying which of the myriad abnormalities that emerge during CNS maturation persist to contribute to long-term brain dysfunction. Childhood-onset dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA exemplifies this challenge. Neurons lacking torsinA develop transient nuclear envelope (NE) malformations during CNS maturation, but no NE defects are described in mature torsinA null neurons. We find that during postnatal CNS maturation torsinA null neurons develop mislocalized and dysfunctional nuclear pore complexes (NPC) that lack NUP358, normally added late in NPC biogenesis. SUN1, a torsinA-related molecule implicated in interphase NPC biogenesis, also exhibits localization abnormalities. Whereas SUN1 and associated nuclear membrane abnormalities resolve in juvenile mice, NPC defects persist into adulthood. These findings support a role for torsinA function in NPC biogenesis during neuronal maturation and implicate altered NPC function in dystonia pathophysiology. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Radiation Hardened NULL Convention Logic Asynchronous Circuit Design

    Directory of Open Access Journals (Sweden)

    Liang Zhou

    2015-10-01

    Full Text Available This paper proposes a radiation hardened NULL Convention Logic (NCL architecture that can recover from a single event latchup (SEL or single event upset (SEU fault without deadlock or any data loss. The proposed architecture is analytically proved to be SEL resistant, and by extension, proved to be SEU resistant. The SEL/SEU resistant version of a 3-stage full-word pipelined NCL 4 × 4 unsigned multiplier was implemented using the IBM cmrf8sf 130 nm 1.2 V process at the transistor level and simulated exhaustively with SEL fault injection to validate the proposed architectures. Compared with the original version, the SEL/SEU resilient version has 1.31× speed overhead, 2.74× area overhead, and 2.79× energy per operation overhead.

  7. The simple map for a single-null divertor tokamak

    International Nuclear Information System (INIS)

    Punjabi, A.; Verma, A.; Boozer, A.

    1996-01-01

    We present the simple map for a single-null divertor tokamak. The simple map is an area-preserving map based on the idea that magnetic field lines are a single-degree-of-freedom time-dependent Hamiltonian system, and that the basic features of such systems near the X-point are generic. We obtain the properties of this map and the resulting footprints of field lines on the divertor plate. These include the width of the stochastic layer, the edge safety factor, the area of the footprint and the amount of magnetic flux diverted. We give the safety factor profile, the average and median values of strike angles, lengths and the Liapunov exponents. We describe how the effects of magnetic perturbations can be included in the simple map. We show how the map can be applied to the problem of the determination of heat flux on the divertor plate in tokamaks. (Author)

  8. Status of the Visible Nulling Coronagraph Technology Demonstration Program

    Science.gov (United States)

    Clampin, M.; Lyon, R.

    2012-01-01

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

  9. Horizons in Matter:. Black Hole Hair Versus Null Big Bang

    Science.gov (United States)

    Bronnikov, K. A.; Zaslavskii, Oleg B.

    It is shown that only particular kinds of matter (in terms of the "radial" pressure-to-density ratio w) can coexist with Killing horizons in black hole or cosmological space-times. Thus, for arbitrary (not necessarily spherically symmetric) static black holes, admissible are vacuum matter (w = -1, i.e. the cosmological constant or its generalization with the same value of w) and matter with certain values of w between 0 and -1, in particular a gas of disordered cosmic strings (w = -1/3). If the cosmological evolution starts from a horizon (the so-called null big bang scenarios), this horizon can coexist with vacuum matter and certain kinds of phantom matter with w ≤ -3. It is concluded that normal matter in such scenarios is entirely created from vacuum.

  10. 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.

  11. 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

  12. Dinucleotide controlled null models for comparative RNA gene prediction.

    Science.gov (United States)

    Gesell, Tanja; Washietl, Stefan

    2008-05-27

    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. 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. SISSIz implements an efficient algorithm to randomize multiple alignments preserving dinucleotide content. It can be used to get more accurate estimates of false positive rates of existing programs, to produce negative controls for the training of machine learning based programs, or as standalone RNA gene finding program. Other applications in comparative genomics that require randomization of multiple alignments can be considered. SISSIz

  13. 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.

  14. 3D Solar Null Point Reconnection MHD Simulations

    Science.gov (United States)

    Baumann, G.; Galsgaard, K.; Nordlund, Å.

    2013-06-01

    Numerical MHD simulations of 3D reconnection events in the solar corona have improved enormously over the last few years, not only in resolution, but also in their complexity, enabling more and more realistic modeling. Various ways to obtain the initial magnetic field, different forms of solar atmospheric models as well as diverse driving speeds and patterns have been employed. This study considers differences between simulations with stratified and non-stratified solar atmospheres, addresses the influence of the driving speed on the plasma flow and energetics, and provides quantitative formulas for mapping electric fields and dissipation levels obtained in numerical simulations to the corresponding solar quantities. The simulations start out from a potential magnetic field containing a null-point, obtained from a Solar and Heliospheric Observatory (SOHO) Michelson Doppler Imager (MDI) magnetogram magnetogram extrapolation approximately 8 hours before a C-class flare was observed. The magnetic field is stressed with a boundary motion pattern similar to - although simpler than - horizontal motions observed by SOHO during the period preceding the flare. The general behavior is nearly independent of the driving speed, and is also very similar in stratified and non-stratified models, provided only that the boundary motions are slow enough. The boundary motions cause a build-up of current sheets, mainly in the fan-plane of the magnetic null-point, but do not result in a flare-like energy release. The additional free energy required for the flare could have been partly present in non-potential form at the initial state, with subsequent additions from magnetic flux emergence or from components of the boundary motion that were not represented by the idealized driving pattern.

  15. Molecular bass for a malic enzyme null mutation

    International Nuclear Information System (INIS)

    Brown, M.L.; Wise, L.S.; Rubin, C.S.

    1987-01-01

    Many tissues from normal (wt) mice have cytosolic malic enzyme (ME) activity and express two mRNAs (2 and 3.1 kb) that code for a single ME polypeptide. Mod-1 null (M-n) mice lack cytosolic ME activity, but express 2.5 and 3.6 kb mRNAs that hybridize with wt ME cDNAs. To investigate the basis for the ME deficiency cDNAs corresponding to M-n ME RNA were cloned. A λgt11 library was prepared using M-n liver mRNA as a template. Wt ME cDNA probes hybridized with several recombinant phages and a 2kb insert with an atypical (non-wt) restriction pattern was subcloned in pGEM 1 and sequenced. The M-n ME cDNA contains an internal directly repeated sequence that corresponds to nts 1109-1617 in the coding region of wt ME cDNA. A restriction fragment from M-n ME cDNA that includes the first 204 bp of repeated sequence and 306 bp of contiguous 5' sequence was subcloned into pGEM 1 and used as a template for synthesizing 32 P-labeled anti-sense RNA. After hybridization with M-n liver RNA the 510 nt transcript was resistant to RNA digestion; after hybridization with wt RNA only fragments corresponding to the normally non-contiguous 204 bp and 306 bp segments of the insert were protected. Thus the partial duplication of coding sequence in M-n ME mRNA is confirmed. Analyses of intron-exon organization in the relevant regions of the wt and M-n ME genes will provide further insights into the mechanism underlying the ME null mutation

  16. Surprising structures hiding in Penrose’s future null infinity

    Science.gov (United States)

    Newman, Ezra T.

    2017-07-01

    Since the late1950s, almost all discussions of asymptotically flat (Einstein-Maxwell) space-times have taken place in the context of Penrose’s null infinity, I+. In addition, almost all calculations have used the Bondi coordinate and tetrad systems. Beginning with a known asymptotically flat solution to the Einstein-Maxwell equations, we show first, that there are other natural coordinate systems, near I+, (analogous to light-cones in flat-space) that are based on (asymptotically) shear-free null geodesic congruences (analogous to the flat-space case). Using these new coordinates and their associated tetrad, we define the complex dipole moment, (the mass dipole plus i times angular momentum), from the l  =  1 harmonic coefficient of a component of the asymptotic Weyl tensor. Second, from this definition, from the Bianchi identities and from the Bondi-Sachs mass and linear momentum, we show that there exists a large number of results—identifications and dynamics—identical to those of classical mechanics and electrodynamics. They include, among many others, {P}=M{v}+..., {L}= {r} × {P} , spin, Newton’s second law with the rocket force term (\\dotM v) and radiation reaction, angular momentum conservation and others. All these relations take place in the rather mysterious H-space rather than in space-time. This leads to the enigma: ‘why do these well known relations of classical mechanics take place in H-space?’ and ‘What is the physical meaning of H-space?’

  17. Is PMI the Hypothesis or the Null Hypothesis?

    Science.gov (United States)

    Tarone, Aaron M; Sanford, Michelle R

    2017-09-01

    Over the past several decades, there have been several strident exchanges regarding whether forensic entomologists estimate the postmortem interval (PMI), minimum PMI, or something else. During that time, there has been a proliferation of terminology reflecting this concern regarding "what we do." This has been a frustrating conversation for some in the community because much of this debate appears to be centered on what assumptions are acknowledged directly and which are embedded within a list of assumptions (or ignored altogether) in the literature and in case reports. An additional component of the conversation centers on a concern that moving away from the use of certain terminology like PMI acknowledges limitations and problems that would make the application of entomology appear less useful in court-a problem for lawyers, but one that should not be problematic for scientists in the forensic entomology community, as uncertainty is part of science that should and can be presented effectively in the courtroom (e.g., population genetic concepts in forensics). Unfortunately, a consequence of the way this conversation is conducted is that even as all involved in the debate acknowledge the concerns of their colleagues, parties continue to talk past one another advocating their preferred terminology. Progress will not be made until the community recognizes that all of the terms under consideration take the form of null hypothesis statements and that thinking about "what we do" as a null hypothesis has useful legal and scientific ramifications that transcend arguments over the usage of preferred terminology. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Observation of a 3D Magnetic Null Point

    Energy Technology Data Exchange (ETDEWEB)

    Romano, P.; Falco, M. [INAF—Osservatorio Astrofisico di Catania, Via S. Sofia 78, I-95123 Catania (Italy); Guglielmino, S. L.; Murabito, M., E-mail: prom@oact.inaf.it [Dipartimento di Fisica e Astronomia—Sezione Astrofisica, Università di Catania, Via S. Sofia 78, I-95123 Catania (Italy)

    2017-03-10

    We describe high-resolution observations of a GOES B-class flare characterized by a circular ribbon at the chromospheric level, corresponding to the network at the photospheric level. We interpret the flare as a consequence of a magnetic reconnection event that occurred at a three-dimensional (3D) coronal null point located above the supergranular cell. The potential field extrapolation of the photospheric magnetic field indicates that the circular chromospheric ribbon is cospatial with the fan footpoints, while the ribbons of the inner and outer spines look like compact kernels. We found new interesting observational aspects that need to be explained by models: (1) a loop corresponding to the outer spine became brighter a few minutes before the onset of the flare; (2) the circular ribbon was formed by several adjacent compact kernels characterized by a size of 1″–2″; (3) the kernels with a stronger intensity emission were located at the outer footpoint of the darker filaments, departing radially from the center of the supergranular cell; (4) these kernels started to brighten sequentially in clockwise direction; and (5) the site of the 3D null point and the shape of the outer spine were detected by RHESSI in the low-energy channel between 6.0 and 12.0 keV. Taking into account all these features and the length scales of the magnetic systems involved in the event, we argue that the low intensity of the flare may be ascribed to the low amount of magnetic flux and to its symmetric configuration.

  19. 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.

  20. An equation satisfied by the tangent to a shear-free, geodesic, null congruence

    International Nuclear Information System (INIS)

    Hogan, P.A.; Dublin Inst. for Advanced Studies

    1987-01-01

    A tensorial equation satisfied by the tangent to a shear-free geodesic, null congruence is presented. If the congruence is neither twist-free nor expansion-free then the equation defines a second, unique, null direction previously obtained, using the spinor formalism, by Somers. Some further properties of the equation are discussed. (orig.)

  1. Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.

    Science.gov (United States)

    Fan, Jing; Stemkowski, Patrick L; Gandini, Maria A; Black, Stefanie A; Zhang, Zizhen; Souza, Ivana A; Chen, Lina; Zamponi, Gerald W

    2016-01-01

    Genetic ablation of cellular prion protein (PrP(C)) has been linked to increased neuronal excitability and synaptic activity in the hippocampus. We have previously shown that synaptic activity in hippocampi of PrP-null mice is increased due to enhanced N-methyl-D-aspartate receptor (NMDAR) function. Here, we focused on the effect of PRNP gene knock-out (KO) on intrinsic neuronal excitability, and in particular, the underlying ionic mechanism in hippocampal neurons cultured from P0 mouse pups. We found that the absence of PrP(C) profoundly affected the firing properties of cultured hippocampal neurons in the presence of synaptic blockers. The membrane impedance was greater in PrP-null neurons, and this difference was abolished by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 (100 μM). HCN channel activity appeared to be functionally regulated by PrP(C). The amplitude of voltage sag, a characteristic of activating HCN channel current (I h), was decreased in null mice. Moreover, I h peak current was reduced, along with a hyperpolarizing shift in activation gating and slower kinetics. However, neither HCN1 nor HCN2 formed a biochemical complex with PrP(C). These results suggest that the absence of PrP downregulates the activity of HCN channels through activation of a cell signaling pathway rather than through direct interactions. This in turn contributes to an increase in membrane impedance to potentiate neuronal excitability.

  2. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  3. Motor Neuron Diseases

    Science.gov (United States)

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  4. Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?

    Science.gov (United States)

    Swanson, Sonja A; Labrecque, Jeremy; Hernán, Miguel A

    2018-05-02

    Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.

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

    International Nuclear Information System (INIS)

    Kumar, Sanjay; Bhattacharyya, R.

    2016-01-01

    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.

  6. Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

    Directory of Open Access Journals (Sweden)

    Andrea R. Yung

    2018-02-01

    Full Text Available During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR, and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots.

  7. Nulling interferometry for the darwin mission: laboratory demonstration experiment

    Science.gov (United States)

    Ollivier, Marc; Léger, Alain; Sekulic, Predrag; Labèque, Alain; Michel, Guy

    2017-11-01

    The DARWIN mission is a project of the European Space Agency that should allow around 2012 the search for extrasolar planets and a spectral analysis of their potential atmosphere in order to evidence gases and particularly tracers of life. The principle of the instrument is based on the Bracewell nulling interferometer. It allows high angular resolution and high dynamic range. However, this concept, proposed more than 20 years ago, has never been experimentally demonstrated in the thermal infrared with high levels of extinction. We present here a laboratory monochromatic experiment dedicated to this goal. A theoretical and numerical approach of the question highlights a strong difficulty: the need for very clean and homogeneous wavefronts, in terms of intensity, phase and polarisation distribution. A classical interferometric approach appears to be insufficient to reach our goals. We have shown theoretically then numerically that this difficulty can be surpassed if we perform an optical filtering of the interfering beams. This technique allows us to decrease strongly the optical requirements and to view very high interferometric contrast measurements with commercial optical pieces. We present here a laboratory interferometer working at 10,6 microns, and implementing several techniques of optical filtering (pinholes and single-mode waveguides), its realisation, and its first promising results. We particularly present measurements that exhibit stable visibility levels better than 99,9% that is to say extinction levels better than 1000.

  8. Constrained Null Space Component Analysis for Semiblind Source Separation Problem.

    Science.gov (United States)

    Hwang, Wen-Liang; Lu, Keng-Shih; Ho, Jinn

    2018-02-01

    The blind source separation (BSS) problem extracts unknown sources from observations of their unknown mixtures. A current trend in BSS is the semiblind approach, which incorporates prior information on sources or how the sources are mixed. The constrained independent component analysis (ICA) approach has been studied to impose constraints on the famous ICA framework. We introduced an alternative approach based on the null space component (NCA) framework and referred to the approach as the c-NCA approach. We also presented the c-NCA algorithm that uses signal-dependent semidefinite operators, which is a bilinear mapping, as signatures for operator design in the c-NCA approach. Theoretically, we showed that the source estimation of the c-NCA algorithm converges with a convergence rate dependent on the decay of the sequence, obtained by applying the estimated operators on corresponding sources. The c-NCA can be formulated as a deterministic constrained optimization method, and thus, it can take advantage of solvers developed in optimization society for solving the BSS problem. As examples, we demonstrated electroencephalogram interference rejection problems can be solved by the c-NCA with proximal splitting algorithms by incorporating a sparsity-enforcing separation model and considering the case when reference signals are available.

  9. 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.

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

    Science.gov (United States)

    Shih, Shui-I

    2013-01-01

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

  11. Conical twist fields and null polygonal Wilson loops

    Science.gov (United States)

    Castro-Alvaredo, Olalla A.; Doyon, Benjamin; Fioravanti, Davide

    2018-06-01

    Using an extension of the concept of twist field in QFT to space-time (external) symmetries, we study conical twist fields in two-dimensional integrable QFT. These create conical singularities of arbitrary excess angle. We show that, upon appropriate identification between the excess angle and the number of sheets, they have the same conformal dimension as branch-point twist fields commonly used to represent partition functions on Riemann surfaces, and that both fields have closely related form factors. However, we show that conical twist fields are truly different from branch-point twist fields. They generate different operator product expansions (short distance expansions) and form factor expansions (large distance expansions). In fact, we verify in free field theories, by re-summing form factors, that the conical twist fields operator product expansions are correctly reproduced. We propose that conical twist fields are the correct fields in order to understand null polygonal Wilson loops/gluon scattering amplitudes of planar maximally supersymmetric Yang-Mills theory.

  12. Lovelock vacua with a recurrent null vector field

    Science.gov (United States)

    Ortaggio, Marcello

    2018-02-01

    Vacuum solutions of Lovelock gravity in the presence of a recurrent null vector field (a subset of Kundt spacetimes) are studied. We first discuss the general field equations, which constrain both the base space and the profile functions. While choosing a "generic" base space puts stronger constraints on the profile, in special cases there also exist solutions containing arbitrary functions (at least for certain values of the coupling constants). These and other properties (such as the p p - waves subclass and the overlap with VSI, CSI and universal spacetimes) are subsequently analyzed in more detail in lower dimensions n =5 , 6 as well as for particular choices of the base manifold. The obtained solutions describe various classes of nonexpanding gravitational waves propagating, e.g., in Nariai-like backgrounds M2×Σn -2. An Appendix contains some results about general (i.e., not necessarily Kundt) Lovelock vacua of Riemann type III/N and of Weyl and traceless-Ricci type III/N. For example, it is pointed out that for theories admitting a triply degenerate maximally symmetric vacuum, all the (reduced) field equations are satisfied identically, giving rise to large classes of exact solutions.

  13. Generation of mice with a conditional Foxp2 null allele

    OpenAIRE

    French, C.; Groszer, M.; Preece, C.; Coupe, A.; Rajewsky, K.; Fisher, S.

    2007-01-01

    Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12?14 of Foxp2; these exons encode the DNA-bindi...

  14. Measurement of high-departure aspheres using subaperture stitching with the Variable Optical Null (VON)

    Science.gov (United States)

    Kulawiec, Andrew; Murphy, Paul; DeMarco, Michael

    2010-10-01

    Aspheric surfaces are proven to provide significant benefits to a wide variety of optical systems, but the ability to produce high-precision aspheric surfaces has historically been limited by the ability (or lack thereof) to measure them. Traditionally, aspheric measurements have required dedicated null optics, but the cost, lead time, and calibration difficulty of using null optics has made the use of aspheres more challenging and less attractive. In the past three years, QED has developed the Subaperture Stitching Interferometer for Aspheres (SSI-A®) to help address this limitation, providing flexible aspheric measurement capability of up to 200 waves of aspheric departure from best-fit sphere. Some aspheres, however, have thousands of waves of departure. We have recently developed Variable Optical Null (VON) technology that can null much of the aspheric departure in a subaperture. The VON is automatically configurable and is adjusted to nearly null each specific subaperture of an asphere. This ability to nearly null a local subaperture of an asphere provides a significant boost in aspheric measurement capability, enabling aspheres with up to 1000 waves of departure to be measured, without the use of dedicated null optics. We outline the basic principles of subaperture stitching and VON technology, demonstrate the extended capability provided by the VON, and present measurement results from the new Aspheric Stitching Interferometer (ASI®).

  15. Shocks and currents in stratified atmospheres with a magnetic null point

    Science.gov (United States)

    Tarr, Lucas A.; Linton, Mark

    2017-08-01

    We use the resistive MHD code LARE (Arber et al 2001) to inject a compressive MHD wavepacket into a stratified atmosphere that has a single magnetic null point, as recently described in Tarr et al 2017. The 2.5D simulation represents a slice through a small ephemeral region or area of plage. The strong gradients in field strength and connectivity related to the presence of the null produce substantially different dynamics compared to the more slowly varying fields typically used in simple sunspot models. The wave-null interaction produces a fast mode shock that collapses the null into a current sheet and generates a set of outward propagating (from the null) slow mode shocks confined to field lines near each separatrix. A combination of oscillatory reconnection and shock dissipation ultimately raise the plasma's internal energy at the null and along each separatrix by 25-50% above the background. The resulting pressure gradients must be balanced by Lorentz forces, so that the final state has contact discontinuities along each separatrix and a persistent current at the null. The simulation demonstrates that fast and slow mode waves localize currents to the topologically important locations of the field, just as their Alfvenic counterparts do, and also illustrates the necessity of treating waves and reconnection as coupled phenomena.

  16. Modular Hamiltonians on the null plane and the Markov property of the vacuum state

    Science.gov (United States)

    Casini, Horacio; Testé, Eduardo; Torroba, Gonzalo

    2017-09-01

    We compute the modular Hamiltonians of regions having the future horizon lying on a null plane. For a CFT this is equivalent to regions with a boundary of arbitrary shape lying on the null cone. These Hamiltonians have a local expression on the horizon formed by integrals of the stress tensor. We prove this result in two different ways, and show that the modular Hamiltonians of these regions form an infinite dimensional Lie algebra. The corresponding group of unitary transformations moves the fields on the null surface locally along the null generators with arbitrary null line dependent velocities, but act non-locally outside the null plane. We regain this result in greater generality using more abstract tools on the algebraic quantum field theory. Finally, we show that modular Hamiltonians on the null surface satisfy a Markov property that leads to the saturation of the strong sub-additive inequality for the entropies and to the strong super-additivity of the relative entropy.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Tarr, Lucas A.; Linton, Mark; Leake, James, E-mail: lucas.tarr.ctr@nrl.navy.mil [U.S. Naval Research Laboratory, 4555 Overlook Ave. SW, Washington, DC 20375 (United States)

    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 {sub 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% (0.036 E {sub 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.

  19. An improved null model for assessing the net effects of multiple stressors on communities.

    Science.gov (United States)

    Thompson, Patrick L; MacLennan, Megan M; Vinebrooke, Rolf D

    2018-01-01

    Ecological stressors (i.e., environmental factors outside their normal range of variation) can mediate each other through their interactions, leading to unexpected combined effects on communities. Determining whether the net effect of stressors is ecologically surprising requires comparing their cumulative impact to a null model that represents the linear combination of their individual effects (i.e., an additive expectation). However, we show that standard additive and multiplicative null models that base their predictions on the effects of single stressors on community properties (e.g., species richness or biomass) do not provide this linear expectation, leading to incorrect interpretations of antagonistic and synergistic responses by communities. We present an alternative, the compositional null model, which instead bases its predictions on the effects of stressors on individual species, and then aggregates them to the community level. Simulations demonstrate the improved ability of the compositional null model to accurately provide a linear expectation of the net effect of stressors. We simulate the response of communities to paired stressors that affect species in a purely additive fashion and compare the relative abilities of the compositional null model and two standard community property null models (additive and multiplicative) to predict these linear changes in species richness and community biomass across different combinations (both positive, negative, or opposite) and intensities of stressors. The compositional model predicts the linear effects of multiple stressors under almost all scenarios, allowing for proper classification of net effects, whereas the standard null models do not. Our findings suggest that current estimates of the prevalence of ecological surprises on communities based on community property null models are unreliable, and should be improved by integrating the responses of individual species to the community level as does our

  20. OBSERVATION OF MAGNETIC RECONNECTION AT A 3D NULL POINT ASSOCIATED WITH A SOLAR ERUPTION

    International Nuclear Information System (INIS)

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

    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 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.

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

    Indian Academy of Sciences (India)

    Present address: Institute of Stem Cells and Regenerative Medicine, Bangalore, India ... [Chandra Shekar P, Naim A, Partha Sarathi D and Kumar S 2011 Argonaute-2-null embryonic stem cells are retarded in self-renewal ..... Research, India.

  2. 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

  3. Vacuum non-expanding horizons and shear-free null geodesic congruences

    International Nuclear Information System (INIS)

    Adamo, T M; Newman, E T

    2009-01-01

    We investigate the geometry of a particular class of null surfaces in spacetime called vacuum non-expanding horizons (NEHs). Using the spin-coefficient equation, we provide a complete description of the horizon geometry, as well as fixing a canonical choice of null tetrad and coordinates on a NEH. By looking for particular classes of null geodesic congruences which live exterior to NEHs but have the special property that their shear vanishes at the intersection with the horizon, a good cut formalism for NEHs is developed which closely mirrors asymptotic theory. In particular, we show that such null geodesic congruences are generated by arbitrary choice of a complex worldline in a complex four-dimensional space, each such choice induces a CR structure on the horizon, and a particular worldline (and hence CR structure) may be chosen by transforming to a privileged tetrad frame.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  5. Are eikonal quasinormal modes linked to the unstable circular null geodesics?

    Directory of Open Access Journals (Sweden)

    R.A. Konoplya

    2017-08-01

    Full Text Available In Cardoso et al. [6] it was claimed that quasinormal modes which any stationary, spherically symmetric and asymptotically flat black hole emits in the eikonal regime are determined by the parameters of the circular null geodesic: the real and imaginary parts of the quasinormal mode are multiples of the frequency and instability timescale of the circular null geodesics respectively. We shall consider asymptotically flat black hole in the Einstein–Lovelock theory, find analytical expressions for gravitational quasinormal modes in the eikonal regime and analyze the null geodesics. Comparison of the both phenomena shows that the expected link between the null geodesics and quasinormal modes is violated in the Einstein–Lovelock theory. Nevertheless, the correspondence exists for a number of other cases and here we formulate its actual limits.

  6. Are eikonal quasinormal modes linked to the unstable circular null geodesics?

    Science.gov (United States)

    Konoplya, R. A.; Stuchlík, Z.

    2017-08-01

    In Cardoso et al. [6] it was claimed that quasinormal modes which any stationary, spherically symmetric and asymptotically flat black hole emits in the eikonal regime are determined by the parameters of the circular null geodesic: the real and imaginary parts of the quasinormal mode are multiples of the frequency and instability timescale of the circular null geodesics respectively. We shall consider asymptotically flat black hole in the Einstein-Lovelock theory, find analytical expressions for gravitational quasinormal modes in the eikonal regime and analyze the null geodesics. Comparison of the both phenomena shows that the expected link between the null geodesics and quasinormal modes is violated in the Einstein-Lovelock theory. Nevertheless, the correspondence exists for a number of other cases and here we formulate its actual limits.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Null geodesics and embedding diagrams of the interior Schwarzschild--de Sitter spacetimes with uniform density

    International Nuclear Information System (INIS)

    Stuchlik, Zdenek; Hledik, Stanislav; Soltes, Jiri; Ostgaard, Erlend

    2001-01-01

    Null geodesics and embedding diagrams of central planes in the ordinary space geometry and the optical reference geometry of the interior Schwarzschild--de Sitter spacetimes with uniform density are studied. For completeness, both positive and negative values of the cosmological constant are considered. The null geodesics are restricted to the central planes of these spacetimes, and their properties can be reflected by an 'effective potential.' If the interior spacetime is extremely compact, the effective potential has a local maximum corresponding to a stable circular null geodesic around which bound null geodesics are concentrated. The upper limit on the size of the interior spacetimes containing bound null geodesics is R=3M, independently of the value of the cosmological constant. The embedding diagrams of the central planes of the ordinary geometry into three-dimensional Euclidean space are well defined for the complete interior of all spacetimes with a repulsive cosmological constant, but the planes cannot be embedded into the Euclidean space in the case of spacetimes with subcritical values of an attractive cosmological constant. On the other hand, the embedding diagrams of the optical geometry are well defined for all of the spacetimes, and the turning points of these diagrams correspond to the radii of the circular null geodesics. All the embedding diagrams, for both the ordinary and optical geometry, are smoothly matched to the corresponding embedding diagrams of the external vacuum Schwarzschild--de Sitter spacetimes

  10. 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.

  11. The data-driven null models for information dissemination tree in social networks

    Science.gov (United States)

    Zhang, Zhiwei; Wang, Zhenyu

    2017-10-01

    For the purpose of detecting relatedness and co-occurrence between users, as well as the distribution features of nodes in spreading path of a social network, this paper explores topological characteristics of information dissemination trees (IDT) that can be employed indirectly to probe the information dissemination laws within social networks. Hence, three different null models of IDT are presented in this article, including the statistical-constrained 0-order IDT null model, the random-rewire-broken-edge 0-order IDT null model and the random-rewire-broken-edge 2-order IDT null model. These null models firstly generate the corresponding randomized copy of an actual IDT; then the extended significance profile, which is developed by adding the cascade ratio of information dissemination path, is exploited not only to evaluate degree correlation of two nodes associated with an edge, but also to assess the cascade ratio of different length of information dissemination paths. The experimental correspondences of the empirical analysis for several SinaWeibo IDTs and Twitter IDTs indicate that the IDT null models presented in this paper perform well in terms of degree correlation of nodes and dissemination path cascade ratio, which can be better to reveal the features of information dissemination and to fit the situation of real social networks.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    International Nuclear Information System (INIS)

    Takubo, Keiyo; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio

    2006-01-01

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

  14. Retinoic acid from the meninges regulates cortical neuron generation.

    Science.gov (United States)

    Siegenthaler, Julie A; Ashique, Amir M; Zarbalis, Konstantinos; Patterson, Katelin P; Hecht, Jonathan H; Kane, Maureen A; Folias, Alexandra E; Choe, Youngshik; May, Scott R; Kume, Tsutomu; Napoli, Joseph L; Peterson, Andrew S; Pleasure, Samuel J

    2009-10-30

    Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

  15. BACE1 Deficiency Causes Abnormal Neuronal Clustering in the Dentate Gyrus

    Directory of Open Access Journals (Sweden)

    Hailong Hou

    2017-07-01

    Full Text Available BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ. Such clusters were rarely observed in wild-type SPZ and not reported in other mouse models. To understand their origins and fates, we examined how neuroblasts in BACE1-null SPZ mature and migrate during early postnatal development. We show that such neuroblasts are destined to form Prox1-positive granule cells in the dentate granule cell layer, and mainly mature to form excitatory neurons, but not inhibitory neurons. Mechanistically, higher levels of reelin potentially contribute to abnormal neurogenesis and timely migration in BACE1-null SPZ. Altogether, we demonstrate that BACE1 is a critical regulator in forming the dentate granule cell layer through timely maturation and migration of SPZ neuroblasts.

  16. Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

    Science.gov (United States)

    van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F

    2012-12-10

    Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

  17. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster

    Science.gov (United States)

    Li, Xianghua; Overton, Ian M.; Baines, Richard A.; Keegan, Liam P.; O’Connell, Mary A.

    2014-01-01

    RNA editing by deamination of specific adenosine bases to inosines during pre-mRNA processing generates edited isoforms of proteins. Recoding RNA editing is more widespread in Drosophila than in vertebrates. Editing levels rise strongly at metamorphosis, and Adar5G1 null mutant flies lack editing events in hundreds of CNS transcripts; mutant flies have reduced viability, severely defective locomotion and age-dependent neurodegeneration. On the other hand, overexpressing an adult dADAR isoform with high enzymatic activity ubiquitously during larval and pupal stages is lethal. Advantage was taken of this to screen for genetic modifiers; Adar overexpression lethality is rescued by reduced dosage of the Rdl (Resistant to dieldrin), gene encoding a subunit of inhibitory GABA receptors. Reduced dosage of the Gad1 gene encoding the GABA synthetase also rescues Adar overexpression lethality. Drosophila Adar5G1 mutant phenotypes are ameliorated by feeding GABA modulators. We demonstrate that neuronal excitability is linked to dADAR expression levels in individual neurons; Adar-overexpressing larval motor neurons show reduced excitability whereas Adar5G1 null mutant or targeted Adar knockdown motor neurons exhibit increased excitability. GABA inhibitory signalling is impaired in human epileptic and autistic conditions, and vertebrate ADARs may have a relevant evolutionarily conserved control over neuronal excitability. PMID:24137011

  18. Selective depletion of microglial progranulin in mice is not sufficient to cause neuronal ceroid lipofuscinosis or neuroinflammation.

    Science.gov (United States)

    Petkau, Terri L; Kosior, Natalia; de Asis, Kathleen; Connolly, Colúm; Leavitt, Blair R

    2017-11-17

    Progranulin deficiency due to heterozygous null mutations in the GRN gene are a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations are thought to be a rare cause of neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout (Grn-null) mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. In the brain, progranulin is predominantly expressed in neurons and microglia, and previously, we demonstrated that neuronal-specific depletion of progranulin does not recapitulate the neuropathological phenotype of Grn-null mice. In this study, we evaluated whether selective depletion of progranulin expression in myeloid-lineage cells, including microglia, causes NCL-like neuropathology or neuroinflammation in mice. We generated mice with progranulin depleted in myeloid-lineage cells by crossing mice homozygous for a floxed progranulin allele to mice expressing Cre recombinase under control of the LyzM promotor (Lyz-cKO). Progranulin expression was reduced by approximately 50-70% in isolated microglia compared to WT levels. Lyz-cKO mice aged to 12 months did not display any increase in lipofuscin deposition, microgliosis, or astrogliosis in the four brain regions examined, though increases were observed for many of these measures in Grn-null animals. To evaluate the functional effect of reduced progranulin expression in isolated microglia, primary cultures were stimulated with controlled standard endotoxin and cytokine release was measured. While Grn-null microglia display a hyper-inflammatory phenotype, Lyz-cKO and WT microglia secreted similar levels of inflammatory cytokines. We conclude that progranulin expression from either microglia or neurons is sufficient to prevent the development of NCL-like neuropathology in mice. Furthermore, microglia that are deficient for progranulin expression but isolated from a progranulin

  19. Kappe neurons, a novel population of olfactory sensory neurons

    OpenAIRE

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons ar...

  20. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  1. PDF and cAMP enhance PER stability in Drosophila clock neurons

    Science.gov (United States)

    Li, Yue; Guo, Fang; Shen, James; Rosbash, Michael

    2014-01-01

    The neuropeptide PDF is important for Drosophila circadian rhythms: pdf01 (pdf-null) animals are mostly arrhythmic or short period in constant darkness and have an advanced activity peak in light–dark conditions. PDF contributes to the amplitude, synchrony, as well as the pace of circadian rhythms within clock neurons. PDF is known to increase cAMP levels in PDR receptor (PDFR)-containing neurons. However, there is no known connection of PDF or of cAMP with the Drosophila molecular clockworks. We discovered that the mutant period gene perS ameliorates the phenotypes of pdf-null flies. The period protein (PER) is a well-studied repressor of clock gene transcription, and the perS protein (PERS) has a markedly short half-life. The result therefore suggests that the PDF-mediated increase in cAMP might lengthen circadian period by directly enhancing PER stability. Indeed, increasing cAMP levels and cAMP-mediated protein kinase A (PKA) activity stabilizes PER, in S2 tissue culture cells and in fly circadian neurons. Adding PDF to fly brains in vitro has a similar effect. Consistent with these relationships, a light pulse causes more prominent PER degradation in pdf01 circadian neurons than in wild-type neurons. The results indicate that PDF contributes to clock neuron synchrony by increasing cAMP and PKA, which enhance PER stability and decrease clock speed in intrinsically fast-paced PDFR-containing clock neurons. We further suggest that the more rapid degradation of PERS bypasses PKA regulation and makes the pace of clock neurons more uniform, allowing them to avoid much of the asynchrony caused by the absence of PDF. PMID:24707054

  2. Spinal cord: motor neuron diseases.

    Science.gov (United States)

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

    Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Oculomotor deficits in aryl hydrocarbon receptor null mouse.

    Directory of Open Access Journals (Sweden)

    Aline Chevallier

    Full Text Available The Aryl hydrocarbon Receptor or AhR, a ligand-activated transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD. Recent studies in Caenorhabditis elegans and Drosophila melanogaster show that the orthologs of the AhR are expressed exclusively in certain types of neurons and are implicated in the development and the homeostasis of the central nervous system. While physiological roles of the AhR were demonstrated in the mammalian heart, liver and gametogenesis, its ontogenic expression and putative neural functions remain elusive. Here, we report that the constitutive absence of the AhR in adult mice (AhR-/- leads to abnormal eye movements in the form of a spontaneous pendular horizontal nystagmus. To determine if the nystagmus is of vestibular, visual, or cerebellar origin, gaze stabilizing reflexes, namely vestibulo-ocular and optokinetic reflexes (VOR and OKR, were investigated. The OKR is less effective in the AhR-/- mice suggesting a deficit in the visuo-motor circuitry, while the VOR is mildly affected. Furthermore, the AhR is expressed in the retinal ganglion cells during the development, however electroretinograms revealed no impairment of retinal cell function. The structure of the cerebellum of the AhR-/- mice is normal which is compatible with the preserved VOR adaptation, a plastic process dependent on cerebellar integrity. Finally, intoxication with TCDD of control adults did not lead to any abnormality of the oculomotor control. These results demonstrate that the absence of the AhR leads to acquired central nervous system deficits in the adults. Given the many common features between both AhR mouse and human infantile nystagmus syndromes, the AhR-/- mice might give insights into the developmental mechanisms which lead to congenital eye disorders.

  4. Metabolic, Reproductive, and Neurologic Abnormalities in Agpat1-Null Mice.

    Science.gov (United States)

    Agarwal, Anil K; Tunison, Katie; Dalal, Jasbir S; Nagamma, Sneha S; Hamra, F Kent; Sankella, Shireesha; Shao, Xinli; Auchus, Richard J; Garg, Abhimanyu

    2017-11-01

    Defects in the biosynthesis of phospholipids and neutral lipids are associated with cell membrane dysfunction, disrupted energy metabolism, and diseases including lipodystrophy. In these pathways, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) enzymes transfer a fatty acid to the sn-2 carbon of sn-1-acylglycerol-3-phosphate (lysophosphatidic acid) to form sn-1, 2-acylglycerol-3-phosphate [phosphatidic acid (PA)]. PA is a precursor for key phospholipids and diacylglycerol. AGPAT1 and AGPAT2 are highly homologous isoenzymes that are both expressed in adipocytes. Genetic defects in AGPAT2 cause congenital generalized lipodystrophy, indicating that AGPAT1 cannot compensate for loss of AGPAT2 in adipocytes. To further explore the physiology of AGPAT1, we characterized a loss-of-function mouse model (Agpat1-/-). The majority of Agpat1-/- mice died before weaning and had low body weight and low plasma glucose levels, independent of plasma insulin and glucagon levels, with reduced percentage of body fat but not generalized lipodystrophy. These mice also had decreased hepatic messenger RNA expression of Igf-1 and Foxo1, suggesting a decrease in gluconeogenesis. In male mice, sperm development was impaired, with a late meiotic arrest near the onset of round spermatid production, and gonadotropins were elevated. Female mice showed oligoanovulation yet retained responsiveness to gonadotropins. Agpat1-/- mice also demonstrated abnormal hippocampal neuron development and developed audiogenic seizures. In summary, Agpat1-/- mice developed widespread disturbances of metabolism, sperm development, and neurologic function resulting from disrupted phospholipid homeostasis. AGPAT1 appears to serve important functions in the physiology of multiple organ systems. The Agpat1-deficient mouse provides an important model in which to study the contribution of phospholipid and triacylglycerol synthesis to physiology and diseases. Copyright © 2017 Endocrine Society.

  5. Influence of choice of null network on small-world parameters of structural correlation networks.

    Directory of Open Access Journals (Sweden)

    S M Hadi Hosseini

    Full Text Available 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.

  6. 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. PMID:23840672

  7. 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

  8. Averaged null energy condition and difference inequalities in quantum field theory

    International Nuclear Information System (INIS)

    Yurtsever, U.

    1995-01-01

    For a large class of quantum states, all local (pointwise) energy conditions widely used in relativity are violated by the renormalized stress-energy tensor of a quantum field. In contrast, certain nonlocal positivity constraints on the quantum stress-energy tensor might hold quite generally, and this possibility has received considerable attention in recent years. In particular, it is now known that the averaged null energy condition, the condition that the null-null component of the stress-energy tensor integrated along a complete null geodesic is non-negative for all states, holds quite generally in a wide class of spacetimes for a minimally coupled scalar field. Apart from the specific class of spacetimes considered (mainly two-dimensional spacetimes and four-dimensional Minkowski space), the most significant restriction on this result is that the null geodesic over which the average is taken must be achronal. Recently, Ford and Roman have explored this restriction in two-dimensional flat spacetime, and discovered that in a flat cylindrical space, although the stress energy tensor itself fails to satisfy the averaged null energy condition (ANEC) along the (nonachronal) null geodesics, when the ''Casimir-vacuum'' contribution is subtracted from the stress-energy the resulting tensor does satisfy the ANEC inequality. Ford and Roman name this class of constraints on the quantum stress-energy tensor ''difference inequalities.'' Here I give a proof of the difference inequality for a minimally coupled massless scalar field in an arbitrary (globally hyperbolic) two-dimensional spacetime, using the same techniques as those we relied on to prove the ANEC in an earlier paper with Wald. I begin with an overview of averaged energy conditions in quantum field theory

  9. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  10. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  11. Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice.

    Directory of Open Access Journals (Sweden)

    Stefano Farioli-Vecchioli

    Full Text Available Neurogenesis in the dentate gyrus of the adult hippocampus has been implicated in neural plasticity and memory, but the molecular mechanisms controlling the proliferation and differentiation of newborn neurons and their integration into the synaptic circuitry are still largely unknown. To investigate this issue, we have analyzed the adult hippocampal neurogenesis in a PC3/Tis21-null mouse model. PC3/Tis21 is a transcriptional co-factor endowed with antiproliferative and prodifferentiative properties; indeed, its upregulation in neural progenitors has been shown to induce exit from cell cycle and differentiation. We demonstrate here that the deletion of PC3/Tis21 causes an increased proliferation of progenitor cells in the adult dentate gyrus and an arrest of their terminal differentiation. In fact, in the PC3/Tis21-null hippocampus postmitotic undifferentiated neurons accumulated, while the number of terminally differentiated neurons decreased of 40%. As a result, PC3/Tis21-null mice displayed a deficit of contextual memory. Notably, we observed that PC3/Tis21 can associate to the promoter of Id3, an inhibitor of proneural gene activity, and negatively regulates its expression, indicating that PC3/Tis21 acts upstream of Id3. Our results identify PC3/Tis21 as a gene required in the control of proliferation and terminal differentiation of newborn neurons during adult hippocampal neurogenesis and suggest its involvement in the formation of contextual memories.

  12. Sim1 Neurons Are Sufficient for MC4R-Mediated Sexual Function in Male Mice.

    Science.gov (United States)

    Semple, Erin; Hill, Jennifer W

    2018-01-01

    Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown. We hypothesized that single-minded homolog 1 (Sim1) neurons play an important role in the melanocortin-mediated regulation of male sexual behavior. To test this hypothesis, we examined the sexual behavior of mice expressing MC4R only on Sim1-positive neurons (tbMC4Rsim1 mice) in comparison with tbMC4R null mice and wild-type controls. In tbMC4Rsim1 mice, MC4R reexpression was found in the medial amygdala and paraventricular nucleus of the hypothalamus. These mice were paired with sexually experienced females, and their sexual function and behavior was scored based on mounting, intromission, and ejaculation. tbMC4R null mice showed a longer latency to mount, a reduced intromission efficiency, and an inability to reach ejaculation. Expression of MC4R only on Sim1 neurons reversed the sexual deficits seen in tbMC4R null mice. This study implicates melanocortin signaling via the MC4R on Sim1 neurons in the central control of male sexual behavior. Copyright © 2018 Endocrine Society.

  13. 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.

  14. 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.

  15. Time asymmetric spacetimes near null and spatial infinity: I. Expansions of developments of conformally flat data

    International Nuclear Information System (INIS)

    Kroon, Juan Antonio Valiente

    2004-01-01

    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

  16. 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

    2011-10-01

    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 flown 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). The VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 108, 109, and ideally 1010 at an inner working angle of 2*λ/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.

  17. Current singularities at finitely compressible three-dimensional magnetic null points

    International Nuclear Information System (INIS)

    Pontin, D.I.; Craig, I.J.D.

    2005-01-01

    The formation of current singularities at line-tied two- and three-dimensional (2D and 3D, respectively) magnetic null points in a nonresistive magnetohydrodynamic environment is explored. It is shown that, despite the different separatrix structures of 2D and 3D null points, current singularities may be initiated in a formally equivalent manner. This is true no matter whether the collapse is triggered by flux imbalance within closed, line-tied null points or driven by externally imposed velocity fields in open, incompressible geometries. A Lagrangian numerical code is used to investigate the finite amplitude perturbations that lead to singular current sheets in collapsing 2D and 3D null points. The form of the singular current distribution is analyzed as a function of the spatial anisotropy of the null point, and the effects of finite gas pressure are quantified. It is pointed out that the pressure force, while never stopping the formation of the singularity, significantly alters the morphology of the current distribution as well as dramatically weakening its strength. The impact of these findings on 2D and 3D magnetic reconnection models is discussed

  18. An in silico agent-based model demonstrates Reelin function in directing lamination of neurons during cortical development.

    Science.gov (United States)

    Caffrey, James R; Hughes, Barry D; Britto, Joanne M; Landman, Kerry A

    2014-01-01

    The characteristic six-layered appearance of the neocortex arises from the correct positioning of pyramidal neurons during development and alterations in this process can cause intellectual disabilities and developmental delay. Malformations in cortical development arise when neurons either fail to migrate properly from the germinal zones or fail to cease migration in the correct laminar position within the cortical plate. The Reelin signalling pathway is vital for correct neuronal positioning as loss of Reelin leads to a partially inverted cortex. The precise biological function of Reelin remains controversial and debate surrounds its role as a chemoattractant or stop signal for migrating neurons. To investigate this further we developed an in silico agent-based model of cortical layer formation. Using this model we tested four biologically plausible hypotheses for neuron motility and four biologically plausible hypotheses for the loss of neuron motility (conversion from migration). A matrix of 16 combinations of motility and conversion rules was applied against the known structure of mouse cortical layers in the wild-type cortex, the Reelin-null mutant, the Dab1-null mutant and a conditional Dab1 mutant. Using this approach, many combinations of motility and conversion mechanisms can be rejected. For example, the model does not support Reelin acting as a repelling or as a stopping signal. In contrast, the study lends very strong support to the notion that the glycoprotein Reelin acts as a chemoattractant for neurons. Furthermore, the most viable proposition for the conversion mechanism is one in which conversion is affected by a motile neuron sensing in the near vicinity neurons that have already converted. Therefore, this model helps elucidate the function of Reelin during neuronal migration and cortical development.

  19. An in silico agent-based model demonstrates Reelin function in directing lamination of neurons during cortical development.

    Directory of Open Access Journals (Sweden)

    James R Caffrey

    Full Text Available The characteristic six-layered appearance of the neocortex arises from the correct positioning of pyramidal neurons during development and alterations in this process can cause intellectual disabilities and developmental delay. Malformations in cortical development arise when neurons either fail to migrate properly from the germinal zones or fail to cease migration in the correct laminar position within the cortical plate. The Reelin signalling pathway is vital for correct neuronal positioning as loss of Reelin leads to a partially inverted cortex. The precise biological function of Reelin remains controversial and debate surrounds its role as a chemoattractant or stop signal for migrating neurons. To investigate this further we developed an in silico agent-based model of cortical layer formation. Using this model we tested four biologically plausible hypotheses for neuron motility and four biologically plausible hypotheses for the loss of neuron motility (conversion from migration. A matrix of 16 combinations of motility and conversion rules was applied against the known structure of mouse cortical layers in the wild-type cortex, the Reelin-null mutant, the Dab1-null mutant and a conditional Dab1 mutant. Using this approach, many combinations of motility and conversion mechanisms can be rejected. For example, the model does not support Reelin acting as a repelling or as a stopping signal. In contrast, the study lends very strong support to the notion that the glycoprotein Reelin acts as a chemoattractant for neurons. Furthermore, the most viable proposition for the conversion mechanism is one in which conversion is affected by a motile neuron sensing in the near vicinity neurons that have already converted. Therefore, this model helps elucidate the function of Reelin during neuronal migration and cortical development.

  20. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  1. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  2. The mirror neuron system.

    Science.gov (United States)

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  3. 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.

  4. The null hypothesis of GSEA, and a novel statistical model for competitive gene set analysis

    DEFF Research Database (Denmark)

    Debrabant, Birgit

    2017-01-01

    MOTIVATION: Competitive gene set analysis intends to assess whether a specific set of genes is more associated with a trait than the remaining genes. However, the statistical models assumed to date to underly these methods do not enable a clear cut formulation of the competitive null hypothesis....... This is a major handicap to the interpretation of results obtained from a gene set analysis. RESULTS: This work presents a hierarchical statistical model based on the notion of dependence measures, which overcomes this problem. The two levels of the model naturally reflect the modular structure of many gene set...... analysis methods. We apply the model to show that the popular GSEA method, which recently has been claimed to test the self-contained null hypothesis, actually tests the competitive null if the weight parameter is zero. However, for this result to hold strictly, the choice of the dependence measures...

  5. A few insights into the nature of classical and quantum gravity via null-strut calculus

    International Nuclear Information System (INIS)

    Kheyfets, Arkady

    1989-01-01

    Null-strut calculus is a 3 + 1 formulation of standard Regge calculus, wherein the dynamics of 3-geometry is propagated in time along light rays, or 'null struts'. However, just as Regge calculus is a discrete and geometric tool for the description of Einstein's theory of gravitation, so too NSC offers itself as a discrete and geometric tool for the description of Einstein's spacetime as the dynamics of discrete spacelike 3-geometries in time, or discrete geometrodynamics. It has for its objectives to provide a discrete model of a 3 + 1 split of spacetime into space plus time, while in so doing to preserve and illuminate the geometric content of Einstein's theory of gravity. The feature of 'light-cone-produced duality' is central to null-strut calculus. This paper will capitalise on this feature, and will attempt to provide some insights into the nature of classical and quantum gravity. (Author)

  6. 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.

  7. The (2, 0) superalgebra, null M-branes and Hitchin's system

    Science.gov (United States)

    Kucharski, P.; Lambert, N.; Owen, M.

    2017-10-01

    We present an interacting system of equations with sixteen supersymmetries and an SO(2) × SO(6) R-symmetry where the fields depend on two space and one null dimensions that is derived from a representation of the six-dimensional (2, 0) superalgebra. The system can be viewed as two M5-branes compactified on {S}-^1× T^2 or equivalently as M2-branes on R+× R^2 , where ± refer to null directions. We show that for a particular choice of fields the dynamics can be reduced to motion on the moduli space of solutions to the Hitchin system. We argue that this provides a description of intersecting null M2-branes and is also related by U-duality to a DLCQ description of four-dimensional maximally supersymmetric Yang-Mills.

  8. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  9. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  10. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  11. From GLC to double-null coordinates and illustration with static black holes

    Energy Technology Data Exchange (ETDEWEB)

    Nugier, Fabien, E-mail: fnugier@ntu.edu.tw [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, Taipei, 10617 Taiwan (China)

    2016-09-01

    We present a system of coordinates deriving directly from the so-called Geodesic Light-Cone (GLC) coordinates and made of two null scalars intersecting on a 2-dimensional sphere parameterized by two constant angles along geodesics. These coordinates are shown to be equivalent to the well-known double-null coordinates. As GLC, they present interesting properties for cosmology and astrophysics. We discuss this latter topic for static black holes, showing simple descriptions for the metric or particles and photons trajectories. We also briefly comment on the time of flight of ultra-relativistic particles.

  12. The Segmented Aperture Interferometric Nulling Testbed (SAINT) I: overview and air-side system description

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter; Ballard, Marlin; Bolcar, Matthew R.; Bolognese, Jeff; Clampin, Mark; Dogoda, Peter; Dworzanski, Daniel; Helmbrecht, Michael A.; Koca, Corina; Shiri, Ron

    2016-07-01

    This work presents an overview of the Segmented Aperture Interferometric Nulling Testbed (SAINT), a project that will pair an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC). SAINT will incorporate the VNC's demonstrated wavefront sensing and control system to refine and quantify end-to-end high-contrast starlight suppression performance. This pathfinder testbed will be used as a tool to study and refine approaches to mitigating instabilities and complex diffraction expected from future large segmented aperture telescopes.

  13. Noncolocated Time-Reversal MUSIC: High-SNR Distribution of Null Spectrum

    Science.gov (United States)

    Ciuonzo, Domenico; Rossi, Pierluigi Salvo

    2017-04-01

    We derive the asymptotic distribution of the null spectrum of the well-known Multiple Signal Classification (MUSIC) in its computational Time-Reversal (TR) form. The result pertains to a single-frequency non-colocated multistatic scenario and several TR-MUSIC variants are here investigated. The analysis builds upon the 1st-order perturbation of the singular value decomposition and allows a simple characterization of null-spectrum moments (up to the 2nd order). This enables a comparison in terms of spectrums stability. Finally, a numerical analysis is provided to confirm the theoretical findings.

  14. In vivo time-gated diffuse correlation spectroscopy at quasi-null source-detector separation.

    Science.gov (United States)

    Pagliazzi, M; Sekar, S Konugolu Venkata; Di Sieno, L; Colombo, L; Durduran, T; Contini, D; Torricelli, A; Pifferi, A; Mora, A Dalla

    2018-06-01

    We demonstrate time domain diffuse correlation spectroscopy at quasi-null source-detector separation by using a fast time-gated single-photon avalanche diode without the need of time-tagging electronics. This approach allows for increased photon collection, simplified real-time instrumentation, and reduced probe dimensions. Depth discriminating, quasi-null distance measurement of blood flow in a human subject is presented. We envision the miniaturization and integration of matrices of optical sensors of increased spatial resolution and the enhancement of the contrast of local blood flow changes.

  15. A class of algebraically general solutions of the Einstein-Maxwell equations for non-null electromagnetic fields

    International Nuclear Information System (INIS)

    Tupper, B.O.J.

    1976-01-01

    In a previous article (Gen. Rel. Grav.; 6 : 345 (1975)) the Einstein-Maxwell field equations for non-null electromagnetic fields were studied under the conditions that the null tetrad is parallel-propagated along both principal null congruences. A solution with twist and shear, but no expansion, was found and was conjectured to be the only expansion-free solution. Here it is shown that this conjecture is false; the general expansion-free solution is found to be a family of space-times depending on a single constant parameter which is the ratio of the (constant) twists of the two principal null congruences. (author)

  16. Parkin protects dopaminergic neurons from excessive Wnt/{beta}-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Rawal, Nina [Laboratory of Molecular Neurobiology, MBB, DBRM, Karolinska Institute, S-17177 Stockholm (Sweden); Corti, Olga [Universite Pierre et Marie Curie-Paris 6, CRICM UMR-S975, Inserm, U975 (France); CNRS, UMR 7225, Paris (France); Sacchetti, Paola [Laboratory of Molecular Neurobiology, MBB, DBRM, Karolinska Institute, S-17177 Stockholm (Sweden); Ardilla-Osorio, Hector [Universite Pierre et Marie Curie-Paris 6, CRICM UMR-S975, Inserm, U975 (France); CNRS, UMR 7225, Paris (France); Sehat, Bita [Cancer Center Karolinska, Karolinska Institute, S-17177 Stockholm (Sweden); Brice, Alexis [Universite Pierre et Marie Curie-Paris 6, CRICM UMR-S975, Inserm, U975 (France); CNRS, UMR 7225, Paris (France); Department of Genetics and Cytogenetics, AP-HP, Groupe Hospitalier Pitie-Salpetriere, Paris (France); Arenas, Ernest, E-mail: Ernest.Arenas@ki.se [Laboratory of Molecular Neurobiology, MBB, DBRM, Karolinska Institute, S-17177 Stockholm (Sweden)

    2009-10-23

    Parkinson's disease (PD) is caused by degeneration of the dopaminergic (DA) neurons of the substantia nigra but the molecular mechanisms underlying the degenerative process remain elusive. Several reports suggest that cell cycle deregulation in post-mitotic neurons could lead to neuronal cell death. We now show that Parkin, an E3 ubiquitin ligase linked to familial PD, regulates {beta}-catenin protein levels in vivo. Stabilization of {beta}-catenin in differentiated primary ventral midbrain neurons results in increased levels of cyclin E and proliferation, followed by increased levels of cleaved PARP and loss of DA neurons. Wnt3a signaling also causes death of post-mitotic DA neurons in parkin null animals, suggesting that both increased stabilization and decreased degradation of {beta}-catenin results in DA cell death. These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and {beta}-catenin-induced cell death.

  17. Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin★

    Science.gov (United States)

    Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L.; Mosher, Christina; Berglund, Eric D.; Elmquist, Joel K.; Zigman, Jeffrey M.

    2013-01-01

    The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreERT2 transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia. PMID:24567905

  18. Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin.

    Science.gov (United States)

    Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L; Mosher, Christina; Berglund, Eric D; Elmquist, Joel K; Zigman, Jeffrey M

    2014-02-01

    The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreER(T2) transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia.

  19. Visualization of odor-induced neuronal activity by immediate early gene expression

    Directory of Open Access Journals (Sweden)

    Bepari Asim K

    2012-11-01

    Full Text Available Abstract Background Sensitive detection of sensory-evoked neuronal activation is a key to mechanistic understanding of brain functions. Since immediate early genes (IEGs are readily induced in the brain by environmental changes, tracing IEG expression provides a convenient tool to identify brain activity. In this study we used in situ hybridization to detect odor-evoked induction of ten IEGs in the mouse olfactory system. We then analyzed IEG induction in the cyclic nucleotide-gated channel subunit A2 (Cnga2-null mice to visualize residual neuronal activity following odorant exposure since CNGA2 is a key component of the olfactory signal transduction pathway in the main olfactory system. Results We observed rapid induction of as many as ten IEGs in the mouse olfactory bulb (OB after olfactory stimulation by a non-biological odorant amyl acetate. A robust increase in expression of several IEGs like c-fos and Egr1 was evident in the glomerular layer, the mitral/tufted cell layer and the granule cell layer. Additionally, the neuronal IEG Npas4 showed steep induction from a very low basal expression level predominantly in the granule cell layer. In Cnga2-null mice, which are usually anosmic and sexually unresponsive, glomerular activation was insignificant in response to either ambient odorants or female stimuli. However, a subtle induction of c-fos took place in the OB of a few Cnga2-mutants which exhibited sexual arousal. Interestingly, very strong glomerular activation was observed in the OB of Cnga2-null male mice after stimulation with either the neutral odor amyl acetate or the predator odor 2, 3, 5-trimethyl-3-thiazoline (TMT. Conclusions This study shows for the first time that in vivo olfactory stimulation can robustly induce the neuronal IEG Npas4 in the mouse OB and confirms the odor-evoked induction of a number of IEGs. As shown in previous studies, our results indicate that a CNGA2-independent signaling pathway(s may activate the

  20. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  1. Neuronal avalanches and learning

    International Nuclear Information System (INIS)

    Arcangelis, Lucilla de

    2011-01-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  2. Propagation of errors from a null balance terahertz reflectometer to a sample's relative water content

    International Nuclear Information System (INIS)

    Hadjiloucas, S; Walker, G C; Bowen, J W; Zafiropoulos, A

    2009-01-01

    The THz water content index of a sample is defined and advantages in using such metric in estimating a sample's relative water content are discussed. The errors from reflectance measurements performed at two different THz frequencies using a quasi-optical null-balance reflectometer are propagated to the errors in estimating the sample water content index.

  3. Partial null astigmatism-compensated interferometry for a concave freeform Zernike mirror

    Science.gov (United States)

    Dou, Yimeng; Yuan, Qun; Gao, Zhishan; Yin, Huimin; Chen, Lu; Yao, Yanxia; Cheng, Jinlong

    2018-06-01

    Partial null interferometry without using any null optics is proposed to measure a concave freeform Zernike mirror. Oblique incidence on the freeform mirror is used to compensate for astigmatism as the main component in its figure, and to constrain the divergence of the test beam as well. The phase demodulated from the partial nulled interferograms is divided into low-frequency phase and high-frequency phase by Zernike polynomial fitting. The low-frequency surface figure error of the freeform mirror represented by the coefficients of Zernike polynomials is reconstructed from the low-frequency phase, applying the reverse optimization reconstruction technology in the accurate model of the interferometric system. The high-frequency surface figure error of the freeform mirror is retrieved from the high-frequency phase adopting back propagating technology, according to the updated model in which the low-frequency surface figure error has been superimposed on the sag of the freeform mirror. Simulations verified that this method is capable of testing a wide variety of astigmatism-dominated freeform mirrors due to the high dynamic range. The experimental result using our proposed method for a concave freeform Zernike mirror is consistent with the null test result employing the computer-generated hologram.

  4. The Harm Done to Reproducibility by the Culture of Null Hypothesis Significance Testing.

    Science.gov (United States)

    Lash, Timothy L

    2017-09-15

    In the last few years, stakeholders in the scientific community have raised alarms about a perceived lack of reproducibility of scientific results. In reaction, guidelines for journals have been promulgated and grant applicants have been asked to address the rigor and reproducibility of their proposed projects. Neither solution addresses a primary culprit, which is the culture of null hypothesis significance testing that dominates statistical analysis and inference. In an innovative research enterprise, selection of results for further evaluation based on null hypothesis significance testing is doomed to yield a low proportion of reproducible results and a high proportion of effects that are initially overestimated. In addition, the culture of null hypothesis significance testing discourages quantitative adjustments to account for systematic errors and quantitative incorporation of prior information. These strategies would otherwise improve reproducibility and have not been previously proposed in the widely cited literature on this topic. Without discarding the culture of null hypothesis significance testing and implementing these alternative methods for statistical analysis and inference, all other strategies for improving reproducibility will yield marginal gains at best. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. High Contrast Vacuum Nuller Testbed (VNT) Contrast, Performance and Null Control

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-01-01

    Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal planeregion extending from 14 D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. TheVNC is a hybrid interferometriccoronagraphic approach for exoplanet science. It operates with high Lyot stopefficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential futureNASA flight telescopes. NASAGoddard Space Flight Center (GSFC) has a well-established effort to develop the VNCand its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and itsenabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry tounprecedented levels. The VNC is based on a modified Mach-Zehnder nulling interferometer, with a W configurationto accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters.We give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, criticaltechnologies and null sensing and control.

  6. Modelling the electromechanical interactions in a null-flux EDS Maglev system

    NARCIS (Netherlands)

    Boeij, de J.; Steinbuch, M.; Gutierrez, H.M.; Fair, H.D.

    2004-01-01

    The fundamental electromechanical interactionsin a passive null-ux EDS maglev system aremediated by the voltages induced in the levita-tion coils by the sled magnets, and by the forcesexerted on the sled as a result of the inducedcurrents. This paper presents a reliable andcompact method to

  7. Parallel-propagated frame along null geodesics in higher-dimensional black hole spacetimes

    International Nuclear Information System (INIS)

    Kubiznak, David; Frolov, Valeri P.; Connell, Patrick; Krtous, Pavel

    2009-01-01

    In [arXiv:0803.3259] the equations describing the parallel transport of orthonormal frames along timelike (spacelike) geodesics in a spacetime admitting a nondegenerate principal conformal Killing-Yano 2-form h were solved. The construction employed is based on studying the Darboux subspaces of the 2-form F obtained as a projection of h along the geodesic trajectory. In this paper we demonstrate that, although slightly modified, a similar construction is possible also in the case of null geodesics. In particular, we explicitly construct the parallel-transported frames along null geodesics in D=4, 5, 6 Kerr-NUT-(A)dS spacetimes. We further discuss the parallel transport along principal null directions in these spacetimes. Such directions coincide with the eigenvectors of the principal conformal Killing-Yano tensor. Finally, we show how to obtain a parallel-transported frame along null geodesics in the background of the 4D Plebanski-Demianski metric which admits only a conformal generalization of the Killing-Yano tensor.

  8. Diversity-Multiplexing-Nulling Trade-Off Analysis of Multiuser MIMO System for Intercell Interference Coordination

    Directory of Open Access Journals (Sweden)

    Jinwoo Kim

    2017-01-01

    Full Text Available A fundamental performance trade-off of multicell multiuser multiple-input multiple-output (MU-MIMO systems is explored for achieving intercell and intracell interference-free conditions. In particular, we analyze the three-dimensional diversity-multiplexing-nulling trade-off (DMNT among the diversity order (i.e., the slope of the error performance curve, multiplexing order (i.e., the number of users that are simultaneously served by MU-MIMO, and nulling order (i.e., the number of users with zero interference in a victim cell. This trade-off quantifies the performance of MU-MIMO in terms of its diversity and multiplexing order, while nulling the intercell interference toward the victim cell in the neighbor. First, we design a precoding matrix to mitigate both intercell and intracell interference for a linear precoding-based MU-MIMO system. Then, the trade-off relationship is obtained by analyzing the distribution of the signal-to-noise ratio (SNR at the user terminals. Furthermore, we demonstrate how DMNT can be applied to estimate the long-term throughput for each mobile station, which allows for determining the optimal number of multiplexing order and throughput loss due to the interference nulling.

  9. Exact null distributions of quadratic distribution-free statistics for two-way classification

    NARCIS (Netherlands)

    Wiel, van de M.A.

    2004-01-01

    Abstract We present new techniques for computing exact distributions of `Friedman-type¿ statistics. Representing the null distribution by a generating function allows for the use of general, not necessarily integer-valued rank scores. Moreover, we use symmetry properties of the multivariate

  10. Pattern Nulling of Linear Antenna Arrays Using Backtracking Search Optimization Algorithm

    Directory of Open Access Journals (Sweden)

    Kerim Guney

    2015-01-01

    Full Text Available An evolutionary method based on backtracking search optimization algorithm (BSA is proposed for linear antenna array pattern synthesis with prescribed nulls at interference directions. Pattern nulling is obtained by controlling only the amplitude, position, and phase of the antenna array elements. BSA is an innovative metaheuristic technique based on an iterative process. Various numerical examples of linear array patterns with the prescribed single, multiple, and wide nulls are given to illustrate the performance and flexibility of BSA. The results obtained by BSA are compared with the results of the following seventeen algorithms: particle swarm optimization (PSO, genetic algorithm (GA, modified touring ant colony algorithm (MTACO, quadratic programming method (QPM, bacterial foraging algorithm (BFA, bees algorithm (BA, clonal selection algorithm (CLONALG, plant growth simulation algorithm (PGSA, tabu search algorithm (TSA, memetic algorithm (MA, nondominated sorting GA-2 (NSGA-2, multiobjective differential evolution (MODE, decomposition with differential evolution (MOEA/D-DE, comprehensive learning PSO (CLPSO, harmony search algorithm (HSA, seeker optimization algorithm (SOA, and mean variance mapping optimization (MVMO. The simulation results show that the linear antenna array synthesis using BSA provides low side-lobe levels and deep null levels.

  11. On the geometry of null cones to infinity under curvature flux bounds

    International Nuclear Information System (INIS)

    Alexakis, Spyros; Shao, Arick

    2014-01-01

    The main objective of this paper is to control the geometry of a future outgoing truncated null cone extending smoothly toward infinity in an Einstein-vacuum spacetime. In particular, we wish to do this under minimal regularity assumptions, namely, at the (weighted) L 2 -curvature level. We show that if the curvature flux and the data on an initial sphere of the cone are sufficiently close to the corresponding values in a standard Minkowski or Schwarzschild null cone, then we can obtain quantitative bounds on the geometry of the entire infinite cone. The same bounds also imply the existence of limits at infinity, along the null cone, of naturally scaled geometric quantities. In Alexakis and Shao (2013 Bounds on the Bondi energy by a flux of curvature arXiv:1308.4170), we will apply these results in order to control various physical quantities—e.g., the Bondi energy and (linear and angular) momenta—associated with such infinite null cones in vacuum spacetimes. (paper)

  12. Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice.

    Science.gov (United States)

    Kyriakides, T R; Zhu, Y H; Yang, Z; Huynh, G; Bornstein, P

    2001-10-01

    The matricellular angiogenesis inhibitor, thrombospondin (TSP) 2, has been shown to be an important modulator of wound healing and the foreign body response. Specifically, TSP2-null mice display improved healing with minimal scarring and form well-vascularized foreign body capsules. In this study we performed subcutaneous implantation of sponges and investigated the resulting angiogenic and fibrogenic responses. Histological and immunohistochemical analysis of sponges, excised at 7, 14, and 21 days after implantation, revealed significant differences between TSP2-null and wild-type mice. Most notably, TSP2-null mice exhibited increased angiogenesis and fibrotic encapsulation of the sponge. However, invasion of dense tissue was compromised, even though its overall density was increased. Furthermore, histomorphometry and biochemical assays demonstrated a significant increase in the extracellular distribution of matrix metalloproteinase (MMP) 2, but no change in the levels of active transforming growth factor-beta(1). The alterations in neovascularization, dense tissue invasion, and MMP2 in TSP2-null mice coincided with the deposition of TSP2 in the extracellular matrix of wild-type animals. These observations support the proposed role of TSP2 as a modulator of angiogenesis and matrix remodeling during tissue repair. In addition, they provide in vivo evidence for a newly proposed function of TSP2 as a modulator of extracellular MMP2 levels.

  13. A Coding of Real Null Four-Momenta into World-Sheet Coordinates

    Directory of Open Access Journals (Sweden)

    David B. Fairlie

    2009-01-01

    Full Text Available The results of minimizing the action for string-like systems on a simply connected world sheet are shown to encode the Cartesian components of real null momentum four-vectors into coordinates on the world sheet. This identification arises consistently from different approaches to the problem.

  14. A Coding of Real Null Four-Momenta into World-Sheet Co-ordinates

    OpenAIRE

    Fairlie, David B.

    2008-01-01

    The results of minimizing the action for string-like systems on a simply-connected world sheet are shown to encode the Cartesian components of real null momentum four-vectors into co-ordinates on the world sheet. This identification arises consistently from different approaches to the problem.

  15. A Panel Test of Purchasing Power Parity Under the Null of Stationarity

    OpenAIRE

    Hunter, J; Simpson, M

    2001-01-01

    Purchasing Power Parity (PPP) is tested using a sample of real exchange rate data for twelve European countries. Acknowledging that Augmented Dickey Fuller tests have low power, we apply a Panel test that considers the null of stationarity and corrects for serial dependence using a non-parametric kernel based method.

  16. Null alleles and sequence variations at primer binding sites of STR loci within multiplex typing systems.

    Science.gov (United States)

    Yao, Yining; Yang, Qinrui; Shao, Chengchen; Liu, Baonian; Zhou, Yuxiang; Xu, Hongmei; Zhou, Yueqin; Tang, Qiqun; Xie, Jianhui

    2018-01-01

    Rare variants are widely observed in human genome and sequence variations at primer binding sites might impair the process of PCR amplification resulting in dropouts of alleles, named as null alleles. In this study, 5 cases from routine paternity testing using PowerPlex ® 21 System for STR genotyping were considered to harbor null alleles at TH01, FGA, D5S818, D8S1179, and D16S539, respectively. The dropout of alleles was confirmed by using alternative commercial kits AGCU Expressmarker 22 PCR amplification kit and AmpFℓSTR ® . Identifiler ® Plus Kit, and sequencing results revealed a single base variation at the primer binding site of each STR locus. Results from the collection of previous reports show that null alleles at D5S818 were frequently observed in population detected by two PowerPlex ® typing systems and null alleles at D19S433 were mostly observed in Japanese population detected by two AmpFℓSTR™ typing systems. Furthermore, the most popular mutation type appeared the transition from C to T with G to A, which might have a potential relationship with DNA methylation. Altogether, these results can provide helpful information in forensic practice to the elimination of genotyping discrepancy and the development of primer sets. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Stitching interferometry of high numerical aperture cylindrical optics without using a fringe-nulling routine.

    Science.gov (United States)

    Peng, Junzheng; Wang, Qingquan; Peng, Xiang; Yu, Yingjie

    2015-11-01

    Stitching interferometry is a common method for measuring the figure error of high numerical aperture optics. However, subaperture measurement usually requires a fringe-nulling routine, thus making the stitching procedure complex and time-consuming. The challenge when measuring a surface without a fringe-nulling routine is that the rays no longer perpendicularly hit the surface. This violation of the null-test condition can lead to high fringe density and introduce high-order misalignment aberrations into the measurement result. This paper demonstrates that the high-order misalignment aberrations can be characterized by low-order misalignment aberrations; then, an efficient method is proposed to separate the high-order misalignment aberrations from subaperture data. With the proposed method, the fringe-nulling routine is not required. Instead, the subaperture data is measured under a nonzero fringe pattern. Then, all possible misalignment aberrations are removed with the proposed method. Finally, the full aperture map is acquired by connecting all subaperture data together. Experimental results showing the feasibility of the proposed procedure are presented.

  18. No association of GSTM1 null polymorphism with endometriosis in women from central and southern Iran

    Directory of Open Access Journals (Sweden)

    Razieh Dehghani Firouzabadi

    2012-01-01

    Full Text Available Background: Endometriosis is one of the most common gynecologic disorders. It is a complex trait and both genetic and environmental factors have been implicated in its pathogenesis. There is growing evidence indicating that exposure to environmental contaminants is a risk factor for endometriosis. Glutathione-S-Transferase M1 (GSTM1 is one of the genes involved in detoxification of endogenous and exogenous compounds. Objective: Several studies have indicated an association between GSTM1 null mutation and endometriosis. In this study, the possible association between the GSTM1 gene null genotype and susceptibility to endometriosis in woman from central and southern Iran was investigated.Materials and Methods: One hundred and one unrelated premenopausal women with endometriosis and 142 unrelated healthy premenopausal women without endometriosis were enrolled in the study. Genomic DNA was extracted from Peripheral blood in all subjects. GSTM1 null genotyping was performed by polymerase chain reaction (PCR.Results: There was no significant difference between frequencies of GSTM1 null genotype in case and control groups (50.5% Vs. 52.1%, p=0.804. Furthermore, this genotype was not associated with severity of endometriosis in our sample (p=0.77. Conclusion: further studies involving gene-environment and gene-gene interactions, particularly combination of GSTM1 and other GST gene family polymorphisms are needed.

  19. High contrast vacuum nuller testbed (VNT) contrast, performance, and null control

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-09-01

    Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal plane region extending from 1 - 4 λ/D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. The VNC is a hybrid interferometric/coronagraphic approach for exoplanet science. It operates with high Lyot stop efficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential future NASA flight telescopes. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop the VNC and its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and its enabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry to unprecedented levels. The VNC 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 give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, critical technologies and null sensing and control.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Development of IR single mode optical fibers for DARWIN-nulling interferometry

    NARCIS (Netherlands)

    Chakkalakkal Abdulla, S.M.; Cheng, L.K.; Bosch, B. van den; Dijkhuizen, N.; Nieuwland, R.A.; Gielesen, W.L.M.; Lucas, J.; Boussard-Plédel, C.; Conseil, C.; Bureau, B.; Carmo, J.P. do

    2014-01-01

    The DARWIN mission aims to detect weak infra-red emission lines from distant orbiting earth-like planets using nulling interferometry. This requires filtering of wavefront errors using single mode waveguides operating at a wavelength range of 6.5-20 μm. This article describes the optical design of

  2. The Need for Nuance in the Null Hypothesis Significance Testing Debate

    Science.gov (United States)

    Häggström, Olle

    2017-01-01

    Null hypothesis significance testing (NHST) provides an important statistical toolbox, but there are a number of ways in which it is often abused and misinterpreted, with bad consequences for the reliability and progress of science. Parts of contemporary NHST debate, especially in the psychological sciences, is reviewed, and a suggestion is made…

  3. Integrable structures and the quantization of free null initial data for gravity

    Science.gov (United States)

    Fuchs, Andreas; Reisenberger, Michael P.

    2017-09-01

    Variables for constraint free null canonical vacuum general relativity are presented which have simple Poisson brackets that facilitate quantization. Free initial data for vacuum general relativity on a pair of intersecting null hypersurfaces has been known since the 1960s. These consist of the ‘main’ data which are set on the bulk of the two null hypersurfaces, and additional ‘surface’ data set only on their intersection 2-surface. More recently the complete set of Poisson brackets of such data has been obtained. However the complexity of these brackets is an obstacle to their quantization. Part of this difficulty may be overcome using methods from the treatment of cylindrically symmetric gravity. Specializing from general to cylindrically symmetric solutions changes the Poisson algebra of the null initial data surprisingly little, but cylindrically symmetric vacuum general relativity is an integrable system, making powerful tools available. Here a transformation is constructed at the cylindrically symmetric level which maps the main initial data to new data forming a Poisson algebra for which an exact deformation quantization is known. (Although an auxiliary condition on the data has been quantized only in the asymptotically flat case, and a suitable representation of the algebra of quantum data by operators on a Hilbert space has not yet been found.) The definition of the new main data generalizes naturally to arbitrary, symmetryless gravitational fields, with the Poisson brackets retaining their simplicity. The corresponding generalization of the quantization is however ambiguous and requires further analysis.

  4. 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

    Neuroglobin is considered to be a novel important pharmacological target in combating stroke and neurodegenerative disorders, although the mechanism by which this protection is accomplished remains an enigma. We hypothesized that if neuroglobin is directly involved in neuroprotection, then perman......, then permanent cerebral ischemia would lead to larger infarct volumes in neuroglobin-null mice than in wild-type mice....

  5. Interpretation of Chinese Overt and Null Embedded Arguments by English-Speaking Learners

    Science.gov (United States)

    Zhao, Lucy Xia

    2012-01-01

    It has been proposed that external interfaces are vulnerable to residue optionality, whereas pure syntax and internal interfaces are acquirable in second language (L2) acquisition (Sorace, 2005, 2011; Sorace and Filiaci, 2006). The proposal was tested in this article through the interpretation of overt and null embedded arguments in L2 Chinese…

  6. Simple Fourier optics formalism for high-angular-resolution systems and nulling interferometry.

    Science.gov (United States)

    Hénault, François

    2010-03-01

    Reviewed are various designs of advanced, multiaperture optical systems dedicated to high-angular-resolution imaging or to the detection of exoplanets by nulling interferometry. A simple Fourier optics formalism applicable to both imaging arrays and nulling interferometers is presented, allowing their basic theoretical relationships to be derived as convolution or cross-correlation products suitable for fast and accurate computation. Several unusual designs, such as a "superresolving telescope" utilizing a mosaicking observation procedure or a free-flying, axially recombined interferometer are examined, and their performance in terms of imaging and nulling capacity are assessed. In all considered cases, it is found that the limiting parameter is the diameter of the individual telescopes. A final section devoted to nulling interferometry shows an apparent superiority of axial versus multiaxial recombining schemes. The entire study is valid only in the framework of first-order geometrical optics and scalar diffraction theory. Furthermore, it is assumed that all entrance subapertures are optically conjugated with their associated exit pupils.

  7. Hamilton-Jacobi formalism for Podolsky's electromagnetic theory on the null-plane

    Science.gov (United States)

    Bertin, M. C.; Pimentel, B. M.; Valcárcel, C. E.; Zambrano, G. E. R.

    2017-08-01

    We develop the Hamilton-Jacobi formalism for Podolsky's electromagnetic theory on the null-plane. The main goal is to build the complete set of Hamiltonian generators of the system as well as to study the canonical and gauge transformations of the theory.

  8. What Constitutes Science and Scientific Evidence: Roles of Null Hypothesis Testing

    Science.gov (United States)

    Chang, Mark

    2017-01-01

    We briefly discuss the philosophical basis of science, causality, and scientific evidence, by introducing the hidden but most fundamental principle of science: the similarity principle. The principle's use in scientific discovery is illustrated with Simpson's paradox and other examples. In discussing the value of null hypothesis statistical…

  9. THE NATURE OF FLARE RIBBONS IN CORONAL NULL-POINT TOPOLOGY

    International Nuclear Information System (INIS)

    Masson, S.; Aulanier, G.; Pariat, E.; Schrijver, C. J.

    2009-01-01

    Flare ribbons are commonly attributed to the low-altitude impact, along the footprints of separatrices or quasi-separatrix layers (QSLs), of particle beams accelerated through magnetic reconnection. If reconnection occurs at a three-dimensional coronal magnetic null point, the footprint of the dome-shaped fan surface would map a closed circular ribbon. This paper addresses the following issues: does the entire circular ribbon brighten simultaneously, as expected because all fan field lines pass through the null point? And since the spine separatrices are singular field lines, do spine-related ribbons look like compact kernels? What can we learn from these observations about current sheet formation and magnetic reconnection in a null-point topology? The present study addresses these questions by analyzing Transition Region and Coronal Explorer and Solar and Heliospheric Observatory/Michelson Doppler Imager observations of a confined flare presenting a circular ribbon. Using a potential field extrapolation, we linked the circular shape of the ribbon with the photospheric mapping of the fan field lines originating from a coronal null point. Observations show that the flare ribbon outlining the fan lines brightens sequentially along the counterclockwise direction and that the spine-related ribbons are elongated. Using the potential field extrapolation as initial condition, we conduct a low-β resistive magnetohydrodynamics simulation of this observed event. We drive the coronal evolution by line-tied diverging boundary motions, so as to emulate the observed photospheric flow pattern associated with some magnetic flux emergence. The numerical analysis allows us to explain several observed features of the confined flare. The vorticity induced in the fan by the prescribed motions causes the spines to tear apart along the fan. This leads to formation of a thin current sheet and induces null-point reconnection. We also find that the null point and its associated topological

  10. Non-Cell Autonomous Influence of the Astrocyte System xc − on Hypoglycaemic Neuronal Cell Death

    Directory of Open Access Journals (Sweden)

    Nicole A Jackman

    2012-01-01

    Full Text Available Despite longstanding evidence that hypoglycaemic neuronal injury is mediated by glutamate excitotoxicity, the cellular and molecular mechanisms involved remain incompletely defined. Here, we demonstrate that the excitotoxic neuronal death that follows GD (glucose deprivation is initiated by glutamate extruded from astrocytes via system xc −– – an amino acid transporter that imports L-cystine and exports L-glutamate. Specifically, we find that depriving mixed cortical cell cultures of glucose for up to 8 h injures neurons, but not astrocytes. Neuronal death is prevented by ionotropic glutamate receptor antagonism and is partially sensitive to tetanus toxin. Removal of amino acids during the deprivation period prevents – whereas addition of L-cystine restores – GD-induced neuronal death, implicating the cystine/glutamate antiporter, system xc−–. Indeed, drugs known to inhibit system xc −– ameliorate GD-induced neuronal death. Further, a dramatic reduction in neuronal death is observed in chimaeric cultures consisting of neurons derived from WT (wild-type mice plated on top of astrocytes derived from sut mice, which harbour a naturally occurring null mutation in the gene (Slc7a11 that encodes the substrate-specific light chain of system xc −– (xCT. Finally, enhancement of astrocytic system xc −– expression and function via IL-1β (interleukin-1β exposure potentiates hypoglycaemic neuronal death, the process of which is prevented by removal of L-cystine and/or addition of system xc −– inhibitors. Thus, under the conditions of GD, our studies demonstrate that astrocytes, via system xc −–, have a direct, non-cell autonomous effect on cortical neuron survival.

  11. Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders.

    Science.gov (United States)

    Zhao, Y; Fung, C; Shin, D; Shin, B-C; Thamotharan, S; Sankar, R; Ehninger, D; Silva, A; Devaskar, S U

    2010-03-01

    Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.

  12. The Zinc Finger Transcription Factor Sp9 Is Required for the Development of Striatopallidal Projection Neurons

    Directory of Open Access Journals (Sweden)

    Qiangqiang Zhang

    2016-08-01

    Full Text Available Striatal medium-sized spiny neurons (MSNs, composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE. We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs and that Sp9 expression is maintained in postmitotic striatopallidal MSNs. Sp9-null mice lose most striatopallidal MSNs because of decreased proliferation of striatopallidal MSN progenitors and increased Bax-dependent apoptosis, whereas the development of striatonigral neurons is largely unaffected. ChIP qPCR provides evidence that Ascl1 directly binds the Sp9 promoter. RNA-seq and in situ hybridization reveal that Sp9 promotes expression of Adora2a, P2ry1, Gpr6, and Grik3 in the LGE and striatum. Thus, Sp9 is crucial for the generation, differentiation, and survival of striatopallidal MSNs.

  13. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  14. 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.

  15. Stochastic neuron models

    CERN Document Server

    Greenwood, Priscilla E

    2016-01-01

    This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

  16. Isolation of two independent allyl alcohol resistant Adh-1 null mutants following selection of pollen and seeds.

    NARCIS (Netherlands)

    Wisman, E.; Ramanna, M.S.; Zabel, P.

    1993-01-01

    The Adh-1 null mutant (B15-1-8) isolated previously was used to establish conditions that allow the selection of ADH-deficient pollen grains and seeds of tomato. New Adh-1 null mutants were then selected among the progenies derived from crosses between the genetically unstable tomato lines Yvms,

  17. Increased Oocyte Degeneration and Follicular Atresia during the Estrous Cycle in Anti-Müllerian Hormone Null Mice

    NARCIS (Netherlands)

    Visser, Jenny A.; Durlinger, Alexandra L.L.; Peters, Isolde J.J.; Heuvel, Edwin R. van den; Rose, Ursula M.; Kramer, Piet; Jong, Frank H. de; Themmen, Axel P.N.

    2007-01-01

    Anti-Müllerian hormone (AMH) plays an important role in folliculogenesis. AMH null mice display an increased recruitment of primordial follicles. Nevertheless, these mice do not have proportionally more preovulatory follicles. Therefore, AMH null mice provide an interesting genetic model to study

  18. Population estimators or progeny tests: what is the best method to assess null allele frequencies at SSR loci?

    NARCIS (Netherlands)

    Oddou-Muratorio, S.; Vendramin, G.G.; Buiteveld, J.; Fady, B.

    2009-01-01

    Nuclear SSRs are notorious for having relatively high frequencies of null alleles, i.e. alleles that fail to amplify and are thus recessive and undetected in heterozygotes. In this paper, we compare two kinds of approaches for estimating null allele frequencies at seven nuclear microsatellite

  19. Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

    Science.gov (United States)

    Doll, Caleb A; Broadie, Kendal

    2016-05-01

    Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

  20. Intermediate Progenitor Cohorts Differentially Generate Cortical Layers and Require Tbr2 for Timely Acquisition of Neuronal Subtype Identity

    Directory of Open Access Journals (Sweden)

    Anca B. Mihalas

    2016-06-01

    Full Text Available Intermediate progenitors (IPs amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice. Upon Tbr2 inactivation, fewer neurons were produced by immediate differentiation and laminar fates were shifted upward. Genesis of subventricular mitoses was, however, not reduced in the context of a Tbr2-null cortex. Instead, neuronal and laminar differentiation were disrupted and delayed. Our findings indicate that upper-layer genesis depends on IPs from many stages of corticogenesis and that Tbr2 regulates the tempo of laminar fate implementation for all cortical layers.

  1. On Bäcklund transformation and vortex filament equation for null Cartan curve in Minkowski 3-space

    Energy Technology Data Exchange (ETDEWEB)

    Grbović, Milica, E-mail: milica.grbovic@kg.ac.rs; Nešović, Emilija, E-mail: nesovickg@sbb.rs [University of Kragujevac, Faculty of Science, Department of Mathematics and Informatics (Serbia)

    2016-12-15

    In this paper we introduce Bäcklund transformation of a null Cartan curve in Minkowski 3-space as a transformation which maps a null Cartan helix to another null Cartan helix, congruent to the given one. We also give the sufficient conditions for a transformation between two null Cartan 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, we derive the vortex filament equation for a null Cartan curve and obtain evolution equation for it’s torsion. As an application, we show that Cartan’s frame vectors generate new solutions of the Da Rios vortex filament equation.

  2. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

    SUN, Xue-Zhi; TAKAHASHI, Sentaro; GUI, Chun; ZHANG, Rui; KOGA, Kazuo; NOUYE, Minoru; MURATA, Yoshiharu

    2002-01-01

    Neuronal cell migration is one of the most significant features during cortical development. After final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. Neuronal migration is guided by radial glial fibers and also needs proper receptors, ligands, and other unknown extracellular factors, requests local signaling (e.g. some emitted by the Cajal-Retz...

  3. A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease.

    Science.gov (United States)

    Westbroek, Wendy; Nguyen, Matthew; Siebert, Marina; Lindstrom, Taylor; Burnett, Robert A; Aflaki, Elma; Jung, Olive; Tamargo, Rafael; Rodriguez-Gil, Jorge L; Acosta, Walter; Hendrix, An; Behre, Bahafta; Tayebi, Nahid; Fujiwara, Hideji; Sidhu, Rohini; Renvoise, Benoit; Ginns, Edward I; Dutra, Amalia; Pak, Evgenia; Cramer, Carole; Ory, Daniel S; Pavan, William J; Sidransky, Ellen

    2016-07-01

    Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1 Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1 To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba(-/-) mice and the control littermate (gba(+/+)) by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba(-/-) neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba(+/+) neurons. This null allele gba(-/-) mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies. © 2016. Published by The Company of Biologists Ltd.

  4. A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease

    Directory of Open Access Journals (Sweden)

    Wendy Westbroek

    2016-07-01

    Full Text Available Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1. Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1. To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba−/− mice and the control littermate (gba+/+ by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba−/− neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba+/+ neurons. This null allele gba−/− mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies.

  5. Neuronal nets in robotics

    International Nuclear Information System (INIS)

    Jimenez Sanchez, Raul

    1999-01-01

    The paper gives a generic idea of the solutions that the neuronal nets contribute to the robotics. The advantages and the inconveniences are exposed that have regarding the conventional techniques. It also describe the more excellent applications as the pursuit of trajectories, the positioning based on images, the force control or of the mobile robots management, among others

  6. Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice

    International Nuclear Information System (INIS)

    Hoffler, Undi; Dixon, Darlene; Peddada, Shyamal; Ghanayem, Burhan I.

    2005-01-01

    Urethane is a multi-site animal carcinogen and was classified as 'reasonably anticipated to be a human carcinogen.' Urethane is a fermentation by-product and found at appreciable levels in alcoholic beverages and foods such as bread and cheese. Recent work in this laboratory demonstrated for the first time that CYP2E1 is the principal enzyme responsible for urethane metabolism. The current studies were undertaken to assess the relationships between CYP2E1-mediated metabolism and urethane-induced genotoxicity and cell proliferation as determined by induction of micronucleated erythrocytes (MN) and expression of Ki-67, respectively, using CYP2E1-null and wild-type mice. Urethane was administered at 0 (vehicle), 1, 10, or 100 mg/kg/day (p.o.), 5 days/week for 6 weeks. A significant dose-dependent increase in MN was observed in wild-type mice; however, a slight increase was measured in the MN-polychromatic erythrocytes in CYP2E1-null mice treated with 100 mg/kg. A significant increase in the expression of Ki-67 was detected in the livers and the lungs (terminal bronchioles, alveoli, and bronchi) of wild-type mice administered 100 mg urethane/kg in comparison to controls. In contrast, CYP2E1-null mice administered this dose exhibited negligible alterations in Ki-67 expression in the livers and lungs compared to controls. Interestingly, while Ki-67 expression in the forestomach decreased in wild-type mice, it increased in CYP2E1-null mice. Subsequent comparative metabolism studies demonstrated that total urethane-derived radioactivity in the plasma, liver, and lung was significantly higher in CYP2E1-null versus wild-type mice and un-metabolized urethane constituted greater than 83% of the radioactivity in CYP2E1-null mice. Un-metabolized urethane was not detectable in the plasma, liver, and lung of wild-type mice. In conclusion, these data demonstrated that CYP2E1-mediated metabolism of urethane, presumably via epoxide formation, is necessary for the induction of

  7. Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain

    Directory of Open Access Journals (Sweden)

    Niurka Trujillo-Paredes

    2016-03-01

    Full Text Available Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs, but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor. Coupling between neurogenesis and dopaminergic differentiation was indicated from the coincident emergence of neuronal and dopaminergic markers. Early in differentiation, decreasing Notch signalling caused a reduction in NPCs and an increase in dopaminergic neurons in association with dynamic changes in the proportion of sequentially-linked dopaminergic NPCs (Msx1/2+, Ngn2+, Nurr1+. These effects in differentiation caused a significant reduction in the number of dopaminergic neurons produced. Accordingly, Dll1 haploinsufficient adult mice, in comparison with their wild-type littermates, have a consistent reduction in neuronal density that was particularly evident in the substantia nigra pars compacta. Our results are in agreement with a mathematical model based on a Dll1-mediated regulatory feedback loop between early progenitors and their dividing precursors that controls the emergence and number of dopaminergic neurons.

  8. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  9. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  10. Null geodesics and wave front singularities in the Gödel space-time

    Science.gov (United States)

    Kling, Thomas P.; Roebuck, Kevin; Grotzke, Eric

    2018-01-01

    We explore wave fronts of null geodesics in the Gödel metric emitted from point sources both at, and away from, the origin. For constant time wave fronts emitted by sources away from the origin, we find cusp ridges as well as blue sky metamorphoses where spatially disconnected portions of the wave front appear, connect to the main wave front, and then later break free and vanish. These blue sky metamorphoses in the constant time wave fronts highlight the non-causal features of the Gödel metric. We introduce a concept of physical distance along the null geodesics, and show that for wave fronts of constant physical distance, the reorganization of the points making up the wave front leads to the removal of cusp ridges.

  11. Luxembourg in the Early Days of the EEC: Null Player or Not?

    Directory of Open Access Journals (Sweden)

    Alexander Mayer

    2018-05-01

    Full Text Available Voters whose yes-or-no decision never makes a difference to the outcome in a simple voting game are known as “null players”. Luxembourg’s role in the Council of Ministers during the first period of the European Economic Community (EEC is often cited as a real-world case. The paper contrasts the textbook claim that Luxembourg was a null player with a more comprehensive picture of Luxembourg’s role in EEC’s voting system. The assessment of Luxembourg’s voting power is sensitive to the role played by the European Commission in the decision-making procedure and the measurement concepts underlying power evaluations.

  12. Enhanced endotoxin sensitivity in fps/fes-null mice with minimal defects in hematopoietic homeostasis.

    Science.gov (United States)

    Zirngibl, Ralph A; Senis, Yotis; Greer, Peter A

    2002-04-01

    The fps/fes proto-oncogene encodes a cytoplasmic protein tyrosine kinase implicated in growth factor and cytokine receptor signaling and thought to be essential for the survival and terminal differentiation of myeloid progenitors. Fps/Fes-null mice were healthy and fertile, displayed slightly reduced numbers of bone marrow myeloid progenitors and circulating mature myeloid cells, and were more sensitive to lipopolysaccharide (LPS). These phenotypes were rescued using a fps/fes transgene. This confirmed that Fps/Fes is involved in, but not required for, myelopoiesis and that it plays a role in regulating the innate immune response. Bone marrow-derived Fps/Fes-null macrophages showed no defects in granulocyte-macrophage colony-stimulating factor-, interleukin 6 (IL-6)-, or IL-3-induced activation of signal transducer and activator of transcription 3 (Stat3) and Stat5A or LPS-induced degradation of I kappa B or activation of p38, Jnk, Erk, or Akt.

  13. Magnetic Nulls and Super-radial Expansion in the Solar Corona

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, Sarah E.; Dalmasse, Kevin; Tomczyk, Steven; Toma, Giuliana de; Burkepile, Joan; Galloy, Michael [National Center for Atmospheric Research, 3080 Center Green Drive, Boulder, CO 80301 (United States); Rachmeler, Laurel A. [NASA Marshall Space Flight Center, Huntsville, AL 35811 (United States); Rosa, Marc L. De, E-mail: sgibson@ucar.edu [Lockheed Martin Solar and Astrophysics Laboratory, 3251 Hanover Street B/252, Palo Alto, CA 94304 (United States)

    2017-05-10

    Magnetic fields in the Sun’s outer atmosphere—the corona—control both solar-wind acceleration and the dynamics of solar eruptions. We present the first clear observational evidence of coronal magnetic nulls in off-limb linearly polarized observations of pseudostreamers, taken by the Coronal Multichannel Polarimeter (CoMP) telescope. These nulls represent regions where magnetic reconnection is likely to act as a catalyst for solar activity. CoMP linear-polarization observations also provide an independent, coronal proxy for magnetic expansion into the solar wind, a quantity often used to parameterize and predict the solar wind speed at Earth. We introduce a new method for explicitly calculating expansion factors from CoMP coronal linear-polarization observations, which does not require photospheric extrapolations. We conclude that linearly polarized light is a powerful new diagnostic of critical coronal magnetic topologies and the expanding magnetic flux tubes that channel the solar wind.

  14. Local differential geometry of null curves in conformally flat space-time

    International Nuclear Information System (INIS)

    Urbantke, H.

    1989-01-01

    The conformally invariant differential geometry of null curves in conformally flat space-times is given, using the six-vector formalism which has generalizations to higher dimensions. This is then paralleled by a twistor description, with a twofold merit: firstly, sometimes the description is easier in twistor terms, sometimes in six-vector terms, which leads to a mutual enlightenment of both; and secondly, the case of null curves in timelike pseudospheres or 2+1 Minkowski space we were only able to treat twistorially, making use of an invariant differential found by Fubini and Cech. The result is the expected one: apart from stated exceptional cases there is a conformally invariant parameter and two conformally invariant curvatures which, when specified in terms of this parameter, serve to characterize the curve up to conformal transformations. 12 refs. (Author)

  15. Bursty, Broadband Electromagnetic Waves Associated with Three-Dimensional Nulls Observed in Turbulent Magnetosheath Reconnection

    Science.gov (United States)

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

    2012-01-01

    We investigate observations of intense bursts of electromagnetic wave energy in association with the thin current layers of turbulent magnetosheath reconnection. These observed emissions - typically detected in the layers immediately outside of the current layer proper - form two distinct types: (i) broadband emissions that extend continuously to lOs of Hertz; and (ii) structured bursts of emitted energy that occur above 80-Hz, often displaying features reminiscent of absorption bands and are observed near the local minima in the magnetic field. We present detailed analyses of these intense bursts of electromagnetic energy and quantify their proximity to X-IO-nulls and magnetic spine connected null pairs, as well as their correlation - if any - to the amount of magnetic energy converted by the process of magnetic reconnection.

  16. Vacuum solutions admitting a geodesic null congruence with shear proportional to expansion

    International Nuclear Information System (INIS)

    Kupeli, A.H.

    1988-01-01

    Algebraically general, nontwisting solutions for the vacuum to vacuum generalized Kerr--Schild (GKS) transformation are obtained. These solutions admit a geodesic null congruence with shear proportional to expansion. In the Newman--Penrose formalism, if l/sup μ/ is chosen to be the null vector of the GKS transformation, this property is stated as σ = arho and Da = 0. It is assumed that a is a constant, and the background is chosen as a pp-wave solution. For generic values of a, the GKS metrics consist of the Kasner solutions. For a = +- (1 +- (2)/sup 1/2/), there are solutions with less symmetries including special cases of the Kota--Perjes and Lukacs solutions

  17. Kinetic modeling of particle acceleration in a solar null point reconnection region

    DEFF Research Database (Denmark)

    Baumann, Gisela; Haugbølle, Troels; Nordlund, Åke

    2013-01-01

    The primary focus of this paper is on the particle acceleration mechanism in solar coronal 3D reconnection null-point regions. Starting from a potential field extrapolation of a SOHO magnetogram taken on 2002 November 16, we first performed MHD simulations with horizontal motions observed by SOHO...... particles and 3.5 billion grid cells of size 17.5\\,km --- these simulations offer a new opportunity to study particle acceleration in solar-like settings....... applied to the photospheric boundary of the computational box. After a build-up of electric current in the fan-plane of the null-point, a sub-section of the evolved MHD data was used as initial and boundary conditions for a kinetic particle-in-cell model of the plasma. We find that sub...

  18. IMPROVING INTERFEROMETRIC NULL DEPTH MEASUREMENTS USING STATISTICAL DISTRIBUTIONS: THEORY AND FIRST RESULTS WITH THE PALOMAR FIBER NULLER

    International Nuclear Information System (INIS)

    Hanot, C.; Riaud, P.; Absil, O.; Mennesson, B.; Martin, S.; Liewer, K.; Loya, F.; Mawet, D.; Serabyn, E.

    2011-01-01

    A new 'self-calibrated' statistical analysis method has been developed for the reduction of nulling interferometry data. The idea is to use the statistical distributions of the fluctuating null depth and beam intensities to retrieve the astrophysical null depth (or equivalently the object's visibility) in the presence of fast atmospheric fluctuations. The approach yields an accuracy much better (about an order of magnitude) than is presently possible with standard data reduction methods, because the astrophysical null depth accuracy is no longer limited by the magnitude of the instrumental phase and intensity errors but by uncertainties on their probability distributions. This approach was tested on the sky with the two-aperture fiber nulling instrument mounted on the Palomar Hale telescope. Using our new data analysis approach alone-and no observations of calibrators-we find that error bars on the astrophysical null depth as low as a few 10 -4 can be obtained in the near-infrared, which means that null depths lower than 10 -3 can be reliably measured. This statistical analysis is not specific to our instrument and may be applicable to other interferometers.

  19. A mycobacterial smc null mutant is proficient in DNA repair and long-term survival.

    Science.gov (United States)

    Güthlein, Carolin; Wanner, Roger M; Sander, Peter; Böttger, Erik C; Springer, Burkhard

    2008-01-01

    SMC (structural maintenance of chromosomes) proteins play fundamental roles in various aspects of chromosome organization and dynamics, including repair of DNA damage. Mutant strains of Mycobacterium smegmatis and Mycobacterium tuberculosis defective in SMC were constructed. Surprisingly, inactivation of smc did not result in recognizable phenotypes in hallmark assays characteristic for the function of these genes. This is in contrast to data for smc null mutants in other species.

  20. A Mycobacterial smc Null Mutant Is Proficient in DNA Repair and Long-Term Survival▿

    OpenAIRE

    Güthlein, Carolin; Wanner, Roger M.; Sander, Peter; Böttger, Erik C.; Springer, Burkhard

    2007-01-01

    SMC (structural maintenance of chromosomes) proteins play fundamental roles in various aspects of chromosome organization and dynamics, including repair of DNA damage. Mutant strains of Mycobacterium smegmatis and Mycobacterium tuberculosis defective in SMC were constructed. Surprisingly, inactivation of smc did not result in recognizable phenotypes in hallmark assays characteristic for the function of these genes. This is in contrast to data for smc null mutants in other species.

  1. Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation

    Directory of Open Access Journals (Sweden)

    Timothy M. Adamo

    2009-09-01

    Full Text Available A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in complex Minkowski space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss by (Bondi’s integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum–conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

  2. Potential of balloon payloads for in flight validation of direct and nulling interferometry concepts

    Science.gov (United States)

    Demangeon, Olivier; Ollivier, Marc; Le Duigou, Jean-Michel; Cassaing, Frédéric; Coudé du Foresto, Vincent; Mourard, Denis; Kern, Pierre; Lam Trong, Tien; Evrard, Jean; Absil, Olivier; Defrere, Denis; Lopez, Bruno

    2010-07-01

    While the question of low cost / low science precursors is raised to validate the concepts of direct and nulling interferometry space missions, balloon payloads offer a real opportunity thanks to their relatively low cost and reduced development plan. Taking into account the flight capabilities of various balloon types, we propose in this paper, several concepts of payloads associated to their flight plan. We also discuss the pros and cons of each concepts in terms of technological and science demonstration power.

  3. Tooth development in a model reptile: functional and null generation teeth in the gecko Paroedura picta

    Czech Academy of Sciences Publication Activity Database

    Zahradníček, Oldřich; Horáček, I.; Tucker, A. S.

    2012-01-01

    Roč. 221, č. 3 (2012), s. 195-208 ISSN 0021-8782 R&D Projects: GA ČR(CZ) GAP305/12/1766 Grant - others:GA AV ČR(CZ) KJB601110910 Program:KJ Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : cusps * gecko * null generation teeth Subject RIV: EA - Cell Biology Impact factor: 2.357, year: 2012

  4. Vascular Response to Intra-arterial Injury in the Thrombospondin-1 Null Mouse

    OpenAIRE

    Budhani, Faisal; Leonard, Katherine A.; Bergdahl, Andreas; Gao, Jimin; Lawler, Jack; Davis, Elaine C.

    2007-01-01

    Thrombospondin-1 (TSP-1) is a multifunctional, extracellular matrix protein that has been implicated in the regulation of smooth muscle cell proliferation, migration and differentiation during vascular development and injury. Vascular injury in wildtype and TSP-1 null mice was carried out by insertion of a straight spring guidewire into the femoral artery via a muscular arterial branch. Blood flow was restored after the muscular branch was ligated. The injury completely denuded the endotheliu...

  5. Null strings and complex Einstein-Maxwell fields with cosmological constant

    International Nuclear Information System (INIS)

    Garcia, A.; Plebanski, J.F.; Robinson, I.

    1977-01-01

    Previous results of Plebanski and Robinson (Phys. Rev. Lett.; 37:493 (1976)) concerning left-degenerate Einstein-flat complex space-times and preliminary results concerning the electromagnetic field, are here generalized and worked out in some detail for the system of Einstein-Maxwell equations with a cosmological constant. On the assumption that there exists a congruence of totally null surfaces, the system is reduced to a pair of equations for the two unknown functions. (author)

  6. The root infinitive stage in a null subject language: Romance in the Balkans

    Directory of Open Access Journals (Sweden)

    Larisa Avram

    2007-01-01

    Full Text Available The aim of the present paper is to determine which early non-finite verbal form is the Root Infinitive analogue in Romanian, an Inflection-licensed null subject language. In particular, we investigate whether the RI-analogue is the imperative, as predicted by Salustri and Hyams’s (2003 hypothesis, or whether it is a language specific underspecified form, overused during the early stages of acquisition, as predicted by Wexler et al. (2004.

  7. Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation

    Directory of Open Access Journals (Sweden)

    Timothy M. Adamo

    2012-01-01

    Full Text Available A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, H-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss by (Bondi's integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum--conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

  8. Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time.

    Directory of Open Access Journals (Sweden)

    Robert M Kaplan

    Full Text Available We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI funded trials has increased over time.We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality.17 of 30 studies (57% published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8% trials published after 2000 (χ2=12.2,df= 1, p=0.0005. There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings.The number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials.gov, may have contributed to the trend toward null findings.

  9. Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation.

    Science.gov (United States)

    Adamo, Timothy M; Newman, Ezra T; Kozameh, Carlos

    2012-01-01

    A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, [Formula: see text]-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell) field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss) by (Bondi's) integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum-conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

  10. Hypersensitivities for Acetaldehyde and Other Agents among Cancer Cells Null for Clinically Relevant Fanconi Anemia Genes

    OpenAIRE

    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, inclu...

  11. Congruences of null strings in complex space-times and some Cauchy--Kovalevski-like problems

    International Nuclear Information System (INIS)

    Robinson, I.; Rozga, K.

    1984-01-01

    It is shown that a problem of construction of a local congruence of null strings is equivalent to a natural Cauchy--Kovalevski-like problem, related to an equation for a spinor field k/sub A/ defining the congruence. Initial data are specified on two-dimensional submanifolds. In left-conformally-flat spaces, the solution of that problem exists for arbitrary initial data

  12. Chronic Toxoplasma gondii in Nurr1-Null Heterozygous Mice Exacerbates Elevated Open Field Activity

    OpenAIRE

    Eells, Jeffrey B.; Varela-Stokes, Andrea; Guo-Ross, Shirley X.; Kummari, Evangel; Smith, Holly M.; Cox, Erin; Lindsay, David S.

    2015-01-01

    Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open fie...

  13. Internalizing Null Extraterrestrial "Signals": An Astrobiological App for a Technological Society

    OpenAIRE

    Chaisson, Eric J.

    2014-01-01

    One of the beneficial outcomes of searching for life in the Universe is that it grants greater awareness of our own problems here on Earth. Lack of contact with alien beings to date might actually comprise a null "signal" pointing humankind toward a viable future. Astrobiology has surprising practical applications to human society; within the larger cosmological context of cosmic evolution, astrobiology clarifies the energetic essence of complex systems throughout the Universe, including tech...

  14. On the dependence of energy confinement on elongation in Single Null divertor plasmas

    International Nuclear Information System (INIS)

    Weisen, H.; Martin, Y.; Moret, J. M.; Others

    2002-03-01

    An analysis of the effect of magnetic geometry on heat flux in a wide range of Single Null diverted discharge configurations with 1.5 κ ∼ 74, based on the configurations in the study. This is very close to dependences from the ITER database for discharge conditions, such as ELMy H-modes, obtained from a large number of experiments in various tokamak devices. (author)

  15. Bi-dimensional null model analysis of presence-absence binary matrices.

    Science.gov (United States)

    Strona, Giovanni; Ulrich, Werner; Gotelli, Nicholas J

    2018-01-01

    Comparing the structure of presence/absence (i.e., binary) matrices with those of randomized counterparts is a common practice in ecology. However, differences in the randomization procedures (null models) can affect the results of the comparisons, leading matrix structural patterns to appear either "random" or not. Subjectivity in the choice of one particular null model over another makes it often advisable to compare the results obtained using several different approaches. Yet, available algorithms to randomize binary matrices differ substantially in respect to the constraints they impose on the discrepancy between observed and randomized row and column marginal totals, which complicates the interpretation of contrasting patterns. This calls for new strategies both to explore intermediate scenarios of restrictiveness in-between extreme constraint assumptions, and to properly synthesize the resulting information. Here we introduce a new modeling framework based on a flexible matrix randomization algorithm (named the "Tuning Peg" algorithm) that addresses both issues. The algorithm consists of a modified swap procedure in which the discrepancy between the row and column marginal totals of the target matrix and those of its randomized counterpart can be "tuned" in a continuous way by two parameters (controlling, respectively, row and column discrepancy). We show how combining the Tuning Peg with a wise random walk procedure makes it possible to explore the complete null space embraced by existing algorithms. This exploration allows researchers to visualize matrix structural patterns in an innovative bi-dimensional landscape of significance/effect size. We demonstrate the rational and potential of our approach with a set of simulated and real matrices, showing how the simultaneous investigation of a comprehensive and continuous portion of the null space can be extremely informative, and possibly key to resolving longstanding debates in the analysis of ecological

  16. Null Geodesics and Strong Field Gravitational Lensing in a String Cloud Background

    International Nuclear Information System (INIS)

    Iftikhar, Sehrish; Sharif, M.

    2015-01-01

    This paper is devoted to studying two interesting issues of a black hole with string cloud background. Firstly, we investigate null geodesics and find unstable orbital motion of particles. Secondly, we calculate deflection angle in strong field limit. We then find positions, magnifications, and observables of relativistic images for supermassive black hole at the galactic center. We conclude that string parameter highly affects the lensing process and results turn out to be quite different from the Schwarzschild black hole

  17. A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

    Science.gov (United States)

    Bernard, Kristine E.; Parkes, Tony L.; Merritt, Thomas J. S.

    2011-01-01

    The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain. PMID

  18. On the Penrose inequality for dust null shells in the Minkowski spacetime of arbitrary dimension

    International Nuclear Information System (INIS)

    Mars, Marc; Soria, Alberto

    2012-01-01

    A particular, yet relevant, case of the Penrose inequality involves null shells propagating in the Minkowski spacetime. Despite previous claims in the literature, the validity of this inequality remains open. In this paper, we rewrite this inequality in terms of the geometry of the surface obtained by intersecting the past null cone of the original surface S with a constant time hyperplane and the 'time height' function of S over this hyperplane. We also specialize to the case when S lies in the past null cone of a point and show the validity of the corresponding inequality in any dimension (in four dimensions this inequality was proved by Tod (1985 Class. Quantum Grav. 2 L65-8). Exploiting properties of convex hypersurfaces in the Euclidean space, we write down the Penrose inequality in the Minkowski spacetime of an arbitrary dimension n + 2 as an inequality for two smooth functions on the sphere S n . We finally obtain a sufficient condition for the validity of the Penrose inequality in the four-dimensional Minkowski spacetime and show that this condition is satisfied by a large class of surfaces. (paper)

  19. A robust null hypothesis for the potential causes of megadrought in western North America

    Science.gov (United States)

    Ault, T.; St George, S.; Smerdon, J. E.; Coats, S.; Mankin, J. S.; Cruz, C. C.; Cook, B.; Stevenson, S.

    2017-12-01

    The western United States was affected by several megadroughts during the last 1200 years, most prominently during the Medieval Climate Anomaly (MCA: 800 to 1300 CE). A null hypothesis is developed to test the possibility that, given a sufficiently long period of time, these events are inevitable and occur purely as a consequence of internal climate variability. The null distribution of this hypothesis is populated by a linear inverse model (LIM) constructed from global sea-surface temperature anomalies and self-calibrated Palmer Drought Severity Index data for North America. Despite being trained only on seasonal data from the late 20th century, the LIM produces megadroughts that are comparable in their duration, spatial scale, and magnitude as the most severe events of the last 12 centuries. The null hypothesis therefore cannot be rejected with much confidence when considering these features of megadrought, meaning that similar events are possible today, even without any changes to boundary conditions. In contrast, the observed clustering of megadroughts in the MCA, as well as the change in mean hydroclimate between the MCA and the 1500-2000 period, are more likely to have been caused by either external forcing or by internal climate variability not well sampled during the latter half of the Twentieth Century. Finally, the results demonstrate the LIM is a viable tool for determining whether paleoclimate reconstructions events should be ascribed to external forcings, "out of sample" climate mechanisms, or if they are consistent with the variability observed during the recent period.

  20. Null-point titration measurements of free magnesium in stored erythrocytes

    International Nuclear Information System (INIS)

    Bock, J.L.; Yusuf, Y.; Puntillo, E.

    1987-01-01

    Free intracellular magnesium concentration (Mg/sub i/) was measured in stored human erythrocytes, using null-point titration with ionophore A23187. For cells stored 31 P NMR spectroscopy, which showed a decrease in Mg/sub i/ with storage. However, the NMR measurements are performed with no pretreatment of the cells, while the null-point method requires an initial washing step, which alters pH/sub i/ and may also alter Mg/sub i/. The titration-measured Mg/sub i/ values are still surprisingly low for long-stored cells, considering that depletion of ATP and 2,3-DPG should release bound Mg. Using the titration-measured Mg/sub i/ values along with measurements of total Mg, ATP, and 2,3-DPG, they estimate that an additional buffer contains about 47% of total Mg in cells stored 21 days. Mg/sub i/ determinations by both 31 P NMR and null-point titration thus indicate that erythrocyte Mg is largely bound to a high-capacity, low-affinity buffer whose relative importance increases during cell storage. Discrepancies between the methods require further investigation

  1. Asymptotic symmetries of Rindler space at the horizon and null infinity

    International Nuclear Information System (INIS)

    Chung, Hyeyoun

    2010-01-01

    We investigate the asymptotic symmetries of Rindler space at null infinity and at the event horizon using both systematic and ad hoc methods. We find that the approaches that yield infinite-dimensional asymptotic symmetry algebras in the case of anti-de Sitter and flat spaces only give a finite-dimensional algebra for Rindler space at null infinity. We calculate the charges corresponding to these symmetries and confirm that they are finite, conserved, and integrable, and that the algebra of charges gives a representation of the asymptotic symmetry algebra. We also use relaxed boundary conditions to find infinite-dimensional asymptotic symmetry algebras for Rindler space at null infinity and at the event horizon. We compute the charges corresponding to these symmetries and confirm that they are finite and integrable. We also determine sufficient conditions for the charges to be conserved on-shell, and for the charge algebra to give a representation of the asymptotic symmetry algebra. In all cases, we find that the central extension of the charge algebra is trivial.

  2. Percentiles of the null distribution of 2 maximum lod score tests.

    Science.gov (United States)

    Ulgen, Ayse; Yoo, Yun Joo; Gordon, Derek; Finch, Stephen J; Mendell, Nancy R

    2004-01-01

    We here consider the null distribution of the maximum lod score (LOD-M) obtained upon maximizing over transmission model parameters (penetrance values, dominance, and allele frequency) as well as the recombination fraction. Also considered is the lod score maximized over a fixed choice of genetic model parameters and recombination-fraction values set prior to the analysis (MMLS) as proposed by Hodge et al. The objective is to fit parametric distributions to MMLS and LOD-M. Our results are based on 3,600 simulations of samples of n = 100 nuclear families ascertained for having one affected member and at least one other sibling available for linkage analysis. Each null distribution is approximately a mixture p(2)(0) + (1 - p)(2)(v). The values of MMLS appear to fit the mixture 0.20(2)(0) + 0.80chi(2)(1.6). The mixture distribution 0.13(2)(0) + 0.87chi(2)(2.8). appears to describe the null distribution of LOD-M. From these results we derive a simple method for obtaining critical values of LOD-M and MMLS. Copyright 2004 S. Karger AG, Basel

  3. Neuronal synchrony: peculiarity and generality.

    Science.gov (United States)

    Nowotny, Thomas; Huerta, Ramon; Rabinovich, Mikhail I

    2008-09-01

    Synchronization in neuronal systems is a new and intriguing application of dynamical systems theory. Why are neuronal systems different as a subject for synchronization? (1) Neurons in themselves are multidimensional nonlinear systems that are able to exhibit a wide variety of different activity patterns. Their "dynamical repertoire" includes regular or chaotic spiking, regular or chaotic bursting, multistability, and complex transient regimes. (2) Usually, neuronal oscillations are the result of the cooperative activity of many synaptically connected neurons (a neuronal circuit). Thus, it is necessary to consider synchronization between different neuronal circuits as well. (3) The synapses that implement the coupling between neurons are also dynamical elements and their intrinsic dynamics influences the process of synchronization or entrainment significantly. In this review we will focus on four new problems: (i) the synchronization in minimal neuronal networks with plastic synapses (synchronization with activity dependent coupling), (ii) synchronization of bursts that are generated by a group of nonsymmetrically coupled inhibitory neurons (heteroclinic synchronization), (iii) the coordination of activities of two coupled neuronal networks (partial synchronization of small composite structures), and (iv) coarse grained synchronization in larger systems (synchronization on a mesoscopic scale). (c) 2008 American Institute of Physics.

  4. From Neurons to Newtons

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2001-01-01

    proteins generate forces, to the macroscopic levels where overt arm movements are vol- untarily controlled within an unpredictable environment by legions of neurons¯ring in orderly fashion. An extensive computer simulation system has been developed for this thesis, which at present contains a neural...... network scripting language for specifying arbitrary neural architectures, de¯nition ¯les for detailed spinal networks, various biologically realistic models of neurons, and dynamic synapses. Also included are structurally accurate models of intrafusal and extra-fusal muscle ¯bers and a general body...... that an explicit function may be derived which expresses the force that the spindle contractile elements must produce to exactly counter spindle unloading during muscle shortening. This information was used to calculate the corresponding "optimal" °-motoneuronal activity level. For some simple arm movement tasks...

  5. Criticality in Neuronal Networks

    Science.gov (United States)

    Friedman, Nir; Ito, Shinya; Brinkman, Braden A. W.; Shimono, Masanori; Deville, R. E. Lee; Beggs, John M.; Dahmen, Karin A.; Butler, Tom C.

    2012-02-01

    In recent years, experiments detecting the electrical firing patterns in slices of in vitro brain tissue have been analyzed to suggest the presence of scale invariance and possibly criticality in the brain. Much of the work done however has been limited in two ways: 1) the data collected is from local field potentials that do not represent the firing of individual neurons; 2) the analysis has been primarily limited to histograms. In our work we examine data based on the firing of individual neurons (spike data), and greatly extend the analysis by considering shape collapse and exponents. Our results strongly suggest that the brain operates near a tuned critical point of a highly distinctive universality class.

  6. Multi-Segment Radius Measurement Using an Absolute Distance Meter Through a Null Assembly

    Science.gov (United States)

    Merle, Cormic; Wick, Eric; Hayden, Joseph

    2011-01-01

    This system was one of the test methods considered for measuring the radius of curvature of one or more of the 18 segmented mirrors that form the 6.5 m diameter primary mirror (PM) of the James Webb Space Telescope (JWST). The assembled telescope will be tested at cryogenic temperatures in a 17-m diameter by 27-m high vacuum chamber at the Johnson Space Center. This system uses a Leica Absolute Distance Meter (ADM), at a wavelength of 780 nm, combined with beam-steering and beam-shaping optics to make a differential distance measurement between a ring mirror on the reflective null assembly and individual PM segments. The ADM is located inside the same Pressure-Tight Enclosure (PTE) that houses the test interferometer. The PTE maintains the ADM and interferometer at ambient temperature and pressure so that they are not directly exposed to the telescope s harsh cryogenic and vacuum environment. This system takes advantage of the existing achromatic objective and reflective null assembly used by the test interferometer to direct four ADM beamlets to four PM segments through an optical path that is coincident with the interferometer beam. A mask, positioned on a linear slide, contains an array of 1.25 mm diameter circular subapertures that map to each of the 18 PM segments as well as six positions around the ring mirror. A down-collimated 4 mm ADM beam simultaneously covers 4 adjacent PM segment beamlets and one ring mirror beamlet. The radius, or spacing, of all 18 segments can be measured with the addition of two orthogonally-oriented scanning pentaprisms used to steer the ADM beam to any one of six different sub-aperture configurations at the plane of the ring mirror. The interferometer beam, at a wavelength of 687 nm, and the ADM beamlets, at a wavelength of 780 nm, pass through the objective and null so that the rays are normally incident on the parabolic PM surface. After reflecting off the PM, both the ADM and interferometer beams return to their respective

  7. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  8. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  9. Metabolic reprogramming during neuronal differentiation.

    Science.gov (United States)

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

  10. The Fourier-Kelvin Stellar Interferometer (FKSI) Nulling Testbed II: Closed-loop Path Length Metrology And Control Subsystem

    Science.gov (United States)

    Frey, B. J.; Barry, R. K.; Danchi, W. C.; Hyde, T. T.; Lee, K. Y.; Martino, A. J.; Zuray, M. S.

    2006-01-01

    The Fourier-Kelvin Stellar Interferometer (FKSI) is a mission concept for an imaging and nulling interferometer in the near to mid-infrared spectral region (3-8 microns), and will be a scientific and technological pathfinder for upcoming missions including TPF-I/DARWIN, SPECS, and SPIRIT. At NASA's Goddard Space Flight Center, we have constructed a symmetric Mach-Zehnder nulling testbed to demonstrate techniques and algorithms that can be used to establish and maintain the 10(exp 4) null depth that will be required for such a mission. Among the challenges inherent in such a system is the ability to acquire and track the null fringe to the desired depth for timescales on the order of hours in a laboratory environment. In addition, it is desirable to achieve this stability without using conventional dithering techniques. We describe recent testbed metrology and control system developments necessary to achieve these goals and present our preliminary results.

  11. Nickel reactivity and filaggrin null mutations--evaluation of the filaggrin bypass theory in a general population

    DEFF Research Database (Denmark)

    Ross-Hansen, Katrine; Menné, Torkil; Johansen, Jeanne D

    2011-01-01

    It was recently shown that filaggrin null mutation carrier status was associated with nickel allergy and self-reported intolerance to costume jewellery. Because of the biochemical characteristics of filaggrin, it may show nickel barrier properties in the stratum corneum....

  12. Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation

    Science.gov (United States)

    Tang, Zhongshu; Arjunan, Pachiappan; Lee, Chunsik; Li, Yang; Kumar, Anil; Hou, Xu; Wang, Bin; Wardega, Piotr; Zhang, Fan; Dong, Lijin; Zhang, Yongqing; Zhang, Shi-Zhuang; Ding, Hao; Fariss, Robert N.; Becker, Kevin G.; Lennartsson, Johan; Nagai, Nobuo; Cao, Yihai

    2010-01-01

    Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions. PMID:20231377

  13. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  14. Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor Identifies Molecular Pathways Implicated in Their Impaired Differentiation

    Directory of Open Access Journals (Sweden)

    Ashvin Iyer

    2017-10-01

    Full Text Available Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD, a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in EDMD, 340 genes were uniquely differentially expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes were uniquely expressed in emerin-null cells; 1706 genes were shared among both wildtype and emerin-null cells. One thousand and forty-seven transcripts showed differential expression during the transition from day 1 to day 2. Four hundred and thirty-one transcripts showed altered expression in both wildtype and emerin-null cells. Two hundred and ninety-five transcripts were differentially expressed only in emerin-null cells and 321 transcripts were differentially expressed only in wildtype cells. DAVID, STRING and Ingenuity Pathway Analysis identified pathways implicated in impaired emerin-null differentiation, including cell signaling, cell cycle checkpoints, integrin signaling, YAP/TAZ signaling, stem cell differentiation, and multiple muscle development and myogenic differentiation pathways. Functional enrichment analysis showed biological functions associated with the growth of muscle tissue and myogenesis of skeletal muscle were inhibited. The large number of differentially expressed transcripts upon differentiation induction suggests emerin functions during transcriptional reprograming of progenitors to committed myoblasts.

  15. Imitation, mirror neurons and autism

    OpenAIRE

    Williams, Justin H.G.; Whiten, Andrew; Suddendorf, Thomas; Perrett, David I.

    2001-01-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show ac...

  16. The biophysics of neuronal growth

    International Nuclear Information System (INIS)

    Franze, Kristian; Guck, Jochen

    2010-01-01

    For a long time, neuroscience has focused on biochemical, molecular biological and electrophysiological aspects of neuronal physiology and pathology. However, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. In this review we briefly summarize the historical background of neurobiophysics and give an overview over the current understanding of neuronal growth from a physics perspective. We show how biophysics has so far contributed to a better understanding of neuronal growth and discuss current inconsistencies. Finally, we speculate how biophysics may contribute to the successful treatment of lesions to the central nervous system, which have been considered incurable until very recently.

  17. Numerical simulations of sheared magnetic lines at the solar null line

    Science.gov (United States)

    Kuźma, B.; Murawski, K.; Solov'ev, A.

    2015-05-01

    Aims: We perform numerical simulations of sheared magnetic lines at the magnetic null line configuration of two magnetic arcades that are settled in a gravitationally stratified and magnetically confined solar corona. Methods: We developed a general analytical model of a 2.5D solar atmospheric structure. As a particular application of this model, we adopted it for the curved magnetic field lines with an inverted Y shape that compose the null line above two magnetic arcades, which are embedded in the solar atmosphere that is specified by the realistic temperature distribution. The physical system is described by 2.5D magnetohydrodynamic equations that are numerically solved by the FLASH code. Results: The magnetic field line shearing, implemented about 200 km below the transition region, results in Alfvén and magnetoacoustic waves that are able to penetrate solar coronal regions above the magnetic null line. As a result of the coupling of these waves, partial reflection from the transition region and scattering from inhomogeneous regions the Alfvén waves experience fast attenuation on time scales comparable to their wave periods, and the physical system relaxes in time. The attenuation time grows with the large amplitude and characteristic growing time of the shearing. Conclusions: By having chosen a different magnetic flux function, the analytical model we devised can be adopted to derive equilibrium conditions for a diversity of 2.5D magnetic structures in the solar atmosphere. Movie associated to Fig. 5 is available in electronic form at http://www.aanda.org

  18. Gap junction mediated intercellular metabolite transfer in the cochlea is compromised in connexin30 null mice.

    Directory of Open Access Journals (Sweden)

    Qing Chang

    Full Text Available Connexin26 (Cx26 and connexin30 (Cx30 are two major protein subunits that co-assemble to form gap junctions (GJs in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a

  19. Null hypothesis significance tests. A mix-up of two different theories

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg

    2015-01-01

    criticisms raised against NHST. As practiced, NHST has been characterized as a ‘null ritual’ that is overused and too often misapplied and misinterpreted. NHST is in fact a patchwork of two fundamentally different classical statistical testing models, often blended with some wishful quasi......-Bayesian interpretations. This is undoubtedly a major reason why NHST is very often misunderstood. But NHST also has intrinsic logical problems and the epistemic range of the information provided by such tests is much more limited than most researchers recognize. In this article we introduce to the scientometric community...

  20. Topology and Singularities in Cosmological Spacetimes Obeying the Null Energy Condition

    Science.gov (United States)

    Galloway, Gregory J.; Ling, Eric

    2018-06-01

    We consider globally hyperbolic spacetimes with compact Cauchy surfaces in a setting compatible with the presence of a positive cosmological constant. More specifically, for 3 + 1 dimensional spacetimes which satisfy the null energy condition and contain a future expanding compact Cauchy surface, we establish a precise connection between the topology of the Cauchy surfaces and the occurrence of past singularities. In addition to the Penrose singularity theorem, the proof makes use of some recent advances in the topology of 3-manifolds and of certain fundamental existence results for minimal surfaces.

  1. Null geodesics in black hole metrics with non-zero cosmological constant

    International Nuclear Information System (INIS)

    Stuchlik, Z.; Calvani, M.

    1990-02-01

    We study the radial motion along null geodesics in the Reissner-Nordstroem-de Sitter and Kerr-de Sitter space-times. We analyze the properties of the effective potential and we discuss circular orbits. We find that the radii of circular geodesics in the Reissner-Nordstroem-de Sitter space-time do not depend on the cosmological constant, and we explain this property using the optical reference geometry. In addition, we describe the unusual consequences of the interplay between rotation of the source and cosmological repulsion. (author). 16 refs, 8 figs

  2. Reply to "Comment on `Null weak values and the past of a quantum particle"'

    Science.gov (United States)

    Duprey, Q.; Matzkin, A.

    2018-04-01

    We discuss the preceding Comment [D. Sokolovski, preceding Comment, Phys. Rev. A 97, 046102 (2018), 10.1103/PhysRevA.97.046102] and conclude that the arguments given there against the relevance of null weak values as representing the absence of a system property are not compelling. We give an example in which the transition matrix elements that make the projector weak values vanish are the same ones that suppress detector clicks in strong measurements. Whether weak values are taken to account for the past of a quantum system or not depend on general interpretational commitments of the quantum formalism itself rather than on peculiarities of the weak measurements framework.

  3. Double null X-point operation in JET with NBI and ICRH heating

    International Nuclear Information System (INIS)

    Tubbing, B.; Bhatnagar, V.

    1989-01-01

    In this paper we report on a selection of experiments on H-modes, in 3 and 3.5MA discharges, in the double null X-point configuration. The first experiment, section 2, is an attempt to couple ICRH power to H-modes. Here we also report on a rather unique H-mode with a smaller than usual distance between plasma and limiter. The second experiment, section 3, is on H-modes in the low density, hot ion regime. (author) 5 refs., 4 figs

  4. The space-time outside a source of gravitational radiation: the axially symmetric null fluid

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, L. [Universidad Central de Venezuela, Escuela de Fisica, Facultad de Ciencias, Caracas (Venezuela, Bolivarian Republic of); Universidad de Salamanca, Instituto Universitario de Fisica Fundamental y Matematicas, Salamanca (Spain); Di Prisco, A. [Universidad Central de Venezuela, Escuela de Fisica, Facultad de Ciencias, Caracas (Venezuela, Bolivarian Republic of); Ospino, J. [Universidad de Salamanca, Departamento de Matematica Aplicada and Instituto Universitario de Fisica Fundamental y Matematicas, Salamanca (Spain)

    2016-11-15

    We carry out a study of the exterior of an axially and reflection symmetric source of gravitational radiation. The exterior of such a source is filled with a null fluid produced by the dissipative processes inherent to the emission of gravitational radiation, thereby representing a generalization of the Vaidya metric for axially and reflection symmetric space-times. The role of the vorticity, and its relationship with the presence of gravitational radiation is put in evidence. The spherically symmetric case (Vaidya) is, asymptotically, recovered within the context of the 1 + 3 formalism. (orig.)

  5. Theory of synergistic effects: Hill-type response surfaces as 'null-interaction' models for mixtures.

    Science.gov (United States)

    Schindler, Michael

    2017-08-02

    The classification of effects caused by mixtures of agents as synergistic, antagonistic or additive depends critically on the reference model of 'null interaction'. Two main approaches are currently in use, the Additive Dose (ADM) or concentration addition (CA) and the Multiplicative Survival (MSM) or independent action (IA) models. We compare several response surface models to a newly developed Hill response surface, obtained by solving a logistic partial differential equation (PDE). Assuming that a mixture of chemicals with individual Hill-type dose-response curves can be described by an n-dimensional logistic function, Hill's differential equation for pure agents is replaced by a PDE for mixtures whose solution provides Hill surfaces as 'null-interaction' models and relies neither on Bliss independence or Loewe additivity nor uses Chou's unified general theory. An n-dimensional logistic PDE decribing the Hill-type response of n-component mixtures is solved. Appropriate boundary conditions ensure the correct asymptotic behaviour. Mathematica 11 (Wolfram, Mathematica Version 11.0, 2016) is used for the mathematics and graphics presented in this article. The Hill response surface ansatz can be applied to mixtures of compounds with arbitrary Hill parameters. Restrictions which are required when deriving analytical expressions for response surfaces from other principles, are unnecessary. Many approaches based on Loewe additivity turn out be special cases of the Hill approach whose increased flexibility permits a better description of 'null-effect' responses. Missing sham-compliance of Bliss IA, known as Colby's model in agrochemistry, leads to incompatibility with the Hill surface ansatz. Examples of binary and ternary mixtures illustrate the differences between the approaches. For Hill-slopes close to one and doses below the half-maximum effect doses MSM (Colby, Bliss, Finney, Abbott) predicts synergistic effects where the Hill model indicates 'null

  6. Comments on correlation functions of large spin operators and null polygonal Wilson loops

    Energy Technology Data Exchange (ETDEWEB)

    Cardona, Carlos A., E-mail: cargicar@iafe.uba.ar [Instituto de Astronomia y Fisica del Espacio (CONICET-UBA), C.C. 67 - Suc. 28, 1428 Buenos Aires (Argentina); Physics Department, University of Buenos Aires, CONICET, Ciudad Universitaria, 1428 Buenos Aires (Argentina)

    2013-02-11

    We discuss the relation between correlation functions of twist-two large spin operators and expectation values of Wilson loops along light-like trajectories. After presenting some heuristic field theoretical arguments suggesting this relation, we compute the divergent part of the correlator in the limit of large 't Hooft coupling and large spins, using a semi-classical world-sheet which asymptotically looks like a GKP rotating string. We show this diverges as expected from the expectation value of a null Wilson loop, namely, as (ln{mu}{sup -2}){sup 2}, {mu} being a cut-off of the theory.

  7. The 10-D chiral null model and the relation to 4-D string solutions

    International Nuclear Information System (INIS)

    Behrndt, K.

    1994-12-01

    The chiral null model is a generalization of the fundamental string and gravitational wave background. It is an example of a conformally invariant model in all orders in α' and has unbroken supersymmetries. In a Kaluza-Klein approach we start in 10 dimensions and reduce the model down to 4 dimensions without making any restrictions. The 4-D field content is given by the metric, torsion, dilaton, a moduli field and 6 gauge fields. This model is self-dual and near the singularities asymptotically free. The relation to known IWP, Taub-NUT and rotating black hole solutions is discussed. (orig.)

  8. A critical discussion of null hypothesis significance testing and statistical power analysis within psychological research

    DEFF Research Database (Denmark)

    Jones, Allan; Sommerlund, Bo

    2007-01-01

    The uses of null hypothesis significance testing (NHST) and statistical power analysis within psychological research are critically discussed. The article looks at the problems of relying solely on NHST when dealing with small and large sample sizes. The use of power-analysis in estimating...... the potential error introduced by small and large samples is advocated. Power analysis is not recommended as a replacement to NHST but as an additional source of information about the phenomena under investigation. Moreover, the importance of conceptual analysis in relation to statistical analysis of hypothesis...

  9. Asymptotically shear-free and twist-free null geodesic congruences

    International Nuclear Information System (INIS)

    Kozameh, Carlos; Newman, Ezra T

    2007-01-01

    The Robinson-Trautman spacetime is a special case of asymptotically flat spacetimes that possess asymptotically shear-free and twist-free (surface forming) null geodesic congruences. In this paper we show that, although they are rare, a larger class of asymptotically flat spacetimes with this property does exist. In particular, we display the class of spacetimes that possess this dual property and demonstrate how these congruences can be found. In addition, we show that in each case the congruence is isolated in the sense that there are no other neighbouring congruences with this dual property

  10. High-contrast visible nulling coronagraph for segmented and arbitrary telescope apertures

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Bolcar, Matthew R.; Clampin, Mark; Petrone, Peter

    2014-08-01

    Exoplanet coronagraphy will be driven by the telescope architectures available and thus the system designer must have available one or more suitable coronagraphic instrument choices that spans the set of telescope apertures, including filled (off-axis), obscured (e.g. with secondary mirror spiders and struts), segmented apertures, such as JWST, and interferometric apertures. In this work we present one such choice of coronagraph, known as the visible nulling coronagraph (VNC), that spans all four types of aperture and also employs differential sensing and control.

  11. Testing the null hypothesis of the nonexistence of a preseizure state

    International Nuclear Information System (INIS)

    Andrzejak, Ralph G.; Kraskov, Alexander; Mormann, Florian; Rieke, Christoph; Kreuz, Thomas; Elger, Christian E.; Lehnertz, Klaus

    2003-01-01

    A rapidly growing number of studies deals with the prediction of epileptic seizures. For this purpose, various techniques derived from linear and nonlinear time series analysis have been applied to the electroencephalogram of epilepsy patients. In none of these works, however, the performance of the seizure prediction statistics is tested against a null hypothesis, an otherwise ubiquitous concept in science. In consequence, the evaluation of the reported performance values is problematic. Here, we propose the technique of seizure time surrogates based on a Monte Carlo simulation to remedy this deficit

  12. Testing the null hypothesis of the nonexistence of a preseizure state

    Energy Technology Data Exchange (ETDEWEB)

    Andrzejak, Ralph G; Kraskov, Alexander [John-von-Neumann Institute for Computing, Forschungszentrum Juelich, 52425 Juelich (Germany); Mormann, Florian; Rieke, Christoph [Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn (Germany); Helmholtz Institut fuer Strahlen- und Kernphysik, University of Bonn, Nussallee 14-16, 53115 Bonn (Germany); Kreuz, Thomas [John-von-Neumann Institute for Computing, Forschungszentrum Juelich, 52425 Juelich (Germany); Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn (Germany); Elger, Christian E; Lehnertz, Klaus [Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn (Germany)

    2003-01-01

    A rapidly growing number of studies deals with the prediction of epileptic seizures. For this purpose, various techniques derived from linear and nonlinear time series analysis have been applied to the electroencephalogram of epilepsy patients. In none of these works, however, the performance of the seizure prediction statistics is tested against a null hypothesis, an otherwise ubiquitous concept in science. In consequence, the evaluation of the reported performance values is problematic. Here, we propose the technique of seizure time surrogates based on a Monte Carlo simulation to remedy this deficit.

  13. Comments on correlation functions of large spin operators and null polygonal Wilson loops

    International Nuclear Information System (INIS)

    Cardona, Carlos A.

    2013-01-01

    We discuss the relation between correlation functions of twist-two large spin operators and expectation values of Wilson loops along light-like trajectories. After presenting some heuristic field theoretical arguments suggesting this relation, we compute the divergent part of the correlator in the limit of large 't Hooft coupling and large spins, using a semi-classical world-sheet which asymptotically looks like a GKP rotating string. We show this diverges as expected from the expectation value of a null Wilson loop, namely, as (lnμ −2 ) 2 , μ being a cut-off of the theory.

  14. Five-dimensional null-cone structure of big bang singularity

    International Nuclear Information System (INIS)

    Lauro, S.; Schucking, E.L.

    1985-01-01

    The Friedmann model PHI of positive space curvature, vanishing pressure and cosmological constant when isometrically imbedded as a hypersurface in five-dimensional Minkowski space M 5 is globally rigid: if F(PHI) and F'(PHI) are isometric embeddings in M 5 there is a motion π of M 5 such that F'=π 0 F. The big bang singularity is the vertex of a null half-cone in M 5 . Global rigidity leads to an invariant characterization of the singularity. The structure of matter at the singularity is governed by the de Sitter group. (author)

  15. Five-dimensional null-cone structure of big bang singularity

    Energy Technology Data Exchange (ETDEWEB)

    Lauro, S.; Schucking, E.L.

    1985-04-01

    The Friedmann model PHI of positive space curvature, vanishing pressure and cosmological constant when isometrically imbedded as a hypersurface in five-dimensional Minkowski space MV is globally rigid: if F(PHI) and F'(PHI) are isometric embeddings in MV there is a motion of MV such that F'= F. The big bang singularity is the vertex of a null half-cone in MV. Global rigidity leads to an invariant characterization of the singularity. The structure of matter at the singularity is governed by the de Sitter group.

  16. Dimension shifting operators and null states in 2D conformally invariant field theories

    International Nuclear Information System (INIS)

    Gervais, J.L.

    1986-01-01

    We discuss the existence and properties of differential operators which transform covariant operators into covariant operators of different weights in two-dimensional conformally invariant field theories. We relate them to null states and the vanishing of the Kac determinant in representations of the conformal algebra, and to the existence of differential equations for Green functions of covariant operators. In this framework, we rederive the essential features of our earlier work on dual models with shifted intercept, which in euclidean space-time gives explicit solutions of the conformal bootstrap equations where all operators are marginal. (orig.)

  17. Network models predict that reduced excitatory fluctuations can give rise to hippocampal network hyper-excitability in MeCP2-null mice.

    Directory of Open Access Journals (Sweden)

    Ernest C Y Ho

    Full Text Available Rett syndrome is a severe pediatric neurological disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2. Although MeCP2 is expressed near ubiquitously, the primary pathophysiology of Rett syndrome stems from impairments of nervous system function. One alteration within different regions of the MeCP2-deficient brain is the presence of hyper-excitable network responses. In the hippocampus, such responses exist despite there being an overall decrease in spontaneous excitatory drive within the network. In this study, we generated and used mathematical, neuronal network models to resolve this apparent paradox. We did this by taking advantage of previous mathematical modelling insights that indicated that decreased excitatory fluctuations, but not mean excitatory drive, more critically explain observed changes in hippocampal network oscillations from MeCP2-null mouse slices. Importantly, reduced excitatory fluctuations could also bring about hyper-excitable responses in our network models. Therefore, these results indicate that diminished excitatory fluctuations may be responsible for the hyper-excitable state of MeCP2-deficient hippocampal circuitry.

  18. Expression of extracellular matrix components is disrupted in the immature and adult estrogen receptor β-null mouse ovary.

    Directory of Open Access Journals (Sweden)

    Alexandra Zalewski

    Full Text Available Within the ovary, Estrogen Receptor β (ERβ is localized to the granulosa cells of growing follicles. 17β-estradiol (E2 acting via ERβ augments the actions of follicle stimulating hormone in granulosa cells, leading to granulosa cell differentiation and formation of a preovulatory follicle. Adult ERβ-null females are subfertile and possess ovaries with reduced numbers of growing follicles and corpora lutea. Because the majority of E2 production by granulosa cells occurs once puberty is reached, a role for ERβ in the ovary prior to puberty has not been well examined. We now provide evidence that lack of ERβ disrupts gene expression as early as post-natal day (PND 13, and in particular, we identify a number of genes of the extracellular matrix (ECM that are significantly higher in ERβ-null follicles than in wildtype (WT follicles. Considerable changes occur to the ECM occur during normal folliculogenesis to allow for the dramatic growth, cellular differentiation, and reorganization of the follicle from the primary to preovulatory stage. Using quantitative PCR and immunofluorescence, we now show that several ECM genes are aberrantly overexpressed in ERβ-null follicles. We find that Collagen11a1, a protein highly expressed in cartilage, is significantly higher in ERβ-null follicles than WT follicles as early as PND 13, and this heightened expression continues through PND 23-29 into adulthood. Similarly, Nidogen 2, a highly conserved basement membrane glycoprotein, is elevated in ERβ-null follicles at PND 13 into adulthood, and is elevated specifically in the ERβ-null focimatrix, a basal lamina-like matrix located between granulosa cells. Focimatrix laminin and Collagen IV expression were also higher in ERβ-null ovaries than in WT ovaries at various ages. Our findings suggest two novel observations: a that ERβ regulates granulosa cell gene expression ovary prior to puberty, and b that ERβ regulates expression of ECM components in the

  19. A near-null magnetic field affects cryptochrome-related hypocotyl growth and flowering in Arabidopsis

    Science.gov (United States)

    Xu, Chunxiao; Yin, Xiao; Lv, Yan; Wu, Changzhe; Zhang, Yuxia; Song, Tao

    2012-03-01

    The blue light receptor, cryptochrome, has been suggested to act as a magnetoreceptor based on the proposition that photochemical reactions are involved in sensing the geomagnetic field. But the effects of the geomagnetic field on cryptochrome remain unclear. Although the functions of cryptochrome have been well demonstrated for Arabidopsis, the effect of the geomagnetic field on the growth of Arabidopsis and its mechanism of action are poorly understood. We eliminated the local geomagnetic field to grow Arabidopsis in a near-null magnetic field and found that the inhibition of Arabidopsis hypocotyl growth by white light was weakened, and flowering time was delayed. The expressions of three cryptochrome-signaling-related genes, PHYB, CO and FT also changed; the transcript level of PHYB was elevated ca. 40%, and that of CO and FT was reduced ca. 40% and 50%, respectively. These data suggest that the effects of a near-null magnetic field on Arabidopsis are cryptochrome-related, which may be revealed by a modification of the active state of cryptochrome and the subsequent signaling cascade.

  20. 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.

  1. Nulling Data Reduction and On-Sky Performance of the Large Binocular Telescope Interferometer

    Science.gov (United States)

    Defrere, D.; Hinz, P. M.; Mennesson, B.; Hoffman, W. F.; Millan-Gabet, R.; Skemer, A. J.; Bailey, V.; Danchi, W. C.; Downy, E. C.; Durney, O.; hide

    2016-01-01

    The Large Binocular Telescope Interferometer (LBTI) is a versatile instrument designed for high angular resolution and high-contrast infrared imaging (1.5-13 micrometers). In this paper, we focus on the mid-infrared (8-13 micrometers) nulling mode and present its theory of operation, data reduction, and on-sky performance as of the end of the commissioning phase in 2015 March. With an interferometric baseline of 14.4 m, the LBTI nuller is specifically tuned to resolve the habitable zone of nearby main-sequence stars, where warm exozodiacal dust emission peaks. Measuring the exozodi luminosity function of nearby main-sequence stars is a key milestone to prepare for future exo-Earth direct imaging instruments. Thanks to recent progress in wavefront control and phase stabilization, as well as in data reduction techniques, the LBTI demonstrated in 2015 February a calibrated null accuracy of 0.05% over a 3 hr long observing sequence on the bright nearby A3V star Beta Leo. This is equivalent to an exozodiacal disk density of 15-30 zodi for a Sun-like star located at 10 pc, depending on the adopted disk model. This result sets a new record for high-contrast mid-infrared interferometric imaging and opens a new window on the study of planetary systems.

  2. Telescopes in Near Space: Balloon Exoplanet Nulling Interferometer (BigBENI)

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Mauk, Robin

    2012-01-01

    A significant and often overlooked path to advancing both science and technology for direct imaging and spectroscopic characterization of exosolar planets is to fly "near space" missions, i.e. balloon borne exosolar missions. A near space balloon mission with two or more telescopes, coherently combined, is capable of achieving a subset of the mission science goals of a single large space telescope at a small fraction of the cost. Additionally such an approach advances technologies toward flight readiness for space flight. Herein we discuss the feasibility of flying two 1.2 meter telescopes, with a baseline separation of 3.6 meters, operating in visible light, on a composite boom structure coupled to a modified visible nulling coronagraph operating to achieve an inner working angle of 60 milli-arcseconds. We discuss the potential science return, atmospheric residuals at 135,000 feet, pointing control and visible nulling and evaluate the state-or-art of these technologies with regards to balloon missions.

  3. Thrombospondin 2-null mice display an altered brain foreign body response to polyvinyl alcohol sponge implants

    International Nuclear Information System (INIS)

    Tian Weiming; Kyriakides, Themis R

    2009-01-01

    Thrombospondin (TSP)-2 is a matricellular protein that participates in the processes of tissue repair and the foreign body response. In addition, TSP2 has been shown to influence synaptogenesis and recovery of the brain following stroke. In the present study we investigated the response following the implantation of polyvinyl alcohol (PVA) sponges in the brain. PVA sponges were implanted into the brain cortex of wild type and TSP2-null mice for a period of 4 and 8 weeks and the response was analyzed by histochemistry and quantitative immunohistochemistry. TSP2 expression was detected in the interstices of the sponge and co-localized with the extracellular matrix and astrocytes. PVA sponge invasion in TSP2-null mice was characterized by dense deposition of extracellular matrix and increased invasion of reactive astrocytes and macrophages/microglia. Furthermore, the angiogenic response was elevated and the detection of mouse serum albumin (MSA) in the brain cortex indicated excessive vessel leakage, suggesting that TSP2 plays a role in the repair/maintenance of the blood brain barrier. Finally, immunostaining demonstrated an increase in the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Taken together, our observations support a role for TSP2 as critical determinant of the brain response to biomaterials.

  4. Optimized scheduling technique of null subcarriers for peak power control in 3GPP LTE downlink.

    Science.gov (United States)

    Cho, Soobum; Park, Sang Kyu

    2014-01-01

    Orthogonal frequency division multiple access (OFDMA) is a key multiple access technique for the long term evolution (LTE) downlink. However, high peak-to-average power ratio (PAPR) can cause the degradation of power efficiency. The well-known PAPR reduction technique, dummy sequence insertion (DSI), can be a realistic solution because of its structural simplicity. However, the large usage of subcarriers for the dummy sequences may decrease the transmitted data rate in the DSI scheme. In this paper, a novel DSI scheme is applied to the LTE system. Firstly, we obtain the null subcarriers in single-input single-output (SISO) and multiple-input multiple-output (MIMO) systems, respectively; then, optimized dummy sequences are inserted into the obtained null subcarrier. Simulation results show that Walsh-Hadamard transform (WHT) sequence is the best for the dummy sequence and the ratio of 16 to 20 for the WHT and randomly generated sequences has the maximum PAPR reduction performance. The number of near optimal iteration is derived to prevent exhausted iterations. It is also shown that there is no bit error rate (BER) degradation with the proposed technique in LTE downlink system.

  5. The gravitational exclusion principle and null states in anti-de Sitter space

    International Nuclear Information System (INIS)

    Castro, Alejandra; Maloney, Alexander; Hartman, Thomas

    2011-01-01

    The holographic principle implies a vast reduction in the number of degrees of freedom of quantum gravity. This idea can be made precise in AdS 3 , where the the stringy or gravitational exclusion principle asserts that certain perturbative excitations are not present in the exact quantum spectrum. We show that this effect is visible directly in the bulk gravity theory: the norm of the offending linearized state is zero or negative. When the norm is negative, the theory is signalling its own breakdown as an effective field theory; this provides a perturbative bulk explanation for the stringy exclusion principle. When the norm vanishes the bulk state is null rather than physical. This implies that certain non-trivial diffeomorphisms must be regarded as gauge symmetries rather than spectrum-generating elements of the asymptotic symmetry group. This leads to subtle effects in the computation of one-loop determinants for Einstein gravity, higher spin theories and topologically massive gravity in AdS 3 . In particular, heat kernel methods do not capture the correct spectrum of a theory with null states. Communicated by S Ross

  6. Modular Hamiltonians for deformed half-spaces and the averaged null energy condition

    Science.gov (United States)

    Faulkner, Thomas; Leigh, Robert G.; Parrikar, Onkar; Wang, Huajia

    2016-09-01

    We study modular Hamiltonians corresponding to the vacuum state for deformed half-spaces in relativistic quantum field theories on {{R}}^{1,d-1} . We show that in addition to the usual boost generator, there is a contribution to the modular Hamiltonian at first order in the shape deformation, proportional to the integral of the null components of the stress tensor along the Rindler horizon. We use this fact along with monotonicity of relative entropy to prove the averaged null energy condition in Minkowski space-time. This subsequently gives a new proof of the Hofman-Maldacena bounds on the parameters appearing in CFT three-point functions. Our main technical advance involves adapting newly developed perturbative methods for calculating entanglement entropy to the problem at hand. These methods were recently used to prove certain results on the shape dependence of entanglement in CFTs and here we generalize these results to excited states and real time dynamics. We also discuss the AdS/CFT counterpart of this result, making connection with the recently proposed gravitational dual for modular Hamiltonians in holographic theories.

  7. OEDGE modeling of the DIII-D double null (CH4)-C-13 puffing experiment

    International Nuclear Information System (INIS)

    Elder, J.D.; Wampler, W.R.; McLean, A.G.; Stangeby, P.C.; Allen, S.L.; Bray, B.D.; Brooks, N.H.; Leonard, A.W.; Unterberg, Ezekial A.; Watkins, J.G.

    2011-01-01

    Unbalanced double null ELMy H-mode configurations in DIII-D are used to simulate the situation in ITER high triangularity, burning plasma magnetic equilibria, where the second X-point lies close to the top of the vacuum vessel, creating a secondary divertor region at the upper blanket modules. The measured plasma conditions in the outer secondary divertor closely duplicated those projected for ITER. (CH4)-C-13 was injected into the secondary outer divertor to simulate sputtering there. The majority of the C-13 found was in the secondary outer divertor. This material migration pattern is radically different than that observed for main wall (CH4)-C-13 injections into single null configurations where the deposition is primarily at the inner divertor. The implications for tritium codeposition resulting from sputtering at the secondary divertor in ITER are significant since release of tritium from Be co-deposits at the main wall bake temperature for ITER, 240 degrees C, is incomplete. The principal features of the measured C-13 deposition pattern have been replicated by the OEDGE interpretive code.

  8. Integrated optics for nulling interferometry in the thermal infrared: progress and recent achievements

    Science.gov (United States)

    Barillot, M.; Barthelemy, E.; Bastard, L.; Broquin, J.-E.; Hawkins, G.; Kirschner, V.; Ménard, S.; Parent, G.; Poinsot, C.; Pradel, A.; Vigreux, C.; Zhang, S.; Zhang, X.

    2017-11-01

    The search for Earth-like exoplanets, orbiting in the habitable zone of stars other than our Sun and showing biological activity, is one of the most exciting and challenging quests of the present time. Nulling interferometry from space, in the thermal infrared, appears as a promising candidate technique for the task of directly observing extra-solar planets. It has been studied for about 10 years by ESA and NASA in the framework of the Darwin and TPF-I missions respectively [1]. Nevertheless, nulling interferometry in the thermal infrared remains a technological challenge at several levels. Among them, the development of the "modal filter" function is mandatory for the filtering of the wavefronts in adequacy with the objective of rejecting the central star flux to an efficiency of about 105. Modal filtering [2] takes benefit of the capability of single-mode waveguides to transmit a single amplitude function, to eliminate virtually any perturbation of the interfering wavefronts, thus making very high rejection ratios possible. The modal filter may either be based on single-mode Integrated Optics (IO) and/or Fiber Optics. In this paper, we focus on IO, and more specifically on the progress of the on-going "Integrated Optics" activity of the European Space Agency.

  9. Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Dipankar Ray

    2011-05-01

    Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

  10. Novel Remarks on Point Mass Sources, Firewalls, Null Singularities and Gravitational Entropy

    Science.gov (United States)

    Perelman, Carlos Castro

    2016-01-01

    A continuous family of static spherically symmetric solutions of Einstein's vacuum field equations with a spatial singularity at the origin r = 0 is found. These solutions are parametrized by a real valued parameter λ (ranging from 0 to 1) and such that the radial horizon's location is displaced continuously towards the singularity ( r = 0 ) as λ increases. In the extreme limit λ = 1, the location of the singularity and horizon merges leading to a null singularity. In this extreme case, any infalling observer hits the null singularity at the very moment he/she crosses the horizon. This fact may have important consequences for the resolution of the fire wall problem and the complementarity controversy in black holes. An heuristic argument is provided how one might avoid the Hawking particle emission process in this extreme case when the singularity and horizon merges. The field equations due to a delta-function point-mass source at r = 0 are solved and the Euclidean gravitational action corresponding to those solutions is evaluated explicitly. It is found that the Euclidean action is precisely equal to the black hole entropy (in Planck area units). This result holds in any dimensions D ≥ 3.

  11. NULLING DATA REDUCTION AND ON-SKY PERFORMANCE OF THE LARGE BINOCULAR TELESCOPE INTERFEROMETER

    Energy Technology Data Exchange (ETDEWEB)

    Defrère, D.; Hinz, P. M.; Hoffmann, W. F.; Skemer, A. J.; Bailey, V.; Downey, E. C.; Durney, O.; Grenz, P.; McMahon, T. J.; Montoya, M.; Spalding, E.; Vaz, A.; Arbo, P.; Brusa, G. [Steward Observatory, Department of Astronomy, University of Arizona, 933 N. Cherry Avenue, Tucson, AZ 85721 (United States); Mennesson, B. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109-8099 (United States); Millan-Gabet, R. [NASA Exoplanet Science Institute, California Institute of Technology, 770 South Wilson Avenue, Pasadena, CA 91125 (United States); Danchi, W. C. [NASA Goddard Space Flight Center, Exoplanets and Stellar Astrophysics Laboratory, Code 667, Greenbelt, MD 20771 (United States); Hill, J. M. [Large Binocular Telescope Observatory, University of Arizona, 933 N. Cherry Avenue, Tucson, AZ 85721 (United States); Absil, O. [Institut d’Astrophysique et de Géophysique, Université de Liège, 19c Allée du Six Août, B-4000 Sart Tilman (Belgium); Bailey, H., E-mail: ddefrere@email.arizona.edu [Lunar and Planetary Laboratory, University of Arizona, 1541 E, University Boulevard, Tucson, AZ 85721 (United States); and others

    2016-06-20

    The Large Binocular Telescope Interferometer (LBTI) is a versatile instrument designed for high angular resolution and high-contrast infrared imaging (1.5–13 μ m). In this paper, we focus on the mid-infrared (8–13 μ m) nulling mode and present its theory of operation, data reduction, and on-sky performance as of the end of the commissioning phase in 2015 March. With an interferometric baseline of 14.4 m, the LBTI nuller is specifically tuned to resolve the habitable zone of nearby main-sequence stars, where warm exozodiacal dust emission peaks. Measuring the exozodi luminosity function of nearby main-sequence stars is a key milestone to prepare for future exo-Earth direct imaging instruments. Thanks to recent progress in wavefront control and phase stabilization, as well as in data reduction techniques, the LBTI demonstrated in 2015 February a calibrated null accuracy of 0.05% over a 3 hr long observing sequence on the bright nearby A3V star β Leo. This is equivalent to an exozodiacal disk density of 15–30 zodi for a Sun-like star located at 10 pc, depending on the adopted disk model. This result sets a new record for high-contrast mid-infrared interferometric imaging and opens a new window on the study of planetary systems.

  12. Positive, negative, or null? The effects of maternal incarceration on children's behavioral problems.

    Science.gov (United States)

    Wildeman, Christopher; Turney, Kristin

    2014-06-01

    We use data from the Fragile Families and Child Wellbeing Study to consider the effects of maternal incarceration on 21 caregiver- and teacher-reported behavioral problems among 9-year-old children. The results suggest three primary conclusions. First, children of incarcerated mothers are a disadvantaged group that exhibit high levels of caregiver- and teacher-reported behavioral problems. Second, after we adjust for selection, the effects of maternal incarceration on children's behavioral problems are consistently null (for 19 of 21 outcomes) and rarely positive (1 of 21) or negative (1 of 21), suggesting that the poor outcomes of these children are driven by disadvantages preceding maternal incarceration rather than incarceration. These effects, however, vary across race/ethnicity, with maternal incarceration diminishing caregiver-reported behavioral problems among non-Hispanic whites. Finally, in models considering both maternal and paternal incarceration, paternal incarceration is associated with more behavioral problems, which is consistent with previous research and suggests that the null effects of maternal incarceration are not artifacts of our sample or analytic decisions.

  13. Conformal gravity, the Einstein equations and spaces of complex null geodesics

    Energy Technology Data Exchange (ETDEWEB)

    Baston, R.J.; Mason, L.J.

    1987-07-01

    The aim of the paper is to give a twistorial characterisation of the field equations of conformal gravity and of Einstein spacetimes. Strong evidence is provided for a particularly concise characterisation of these equations in terms of 'formal neighbourhoods'of the space of complex null geodesics. Second-order perturbations of the metric of complexified Minkowski space are considered. These correspond to certain infinitesimal deformations of its space of complex null geodesics, PN. PN has a natural codimension one embedding into a larger space. It is shown that deformations extend automatically to the fourth-order embedding (that is, the fourth formal neighbourhood). They extend to the fifth formal neighbourhood if and only if the corresponding perturbation in the metric has vanishing Bach tensor. Finally, deformations which extend to the sixth formal neighbourhood correspond to perturbations in the metric that are conformally related to ones satisfying the Einstein equations. The authors present arguments which suggest that the results will also hold when spacetime is fully curved.

  14. Conformal gravity, the Einstein equations and spaces of complex null geodesics

    International Nuclear Information System (INIS)

    Baston, R.J.; Mason, L.J.

    1987-01-01

    The aim of the paper is to give a twistorial characterisation of the field equations of conformal gravity and of Einstein spacetimes. Strong evidence is provided for a particularly concise characterisation of these equations in terms of 'formal neighbourhoods'of the space of complex null geodesics. Second-order perturbations of the metric of complexified Minkowski space are considered. These correspond to certain infinitesimal deformations of its space of complex null geodesics, PN. PN has a natural codimension one embedding into a larger space. It is shown that deformations extend automatically to the fourth-order embedding (that is, the fourth formal neighbourhood). They extend to the fifth formal neighbourhood if and only if the corresponding perturbation in the metric has vanishing Bach tensor. Finally, deformations which extend to the sixth formal neighbourhood correspond to perturbations in the metric that are conformally related to ones satisfying the Einstein equations. The authors present arguments which suggest that the results will also hold when spacetime is fully curved. (author)

  15. Approaches for achieving broadband achromatic phase shifts for visible nulling coronagraphy

    Science.gov (United States)

    Bolcar, Matthew R.; Lyon, Richard G.

    2012-07-01

    Visible nulling coronagraphy is one of the few approaches to the direct detection and characterization of Jovian and Terrestrial exoplanets that works with segmented aperture telescopes. Jovian and Terrestrial planets require at least 10-9 and 10-10 image plane contrasts, respectively, within the spectral bandpass and thus require a nearly achromatic π-phase difference between the arms of the interferometer. An achromatic π-phase shift can be achieved by several techniques, including sequential angled thick glass plates of varying dispersive materials, distributed thin-film multilayer coatings, or techniques that leverage the polarization-dependent phase shift of total-internal reflections. Herein we describe two implementations of such techniques: sequential thick glass plates and Fresnel rhomb prisms. A viable technique must achieve the achromatic phase shift while simultaneously minimizing the intensity difference, chromatic beam spread and polarization variation between the interferometer arms. In this paper we describe the above implementations and report on the trades associated with each technique that will lead to an implementation of the most promising one in Goddard's Visible Nulling Coronagraph (VNC).

  16. Identifying the null subject: evidence from event-related brain potentials.

    Science.gov (United States)

    Demestre, J; Meltzer, S; García-Albea, J E; Vigil, A

    1999-05-01

    Event-related brain potentials (ERPs) were recorded during spoken language comprehension to study the on-line effects of gender agreement violations in controlled infinitival complements. Spanish sentences were constructed in which the complement clause contained a predicate adjective marked for syntactic gender. By manipulating the gender of the antecedent (i.e., the controller) of the implicit subject while holding constant the gender of the adjective, pairs of grammatical and ungrammatical sentences were created. The detection of such a gender agreement violation would indicate that the parser had established the coreference relation between the null subject and its antecedent. The results showed a complex biphasic ERP (i.e., an early negativity with prominence at anterior and central sites, followed by a centroparietal positivity) in the violating condition as compared to the non-violating conditions. The brain reacts to NP-adjective gender agreement violations within a few hundred milliseconds of their occurrence. The data imply that the parser has properly coindexed the null subject of an infinitive clause with its antecedent.

  17. Catastrophe in the stochastic layer due to dipole perturbation for a single-null divertor Tokamak

    International Nuclear Information System (INIS)

    Ali, H.; Watson, M.; Punjabi, A.; Boozer, A.

    1996-01-01

    We use the method of maps developed by Punjabi and Boozer to investigate the motion of magnetic field lines in stochastic scrape-off layer in the presence of dipole perturbation of a single-null divertor Tokamak. This method is based on the idea that the magnetic field line trajectories in a divertor tokamak are mathematically equivalent to a single degree of freedom, time dependent Hamiltonian System, and that the basic features of motion near a separatrix broadened by asymmetric perturbations are generic for such Hamiltonian and near-Hamiltonian systems. The magnetic topology of a single-null divertor tokamak with the effects on dipole perturbations is represented by the Symmetric Simple Map followed by Dipole Map. We have found that as the amplitude of the dipole perturbation increases, the width of the stochastic layer also increases. At some critical value of the amplitude is reached, there is a catastrophic increase in the width of stochastic layer. This may have significant implications for tokamak divertor physics

  18. Null stream analysis of Pulsar Timing Array data: localisation of resolvable gravitational wave sources

    Science.gov (United States)

    Goldstein, Janna; Veitch, John; Sesana, Alberto; Vecchio, Alberto

    2018-04-01

    Super-massive black hole binaries are expected to produce a gravitational wave (GW) signal in the nano-Hertz frequency band which may be detected by pulsar timing arrays (PTAs) in the coming years. The signal is composed of both stochastic and individually resolvable components. Here we develop a generic Bayesian method for the analysis of resolvable sources based on the construction of `null-streams' which cancel the part of the signal held in common for each pulsar (the Earth-term). For an array of N pulsars there are N - 2 independent null-streams that cancel the GW signal from a particular sky location. This method is applied to the localisation of quasi-circular binaries undergoing adiabatic inspiral. We carry out a systematic investigation of the scaling of the localisation accuracy with signal strength and number of pulsars in the PTA. Additionally, we find that source sky localisation with the International PTA data release one is vastly superior than what is achieved by its constituent regional PTAs.

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

    Science.gov (United States)

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

    2016-02-01

    This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Canonical theory of spherically symmetric spacetimes with cross-streaming null dusts

    Science.gov (United States)

    Bičák, Jiří; Hájíček, Petr

    2003-11-01

    The Hamiltonian dynamics of two-component spherically symmetric null dust is studied with regard to the quantum theory of gravitational collapse. The components—the ingoing and outgoing dusts—are assumed to interact only through gravitation. Different kinds of singularities, naked or “clothed,” which can form during collapse processes are described. The general canonical formulation of the one-component null-dust dynamics by Bičák and Kuchař is restricted to the spherically symmetric case and used to construct an action for the two components. The transformation from a metric variable to the quasilocal mass is shown to simplify the mathematics. The action is reduced by a choice of gauge and the corresponding true Hamiltonian is written down. Asymptotic coordinates and energy densities of dust shells are shown to form a complete set of Dirac observables. The action of the asymptotic time translation on the observables is defined but it has been calculated explicitly only in the case of one-component dust (Vaidya metric).

  1. The Neuronal Ceroid-Lipofuscinoses

    Science.gov (United States)

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  2. The straintronic spin-neuron

    International Nuclear Information System (INIS)

    Biswas, Ayan K; Bandyopadhyay, Supriyo; Atulasimha, Jayasimha

    2015-01-01

    In artificial neural networks, neurons are usually implemented with highly dissipative CMOS-based operational amplifiers. A more energy-efficient implementation is a ‘spin-neuron’ realized with a magneto-tunneling junction (MTJ) that is switched with a spin-polarized current (representing weighted sum of input currents) that either delivers a spin transfer torque or induces domain wall motion in the soft layer of the MTJ to mimic neuron firing. Here, we propose and analyze a different type of spin-neuron in which the soft layer of the MTJ is switched with mechanical strain generated by a voltage (representing weighted sum of input voltages) and term it straintronic spin-neuron. It dissipates orders of magnitude less energy in threshold operations than the traditional current-driven spin neuron at 0 K temperature and may even be faster. We have also studied the room-temperature firing behaviors of both types of spin neurons and find that thermal noise degrades the performance of both types, but the current-driven type is degraded much more than the straintronic type if both are optimized for maximum energy-efficiency. On the other hand, if both are designed to have the same level of thermal degradation, then the current-driven version will dissipate orders of magnitude more energy than the straintronic version. Thus, the straintronic spin-neuron is superior to current-driven spin neurons. (paper)

  3. Calculation of null points in SPAIR, FLAIR, and STIR. Part 2. Application to pelvic diffusion-weighted imaging with SPAIR at 3T

    International Nuclear Information System (INIS)

    Kita, Miho; Kawano, Kazuhiro; Kometani, Katsuya; Kondo, Toshihiko; Shimamoto, Kazuhiro; Tanaka, Humihiro; Oda, Hideyuki; Kojima, Akihiro; Sato, Morio

    2013-01-01

    Diffusion-weighted imaging (DWI) requires adequate fat suppression because of its sensitivity to chemical shift artifacts, especially at 3 Tesla (T). We investigated the utility of calculating the inversion time of the null point (TI null ) in pelvic DWI with spectral attenuated inversion recovery (SPAIR) at 3 T for obtaining adequate fat suppression. Thirteen volunteers underwent pelvic SPAIR-DWI using various SPAIR inversion delay times (TI) at 5-ms intervals in the range of the calculated TI null ±25 ms. The degree of fat suppression was evaluated into 3 grades and was compared among the various SPAIR-TIs with the calculated TI null . In 65 cases of prostatic disease, we evaluated the ratio of adequate fat suppression obtained using the calculated TI null . We obtained adequate fat suppression in all 13 volunteers and in 61 (94%) of the 65 patients using the calculated TI null . Fat suppression was best when the calculated TI null was used (P null (P null increased. In conclusion, this method of calculating the TI null may be useful for obtaining adequate fat suppression for pelvic SPAIR-DWI at 3T. (author)

  4. Neuronal discrimination capacity

    International Nuclear Information System (INIS)

    Deng Yingchun; Williams, Peter; Feng Jianfeng; Liu Feng

    2003-01-01

    We explore neuronal mechanisms of discriminating between masked signals. It is found that when the correlation between input signals is zero, the output signals are separable if and only if input signals are separable. With positively (negatively) correlated signals, the output signals are separable (mixed) even when input signals are mixed (separable). Exact values of discrimination capacity are obtained for two most interesting cases: the exactly balanced inhibitory and excitatory input case and the uncorrelated input case. Interestingly, the discrimination capacity obtained in these cases is independent of model parameters, input distribution and is universal. Our results also suggest a functional role of inhibitory inputs and correlated inputs or, more generally, the large variability of efferent spike trains observed in in vivo experiments: the larger the variability of efferent spike trains, the easier it is to discriminate between masked input signals

  5. Neuronal discrimination capacity

    Energy Technology Data Exchange (ETDEWEB)

    Deng Yingchun [Department of Mathematics, Hunan Normal University 410081, Changsha (China); COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Williams, Peter; Feng Jianfeng [COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Liu Feng [COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Physics Department, Nanjing University (China)

    2003-12-19

    We explore neuronal mechanisms of discriminating between masked signals. It is found that when the correlation between input signals is zero, the output signals are separable if and only if input signals are separable. With positively (negatively) correlated signals, the output signals are separable (mixed) even when input signals are mixed (separable). Exact values of discrimination capacity are obtained for two most interesting cases: the exactly balanced inhibitory and excitatory input case and the uncorrelated input case. Interestingly, the discrimination capacity obtained in these cases is independent of model parameters, input distribution and is universal. Our results also suggest a functional role of inhibitory inputs and correlated inputs or, more generally, the large variability of efferent spike trains observed in in vivo experiments: the larger the variability of efferent spike trains, the easier it is to discriminate between masked input signals.

  6. Orexin neurons receive glycinergic innervations.

    Directory of Open Access Journals (Sweden)

    Mari Hondo

    Full Text Available Glycine, a nonessential amino-acid that acts as an inhibitory neurotransmitter in the central nervous system, is currently used as a dietary supplement to improve the quality of sleep, but its mechanism of action is poorly understood. We confirmed the effects of glycine on sleep/wakefulness behavior in mice when administered peripherally. Glycine administration increased non-rapid eye movement (NREM sleep time and decreased the amount and mean episode duration of wakefulness when administered in the dark period. Since peripheral administration of glycine induced fragmentation of sleep/wakefulness states, which is a characteristic of orexin deficiency, we examined the effects of glycine on orexin neurons. The number of Fos-positive orexin neurons markedly decreased after intraperitoneal administration of glycine to mice. To examine whether glycine acts directly on orexin neurons, we examined the effects of glycine on orexin neurons by patch-clamp electrophysiology. Glycine directly induced hyperpolarization and cessation of firing of orexin neurons. These responses were inhibited by a specific glycine receptor antagonist, strychnine. Triple-labeling immunofluorescent analysis showed close apposition of glycine transporter 2 (GlyT2-immunoreactive glycinergic fibers onto orexin-immunoreactive neurons. Immunoelectron microscopic analysis revealed that GlyT2-immunoreactive terminals made symmetrical synaptic contacts with somata and dendrites of orexin neurons. Double-labeling immunoelectron microscopy demonstrated that glycine receptor alpha subunits were localized in the postsynaptic membrane of symmetrical inhibitory synapses on orexin neurons. Considering the importance of glycinergic regulation during REM sleep, our observations suggest that glycine injection might affect the activity of orexin neurons, and that glycinergic inhibition of orexin neurons might play a role in physiological sleep regulation.

  7. Cerebellar defects in a mouse model of juvenile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Weimer, Jill M; Benedict, Jared W; Getty, Amanda L; Pontikis, Charlie C; Lim, Ming J; Cooper, Jonathan D; Pearce, David A

    2009-04-17

    Juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, is a neurodegenerative disease resulting from a mutation in CLN3, which presents clinically with visual deterioration, seizures, motor impairments, cognitive decline, hallucinations, loss of circadian rhythm, and premature death in the late-twenties to early-thirties. Using a Cln3 null (Cln3(-/-)) mouse, we report here several deficits in the cerebellum in the absence of Cln3, including cell loss and early onset motor deficits. Surprisingly, early onset glial activation and selective neuronal loss within the mature fastigial pathway of the deep cerebellar nuclei (DCN), a region critical for balance and coordination, are seen in many regions of the Cln3(-/-) cerebellum. Additionally, there is a loss of Purkinje cells (PC) in regions of robust Bergmann glia activation in Cln3(-/-) mice and human JNCL post-mortem cerebellum. Moreover, the Cln3(-/-) cerebellum had a mis-regulation in granule cell proliferation and maintenance of PC dendritic arborization and spine density. Overall, this study defines a novel multi-faceted, early-onset cerebellar disruption in the Cln3 null brain, including glial activation, cell loss, and aberrant cell proliferation and differentiation. These early alterations in the maturation of the cerebellum could underlie some of the motor deficits and pathological changes seen in JNCL patients.

  8. Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity

    Science.gov (United States)

    Parras, Carlos M.; Schuurmans, Carol; Scardigli, Raffaella; Kim, Jaesang; Anderson, David J.; Guillemot, François

    2002-01-01

    The neural bHLH genes Mash1 and Ngn2 are expressed in complementary populations of neural progenitors in the central and peripheral nervous systems. Here, we have systematically compared the activities of the two genes during neural development by generating replacement mutations in mice in which the coding sequences of Mash1 and Ngn2 were swapped. Using this approach, we demonstrate that Mash1 has the capacity to respecify the identity of neuronal populations normally derived from Ngn2-expressing progenitors in the dorsal telencephalon and ventral spinal cord. In contrast, misexpression of Ngn2 in Mash1-expressing progenitors does not result in any overt change in neuronal phenotype. Taken together, these results demonstrate that Mash1 and Ngn2 have divergent functions in specification of neuronal subtype identity, with Mash1 having the characteristics of an instructive determinant whereas Ngn2 functions as a permissive factor that must act in combination with other factors to specify neuronal phenotypes. Moreover, the ectopic expression of Ngn2 can rescue the neurogenesis defects of Mash1 null mutants in the ventral telencephalon and sympathetic ganglia but not in the ventral spinal cord and the locus coeruleus, indicating that Mash1 contribution to the specification of neuronal fates varies greatly in different lineages, presumably depending on the presence of other determinants of neuronal identity. PMID:11825874

  9. Anti-Epileptic Drugs Delay Age-Related Loss of Spiral Ganglion Neurons via T-type Calcium Channel

    Science.gov (United States)

    Lei, Debin; Gao, Xia; Perez, Philip; Ohlemiller, Kevin K; Chen, Chien-Chang; Campbell, Kevin P.; Hood, Aizhen Yang; Bao, Jianxin

    2011-01-01

    Loss of spiral ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Cav3.1, Cav3.2, and Cav3.3), based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of spiral ganglion neurons in α1H null and heterozygous mice, clearly demonstrating an important role for Cav3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve spiral ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of spiral ganglion neurons. PMID:21640179

  10. MONOMERIC ß-AMYLOID INTERACTS WITH TYPE-1 INSULIN-LIKE GROWTH FACTOR RECEPTORS TO PROVIDE ENERGY SUPPLY TO NEURONS

    Directory of Open Access Journals (Sweden)

    Maria Laura eGiuffrida

    2015-08-01

    Full Text Available ß-amyloid (Aß1-42 is produced by proteolytic cleavage of the transmembrane type-1 protein, amyloid precursor protein. Under pathological conditions, Aß1-42 self-aggregates into oligomers, which cause synaptic dysfunction and neuronal loss, and are considered the culprit of Alzheimer’s disease (AD. However, Aß1-42 is mainly monomeric at physiological concentrations, and the precise role of monomeric Aß1-42 in neuronal function is largely unknown. We report that the monomer of Aß1-42 activates type-1 insulin-like growth factor receptors and enhances glucose uptake in neurons and peripheral cells by promoting the translocation of the Glut3 glucose transporter from the cytosol to the plasma membrane. In neurons, activity-dependent glucose uptake was blunted after blocking endogenous Aß production, and re-established in the presence of cerebrospinal fluid Aß. APP-null neurons failed to enhance depolarization-stimulated glucose uptake unless exogenous monomeric Aß1-42 was added. These data suggest that Aß1-42 monomers were critical for maintaining neuronal glucose homeostasis. Accordingly, exogenous Aß1-42 monomers were able to rescue the low levels of glucose consumption observed in brain slices from AD mutant mice.

  11. No actual measurement … was required: Maxwell and Cavendish's null method for the inverse square law of electrostatics.

    Science.gov (United States)

    Falconer, Isobel

    In 1877 James Clerk Maxwell and his student Donald MacAlister refined Henry Cavendish's 1773 null experiment demonstrating the absence of electricity inside a charged conductor. This null result was a mathematical prediction of the inverse square law of electrostatics, and both Cavendish and Maxwell took the experiment as verifying the law. However, Maxwell had already expressed absolute conviction in the law, based on results of Michael Faraday's. So, what was the value to him of repeating Cavendish's experiment? After assessing whether the law was as secure as he claimed, this paper explores its central importance to the electrical programme that Maxwell was pursuing. It traces the historical and conceptual re-orderings through which Maxwell established the law by constructing a tradition of null tests and asserting the superior accuracy of the method. Maxwell drew on his developing 'doctrine of method' to identify Cavendish's experiment as a member of a wider class of null methods. By doing so, he appealed to the null practices of telegraph engineers, diverted attention from the flawed logic of the method, and sought to localise issues around the mapping of numbers onto instrumental indications, on the grounds that 'no actual measurement … was required'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Limit structure of future null infinity tangent-topology of the event horizon and gravitational wave tail

    International Nuclear Information System (INIS)

    Tomizawa, Shinya; Siino, Masaru

    2006-01-01

    We investigated the relation between the behaviour of gravitational waves at late time and the limit structure of future null infinity tangent which will determine the topology of the event horizon far in the future. In the present paper, we mainly consider a spacetime with two black holes. Although in most cases, the black holes coalesce and the event horizon is topologically a single sphere far in the future, there are several possibilities that the black holes never coalesce and such exact solutions as examples. In our formulation, the tangent vector of future null infinity is, under conformal embedding, related to the number of black holes far in the future through the Poincare-Hopf theorem. Under the conformal embedding, the topology of the event horizon far in the future will be affected by the geometrical structure of the future null infinity. In this paper, we relate the behaviour of Weyl curvature to this limit behaviour of the generator vector of the future null infinity. We show if Weyl curvature decays sufficiently slowly at late time in the neighbourhood of future null infinity, two black holes never coalesce

  13. Morphological and Physiological Interactions Between GnRH3 and Hypocretin/Orexin Neuronal Systems in Zebrafish (Danio rerio).

    Science.gov (United States)

    Zhao, Yali; Singh, Chanpreet; Prober, David A; Wayne, Nancy L

    2016-10-01

    GnRH neurons integrate internal and external cues to control sexual maturation and fertility. Homeostasis of energy balance and food intake correlates strongly with the status of reproduction. Neuropeptides secreted by the hypothalamus involved in modulating energy balance and feeding may play additional roles in the regulation of reproduction. Hypocretin (Hcrt) (also known as orexin) is one such peptide, primarily controlling sleep/wakefulness, food intake, and reward processing. There is a growing body of evidence indicating that Hcrt/orexin (Hcrt) modulates reproduction through interacting with the hypothalamo-pituitary-gonadal axis in mammals. To explore potential morphological and functional interactions between the GnRH and Hcrt neuronal systems, we employed a variety of experimental approaches including confocal imaging, immunohistochemistry, and electrophysiology in transgenic zebrafish, in which fluorescent proteins are genetically expressed in GnRH3 and Hcrt neurons. Our imaging data revealed close apposition and direct connection between GnRH3 and Hcrt neuronal systems in the hypothalamus during larval development through adulthood. Furthermore, the Hcrt receptor (HcrtR) is expressed in GnRH3 neurons. Electrophysiological data revealed a reversible inhibitory effect of Hcrt on GnRH3 neuron electrical activity, which was blocked by the HcrtR antagonist almorexant. In addition, Hcrt had no effect on the electrical activity of GnRH3 neurons in the HcrtR null mutant zebrafish (HcrtR -/- ). Our findings demonstrate a close anatomical and functional relationship between Hcrt and GnRH neuronal systems in zebrafish. It is the first demonstration of a link between neuronal circuits controlling sleeping/arousal/feeding and reproduction in zebrafish, an important animal model for investigating the molecular genetics of development.

  14. A Solution Space for a System of Null-State Partial Differential Equations: Part 2

    Science.gov (United States)

    Flores, Steven M.; Kleban, Peter

    2015-01-01

    This article is the second of four that completely and rigorously characterize a solution space for a homogeneous system of 2 N + 3 linear partial differential equations in 2 N variables that arises in conformal field theory (CFT) and multiple Schramm-Löwner evolution (SLE). The system comprises 2 N null-state equations and three conformal Ward identities which govern CFT correlation functions of 2 N one-leg boundary operators. In the first article (Flores and Kleban, Commun Math Phys, arXiv:1212.2301, 2012), we use methods of analysis and linear algebra to prove that dim , with C N the Nth Catalan number. The analysis of that article is complete except for the proof of a lemma that it invokes. The purpose of this article is to provide that proof. The lemma states that if every interval among ( x 2, x 3), ( x 3, x 4),…,( x 2 N-1, x 2 N ) is a two-leg interval of (defined in Flores and Kleban, Commun Math Phys, arXiv:1212.2301, 2012), then F vanishes. Proving this lemma by contradiction, we show that the existence of such a nonzero function implies the existence of a non-vanishing CFT two-point function involving primary operators with different conformal weights, an impossibility. This proof (which is rigorous in spite of our occasional reference to CFT) involves two different types of estimates, those that give the asymptotic behavior of F as the length of one interval vanishes, and those that give this behavior as the lengths of two intervals vanish simultaneously. We derive these estimates by using Green functions to rewrite certain null-state PDEs as integral equations, combining other null-state PDEs to obtain Schauder interior estimates, and then repeatedly integrating the integral equations with these estimates until we obtain optimal bounds. Estimates in which two interval lengths vanish simultaneously divide into two cases: two adjacent intervals and two non-adjacent intervals. The analysis of the latter case is similar to that for one vanishing

  15. Nulling interferometry: impact of exozodiacal clouds on the performance of future life-finding space missions

    Science.gov (United States)

    Defrère, D.; Absil, O.; den Hartog, R.; Hanot, C.; Stark, C.

    2010-01-01

    Context. Earth-sized planets around nearby stars are being detected for the first time by ground-based radial velocity and space-based transit surveys. This milestone is opening the path toward the definition of instruments able to directly detect the light from these planets, with the identification of bio-signatures as one of the main objectives. In that respect, both the European Space Agency (ESA) and the National Aeronautics and Space Administration (NASA) have identified nulling interferometry as one of the most promising techniques. The ability to study distant planets will however depend on the amount of exozodiacal dust in the habitable zone of the target stars. Aims: We assess the impact of exozodiacal clouds on the performance of an infrared nulling interferometer in the Emma X-array configuration. The first part of the study is dedicated to the effect of the disc brightness on the number of targets that can be surveyed and studied by spectroscopy during the mission lifetime. In the second part, we address the impact of asymmetric structures in the discs such as clumps and offset which can potentially mimic the planetary signal. Methods: We use the DarwinSIM software which was designed and validated to study the performance of space-based nulling interferometers. The software has been adapted to handle images of exozodiacal discs and to compute the corresponding demodulated signal. Results: For the nominal mission architecture with 2-m aperture telescopes, centrally symmetric exozodiacal dust discs about 100 times denser than the solar zodiacal cloud can be tolerated in order to survey at least 150 targets during the mission lifetime. Considering modeled resonant structures created by an Earth-like planet orbiting at 1 AU around a Sun-like star, we show that this tolerable dust density goes down to about 15 times the solar zodiacal density for face-on systems and decreases with the disc inclination. Conclusions: Whereas the disc brightness only affects

  16. 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

  17. Chemical changes in DMP1-null murine bone & silica based pecvd coatings for titanium implant osseoapplications

    Science.gov (United States)

    Maginot, Megen

    In order to improve clinical outcomes in bone-implant systems, a thorough understanding of both local bone chemistry and implant surface chemistry is necessary. This study consists, therefore, of two main parts: one focused on determining the nature of the changes in bone chemistry in a DMP1-null transgenic disease model and the other on the development of amorphous silica-based coatings for potential use as titanium bone implant coatings. For the study of bone mineral in the DMP1 transgenic model, which is known to have low serum phosphate levels, transgenic DMP1-null and wild type mice were fed a high phosphate diet, sacrificed, and had their long bone harvested. This bone was characterized using SEM, FTIR, microCT and XANES and compared to DMP1-null and wild type control groups to assess the therapeutic effect of high Pi levels on the phenotype and the role of DMP1 in mineralization in vivo. Findings suggest that though the high phosphate diet results in restoring serum phosphate levels, it does not completely rescue the bone mineral phenotype at an ultrastructural level and implicates DMP1 in phosphate nucleation. Since plasma enhanced chemical vapor deposition (PECVD) silica like coatings have not previously been fabricated for use in oessoapplications, the second part of this study initially focused on the characterization of novel SiOx chemistries fabricated via a chemical vapor deposition process that were designed specifically to act as bioactive coatings with a loose, hydrogenated structure. These coatings were then investigated for their potential initial stage response to bone tissue through immersion in a simulated body fluid and through the culture of MC3T3 cells on the coating surfaces. Coating surfaces were characterized by SEM, FTIR, contact angle measurements, and XANES. Coating dissolution and ionic release were also investigated by ICP-OES. Findings suggest that some SiOx chemistries may form a bioactive coating while more highly substituted

  18. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  19. Three genes for mitochondrial proteins suppress null-mutations in both Afg3 and Rca1 when over-expressed.

    Science.gov (United States)

    Rep, M; Nooy, J; Guélin, E; Grivell, L A

    1996-08-01

    The AFG3 gene of Saccharomyces cerevisiae encodes a mitochondrial inner membrane protein with ATP-dependent protease activity. To gain more insight into the function of this protein, multi-copy suppressors of an afg3-null mutation were isolated. Three genes were found that restored partial growth on non-fermentable carbon sources, all of which affect the biogenesis of respiratory competent mitochondria: PIM1(LON) encodes a matrix-localized ATP-dependent protease involved in the turnover of matrix proteins; OXA1(PET1402) encodes a putative mitochondrial inner membrane protein involved in the biogenesis of the respiratory chain; and MBA1 encodes a mitochondrial protein required for optimal respiratory growth. All three genes also suppressed a null mutation in a related gene, RCA1, as well as in the combination of afg3- and rca1-null.

  20. Generalized Robertson-Walker Space-Time Admitting Evolving Null Horizons Related to a Black Hole Event Horizon.

    Science.gov (United States)

    Duggal, K L

    2016-01-01

    A new technique is used to study a family of time-dependent null horizons, called " Evolving Null Horizons " (ENHs), of generalized Robertson-Walker (GRW) space-time [Formula: see text] such that the metric [Formula: see text] satisfies a kinematic condition. This work is different from our early papers on the same issue where we used (1 + n )-splitting space-time but only some special subcases of GRW space-time have this formalism. Also, in contrast to previous work, we have proved that each member of ENHs is totally umbilical in [Formula: see text]. Finally, we show that there exists an ENH which is always a null horizon evolving into a black hole event horizon and suggest some open problems.

  1. Drosophila Atlastin in motor neurons is required for locomotion and presynaptic function.

    Science.gov (United States)

    De Gregorio, Cristian; Delgado, Ricardo; Ibacache, Andrés; Sierralta, Jimena; Couve, Andrés

    2017-10-15

    Hereditary spastic paraplegias (HSPs) are characterized by spasticity and weakness of the lower limbs, resulting from length-dependent axonopathy of the corticospinal tracts. In humans, the HSP-related atlastin genes ATL1 - ATL3 catalyze homotypic membrane fusion of endoplasmic reticulum (ER) tubules. How defects in neuronal Atlastin contribute to axonal degeneration has not been explained satisfactorily. Using Drosophila , we demonstrate that downregulation or overexpression of Atlastin in motor neurons results in decreased crawling speed and contraction frequency in larvae, while adult flies show progressive decline in climbing ability. Broad expression in the nervous system is required to rescue the atlastin -null Drosophila mutant ( atl 2 ) phenotype. Importantly, both spontaneous release and the reserve pool of synaptic vesicles are affected. Additionally, axonal secretory organelles are abnormally distributed, whereas presynaptic proteins diminish at terminals and accumulate in distal axons, possibly in lysosomes. Our findings suggest that trafficking defects produced by Atlastin dysfunction in motor neurons result in redistribution of presynaptic components and aberrant mobilization of synaptic vesicles, stressing the importance of ER-shaping proteins and the susceptibility of motor neurons to their mutations or depletion. © 2017. Published by The Company of Biologists Ltd.

  2. Simulating synchronization in neuronal networks

    Science.gov (United States)

    Fink, Christian G.

    2016-06-01

    We discuss several techniques used in simulating neuronal networks by exploring how a network's connectivity structure affects its propensity for synchronous spiking. Network connectivity is generated using the Watts-Strogatz small-world algorithm, and two key measures of network structure are described. These measures quantify structural characteristics that influence collective neuronal spiking, which is simulated using the leaky integrate-and-fire model. Simulations show that adding a small number of random connections to an otherwise lattice-like connectivity structure leads to a dramatic increase in neuronal synchronization.

  3. Glial tumors with neuronal differentiation.

    Science.gov (United States)

    Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

    2015-01-01

    Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Mechanosensing in hypothalamic osmosensory neurons.

    Science.gov (United States)

    Prager-Khoutorsky, Masha

    2017-11-01

    Osmosensory neurons are specialized cells activated by increases in blood osmolality to trigger thirst, secretion of the antidiuretic hormone vasopressin, and elevated sympathetic tone during dehydration. In addition to multiple extrinsic factors modulating their activity, osmosensory neurons are intrinsically osmosensitive, as they are activated by increased osmolality in the absence of neighboring cells or synaptic contacts. This intrinsic osmosensitivity is a mechanical process associated with osmolality-induced changes in cell volume. This review summarises recent findings revealing molecular mechanisms underlying the mechanical activation of osmosensory neurons and highlighting important roles of microtubules, actin, and mechanosensitive ion channels in this process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Different relationships between temporal phylogenetic turnover and phylogenetic similarity and in two forests were detected by a new null model.

    Science.gov (United States)

    Huang, Jian-Xiong; Zhang, Jian; Shen, Yong; Lian, Ju-yu; Cao, Hong-lin; Ye, Wan-hui; Wu, Lin-fang; Bin, Yue

    2014-01-01

    Ecologists have been monitoring community dynamics with the purpose of understanding the rates and causes of community change. However, there is a lack of monitoring of community dynamics from the perspective of phylogeny. We attempted to understand temporal phylogenetic turnover in a 50 ha tropical forest (Barro Colorado Island, BCI) and a 20 ha subtropical forest (Dinghushan in southern China, DHS). To obtain temporal phylogenetic turnover under random conditions, two null models were used. The first shuffled names of species that are widely used in community phylogenetic analyses. The second simulated demographic processes with careful consideration on the variation in dispersal ability among species and the variations in mortality both among species and among size classes. With the two models, we tested the relationships between temporal phylogenetic turnover and phylogenetic similarity at different spatial scales in the two forests. Results were more consistent with previous findings using the second null model suggesting that the second null model is more appropriate for our purposes. With the second null model, a significantly positive relationship was detected between phylogenetic turnover and phylogenetic similarity in BCI at a 10 m×10 m scale, potentially indicating phylogenetic density dependence. This relationship in DHS was significantly negative at three of five spatial scales. This could indicate abiotic filtering processes for community assembly. Using variation partitioning, we found phylogenetic similarity contributed to variation in temporal phylogenetic turnover in the DHS plot but not in BCI plot. The mechanisms for community assembly in BCI and DHS vary from phylogenetic perspective. Only the second null model detected this difference indicating the importance of choosing a proper null model.

  6. Alfvén wave dynamics at the neighborhood of a 2.5D magnetic null-point

    Science.gov (United States)

    Sabri, S.; Vasheghani Farahani, S.; Ebadi, H.; Hosseinpour, M.; Fazel, Z.

    2018-05-01

    The aim of the present study is to highlight the energy transfer via the interaction of magnetohydrodynamic waves with a 2.5D magnetic null-point in a finite plasma-β regime of the solar corona. An initially symmetric Alfvén pulse at a specific distance from a magnetic null-point is kicked towards the isothermal null-point. A shock-capturing Godunov-type PLUTO code is used to solve the ideal magnetohydrodynamic set equations in the context of wave-plasma energy transfer. As the Alfvén wave propagates towards the magnetic null-point it experiences speed lowering which ends up in releasing energy along the separatrices. In this line owing to the Alfvén wave, a series of events take place that contribute towards coronal heating. Nonlinear induced waves are by products of the torsional Alfvén interaction with magnetic null-points. The energy of these induced waves which are fast magnetoacoustic (transverse) and slow magnetoacoustic (longitudinal) waves are supplied by the Alfvén wave. The nonlinearly induced density perturbations are proportional to the Alfvén wave energy loss. This supplies energy for the propagation of fast and slow magnetoacoustic waves, where in contrast to the fast wave the slow wave experiences a continuous energy increase. As such, the slow wave may transfer its energy to the medium at later times, maintaining a continuous heating mechanism at the neighborhood of a magnetic null-point.

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

    Directory of Open Access Journals (Sweden)

    Carol M. Collins

    2017-04-01

    Full Text Available 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 that 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 that 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 wild-type and emerin-null myogenic progenitors, but did not affect cell cycle exit. Downregulation of emerin was previously shown to affect the p38 MAPK and ERK/MAPK pathways in C2C12 myoblast differentiation. Using a pure population of myogenic progenitors completely lacking emerin expression, we show that these pathways are also disrupted. ERK inhibition improved MyHC expression in emerin-null cells, but failed to rescue myotube formation or cell cycle exit. Inhibition of p38 MAPK prevented differentiation in both wild-type and emerin-null progenitors. These results show that each of these molecular pathways specifically regulates a particular stage 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.

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

    Directory of Open Access Journals (Sweden)

    Erin E Cummings

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

  9. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  10. From Neurons to Brain: Adaptive Self-Wiring of Neurons

    OpenAIRE

    Segev, Ronen; Ben-Jacob, Eshel

    1998-01-01

    During embryonic morpho-genesis, a collection of individual neurons turns into a functioning network with unique capabilities. Only recently has this most staggering example of emergent process in the natural world, began to be studied. Here we propose a navigational strategy for neurites growth cones, based on sophisticated chemical signaling. We further propose that the embryonic environment (the neurons and the glia cells) acts as an excitable media in which concentric and spiral chemical ...

  11. Demonstrating Broadband Billion-to-One Contrast with the Visible Nulling Coronagraph

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter, III; Miller, Ian J.; Bolcar, Matthew R.; Clampin, Mark; Helmbrecht, Michael A.; Mallik, Udayan

    2015-01-01

    The key to broadband operation of the Visible Nulling Coronagraph (VNC) is achieving a condition of quasi- achromatic destructive interference between combined beams. Here we present efforts towards meeting this goal using Fresnel rhombs in each interferometric arm as orthogonally aligned half wave phase retarders. The milestone goal of the demonstration is to achieve 1 × 10-9 contrast at 2/D over a 40 nm bandpass centered at 633 nm. Rhombs have been designed and fabricated, and a multi-step approach to alignment using coarse positioners for each rhomb and pair has been developed to get within range of piezo stages used for fine positioning. The previously demonstrated narrowband VNC sensing and control approach that uses a segmented deformable mirror is being adapted to broadband to include fine positioning of the piezo-mounted rhombs, all demonstrated in a low-pressure environment.

  12. Inverse source problem and null controllability for multidimensional parabolic operators of Grushin type

    International Nuclear Information System (INIS)

    Beauchard, K; Cannarsa, P; Yamamoto, M

    2014-01-01

    The approach to Lipschitz stability for uniformly parabolic equations introduced by Imanuvilov and Yamamoto in 1998 based on Carleman estimates, seems hard to apply to the case of Grushin-type operators of interest to this paper. Indeed, such estimates are still missing for parabolic operators degenerating in the interior of the space domain. Nevertheless, we are able to prove Lipschitz stability results for inverse source problems for such operators, with locally distributed measurements in an arbitrary space dimension. For this purpose, we follow a mixed strategy which combines the approach due to Lebeau and Robbiano, relying on Fourier decomposition and Carleman inequalities for heat equations with non-smooth coefficients (solved by the Fourier modes). As a corollary, we obtain a direct proof of the observability of multidimensional Grushin-type parabolic equations, with locally distributed observations—which is equivalent to null controllability with locally distributed controls. (paper)

  13. Null to time-like infinity Green’s functions for asymptotic symmetries in Minkowski spacetime

    International Nuclear Information System (INIS)

    Campiglia, Miguel

    2015-01-01

    We elaborate on the Green’s functions that appeared in http://dx.doi.org/10.1007/JHEP07(2015)115http://arxiv.org/abs/1509.01406 when generalizing, from massless to massive particles, various equivalences between soft theorems and Ward identities of large gauge symmetries. We analyze these Green’s functions in considerable detail and show that they form a hierarchy of functions which describe ‘boundary to bulk’ propagators for large U(1) gauge parameters, supertranslations and sphere vector fields respectively. As a consistency check we verify that the Green’s functions associated to the large diffeomorphisms map the Poincare group at null infinity to the Poincare group at time-like infinity.

  14. 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

    and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium...... 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...... responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor...

  15. On null tests of time-reversal invariance in scattering and reactions

    International Nuclear Information System (INIS)

    Conzett, H.E.

    1993-01-01

    There have been suggestions in the literature, both recently and in the more distant past, that, in the lowest-order Born approximation, time-reversal (T)-odd experimental observables in certain reactions are required by T-symmetry to vanish. These observables are the final-state spin-correlation coefficient C xy in the reaction e + e - → τ + τ - and the target analysing power A oy in the inclusive process ep → eX with a polarized proton target. These assertions are in direct conflict with a theorem that states that there can be no null-test of T-symmetry in such processes; that is, T-symmetry does not require any single observable to vanish. This talk addresses the resolution of that conflict

  16. Null geodesics and shadow of a rotating black hole in extended Chern-Simons modified gravity

    International Nuclear Information System (INIS)

    Amarilla, Leonardo; Eiroa, Ernesto F.; Giribet, Gaston

    2010-01-01

    The Chern-Simons modification to general relativity in four dimensions consists of adding to the Einstein-Hilbert term a scalar field that couples to the first-class Pontryagin density. In this theory, which has attracted considerable attention recently, the Schwarzschild metric persists as an exact solution, and this is why this model resists several observational constraints. In contrast, the spinning black hole solution of the theory is not given by the Kerr metric but by a modification of it, so far only known for slow rotation and small coupling constant. In the present paper, we show that, in this approximation, the null geodesic equation can be integrated, and this allows us to investigate the shadow cast by a black hole. We discuss how, in addition to the angular momentum of the solution, the coupling to the Chern-Simons term deforms the shape of the shadow.

  17. Estimating the Proportion of True Null Hypotheses in Multiple Testing Problems

    Directory of Open Access Journals (Sweden)

    Oluyemi Oyeniran

    2016-01-01

    Full Text Available The problem of estimating the proportion, π0, of the true null hypotheses in a multiple testing problem is important in cases where large scale parallel hypotheses tests are performed independently. While the problem is a quantity of interest in its own right in applications, the estimate of π0 can be used for assessing or controlling an overall false discovery rate. In this article, we develop an innovative nonparametric maximum likelihood approach to estimate π0. The nonparametric likelihood is proposed to be restricted to multinomial models and an EM algorithm is also developed to approximate the estimate of π0. Simulation studies show that the proposed method outperforms other existing methods. Using experimental microarray datasets, we demonstrate that the new method provides satisfactory estimate in practice.

  18. Divertor target profiles and recycling studies in TCV single null lower standard discharges

    International Nuclear Information System (INIS)

    Pitts, R.A.; Nieswand, C.; Weisen, H.

    1996-05-01

    A 'standard', single null lower diverted discharge has been developed to enable continuous monitoring of the first wall conditions and to characterise the effectiveness and influence of wall conditioning in the TCV tokamak. Measurements over a period encompassing nearly 2000 ohmic discharges of varying configuration and input power show the global confinement time and main plasma impurity concentrations to be good general indicators of the first wall condition, whilst divertor target profiles demonstrate strikingly the short term beneficial effects of He glow. Good agreement, consistent with a reduction in recycling at the plates is found between the predictions of the fluid code UEDGE and the observed outer divertor profiles of T e and n e before and after He glow. (author) 5 figs., 7 refs

  19. Development of a two-dimensional skin friction balance nulling circuit using multivariable control theory

    Science.gov (United States)

    Tripp, John S.; Patek, Stephen D.

    1988-01-01

    Measurement of planar skin friction forces in aerodynamic testing currently requires installation of two perpendicularly mounted, single-axis balances; consequently, force components must be sensed at two distinct locations. A two-axis instrument developed at the Langley Research Center to overcome this disadvantage allows measurement of a two-dimensional force at one location. This paper describes a feedback-controlled nulling circuit developed for the NASA two-axis balance which, without external compensation, is inherently unstable because of its low friction mechanical design. Linear multivariable control theory is applied to an experimentally validated mathematical model of the balance to synthesize a state-variable feedback control law. Pole placement techniques and computer simulation studies are employed to select eigenvalues which provide ideal transient response with decoupled sensing dynamics.

  20. Preamble and pilot symbol design for channel estimation in OFDM systems with null subcarriers

    Directory of Open Access Journals (Sweden)

    Ohno Shuichi

    2011-01-01

    Full Text Available Abstract In this article, design of preamble for channel estimation and pilot symbols for pilot-assisted channel estimation in orthogonal frequency division multiplexing system with null subcarriers is studied. Both the preambles and pilot symbols are designed to minimize the l 2 or the l ∞ norm of the channel estimate mean-squared errors (MSE in frequency-selective environments. We use convex optimization technique to find optimal power distribution to the preamble by casting the MSE minimization problem into a semidefinite programming problem. Then, using the designed optimal preamble as an initial value, we iteratively select the placement and optimally distribute power to the selected pilot symbols. Design examples consistent with IEEE 802.11a as well as IEEE 802.16e are provided to illustrate the superior performance of our proposed method over the equi-spaced equi-powered pilot symbols and the partially equi-spaced pilot symbols.

  1. Null Geodesics and Strong Field Gravitational Lensing of Black Hole with Global Monopole

    International Nuclear Information System (INIS)

    Iftikhar, Sehrish; Sharif, M.

    2015-01-01

    We study two interesting features of a black hole with an ordinary as well as phantom global monopole. Firstly, we investigate null geodesics which imply unstable orbital motion of particles for both cases. Secondly, we evaluate deflection angle in strong field regime. We then find Einstein rings, magnifications, and observables of the relativistic images for supermassive black hole at the center of galaxy NGC4486B. We also examine time delays for different galaxies and present our results numerically. It is found that the deflection angle for ordinary/phantom global monopole is greater/smaller than that of Schwarzschild black hole. In strong field limit, the remaining properties of these black holes are quite different from the Schwarzschild black hole

  2. Calculations of transient fields in the Felix experiments at Argonne using null field integrated techniques

    International Nuclear Information System (INIS)

    Han, H.C.; Davey, K.R.; Turner, L.

    1985-08-01

    The transient eddy current problem is characteristically computationally intensive. The motivation for this research was to realize an efficient, accurate, solution technique involving small matrices via an eigenvalue approach. Such a technique is indeed realized and tested using the null field integral technique. Using smart (i.e., efficient, global) basis functions to represent unknowns in terms of a minimum number of unknowns, homogeneous eigenvectors and eigenvalues are first determined. The general excitatory response is then represented in terms of these eigenvalues/eigenvectors. Excellent results are obtained for the Argonne Felix cylinder experiments using a 4 x 4 matrix. Extension to the 3-D problem (short cylinder) is set up in terms of an 8 x 8 matrix

  3. Null Space Integration Method for Constrained Multibody Systems with No Constraint Violation

    International Nuclear Information System (INIS)

    Terze, Zdravko; Lefeber, Dirk; Muftic, Osman

    2001-01-01

    A method for integrating equations of motion of constrained multibody systems with no constraint violation is presented. A mathematical model, shaped as a differential-algebraic system of index 1, is transformed into a system of ordinary differential equations using the null-space projection method. Equations of motion are set in a non-minimal form. During integration, violations of constraints are corrected by solving constraint equations at the position and velocity level, utilizing the metric of the system's configuration space, and projective criterion to the coordinate partitioning method. The method is applied to dynamic simulation of 3D constrained biomechanical system. The simulation results are evaluated by comparing them to the values of characteristic parameters obtained by kinematics analysis of analyzed motion based unmeasured kinematics data

  4. Topology optimization of piezo modal transducers with null-polarity phases

    DEFF Research Database (Denmark)

    Donoso, A.; Sigmund, O.

    2016-01-01

    Piezo modal transducers in 2d can be designed theoretically by tailoring polarity of the surface electrodes. However, it is also necessary to include null-polarity phases of known width separating areas of opposite polarity in the manufacturing process in order to avoid short-circuiting. Otherwise...... the performance of such devices could be spoiled. In this work, we propose an appropriate topology optimization interpolation function for the electrode profile such that the effect of this new phase (hereafter gap-phase) is included in the formulation of the design problem. The approach is density-based, where...... the interface is controlled by including the gradient norm in the electrode profile interpolation. Through a detailed case study in 1d, conclusions on how to control the width of this gap-phase are extracted, and subsequently extended to the 2d case....

  5. Failure to CAPTCHA Attention: Null Results from an Honesty Priming Experiment in Guatemala.

    Science.gov (United States)

    Kettle, Stewart; Hernandez, Marco; Sanders, Michael; Hauser, Oliver; Ruda, Simon

    2017-04-28

    We report results from a large online randomised tax experiment in Guatemala. The trial involves short messages and choices presented to taxpayers as part of a CAPTCHA pop-up window immediately before they file a tax return, with the aim of priming honest declarations. In total our sample includes 627,242 taxpayers and 3,232,430 tax declarations made over four months. Treatments include: honesty declaration; information about public goods; information about penalties for dishonesty, questions allowing a taxpayer to choose which public good they think tax money should be spent on; or questions allowing a taxpayer to state a view on the penalty for not declaring honestly. We find no impact of any of these treatments on the average amount of tax declared. We discuss potential causes for this null effect and implications for 'online nudges' around honesty priming.

  6. Demonstrating broadband billion-to-one contrast with the Visible Nulling Coronagraph

    Science.gov (United States)

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

    2015-09-01

    The key to broadband operation of the Visible Nulling Coronagraph (VNC) is achieving a condition of quasi-achromatic destructive interference between combined beams. Here we present efforts towards meeting this goal using Fresnel rhombs in each interferometric arm as orthogonally aligned half wave phase retarders. The milestone goal of the demonstration is to achieve 1 × 10-9 contrast at 2λ/D over a 40 nm bandpass centered at 633 nm. Rhombs have been designed and fabricated, and a multi-step approach to alignment using coarse positioners for each rhomb and pair has been developed to get within range of piezo stages used for fine positioning. The previously demonstrated narrowband VNC sensing and control approach that uses a segmented deformable mirror is being adapted to broadband to include fine positioning of the piezo-mounted rhombs, all demonstrated in a low-pressure environment.

  7. Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin aα null mice

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Reddy, Ramesh N; Price, S Russ

    2013-01-01

    to thrive and early lethality of most null pups. Work in our laboratory led to the rescue of CnAα-/- mice by supplemental feeding to compensate for a defect in salivary enzyme secretion. The data revealed that, without intervention, knockout mice suffer from severe caloric restriction. Since nutritional...... deprivation is known to significantly alter development, it is imperative that previous conclusions based on CnAα-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAα. In this study, we find that defects in renal development...... and function persist in adult CnAα-/- mice including a significant decrease in glomerular filtration rate and an increase in blood urea nitrogen levels. These data indicate that impaired renal development we previously reported was not due to caloric restriction but rather a specific role for CnAα in renal...

  8. Null polygonal Wilson loops and minimal surfaces in Anti-de-Sitter space

    International Nuclear Information System (INIS)

    Alday, Luis F.; Maldacena, Juan

    2009-01-01

    We consider minimal surfaces in three dimensional anti-de-Sitter space that end at the AdS boundary on a polygon given by a sequence of null segments. The problem can be reduced to a certain generalized Sinh-Gordon equation and to SU(2) Hitchin equations. We describe in detail the mathematical problem that needs to be solved. This problem is mathematically the same as the one studied by Gaiotto, Moore and Neitzke in the context of the moduli space of certain supersymmetric theories. Using their results we can find the explicit answer for the area of a surface that ends on an eight-sided polygon. Via the gauge/gravity duality this can also be interpreted as a certain eight-gluon scattering amplitude at strong coupling. In addition, we give fairly explicit solutions for regular polygons.

  9. Theoretical size distribution of fossil taxa: analysis of a null model

    Directory of Open Access Journals (Sweden)

    Hughes Barry D

    2007-03-01

    Full Text Available Abstract Background This article deals with the theoretical size distribution (of number of sub-taxa of a fossil taxon arising from a simple null model of macroevolution. Model New species arise through speciations occurring independently and at random at a fixed probability rate, while extinctions either occur independently and at random (background extinctions or cataclysmically. In addition new genera are assumed to arise through speciations of a very radical nature, again assumed to occur independently and at random at a fixed probability rate. Conclusion The size distributions of the pioneering genus (following a cataclysm and of derived genera are determined. Also the distribution of the number of genera is considered along with a comparison of the probability of a monospecific genus with that of a monogeneric family.

  10. String vacuum backgrounds with covariantly constant null Killing vector and two-dimensional quantum gravity

    International Nuclear Information System (INIS)

    Tseytlin, A.A.

    1993-01-01

    We consider a two-dimensional sigma model with a (2+N)-dimensional Minkowski signature target space metric having a covariantly constant null Killing vector. We study solutions of the conformal invariance conditions in 2+N dimensions and find that generic solutions can be represented in terms of the RG flow in N-dimensional 'transverse space' theory. The resulting conformal invariant sigma model is interpreted as a quantum action of the two-dimensional scalar ('dilaton') quantum gravity model coupled to a (non-conformal) 'transverse' sigma model. The conformal factor of the two-dimensional metric is identified with a light-cone coordinate of the (2+N)-dimensional sigma model. We also discuss the case when the transverse theory is conformal (with or without the antisymmetric tensor background) and reproduce in a systematic way the solutions with flat transverse space known before. (orig.)

  11. Reaction Null Space of a multibody system with applications in robotics

    Directory of Open Access Journals (Sweden)

    D. N. Nenchev

    2013-02-01

    Full Text Available This paper provides an overview of implementation examples based on the Reaction Null Space formalism, developed initially to tackle the problem of satellite-base disturbance of a free-floating space robot, when the robot arm is activated. The method has been applied throughout the years to other unfixed-base systems, e.g. flexible-base and macro/mini robot systems, as well as to the balance control problem of humanoid robots. The paper also includes most recent results about complete dynamical decoupling of the end-link of a fixed-base robot, wherein the end-link is regarded as the unfixed-base. This interpretation is shown to be useful with regard to motion/force control scenarios. Respective implementation results are provided.

  12. Characterisation of connective tissue from the hypertrophic skeletal muscle of myostatin null mice.

    Science.gov (United States)

    Elashry, Mohamed I; Collins-Hooper, Henry; Vaiyapuri, Sakthivel; Patel, Ketan

    2012-06-01

    Myostatin is a potent inhibitor of muscle development. Genetic deletion of myostatin in mice results in muscle mass increase, with muscles often weighing three times their normal values. Contracting muscle transfers tension to skeletal elements through an elaborate connective tissue network. Therefore, the connective tissue of skeletal muscle is an integral component of the contractile apparatus. Here we examine the connective tissue architecture in myostatin null muscle. We show that the hypertrophic muscle has decreased connective tissue content compared with wild-type muscle. Secondly, we show that the hypertrophic muscle fails to show the normal increase in muscle connective tissue content during ageing. Therefore, genetic deletion of myostatin results in an increase in contractile elements but a decrease in connective tissue content. We propose a model based on the contractile profile of muscle fibres that reconciles this apparent incompatible tissue composition phenotype. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  13. Imaging of intracranial neuronal and mixed neuronal-glial tumours

    International Nuclear Information System (INIS)

    Cui Shimin; Qin Jinxi; Zhang Leili; Liu Meili; Jin Song; Yan Shixin; Liu Li; Dai Weiying; Li Tao; Gao Man

    2001-01-01

    Objective: To investigate the characteristic clinical, imaging , and pathologic findings of intracranial neuronal and mixed neuronal-glial tumours. Methods: The imaging findings of surgery and pathobiology proved intracranial neuronal and mixed neuronal-glial tumours in 14 cases (7 male and 7 female, ranging in age from 6-56 years; mean age 33.8 years) were retrospectively analyzed. Results: Eight gangliogliomas were located in the frontal lobe (4 cases), temporal lobe (1 case), front- temporal lobe (2 cases), and pons (1 case). They appeared as iso-or low density on CT, iso-or low signal intensity on T 1 WI, and high signal intensity on T 2 WI on MR imaging. Two central neurocytomas were located in the supratentorial ventricles. Four desmoplastic gangliogliomas were seen as cystic masses, appearing as low signal intensity on T 1 WI and high signal intensity on T 2 WI. Conclusion: Intracranial neuronal and mixed neuronal-glial tumours had imaging characteristics. Combined with clinical history, it was possible to make a tendency preoperative diagnosis using CT or MR

  14. Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

    Science.gov (United States)

    Chaplin, Tristan A; Allitt, Benjamin J; Hagan, Maureen A; Price, Nicholas S C; Rajan, Ramesh; Rosa, Marcello G P; Lui, Leo L

    2017-09-01

    Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural

  15. Detection of Fatigue Cracks at Rivets with Self-Nulling Probe

    Science.gov (United States)

    Wincheski, Buzz; Fulton, Jim; Nath, Shridhar; Namkung, Min

    1994-01-01

    A new eddy current probe developed at NASA Langley Research Center has been used to detect small cracks at rivets in aircraft lap splices [1]. The device has earlier been used to detect isolated fatigue cracks with a minimum detectable flaw size of roughly 1/2 to 1/3 the diameter of the probe [2]. The present work shows that the detectable flaw size for cracks originating at rivets can be greatly improved upon from that of isolated flaws. The use of a rotating probe method combined with spatial filtering has been used to detect 0.18 cm EDM notches, as measured from the rivet shank, with a 1.27 cm diameter probe and to detect flaws buried under the rivet head, down to a length of 0.076 cm, using a 0.32 cm diameter probe. The Self-Nulling Electromagnetic Flaw Detector induces a high density eddy current ring in the sample under test. A ferromagnetic flux focusing lens is incorporated such that in the absence of any inhomogeneities in the material under test only a minimal magnetic field will reach the interior of the probe. A magnetometer (pickup coil) located in the center of the probe therefore registers a null voltage in the absence of material defects. When a fatigue crack or other discontinuity is present in the test article the path of the eddy currents in the material is changed. The magnetic field associated with these eddy currents then enter into the interior of the probe, producing a large output voltage across the pickup coil leads. Further

  16. A symplectic map for trajectories of magnetic field lines in double-null divertor tokamaks

    Science.gov (United States)

    Crank, Willie; Ali, Halima; Punjabi, Alkesh

    2009-11-01

    The coordinates of the area-preserving map equations for integration of magnetic field line trajectories in tokamaks can be any coordinates for which a transformation to (ψ,θ,φ) coordinates exists [A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Lett. A 364, 140 (2007)]. ψ is toroidal magnetic flux, θ is poloidal angle, and φ is toroidal angle. This freedom is exploited to construct a map that represents the magnetic topology of double-null divertor tokamaks. For this purpose, the generating function of the simple map [A. Punjabi, A. Verma, and A. Boozer, Phys. Rev. Lett. 69, 3322 (1992)] is slightly modified. The resulting map equations for the double-null divertor tokamaks are: x1=x0-ky0(1-y0^2 ), y1=y0+kx1. k is the map parameter. It represents the generic topological effects of toroidal asymmetries. The O-point is at (0.0). The X-points are at (0,±1). The equilibrium magnetic surfaces are calculated. These surfaces are symmetric about the x- and y- axes. The widths of stochastic layer near the X-points in the principal plane, and the fractal dimensions of the magnetic footprints on the inboard and outboard side of upper and lower X-points are calculated from the map. This work is supported by US Department of Energy grants DE-FG02-07ER54937, DE-FG02-01ER54624 and DE-FG02-04ER54793.

  17. Null missense ABCR (ABCA4) mutations in a family with stargardt disease and retinitis pigmentosa.

    Science.gov (United States)

    Shroyer, N F; Lewis, R A; Yatsenko, A N; Lupski, J R

    2001-11-01

    To determine the type of ABCR mutations that segregate in a family that manifests both Stargardt disease (STGD) and retinitis pigmentosa (RP), and the functional consequences of the underlying mutations. Direct sequencing of all 50 exons and flanking intronic regions of ABCR was performed for the STGD- and RP-affected relatives. RNA hybridization, Western blot analysis, and azido-adenosine triphosphate (ATP) labeling was used to determine the effect of disease-associated ABCR mutations in an in vitro assay system. Compound heterozygous missense mutations were identified in patients with STGD and RP. STGD-affected individual AR682-03 was compound heterozygous for the mutation 2588G-->C and a complex allele, [W1408R; R1640W]. RP-affected individuals AR682-04 and-05 were compound heterozygous for the complex allele [W1408R; R1640W] and the missense mutation V767D. Functional analysis of the mutation V767D by Western blot and ATP binding revealed a severe reduction in protein expression. In vitro analysis of ABCR protein with the mutations W1408R and R1640W showed a moderate effect of these individual mutations on expression and ATP-binding; the complex allele [W1408R; R1640W] caused a severe reduction in protein expression. These data reveal that missense ABCR mutations may be associated with RP. Functional analysis reveals that the RP-associated missense ABCR mutations are likely to be functionally null. These studies of the complex allele W1408R; R1640W suggest a synergistic effect of the individual mutations. These data are congruent with a model in which RP is associated with homozygous null mutations and with the notion that severity of retinal disease is inversely related to residual ABCR activity.

  18. Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice.

    Directory of Open Access Journals (Sweden)

    Kirsten Madsen

    Full Text Available Mice lacking the α isoform of the catalytic subunit of calcineurin (CnAα were first reported in 1996 and have been an important model to understand the role of calcineurin in the brain, immune system, bones, muscle, and kidney. Research using the mice has been limited, however, by failure to thrive and early lethality of most null pups. Work in our laboratory led to the rescue of CnAα-/- mice by supplemental feeding to compensate for a defect in salivary enzyme secretion. The data revealed that, without intervention, knockout mice suffer from severe caloric restriction. Since nutritional deprivation is known to significantly alter development, it is imperative that previous conclusions based on CnAα-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAα. In this study, we find that defects in renal development and function persist in adult CnAα-/- mice including a significant decrease in glomerular filtration rate and an increase in blood urea nitrogen levels. These data indicate that impaired renal development we previously reported was not due to caloric restriction but rather a specific role for CnAα in renal development and function. In contrast, we find that rather than being hypoglycemic, rescued mice are mildly hyperglycemic and insulin resistant. Examination of muscle fiber types shows that previously reported reductions in type I muscle fibers are no longer evident in rescued null mice. Rather, loss of CnAα likely alters insulin response due to a reduction in insulin receptor substrate-2 (IRS2 expression and signaling in muscle. This study illustrates the importance of re-examining the phenotypes of CnAα-/- mice and the advances that are now possible with the use of adult, rescued knockout animals.

  19. Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.

    Directory of Open Access Journals (Sweden)

    Huan Cai

    Full Text Available Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT, ghrelin knockout (ghrelin(-/-, and GOAT knockout (GOAT(-/- mice. Ghrelin(-/- mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/- mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/- and GOAT(-/- mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/- mice, yet potentiated in GOAT(-/- mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/- mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/- and GOAT(-/- mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities.

  20. Twisting null geodesic congruences, scri, H-space and spin-angular momentum

    International Nuclear Information System (INIS)

    Kozameh, Carlos; Newman, E T; Silva-Ortigoza, Gilberto

    2005-01-01

    The purpose of this work is to return, with a new observation and rather unconventional point of view, to the study of asymptotically flat solutions of Einstein equations. The essential observation is that from a given asymptotically flat spacetime with a given Bondi shear, one can find (by integrating a partial differential equation) a class of asymptotically shear-free (but, in general, twisting) null geodesic congruences. The class is uniquely given up to the arbitrary choice of a complex analytic world line in a four-parameter complex space. Surprisingly, this parameter space turns out to be the H-space that is associated with the real physical spacetime under consideration. The main development in this work is the demonstration of how this complex world line can be made both unique and also given a physical meaning. More specifically, by forcing or requiring a certain term in the asymptotic Weyl tensor to vanish, the world line is uniquely determined and becomes (by several arguments) identified as the 'complex centre of mass'. Roughly, its imaginary part becomes identified with the intrinsic spin-angular momentum while the real part yields the orbital angular momentum. One should think of this work as developing a generalization of the properties of the algebraically special spacetimes in the sense that the term that is forced here to vanish is automatically vanishing (among many other terms) for all the algebraically special metrics. This is demonstrated in the several given examples. It was, in fact, an understanding of the algebraically special metrics and their associated shear-free null congruence that led us to this construction of the asymptotically shear-free congruences and the unique complex world line. The Robinson-Trautman metrics and the Kerr and charged Kerr metrics with their properties are explicit examples of the construction given here

  1. The maintenance of elevated active chlorine levels in the Antarctic lower stratosphere through HCl null cycles

    Science.gov (United States)

    Müller, Rolf; Grooß, Jens-Uwe; Mannan Zafar, Abdul; Robrecht, Sabine; Lehmann, Ralph

    2018-03-01

    The Antarctic ozone hole arises from ozone destruction driven by elevated levels of ozone destroying (active) chlorine in Antarctic spring. These elevated levels of active chlorine have to be formed first and then maintained throughout the period of ozone destruction. It is a matter of debate how this maintenance of active chlorine is brought about in Antarctic spring, when the rate of formation of HCl (considered to be the main chlorine deactivation mechanism in Antarctica) is extremely high. Here we show that in the heart of the ozone hole (16-18 km or 85-55 hPa, in the core of the vortex), high levels of active chlorine are maintained by effective chemical cycles (referred to as HCl null cycles hereafter). In these cycles, the formation of HCl is balanced by immediate reactivation, i.e. by immediate reformation of active chlorine. Under these conditions, polar stratospheric clouds sequester HNO3 and thereby cause NO2 concentrations to be low. These HCl null cycles allow active chlorine levels to be maintained in the Antarctic lower stratosphere and thus rapid ozone destruction to occur. For the observed almost complete activation of stratospheric chlorine in the lower stratosphere, the heterogeneous reaction HCl + HOCl is essential; the production of HOCl occurs via HO2 + ClO, with the HO2 resulting from CH2O photolysis. These results are important for assessing the impact of changes of the future stratospheric composition on the recovery of the ozone hole. Our simulations indicate that, in the lower stratosphere, future increased methane concentrations will not lead to enhanced chlorine deactivation (through the reaction CH4 + Cl → HCl + CH3) and that extreme ozone destruction to levels below ≈ 0.1 ppm will occur until mid-century.

  2. Evidence for complete epistasis of null mutations in murine Fanconi anemia genes Fanca and Fancg.

    Science.gov (United States)

    van de Vrugt, Henri J; Koomen, Mireille; Bakker, Sietske; Berns, Mariska A D; Cheng, Ngan Ching; van der Valk, Martin A; de Vries, Yne; Rooimans, Martin A; Oostra, Anneke B; Hoatlin, Maureen E; Te Riele, Hein; Joenje, Hans; Arwert, Fré

    2011-12-10

    Fanconi anemia (FA) is a heritable disease characterized by bone marrow failure, congenital abnormalities, and cancer predisposition. The 15 identified FA genes operate in a molecular pathway to preserve genomic integrity. Within this pathway the FA core complex operates as an ubiquitin ligase that activates the complex of FANCD2 and FANCI to coordinate DNA repair. The FA core complex is formed by at least 12 proteins. However, only the FANCL subunit displays ubiquitin ligase activity. FANCA and FANCG are members of the FA core complex for which no other functions have been described than to participate in protein interactions. In this study we generated mice with combined null alleles for Fanca and Fancg to identify extended functions for these genes by characterizing the double mutant mice and cells. Double mutant a(-/-)/g(-/-) mice were born at near Mendelian frequencies without apparent developmental abnormalities. Histological analysis of a(-/-)/g(-/-) mice revealed a Leydig cell hyperplasia and frequent vacuolization of Sertoli cells in testes, while ovaries were depleted from developing follicles and displayed an interstitial cell hyperplasia. These gonadal aberrations were associated with a compromised fertility of a(-/-)/g(-/-) males and females. During the first year of life a(-/-)/g(-/-) did not develop malignancies or bone marrow failure. At the cellular level a(-/-)/g(-/-), Fanca(-/-), and Fancg(-/-) cells proved equally compromised in DNA crosslink and homology-directed repair. Overall the phenotype of a(-/-)/g(-/-) double knockout mice and cells appeared highly similar to the phenotype of Fanca or Fancg single knockouts. The lack of an augmented phenotype suggest that null mutations in Fanca or Fancg are fully epistatic, making additional important functions outside of the FA core complex highly unlikely. 2011 Elsevier B.V. All rights reserved.

  3. ORAL EXPOSURE TO ACROLEIN EXACERBATES ATHEROSCLEROSIS IN APO E-NULL MICE

    Science.gov (United States)

    Srivastava, Sanjay; Sithu, Srinivas D.; Vladykovskaya, Elena; Haberzettl, Petra; Hoetker, David J.; Siddiqui, Maqsood A.; Conklin, Daniel J.; D'Souza, Stanley E.; Bhatnagar, Aruni

    2011-01-01

    Background Acrolein is a dietary aldehyde that is present in high concentrations in alcoholic beverages and foods including cheese, donuts and coffee. It is also abundant in tobacco smoke, automobile exhaust and industrial waste and is generated in vivo during inflammation and oxidative stress. Objectives The goal of this study was to examine the effects of dietary acrolein on atherosclerosis. Methods Eight-week old male apoE-null mice were gavage-fed acrolein (2.5 mg/kg/day) for 8 weeks. Atherosclerotic lesion formation and composition and plasma lipids and platelet factor 4 (PF4) levels were measured. Effects of acrolein and PF4 on endothelial cell function was measured in vitro. Results Acrolein feeding increased the concentration of cholesterol in the plasma. NMR analysis of the lipoproteins showed that acrolein feeding increased the abundance of small and medium VLDL particles. Acrolein feeding also increased atherosclerotic lesion formation in the aortic valve and the aortic arch. Immunohistochemical analysis showed increased macrophage accumulation in the lesions of acrolein-fed mice. Plasma PF4 levels and accumulation of PF4 in atherosclerotic lesions was increased in the acrolein-fed mice. Incubation of endothelial cells with the plasma of acrolein-fed mice augmented transmigration of monocytic cells, which was abolished by anti-PF4 antibody treatment. Conclusions Dietary exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Consumption of foods and beverages rich in unsaturated aldehydes such as acrolein may be a contributing factor to the progression of atherosclerotic lesions. PMID:21371710

  4. Atmospheric reaction systems as null-models to identify structural traces of evolution in metabolism.

    Directory of Open Access Journals (Sweden)

    Petter Holme

    Full Text Available The metabolism is the motor behind the biological complexity of an organism. One problem of characterizing its large-scale structure is that it is hard to know what to compare it to. All chemical reaction systems are shaped by the same physics that gives molecules their stability and affinity to react. These fundamental factors cannot be captured by standard null-models based on randomization. The unique property of organismal metabolism is that it is controlled, to some extent, by an enzymatic machinery that is subject to evolution. In this paper, we explore the possibility that reaction systems of planetary atmospheres can serve as a null-model against which we can define metabolic structure and trace the influence of evolution. We find that the two types of data can be distinguished by their respective degree distributions. This is especially clear when looking at the degree distribution of the reaction network (of reaction connected to each other if they involve the same molecular species. For the Earth's atmospheric network and the human metabolic network, we look into more detail for an underlying explanation of this deviation. However, we cannot pinpoint a single cause of the difference, rather there are several concurrent factors. By examining quantities relating to the modular-functional organization of the metabolism, we confirm that metabolic networks have a more complex modular organization than the atmospheric networks, but not much more. We interpret the more variegated modular arrangement of metabolism as a trace of evolved functionality. On the other hand, it is quite remarkable how similar the structures of these two types of networks are, which emphasizes that the constraints from the chemical properties of the molecules has a larger influence in shaping the reaction system than does natural selection.

  5. Impairment of Infectivity and Immunoprotective Effect of a LYT1 Null Mutant of Trypanosoma cruzi▿

    Science.gov (United States)

    Zago, M. Paola; Barrio, Alejandra B.; Cardozo, Rubén M.; Duffy, Tomás; Schijman, Alejandro G.; Basombrío, Miguel A.

    2008-01-01

    Trypanosoma cruzi infection of host cells is a complex process in which many proteins participate but only a few of these proteins have been identified experimentally. One parasite factor likely to be involved is the protein product of LYT1, a single-copy gene cloned, sequenced, and characterized by Manning-Cela et al. (Infect. Immun. 69:3916-3923, 2001). This gene was potentially associated with infectivity, since the deletion of both LYT1 alleles in the CL Brenner strain (the wild type [WT]) resulted in a null mutant T. cruzi clone (L16) that shows an attenuated phenotype in cell culture models. The aim of this work was to characterize the infective behavior of L16 in the insect vector and murine models. The infection of adult Swiss mice with 103 trypomastigotes of both clones revealed a significant reduction in infective behavior of L16, as shown by direct parasitemia, spleen index, and quantitation of tissue parasite burden, suggesting the loss of virulence in the null mutant clone. Although L16 blood counts were almost undetectable, blood-based PCRs indicated the presence of latent and persistent infection during all of the study period and epimastigotes were reisolated from hemocultures until 12 months postinfection. Nevertheless, virulence was not restored in L16 by serial passages in mice, and reisolated parasites lacking the LYT1 gene and bearing the antibiotic resistance genes revealed the stability of the genetic manipulation. Histopathological studies showed a strong diminution in the muscle inflammatory response triggered by L16 compared to that triggered by the WT group, consistent with a lower tissue parasite load. A strong protection against a virulent challenge in both L16- and WT-infected mice was observed; however, the immunizing infection by the genetically modified parasite was highly attenuated. PMID:17938222

  6. Tinbergen on mirror neurons

    Science.gov (United States)

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology—the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible ‘best explanation’ for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of ‘survival value’, should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding—or another social cognitive function—by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories. PMID:24778376

  7. Neurons on the couch.

    Science.gov (United States)

    Marić, Nadja P; Jašović-Gašić, Miroslava

    2010-12-01

    A hundred years after psychoanalysis was introduced, neuroscience has taken a giant step forward. It seems nowadays that effects of psychotherapy could be monitored and measured by state-of-the art brain imaging techniques. Today, the psychotherapy is considered as a strategic and purposeful environmental influence intended to enhance learning. Since gene expression is regulated by environmental influences throughout life and these processes create brain architecture and influence the strength of synaptic connections, psychotherapy (as a kind of learning) should be explored in the context of aforementioned paradigm. In other words, when placing a client on the couch, therapist actually placed client's neuronal network; while listening and talking, expressing and analyzing, experiencing transference and counter transference, therapist tends to stabilize synaptic connections and influence dendritic growth by regulating gene-transcriptional activity. Therefore, we strongly believe that, in the near future, an increasing knowledge on cellular and molecular interactions and mechanisms of action of different psycho- and pharmaco-therapeutic procedures will enable us to tailor a sophisticated therapeutic approach toward a person, by combining major therapeutic strategies in psychiatry on the basis of rational goals and evidence-based therapeutic expectations.

  8. Tinbergen on mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2014-01-01

    Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.

  9. Understanding Neuronal Mechanisms of Epilepsy ...

    Indian Academy of Sciences (India)

    Admin

    α subunit of Rat Brain type IIA Voltage Gated Sodium Channel and geneticin selection ..... scaling the mother wavelet. Scale = 1/ .... through dynamic clamp. Dynamic Clamp ... It has been shown that like in vivo neurons, cortical networks in.

  10. Imitation, mirror neurons and autism.

    Science.gov (United States)

    Williams, J H; Whiten, A; Suddendorf, T; Perrett, D I

    2001-06-01

    Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.

  11. Information processing by neuronal populations

    National Research Council Canada - National Science Library

    Hölscher, Christian; Munk, Matthias

    2009-01-01

    ... simultaneously recorded spike trains 120 Mark Laubach, Nandakumar S. Narayanan, and Eyal Y. Kimchi Part III Neuronal population information coding and plasticity in specific brain areas 149 7 F...

  12. A mathematical model of communication between groups of circadian neurons in Drosophila melanogaster.

    Science.gov (United States)

    Risau-Gusman, Sebastián; Gleiser, Pablo M

    2014-12-01

    In the fruit fly, circadian behavior is controlled by a small number of specialized neurons, whose molecular clocks are relatively well known. However, much less is known about how these neurons communicate among themselves. In particular, only 1 circadian neuropeptide, pigment-dispersing factor (PDF), has been identified, and most aspects of its interaction with the molecular clock remain to be elucidated. Furthermore, it is speculated that many other peptides should contribute to circadian communication. We have developed a relatively detailed model of the 2 main groups of circadian pacemaker neurons (sLNvs and LNds) to investigate these issues. We have proposed many possible mechanisms for the interaction between the synchronization factors and the molecular clock, and we have compared the outputs with the experimental results reported in the literature both for the wild-type and PDF-null mutant. We have studied how different the properties of each neuron should be to account for the observations reported for the sLNvs in the mutant. We have found that only a few mechanisms, mostly related to the slowing down of nuclear entry of a circadian protein, can synchronize neurons that present these differences. Detailed immunofluorescent recordings have suggested that, whereas in the mutant, LNd neurons are synchronized, in the wild-type, a subset of the LNds oscillate faster than the rest. With our model, we find that a more likely explanation for the same observations is that this subset is being driven outside its synchronization range and displays therefore a complex pattern of oscillation.

  13. Regional and Large-Scale Climate Influences on Tree-Ring Reconstructed Null Zone Position in San Francisco Bay

    Science.gov (United States)

    Stahle, D.; Griffin, D.; Cleaveland, M.; Fye, F.; Meko, D.; Cayan, D.; Dettinger, M.; Redmond, K.

    2007-05-01

    A new network of 36 moisture sensitive tree-ring chronologies has been developed in and near the drainage basins of the Sacramento and San Joaquin Rivers. The network is based entirely on blue oak (Quercus douglasii), which is a California endemic found from the lower forest border up into the mixed conifer zone in the Coast Ranges, Sierra Nevada, and Cascades. These blue oak tree-ring chronologies are highly correlated with winter-spring precipitation totals, Sacramento and San Joaquin streamflow, and with seasonal variations in salinity and null zone position in San Francisco Bay. Null zone is the non-tidal bottom water location where density-driven salinity and river-driven freshwater currents balance (zero flow). It is the area of highest turbidity, water residence time, sediment accumulation, and net primary productivity in the estuary. Null zone position is measured by the distance from the Golden Gate of the 2 per mil bottom water isohaline and is primarily controlled by discharge from the Sacramento and San Joaquin Rivers (and ultimately by winter-spring precipitation). The location of the null zone is an estuarine habitat indicator, a policy variable used for ecosystem management, and can have a major impact on biological resources in the San Francisco estuary. Precipitation-sensitive blue oak chronologies can be used to estimate null zone position based on the strong biogeophysical interaction among terrestrial, aquatic, and estuarine ecosystems, orchestrated by precipitation. The null zone reconstruction is 626-years long and provides a unique long term perspective on the interannual to decadal variability of this important estuarine habitat indicator. Consecutive two-year droughts (or longer) allow the null zone to shrink into the confined upper reaches of Suisun Bay, causing a dramatic reduction in phytoplankton production and favoring colonization of the estuary by marine biota. The reconstruction indicates an approximate 10 year recurrence interval

  14. Chimera states in bursting neurons

    OpenAIRE

    Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.

    2015-01-01

    We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of stability function in the incoherent (i.e. disorder), coherent, chimera and multi-chimera states. Surprisingly, we find that chimera and multi-chimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is i...

  15. TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons.

    Directory of Open Access Journals (Sweden)

    Marie E Barabas

    Full Text Available Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J DRG neurons. Approximately 80% of all small-diameter (<27 µm neurons from lumbar 1-6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79% or cinnamaldehyde (84% were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81% cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66% of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2-4% responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter responded to AITC (6% or cinnamaldehyde (4%, confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is

  16. TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons

    Science.gov (United States)

    Stucky, Cheryl L.

    2012-01-01

    Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons. Approximately 80% of all small-diameter (neurons from lumbar 1–6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2–4%) responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter) responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is functionally expressed

  17. Mitochondrial Alterations by PARKIN in Dopaminergic Neurons Using PARK2 Patient-Specific and PARK2 Knockout Isogenic iPSC Lines

    Directory of Open Access Journals (Sweden)

    Atossa Shaltouki

    2015-05-01

    Full Text Available In this study, we used patient-specific and isogenic PARK2-induced pluripotent stem cells (iPSCs to show that mutations in PARK2 alter neuronal proliferation. The percentage of TH+ neurons was decreased in Parkinson’s disease (PD patient-derived neurons carrying various mutations in PARK2 compared with an age-matched control subject. This reduction was accompanied by alterations in mitochondrial:cell volume fraction (mitochondrial volume fraction. The same phenotype was confirmed in isogenic PARK2 null lines. The mitochondrial phenotype was also seen in non-midbrain neurons differentiated from the PARK2 null line, as was the functional phenotype of reduced proliferation in culture. Whole genome expression profiling at various stages of differentiation confirmed the mitochondrial phenotype and identified pathways altered by PARK2 dysfunction that include PD-related genes. Our results are consistent with current model of PARK2 function where damaged mitochondria are targeted for degradation via a PARK2/PINK1-mediated mechanism.

  18. Communication among neurons.

    Science.gov (United States)

    Marner, Lisbeth

    2012-04-01

    The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are

  19. Which randomizations detect convergence and divergence in trait-based community assembly? A test of commonly used null models

    Czech Academy of Sciences Publication Activity Database

    Götzenberger, Lars; Botta-Dukát, Z.; Lepš, Jan; Pärtel, M.; Zobel, M.; de Bello, Francesco

    2016-01-01

    Roč. 27, č. 6 (2016), s. 1275-1287 ISSN 1100-9233 R&D Projects: GA ČR GAP505/12/1296 Institutional support: RVO:67985939 ; RVO:60077344 Keywords : Community ecology * Competition * Null model Subject RIV: EH - Ecology, Behaviour Impact factor: 2.924, year: 2016

  20. 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 mol...

  1. Null Space Based Preemptive Scheduling For Joint URLLC and eMBB Traffic in 5G Networks

    DEFF Research Database (Denmark)

    Abdul-Mawgood Ali Ali Esswie, Ali; Pedersen, Klaus

    2018-01-01

    In this paper, we propose a null-space-based preemptive scheduling framework for cross-objective optimization to always guarantee robust URLLC performance, while extracting the maximum possible eMBB capacity. The proposed scheduler perpetually grants incoming URLLC traffic a higher priority for i...

  2. 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

    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...

  3. A Common LPA Null Allele Associates With Lower Lipoprotein(a) Levels and Coronary Artery Disease Risk

    NARCIS (Netherlands)

    Kyriakou, Theodosios; Seedorf, Udo; Goel, Anuj; Hopewell, Jemma C.; Clarke, Robert; Watkins, Hugh; Farrall, Martin; van der Hout, A.H.

    Objective-Increased levels of lipoprotein(a) are a highly heritable risk factor for coronary artery disease (CAD). The genetic determinants of lipoprotein(a) levels are mainly because of genetic variation in the apolipoprotein(a) gene (LPA). We have tested the association of a relatively common null

  4. Homozygous mutation of focal adhesion kinase in embryonic stem cell derived neurons: normal electrophysiological and morphological properties in vitro

    Directory of Open Access Journals (Sweden)

    Komiyama NH

    2006-06-01

    Full Text Available Abstract Background Genetically manipulated embryonic stem (ES cell derived neurons (ESNs provide a powerful system with which to study the consequences of gene manipulation in mature, synaptically connected neurons in vitro. Here we report a study of focal adhesion kinase (FAK, which has been implicated in synapse formation and regulation of ion channels, using the ESN system to circumvent the embryonic lethality of homozygous FAK mutant mice. Results Mouse ES cells carrying homozygous null mutations (FAK-/- were generated and differentiated in vitro into neurons. FAK-/- ESNs extended axons and dendrites and formed morphologically and electrophysiologically intact synapses. A detailed study of NMDA receptor gated currents and voltage sensitive calcium currents revealed no difference in their magnitude, or modulation by tyrosine kinases. Conclusion FAK does not have an obligatory role in neuronal differentiation, synapse formation or the expression of NMDA receptor or voltage-gated calcium currents under the conditions used in this study. The use of genetically modified ESNs has great potential for rapidly and effectively examining the consequences of neuronal gene manipulation and is complementary to mouse studies.

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

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    Nazila Alizadeh

    2016-07-01

    Full Text Available 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.

  6. 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

  7. Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder.

    Directory of Open Access Journals (Sweden)

    Daniela Brunner

    Full Text Available Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept14Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of

  8. Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

    Science.gov (United States)

    POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

    2015-01-01

    Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

  9. Spinal cord compression injury in lysophosphatidic acid 1 receptor-null mice promotes maladaptive pronociceptive descending control.

    Science.gov (United States)

    Suardíaz, M; Galan-Arriero, I; Avila-Martin, G; Estivill-Torrús, G; de Fonseca, F R; Chun, J; Gómez-Soriano, J; Bravo-Esteban, E; Taylor, J

    2016-02-01

    Although activation of the lysophosphatidic acid receptor 1 (LPA1) is known to mediate pronociceptive effects in peripheral pain models, the role of this receptor in the modulation of spinal nociception following spinal cord injury (SCI) is unknown. In this study, LPA1 regulation of spinal excitability mediated by supraspinal descending antinociceptive control systems was assessed following SCI in both wild-type (WT) and maLPA1-null receptor mice. The effect of a T8 spinal compression in WT and maLPA1-null mice was assessed up to 1 month after SCI using histological, immunohistochemical and behavioural techniques analysis including electrophysiological recording of noxious toes-Tibialis Anterior (TA) stimulus-response reflex activity. The effect of a T3 paraspinal transcutaneous electrical conditioning stimulus on TA noxious reflex temporal summation was also assessed. Histological analysis demonstrated greater dorsolateral funiculus damage after SCI in maLPA1-null mice, without a change in the stimulus-response function of the TA noxious reflex when compared to WT mice. While T3 conditioning stimulation in the WT group inhibited noxious TA reflex temporal summation after SCI, this stimulus strongly excited TA reflex temporal summation in maLPA1-null mice. The functional switch from descending inhibition to maladaptive facilitation of central excitability of spinal nociception demonstrated in maLPA1-null mice after SCI was unrelated to a general change in reflex activity. These data suggest that the LPA1 receptor is necessary for inhibition of temporal summation of noxious reflex activity, partly mediated via long-tract descending modulatory systems acting at the spinal level. © 2015 European Pain Federation - EFIC®

  10. Characterization of the Stabilized Test Bench of Nulling Interferometry PERSÉE

    Science.gov (United States)

    Lozi, Julien; Ollivier, M.; Cassaing, F.; Le Duigou, J.; CNES; Onera/Dota/HRA; IAS; LESIA; OCA; TAS

    2013-01-01

    There are two problems with the observation of exoplanets: the contrast between the planet and the star and their very low separation. One technique solving these problems is nulling interferometry: two pupils are recombined to make a destructive interference on the star, and their base is adjusted to create a constructive interference on the planet. However, to ensure a sufficient extinction of the star, the optical path difference between the beams must be around the nanometer, and the pointing must be better than one hundredth of Airy disk, despite the external disturbances.To validate the critical points of such a space mission, a laboratory demonstrator, PERSÉE, was defined by a consortium led by the french space agency CNES, including IAS, LESIA, ONERA, OCA and Thales Alenia Space and integrated in Paris Observatory. This bench simulates the entire space mission (interferometer and nanometric cophasing system). Its goal is to deliver and maintain an extinction of 10^-4 stable at better than 10^-5 over a few hours in the presence of typical injected disturbances.My thesis work consisted in integrating the bench in successive stages and to develop calibration procedures. This helped me to characterize the critical elements separately before grouping them. After having implemented the control loops of the cophasing system, their precise analysis helped me to reduce down to 0.3 nm rms the residual OPD, and 0.4 % of the Airy disk the residual tip/tilt, despite disturbances of tens of nanometers, consisting of several tens of vibrational frequencies between 1 and 100 Hz. This has been achieved by the implementation of a linear quadratic Gaussian controller, parameterized by the preliminary measurement of the disturbance to minimize. Thanks to these excellent results, I obtained on the band [1.65 - 2.45] µm a record null rate of 8.8x10^-6 stabilized at 9x10^-7 over a few hours, a decade better than the original specifications. An extrapolation of these results to

  11. Learning of time series through neuron-to-neuron instruction

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Y [Department of Physics, Kyoto University, Kyoto 606-8502, (Japan); Kinzel, W [Institut fuer Theoretische Physik, Universitaet Wurzburg, 97074 Wurzburg (Germany); Shinomoto, S [Department of Physics, Kyoto University, Kyoto (Japan)

    2003-02-07

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space.

  12. Learning of time series through neuron-to-neuron instruction

    International Nuclear Information System (INIS)

    Miyazaki, Y; Kinzel, W; Shinomoto, S

    2003-01-01

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space

  13. The mirror-neuron system.

    Science.gov (United States)

    Rizzolatti, Giacomo; Craighero, Laila

    2004-01-01

    A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.

  14. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. © 2015 The Author(s).

  15. Energy Model of Neuron Activation.

    Science.gov (United States)

    Romanyshyn, Yuriy; Smerdov, Andriy; Petrytska, Svitlana

    2017-02-01

    On the basis of the neurophysiological strength-duration (amplitude-duration) curve of neuron activation (which relates the threshold amplitude of a rectangular current pulse of neuron activation to the pulse duration), as well as with the use of activation energy constraint (the threshold curve corresponds to the energy threshold of neuron activation by a rectangular current pulse), an energy model of neuron activation by a single current pulse has been constructed. The constructed model of activation, which determines its spectral properties, is a bandpass filter. Under the condition of minimum-phase feature of the neuron activation model, on the basis of Hilbert transform, the possibilities of phase-frequency response calculation from its amplitude-frequency response have been considered. Approximation to the amplitude-frequency response by the response of the Butterworth filter of the first order, as well as obtaining the pulse response corresponding to this approximation, give us the possibility of analyzing the efficiency of activating current pulses of various shapes, including analysis in accordance with the energy constraint.

  16. Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation.

    Science.gov (United States)

    Pontikis, Charlie C; Cella, Claire V; Parihar, Nisha; Lim, Ming J; Chakrabarti, Shubhodeep; Mitchison, Hannah M; Mobley, William C; Rezaie, Payam; Pearce, David A; Cooper, Jonathan D

    2004-10-15

    Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.

  17. Loss of Kdm5c Causes Spurious Transcription and Prevents the Fine-Tuning of Activity-Regulated Enhancers in Neurons

    Directory of Open Access Journals (Sweden)

    Marilyn Scandaglia

    2017-10-01

    Full Text Available During development, chromatin-modifying enzymes regulate both the timely establishment of cell-type-specific gene programs and the coordinated repression of alternative cell fates. To dissect the role of one such enzyme, the intellectual-disability-linked lysine demethylase 5C (Kdm5c, in the developing and adult brain, we conducted parallel behavioral, transcriptomic, and epigenomic studies in Kdm5c-null and forebrain-restricted inducible knockout mice. Together, genomic analyses and functional assays demonstrate that Kdm5c plays a critical role as a repressor responsible for the developmental silencing of germline genes during cellular differentiation and in fine-tuning activity-regulated enhancers during neuronal maturation. Although the importance of these functions declines after birth, Kdm5c retains an important genome surveillance role preventing the incorrect activation of non-neuronal and cryptic promoters in adult neurons.

  18. Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons.

    Science.gov (United States)

    Miranda-Vizuete, Antonio; Fierro González, Juan Carlos; Gahmon, Gabriele; Burghoorn, Jan; Navas, Plácido; Swoboda, Peter

    2006-01-23

    Thioredoxins are a class of small proteins that play a key role in regulating many cellular redox processes. We report here the characterization of the first member of the thioredoxin family in metazoans that is mainly associated with neurons. The Caenorhabditis elegans gene B0228.5 encodes a thioredoxin (TRX-1) that is expressed in ASJ ciliated sensory neurons, and to some extent also in the posterior-most intestinal cells. TRX-1 is active at reducing protein disulfides in the presence of a heterologous thioredoxin reductase. A mutant worm strain carrying a null allele of the trx-1 gene displays a reproducible decrease in both mean and maximum lifespan when compared to wild-type. The identification and characterization of TRX-1 paves the way to use C. elegans as an in vivo model to study the role of thioredoxins in lifespan and nervous system physiology and pathology.

  19. A single test for rejecting the null hypothesis in subgroups and in the overall sample.

    Science.gov (United States)

    Lin, Yunzhi; Zhou, Kefei; Ganju, Jitendra

    2017-01-01

    In clinical trials, some patient subgroups are likely to demonstrate larger effect sizes than other subgroups. For example, the effect size, or informally the benefit with treatment, is often greater in patients with a moderate condition of a disease than in those with a mild condition. A limitation of the usual method of analysis is that it does not incorporate this ordering of effect size by patient subgroup. We propose a test statistic which supplements the conventional test by including this information and simultaneously tests the null hypothesis in pre-specified subgroups and in the overall sample. It results in more power than the conventional test when the differences in effect sizes across subgroups are at least moderately large; otherwise it loses power. The method involves combining p-values from models fit to pre-specified subgroups and the overall sample in a manner that assigns greater weight to subgroups in which a larger effect size is expected. Results are presented for randomized trials with two and three subgroups.

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

    Directory of Open Access Journals (Sweden)

    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.