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.

SmallSats, Iodine Propulsion Technology, Applications to Low-Cost Lunar Missions, and the Iodine Satellite (iSAT) Project

Science.gov (United States)

Dankanich, John W.

2014-01-01

Closing Remarks: ?(1) SmallSats hold significant potential for future low cost high value missions; (2) Propulsion remains a key limiting capability for SmallSats that Iodine can address: High ISP * Density for volume constrained spacecraft; Indefinite quiescence, unpressurized and non-hazardous as a secondary payload; (3) Iodine enables MicroSat and SmallSat maneuverability: Enables transfer into high value orbits, constellation deployment and deorbit; (4) Iodine may enable a new class of planetary and exploration class missions: Enables GTO launched secondary spacecraft to transit to the moon, asteroids, and other interplanetary destinations for approximately 150 million dollars full life cycle cost including the launch; (5) ESPA based OTVs are also volume constrained and a shift from xenon to iodine can significantly increase the transfer vehicle change in volume capability including transfers from GTO to a range of Lunar Orbits; (6) The iSAT project is a fast pace high value iodine Hall technology demonstration mission: Partnership with NASA GRC and NASA MSFC with industry partner - Busek; (7) The iSAT mission is an approved project with PDR in November of 2014 and is targeting a flight opportunity in FY17.

Augmented hepatic injury followed by impaired regeneration in metallothionein-I/II knockout mice after treatment with thioacetamide

International Nuclear Information System (INIS)

Oliver, Jordan R.; Jiang, Sean; Cherian, M. George

2006-01-01

A previous study (Oliver, J.R., Mara, T.W., Cherian, M.G. 2005. Impaired hepatic regeneration in metallothionein-I/II knockout mice after partial hepatectomy. Exp. Biol. Med. 230, 61-67) has shown an impairment of liver regeneration following partial hepatectomy (PH) in metallothionein (MT)-I and MT-II gene knockout (MT-null) mice, thus suggesting a requirement for MT in cellular growth. The present study was undertaken to investigate whether MT may play a similar role in hepatic injury and regeneration after acute treatment with thioacetamide (TAA). Hepatotoxicity of TAA is caused by the generation of oxidative stress. TAA was injected ip to both wild-type (WT) and MT-null mice. Mice were killed at 6, 12, 24, 48, 60, and 72 h after injection of TAA (125 mg/kg) or 48 h after injection of saline (vehicle control), and different parameters of hepatic injury were measured. The levels of hepatic lipid peroxidation were increased at 12 h in both types of mice; however, lipid peroxidation was significantly less in WT mice than MT-null mice at 48 h after injection of TAA. Analysis of hepatic glutathione (GSH) levels after TAA injection showed depletion of GSH at 12 h in WT mice and at 6 h in MT-null mice; however, significantly more GSH was depleted early (6-24 h) in MT-null mice than WT mice. An increase in hepatic iron (Fe) levels was observed in both types of mice after injection of TAA, but Fe levels were significantly higher in MT-null mice than WT mice at 6-60 h. The levels of hepatic copper (Cu) and zinc (Zn) were significantly higher in WT mice than MT-null mice at 6-60 h for Cu, and at 24 h and 60 h for Zn, respectively. Histopathological examination showed hemorrhagic necrosis in the liver of both types of mice at 12-72 h, with hepatic injury being more prominent in MT-null mice than WT mice. The hepatic MT levels were increased in WT mice after injection of TAA, and were highest at 24-72 h. Immunohistochemical staining for MT in WT mice indicated the presence

Spinal cord compression injury in lysophosphatidic acid 1 receptor-null mice promotes maladaptive pronociceptive descending control.

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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®

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

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Hongshan Liu

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

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....

A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficient mice

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Raquel Riquelme

2010-06-01

Full Text Available Insulin-like growth factor-I (IGF-I belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to

Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.

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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.

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

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

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

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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.

CNS wound healing is severely depressed in metallothionein I- and II-deficient mice

DEFF Research Database (Denmark)

Penkowa, M; Carrasco, J; Giralt, M

1999-01-01

. In contrast to normal mice, at 20 dpl no wound healing had occurred. The rate of apoptosis, as determined by using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, was drastically increased in neurons of ipsilateral cortex of the MT-I+II null mice. Our results demonstrate that MT...

Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

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Theresa Alexandra Mattioli

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

Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice

Science.gov (United States)

Portal-Núñez, Sergio; Murillo-Cuesta, Silvia; Lozano, Daniel; Cediel, Rafael; Esbrit, Pedro

2014-01-01

Insulin-like growth factor-I (IGF-I) deficiency causes growth delay, and IGF-I has been shown to partially mediate bone anabolism by parathyroid hormone (PTH). PTH-related protein (PTHrP) is abundant in bone, and has osteogenic features by poorly defined mechanisms. We here examined the capacity of PTHrP (1–36) and PTHrP (107–111) (osteostatin) to reverse the skeletal alterations associated with IGF-I deficiency. Igf1-null mice and their wild type littermates were treated with each PTHrP peptide (80 µg/Kg/every other day/2 weeks; 2 males and 4 females for each genotype) or saline vehicle (3 males and 3 females for each genotype). We found that treatment with either PTHrP peptide ameliorated trabecular structure in the femur in both genotypes. However, these peptides were ineffective in normalizing the altered cortical structure at this bone site in Igf1-null mice. An aberrant gene expression of factors associated with osteoblast differentiation and function, namely runx2, osteoprotegerin/receptor activator of NF-κB ligand ratio, Wnt3a , cyclin D1, connexin 43, catalase and Gadd45, as well as in osteocyte sclerostin, was found in the long bones of Igf1-null mice. These mice also displayed a lower amount of trabecular osteoblasts and osteoclasts in the tibial metaphysis than those in wild type mice. These alterations in Igf1-null mice were only partially corrected by each PTHrP peptide treatment. The skeletal expression of Igf2, Igf1 receptor and Irs2 was increased in Igf1-null mice, and this compensatory profile was further improved by treatment with each PTHrP peptide related to ERK1/2 and FoxM1 activation. In vitro, PTHrP (1–36) and osteostatin were effective in promoting bone marrow stromal cell mineralization in normal mice but not in IGF-I-deficient mice. Collectively, these findings indicate that PTHrP (1–36) and osteostatin can exert several osteogenic actions even in the absence of IGF-I in the mouse bone. PMID:24503961

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

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

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Deug-Nam Kwon

2014-01-01

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

Thermal Analysis of Iodine Satellite (iSAT)

Science.gov (United States)

Mauro, Stephanie

2015-01-01

This paper presents the progress of the thermal analysis and design of the Iodine Satellite (iSAT). The purpose of the iSAT spacecraft (SC) is to demonstrate the ability of the iodine Hall Thruster propulsion system throughout a one year mission in an effort to mature the system for use on future satellites. The benefit of this propulsion system is that it uses a propellant, iodine, that is easy to store and provides a high thrust-to-mass ratio. The spacecraft will also act as a bus for an earth observation payload, the Long Wave Infrared (LWIR) Camera. Four phases of the mission, determined to either be critical to achieving requirements or phases of thermal concern, are modeled. The phases are the Right Ascension of the Ascending Node (RAAN) Change, Altitude Reduction, De-Orbit, and Science Phases. Each phase was modeled in a worst case hot environment and the coldest phase, the Science Phase, was also modeled in a worst case cold environment. The thermal environments of the spacecraft are especially important to model because iSAT has a very high power density. The satellite is the size of a 12 unit cubesat, and dissipates slightly more than 75 Watts of power as heat at times. The maximum temperatures for several components are above their maximum operational limit for one or more cases. The analysis done for the first Design and Analysis Cycle (DAC1) showed that many components were above or within 5 degrees Centigrade of their maximum operation limit. The battery is a component of concern because although it is not over its operational temperature limit, efficiency greatly decreases if it operates at the currently predicted temperatures. In the second Design and Analysis Cycle (DAC2), many steps were taken to mitigate the overheating of components, including isolating several high temperature components, removal of components, and rearrangement of systems. These changes have greatly increased the thermal margin available.

Joint dysfunction and functional decline in middle age myostatin null mice.

Science.gov (United States)

Guo, Wen; Miller, Andrew D; Pencina, Karol; Wong, Siu; Lee, Amanda; Yee, Michael; Toraldo, Gianluca; Jasuja, Ravi; Bhasin, Shalender

2016-02-01

Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative metabolism of methacrylonitrile and acrylonitrile to cyanide using cytochrome P4502E1 and microsomal epoxide hydrolase-null mice

International Nuclear Information System (INIS)

El Hadri, L.; Chanas, B.; Ghanayem, B.I.

2005-01-01

Methacrylonitrile (MAN) and acrylonitrile (AN) are metabolized via glutathione (GSH) conjugation or epoxide formation. We have recently shown that CYP2E1 is essential for AN epoxidation and subsequent cyanide liberation. Current studies were designed to compare the enzymatic basis of MAN vs. AN metabolism to cyanide using wild-type (WT), CYP2E1-, and mEH-null mice. Mice received a single gavage dose of 0.047, 0.095, 0.19, or 0.38 mmol/kg of MAN or AN, and blood cyanide was measured at 1 or 3 h later. Blood cyanide levels in WT mice treated with AN or MAN were dose and time dependent. At equimolar doses, significantly higher levels of cyanide were detected in the blood of MAN- vs. AN-treated mice. Further, while significant reduction in blood cyanide levels occurred in MAN-treated CYP2E1-null vs. WT mice, AN metabolism to cyanide was largely abolished in CYP2E1-null mice. Pretreatment of mice with 1-aminobenzotriazole (ABT, CYP inhibitor) demonstrated that CYPs other than CYP2E1 also contribute to MAN metabolism to cyanide. Blood cyanide levels in mEH-null mice treated with aliphatic nitriles are generally lower than levels in similarly treated WT mice. Western blot analysis showed that expression of sEH was greater in male vs. female mice. The role of various epoxide hydrolases (EHs) in the production of cyanide from aliphatic nitriles is apparently structure and dose dependent. Regardless of genotype, significantly higher levels of cyanide were measured in the blood of male vs. female mice treated with MAN or AN. In conclusion, these data showed that (1) at equimolar doses, higher blood cyanide levels were detected in mice treated with MAN vs. AN; (2) while CYP2E1 is the only enzyme responsible for AN metabolism to cyanide, other CYPs also contribute to MAN metabolism; and (3) significantly higher levels of cyanide were measured in the blood of male vs. female treated with either nitrile. Higher blood cyanide levels in male vs. female mice and in MAN- vs. AN

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...

Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

DEFF Research Database (Denmark)

Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

2003-01-01

of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

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

Science.gov (United States)

Ali, Niwa; Flutter, Barry; Sanchez Rodriguez, Robert; Sharif-Paghaleh, Ehsan; Barber, Linda D; Lombardi, Giovanna; Nestle, Frank O

2012-01-01

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

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

Directory of Open Access Journals (Sweden)

Niwa Ali

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

Carrageenan-Induced Colonic Inflammation Is Reduced in Bcl10 Null Mice and Increased in IL-10-Deficient Mice

Directory of Open Access Journals (Sweden)

Sumit Bhattacharyya

2013-01-01

Full Text Available The common food additive carrageenan is a known activator of inflammation in mammalian tissues and stimulates both the canonical and noncanonical pathways of NF-κB activation. Exposure to low concentrations of carrageenan (10 μg/mL in the water supply has produced glucose intolerance, insulin resistance, and impaired insulin signaling in C57BL/6 mice. B-cell leukemia/lymphoma 10 (Bcl10 is a mediator of inflammatory signals from Toll-like receptor (TLR 4 in myeloid and epithelial cells. Since the TLR4 signaling pathway is activated in diabetes and by carrageenan, we addressed systemic and intestinal inflammatory responses following carrageenan exposure in Bcl10 wild type, heterozygous, and null mice. Fecal calprotectin and circulating keratinocyte chemokine (KC, nuclear RelA and RelB, phospho(Thr559-NF-κB-inducing kinase (NIK, and phospho(Ser36-IκBα in the colonic epithelial cells were significantly less (P<0.001 in the carrageenan-treated Bcl10 null mice than in controls. IL-10-deficient mice exposed to carrageenan in a germ-free environment showed an increase in activation of the canonical pathway of NF-κB (RelA activation, but without increase in RelB or phospho-Bcl10, and exogenous IL-10 inhibited only the canonical pathway of NF-κB activation in cultured colonic cells. These findings demonstrate a Bcl10 requirement for maximum development of carrageenan-induced inflammation and lack of complete suppression by IL-10 of carrageenan-induced inflammation.

Perturbed desmosomal cadherin expression in grainy head-like 1-null mice.

Science.gov (United States)

Wilanowski, Tomasz; Caddy, Jacinta; Ting, Stephen B; Hislop, Nikki R; Cerruti, Loretta; Auden, Alana; Zhao, Lin-Lin; Asquith, Stephen; Ellis, Sarah; Sinclair, Rodney; Cunningham, John M; Jane, Stephen M

2008-03-19

In Drosophila, the grainy head (grh) gene plays a range of key developmental roles through the regulation of members of the cadherin gene family. We now report that mice lacking the grh homologue grainy head-like 1 (Grhl1) exhibit hair and skin phenotypes consistent with a reduction in expression of the genes encoding the desmosomal cadherin, desmoglein 1 (Dsg1). Grhl1-null mice show an initial delay in coat growth, and older mice exhibit hair loss as a result of poor anchoring of the hair shaft in the follicle. The mice also develop palmoplantar keratoderma, analogous to humans with DSG1 mutations. Sequence analysis, DNA binding, and chromatin immunoprecipitation experiments demonstrate that the human and mouse Dsg1 promoters are direct targets of GRHL1. Ultrastructural analysis reveals reduced numbers of abnormal desmosomes in the interfollicular epidermis. These findings establish GRHL1 as an important regulator of the Dsg1 genes in the context of hair anchorage and epidermal differentiation, and suggest that cadherin family genes are key targets of the grainy head-like genes across 700 million years of evolution.

Flexible High-Efficiency Solar Panels for SmallSats and CubeSats, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — MicroLink proposes to develop and test, a new type of photovoltaic module that will be suitable for use in SmallSat and CubeSat platforms requiring maximum power in...

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.

A review of planetary and space science projects presented at iCubeSat, the Interplanetary CubeSat Workshop

Science.gov (United States)

Johnson, Michael

2015-04-01

iCubeSat, the Interplanetary CubeSat Workshop, is an annual technical workshop for researchers working on an exciting new standardised platform and opportunity for planetary and space scientists. The first workshop was held in 2012 at MIT, 2013 at Cornell, 2014 at Caltech with the 2015 workshop scheduled to take place on the 26-27th May 2015 at Imperial College London. Mission concepts and flight projects presented since 2012 have included orbiters and landers targeting asteroids, the moon, Mars, Venus, Saturn and their satellites to perform science traditionally reserved for flagship missions at a fraction of their cost. Some of the first missions proposed are currently being readied for flight in Europe, taking advantage of multiple ride share launch opportunities and technology providers. A review of these and other interplanetary CubeSat projects will be presented, covering details of their science objectives, instrument capabilities, technology, team composition, budget, funding sources, and the other programattic elements required to implement this potentially revolutionary new class of mission.

The Iodine Satellite (iSat) Project Development Towards Critical Design Review (CDR)

Science.gov (United States)

Dankanich, John W.; Selby, Michael; Polzin, Kurt A.; Kamhawi, Hani; Hickman, Tyler; Byrne, Larry

2016-01-01

Despite the prevalence of Small Satellites in recent years, the systems flown to date have very limited propulsion capability. SmallSats are typically secondary payloads and have significant constraints for volume, mass, and power in addition to limitations on the use of hazardous propellants or stored energy (i.e. high pressure vessels). These constraints limit the options for SmallSat maneuverability. NASA's Space Technology Mission Directorate approved the iodine Satellite flight project for a rapid demonstration of iodine Hall thruster technology in a 12U configuration under the Small Spacecraft Technology Program. The project formally began in FY15 as a partnership between NASA MSFC, NASA GRC, and Busek Co, Inc., with the Air Force supporting the propulsion technology maturation. The team is in final preparation of the Critical Design Review prior to initiating the fabrication and integration phase of the project. The iSat project is on schedule for a launch opportunity in November 2017.

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

Directory of Open Access Journals (Sweden)

Sercarz Eli E

2011-07-01

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

Effects of Aging and Oxidative Stress on Spermatozoa of Superoxide-Dismutase 1- and Catalase-Null Mice.

Science.gov (United States)

Selvaratnam, Johanna S; Robaire, Bernard

2016-09-01

Advanced paternal age is linked to complications in pregnancy and genetic diseases in offspring. Aging results in excess reactive oxygen species (ROS) and DNA damage in spermatozoa; this damage can be transmitted to progeny with detrimental consequences. Although there is a loss of antioxidants with aging, the impact on aging male germ cells of the complete absence of either catalase (CAT) or superoxide dismutase 1 (SOD1) has not been investigated. We used CAT-null (Cat(-/-)) and SOD1-null (Sod(-/-)) mice to determine whether loss of these antioxidants increases germ cell susceptibility to redox dysfunction with aging. Aging reduced fertility and the numbers of Sertoli and germ cells in all mice. Aged Sod(-/-) mice displayed an increased loss of fertility compared to aged wild-type mice. Treatment with the pro-oxidant SIN-10 increased ROS in spermatocytes of aged wild-type and Sod(-/-) mice, while aged Cat(-/-) mice were able to neutralize this ROS. The antioxidant peroxiredoxin 1 (PRDX1) increased with age in wild-type and Cat(-/-) mice but was consistently low in young and aged Sod(-/-) mice. DNA damage and repair markers (γ-H2AX and 53BP1) were reduced with aging and lower in young Sod(-/-) and Cat(-/-) mice. Colocalization of γ-H2AX and 53BP1 suggested active repair in young wild-type mice but reduced in young Cat(-/-) and in Sod(-/-) mice and with age. Oxidative DNA damage (8-oxodG) increased in young Sod(-/-) mice and with age in all mice. These studies show that aged Sod(-/-) mice display severe redox dysfunction, while wild-type and Cat(-/-) mice have compensatory mechanisms to partially alleviate oxidative stress and reduce age-related DNA damage in spermatozoa. Thus, SOD1 but not CAT is critical to the maintenance of germ cell quality with aging. © 2016 by the Society for the Study of Reproduction, Inc.

SATS 14

DEFF Research Database (Denmark)

Frølunde, Lisbeth; Andreasen, Lars Birch; Hansen, Susanne Pihl

SATS14 projektet har drejet sig om at undersøge mulighederne i at kunne tilbyde en særlig indsats til de produktionsskoleelever, der har brug for det, så vidt muligt lokalt på deres skole. Projektets formål har været at indhente erfaringer med at tilbyde elever på 14 produktionsskoler på Sjælland...... mål. SATS14 kan dermed ses i en større social sammenhæng. Der er en stigende erkendelse af behovet for initiativer til at hjælpe de elever, der oplever psykiske vanskeligheder. I forordet til en rapport fra Undervisningsministeriet om erhvervsuddannelser beskrives målet: ”95 procent af en...... ungdomsårgang i 2015 skal gennemføre en ungdomsuddannelse… For at opfylde regeringens mål… er det nødvendigt med en særlig indsats for at fastholde de unge, som begynder i en uddannelse, herunder også de bogligt svage” (Kirkegaard og Nielsen, 2008). Da SATS14 projektet startede, var der ikke megen opmærksomhed...

Cardiomyocyte-Restricted Deletion of PPARβ/δ in PPARα-Null Mice Causes Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of Myocardial Fatty Acid Oxidation

Directory of Open Access Journals (Sweden)

Jian Liu

2011-01-01

Full Text Available It is well documented that PPARα and PPARβ/δ share overlapping functions in regulating myocardial lipid metabolism. However, previous studies demonstrated that cardiomyocyte-restricted PPARβ/δ deficiency in mice leads to severe cardiac pathological development, whereas global PPARα knockout shows a benign cardiac phenotype. It is unknown whether a PPARα-null background would alter the pathological development in mice with cardiomyocyte-restricted PPARβ/δ deficiency. In the present study, a mouse model with long-term PPARβ/δ deficiency in PPARα-null background showed a comparably reduced cardiac expression of lipid metabolism to those of single PPAR-deficient mouse models. The PPARα-null background did not rescue or aggravate the cardiac pathological development linked to cardiomyocyte-restricted PPARβ/δ deficiency. Moreover, PPARα-null did not alter the phenotypic development in adult mice with the short-term deletion of PPARβ/δ in their hearts, which showed mitochondrial abnormalities, depressed cardiac performance, and cardiac hypertrophy with attenuated expression of key factors in mitochondrial biogenesis and defense. The present study demonstrates that cardiomyocyte-restricted deletion of PPARβ/δ in PPARα-null mice causes impaired mitochondrial biogenesis and defense, but no further depression of fatty acid oxidation. Therefore, PPARβ/δ is essential for maintaining mitochondrial biogenesis and defense in cardiomyocytes independent of PPARα.

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...

Overview of SAT

International Nuclear Information System (INIS)

Spinney, R.

1995-01-01

The overview of the Systematic Approach to Training (SAT) was presented, with particular emphasis given to the applied model (versus the theoretical model) and to the involvement of plant management. Discussion included the benefits and advantages of applied SAT compared to the conventional approach, (which likely was not systematic in nature). For example, formal structured on-the-job training (OJT) was compared to the traditional ''Come, I show you'' form of OJT. Each of the five phases of SAT - analysis, design, development, implementation, and evaluation - was presented and with a focus on two aspects of SAT. First, SAT is a dynamic continuous not discrete model; and second, two phases are critical to the overall success of SAT implementation - analysis (especially needs analysis) and evaluation (especially feedback). These two phases are absolutely essential to ensure the ''self-correcting'' attribute of the SAT model. Finally, examples of problems that could occur if the SAT model fails or weakens; for instance, if OJT becomes unstructured, or if training materials are not kept current

The Iodine Satellite (iSAT) Hall Thruster Demonstration Mission Concept and Development

Science.gov (United States)

Dankanich, John W.; Polzin, Kurt A.; Calvert, Derek; Kamhawi, Hani

2014-01-01

The use of iodine propellant for Hall thrusters has been studied and proposed by multiple organizations due to the potential mission benefits over xenon. In 2013, NASA Marshall Space Flight Center competitively selected a project for the maturation of an iodine flight operational feed system through the Technology Investment Program. Multiple partnerships and collaborations have allowed the team to expand the scope to include additional mission concept development and risk reduction to support a flight system demonstration, the iodine Satellite (iSAT). The iSAT project was initiated and is progressing towards a technology demonstration mission preliminary design review. The current status of the mission concept development and risk reduction efforts in support of this project is presented.

Induction and persistence of abnormal testicular germ cells following gestational exposure to di-(n-butyl) phthalate in p53-null mice.

Science.gov (United States)

Saffarini, Camelia M; Heger, Nicholas E; Yamasaki, Hideki; Liu, Tao; Hall, Susan J; Boekelheide, Kim

2012-01-01

Phthalate esters are commonly used plasticizers found in many household items, personal care products, and medical devices. Animal studies have shown that in utero exposure to di-(n-butyl) phthalate (DBP) within a critical window during gestation causes male reproductive tract abnormalities resembling testicular dysgenesis syndrome. Our studies utilized p53-deficient mice for their ability to display greater resistance to apoptosis during development. This model was chosen to determine whether multinucleated germ cells (MNG) induced by gestational DBP exposure could survive postnatally and evolve into testicular germ cell cancer. Pregnant dams were exposed to DBP (500 mg/kg/day) by oral gavage from gestational day 12 until birth. Perinatal effects were assessed on gestational day 19 and postnatal days 1, 4, 7, and 10 for the number of MNGs present in control and DBP-treated p53-heterozygous and null animals. As expected, DBP exposure induced MNGs, with greater numbers found in p53-null mice. Additionally, there was a time-dependent decrease in the incidence of MNGs during the early postnatal period. Histologic examination of adult mice exposed in utero to DBP revealed persistence of abnormal germ cells only in DBP-treated p53-null mice, not in p53-heterozygous or wild-type mice. Immunohistochemical staining of perinatal MNGs and adult abnormal germ cells was negative for both octamer-binding protein 3/4 and placental alkaline phosphatase. This unique model identified a role for p53 in the perinatal apoptosis of DBP-induced MNGs and provided insight into the long-term effects of gestational DBP exposure within a p53-null environment.

The Iodine Satellite (iSat) Project Development Towards Critical Design Review

Science.gov (United States)

Dankanich, John W.; Calvert, Derek; Kamhawi, Hani; Hickman, Tyler; Szabo, James; Byrne, Lawrence

2015-01-01

Despite the prevalence of small satellites in recent years, the systems flown to date have very limited propulsion capability. SmallSats are typically secondary payloads and have significant constraints for volume, mass, and power in addition to limitations on the use of hazardous propellants or stored energy. These constraints limit the options for SmallSat maneuverability. NASA's Space Technology Mission Directorate approved the iodine Satellite flight project for a rapid demonstration of iodine Hall thruster technology in a 12U (cubesat units) configuration under the Small Spacecraft Technology Program. The mission is a partnership between NASA MSFC, NASA GRC, and Busek Co, Inc., with the Air Force supporting the propulsion technology maturation. The team is working towards the critical design review in the final design and fabrication phase of the project. The current design shows positive technical performance margins in all areas. The iSat project is planned for launch readiness in the spring of 2017.

iSAT: The Integrated Satellite and Acoustic Telemetry system for tracking marine megafauna

KAUST Repository

De La Torre, Pedro R.

2014-05-01

In this dissertation an innovative technology to study whale sharks, Rhincodon typus is presented. The Integrated Satellite and Acoustic Telemetry project (iSAT) combines underwater acoustic telemetry, autonomous navigation and radio frequency communications into a standalone system. The whale shark, a resident of the Saudi Arabian Red Sea, is the target of the study. The technology presented is designed to help close current gaps in the knowledge of whale shark biology; these are gaps that prohibit the design of optimal conservation strategies. Unfortunately, the various existing tracking technologies each have limitations and are unable to solve all the unanswered questions. Whale shark populations are increasingly threatened by anthropogenic activities such as targeted and indirect fishing pressure, creating an urgent need for better management practices. This dissertation addresses the current state-of-the-art of relevant technologies, including autonomous surface vehicles (ASVs), sensors for research in the ocean and remote monitoring of wild fauna (biotelemetry). iSAT contains components of all of these technologies, but the primary achievement of this dissertation is the development of iSAT’s Acoustic Tracking System (ATS). Underwater, the most efficient way of transmitting energy through long distances is sound. An electronic tag is attached to an animal and works as its acoustic identifier. iSAT’s hydrophone array detects the presence and direction of the acoustic signal generated by the tag. The expected performance, range, and capacity to tell the direction to the tag are explained and compared to the actual measured values. The first operational iSAT ATS is demonstrated. This work represents significant advancement towards a fully autonomous iSAT system. Developments on the power electronics, navigation, renewable energy harvesting, and other modules are included in this research. With the recent integration of digital acquisition systems, i

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.

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

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...

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

Maturation Stage Enamel Malformations in Amtn and Klk4 Null Mice

Science.gov (United States)

Nunez, Stephanie M.; Chun, Yong-Hee P.; Ganss, Bernhard; Hu, Yuanyuan; Richardson, Amelia S; Schmitz, James E.; Fajardo, Roberto; Yang, Jie; Hu, Jan C-C.; Simmer, James P.

2015-01-01

Amelotin (AMTN) and kallikrein-4 (KLK4) are secreted proteins specialized for enamel biomineralization. We characterized enamel from wild-type, Amtn−/−, Klk4−/−, Amtn+/−Klk4+/− and Amtn−/−Klk4−/− mice to gain insights into AMTN and KLK4 functions during amelogenesis. All of the null mice were healthy and fertile. The mandibular incisors in Amtn−/−, Klk4−/− and Amtn−/−Klk4−/− mice were chalky-white and chipped. No abnormalities except in enamel were observed, and no significant differences were detected in enamel thickness or volume, or in rod decussation. Micro-computed tomography (µCT) maximum intensity projections localized the onset of enamel maturation in wild-type incisors distal to the first molar, but mesial to this position in Amtn−/−, Klk4−/− and Amtn−/−Klk4−/− mice, demonstrating a delay in enamel maturation in Amtn−/− incisors. Micro-CT detected significantly reduced enamel mineral density (2.5 and 2.4 gHA/cm3) in the Klk4−/− and Amtn−/−Klk4−/− mice respectively, compared with wild-type enamel (3.1 gHA/cm3). Backscatter scanning electron microscopy showed that mineral density progressively diminished with enamel depth in the Klk4−/− and Amtn−/−Klk4−/− mice. Knoop hardness of Amtn−/− outer enamel was significantly reduced relative to the wild-type and was not as hard as the middle or inner enamel. Klk4−/− enamel hardness was significantly reduced at all levels, but the outer enamel was significantly harder than the inner and middle enamel. Thus the hardness patterns of the Amtn−/− and Klk4−/− mice were distinctly different, while the Amtn−/−Klk4−/− outer enamel was not as hard as in the Amtn−/− and Klk4−/− mice. We conclude that AMTN and KLK4 function independently, but are both necessary for proper enamel maturation. PMID:26620968

Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

Science.gov (United States)

Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

2016-01-01

The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

Directory of Open Access Journals (Sweden)

Sara N. Koenig

2015-03-01

Full Text Available Thoracic aortic aneurysms (TAA are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/−; Nos3−/− mice. Echocardiographic analysis of Notch1+/−; Nos3−/− mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/−; Nos3−/− mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

SmallSat Database

Science.gov (United States)

Petropulos, Dolores; Bittner, David; Murawski, Robert; Golden, Bert

2015-01-01

required. When completed it will interface with the SCENIC environment to allow modeling of smallSats. The SmallSat Relational Database can also be integrated with the SCENIC Simulation modeling system that is currently in development. The SmallSat Relational Database simulation will be of great significance in assisting the NASA SCaN group to understand the impact the smallSats have made which have populated the lower orbit around our mother earth. What I have created and worked on this summer session 2015, is the basis for a tool that will be of value to the NASA SCaN SCENIC Simulation Environment for years to come.

Polymicrobial infection with major periodontal pathogens induced periodontal disease and aortic atherosclerosis in hyperlipidemic ApoE(null mice.

Directory of Open Access Journals (Sweden)

Mercedes F Rivera

Full Text Available Periodontal disease (PD and atherosclerosis are both polymicrobial and multifactorial and although observational studies supported the association, the causative relationship between these two diseases is not yet established. Polymicrobial infection-induced periodontal disease is postulated to accelerate atherosclerotic plaque growth by enhancing atherosclerotic risk factors of orally infected Apolipoprotein E deficient (ApoE(null mice. At 16 weeks of infection, samples of blood, mandible, maxilla, aorta, heart, spleen, and liver were collected, analyzed for bacterial genomic DNA, immune response, inflammation, alveolar bone loss, serum inflammatory marker, atherosclerosis risk factors, and aortic atherosclerosis. PCR analysis of polymicrobial-infected (Porphyromonas gingivalis [P. gingivalis], Treponema denticola [T. denticola], and Tannerella forsythia [T. forsythia] mice resulted in detection of bacterial genomic DNA in oral plaque samples indicating colonization of the oral cavity by all three species. Fluorescent in situ hybridization detected P. gingivalis and T. denticola within gingival tissues of infected mice and morphometric analysis showed an increase in palatal alveolar bone loss (p<0.0001 and intrabony defects suggesting development of periodontal disease in this model. Polymicrobial-infected mice also showed an increase in aortic plaque area (p<0.05 with macrophage accumulation, enhanced serum amyloid A, and increased serum cholesterol and triglycerides. A systemic infection was indicated by the detection of bacterial genomic DNA in the aorta and liver of infected mice and elevated levels of bacterial specific IgG antibodies (p<0.0001. This study was a unique effort to understand the effects of a polymicrobial infection with P. gingivalis, T. denticola and T. forsythia on periodontal disease and associated atherosclerosis in ApoE(null mice.

High Power Radiation Tolerant CubeSat Power System, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — No vendor has yet to provide a radiation tolerant, high efficiency, small Power Management and Distribution module for the SmallSat and CubeSat market yet. Let alone...

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.

Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

Science.gov (United States)

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 field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

Directory of Open Access Journals (Sweden)

Jeffrey B Eells

Full Text Available 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 field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.

Ghrelin is produced in taste cells and ghrelin receptor null mice show reduced taste responsivity to salty (NaCl and sour (citric acid tastants.

Directory of Open Access Journals (Sweden)

Yu-Kyong Shin

2010-09-01

Full Text Available The gustatory system plays a critical role in determining food preferences, food intake and energy balance. The exact mechanisms that fine tune taste sensitivity are currently poorly defined, but it is clear that numerous factors such as efferent input and specific signal transduction cascades are involved.Using immunohistochemical analyses, we show that ghrelin, a hormone classically considered to be an appetite-regulating hormone, is present within the taste buds of the tongue. Prepro-ghrelin, prohormone convertase 1/3 (PC 1/3, ghrelin, its cognate receptor (GHSR, and ghrelin-O-acyltransferase (GOAT , the enzyme that activates ghrelin are expressed in Type I, II, III and IV taste cells of mouse taste buds. In addition, ghrelin and GHSR co-localize in the same taste cells, suggesting that ghrelin works in an autocrine manner in taste cells. To determine a role for ghrelin in modifying taste perception, we performed taste behavioral tests using GHSR null mice. GHSR null mice exhibited significantly reduced taste responsivity to sour (citric acid and salty (sodium chloride tastants.These findings suggest that ghrelin plays a local modulatory role in determining taste bud signaling and function and could be a novel mechanism for the modulation of salty and sour taste responsivity.

Hvorfor lejere bliver sat ud af deres bolig

DEFF Research Database (Denmark)

Nielsen, Torben Heien; Christensen, Gunvor

Antallet af lejere, der bliver sat ud af deres bolig, er steget fra 1499 i 2002 til 2589 i 2006. Lejere kan blive sat ud af deres bolig, hvis de ikke betaler deres husleje til tiden, eller hvis de ikke overholder husordenen det sted de bor. Denne rapport beskriver årsager til, at lejere bliver sat...... ud af deres boliger og baggrunden for stigningen i antallet af udsættelser. desuden beskriver rapporten konsekvenser af en udsættelse og kommer med en række anbefalinger til indsatsområder. Af afgørende betydning for, at lejere bliver sat ud af deres bolig, er lav indkomst, lavt rådighedsbeløb, stor...

Lejere der bliver sat ud af deres bolig

DEFF Research Database (Denmark)

Christensen, Gunvor; Nielsen, Torben Heien

Antallet af lejere, der bliver sat ud af deres bolig, er steget i perioden 2002-06. I 2006 blev 2600 husstande, svarende til 0,1 pct. af samtlige husstande i Danmark, sat ud af deres bolig. Stigningen er især sket i de fem største byer: København, Århus, Odense, Ålborg og Esbjerg. I dette...... skal give viden om, hvilke årsager der er til, at nogle lejere bliver sat ud af deres bolig, og hvorfor der er sket en stigning i antallet af udsættelser. Den endelige afrapportering af undersøgelsen af udsættelser i Danmark vil ske i foråret 2008. Undersøgelsen er finansieret af Socialministeriet....

CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

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Crockett Elahé T

2007-05-01

Full Text Available Abstract Background Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R. P-selectin and the intercellular adhesion molecule (ICAM-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R. Methods Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study. Liver injury was assessed by plasma level of alanine aminotransferase (ALT and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA. Results Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group. Conclusion While ICAM-1 and P

AAV-Mediated Administration of Myostatin Pro-Peptide Mutant in Adult Ldlr Null Mice Reduces Diet-Induced Hepatosteatosis and Arteriosclerosis

Science.gov (United States)

Guo, Wen; Wong, Siu; Bhasin, Shalender

2013-01-01

Genetic disruption of myostatin or its related signaling is known to cause strong protection against diet-induced metabolic disorders. The translational value of these prior findings, however, is dependent on whether such metabolically favorable phenotype can be reproduced when myostatin blockade begins at an adult age. Here, we reported that AAV-mediated delivery of a myostatin pro-peptide D76A mutant in adult mice attenuates the development of hepatic steatosis and arteriosclerosis, two common diet-induced metabolic diseases. A single dose of AAV-D76A in adult Ldlr null mice resulted in sustained expression of myostatin pro-peptide in the liver. Compared to vehicle-treated mice, D76A-treated mice gained similar amount of lean and fat mass when fed a high fat diet. However, D76A-treated mice displayed significantly reduced aortic lesions and liver fat, in association with a reduction in hepatic expression of lipogenic genes and improvement in liver insulin sensitivity. This suggests that muscle and fat may not be the primary targets of treatment under our experimental condition. In support to this argument, we show that myostatin directly up-regulated lipogenic genes and increased fat accumulation in cultured liver cells. We also show that both myostatin and its receptor were abundantly expressed in mouse aorta. Cultured aortic endothelial cells responded to myostatin with a reduction in eNOS phosphorylation and an increase in ICAM-1 and VCAM-1 expression. Conclusions: AAV-mediated expression of myostatin pro-peptide D76A mutant in adult Ldlr null mice sustained metabolic protection without remarkable impacts on body lean and fat mass. Further investigations are needed to determine whether direct impact of myostatin on liver and aortic endothelium may contribute to the related metabolic phenotypes. PMID:23936482

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

Science.gov (United States)

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

2014-03-13

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

Lightweight Flexible Thermal Energy Management Panels for CubeSats, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — In response to significant gaps in advanced thermal control systems onboard CubeSats and SmallSats, and building off of the successful development of space-based...

Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice.

Science.gov (United States)

Sheward, W John; Maywood, Elizabeth S; French, Karen L; Horn, Jacqueline M; Hastings, Michael H; Seckl, Jonathan R; Holmes, Megan C; Harmar, Anthony J

2007-04-18

The master clock driving mammalian circadian rhythms is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained by daily light/dark cycles. SCN lesions abolish circadian rhythms of behavior and result in a loss of synchronized circadian rhythms of clock gene expression in peripheral organs (e.g., the liver) and of hormone secretion (e.g., corticosterone). We examined rhythms of behavior, hepatic clock gene expression, and corticosterone secretion in VPAC2 receptor-null (Vipr2-/-) mice, which lack a functional SCN clock. Unexpectedly, although Vipr2-/- mice lacked robust circadian rhythms of wheel-running activity and corticosterone secretion, hepatic clock gene expression was strongly rhythmic, but advanced in phase compared with that in wild-type mice. The timing of food availability is thought to be an important entrainment signal for circadian clocks outside the SCN. Vipr2-/- mice consumed food significantly earlier in the 24 h cycle than wild-type mice, consistent with the observed timing of peripheral rhythms of circadian gene expression. When restricted to feeding only during the daytime (RF), mice develop rhythms of activity and of corticosterone secretion in anticipation of feeding time, thought to be driven by a food-entrainable circadian oscillator, located outside the SCN. Under RF, mice of both genotypes developed food-anticipatory rhythms of activity and corticosterone secretion, and hepatic gene expression rhythms also became synchronized to the RF stimulus. Thus, food intake is an effective zeitgeber capable of coordinating circadian rhythms of behavior, peripheral clock gene expression, and hormone secretion, even in the absence of a functional SCN clock.

The integrated satellite-acoustic telemetry (iSAT) system for tracking marine megafauna

KAUST Repository

De la Torre, Pedro

2012-10-06

This document describes the integrated satellite-acoustic telemetry (iSAT) system: an autonomous modular system for tracking the movements of large pelagic fish using acoustic telemetry and satellite communications. The sensor platform is described along with the propulsion and navigation systems. An application for tracking the whale shark (Rhincodon typus) in the Red Sea is included along with a discussion of the technical difficulties that such a system faces.

The integrated satellite-acoustic telemetry (iSAT) system for tracking marine megafauna

KAUST Repository

De la Torre, Pedro; Berumen, Michael L.; Salama, Khaled N.; Smith, E. Lloyd

2012-01-01

This document describes the integrated satellite-acoustic telemetry (iSAT) system: an autonomous modular system for tracking the movements of large pelagic fish using acoustic telemetry and satellite communications. The sensor platform is described along with the propulsion and navigation systems. An application for tracking the whale shark (Rhincodon typus) in the Red Sea is included along with a discussion of the technical difficulties that such a system faces.

Test anxiety and performance-avoidance goals explain gender differences in SAT-V, SAT-M, and overall SAT scores.

Science.gov (United States)

Hannon, Brenda

2012-11-01

This study uses analysis of co-variance in order to determine which cognitive/learning (working memory, knowledge integration, epistemic belief of learning) or social/personality factors (test anxiety, performance-avoidance goals) might account for gender differences in SAT-V, SAT-M, and overall SAT scores. The results revealed that none of the cognitive/learning factors accounted for gender differences in SAT performance. However, the social/personality factors of test anxiety and performance-avoidance goals each separately accounted for all of the significant gender differences in SAT-V, SAT-M, and overall SAT performance. Furthermore, when the influences of both of these factors were statistically removed simultaneously, all non-significant gender differences reduced further to become trivial by Cohen's (1988) standards. Taken as a whole, these results suggest that gender differences in SAT-V, SAT-M, and overall SAT performance are a consequence of social/learning factors.

PhoneSat - The Smartphone Nanosatellite

Science.gov (United States)

Westley, Deborah; Yost, Bruce; Petro, Andrew

2013-01-01

PhoneSat 2.4, carried into space on November 19, 2013 aboard a Minotaur I rocket from the Mid-Atlantic Regional Spaceport at NASAs Wallops Flight Facility in Virginia, is the first of the PhoneSat family to use a two-way S-band radio to allow engineers to command the satellite from Earth. This mission also serves as a technology demonstration for a novel attitude determination and control system (ADCS) that establishes and stabilizes the satellites attitude relative to Earth. Unlike the earlier PhoneSats that used a Nexus One, PhoneSat 2.4 uses the Nexus S smartphone, which runs Googles Android operating system, and is made by Samsung Electronics Co., Suwon, So. Korea. The smartphone provides many of the functions needed by the satellite such as a central computer, data memory, ready-made interfaces for communications, navigation and power all pre-assembled in a rugged electronics package.

An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rγnull mice allows HIV replication and development of anti-HIV immune responses.

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Maneesh Singh

Full Text Available Cord blood hematopoietic progenitor cells (CB-HPCs transplanted immunodeficient NOD/LtsZ-scidIL2Rγ(null (NSG and NOD/SCID/IL2Rγ(null (NOG mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials.

Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice.

Science.gov (United States)

Aleksunes, Lauren M; Reisman, Scott A; Yeager, Ronnie L; Goedken, Michael J; Klaassen, Curtis D

2010-04-01

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) induces a battery of cytoprotective genes after oxidative stress. Nrf2 aids in liver regeneration by altering insulin signaling; however, whether Nrf2 participates in hepatic glucose homeostasis is unknown. Compared with wild-type mice, mice lacking Nrf2 (Nrf2-null) have lower basal serum insulin and prolonged hyperglycemia in response to an intraperitoneal glucose challenge. In the present study, blood glucose, serum insulin, urine flow rate, and hepatic expression of glucose-related genes were quantified in male diabetic wild-type and Nrf2-null mice. Type 1 diabetes was induced with a single intraperitoneal dose (200 mg/kg) of streptozotocin (STZ). Histopathology and serum insulin levels confirmed depleted pancreatic beta-cells in STZ-treated mice of both genotypes. Five days after STZ, Nrf2-null mice had higher blood glucose levels than wild-type mice. Nine days after STZ, polyuria occurred in both genotypes with more urine output from Nrf2-null mice (11-fold) than wild-type mice (7-fold). Moreover, STZ-treated Nrf2-null mice had higher levels of serum beta-hydroxybutyrate, triglycerides, and fatty acids 10 days after STZ compared with wild-type mice. STZ reduced hepatic glycogen in both genotypes, with less observed in Nrf2-null mice. Increased urine output and blood glucose in STZ-treated Nrf2-null mice corresponded with enhanced gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase)- and reduced glycolysis (pyruvate kinase)-related mRNA expression in their livers. Furthermore, the Nrf2 activator oltipraz lowered blood glucose in wild-type but not Nrf2-null mice administered STZ. Collectively, these data indicate that the absence of Nrf2 worsens hyperglycemia in type I diabetic mice and Nrf2 may represent a therapeutic target for reducing circulating glucose levels.

Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.

Science.gov (United States)

Noguchi, Fumihito; Nakajima, Takeshi; Inui, Shigeki; Reddy, Janardan K; Itami, Satoshi

2014-01-01

MED1 (Mediator complex subunit 1) is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1(epi-/-)) that develop epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1(epi-/-) and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi-/-) mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1(epi-/-) mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1(epi-/-) keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1(epi-/-) keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1(epi-/-) keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1(epi-/-) keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1(epi-/-) mice. On the other hand, skin wound healing in 6-month-old Med1(epi-/-) mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1(epi-/-) mice, indicating a decreased contribution of hair

Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.

Directory of Open Access Journals (Sweden)

Fumihito Noguchi

Full Text Available MED1 (Mediator complex subunit 1 is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1(epi-/- that develop epidermal hyperplasia. Herein, to investigate the function(s of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1(epi-/- and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi-/- mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1(epi-/- mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1(epi-/- keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1(epi-/- keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1(epi-/- keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1(epi-/- keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1(epi-/- mice. On the other hand, skin wound healing in 6-month-old Med1(epi-/- mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1(epi-/- mice, indicating a decreased contribution of hair

Renoprotective Effects of Vitex megapotamica (Spreng. Moldenke in C57BL/6 LDLr-Null Mice Undergoing High Fat Diet

Directory of Open Access Journals (Sweden)

Valdinei de Oliveira Araújo

2015-01-01

Full Text Available Although Vitex megapotamica (Spreng. Moldenke is used in Brazilian folk medicine as hypolipidemic drug no study has been conducted to evaluate the effects of this species in an experimental model of atherosclerosis. So, the aim of this study was to evaluate the possible renoprotective activity of methanolic extract obtained from Vitex megapotamica (MEVM using C57BL/6 LDLr-null mice submitted to high fat diet (HFD. MEVM was orally administered at doses of 30, 100, and 300 mg/kg, for three weeks, starting from the 2nd week of HFD. Systolic blood pressure (SBP and diuretic activity were measured weekly. At the end of experiments the serum lipids, atherogenic index serum (AIS, oxidative stress, and markers of renal function were determined. HFD induced a significant increase in the systolic blood pressure, dyslipidemia, increase in AIS, and lipid peroxidation accompanied by an important reduction in renal function. Treatment with MEVM was able to prevent increase in SBP, total cholesterol, triglycerides, AIS, urea, and creatinine levels in LDLr-null mice. These effects were accompanied by a significant reduction in oxidative stress and renal injury. The data reported here support the potential of Vitex megapotamica as candidate to be an herbal medicine used in cardiovascular or renal diseases.

Prevention of the disrupted enamel phenotype in Slc4a4-null mice using explant organ culture maintained in a living host kidney capsule.

Directory of Open Access Journals (Sweden)

Xin Wen

Full Text Available Slc4a4-null mice are a model of proximal renal tubular acidosis (pRTA. Slc4a4 encodes the electrogenic sodium base transporter NBCe1 that is involved in transcellular base transport and pH regulation during amelogenesis. Patients with mutations in the SLC4A4 gene and Slc4a4-null mice present with dysplastic enamel, amongst other pathologies. Loss of NBCe1 function leads to local abnormalities in enamel matrix pH regulation. Loss of NBCe1 function also results in systemic acidemic blood pH. Whether local changes in enamel pH and/or a decrease in systemic pH are the cause of the abnormal enamel phenotype is currently unknown. In the present study we addressed this question by explanting fetal wild-type and Slc4a4-null mandibles into healthy host kidney capsules to study enamel formation in the absence of systemic acidemia. Mandibular E11.5 explants from NBCe1-/- mice, maintained in host kidney capsules for 70 days, resulted in teeth with enamel and dentin with morphological and mineralization properties similar to cultured NBCe1+/+ mandibles grown under identical conditions. Ameloblasts express a number of proteins involved in dynamic changes in H+/base transport during amelogenesis. Despite the capacity of ameloblasts to dynamically modulate the local pH of the enamel matrix, at least in the NBCe1-/- mice, the systemic pH also appears to contribute to the enamel phenotype. Extrapolating these data to humans, our findings suggest that in patients with NBCe1 mutations, correction of the systemic metabolic acidosis at a sufficiently early time point may lead to amelioration of enamel abnormalities.

Compound heterozygosity of the functionally null Cdh23(v-ngt) and hypomorphic Cdh23(ahl) alleles leads to early-onset progressive hearing loss in mice.

Science.gov (United States)

Miyasaka, Yuki; Suzuki, Sari; Ohshiba, Yasuhiro; Watanabe, Kei; Sagara, Yoshihiko; Yasuda, Shumpei P; Matsuoka, Kunie; Shitara, Hiroshi; Yonekawa, Hiromichi; Kominami, Ryo; Kikkawa, Yoshiaki

2013-01-01

The waltzer (v) mouse mutant harbors a mutation in Cadherin 23 (Cdh23) and is a model for Usher syndrome type 1D, which is characterized by congenital deafness, vestibular dysfunction, and prepubertal onset of progressive retinitis pigmentosa. In mice, functionally null Cdh23 mutations affect stereociliary morphogenesis and the polarity of both cochlear and vestibular hair cells. In contrast, the murine Cdh23(ahl) allele, which harbors a hypomorphic mutation, causes an increase in susceptibility to age-related hearing loss in many inbred strains. We produced congenic mice by crossing mice carrying the v niigata (Cdh23(v-ngt)) null allele with mice carrying the hypomorphic Cdh23(ahl) allele on the C57BL/6J background, and we then analyzed the animals' balance and hearing phenotypes. Although the Cdh23(v-ngt/ahl) compound heterozygous mice exhibited normal vestibular function, their hearing ability was abnormal: the mice exhibited higher thresholds of auditory brainstem response (ABR) and rapid age-dependent elevation of ABR thresholds compared with Cdh23(ahl/ahl) homozygous mice. We found that the stereocilia developed normally but were progressively disrupted in Cdh23(v-ngt/ahl) mice. In hair cells, CDH23 localizes to the tip links of stereocilia, which are thought to gate the mechanoelectrical transduction channels in hair cells. We hypothesize that the reduction of Cdh23 gene dosage in Cdh23(v-ngt/ahl) mice leads to the degeneration of stereocilia, which consequently reduces tip link tension. These findings indicate that CDH23 plays an important role in the maintenance of tip links during the aging process.

CubeSat Launch Initiative Overview and CubeSat 101

Science.gov (United States)

Higginbotham, Scott

2017-01-01

The National Aeronautics and Space Administration (NASA) recognizes the tremendous potential that CubeSats (very small satellites) have to inexpensively demonstrate advanced technologies, collect scientific data, and enhance student engagement in Science, Technology, Engineering, and Mathematics (STEM). The CubeSat Launch Initiative (CSLI) was created to provide launch opportunities for CubeSats developed by academic institutions, non-profit entities, and NASA centers. This presentation will provide an overview of the CSLI, its benefits, and its results. This presentation will also provide high level CubeSat 101 information for prospective CubeSat developers, describing the development process from concept through mission operations while highlighting key points that developers need to be mindful of.

Sat-Expo 2008: nuovi scenari per i location based services

Directory of Open Access Journals (Sweden)

Gianluca Pititto

2008-03-01

Full Text Available SAT-Expo Europe 2008: new scenarios for Location Based Services From the 27th to the 29th of March, the 14th edition of SAT-Expo Europe 2008 was held in Rome. The exhibition showed some of the latest innovations and initiatives, by italian and european aerospace industries, regarding satellite technologies and satellite applications. Workshops and conference meetings have been organized with industry managers and public administrators around the main topics, while thousands of visitors were visiting stands and meet professionals of the space sector.

Sat-Expo 2008: nuovi scenari per i location based services

Directory of Open Access Journals (Sweden)

Gianluca Pititto

2008-03-01

Full Text Available SAT-Expo Europe 2008: new scenarios for Location Based ServicesFrom the 27th to the 29th of March, the 14th edition of SAT-Expo Europe 2008 was held in Rome. The exhibition showed some of the latest innovations and initiatives, by italian and european aerospace industries, regarding satellite technologies and satellite applications. Workshops and conference meetings have been organized with industry managers and public administrators around the main topics, while thousands of visitors were visiting stands and meet professionals of the space sector.

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

Assessment of benzene-induced hematotoxicity using a human-like hematopoietic lineage in NOD/Shi-scid/IL-2Rγnull mice.

Directory of Open Access Journals (Sweden)

Masayuki Takahashi

Full Text Available Despite recent advancements, it is still difficult to evaluate in vivo responses to toxicants in humans. Development of a system that can mimic the in vivo responses of human cells will enable more accurate health risk assessments. A surrogate human hematopoietic lineage can be established in NOD/Shi-scid/IL-2Rγ(null (NOG mice by transplanting human hematopoietic stem/progenitor cells (Hu-NOG mice. Here, we first evaluated the toxic response of human-like hematopoietic lineage in NOG mice to a representative toxic agent, benzene. Flow cytometric analysis showed that benzene caused a significant decrease in the number of human hematopoietic stem/progenitor cells in the bone marrow and the number of human leukocytes in the peripheral blood and hematopoietic organs. Next, we established chimeric mice by transplanting C57BL/6 mouse-derived bone marrow cells into NOG mice (Mo-NOG mice. A comparison of the degree of benzene-induced hematotoxicity in donor-derived hematopoietic lineage cells within Mo-NOG mice indicated that the toxic response of Hu-NOG mice reflected interspecies differences in susceptibilities to benzene. Responses to the toxic effects of benzene were greater in lymphoid cells than in myeloid cells in Mo-NOG and Hu-NOG mice. These findings suggested that Hu-NOG mice may be a powerful in vivo tool for assessing hematotoxicity in humans, while accounting for interspecies differences.

Wild-type offspring of heterozygous prolactin receptor-null female mice have maladaptive β-cell responses during pregnancy.

Science.gov (United States)

Huang, Carol

2013-03-01

Abstract  β-Cell mass increases during pregnancy in adaptation to the insulin resistance of pregnancy. This increase is accompanied by an increase in β-cell proliferation, a process that requires intact prolactin receptor (Prlr) signalling. Previously, it was found that during pregnancy, heterozygous prolactin receptor-null (Prlr(+/-)) mice had lower number of β-cells, lower serum insulin and higher blood glucose levels than wild-type (Prlr(+/+)) mice. An unexpected observation was that the glucose homeostasis of the experimental mouse depends on the genotype of her mother, such that within the Prlr(+/+) group, the Prlr(+/+) offspring derived from Prlr(+/+) mothers (Prlr(+/+(+/+))) had higher β-cell mass and lower blood glucose than those derived from Prlr(+/-) mothers (Prlr(+/+(+/-))). Pathways that are known to regulate β-cell proliferation during pregnancy include insulin receptor substrate-2, Akt, menin, the serotonin synthetic enzyme tryptophan hydroxylase-1, Forkhead box M1 and Forkhead box D3. The aim of the present study was to determine whether dysregulation in these signalling molecules in the islets could explain the maternal effect on the phenotype of the offspring. It was found that the pregnancy-induced increases in insulin receptor substrate-2 and Akt expression in the islets were attenuated in the Prlr(+/+(+/-)) mice in comparison to the Prlr(+/+(+/+)) mice. The expression of Forkhead box D3, which plays a permissive role for β-cell proliferation during pregnancy, was also lower in the Prlr(+/+(+/-)) mice. In contrast, the pregnancy-induced increases in phospho-Jak2, tryptophan hydroxylase-1 and FoxM1, as well as the pregnancy-associated reduction in menin expression, were comparable between the two groups. There was also no difference in expression levels of genes that regulate insulin synthesis and secretion (i.e. glucose transporter 2, glucokinase and pancreatic and duodenal homeobox-1) between these two groups. Taken together, these

types sat 1 and sat 2 in bhk, bk, vero and lk cell

African Journals Online (AJOL)

BSN

i\\IATERIALS AND i\\IETllODS. Viruses: 1\\ total or 14 F~~[) ,·1rus isolates \\\\l'l"L' used. I hesc include. :\\ig I 9..J ..... CELLS LOG TCI. DR50. 3.24. 119 ... 3.4 1. 4.25. 4.56. 5.25. 4.38. ·---. --I. I. TABLE IV: TITRE OF SOME SAT 2 STRAINS OF F\\1D IN BTY urns AND BHK - 21. CELLS. VIRUS STRAINS TITRE IN BTY. 1 l"IRE 11 IBRS ...

Aerobic Training Prevents Heatstrokes in Calsequestrin-1 Knockout Mice by Reducing Oxidative Stress

Directory of Open Access Journals (Sweden)

Flávia Alessandra Guarnier

2018-01-01

Full Text Available Calsequestrin-1 knockout (CASQ1-null mice suffer lethal episodes when exposed to strenuous exercise and environmental heat, crises known as exertional/environmental heatstroke (EHS. We previously demonstrated that administration of exogenous antioxidants (N-acetylcysteine and trolox reduces CASQ1-null mortality during exposure to heat. As aerobic training is known to boost endogenous antioxidant protection, we subjected CASQ1-null mice to treadmill running for 2 months at 60% of their maximal speed for 1 h, 5 times/week. When exposed to heat stress protocol (41°C/1 h, the mortality rate of CASQ1-null mice was significantly reduced compared to untrained animals (86% versus 16%. Protection from heatstrokes was accompanied by a reduced increase in core temperature during the stress protocol and by an increased threshold of response to caffeine of isolated extensor digitorum longus muscles during in vitro contracture test. At cellular and molecular levels, aerobic training (i improved mitochondrial function while reducing their damage and (ii lowered calpain activity and lipid peroxidation in membranes isolated from sarcoplasmic reticulum and mitochondria. Based on this evidence, we hypothesize that the protective effect of aerobic training is essentially mediated by a reduction in oxidative stress during exposure of CASQ1-null mice to adverse environmental conditions.

Rad-hard Smallsat / CubeSat Avionics Board, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — VORAGO will design a rad-hard Smallsat / CubeSat Avionics single board that has the necessary robustness needed for long duration missions in harsh mission...

Optical Intersatellite Communications for CubeSat Swarms, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — The growing interest in CubeSat swarm and constellation systems by NASA, the Department of Defense and commercial ventures has created a need for self-managed...

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

Science.gov (United States)

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

2016-01-01

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

Comparative study on 2,2′,4,5,5′-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice

Energy Technology Data Exchange (ETDEWEB)

Kato, Yoshihisa, E-mail: kato@kph.bunri-u.ac.jp [Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa 769-2193 (Japan); Tamaki, Sekihiro [School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526 (Japan); Haraguchi, Koichi [Daiichi College of Pharmaceutical Sciences, Fukuoka 815-8511 (Japan); Ikushiro, Shin-ichi [Faculty of Engineering, Toyama Prefectural University, Toyama 939-0398 (Japan); Sekimoto, Masashi [School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526 (Japan); Ohta, Chiho [Faculty of Nutritional Sciences, Nakamura Gakuen University, Fukuoka 814-0198 (Japan); Endo, Tetsuya [Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Hokkaido 061-0293 (Japan); Koga, Nobuyuki [Faculty of Nutritional Sciences, Nakamura Gakuen University, Fukuoka 814-0198 (Japan); Yamada, Shizuo; Degawa, Masakuni [School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526 (Japan)

2012-09-15

The relationships between the changes in the levels of serum total thyroxine (T{sub 4}), serum T{sub 4}-transthyretin (TTR) complex, and accumulation of T{sub 4} in tissues by 2,2′,4,5,5′-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T{sub 4} was much higher in WT mice than in TTR-null mice. In WT mice 4 days after a single intraperitoneal injection with PentaCB (112 mg/kg), serum total T{sub 4} level was significantly decreased along with a decrease in serum T{sub 4}–TTR complex, and the levels of serum total T{sub 4} in the PentaCB-treated WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T{sub 4} by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [{sup 125}I]T{sub 4} from the serum after [{sup 125}I]T{sub 4}-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [{sup 125}I]T{sub 4} in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [{sup 125}I]T{sub 4} and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T{sub 4} level occurs mainly through increase in accumulation level of T{sub 4} in the liver and further indicate that the increased accumulation of T{sub 4} in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T{sub 4}–TTR complex formation.

CubeSat Communications Research Competes in NASA iTech

OpenAIRE

Ehrlich, Michael; Imbukwa, Khaboshi

2017-01-01

News Stories Archive Research into how small satellites, known as CubeSats, communicate with each other and the Earth performed by a team of researchers in the Naval Postgraduate School's (NPS) Space Systems Academic Group...

Collagen VI Null Mice as a Model for Early Onset Muscle Decline in Aging

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Daniele Capitanio

2017-10-01

Full Text Available Collagen VI is an extracellular matrix (ECM protein playing a key role in skeletal muscles and whose deficiency leads to connective tissue diseases in humans and in animal models. However, most studies have been focused on skeletal muscle features. We performed an extensive proteomic profiling in two skeletal muscles (diaphragm and gastrocnemius of wild-type and collagen VI null (Col6a1−/− mice at different ages, from 6- (adult to 12- (aged month-old to 24 (old month-old. While in wild-type animals the number of proteins and the level of modification occurring during aging were comparable in the two analyzed muscles, Col6a1−/− mice displayed a number of muscle-type specific variations. In particular, gastrocnemius displayed a limited number of dysregulated proteins in adult mice, while in aged muscles the modifications were more pronounced in terms of number and level. In diaphragm, the differences displayed by 6-month-old Col6a1−/− mice were more pronounced compared to wild-type mice and persisted at 12 months of age. In adult Col6a1−/− mice, the major variations were found in the enzymes belonging to the glycolytic pathway and the tricarboxylic acid (TCA cycle, as well as in autophagy-related proteins. When compared to wild-type animals Col6a1−/− mice displayed a general metabolic rewiring which was particularly prominent the diaphragm at 6 months of age. Comparison of the proteomic features and the molecular analysis of metabolic and autophagic pathways in adult and aged Col6a1−/− diaphragm indicated that the effects of aging, culminating in lipotoxicity and autophagic impairment, were already present at 6 months of age. Conversely, the effects of aging in Col6a1−/− gastrocnemius were similar but delayed becoming apparent at 12 months of age. A similar metabolic rewiring and autophagic impairment was found in the diaphragm of 24-month-old wild-type mice, confirming that fatty acid synthase (FASN increment and

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.

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

Mass loss of Greenland from GRACE, IceSat and CryoSat

DEFF Research Database (Denmark)

Forsberg, René; Sørensen, Louise Sandberg; Fredenslund Levinsen, Joanna

2013-01-01

CryoSat data over the Greenland Ice Sheet are used to continue elevation height change data over the Greenland ice sheet, following a decade of detailed monitoring of ice sheet changes with GRACE and IceSat. The combination and validation of the different data for measuring changes is quantified...... by using available airborne lidar data from IceBridge and CryoVEx. There is a special challenge of using CryoSat as fill-in between EnviSat and Sentinel-3 for the longterm measurements of surface elevation changes, a key essential climate variable in the ESA Climate Change Initiative. Another challenge...... is the joint utilization of both altimetry and gravity field change measurements for consistent estimates of regional change patterns. In the paper we analyze GRACE, IceSat and CryoSat data since 2003, and present consistent estimates of overall mass changes with average values around -220 GT/year, showing...

PhoneSat

Data.gov (United States)

National Aeronautics and Space Administration — The PhoneSat series of missions demonstrated the use of a commercial mobile phone as an on-board computer for CubeSats. The project also demonstrated the...

DRG-based CubeSat Inertial Reference Unit (DCIRU), Phase I

Data.gov (United States)

National Aeronautics and Space Administration — CubeSats currently lack adequate inertial attitude knowledge and control required for future sophisticated science missions. Boeing?s Disc Resonator Gyro (DRG)...

CubeSat evolution: Analyzing CubeSat capabilities for conducting science missions

Science.gov (United States)

Poghosyan, Armen; Golkar, Alessandro

2017-01-01

Traditionally, the space industry produced large and sophisticated spacecraft handcrafted by large teams of engineers and budgets within the reach of only a few large government-backed institutions. However, over the last decade, the space industry experienced an increased interest towards smaller missions and recent advances in commercial-off-the-shelf (COTS) technology miniaturization spurred the development of small spacecraft missions based on the CubeSat standard. CubeSats were initially envisioned primarily as educational tools or low cost technology demonstration platforms that could be developed and launched within one or two years. Recently, however, more advanced CubeSat missions have been developed and proposed, indicating that CubeSats clearly started to transition from being solely educational and technology demonstration platforms to offer opportunities for low-cost real science missions with potential high value in terms of science return and commercial revenue. Despite the significant progress made in CubeSat research and development over the last decade, some fundamental questions still habitually arise about the CubeSat capabilities, limitations, and ultimately about their scientific and commercial value. The main objective of this review is to evaluate the state of the art CubeSat capabilities with a special focus on advanced scientific missions and a goal of assessing the potential of CubeSat platforms as capable spacecraft. A total of over 1200 launched and proposed missions have been analyzed from various sources including peer-reviewed journal publications, conference proceedings, mission webpages as well as other publicly available satellite databases and about 130 relatively high performance missions were downselected and categorized into six groups based on the primary mission objectives including "Earth Science and Spaceborne Applications", "Deep Space Exploration", "Heliophysics: Space Weather", "Astrophysics", "Spaceborne In Situ

High-Strain Composite Deployable Radiators for CubeSats, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — In response to NASA's need for compact, lightweight and efficient, low-cost deployable radiators for CubeSats, Roccor proposes to develop a high-strain laminate...

Polymicrobial Oral Infection with Four Periodontal Bacteria Orchestrates a Distinct Inflammatory Response and Atherosclerosis in ApoE null Mice.

Science.gov (United States)

Chukkapalli, Sasanka S; Velsko, Irina M; Rivera-Kweh, Mercedes F; Zheng, Donghang; Lucas, Alexandra R; Kesavalu, Lakshmyya

2015-01-01

Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). To investigate how a polybacterial microbiome infection influences atherosclerotic plaque progression, we infected the oral cavity of ApoE null mice with a polybacterial consortium of 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia and Fusobacterium nucleatum, that have been identified in human atherosclerotic plaque by DNA screening. We assessed periodontal disease characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Polybacterial infections have established gingival colonization in ApoE null hyperlipidemic mice and displayed invasive characteristics with hematogenous dissemination into cardiovascular tissues such as the heart and aorta. Polybacterial infection induced significantly higher levels of serum risk factors oxidized LDL (p Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules. This study demonstrates unique differences in the host immune response to a polybacterial periodontal infection with atherosclerotic lesion progression in a mouse model.

SAT project introduction: management issues

International Nuclear Information System (INIS)

Kazennov, A.Yu.

1998-01-01

Management issues of introducing SAT Project include main objectives and expectations; SAT goal and management; major phases of SAT implementation; project quality assurance; SAT based training system and procedures; role of the project team qualifications

Absence of Wip1 partially rescues Atm deficiency phenotypes in mice

Science.gov (United States)

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

2011-01-01

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

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

Science.gov (United States)

Tsokas, Panayiotis; Hsieh, Changchi; Yao, Yudong; Lesburguères, Edith; Wallace, Emma Jane Claire; Tcherepanov, Andrew; Jothianandan, Desingarao; Hartley, Benjamin Rush; Pan, Ling; Rivard, Bruno; Farese, Robert V; Sajan, Mini P; Bergold, Peter John; Hernández, Alejandro Iván; Cottrell, James E; Shouval, Harel Z; Fenton, André Antonio; Sacktor, Todd Charlton

2016-05-17

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

The achievement gap: Should we rely on SAT scores to tell us anything about it?

Directory of Open Access Journals (Sweden)

Dale Whittington

2004-04-01

Full Text Available Increasing numbers of students taking the SAT have declined to identify their race/ethnicity. I examined the impact of non-respondents on the validity of reported racial/ethnic differences and year-to-year changes in test performance. Using an analysis reported by Wainer (1988 and SAT data from 1996 to 2003, I confirmed Wainer’s findings that non-respondents prevent accurate estimations of group differences based on SAT data. I then explored the impact of College Board press release information on news reports about the achievement gap. I found frequent reports of racial/ethnic differences in SAT scores and year-to-year changes in scores but negligible consideration of non-respondents. Press releases and media reports should include information about non-respondents and their impact on accuracy of reported differences based on race/ethnicity.

Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice

Directory of Open Access Journals (Sweden)

Brigitte Picard

2016-05-01

Full Text Available Hsp27—encoded by HspB1—is a member of the small heat shock proteins (sHsp, 12–43 kDa (kilodalton family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse. Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1-null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1, contraction (TnnT3, energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1 and the Hsp proteins family (HspA9. These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps.

iPLA2β deficiency attenuates obesity and hepatic steatosis in ob/ob mice through hepatic fatty-acyl phospholipid remodeling.

Science.gov (United States)

Deng, Xiuling; Wang, Jiliang; Jiao, Li; Utaipan, Tanyarath; Tuma-Kellner, Sabine; Schmitz, Gerd; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

2016-05-01

PLA2G6 or GVIA calcium-independent PLA2 (iPLA2β) is identified as one of the NAFLD modifier genes in humans, and thought to be a target for NAFLD therapy. iPLA2β is known to play a house-keeping role in phospholipid metabolism and remodeling. However, its role in NAFLD pathogenesis has not been supported by results obtained from high-fat feeding of iPLA2β-null (PKO) mice. Unlike livers of human NAFLD and genetically obese rodents, fatty liver induced by high-fat diet is not associated with depletion of hepatic phospholipids. We therefore tested whether iPLA2β could regulate obesity and hepatic steatosis in leptin-deficient mice by cross-breeding PKO with ob/ob mice to generate ob/ob-PKO mice. Here we observed an improvement in ob/ob-PKO mice with significant reduction in serum enzymes, lipids, glucose, insulin as well as improved glucose tolerance, and reduction in islet hyperplasia. The improvement in hepatic steatosis measured by liver triglycerides, fatty acids and cholesterol esters was associated with decreased expression of PPARγ and de novo lipogenesis genes, and the reversal of β-oxidation gene expression. Notably, ob/ob livers contained depleted levels of lysophospholipids and phospholipids, and iPLA2β deficiency in ob/ob-PKO livers lowers the former, but replenished the latter particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC) that contained arachidonic (AA) and docosahexaenoic (DHA) acids. Compared with WT livers, PKO livers also contained increased PE and PC containing AA and DHA. Thus, iPLA2β deficiency protected against obesity and ob/ob fatty liver which was associated with hepatic fatty-acyl phospholipid remodeling. Our results support the deleterious role of iPLA2β in severe obesity associated NAFLD. Copyright © 2016 Elsevier B.V. All rights reserved.

Restoration of Lepr in β cells of Lepr null mice does not prevent hyperinsulinemia and hyperglycemia

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Anna M. D'souza

2017-06-01

Full Text Available Objective: The adipose-derived hormone leptin plays an important role in regulating body weight and glucose homeostasis. Leptin receptors are expressed in the central nervous system as well as peripheral tissues involved in regulating glucose homeostasis, including insulin-producing β cells of the pancreas. Previous studies assessing the role of leptin receptors in β cells used Cre-loxP to disrupt the leptin receptor gene (Lepr in β cells, but variable results were obtained. Furthermore, recombination of Lepr was observed in the hypothalamus or exocrine pancreas, in addition to the β cells, and Lepr in non-β cells may have compensated for the loss of Lepr in β cells, thus making it difficult to assess the direct effects of Lepr in β cells. To determine the significance of Lepr exclusively in β cells, we chose to selectively restore Lepr in β cells of Lepr null mice (LeprloxTB/loxTB. Materials and methods: We used a mouse model in which endogenous expression of Lepr was disrupted by a loxP-flanked transcription blocker (LeprloxTB/loxTB, but was restored by Cre recombinase knocked into the Ins1 gene, which is specifically expressed in β cells (Ins1Cre. We bred LeprloxTB/loxTB and Ins1Cre mice to generate LeprloxTB/loxTB and LeprloxTB/loxTB Ins1Cre mice, as well as Leprwt/wt and Leprwt/wt Ins1Cre littermate mice. Male and female mice were weighed weekly between 6 and 11 weeks of age and fasting blood glucose was measured during this time. Oral glucose was administered to mice aged 7–12 weeks to assess glucose tolerance and insulin secretion. Relative β and α cell area and islet size were also assessed by immunostaining and analysis of pancreas sections of 12–14 week old mice. Results: Male and female LeprloxTB/loxTB mice, lacking whole-body expression of Lepr, had a phenotype similar to db/db mice characterized by obesity, hyperinsulinemia, glucose intolerance, and impaired glucose stimulated insulin secretion. Despite restoring

EMK protein kinase-null mice: dwarfism and hypofertility associated with alterations in the somatotrope and prolactin pathways.

Science.gov (United States)

Bessone, S; Vidal, F; Le Bouc, Y; Epelbaum, J; Bluet-Pajot, M T; Darmon, M

1999-10-01

Gene trapping was used in embryonic stem (ES) cells in an attempt to inactivate genes involved in development. The Emk (ELKL motif kinase) gene has been disrupted and a mutant mouse line derived. Previous work had shown that EMK kinases, called MARK in the rat, exert a major control on microtubule stability by phosphorylating microtubule-associated proteins and that genes homologous to Emk in yeast or Caenorhabditis elegans are essential for cell and embryonic polarity. Although we found the Emk gene to be active in the preimplantation mouse embryo and then to show a widespread expression, Emk-null mice had no embryonic defect and were viable. They show an overall proportionate dwarfism and a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are fertile in other types of crosses. Insulin-like growth factor I (IGF I) and IGF-binding protein 3 (IGFBP3) were reduced in the plasma of homozygotes of both sexes. A direct implication of the EMK kinase in IGF I plasmatic production is unlikely because the Emk gene does not seem to be expressed in hepatocytes. Nevertheless, GH assayed at arbitrary times in plasma did not show differences between genotypes and GH concentrations in pituitary extracts were not found to be altered in homozygotes. Our results, though, do not exclude the possibility that in the mutants the overall quantity of GH secreted daily is reduced. Our observation of a smaller size of the pituitaries of the mutants is in favor of this hypothesis. The prolactin concentration in the pituitaries was much lowered in homozygous females, but it was normal in males. The possible involvement of EMK protein kinase in hormone secretion in the pituitary and/or the hypothalamus, via the microtubule network, is discussed. Copyright 1999 Academic Press.

Modified Ionic Liquids for Thermal Properties in CubeSats, Phase I

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National Aeronautics and Space Administration — NASA desires new phase change systems to regulate heat transfer among components within a CubeSat small spacecraft. The temperature variation within the small...

Impaired cutaneous wound healing in mice lacking tetranectin

DEFF Research Database (Denmark)

Iba, Kousuke; Hatakeyama, Naoko; Kojima, Takashi

2009-01-01

disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin-null mice compared with wild-type mice. A single full-thickness incision was made in the dorsal skin. By 14 days after the incision......, the wounds fully healed in all wild-type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild-type mice showed complete reepithelialization and healed by 14 days after the incision....... However, those of tetranectin-null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process....

Role of CYP2B in Phenobarbital-Induced Hepatocyte Proliferation in Mice.

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Li, Lei; Bao, Xiaochen; Zhang, Qing-Yu; Negishi, Masahiko; Ding, Xinxin

2017-08-01

Phenobarbital (PB) promotes liver tumorigenesis in rodents, in part through activation of the constitutive androstane receptor (CAR) and the consequent changes in hepatic gene expression and increases in hepatocyte proliferation. A typical effect of CAR activation by PB is a marked induction of Cyp2b10 expression in the liver; the latter has been suspected to be vital for PB-induced hepatocellular proliferation. This hypothesis was tested here by using a Cyp2a(4/5)bgs -null (null) mouse model in which all Cyp2b genes are deleted. Adult male and female wild-type (WT) and null mice were treated intraperitoneally with PB at 50 mg/kg once daily for 5 successive days and tested on day 6. The liver-to-body weight ratio, an indicator of liver hypertrophy, was increased by 47% in male WT mice, but by only 22% in male Cyp2a(4/5)bgs -null mice, by the PB treatment. The fractions of bromodeoxyuridine-positive hepatocyte nuclei, assessed as a measure of the rate of hepatocyte proliferation, were also significantly lower in PB-treated male null mice compared with PB-treated male WT mice. However, whereas few proliferating hepatocytes were detected in saline-treated mice, many proliferating hepatocytes were still detected in PB-treated male null mice. In contrast, female WT mice were much less sensitive than male WT mice to PB-induced hepatocyte proliferation, and PB-treated female WT and PB-treated female null mice did not show significant difference in rates of hepatocyte proliferation. These results indicate that CYP2B induction plays a significant, but partial, role in PB-induced hepatocyte proliferation in male mice. U.S. Government work not protected by U.S. copyright.

Antibody repertoires in humanized NOD-scid-IL2Rγ(null mice and human B cells reveals human-like diversification and tolerance checkpoints in the mouse.

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Gregory C Ippolito

Full Text Available Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγ(null engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH and light (IGK and IGL genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγ(null mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3 repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential D(H-J(H pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by

Modular NanoSat Launcher Design for Lowest Mission Cost, Phase I

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National Aeronautics and Space Administration — As minimum cost will be required for a dedicated NanoSat Launch Vehicle, a series and parallel staged, highly modular vehicle architecture is proposed for design...

TechEdSat

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National Aeronautics and Space Administration — TechEdSat is a 1U CubeSat built by San Jose State University in partnership with NASA Ames Research Center and AAC Microtec. Its mission is to evaluate Space...

Regulatory point of view of SAT application

International Nuclear Information System (INIS)

Juhasz, L.

2002-01-01

I present the regulatory system for monitoring operator training and check competency of operator personnel in Hungary and the effects of SAT to the regulatory framework/practice related to recruitment, training and authorisation of operating personnel. Also I introduce an application to manage the initial and refreshing training to regulatory bodies. (author)

SAT administrator

International Nuclear Information System (INIS)

Havas, A.

1998-01-01

SAT Administrator is the Information System for Nuclear Power Plant Personnel Training Program Design. It supports the design of training programs in the following phases: job analysis; task analysis; competency analysis; task competency association; definition of learning objectives to competencies; training program design; definition of test items. The general structure of the database and management software supports application of the SAT Administrator in any nuclear power installation

End of mission report on sat-based personnel training for nuclear power plants

International Nuclear Information System (INIS)

Billard, P.; Gonzalez, M.; Kazennov, A.; Lecuyer, F.; Spinney, R.; Youjakov, A.

1995-01-01

The overview of the Systematic Approach to Training (SAT) was presented, with particular emphasis given to the applied model (versus the theoretical model) and to the involvement of plant management. Discussion included the benefits and advantages of applied SAT compared to the conventional approach, (which likely was not systematic in nature). For example, formal structured on-the-job training (OJT) was compared to the traditional ''Come, I show you'' form of OJT. Each of the five phases of SAT - analysis, design, development, implementation, and evaluation - was presented and with a focus on two aspects of SAT. First, SAT is a dynamic continuous not discrete model; and second, two phases are critical to the overall success of SAT implementation - analysis (especially needs analysis) and evaluation (especially feedback). These two phases are absolutely essential to ensure the ''self-correcting'' attribute of the SAT model. Finally, examples of problems that could occur if the SAT model fails or weakens; for instance, if OJT becomes unstructured, or if training materials are not kept current

BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice.

Science.gov (United States)

Xu, Guogang; Vogel, Kristine S; McMahan, C Alex; Herbert, Damon C; Walter, Christi A

2010-12-01

During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax-null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wild-type mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis.

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...

Sensorimotor Gating in Neurotensin-1 Receptor Null Mice

Science.gov (United States)

Feifel, D.; Pang, Z.; Shilling, P.D.; Melendez, G.; Schreiber, R.; Button, D.

2009-01-01

BACKGROUND Converging evidence has implicated endogenous neurotensin (NT) in the pathophysiology of brain processes relevant to schizophrenia. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating and considered to be of strong relevance to neuropsychiatric disorders associated with psychosis and cognitive dysfunction. Mice genetically engineered to not express NT display deficits in PPI that model the PPI deficits seen in schizophrenia patients. NT1 receptors have been most strongly implicated in mediating the psychosis relevant effects of NT such as attenuating PPI deficits. To investigate the role of NT1 receptors in the regulation of PPI, we measured baseline PPI in wildtype (WT) and NT1 knockout (KO) mice. We also tested the effects of amphetamine and dizocilpine, a dopamine agonist and NMDA antagonist, respectively, that reduce PPI as well as the NT1 selective receptor agonist, PD149163, known to increase PPI in rats. METHODS Baseline PPI and acoustic startle response were measured in WT and NT1 knockout KO mice. After baseline testing, mice were tested again after receiving intraperatoneal (IP) saline or one of three doses of amphetamine (1.0, 3.0 and 10.0 mg/kg), dizocilpine (0.3, 1.0 and 3.0 mg/kg) and PD149163 (0.5, 2.0 and 6.0 mg/kg) on separate test days. RESULTS Baseline PPI and acoustic startle response in NT1 KO mice were not significantly different from NT1 WT mice. WT and KO mice exhibited similar responses to the PPI-disrupting effects of dizocilpine and amphetamine. PD149163 significantly facilitated PPI (P < 0.004) and decreased the acoustic startle response (P < 0.001) in WT but not NT1 KO mice. CONCLUSIONS The data does not support the regulation of baseline PPI or the PPI disruptive effects of amphetamine or dizocilpine by endogenous NT acting at the NT1 receptor, although they support the antipsychotic potential of pharmacological activation of NT1 receptors by NT1 agonists. PMID:19596359

A novel auditory ossicles membrane and the development of conductive hearing loss in Dmp1-null mice.

Science.gov (United States)

Lv, Kun; Huang, Haiyang; Yi, Xing; Chertoff, Mark E; Li, Chaoyuan; Yuan, Baozhi; Hinton, Robert J; Feng, Jian Q

2017-10-01

Genetic mouse models are widely used for understanding human diseases but we know much less about the anatomical structure of the auditory ossicles in the mouse than we do about human ossicles. Furthermore, current studies have mainly focused on disease conditions such as osteomalacia and rickets in patients with hypophosphatemia rickets, although the reason that these patients develop late-onset hearing loss is unknown. In this study, we first analyzed Dmp1 lac Z knock-in auditory ossicles (in which the blue reporter is used to trace DMP1 expression in osteocytes) using X-gal staining and discovered a novel bony membrane surrounding the mouse malleus. This finding was further confirmed by 3-D micro-CT, X-ray, and alizarin red stained images. We speculate that this unique structure amplifies and facilitates sound wave transmissions in two ways: increasing the contact surface between the eardrum and malleus and accelerating the sound transmission due to its mineral content. Next, we documented a progressive deterioration in the Dmp1-null auditory ossicle structures using multiple imaging techniques. The auditory brainstem response test demonstrated a conductive hearing loss in the adult Dmp1-null mice. This finding may help to explain in part why patients with DMP1 mutations develop late-onset hearing loss, and supports the critical role of DMP1 in maintaining the integrity of the auditory ossicles and its bony membrane. Copyright © 2017 Elsevier Inc. All rights reserved.

High Power CubeSat Control Sub-system (HPoCCS), Phase I

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National Aeronautics and Space Administration — To date, most CubeSat designs have been 6U or smaller and have operated within power budgets in the 10s of W or less. However, as the demand grows for greater...

Kharon1 null mutants of Leishmania mexicana are avirulent in mice and exhibit a cytokinesis defect within macrophages.

Directory of Open Access Journals (Sweden)

Khoa D Tran

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

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

Perception of sweet taste is important for voluntary alcohol consumption in mice.

Science.gov (United States)

Blednov, Y A; Walker, D; Martinez, M; Levine, M; Damak, S; Margolskee, R F

2008-02-01

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.

Integrated CubeSat ADACS with Reaction Wheels and Star Tracker, Phase I

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National Aeronautics and Space Administration — A high performance ADACS (Attitude Determination and Control System) for CubeSats incorporating Miniature Star Trackers is proposed. The proposed program will focus...

KickSat: A Crowd-Funded Technology Demonstration Mission for the Sprite ChipSat

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National Aeronautics and Space Administration — KickSat is a cubesat technology demonstration mission designed to demonstrate the deployment and operation of prototype sprite "ChipSats" (femtosatellites) developed...

CubeSat Launch Initiative

Science.gov (United States)

Higginbotham, Scott

2016-01-01

The National Aeronautics and Space Administration (NASA) recognizes the tremendous potential that CubeSats (very small satellites) have to inexpensively demonstrate advanced technologies, collect scientific data, and enhance student engagement in Science, Technology, Engineering, and Mathematics (STEM). The CubeSat Launch Initiative (CSLI) was created to provide launch opportunities for CubeSats developed by academic institutions, non-profit entities, and NASA centers. This presentation will provide an overview of the CSLI, its benefits, and its results.

PowerCube: Integrated Power, Propulsion, and Pointing for CubeSats, Phase I

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National Aeronautics and Space Administration — Tethers Unlimited, Inc. proposes to develop the PowerCube, an integrated power, propulsion, and pointing solution for CubeSats. The PowerCube combines three...

SmallSat Stirling Cryocooler for Earth Science and Interplanetary Exploration, Phase I

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National Aeronautics and Space Administration — West Coast Solutions (WCS) and the Georgia Institute of Technology, in collaboration with Creare and Micro Cooling Concepts, proposes the development a SmallSat...

Liver-specific rescuing of CEACAM1 reverses endothelial and cardiovascular abnormalities in male mice with null deletion of Ceacam1 gene

Directory of Open Access Journals (Sweden)

Lucia Russo

2018-03-01

Full Text Available Objective: Mice with global null mutation of Ceacam1 (Cc1−/−, display impairment of insulin clearance that causes hyperinsulinemia followed by insulin resistance, elevated hepatic de novo lipogenesis, and visceral obesity. In addition, they manifest abnormal vascular permeability and elevated blood pressure. Liver-specific rescuing of Ceacam1 reversed all of the metabolic abnormalities in Cc1−/−liver+ mice. The current study examined whether Cc1−/− male mice develop endothelial and cardiac dysfunction and whether this relates to the metabolic abnormalities caused by defective insulin extraction. Methods and results: Myography studies showed reduction of agonist-stimulated nitric oxide production in resistance arterioles in Cc1−/−, but not Cc1−/−liver+ mice. Liver-based rescuing of CEACAM1 also attenuated the abnormal endothelial adhesiveness to circulating leukocytes in parallel to reducing plasma endothelin-1 and recovering plasma nitric oxide levels. Echocardiography studies revealed increased septal wall thickness, cardiac hypertrophy and reduced cardiac performance in Cc1−/−, but not Cc1−/−xliver+ mice. Insulin signaling experiments indicated compromised IRS1/Akt/eNOS pathway leading to lower nitric oxide level, and activated Shc/MAPK pathway leading to more endothelin-1 production in the aortae and hearts of Cc1−/−, but not Cc1−/−xliver+ mice. The increase in the ratio of endothelin-1 receptor A/B indicated an imbalance in the vasomotor activity of Cc1−/− mice, which was normalized in Cc1−/−xliver+ mice. Conclusions: The data underscore a critical role for impaired CEACAM1-dependent hepatic insulin clearance pathways and resulting hyperinsulinemia and lipid accumulation in aortae and heart in regulating the cardiovascular function. Keywords: Insulin clearance, Hyperinsulinemia, Insulin resistance, Endothelial function, Cardiomyopathy

CubeSat Ambipolar Thruster for LEO and Deep Space Missions, Phase I

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National Aeronautics and Space Administration — Aether Industries proposes the development of a novel, primary plasma propulsion system that is well suited for small spacecraft. This technology, called the CubeSat...

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

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)

Achilles tendons from decorin- and biglycan-null mouse models have inferior mechanical and structural properties predicted by an image-based empirical damage model.

Science.gov (United States)

Gordon, J A; Freedman, B R; Zuskov, A; Iozzo, R V; Birk, D E; Soslowsky, L J

2015-07-16

Achilles tendons are a common source of pain and injury, and their pathology may originate from aberrant structure function relationships. Small leucine rich proteoglycans (SLRPs) influence mechanical and structural properties in a tendon-specific manner. However, their roles in the Achilles tendon have not been defined. The objective of this study was to evaluate the mechanical and structural differences observed in mouse Achilles tendons lacking class I SLRPs; either decorin or biglycan. In addition, empirical modeling techniques based on mechanical and image-based measures were employed. Achilles tendons from decorin-null (Dcn(-/-)) and biglycan-null (Bgn(-/-)) C57BL/6 female mice (N=102) were used. Each tendon underwent a dynamic mechanical testing protocol including simultaneous polarized light image capture to evaluate both structural and mechanical properties of each Achilles tendon. An empirical damage model was adapted for application to genetic variation and for use with image based structural properties to predict tendon dynamic mechanical properties. We found that Achilles tendons lacking decorin and biglycan had inferior mechanical and structural properties that were age dependent; and that simple empirical models, based on previously described damage models, were predictive of Achilles tendon dynamic modulus in both decorin- and biglycan-null mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rγnull mice

Science.gov (United States)

Singh, Maneesh; Singh, Pratibha; Vaira, Dolores; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

2014-01-01

More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rγnull mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV. PMID:24409837

Back to Basics: Solving Games with SAT

Directory of Open Access Journals (Sweden)

QUER, S.

2016-08-01

Full Text Available Games became popular, within the formal verification community, after their application to automatic synthesis of circuits from specifications, and they have been receiving more and more attention since then. This paper focuses on coding the "Sokoban" puzzle, i.e., a very complex single-player strategy game. We show how its solution can be encoded and represented as a Bounded Model Checking problem, and then solved with a SAT solver. After that, to cope with very complex instances of the game, we propose two different ad-hoc divide-and-conquer strategies. Those strategies, somehow similar to state-of-the-art abstraction-and-refinement schemes, are able to decompose deep Bounded Model Checking instances into easier subtasks, trading-off between efficiency and completeness. We analyze a vast set of difficult hard-to-solve benchmark games, trying to push forward the applicability of state-of-the-art SAT solvers in the field. Those results show that games may provide one of the next frontier for the SAT community.

Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.

Science.gov (United States)

Lukong, Kiven E; Richard, Stéphane

2008-06-03

The role of RNA-binding proteins in the central nervous system and more specifically their role in motor coordination and learning are poorly understood. We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in females. Sam68 however is highly expressed in most regions of the brain especially the cerebellum and thus we investigated the cerebellar-related manifestations in Sam68-null mice. We analyzed the mice for motor function, sensory function, and learning and memory abilities. Herein, we report that Sam68-null mice have motor coordination defects as assessed by beam walking and rotorod performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild-type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in beam walking tests and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls. The Sam68-null mice were, however, normal for forelimb strength, tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion. Our findings support a role for Sam68 in the central nervous system in the regulation of motor coordination.

Propulsion for CubeSats

Science.gov (United States)

Lemmer, Kristina

2017-05-01

At present, very few CubeSats have flown in space featuring propulsion systems. Of those that have, the literature is scattered, published in a variety of formats (conference proceedings, contractor websites, technical notes, and journal articles), and often not available for public release. This paper seeks to collect the relevant publically releasable information in one location. To date, only two missions have featured propulsion systems as part of the technology demonstration. The IMPACT mission from the Aerospace Corporation launched several electrospray thrusters from Massachusetts Institute of Technology, and BricSAT-P from the United States Naval Academy had four micro-Cathode Arc Thrusters from George Washington University. Other than these two missions, propulsion on CubeSats has been used only for attitude control and reaction wheel desaturation via cold gas propulsion systems. As the desired capability of CubeSats increases, and more complex missions are planned, propulsion is required to accomplish the science and engineering objectives. This survey includes propulsion systems that have been designed specifically for the CubeSat platform and systems that fit within CubeSat constraints but were developed for other platforms. Throughout the survey, discussion of flight heritage and results of the mission are included where publicly released information and data have been made available. Major categories of propulsion systems that are in this survey are solar sails, cold gas propulsion, electric propulsion, and chemical propulsion systems. Only systems that have been tested in a laboratory or with some flight history are included.

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

International Nuclear Information System (INIS)

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

1988-01-01

Electrophoretic screening of (C57BL/6J x DBA/2J)F 1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (Ca II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus

Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.

Science.gov (United States)

Maier, Jennifer A; Harfe, Brian D

2011-11-15

The transition of the mouse embryonic notochord into nuclei pulposi was determined ("fate mapped") in vivo in growth and differentiating factor-5 (GDF-5)-null mice using the Shhcre and R26R alleles. To determine whether abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5-null mice. The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5-null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5-null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or result from progressive postnatal degeneration of nuclei pulposi. Gdf-5 messenger RNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5-null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24-week-old mice. Our Gdf-5 messenger RNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate-mapping experiments revealed that notochord cells in Gdf-5-null mice correctly form nuclei pulposi. Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5-null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

International Nuclear Information System (INIS)

Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

2012-01-01

Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver. �

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu

2012-11-01

Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver. �

Increasing brain serotonin corrects CO2 chemosensitivity in methyl-CpG-binding protein 2 (Mecp2)-deficient mice

Science.gov (United States)

Toward, Marie A.; Abdala, Ana P.; Knopp, Sharon J.; Paton, Julian F. R.; Bissonnette, John M.

2013-01-01

Mice deficient in the transcription factor methyl-CpG-binding protein 2 (Mecp2), a mouse model of Rett syndrome, display reduced CO2 chemosensitivity, which may contribute to their breathing abnormalities. In addition, patients with Rett syndrome and male mice that are null for Mecp2 show reduced levels of brain serotonin (5-HT). Serotonin is known to play a role in central chemosensitivity, and we hypothesized that increasing the availability of 5-HT in this mouse model would improve their respiratory response to CO2. Here we determined the apnoeic threshold in heterozygous Mecp2-deficient female mice and examined the effects of blocking 5-HT reuptake on the CO2 response in Mecp2-null male mice. Studies were performed in B6.129P2(C)-Mecp2τm1.1Bird null males and heterozygous females. In an in situ preparation, seven of eight Mecp2-deficient heterozygous females showed arrest of phrenic nerve activity when arterial CO2 was lowered to 3%, whereas the wild-types maintained phrenic nerve amplitude at 53 ± 3% of maximal. In vivo plethysmography studies were used to determine CO2 chemosensitivity in null males. These mice were exposed sequentially to 1, 3 and 5% CO2. The percentage increase in minute ventilation in response to increased inspired CO2 was less in Mecp2−/y than in Mecp2+/y mice. Pretreatment with citalopram, a selective 5-HT reuptake inhibitor (2.5 mg kg−1 I.P.), 40 min prior to CO2 exposure, in Mecp2−/y mice resulted in an improvement in CO2 chemosensitivity to wild-type levels. These results suggest that decreased 5-HT in Mecp2-deficient mice reduces CO2 chemosensitivity, and restoring 5-HT levels can reverse this effect. PMID:23180809

SAT math prep course

CERN Document Server

Kolby, Jeff

2011-01-01

Comprehensive Prep for SAT Math Every year, students pay 1,000 and more to test prep companies to prepare for the math section of the new SAT. Now you can get the same preparation in a book. Features: * Comprehensive Review: Twenty-three chapters provide complete review of SAT math. * Practice: Includes 164 examples and more than 500 exercises! Arranged from easy to medium to hard to very hard. * Diagnostic Test: The diagnostic test measures your strengths and weaknesses and directs you to areas you need to study more. * Performance: If your target is a 700+ score, this is the book!

SHA-1, SAT-solving, and CNF

CSIR Research Space (South Africa)

Motara, YM

2017-09-01

Full Text Available the intersection between the SHA-1 preimage problem, the encoding of that problem for SAT-solving, and SAT-solving. The results demonstrate that SAT-solving is not yet a viable approach to take to solve the preimage problem, and also indicate that some...

SAT projects' effectiveness: managerial aspects

International Nuclear Information System (INIS)

Kazennov, A.; Zlokazov, A.; Kossilov, A.

2003-01-01

Discussion provided below in the text and on the presentation transparencies is based on hands-on experience of SAT projects' implementation which have been or being conducted in several countries, and intended to develop or upgrade NPP personnel training. We will 'risk' to say that no comprehensive system, training system in particular, can work without feedback. A powerful tool to establish a controllability of a training process is to measure (using certain criteria) trainees' performance., training process, employees' qualification, on-job human performance, overall plant performance, and then (using certain algorithms) to provide feedback control to training and the whole organization with clear understanding and grading whether we deal with training-related root causes or not. In this way a training effectiveness may be considered as a feature that shows to what extent training is producing a desired result (e.g. developing needed skills, knowledge and attitudes, enhancing quality, safety and productivity, establishing cost-effective training, etc.). In order to design a training system with the features of feedback control, the SAT projects are implemented. In this respect SAT is more 'systems' rather than 'systematic' approach. Obviously, the criteria to evaluate a training system should be established. SAT implementation may be considered as a corrective action to fix the problems associated with the deficiencies in personnel competence or ineffectiveness of training system. But each corrective action or initiative related to a training system development should be generated and justified through normal process of evaluation and systematic needs analysis. The effectiveness of a training development project shall be evaluated against the overall goal and specific objectives of a project. The ultimate overall goal of SAT project implementation is to develop or upgrade NPP personnel training programmes and the whole training system in order to provide

Sex differences in complex regional pain syndrome type I (CRPS-I) in mice.

Science.gov (United States)

Tang, Chaoliang; Li, Juan; Tai, Wai Lydia; Yao, Weifeng; Zhao, Bo; Hong, Junmou; Shi, Si; Wang, Song; Xia, Zhongyuan

2017-01-01

Sex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I. Chronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines. Both male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion. Our results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS.

Preventive effect of dipeptidyl peptidase-4 inhibitor on atherosclerosis is mainly attributable to incretin's actions in nondiabetic and diabetic apolipoprotein E-null mice.

Directory of Open Access Journals (Sweden)

Michishige Terasaki

Full Text Available AIM: Several recent reports have revealed that dipeptidyl peptidase (DPP-4 inhibitors have suppressive effects on atherosclerosis in apolipoprotein E-null (Apoe (-/- mice. It remains to be seen, however, whether this effect stems from increased levels of the two active incretins, glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic polypeptide (GIP. METHODS: Nontreated Apoe (-/- mice, streptozotocin-induced diabetic Apoe (-/- mice, and db/db diabetic mice were administered the DPP-4 inhibitor vildagliptin in drinking water and co-infused with either saline, the GLP-1 receptor blocker, exendin(9-39, the GIP receptor blocker, (Pro(3GIP, or both via osmotic minipumps for 4 weeks. Aortic atherosclerosis and oxidized low-density lipoprotein-induced foam cell formation in exudate peritoneal macrophages were determined. RESULTS: Vildagliptin increased plasma GLP-1 and GIP levels without affecting food intake, body weight, blood pressure, or plasma lipid profile in any of the animals tested, though it reduced HbA1c in the diabetic mice. Diabetic Apoe (-/- mice exhibited further-progressed atherosclerotic lesions and foam cell formation compared with nondiabetic counterparts. Nondiabetic and diabetic Apoe (-/- mice showed a comparable response to vildagliptin, namely, remarkable suppression of atherosclerotic lesions with macrophage accumulation and foam cell formation in peritoneal macrophages. Exendin(9-39 or (Pro(3GIP partially attenuated the vildagliptin-induced suppression of atherosclerosis. The two blockers in combination abolished the anti-atherosclerotic effect of vildagliptin in nondiabetic mice but only partly attenuated it in diabetic mice. Vildagliptin suppressed macrophage foam cell formation in nondiabetic and diabetic mice, and this suppressive effect was abolished by infusions with exendin(9-39+(Pro(3GIP. Incubation of DPP-4 or vildagliptin in vitro had no effect on macrophage foam cell formation. CONCLUSIONS: Vildagliptin

CarbonSat Constellation

Science.gov (United States)

Sun, Wei; Tobehn, Carsten; Ernst, Robert; Bovensmann, Heinrich; Buchwitz, Michael; Burrows, John P.; Notholt, John

1 Carbon dioxide (CO2) and methane (CH4) are the most important manmade greenhouse gases (GHGs) which are driving global climate change. Currently, the CO2 measurements from the ground observing network are still the main sources of information but due to the limited number of measurement stations the coverage is limited. In addition, CO2 monitoring and trading is often based mainly on bottom-up calculations and an independent top down verification is limited due to the lack of global measurement data with local resolution. The first CO2 and CH4 mapping from SCIAMACHY on ENVISAT shows that satellites add important missing global information. Current GHG measurement satellites (GOSAT)are limited either in spatial or temporal resolution and coverage. These systems have to collect data over a year or even longer to produce global regional fluxes products. Conse-quently global, timely, higher spatial resolution and high accuracy measurement are required for: 1. A good understanding of the CO2 and CH4 sources and sinks for reliable climate predic-tion; and 2. Independent and transparent verification of accountable sources and sinks in supporting Kyoto and upcoming protocols The CarbonSat constellation idea comes out the trade off of resolution and swath width during CarbonSat mission definition studies. In response to the urgent need to support the Kyoto and upcoming protocols, a feasibility study has been carried out. The proposed solution is a constellation of five CarbonSat satellites in 614km LTAN 13:00, which is able to provide global, daily CO2 and CH4 measurement everywhere on the Earth with high spatial resolution 2 × 2 km and low uncertainty lt;2ppm (CO2) and lt;8ppb (CH4). The unique global daily measurement capability significantly increases the number of cloud free measurements, which enables more reliable services associated with reduced uncertainty, e.g. to 0.15ppm (CO2) per month in 10km and even more timely products. The CarbonSat Constellation in

Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6.

Science.gov (United States)

Ladenheim, B; Krasnova, I N; Deng, X; Oyler, J M; Polettini, A; Moran, T H; Huestis, M A; Cadet, J L

2000-12-01

Increasing evidence implicates apoptosis as a major mechanism of cell death in methamphetamine (METH) neurotoxicity. The involvement of a neuroimmune component in apoptotic cell death after injury or chemical damage suggests that cytokines may play a role in METH effects. In the present study, we examined if the absence of IL-6 in knockout (IL-6-/-) mice could provide protection against METH-induced neurotoxicity. Administration of METH resulted in a significant reduction of [(125)I]RTI-121-labeled dopamine transporters in the caudate-putamen (CPu) and cortex as well as depletion of dopamine in the CPu and frontal cortex of wild-type mice. However, these METH-induced effects were significantly attenuated in IL-6-/- animals. METH also caused a decrease in serotonin levels in the CPu and hippocampus of wild-type mice, but no reduction was observed in IL-6-/- animals. Moreover, METH induced decreases in [(125)I]RTI-55-labeled serotonin transporters in the hippocampal CA3 region and in the substantia nigra-reticulata but increases in serotonin transporters in the CPu and cingulate cortex in wild-type animals, all of which were attenuated in IL-6-/- mice. Additionally, METH caused increased gliosis in the CPu and cortices of wild-type mice as measured by [(3)H]PK-11195 binding; this gliotic response was almost completely inhibited in IL-6-/- animals. There was also significant protection against METH-induced DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeled (TUNEL) cells in the cortices. The protective effects against METH toxicity observed in the IL-6-/- mice were not caused by differences in temperature elevation or in METH accumulation in wild-type and mutant animals. Therefore, these observations support the proposition that IL-6 may play an important role in the neurotoxicity of METH.

Pilot study: whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with lipedema.

Science.gov (United States)

Herbst, Karen L; Ussery, Christopher; Eekema, Alyna

2017-09-20

Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

Reduced alcohol consumption in mice lacking preprodynorphin.

Science.gov (United States)

Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

2006-10-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

PhoneSat - The Smartphone Nanosatellite

Science.gov (United States)

Cockrell, James J.; Yost, Bruce; Petro, Andrew

2013-01-01

NASA's PhoneSat project tests whether spacecraft can be built using smartphones to launch the lowest-cost satellites ever flown in space. Each PhoneSat nanosatellite is one cubesat unit - a satellite in a 10 cm (approx. 4 inches) cube or about the size of a tissue box - and weighs approximately 1 kg (2.2 pounds). Engineers believe PhoneSat technology will enable NASA to launch multiple new satellites capable of conducting science and exploration missions at a small fraction of the cost of conventional satellites.

Sats14: Hurtig indsats over for frafaldstruede produktionsskoleelever

DEFF Research Database (Denmark)

Frølunde, Lisbeth; Hansen, Susanne Pihl; Andreasen, Lars Birch

Sats 14 projektet drejede sig om at undersøge mulighederne i lokalt at tilbyde fx psykologbistand, social- eller specialpædagogisk bistand til produktionsskoleelever med særlige behov. Evalueringen fremhæver projektets resultater og vigtigste pointer: at en stor gruppe elever kan blive hjulpet til...

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

Solving SAT problem by heuristic polarity decision-making algorithm

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

This paper presents a heuristic polarity decision-making algorithm for solving Boolean satisfiability (SAT). The algorithm inherits many features of the current state-of-the-art SAT solvers, such as fast BCP, clause recording, restarts, etc. In addition, a preconditioning step that calculates the polarities of variables according to the cover distribution of Karnaugh map is introduced into DPLL procedure, which greatly reduces the number of conflicts in the search process. The proposed approach is implemented as a SAT solver named DiffSat. Experiments show that DiffSat can solve many "real-life" instances in a reasonable time while the best existing SAT solvers, such as Zchaff and MiniSat, cannot. In particular, DiffSat can solve every instance of Bart benchmark suite in less than 0.03 s while Zchaff and MiniSat fail under a 900 s time limit. Furthermore, DiffSat even outperforms the outstanding incomplete algorithm DLM in some instances.

A Study for Optimum Space-to-Ground Communication Concept for CubeSat and SmallSat Platforms

Data.gov (United States)

National Aeronautics and Space Administration — This study is to explore the communication architecture for future space-to-ground CubeSat/SmallSat communication, through simulations, analyses, and identifying...

Massively Clustered CubeSats NCPS Demo Mission

Science.gov (United States)

Robertson, Glen A.; Young, David; Kim, Tony; Houts, Mike

2013-01-01

Technologies under development for the proposed Nuclear Cryogenic Propulsion Stage (NCPS) will require an un-crewed demonstration mission before they can be flight qualified over distances and time frames representative of a crewed Mars mission. In this paper, we describe a Massively Clustered CubeSats platform, possibly comprising hundreds of CubeSats, as the main payload of the NCPS demo mission. This platform would enable a mechanism for cost savings for the demo mission through shared support between NASA and other government agencies as well as leveraged commercial aerospace and academic community involvement. We believe a Massively Clustered CubeSats platform should be an obvious first choice for the NCPS demo mission when one considers that cost and risk of the payload can be spread across many CubeSat customers and that the NCPS demo mission can capitalize on using CubeSats developed by others for its own instrumentation needs. Moreover, a demo mission of the NCPS offers an unprecedented opportunity to invigorate the public on a global scale through direct individual participation coordinated through a web-based collaboration engine. The platform we describe would be capable of delivering CubeSats at various locations along a trajectory toward the primary mission destination, in this case Mars, permitting a variety of potential CubeSat-specific missions. Cameras on various CubeSats can also be used to provide multiple views of the space environment and the NCPS vehicle for video monitoring as well as allow the public to "ride along" as virtual passengers on the mission. This collaborative approach could even initiate a brand new Science, Technology, Engineering and Math (STEM) program for launching student developed CubeSat payloads beyond Low Earth Orbit (LEO) on future deep space technology qualification missions. Keywords: Nuclear Propulsion, NCPS, SLS, Mars, CubeSat.

DebriSat Project Update and Planning

Science.gov (United States)

Sorge, M.; Krisko, P. H.

2016-01-01

DebriSat Reporting Topics: DebriSat Fragment Analysis Calendar; Near-term Fragment Extraction Strategy; Fragment Characterization and Database; HVI (High-Velocity Impact) Considerations; Requirements Document.

Cafesat: A modern sat solver for scala

OpenAIRE

Blanc Régis

2013-01-01

We present CafeSat a SAT solver written in the Scala programming language. CafeSat is a modern solver based on DPLL and featuring many state of the art techniques and heuristics. It uses two watched literals for Boolean constraint propagation conict driven learning along with clause deletion a restarting strategy and the VSIDS heuristics for choosing the branching literal. CafeSat is both sound and complete. In order to achieve reasonable performance low level and hand tuned data structures a...

Integrated monitoring technologies for the management of a Soil-Aquifer-Treatment (SAT) system.

Science.gov (United States)

Papadopoulos, Alexandros; Kallioras, Andreas; Kofakis, Petros; Bumberger, Jan; Schmidt, Felix; Athanasiou, Georgios; Uzunoglou, Nikolaos; Amditis, Angelos; Dietrich, Peter

2016-04-01

Artificial recharge of groundwater has an important role to play in water reuse as treated wastewater effluent can be infiltrated into the ground for aquifer recharge. As the effluent moves through the soil and the aquifer, it undergoes significant quality improvements through physical, chemical, and biological processes in the underground environment. Collectively, these processes and the water quality improvement obtained are called soil-aquifer-treatment (SAT) or geopurification. The pilot site of Lavrion Technological & Cultural Park (LTCP) of the National Technical University of Athens (NTUA), involves the employment of plot infiltration basins at experimental scale, which will be using waters of impaired quality as a recharge source, and hence acting as a Soil-Aquifer-Treatment, SAT, system. Τhe LTCP site will be employed as a pilot SAT system complemented by new technological developments, which will be providing continuous monitoring of the quantitative and qualitative characteristics of infiltrating groundwater through all hydrologic zones (i.e. surface, unsaturated and saturated zone). This will be achieved by the development and installation of an integrated system of prototype sensing technologies, installed on-site, and offering a continuous evaluation of the performance of the SAT system. An integrated approach of the performance evaluation of any operating SAT system should aim at parallel monitoring of all hydrologic zones, proving the sustainability of all involved water quality treatment processes within unsaturated and saturated zone. Hence a prototype system of Time and Frequency Domain Reflectometry (TDR & FDR) sensors is developed and will be installed, in order to achieve continuous quantitative monitoring of the unsaturated zone through the entire soil column down to significant depths below the SAT basin. Additionally, the system contains two different radar-based sensing systems that will be offering (i) identification of preferential

Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo.

Science.gov (United States)

Jurkowska, Halina; Niewiadomski, Julie; Hirschberger, Lawrence L; Roman, Heather B; Mazor, Kevin M; Liu, Xiaojing; Locasale, Jason W; Park, Eunkyue; Stipanuk, Martha H

2016-03-01

The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated in liver of Cdo1-null and Csad-null mice and lowered to wild-type levels by dietary taurine supplementation. The mechanism by which taurine status affects hepatic CSAD and BHMT expression appears to be complex and to require factors outside of hepatocytes. Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation.

The epidermis of grhl3-null mice displays altered lipid processing and cellular hyperproliferation.

Science.gov (United States)

Ting, Stephen B; Caddy, Jacinta; Wilanowski, Tomasz; Auden, Alana; Cunningham, John M; Elias, Peter M; Holleran, Walter M; Jane, Stephen M

2005-04-01

The presence of an impermeable surface barrier is an essential homeostatic mechanism in almost all living organisms. We have recently described a novel gene that is critical for the developmental instruction and repair of the integument in mammals. This gene, Grainy head-like 3 (Grhl3) is a member of a large family of transcription factors that are homologs of the Drosophila developmental gene grainy head (grh). Mice lacking Grhl3 fail to form an adequate skin barrier, and die at birth due to dehydration. These animals are also unable to repair the epidermis, exhibiting failed wound healing in both fetal and adult stages of development. These defects are due, in part, to diminished expression of a Grhl3 target gene, Transglutaminase 1 (TGase 1), which encodes a key enzyme involved in cross-linking of epidermal structural proteins and lipids into the cornified envelope (CE). Remarkably, the Drosophila grh gene plays an analogous role, regulating enzymes involved in the generation of quinones, which are essential for cross-linking structural components of the fly epidermis. In an extension of our initial analyses, we focus this report on additional defects observed in the Grhl3-null epidermis, namely defective extra-cellular lipid processing, altered lamellar lipid architecture and cellular hyperproliferation. These abnormalities suggest that Grhl3 plays diverse mechanistic roles in maintaining homeostasis in the skin.

Enhancing SAT-Based Test Pattern Generation

Institute of Scientific and Technical Information of China (English)

LIU Xin; XIONG You-lun

2005-01-01

This paper presents modeling tools based on Boolean satisfiability (SAT) to solve problems of test generation for combinational circuits. It exploits an added layer to maintain circuit-related information and value justification relations to a generic SAT algorithm. It dovetails binary decision graphs (BDD) and SAT techniques to improve the efficiency of automatic test pattern generation (ATPG). More specifically, it first exploits inexpensive reconvergent fanout analysis of circuit to gather information on the local signal correlation by using BDD learning, then uses the above learned information to restrict and focus the overall search space of SAT-based ATPG. Its learning technique is effective and lightweight. The experimental results demonstrate the effectiveness of the approach.

PhoneSat In-flight Experience Results

Science.gov (United States)

Salas, Alberto Guillen; Attai, Watson; Oyadomari, Ken Y.; Priscal, Cedric; Schimmin, Rogan S.; Gazulla, Oriol Tintore; Wolfe, Jasper L.

2014-01-01

Over the last decade, consumer technology has vastly improved its performances, become more affordable and reduced its size. Modern day smartphones offer capabilities that enable us to figure out where we are, which way we are pointing, observe the world around us, and store and transmit this information to wherever we want. These capabilities are remarkably similar to those required for multi-million dollar satellites. The PhoneSat project at NASA Ames Research Center is building a series of CubeSat-size spacecrafts using an off-the-shelf smartphone as its on-board computer with the goal of showing just how simple and cheap space can be. Since the PhoneSat project started, different suborbital and orbital flight activities have proven the viability of this revolutionary approach. In early 2013, the PhoneSat project launched the first triage of PhoneSats into LEO. In the five day orbital life time, the nano-satellites flew the first functioning smartphone-based satellites (using the Nexus One and Nexus S phones), the cheapest satellite (a total parts cost below $3,500) and one of the fastest on-board processors (CPU speed of 1GHz). In this paper, an overview of the PhoneSat project as well as a summary of the in-flight experimental results is presented.

KidSat: Image User's Manual

Science.gov (United States)

Way, JoBea; Andres, Paul; Baker, John; Goodson, Greg; Marshall, William; McGuire, John; Rackley, Kathleen; Stork, Elizabeth Jones; Yiu, Lisa

1999-01-01

The goal of KidSat was to provide young students with the opportunity to participate directly in the NASA space program and to enhance learning in the process. The KidSat pilot project was focused on using a color digital camera, mounted on the space shuttle, to take pictures of the Earth. These could be used to enhance middle school curricula. The project not only benefited middle school students, who were essentially the Science Team, responsible for deciding where to take pictures, but it also benefited high school students and undergraduates, who were essentially the Project Team, responsible for the development and implementation of the project. KidSat flew on three missions as part of the pilot project: STS-76, STS-81, and STS-86. This document describes the goals, project elements, results, and data for the three KidSat missions that made up the pilot program. It serves as a record for this pilot project and may be used as a reference for similar projects. It can also be a too] in using the data to its fullest extent. The KidSat Web page remains on-line at http://kidsat.jpl.nasa.gov/kidsat, and the images may be downloaded in their full resolution.

Evaluation of the Impact of an Additive Manufacturing Enhanced CubeSat Architecture on the CubeSat Development Process

Science.gov (United States)

2016-09-15

thermoplastic PCB Printed Circuit Board PIC Programmable Intelligent Computer RAMPART RApidprototyped MEMS Propulsion and Radiation Test RF Radio Frequency S...V for printed propulsion systems of varying volumes ........... 66 Figure 23. Predicted radiation attenuation of aluminum and AM composite CubeSat...Delta V data and estimates for standard CubeSat propulsion systems ............... 42 Table 5. Delta V for RAMPART printed CubeSat propulsion

Advances in Ka-Band Communication System for CubeSats and SmallSats

Science.gov (United States)

Kegege, Obadiah; Wong, Yen F.; Altunc, Serhat

2016-01-01

A study was performed that evaluated the feasibility of Ka-band communication system to provide CubeSat/SmallSat high rate science data downlink with ground antennas ranging from the small portable 1.2m/2.4m to apertures 5.4M, 7.3M, 11M, and 18M, for Low Earth Orbit (LEO) to Lunar CubeSat missions. This study included link analysis to determine the data rate requirement, based on the current TRL of Ka-band flight hardware and ground support infrastructure. Recent advances in Ka-band transceivers and antennas, options of portable ground stations, and various coverage distances were included in the analysis. The link/coverage analysis results show that Cubesat/Smallsat missions communication requirements including frequencies and data rates can be met by utilizing Near Earth Network (NEN) Ka-band support with 2 W and high gain (>6 dBi) antennas.

Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

Science.gov (United States)

Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

2006-01-01

Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

Gezgin satıcı problemi için yeni bir meta-sezgisel: kör fare algoritması

Directory of Open Access Journals (Sweden)

Tevfik YILDIRIM

2016-02-01

Full Text Available Gezgin Satıcı Problemi (GSP, başlangıç ve bitiş şehirleri aynı olan ve her şehrin sadece bir kez ziyaret edildiği minimum mesafeli turu bulma problemidir. Şehir sayısı arttıkça, kesin yöntemler ile kabul edilebilir sürelerde bir optimum çözüm bulunması zordur. Bu nedenle, son elli yılda GSP’nin çözümü için doğadan ve biyolojiden esinlenen birçok meta-sezgisel yöntem geliştirilmiştir. Bu çalışmada, toprak altındaki bireysel tünel sistemlerinde yaşayan kör farelerin toprak altındaki engelleri geçme stratejisinden esinlenilerek GSP’nin çözümü için yeni bir meta-sezgisel tasarlanmıştır. Geliştirilen yönteme Kör Fare Algoritması adı verilmiştir. Bu yeni sezgisel ile farklı boyutlardaki simetrik test veri setleri için deneyler yapılmış ve sonuçları bilinen en iyi sonuçlar ile kıyaslanmıştır. Önerilen meta-sezgisel henüz literatürdeki diğer algoritmalarla yarışabilecek düzeyde olmamasına rağmen, başlangıç test çözümlerinin umut verici olduğu söylenebilir.Anahtar Kelimeler: Gezgin satıcı problemi, Kombinatoryel eniyileme, Meta-Sezgisel, Kör fare algoritması

TechEdSat Nano-Satellite Series Fact Sheet

Science.gov (United States)

Murbach, Marcus; Martinez, Andres; Guarneros Luna, Ali

2014-01-01

TechEdSat-3p is the second generation in the TechEdSat-X series. The TechEdSat Series uses the CubeSat standards established by the California Polytechnic State University Cal Poly), San Luis Obispo. With typical blocks being constructed from 1-unit (1U 10x10x10 cm) increments, the TechEdSat-3p has a 3U volume with a 30 cm length. The project uniquely pairs advanced university students with NASA researchers in a rapid design-to-flight experience lasting 1-2 semesters.The TechEdSat Nano-Satellite Series provides a rapid platform for testing technologies for future NASA Earth and planetary missions, as well as providing students with an early exposure to flight hardware development and management.

Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol

Science.gov (United States)

Blednov, Y.A.; Harris, R.A.

2009-01-01

The vanilloid receptor TRPV1 is activated by ethanol and this may be important for some of the central and peripheral actions of ethanol. To determine if this receptor has a role in ethanol-mediated behaviors, we studied null mutant mice in which the Trpv1 gene was deleted. Mice lacking this gene showed significantly higher preference for ethanol and consumed more ethanol in a two-bottle choice test as compared with wild type littermates. Null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol (2 g/kg). However, there were no differences between null mutant and wild type mice in severity of ethanol-induced acute withdrawal (4 g/kg) or conditioned taste aversion to ethanol (2.5 g/kg). Two behavioral phenotypes (decreased sensitivity to ethanol-induced sedation and faster recovery from ethanol-induced motor incoordination) seen in null mutant mice were reproduced in wild type mice by injection of a TRPV1 antagonist, capsazepine (10 mg/kg). These two ethanol behaviors were changed in the opposite direction after injection of capsaicin, a selective TRPV1 agonist, in wild type mice. The studies provide the first evidence that TRPV1 is important for specific behavioral actions of ethanol. PMID:19705551

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

Two-year body composition analyses of long-lived GHR null mice.

Science.gov (United States)

Berryman, Darlene E; List, Edward O; Palmer, Amanda J; Chung, Min-Yu; Wright-Piekarski, Jacob; Lubbers, Ellen; O'Connor, Patrick; Okada, Shigeru; Kopchick, John J

2010-01-01

Growth hormone receptor gene-disrupted (GHR-/-) mice exhibit increased life span and adipose tissue mass. Although this obese phenotype has been reported extensively for young adult male GHR-/- mice, data for females and for other ages in either gender are lacking. Thus, the purpose of this study was to evaluate body composition longitudinally in both male and female GHR-/- mice. Results show that GHR-/- mice have a greater percent fat mass with no significant difference in absolute fat mass throughout life. Lean mass shows an opposite trend with percent lean mass not significantly different between genotypes but absolute mass reduced in GHR-/- mice. Differences in body composition are more pronounced in male than in female mice, and both genders of GHR-/- mice show specific enlargement of the subcutaneous adipose depot. Along with previously published data, these results suggest a consistent and intriguing protective effect of excess fat mass in the subcutaneous region.

CarbonSat: ESA's Earth Explorer 8 Candidate Mission

Science.gov (United States)

Meijer, Y. J.; Ingmann, P.; Löscher, A.

2012-04-01

The CarbonSat candidate mission is part of ESA's Earth Explorer Programme. In 2010, two candidate opportunity missions had been selected for feasibility and preliminary definition studies. The missions, called FLEX and CarbonSat, are now in competition to become ESA's eighth Earth Explorer, both addressing key climate and environmental change issues. In this presentation we will provide a mission overview of CarbonSat with a focus on science. CarbonSat's primary mission objective is the quantification and monitoring of CO2 and CH4 sources and sinks from the local to the regional scale for i) a better understanding of the processes that control carbon cycle dynamics and ii) an independent estimate of local greenhouse gas emissions (fossil fuel, geological CO2 and CH4, etc.) in the context of international treaties. A second priority objective is the monitoring/derivation of CO2 and CH4 fluxes on regional to global scale. These objectives will be achieved by a unique combination of frequent, high spatial resolution (2 x 2 km2) observations of XCO2 and XCH4 coupled to inverse modelling schemes. The required random error of a single measurement at ground-pixel resolution is of the order of between 1 and 3 ppm for XCO2 and between 9 and 17 ppb for XCH4. High spatial resolution is essential in order to maximize the probability for clear-sky observations and to identify flux hot spots. Ideally, CarbonSat shall have a wide swath allowing a 6-day global repeat cycle. The CarbonSat observations will enable CO2 emissions from coal-fired power plants, localized industrial complexes, cities, and other large emitters to be objectively assessed at a global scale. Similarly, the monitoring of natural gas pipelines and compressor station leakage will become feasible. The detection and quantification of the substantial geological greenhouse gas emission sources such as seeps, volcanoes and mud volcanoes will be achieved for the first time. CarbonSat's Greenhouse Gas instrument will

Enhanced Autophagy in Polycystic Kidneys of AQP11 Null Mice

Directory of Open Access Journals (Sweden)

Yasuko Tanaka

2016-11-01

Full Text Available Aquaporin-11 (AQP11 is an intracellular water channel expressed at the endoplasmic reticulum (ER of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(−/− kidneys. PCR analysis showed the increased expression of the transcript encoding LC3 (Map1lc3b as well as other autophagy-related genes in AQP11(−/− mice. Using green fluorescent protein (GFP-LC3 transgenic mice and AQP11(−/− mice, we found that the number of GFP-LC3–positive puncta was increased in the proximal tubule of AQP11(−/− mice before the cyst formation. Interestingly, they were also observed in the cyst-lining epithelial cell. Further PCR analyses revealed the enhanced expression of apoptosis-related and ER stress–related caspase genes before and after the cyst formation, which may cause the enhanced autophagy. These results suggest the involvement of autophagy in the development and maintenance of kidney cysts in AQP11(−/− mice.

A Green, Safe, Dual-pulse Solid Motor for CubeSat Orbit Changing, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Small satellites such as CubeSats are in need of responsive propulsion, but are limited due to their size. Though single pulse, AP/HTPB fueled solid rocket motors...

Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

Directory of Open Access Journals (Sweden)

Hale Gregory

2009-11-01

Full Text Available Abstract Background PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity. Results We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls. Conclusion We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.

Solving the SAT problem using Genetic Algorithm

Directory of Open Access Journals (Sweden)

Arunava Bhattacharjee

2017-08-01

Full Text Available In this paper we propose our genetic algorithm for solving the SAT problem. We introduce various crossover and mutation techniques and then make a comparative analysis between them in order to find out which techniques are the best suited for solving a SAT instance. Before the genetic algorithm is applied to an instance it is better to seek for unit and pure literals in the given formula and then try to eradicate them. This can considerably reduce the search space, and to demonstrate this we tested our algorithm on some random SAT instances. However, to analyse the various crossover and mutation techniques and also to evaluate the optimality of our algorithm we performed extensive experiments on benchmark instances of the SAT problem. We also estimated the ideal crossover length that would maximise the chances to solve a given SAT instance.

iNOS inhibits hair regeneration in obese diabetic (ob/ob) mice.

Science.gov (United States)

Sasaki, Mari; Shinozaki, Shohei; Morinaga, Hironobu; Kaneki, Masao; Nishimura, Emi; Shimokado, Kentaro

2018-07-02

Previous studies have shown that androgenic alopecia is associated with metabolic syndrome and diabetes. However, the detailed mechanism whereby diabetes causes alopecia still remains unclear. We focused on the inflammatory response that is caused by diabetes or obesity, given that inflammation is a risk factor for hair loss. Inducible nitric oxide synthase (iNOS) is known to be upregulated under conditions of acute or chronic inflammation. To clarify the potential role of iNOS in diabetes-related alopecia, we generated obese diabetic iNOS-deficient (ob/ob; iNOS-KO mice). We observed that ob/ob; iNOS-KO mice were potentiated for the transition from telogen (rest phase) to anagen (growth phase) in the hair cycle compared with iNOS-proficient ob/ob mice. To determine the effect of nitric oxide (NO) on the hair cycle, we administered an iNOS inhibitor intraperitoneally (compound 1400 W, 10 mg/kg) or topically (10% aminoguanidine) in ob/ob mice. We observed that iNOS inhibitors promoted anagen transition in ob/ob mice. Next, we administered an NO donor (S-nitrosoglutathione, GSNO), to test whether NO has the telogen elongation effects. The NO donor was sufficient to induce telogen elongation in wild-type mice. Together, our data indicate that iNOS-derived NO plays a role in telogen elongation under the inflammatory conditions associated with diabetes in mice. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Touchscreen Sustained Attention Task (SAT) for Rats.

Science.gov (United States)

Bangasser, Debra A; Wicks, Brittany; Waxler, David E; Eck, Samantha R

2017-09-15

Sustained attention is the ability to monitor intermittent and unpredictable events over a prolonged period of time. This attentional process subserves other aspects of cognition and is disrupted in certain neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Thus, it is clinically important to identify mechanisms that impair and improve sustained attention. Such mechanisms are often first discovered using rodent models. Therefore, several behavior procedures for testing aspects of sustained attention have been developed for rodents. One, first described by McGaughy and Sarter (1995), called the sustained attention task (SAT), trains rats to distinguish between signal (i.e., brief light presentation) and non-signal trials. The signals are short and thus require careful attention to be perceived. Attentional demands can be increased further by introducing a distractor (e.g., flashing houselight). We have modified this task for touchscreen operant chambers, which are configured with a touchscreen on one wall that can present stimuli and record responses. Here we detail our protocol for SAT in touchscreen chambers. Additionally, we present standard measures of performance in male and female Sprague-Dawley rats. Comparable performance on this task in both sexes highlights its use for attention studies, especially as more researchers are including female rodents in their experimental design. Moreover, the easy implementation of SAT for the increasingly popular touchscreen chambers increases its utility.

PERCEPTION OF SWEET TASTE IS IMPORTANT FOR VOLUNTARY ALCOHOL CONSUMPTION IN MICE

OpenAIRE

Blednov, Y.A.; Walker, D.; Martinez, M.; Levine, M.; Damak, S.; Margolskee, R.F.

2007-01-01

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solution...

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.

High Data Rates for AubieSat-2 A & B, Two CubeSats Performing High Energy Science in the Upper Atmosphere

Science.gov (United States)

Sims, William H.

2015-01-01

This paper will discuss a proposed CubeSat size (3 Units / 6 Units) telemetry system concept being developed at Marshall Space Flight Center (MSFC) in cooperation with Auburn University. The telemetry system incorporates efficient, high-bandwidth communications by developing flight-ready, low-cost, PROTOFLIGHT software defined radio (SDR) payload for use on CubeSats. The current telemetry system is slightly larger in dimension of footprint than required to fit within a 0.75 Unit CubeSat volume. Extensible and modular communications for CubeSat technologies will provide high data rates for science experiments performed by two CubeSats flying in formation in Low Earth Orbit. The project is a collaboration between the University of Alabama in Huntsville and Auburn University to study high energy phenomena in the upper atmosphere. Higher bandwidth capacity will enable high-volume, low error-rate data transfer to and from the CubeSats, while also providing additional bandwidth and error correction margin to accommodate more complex encryption algorithms and higher user volume.

Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

International Nuclear Information System (INIS)

Noda, Kazuo; Nakamura, Tomoyuki; Komatsu, Yoshihiro

2015-01-01

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.

Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

Energy Technology Data Exchange (ETDEWEB)

Noda, Kazuo, E-mail: knoda@kuhp.kyoto-u.ac.jp [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Nakamura, Tomoyuki [Department of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010 (Japan); Komatsu, Yoshihiro [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Graduate Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States)

2015-10-23

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.

Loss of ATM kinase activity leads to embryonic lethality in mice

DEFF Research Database (Denmark)

Daniel, J.A.; Pellegrini, M.; Filsuf, D.

2012-01-01

whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice......, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate...

On Cafesat: A Modern SAT Solver for Scala

OpenAIRE

Blanc, Régis William

2013-01-01

We present CafeSat, a SAT solver written in the Scala programming language. CafeSat is a modern solver based on DPLL and featuring many state-of-the-art techniques and heuristics. It uses two-watched literals for Boolean constraint propagation, conflict-driven learning along with clause deletion, a restarting strategy, and the VSIDS heuristics for choosing the branching literal. CafeSat is both sound and complete. In order to achieve reasonnable performances, low level and hand-tuned data ...

SirT1 regulates energy metabolism and response to caloric restriction in mice.

Directory of Open Access Journals (Sweden)

Gino Boily

Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

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

Directory of Open Access Journals (Sweden)

Jurczyk A

2013-12-01

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

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.

Integrated Propulsion and Primary Structure Module for Small Satellite and CubeSat Applications, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Over the last decade, the CubeSat platform has emerged as a viable alternative for both innovative technology development and scientific investigation. However, to...

Dietary rose hip exerts antiatherosclerotic effects and increases nitric oxide-mediated dilation in ApoE-null mice.

Science.gov (United States)

Cavalera, Michele; Axling, Ulrika; Rippe, Catarina; Swärd, Karl; Holm, Cecilia

2017-06-01

Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans. The aim of this study was to elucidate the mechanisms by which rose hip lowers plasma cholesterol and to evaluate its effects on atherosclerotic plaque formation. ApoE-null mice were fed either an HFD (CTR) or HFD with rose hip supplementation (RH) for 24 weeks. At the end of the study, we found that blood pressure and atherosclerotic plaques, together with oxidized LDL, total cholesterol and fibrinogen levels were markedly reduced in the RH group. Fecal cholesterol content, liver expression of Ldlr and selected reverse cholesterol transport (RCT) genes such as Abca1, Abcg1 and Scarb1 were significantly increased upon RH feeding. In the aorta, the scavenger receptor Cd36 and the proinflammatory Il1β genes were markedly down-regulated compared to the CTR mice. Finally, we found that RH increased nitric oxide-mediated dilation of the caudal artery. Taken together, these results suggest that rose hip is a suitable dietary supplement for preventing atherosclerotic plaques formation by modulating systemic blood pressure and the expression of RCT and inflammatory genes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Ethics in Personal Selling: Investigating Ethical Attitudes of Medical Sales Representatives in Adana Kişisel Satışta Etik: Adana İlindeki Tıbbi Satış Temsilcilerinin Etik Tutumlarının İncelenmesi

Directory of Open Access Journals (Sweden)

Sezen BOZYİĞİT

2013-09-01

Full Text Available Personal selling is common in ethics related studies. It can be said that the mostimportant reason for this, is the pressure of achieving the targets or fulfilling quotas, whichcause sales representatives to behave unethically.The purpose of this research is to define ethical attitudes of medical salesrepresentatives and analyze the differences among them in terms of their demographicfeatures in their ethical attitudes. According to the findings; there is no significantdifference among gender, age, work experince and income level. On the other hand, thereare significant differences in the origin of the companies in terms of general ethicalattitudes, sales pressure, sales quotas and the beliefs regarding whether the ethicalproblems will be resolved.Etik konulu araştırmalar içinde kişisel satış yaygındır. Bunun temel nedeninin,hedeflere ulaşma veya kotaları doldurma baskısının, satış temsilcilerini etik olmayandavranışlarda bulunmaya zorlaması olduğu söylenebilmektedir.Bu çalışmanın amacı, tıbbi satış temsilcilerinin kişisel satış süreçlerindeki etiktutumlarını belirlemek ve satış temsilcilerinin demografik özellikleri arasında etik tutumlaraçısından farklılıkları incelemektir. Bulgulara göre; cinsiyet, yaş, iş deneyimi ve gelirdüzeyi grupları arasınd, anlamlı bir fark yoktur. Diğer yandan firmaların menşeine göregenel etik tutumlar, satış baskısı, satış kotaları ve etik sorunların çözüleceğine dair inançaçısından anlamlı farklılıklar vardır.

CryoSat product quality and evolutions

Science.gov (United States)

Bouffard, Jérome; Parrinello, Tommaso; Féménias, Pierre

2017-04-01

The main CryoSat mission objectives are to measure the regional and basin-scale changes in the thickness of the sea-ice and, in the elevation of the ice sheets and mountain glaciers. Beside its ice-monitoring objective, CryoSat also provides valuable observations for the oceanographic community. The CryoSat data are processed by ESA both over the ocean and ice surfaces with two independent processors. These data need to be routinely Quality-Controlled and thoroughly Validated (QCV). Based on the QCV outcomes from ESA multi-national partners and the feedback from the scientific community, the data products continuously evolve in order to accommodate a wide range of users over the Sea ice, the Land Ice and the Ocean domains. The main objectives of this paper are to give an overview of main CryoSat QCV results and product improvements; as well as to present the processing algorithm upgrades being implemented for future ice and ocean Baselines.

Achieving Science with CubeSats: Thinking Inside the Box

Science.gov (United States)

Zurbuchen, Thomas H.; Lal, Bhavya

2017-01-01

We present the results of a study conducted by the National Academies of Sciences, Engineering, and Medicine. The study focused on the scientific potential and technological promise of CubeSats. We will first review the growth of the CubeSat platform from an education-focused technology toward a platform of importance for technology development, science, and commercial use, both in the United States and internationally. The use has especially exploded in recent years. For example, of the over 400 CubeSats launched since 2000, more than 80% of all science-focused ones have been launched just in the past four years. Similarly, more than 80% of peer-reviewed papers describing new science based on CubeSat data have been published in the past five years.We will then assess the technological and science promise of CubeSats across space science disciplines, and discuss a subset of priority science goals that can be achieved given the current state of CubeSat capabilities. Many of these goals address targeted science, often in coordination with other spacecraft, or by using sacrificial or high-risk orbits that lead to the demise of the satellite after critical data have been collected. Other goals relate to the use of CubeSats as constellations or swarms, deploying tens to hundreds of CubeSats that function as one distributed array of measurements.Finally, we will summarize our conclusions and recommendations from this study; especially those focused on nearterm investment that could improve the capabilities of CubeSats toward increased science and technological return and enable the science communities’ use of CubeSats.

Effect of aminoguanidine and albendazole on inducible nitric oxide synthase (iNOS activity in <i>T. spiralisi>-infected mice muscles

Directory of Open Access Journals (Sweden)

Iwona Mozer-Lisewska

2011-08-01

Full Text Available The aim of this study was to provide evidence for the expression of iNOS in the cells of inflammatory infiltrates around larvae in skeletal muscles of T. spiralis infected mice. The BALB/c mice (n=8 divided into subgroups, received either aminoguanidine (AMG - a specific iNOS inhibitor or albendazole (ALB - an antiparasitic drug of choice in trichinellosis treatment. Control animals (n=2 in each subgroup were either uninfected and treated or uninfected and untreated. Frozen sections of hind leg muscles from mice sacrificed at various time intervals after infection were cut and subjected to immunohistochemistry, using monoclonal anti-iNOS antibody. The ALB-treated mice revealed stronger iNOS staining in the infiltrating cells around larvae than the infected and untreated animals. On the contrary, in the AMG-treated animals, the infiltrating cells did not show any specific iNOS reaction. These data confirm the specificity of iNOS staining in the cellular infiltrates around <i>T. spiralisi> larvae and shed some light on the role of nitric oxide during ALB treatment in experimental trichinellosis.

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

CubeSat Integration into the Space Situational Awareness Architecture

Science.gov (United States)

Morris, K.; Wolfson, M.; Brown, J.

2013-09-01

Lockheed Martin Space Systems Company has recently been involved in developing GEO Space Situational Awareness architectures, which allows insights into how cubesats can augment the current national systems. One hole that was identified in the current architecture is the need for timelier metric track observations to aid in the chain of custody. Obtaining observations of objects at GEO can be supported by CubeSats. These types of small satellites are increasing being built and flown by government agencies like NASA and SMDC. CubeSats are generally mass and power constrained allowing for only small payloads that cannot typically mimic traditional flight capability. CubeSats do not have a high reliability and care must be taken when choosing mission orbits to prevent creating more debris. However, due to the low costs, short development timelines, and available hardware, CubeSats can supply very valuable benefits to these complex missions, affordably. For example, utilizing CubeSats for advanced focal plane demonstrations to support technology insertion into the next generation situational awareness sensors can help to lower risks before the complex sensors are developed. CubeSats can augment the planned ground and space based assets by creating larger constellations with more access to areas of interest. To aid in maintaining custody of objects, a CubeSat constellation at 500 km above GEO would provide increased point of light tracking that can augment the ground SSA assets. Key features of the Cubesat include a small visible camera looking along the GEO belt, a small propulsion system that allows phasing between CubeSats, and an image processor to reduce the data sent to the ground. An elegant communications network will also be used to provide commands to and data from multiple CubeSats. Additional CubeSats can be deployed on GSO launches or through ride shares to GEO, replenishing or adding to the constellation with each launch. Each CubeSat would take images of

Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution.

Directory of Open Access Journals (Sweden)

Stewart I Head

Full Text Available Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i an increased rate of decay of the twitch transient; (ii a fourfold increase in the rate of SR Ca2+ leak; (iii a threefold increase in the rate of SR Ca2+ pumping; and (iv enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments

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

Buffering of protons released by mineral formation during amelogenesis in mice.

Science.gov (United States)

Bronckers, Antonius L J J; Lyaruu, Don M; Jalali, Rozita; DenBesten, Pamela K

2016-10-01

Regulation of pH by ameloblasts during amelogenesis is critical for enamel mineralization. We examined the effects of reduced bicarbonate secretion and the presence or absence of amelogenins on ameloblast modulation and enamel mineralization. To that end, the composition of fluorotic and non-fluorotic enamel of several different mouse mutants, including enamel of cystic fibrosis transmembrane conductance regulator-deficient (Cftr null), anion exchanger-2-deficient (Ae2a,b null), and amelogenin-deficient (Amelx null) mice, was determined by quantitative X-ray microanalysis. Correlation analysis was carried out to compare the effects of changes in the levels of sulfated-matrix (S) and chlorine (Cl; for bicarbonate secretion) on mineralization and modulation. The chloride (Cl - ) levels in forming enamel determined the ability of ameloblasts to modulate, remove matrix, and mineralize enamel. In general, the lower the Cl - content, the stronger the negative effects. In Amelx-null mice, modulation was essentially normal and the calcium content was reduced least. Retention of amelogenins in enamel of kallikrein-4-deficient (Klk4-null) mice resulted in decreased mineralization and reduced the length of the first acid modulation band without changing the total length of all acidic bands. These data suggest that buffering by bicarbonates is critical for modulation, matrix removal and enamel mineralization. Amelogenins also act as a buffer but are not critical for modulation. © 2016 Eur J Oral Sci.

DebriSat Hypervelocity Impact Test

Science.gov (United States)

2015-08-01

public release; distribution unlimited.  Targets: Scaled Multishock Shield, DebrisLV, and DebriSat  500-600 g hollow aluminum and nylon projectile... insulation . DebriSat’s internal components were structurally similar to real flight hardware but were nonfunctional. AEDC-TR-15-S-2 6...structures with an AL 5052 honeycomb core and M55J carbon fiber face sheets. The basic system characteristics of the DebriSat are given in Table 1

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

Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet

International Nuclear Information System (INIS)

Zhang, Yu-Kun Jennifer; Yeager, Ronnie L.; Tanaka, Yuji; Klaassen, Curtis D.

2010-01-01

Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gstα1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.

Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development.

Science.gov (United States)

Ruan, W; Powell-Braxton, L; Kopchick, J J; Kleinberg, D L

1999-05-01

Insulin-like growth factor I (IGF-I) has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IGF-I and prostate development or cancer in vivo has been established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in IGF-I(-/-) null mice and wild-type littermates. Glands from 44-day-old IGF-I-deficient animals were not only smaller than those from wild-type mice, but also had fewer terminal duct tips and branch points and deficits in tertiary and quaternary branching (P deficit by increasing those parameters of prostate development (P growth as an extension of a normal process.

Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

Energy Technology Data Exchange (ETDEWEB)

Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Merchant, Michael L. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Division of Nephrology, Department of Medicine, University of Louisville, Louisville, KY 40292 (United States); Prough, Russell A. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States); Williams, Jessica D. [University of Cincinnati College of Medicine, Internal Medicine, Cincinnati, OH 45267 (United States); Prabhu, Sumanth D. [Division of Cardiovascular Disease, University of Alabama-Birmingham, Birmingham, AL 35294 (United States); Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States)

2015-06-01

High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

International Nuclear Information System (INIS)

Conklin, Daniel J.; Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid; Merchant, Michael L.; Prough, Russell A.; Williams, Jessica D.; Prabhu, Sumanth D.; Bhatnagar, Aruni

2015-01-01

High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4

International Nuclear Information System (INIS)

Mirandola, Leonardo; Yu, Yuefei; Jenkins, Marjorie R; Chiaramonte, Raffaella; Cobos, Everardo; John, Constance M; Chiriva-Internati, Maurizio

2011-01-01

Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease. Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4. Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45. We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth in vivo and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies

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...

Nonylphenol-mediated CYP induction is PXR-dependent: The use of humanized mice and human hepatocytes suggests that hPXR is less sensitive than mouse PXR to nonylphenol treatment

International Nuclear Information System (INIS)

Mota, Linda C.; Barfield, Christina; Hernandez, Juan P.; Baldwin, William S.

2011-01-01

Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investigating the role of PXR in protecting individuals from NP. Wild-type (WT), PXR-null, and humanized PXR (hPXR) mice were treated with NP at 0, 50 or 75 mg/kg/day for one week, and cytochrome P450 (CYP) induction, liver histopathology, and serum NP concentrations were examined. WT mice treated with NP showed induction of Cyp2b, and male-specific induction of Cyp2c and Cyp3a. CYPs were not induced in PXR-null mice, demonstrating that PXR is necessary for NP-mediated CYP induction. CAR-mediated CYP induction was not observed in the PXR-null mice despite previous data demonstrating that NP is also a CAR activator. hPXR mice only showed moderate Cyp induction, suggesting that hPXR is not as sensitive to NP as mPXR in vivo. NP-mediated Cyp3a induction from three human hepatocyte donors was not significant, confirming that hPXR is not very sensitive to NP-mediated CYP induction. Lastly, mice with PXR (mPXR and hPXR) showed lower NP serum concentrations than PXR-null mice treated with NP suggesting that PXR plays a role in decreasing liver toxicity by basally regulating phase I-III detoxification enzymes that promote the metabolism and elimination of NP. In summary, PXR is required for NP-mediated CYP-induction, mPXR mediates greater CYP induction than hPXR in vivo, and the presence of PXR, especially mPXR, is associated with altered histopathology and increased clearance of NP.

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.

The autonomous vision system on TeamSat

DEFF Research Database (Denmark)

Betto, Maurizio; Jørgensen, John Leif; Riis, Troels

1999-01-01

The second qualification flight of Ariane 5 blasted off-the European Space Port in French Guiana on October 30, 1997, carrying on board a small technology demonstration satellite called TeamSat. Several experiments were proposed by various universities and research institutions in Europe and five...... of them were finally selected and integrated into TeamSat, namely FIPEX, VTS, YES, ODD and the Autonomous Vision System, AVS, a fully autonomous star tracker and vision system. This paper gives short overview of the TeamSat satellite; design, implementation and mission objectives. AVS is described in more...

Preparing for the SAT: A Review

Science.gov (United States)

Appelrouth, Jed I.; Zabrucky, Karen M.

2017-01-01

In 2016, more than 1.6 million students took the Scholastic Aptitude Test (SAT), a standardized college admissions test (College Board 2016a). Researchers have estimated that 33 percent of students who take the SAT participate in some mode of formal test preparation, such as private tutoring or classes, to prepare for the exam (Buchmann, Condron…

GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice

Science.gov (United States)

Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Leiter, Courtney R.; Osterndorff-Kahanek, Elizabeth; Johnson, David; Borghese, Cecilia M.; Hanrahan, Jane R.; Johnston, Graham A. R.; Chebib, Mary; Harris, R. Adron

2014-01-01

GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ1” antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ2” antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo. PMID:24454882

GABAA receptors containing ρ1 subunits contribute to in vivo effects of ethanol in mice.

Directory of Open Access Journals (Sweden)

Yuri A Blednov

Full Text Available GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR, and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ1" antagonist, when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests, but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ2" antagonist did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.

Alterations in gene expression in mutant amyloid precursor protein transgenic mice lacking Niemann-Pick type C1 protein.

Directory of Open Access Journals (Sweden)

Mahua Maulik

Full Text Available Niemann-Pick type C (NPC disease, a rare autosomal recessive disorder caused mostly by mutation in NPC1 gene, is pathologically characterized by the accumulation of free cholesterol in brain and other tissues. This is accompanied by gliosis and loss of neurons in selected brain regions, including the cerebellum. Recent studies have shown that NPC disease exhibits intriguing parallels with Alzheimer's disease, including the presence of neurofibrillary tangles and increased levels of amyloid precursor protein (APP-derived β-amyloid (Aβ peptides in vulnerable brain neurons. To evaluate the role of Aβ in NPC disease, we determined the gene expression profile in selected brain regions of our recently developed bigenic ANPC mice, generated by crossing APP transgenic (Tg mice with heterozygous Npc1-deficient mice. The ANPC mice exhibited exacerbated neuronal and glial pathology compared to other genotypes [i.e., APP-Tg, double heterozygous (Dhet, Npc1-null and wild-type mice]. Analysis of expression profiles of 86 selected genes using real-time RT-PCR arrays showed a wide-spectrum of alterations in the four genotypes compared to wild-type controls. The changes observed in APP-Tg and Dhet mice are limited to only few genes involved mostly in the regulation of cholesterol metabolism, whereas Npc1-null and ANPC mice showed alterations in the expression profiles of a number of genes regulating cholesterol homeostasis, APP metabolism, vesicular trafficking and cell death mechanism in both hippocampus and cerebellum compared to wild-type mice. Intriguingly, ANPC and Npc1-null mice, with some exceptions, exhibited similar changes, although more genes were differentially expressed in the affected cerebellum than the relatively spared hippocampus. The altered gene profiles were found to match with the corresponding protein levels. These results suggest that lack of Npc1 protein can alter the expression profile of selected transcripts as well as proteins, and

Hepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT regulates metabolism in mice.

Directory of Open Access Journals (Sweden)

Christopher H Scott

Full Text Available Aryl hydrocarbon Receptor Nuclear Translocator (ARNT and its partners hypoxia-inducible factors (HIF-1α and HIF-2α are candidate factors for the well-known link between the liver, metabolic dysfunction and elevation in circulating lipids and glucose. Methods: Hepatocyte-specific ARNT-null (LARNT, HIF-1α-null (LHIF1α and HIF-2α-null (LHIF2α mice were created.LARNT mice had increased fasting glucose, impaired glucose tolerance, increased glucose production, raised post-prandial serum triglycerides (TG and markedly lower hepatic ATP versus littermate controls. There was increased expression of G6Pase, Chrebp, Fas and Scd-1 mRNAs in LARNT animals. Surprisingly, LHIF1α and LHIF2α mice exhibited no alterations in any metabolic parameter assessed.These results provide convincing evidence that reduced hepatic ARNT can contribute to inappropriate hepatic glucose production and post-prandial dyslipidaemia. Hepatic ARNT may be a novel therapeutic target for improving post-prandial hypertriglyceridemia and glucose homeostasis.

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

Science.gov (United States)

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

2002-01-01

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

X-Band CubeSat Communication System Demonstration

Science.gov (United States)

Altunc, Serhat; Kegege, Obadiah; Bundick, Steve; Shaw, Harry; Schaire, Scott; Bussey, George; Crum, Gary; Burke, Jacob C.; Palo, Scott; O'Conor, Darren

2015-01-01

Today's CubeSats mostly operate their communications at UHF- and S-band frequencies. UHF band is presently crowded, thus downlink communications are at lower data rates due to bandwidth limitations and are unreliable due to interference. This research presents an end-to-end robust, innovative, compact, efficient and low cost S-band uplink and X-band downlink CubeSat communication system demonstration between a balloon and a Near Earth Network (NEN) ground system. Since communication systems serve as umbilical cords for space missions, demonstration of this X-band communication system is critical for successfully supporting current and future CubeSat communication needs. This research has three main objectives. The first objective is to design, simulate, and test a CubeSat S- and X-band communication system. Satellite Tool Kit (STK) dynamic link budget calculations and HFSS Simulations and modeling results have been used to trade the merit of various designs for small satellite applications. S- and X-band antennas have been tested in the compact antenna test range at Goddard Space Flight Center (GSFC) to gather radiation pattern data. The second objective is simulate and test a CubeSat compatible X-band communication system at 12.5Mbps including S-band antennas, X-band antennas, Laboratory for Atmospheric and Space Physics (LASP) /GSFC transmitter and an S-band receiver from TRL-5 to TRL-8 by the end of this effort. Different X-band communication system components (antennas, diplexers, etc.) from GSFC, other NASA centers, universities, and private companies have been investigated and traded, and a complete component list for the communication system baseline has been developed by performing analytical and numerical analysis. This objective also includes running simulations and performing trades between different X-band antenna systems to optimize communication system performance. The final objective is to perform an end-to-end X-band CubeSat communication system

SAT in operations training

International Nuclear Information System (INIS)

Gonzalez, M.

1995-01-01

The selection of tasks for analysis is made based on the decision tree that incorporates management's expectations of task difficulty and importance. The training setting (e.g., OJT, classroom, simulator, or laboratory) and the steps necessary to prepare the final training plan (along with example training plans for RO/SRO) was presented. The On-the-Job Training Manual is composed of a special video of each system that guides the trainee through a specified route in the plant showing the keypoints about the specific system. This Manual includes scanned photos of the main components and very detailed layout drawings to quickly walk-through a system. Two data bases were established to keep track of all the systems and tasks associated with a job post and to maintain the JPMs. SAT application in Spain, Argentina, Novovoronezh (Russia), and Hungary has varied by the time and human resources necessary to develop a complete SAT or a simplified SAT (which omits the taxonomic code for obtaining knowledge and skills associated to each task). An example of simulator training program materials and its correlation with the JPMs was presented along with a simulator evaluation guide showing how to assess RO/SRO behaviour

Modular Heat Dissipation Technique for a CubeSat

Science.gov (United States)

2015-07-28

Research Overview Even though the interest in CubeSats has increased over the past decade, there is little publicly released research about thermal...understanding of the thermal design and analysis effort of CubeSats in the past decade, a research overview was provided. 25 III. Methodology The...CubeSats, because it leaves a considerable area for circuitry on the board and has a simple scheme [ Pumpkin , 2013]. Assuming there are high power

Integration of a MicroCAT Propulsion System and a PhoneSat Bus into a 1.5U CubeSat

Science.gov (United States)

Agasid, Elwood Floyd; Perez, Andres Dono; Gazulla, Oriol Tintore; Trinh, Greenfield Tran; Uribe, Eddie Anthony; Keidar, Michael; Haque, Samudra; Teel, George

2014-01-01

NASA Ames Research Center and the George Washington University have developed an electric propulsion subsystem that can be integrated into the PhoneSat bus. Experimental tests have shown a reliable performance by firing three different thrusters at various frequencies in vacuum conditions. The three thrusters were controlled by a SmartPhone that was running the PhoneSat software. The subsystem is fully operational and it requires low average power to function (about 0.1 W). The interface consists of a microcontroller that sends a trigger pulses to the PPU (Plasma Processing Unit), which is responsible for the thruster operation. Frequencies ranging from 1 to 50Hz have been tested, showing a strong flexibility. A SmartPhone acts as the main user interface for the selection of commands that control the entire system. The micro cathode arc thruster MicroCAT provides a high 1(sub sp) of 3000s that allows a 4kg satellite to obtain a (delta)V of 300m/s. The system mass is only 200g with a total of volume of 200(cu cm). The propellant is based on a solid cylinder made of Titanium, which is the cathode at the same time. This simplicity in the design avoids miniaturization and manufacturing problems. The characteristics of this thruster allow an array of MicroCATs to perform attitude control and orbital correcton maneuvers that will open the door for the implementation of an extensive collection of new mission concepts and space applications for CubeSats. NASA Ames is currently working on the integration of the system to fit the thrusters and PPU inside a 1.5U CubeSat together with the PhoneSat bus into a 1.5U CubeSat. This satellite is intended to be deployed from the ISS in 2015 and test the functionality of the thrusters by spinning the satellite around its long axis and measure the rotational speed with the phone byros. This test flight will raise the TRL of the propulsion system from 5 to 7 and will be a first test for further CubeSats with propulsion systems, a key

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...

3D Printing the Complete CubeSat

Science.gov (United States)

Kief, Craig

2015-01-01

The 3D Printing the Complete CubeSat project is designed to advance the state-of-the-art in 3D printing for CubeSat applications. Printing in 3D has the potential to increase reliability, reduce design iteration time and provide greater design flexibility in the areas of radiation mitigation, communications, propulsion, and wiring, among others. This project is investigating the possibility of including propulsion systems into the design of printed CubeSat components. One such concept, an embedded micro pulsed plasma thruster (mPPT), could provide auxiliary reaction control propulsion for a spacecraft as a means to desaturate momentum wheels.

JC2Sat-FF : An International Collaboration Nano-Sat Project Overview of the System Analyses and Design

Science.gov (United States)

Yoshihara, K.; van Mierlo, M.; Ng, A.; Shankar Kumar, B.; De Ruiter, A.; Komatsu, Y.; Horiguchi, H.; Hashimoto, H.

2008-08-01

This paper introduces the Japan Canada Joint Collaboration Satellites - Formation Flying (JC2Sat-FF) project. JC2Sat-FF is a joint project between the Canadian Space Agency (CSA) and the Japan Aerospace Exploration Agency (JAXA) with the end goal of building, launching and operating two 20kg- class nanosatellites for technical demonstration of formation flight (FF) using differential drag technique, relative navigation using commercial off-the-shelf (COTS) dual band GPS receivers and far infra-red radiance measurement. A unique aspect of this project is that the two JC2Sats are developed by a united small team consisting of engineers and researchers from both agencies. Technical exchange in this international team gives stimulation to the members and generates a synergistic effect for the project.

Cyclooxygenase-2 mediates the febrile response of mice to interleukin-1beta.

Science.gov (United States)

Li, S; Ballou, L R; Morham, S G; Blatteis, C M

2001-08-10

Various lines of evidence have implicated cyclooxygenase (COX)-2 as a modulator of the fever induced by the exogenous pyrogen lipopolysaccharide (LPS). Thus, treatment with specific inhibitors of COX-2 suppresses the febrile response without affecting basal body (core) temperature (T(c)). Furthermore, COX-2 gene-ablated mice are unable to develop a febrile response to intraperitoneal (i.p.) LPS, whereas their COX-1-deficient counterparts produce fevers not different from their wild-type (WT) controls. To extend the apparently critical role of COX-2 for LPS-induced fevers to fevers produced by endogenous pyrogens, we studied the thermal responses of COX-1- and COX-2 congenitally deficient mice to i.p. and intracerebroventricular (i.c.v.) injections of recombinant murine (rm) interleukin (IL)-1beta. We also assessed the effects of one selective COX-1 inhibitor, SC-560, and two selective COX-2 inhibitors, nimesulide (NIM) and dimethylfuranone (DFU), on the febrile responses of WT and COX-1(-/-) mice to LPS and rmIL-1beta, i.p. Finally, we verified the integrity of the animals' responses to PGE2, i.c.v. I.p. and i.c.v. rmIL-1beta induced similar fevers in WT and COX-1 knockout mice, but provoked no rise in the T(c)s of COX-2 null mutants. The fever produced in WT mice by i.p. LPS was not affected by SC-560, but it was attenuated and abolished by NIM and DFU, respectively, while that caused by i.p. rmIL-1beta was converted into a T(c) fall by DFU. There were no differences in the responses to i.c.v. PGE2 among the WT and COX knockout mice. These results, therefore, further support the notion that the production of PGE2 in response to pyrogens is critically dependent on COX-2 expression.

CubeSat Material Limits for Design for Demise

Science.gov (United States)

Kelley, R. L.; Jarkey, D. R.

2014-01-01

The CubeSat form factor of nano-satellite (a satellite with a mass between one and ten kilograms) has grown in popularity due to their ease of construction and low development and launch costs. In particular, their use as student led payload design projects has increased due to the growing number of launch opportunities. CubeSats are often deployed as secondary or tertiary payloads on most US launch vehicles or they may be deployed from the ISS. The focus of this study will be on CubeSats launched from the ISS. From a space safety standpoint, the development and deployment processes for CubeSats differ significantly from that of most satellites. For large satellites, extensive design reviews and documentation are completed, including assessing requirements associated with re-entry survivability. Typical CubeSat missions selected for ISS deployment have a less rigorous review process that may not evaluate aspects beyond overall design feasibility. CubeSat design teams often do not have the resources to ensure their design is compliant with re-entry risk requirements. A study was conducted to examine methods to easily identify the maximum amount of a given material that can be used in the construction of a CubeSats without posing harm to persons on the ground. The results demonstrate that there is not a general equation or relationship that can be used for all materials; instead a limiting value must be defined for each unique material. In addition, the specific limits found for a number of generic materials that have been previously used as benchmarking materials for re-entry survivability analysis tool comparison will be discussed.

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.

Neonatal periostin knockout mice are protected from hyperoxia-induced alveolar simplication.

Directory of Open Access Journals (Sweden)

Paul D Bozyk

Full Text Available In bronchopulmonary dysplasia (BPD, alveolar septae are thickened with collagen and α-smooth muscle actin, transforming growth factor (TGF-β-positive myofibroblasts. Periostin, a secreted extracellular matrix protein, is involved in TGF-β-mediated fibrosis and myofibroblast differentiation. We hypothesized that periostin expression is required for hypoalveolarization and interstitial fibrosis in hyperoxia-exposed neonatal mice, an animal model for this disease. We also examined periostin expression in neonatal lung mesenchymal stromal cells and lung tissue of hyperoxia-exposed neonatal mice and human infants with BPD. Two-to-three day-old wild-type and periostin null mice were exposed to air or 75% oxygen for 14 days. Mesenchymal stromal cells were isolated from tracheal aspirates of premature infants. Hyperoxic exposure of neonatal mice increased alveolar wall periostin expression, particularly in areas of interstitial thickening. Periostin co-localized with α-smooth muscle actin, suggesting synthesis by myofibroblasts. A similar pattern was found in lung sections of infants dying of BPD. Unlike wild-type mice, hyperoxia-exposed periostin null mice did not show larger air spaces or α-smooth muscle-positive myofibroblasts. Compared to hyperoxia-exposed wild-type mice, hyperoxia-exposed periostin null mice also showed reduced lung mRNA expression of α-smooth muscle actin, elastin, CXCL1, CXCL2 and CCL4. TGF-β treatment increased mesenchymal stromal cell periostin expression, and periostin treatment increased TGF-β-mediated DNA synthesis and myofibroblast differentiation. We conclude that periostin expression is increased in the lungs of hyperoxia-exposed neonatal mice and infants with BPD, and is required for hyperoxia-induced hypoalveolarization and interstitial fibrosis.

Aberrant Bone Density in Aging Mice Lacking the Adenosine Transporter ENT1

Science.gov (United States)

Hinton, David J.; McGee-Lawrence, Meghan E.; Lee, Moonnoh R.; Kwong, Hoi K.; Westendorf, Jennifer J.; Choi, Doo-Sup

2014-01-01

Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1) is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months) compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density. PMID:24586402

Aberrant bone density in aging mice lacking the adenosine transporter ENT1.

Directory of Open Access Journals (Sweden)

David J Hinton

Full Text Available Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1 is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP, an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density.

Impaired Sperm Maturation in Rnase9 Knockout Mice1

Science.gov (United States)

Westmuckett, Andrew D.; Nguyen, Edward B.; Herlea-Pana, Oana M.; Alvau, Antonio; Salicioni, Ana M.; Moore, Kevin L.

2014-01-01

ABSTRACT Ribonuclease, RNase A family, 9 (RNASE9) is a ribonuclease A superfamily member that is expressed only in the epididymis. It is a small, secreted polypeptide, it lacks ribonuclease activity, and its function(s) is unknown. However, epididymis-specific expression suggests a role in sperm maturation. We generated Rnase9−/− mice to study RNASE9 function in vivo. We confirm that RNASE9 expression is restricted to the epididymis. Within the epididymis, RNASE9 is first detected in midcaput, persists through the distal caput and corpus, and wanes in the cauda. Rnase9−/− mice are born at the expected Mendelian ratio, have normal postnatal growth and development, and have no outwardly apparent phenotype. Spermatogenesis is normal, and Rnase9-null sperm are morphologically normal. Rnase9−/− males have normal fertility in unrestricted mating trials, and fertilization rates in in vitro fertilization assays are indistinguishable from wild-type mice. Visual observations coupled with analyses of sperm velocities shortly after swim out from the corpus shows that motility of Rnase9-null sperm is significantly impaired. However, no differences between wild-type and Rnase9-null sperm are detected by computer-assisted sperm analysis 10–90 min after sperm isolation from the corpus or cauda. Assessment of capacitation-dependent signaling pathways in Rnase9-null sperm showed that, while levels of tyrosine phosphorylation of sperm proteins were normal, there was decreased phosphorylation of protein kinase A substrates upon capacitation compared to wild-type mice. In conclusion, RNASE9 is dispensable for fertility, but the absence of RNASE9 during epididymal transit results in impaired sperm maturation. PMID:24719258

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

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.

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.)

Reduced hepatic tumor incidence in cyclin G1-deficient mice

DEFF Research Database (Denmark)

Jensen, Michael Rugaard; Factor, Valentina M; Fantozzi, Anna

2003-01-01

found that the p53 levels in the cyclin G1-deficient mice are 2-fold higher that in wild-type mice. Moreover, we showed that treatment of mice with the alkylating agent 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin), followed by partial hepatectomy, decreased G1-S transition in cyclin G1-null...

SAT in engineering support personnel training

International Nuclear Information System (INIS)

Gonzalez, M.

1995-01-01

The NPP engineering support functional area comprises seven common positions: reactor engineer, in-service inspection engineer, performance reliability engineer, system-maintenance engineer, station modification engineer, quality assurance engineer, and regulatory compliance engineer. The primary duties and tasks of each was presented. In Spain, a simplified SAT approach was used to analyze the training needs of these positions. The basic difference between the comprehensive SAT and the simplified method is that the simplified approach uses no taxonomy codes and the task elements are not analyzed to obtain the knowledge and skills. Resulting in an economy of time and personnel resources, this process makes use of job competencies and a top table analysis conducted by subject matter experts. An example of a JPM prepared using the simplified SAT approach was shown. Examples of the simplified approaches used in Russia, France, and USA were also discussed

Miniature scientific-grade magnetic sensors for CubeSats

Science.gov (United States)

Pronenko, Vira; Belyayev, Serhiy

2016-07-01

Micro- and nanosatellites have become more attractive due to their low development and launch cost. A class of nanosatellites defined by the CubeSat standard allows standardizing CubeSat preparation and launch, thus making the projects more affordable. Because of the complexity of sensors miniaturization to install them onboard CubeSat, the majority of CubeSat launches are aimed the technology demonstration or education missions. The scientific success of CubeSat mission depends on the sensors quality. In spite that the sensitivity of the magnetic sensors strongly depends on their size, the recent development in this branch allows us to propose tiny but sensitive both AC and DC magnetometers. The goal of the present report is to introduce the new design of miniature three-component sensors for measurement of vector magnetic fields - for quasi-stationary and slowly fluctuating - flux-gate magnetometer (FGM) - and for alternative ones - search-coil magnetometer (SCM). In order to create magnetometers with the really highest possible level of parameters, a set of scientific and technological problems, mostly aimed at the sensor construction improvement, was solved. The most important parameter characterizing magnetometer quality is its own magnetic noise level (NL). The analysis of the NL influencing factors is made and the ways to decrease it are discussed in the report. Construction details and technical specifications of miniature but sensitive FGM and SCM for the CubeSat mission are presented. This work is supported by EC Framework 7 funded project 607197.

A novel solid-angle tomosynthesis (SAT) scanning scheme

International Nuclear Information System (INIS)

Zhang Jin; Yu, Cedric

2010-01-01

Purpose: Digital tomosynthesis (DTS) recently gained extensive research interests in both diagnostic and radiation therapy fields. Conventional DTS images are generated by scanning an x-ray source and flat-panel detector pair on opposite sides of an object, with the scanning trajectory on a one-dimensional curve. A novel tomosynthesis method named solid-angle tomosynthesis (SAT) is proposed, where the x-ray source scans on an arbitrary shaped two-dimensional surface. Methods: An iterative algorithm in the form of total variation regulated expectation maximization is developed for SAT image reconstruction. The feasibility and effectiveness of SAT is corroborated by computer simulation studies using three-dimensional (3D) numerical phantoms including a 3D Shepp-Logan phantom and a volumetric CT image set of a human breast. Results: SAT is able to cover more space in Fourier domain more uniformly than conventional DTS. Greater coverage and more isotropy in the frequency domain translate to fewer artifacts and more accurately restored features in the in-plane reconstruction. Conclusions: Comparing with conventional DTS, SAT allows cone-shaped x-ray beams to project from more solid angles, thus provides more coverage in the spatial-frequency domain, resulting in better quality of reconstructed image.

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

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.

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.

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.

SAT-Based Software Certification

National Research Council Canada - National Science Library

Chaki, Sagar

2006-01-01

... predicate abstraction and validated by generating and proving verification conditions. In addition, the first part of the report proposes the use of theorem provers based on Boolean propositional satisfiability (SAT...

SAT vs. conventional one: comparison and benefits

International Nuclear Information System (INIS)

Kazennov, A.Yu.

1998-01-01

This paper emphasised the importance of management support to the success of training and qualification programmes, management understanding and commitment to the need of SAT, appropriate training policies, provision of human and financial resources, training of management and supervisory personnel as relevant regulatory body personnel in the field of SAT methodology principles in order to achieve their support

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

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

Evaluation of multi-mode CryoSat-2 altimetry data over the Po River against in situ data and a hydrodynamic model

DEFF Research Database (Denmark)

Schneider, Raphael; Tarpanelli, Angelica; Nielsen, Karina

2018-01-01

Coverage of in situ observations to monitor surface waters is insufficient on the global scale, and decreasing across the globe. Satellite altimetry has become an increasingly important monitoring technology for continental surface waters. The ESA CryoSat-2 altimetry mission, launched in 2010, has...... two novel features. (i) The radar altimeter instrument on board of CryoSat-2 is operated in three modes; two of them reduce the altimeter footprint by using Delay-Doppler processing. (ii) CryoSat-2 is placed on a distinct orbit with a repeat cycle of 369 days, leading to a drifting ground track...... pattern. The drifting ground track pattern challenges many common methods of processing satellite altimetry data over rivers. This study evaluates the observation error of CryoSat-2 water level observations over the Po River, Italy, against in situ observations. The average RMSE between CryoSat-2...

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.

Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice.

Science.gov (United States)

Ohno, Y; Egawa, T; Yokoyama, S; Nakai, A; Sugiura, T; Ohira, Y; Yoshioka, T; Goto, K

2015-12-01

Effects of heat shock transcription factor 1 (HSF1) deficiency on heat stress-associated increase in slow soleus muscle mass of mice were investigated. Both HSF1-null and wild-type mice were randomly assigned to control and heat-stressed groups. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anaesthesia. Significant increase in wet and dry weights, and protein content of soleus muscle in wild-type mice was observed seven days after the application of the heat stress. However, heat stress had no impact on soleus muscle mass in HSF1-null mice. Neither type of mice exhibited much effect of heat stress on HSF mRNA expression (HSF1, HSF2 and HSF4). On the other hand, heat stress upregulated heat shock proteins (HSPs) at the mRNA (HSP72) and protein (HSP72 and HSP110) levels in wild-type mice, but not in HSF1-null mice. The population of Pax7-positive nuclei relative to total myonuclei of soleus muscle in wild-type mice was significantly increased by heat stress, but not in HSF1-null mice. Furthermore, the absence of HSF1 gene suppressed heat stress-associated phosphorylation of Akt and p70 S6 kinase (p-p70S6K) in soleus muscle. Heat stress-associated increase in skeletal muscle mass may be induced by HSF1 and/or HSF1-mediated stress response that activates muscle satellite cells and Akt/p70S6K signalling pathway. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

College Math Assessment: SAT Scores vs. College Math Placement Scores

Science.gov (United States)

Foley-Peres, Kathleen; Poirier, Dawn

2008-01-01

Many colleges and university's use SAT math scores or math placement tests to place students in the appropriate math course. This study compares the use of math placement scores and SAT scores for 188 freshman students. The student's grades and faculty observations were analyzed to determine if the SAT scores and/or college math assessment scores…

CloudSat Safety Operations at Vandenberg AFB

Science.gov (United States)

Greenberg, Steve

2006-01-01

CloudSat safety operations at Vendenberg AFB is given. The topics include: 1) CloudSat Project Overview; 2) Vandenberg Ground Operations; 3) Delta II Launch Vehicle; 4) The A-Train; 5) System Safety Management; 6) CALIPSO Hazards Assessment; 7) CALIPSO Supplemental Safeguards; 8) Joint System Safety Operations; 9) Extended Stand-down; 10) Launch Delay Safety Concerns; and 11) Lessons Learned.

Evolving effective incremental SAT solvers with GP

OpenAIRE

Bader, Mohamed; Poli, R.

2008-01-01

Hyper-Heuristics could simply be defined as heuristics to choose other heuristics, and it is a way of combining existing heuristics to generate new ones. In a Hyper-Heuristic framework, the framework is used for evolving effective incremental (Inc*) solvers for SAT. We test the evolved heuristics (IncHH) against other known local search heuristics on a variety of benchmark SAT problems.

Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy

Science.gov (United States)

Criswell, D. S.; Booth, F. W.; DeMayo, F.; Schwartz, R. J.; Gordon, S. E.; Fiorotto, M. L.

1998-01-01

This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

Development of severe accident guidance module for the SATS simulator

International Nuclear Information System (INIS)

Kim, K.R.; Park, S.H.; Kim, D.H.; Song, Y.M.

2004-01-01

Recently KAERI has developed the severe accident management guidance to establish Korea standard severe accident management system. On the other hand the PC-based severe accident training simulator SATS has been developed, which uses MELCOR code as the simulation engine. SATS graphically displays and simulates the severe accidents with interactive user commands. The control capability of SATS could make severe accident training course more interesting and effective. In this paper we will describe the development and functions of the electrical hypertext guidance module HyperKAMG and the SATS-HyperKAMG linkage system for the severe accident management. (author)

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

Microwave Atmospheric Sounder on CubeSat

Science.gov (United States)

Padmanabhan, S.; Brown, S. E.; Kangaslahti, P.; Cofield, R.; Russell, D.; Stachnik, R. A.; Su, H.; Wu, L.; Tanelli, S.; Niamsuwan, N.

2014-12-01

To accurately predict how the distribution of extreme events may change in the future we need to understand the mechanisms that influence such events in our current climate. Our current observing system is not well-suited for observing extreme events globally due to the sparse sampling and in-homogeneity of ground-based in-situ observations and the infrequent revisit time of satellite observations. Observations of weather extremes, such as extreme precipitation events, temperature extremes, tropical and extra-tropical cyclones among others, with temporal resolution on the order of minutes and spatial resolution on the order of few kms (cost passive microwave sounding and imaging sensors on CubeSats that would work in concert with traditional flagship observational systems, such as those manifested on large environmental satellites (i.e. JPSS,WSF,GCOM-W), to monitor weather extremes. A 118/183 GHz sensor would enable observations of temperature and precipitation extremes over land and ocean as well as tropical and extra-tropical cyclones. This proposed project would enable low cost, compact radiometer instrumentation at 118 and 183 GHz that would fit in a 6U Cubesat with the objective of mass-producing this design to enable a suite of small satellites to image the key geophysical parameters needed to improve prediction of extreme weather events. We take advantage of past and current technology developments at JPL viz. HAMSR (High Altitude Microwave Scanning Radiometer), Advanced Component Technology (ACT'08) to enable low-mass, low-power high frequency airborne radiometers. In this paper, we will describe the design and implementation of the 118 GHz temperature sounder and 183 GHz humidity sounder on the 6U CubeSat. In addition, a summary of radiometer calibration and retrieval techniques of temperature and humidity will be discussed. The successful demonstration of this instrument on the 6U CubeSat would pave the way for the development of a constellation which

MethaneSat: Detecting Methane Emissions in the Barnett Shale Region

Science.gov (United States)

Propp, A. M.; Benmergui, J. S.; Turner, A. J.; Wofsy, S. C.

2017-12-01

In this study, we investigate the new information that will be provided by MethaneSat, a proposed satellite that will measure the total column dry-air mole fraction of methane at 1x1 km or 2x2 km spatial resolution with 0.1-0.2% random error. We run an atmospheric model to simulate MethaneSat's ability to characterize methane emissions from the Barnett Shale, a natural gas province in Texas. For comparison, we perform observation system simulation experiments (OSSEs) for MethaneSat, the National Oceanic and Atmospheric administration (NOAA) surface and aircraft network, and Greenhouse Gases Observing Satellite (GOSAT). The results demonstrate the added benefit that MethaneSat would provide in our efforts to monitor and report methane emissions. We find that MethaneSat successfully quantifies total methane emissions in the region, as well as their spatial distribution and steep gradients. Under the same test conditions, both the NOAA network and GOSAT fail to capture this information. Furthermore, we find that the results for MethaneSat depend far less on the prior emission estimate than do those for the other observing systems, demonstrating the benefit of high sampling density. The results suggest that MethaneSat would be an incredibly useful tool for obtaining detailed methane emission information from oil and gas provinces around the world.

Sirt6 Promotes DNA End Joining in iPSCs Derived from Old Mice

Directory of Open Access Journals (Sweden)

Wen Chen

2017-03-01

Full Text Available Induced pluripotent stem cells (iPSCs have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ, rather than homologous recombination (HR, is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ. Rescue experiments show that introducing a combination of Sirt6 and the Yamanaka factors during reprogramming significantly promotes DNA double-strand break (DSB repair by activating NHEJ in iPSCs derived from old mice. Thus, our study suggests a strategy to improve the quality of iPSCs derived from old donors by activating NHEJ and stabilizing the genome.

AMF3 CloudSat Overpasses Field Campaign Report

Energy Technology Data Exchange (ETDEWEB)

Matrosov, Sergey [University of Colorado, Boulder; National Oceanic and Atmospheric Administration (NOAA), Boulder, CO (United States). Earth System Research Lab.; Hardin, Joseph [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); De Boer, Gijs [University of Colorado, Boulder; National Oceanic and Atmospheric Administration (NOAA), Boulder, CO (United States). Earth System Research Lab.; Shupe, Matthew [University of Colorado, Boulder; National Oceanic and Atmospheric Administration (NOAA), Boulder, CO (United States). Earth System Research Lab.; Maahn, Maximillian [National Oceanic and Atmospheric Administration (NOAA), Boulder, CO (United States). Earth System Research Lab.; Williams, Christopher [University of Colorado, Boulder; National Oceanic and Atmospheric Administration (NOAA), Boulder, CO (United States). Earth System Research Lab.

2017-10-15

Synergy between ground-based and satellite radar observations of clouds and precipitation is important for refining the algorithms to retrieve hydrometeor microphysical parameters, improvements in the retrieval accuracy, and better understanding the advantages and limitations of different retrieval approaches. The new dual-frequency (Ka- and W-band, 35 GHz and 94 GHz) fully polarimetric scanning U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Research Facility cloud radars (SACRs-2) are advanced sensors aimed to significantly enhance remote sensing capabilities (Kollias et al. 2016). One of these radars was deployed as part of the third ARM Mobile Facility (AMF3) at Oliktok Point, Alaska (70.495o N, 149.886oW). The National Aeronautics and Space Administration (NASA) CloudSat satellite, which is part of the polar-orbiting A-train satellite constellation, passes over the vicinity of the AMF3 location (typically within 0-7 km depending on a particular overpass) on a descending orbit every 16 days at approximately 13:21 UTC. The nadir pointing W-band CloudSat cloud profiling radar (CPR) provides vertical profiles of reflectivity that are then used for retrievals of hydrometeor parameters (Tanelli et al. 2008). The main objective of the AMF3 CloudSat overpasses intensive operating period (IOP) campaign was to collect approximately collocated in space and time radar data from the SACR-2 and the CloudSat CPR measurements for subsequent joint analysis of radar variables and microphysical retrievals of cloud and precipitation parameters. Providing the reference for the SACR-2 absolute calibration from the well-calibrated CloudSat CPR was another objective of this IOP. The IOP objectives were achieved by conducting seven special SACR-2 scans during the 10.5-min period centered at the exact time of the CloudSat overpass over the AMF3 (~1321 UTC) on six dates of the CloudSat overpasses during the three-month period allocated to this IOP. These six days

LifeSat - Radiation research

International Nuclear Information System (INIS)

Nelson, G.A.

1990-01-01

Spaceflight crews will be exposed to levels of radiation which exceed those experienced on the ground. In order to reduce the uncertainty in the evaluation of risks it is necessary to validate the responses of biological systems in space under conditions which simulate exposure levels expected during exploration class missions. The LifeSat system provides the experimental capabilities to satisfy these goals. Specifically, LifeSat is capable of long duration flights of up to 60 days, is able to fly directly into trapped radiation belts and in circular or eccentric polar orbits, has the ability to provide artificial gravity and imposes fewer restrictions than the STS on the use of hazardous materials such as chemical fixatives. These features along with reference missions and experiments are discussed with respect to radiation research goals

Integrated Solar-Panel Antenna Array for CubeSats (ISAAC)

Data.gov (United States)

National Aeronautics and Space Administration — This project will develop a new subsystem technology for CubeSats. Integrated Solar-Panel Antenna Array for CubeSats (ISAAC) is an efficient, compact, high gain, low...

CloudSat Education Network: Partnerships for Outreach

Science.gov (United States)

TeBockhorst, D.

2014-12-01

CloudSat Education Network (CEN): Partnerships to improve the understanding of clouds in formal and informal settings. Since The CloudSat satellite launched in 2006 the Formal and Informal education programs for the mission have been focused on bringing an understanding about the mission science and the importance of clouds, climate & weather science. This has been done by creating and strengthening partnership and collaboration within scientific and educational communities around the country and the world. Because CloudSat was formally recognized as a Earth System Science Pathfinder campaign with the GLOBE program, the CEN developed a set of field protocols for student observations that augmented the GLOBE atmosphere protocols when there was a satellite overpass. This shared process between GLOBE & CloudSat resulted in the training & creation of CEN schools that are both GLOBE schools and CloudSat schools, and also produced three GLOBE partnerships that specialize in cloud science education and outreach. In addition, the CEN has developed productive relationships with other NASA missions and EPO teams. Specifically, in collaboration with the NASA CERES mission projects S'Cool and MyNASAData, we have co-presented at NSTA conferences and with schools participating in a NASA EPOESS-funded formal education project. This collaborative work has been a very real benefit to a wide variety of audiences needing to strengthen their understanding of clouds and their roles in the earth system, and we hope will serve as a model to future missions looking to involve the public in mission science.

Satélites de comunicación

Directory of Open Access Journals (Sweden)

Francisco Sacristán Romero

2015-01-01

Full Text Available Parte de que los satélites de comunicación son unos artilugios recién nacidos y en fase de desarrolllo. Describe la trayectoria histórica de éstos tres, el uso del satélite y el servicio de televisión, las redes, el HISPASAT enlace entre España y América dificultades y soluciones.

Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

International Nuclear Information System (INIS)

Nakashima, Ryosuke; Hayashi, Yumi; Khalequzzaman, Md.; Jia, Xiaofang; Wang, Dong; Naito, Hisao; Ito, Yuki; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

2013-01-01

Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels

Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress.

Science.gov (United States)

Abdelmegeed, Mohamed A; Choi, Youngshim; Ha, Seung-Kwoon; Song, Byoung-Joon

2017-11-01

The aim of this study was to investigate the role of cytochrome P450-2E1 (CYP2E1) in aging-dependent kidney damage since it is poorly understood. Young (7 weeks) and aged female (16-17 months old) wild-type (WT) and Cyp2e1-null mice were used. Kidney histology showed that aged WT mice exhibited typical signs of kidney aging such as cell vacuolation, inflammatory cell infiltration, cellular apoptosis, glomerulonephropathy, and fibrosis, along with significantly elevated levels of renal TNF-α and serum creatinine than all other groups. Furthermore, the highest levels of renal hydrogen peroxide, protein carbonylation and nitration were observed in aged WT mice. These increases in the aged WT mice were accompanied by increased levels of iNOS and mitochondrial nitroxidative stress through altered amounts and activities of the mitochondrial complex proteins and significantly reduced levels of the antioxidant glutathione (GSH). In contrast, the aged Cyp2e1-null mice exhibited significantly higher antioxidant capacity with elevated heme oxygenase-1 and catalase activities compared to all other groups, while maintaining normal GSH levels with significantly less mitochondrial nitroxidative stress compared to the aged WT mice. Thus, CYP2E1 is important in causing aging-related kidney damage most likely through increasing nitroxidative stress and that CYP2E1 could be a potential target in preventing aging-related kidney diseases. Published by Elsevier Ltd.

Using Additive Manufacturing to Print a CubeSat Propulsion System

Science.gov (United States)

Marshall, William M.

2015-01-01

CubeSats are increasingly being utilized for missions traditionally ascribed to larger satellites CubeSat unit (1U) defined as 10 cm x 10 cm x 11 cm. Have been built up to 6U sizes. CubeSats are typically built up from commercially available off-the-shelf components, but have limited capabilities. By using additive manufacturing, mission specific capabilities (such as propulsion), can be built into a system. This effort is part of STMD Small Satellite program Printing the Complete CubeSat. Interest in propulsion concepts for CubeSats is rapidly gaining interest-Numerous concepts exist for CubeSat scale propulsion concepts. The focus of this effort is how to incorporate into structure using additive manufacturing. End-use of propulsion system dictates which type of system to develop-Pulse-mode RCS would require different system than a delta-V orbital maneuvering system. Team chose an RCS system based on available propulsion systems and feasibility of printing using a materials extrusion process. Initially investigated a cold-gas propulsion system for RCS applications-Materials extrusion process did not permit adequate sealing of part to make this a functional approach.

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.

Foot-and-mouth disease virus serotype SAT1 in cattle, Nigeria.

Science.gov (United States)

Ehizibolo, D O; Haegeman, A; De Vleeschauwer, A R; Umoh, J U; Kazeem, H M; Okolocha, E C; Van Borm, S; De Clercq, K

2017-06-01

The knowledge of foot-and-mouth disease virus (FMDV) dynamics and epidemiology in Nigeria and the West Africa subregion is important to support local and regional control plans and international risk assessment. Foot-and-mouth disease virus serotype South African territories (SAT)1 was isolated, identified and characterized from an FMD outbreak in cattle in Nigeria in 2015, 35 years after the last report of FMDV SAT1 in West Africa. The VP1 coding sequence of the Nigerian 2015 SAT1 isolates diverges from reported SAT1 topotypes resulting in a separate topotype. The reporting of a novel FMDV SAT1 strain in the virus pool 5 (West and Central Africa) highlights the dynamic and complex nature of FMDV in this region of Africa. Sustained surveillance is needed to understand the origin, the extent and distribution of this novel SAT1 topotype in the region as well as to detect and monitor the occurrence of (re-)emerging FMDV strains. © 2017 Blackwell Verlag GmbH.

A SAT-Based Algorithm for Reparameterization in Symbolic Simulation

National Research Council Canada - National Science Library

Chauhan, Pankaj; Kroening, Daniel; Clarke, Edmund

2003-01-01

.... Efficient SAT solvers have been applied successfully for many verification problems. This paper presents a novel SAT-based reparameterization algorithm that is largely immune to the large number of input variables that need to be quantified...

Loss of ATM kinase activity leads to embryonic lethality in mice.

Science.gov (United States)

Daniel, Jeremy A; Pellegrini, Manuela; Lee, Baeck-Seung; Guo, Zhi; Filsuf, Darius; Belkina, Natalya V; You, Zhongsheng; Paull, Tanya T; Sleckman, Barry P; Feigenbaum, Lionel; Nussenzweig, André

2012-08-06

Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis.

Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure.

Science.gov (United States)

Rama Rao, Kakulavarapu V; Verkman, A S; Curtis, Kevin M; Norenberg, Michael D

2014-03-01

Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6% ± 0.3 and 2.3 ± 0.4%, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. Published by Elsevier Inc.

On the verge of an astronomy CubeSat revolution

Science.gov (United States)

Shkolnik, Evgenya L.

2018-05-01

CubeSats are small satellites built in standard sizes and form factors, which have been growing in popularity but have thus far been largely ignored within the field of astronomy. When deployed as space-based telescopes, they enable science experiments not possible with existing or planned large space missions, filling several key gaps in astronomical research. Unlike expensive and highly sought after space telescopes such as the Hubble Space Telescope, whose time must be shared among many instruments and science programs, CubeSats can monitor sources for weeks or months at time, and at wavelengths not accessible from the ground such as the ultraviolet, far-infrared and low-frequency radio. Science cases for CubeSats being developed now include a wide variety of astrophysical experiments, including exoplanets, stars, black holes and radio transients. Achieving high-impact astronomical research with CubeSats is becoming increasingly feasible with advances in technologies such as precision pointing, compact sensitive detectors and the miniaturization of propulsion systems. CubeSats may also pair with the large space- and ground-based telescopes to provide complementary data to better explain the physical processes observed.

Evaluation of multi-mode CryoSat-2 altimetry data over the Po River against in situ data and a hydrodynamic model

Science.gov (United States)

Schneider, Raphael; Tarpanelli, Angelica; Nielsen, Karina; Madsen, Henrik; Bauer-Gottwein, Peter

2018-02-01

Coverage of in situ observations to monitor surface waters is insufficient on the global scale, and decreasing across the globe. Satellite altimetry has become an increasingly important monitoring technology for continental surface waters. The ESA CryoSat-2 altimetry mission, launched in 2010, has two novel features. (i) The radar altimeter instrument on board of CryoSat-2 is operated in three modes; two of them reduce the altimeter footprint by using Delay-Doppler processing. (ii) CryoSat-2 is placed on a distinct orbit with a repeat cycle of 369 days, leading to a drifting ground track pattern. The drifting ground track pattern challenges many common methods of processing satellite altimetry data over rivers. This study evaluates the observation error of CryoSat-2 water level observations over the Po River, Italy, against in situ observations. The average RMSE between CryoSat-2 and in situ observations was found to be 0.38 meters. CryoSat-2 was also shown to be useful for channel roughness calibration in a hydrodynamic model of the Po River. The small across-track distance of CryoSat-2 means that observations are distributed almost continuously along the river. This allowed resolving channel roughness with higher spatial resolution than possible with in situ or virtual station altimetry data. Despite the Po River being extensively monitored, CryoSat-2 still provides added value thanks to its unique spatio-temporal sampling pattern.

Solving SAT Problem Based on Hybrid Differential Evolution Algorithm

Science.gov (United States)

Liu, Kunqi; Zhang, Jingmin; Liu, Gang; Kang, Lishan

Satisfiability (SAT) problem is an NP-complete problem. Based on the analysis about it, SAT problem is translated equally into an optimization problem on the minimum of objective function. A hybrid differential evolution algorithm is proposed to solve the Satisfiability problem. It makes full use of strong local search capacity of hill-climbing algorithm and strong global search capability of differential evolution algorithm, which makes up their disadvantages, improves the efficiency of algorithm and avoids the stagnation phenomenon. The experiment results show that the hybrid algorithm is efficient in solving SAT problem.

SAT-Expo 2009: parola d’ordine “applicazioni integrate”

Directory of Open Access Journals (Sweden)

Gianluca Pititto

2009-03-01

Full Text Available SAT-Expo Europe 2009 and integrated applicationsSAT-Expo was an exhibition held in Rome from the 19th until the 21st of March. SAT-Expo is the main euro-mediterranean satellite technology and services showcase.The 2009 edition featured 114 companies, 20 meeting sessions and more than 5400 attendees. This year's edition brought 10 foreign delegations, including France and China, together. The event focused on all the major topics regarding the satellite sector, including navigation, Earth Observation and communications.

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.

MoMoSat -- Mobile Service for Monitoring with GeoNotes via Satellite

Energy Technology Data Exchange (ETDEWEB)

Niemeyer, Irmgard [Forschungszentrum Juelich (Germany). Programme Group Systems Analysis and Technology Evaluation (STE); Jonas, Karl [Univ. of Applied Science Bonn-Rhein-Sieg, Sankt Augustin (Germany). FhG FOKUS CC SATCom; Horz, Alexander [horz informatik, Sankt Augustin (Germany); Wettschereck, Dietrich; Schmidt, Dirk [DIALOGIS GmbH, Bonn (Germany)

2003-05-01

The MoMoSat service will enable mobile end-users to view, manage, annotate, and communicate mapbased information in the field. The handled information exists of a huge volume of raster (satellite or aerial images) and vector data (i.e. street networks, cadastral maps or points of interest), as well as text-specific geo-referenced textual notes (the so-called 'GeoNotes') and real-time voice. A secure real-time communication between mobile units and the primary data store is an essential task of the MoMoSat service. The basic information is stored in the primary database that is accessible through a virtual private network (VPN) and cached at a server at a base station in order to ensure data availability. The base station may be installed in a car or another mobile vehicle. The two servers will periodically communicate with each other via secure satellite communication in order to check for updates. The base station supplies the relevant GIS data for the mobile units (people or even robots in the field at remote solutions). The communication between the mobile units is based on a peer-to-peer wireless local area network (WLAN) architecture. The mobile units are equipped with mobile computers (i.e. laptop, tablet PC or PDA) combined with a satellite-based positioning system (GPS) that enables them to request the proper geographic data sets from yhe base station's map server. An interactive mapping software shows the actual location on the map and allows the user to navigate (zoom, pan) through the high-resolution map display. The user can switch 'on' or 'off' several thematic layers (i.e. street network or points of interest) on the map. The software also supports collaborative aspects of MoMoSat by offering tools for the management of the GeoNotes that can be visualized by categories. The user can extend the existing GeoNotes with his personnel comments or create new GeoNotes by defining categories, recipients and the level of

CubeSat Nighttime Earth Observations

Science.gov (United States)

Pack, D. W.; Hardy, B. S.; Longcore, T.

2017-12-01

Satellite monitoring of visible emissions at night has been established as a useful capability for environmental monitoring and mapping the global human footprint. Pioneering work using Defense Meteorological Support Program (DMSP) sensors has been followed by new work using the more capable Visible Infrared Imaging Radiometer Suite (VIIRS). Beginning in 2014, we have been investigating the ability of small visible light cameras on CubeSats to contribute to nighttime Earth science studies via point-and-stare imaging. This paper summarizes our recent research using a common suite of simple visible cameras on several AeroCube satellites to carry out nighttime observations of urban areas and natural gas flares, nighttime weather (including lighting), and fishing fleet lights. Example results include: urban image examples, the utility of color imagery, urban lighting change detection, and multi-frame sequences imaging nighttime weather and large ocean areas with extensive fishing vessel lights. Our results show the potential for CubeSat sensors to improve monitoring of urban growth, light pollution, energy usage, the urban-wildland interface, the improvement of electrical power grids in developing countries, light-induced fisheries, and oil industry flare activity. In addition to orbital results, the nighttime imaging capabilities of new CubeSat sensors scheduled for launch in October 2017 are discussed.

[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.

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.

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

First report of [i]Enterocytozoon[/i] bieneusi and [i]Encephalitozoon intestinalis[/i] infection of wild mice in Slovakia

Directory of Open Access Journals (Sweden)

Oľga Danišová

2015-05-01

Full Text Available Increased risk of zoonotic transmission of the potential human pathogenic species [i]Enterocytozoon bieneusi[/i], [i]Encephalitozoon intestinalis[/i] and [i]Encephalitozoon cuniculi [/i]was detected in wild immunocompetent mice (Mus musculus musculus; n=280. Analysis was conducted with the use of PMP1/PMP2 primers and SYBR Green RT-PCR. Using Real Time PCR and comparing the sequences with sequences in the GenBank, [i]E. bieneusi[/i] was detected in 3 samples (1.07 %, [i]E. cuniculi [/i]in 1 sample (0.35 % and [i]E. intestinalis[/i] in 1 sample (0.35 %. The results of this report document the low host specificity of detected microsporidia species, and imply the importance of synanthropic rodents as a potential source of human microsporidial infection.

SAT-WIND project. Final report[Winds from satellites for offshore and coastal wind energy mapping and wind-indexing

Energy Technology Data Exchange (ETDEWEB)

Hasager, C.B.; Astrup, P.; Nielsen, M. (and others)

2007-04-15

The SAT-WIND project 'Winds from satellites for offshore and coastal wind energy mapping and wind-indexing' was a research project funded by STVF/DSF in the years 2003 to 2006 (Sagsnr. 2058-03-0006). The goal of the project was to verify the applicability of satellite wind maps derived from passive microwave, altimeter, scatterometer and imaging Synthetic Aperture Radar (SAR) technologies for wind energy tools for wind resources and wind-indexing. The study area was the Danish Seas including the North Sea, interior seas and the Baltic Sea. The report describes technical details on the satellite data sources including: 1) passive microwave (SSM/I, AMSR-E), 2) passive microwave polarimetric (WindSat), 3) scatterometer (ERS, QuikSCAT, Midori-2 and NSCAT), 4) altimeter (ERS, Topex, Poseidon, GFO-1, Jason-1), 5) SAR (ERS, Envisat). The SAR wind maps were treated in S-WAsP developed by Risoe National Laboratory in cooperation with GRAS A/S in the innovative project SAT-WIND-SMV (Sagsnr. 2104-05-0084) in the years 2005 and 2006 in parallel with SAT-WIND. The results from the SAT-WIND project are presented. These include ocean wind statistics, offshore wind resource estimates and comparison results for wind-indexing. (au)

SAT-WIND project. Final report[Winds from satellites for offshore and coastal wind energy mapping and wind-indexing

Energy Technology Data Exchange (ETDEWEB)

Hasager, C B; Astrup, P; Nielsen, M [and others

2007-04-15

The SAT-WIND project 'Winds from satellites for offshore and coastal wind energy mapping and wind-indexing' was a research project funded by STVF/DSF in the years 2003 to 2006 (Sagsnr. 2058-03-0006). The goal of the project was to verify the applicability of satellite wind maps derived from passive microwave, altimeter, scatterometer and imaging Synthetic Aperture Radar (SAR) technologies for wind energy tools for wind resources and wind-indexing. The study area was the Danish Seas including the North Sea, interior seas and the Baltic Sea. The report describes technical details on the satellite data sources including: 1) passive microwave (SSM/I, AMSR-E), 2) passive microwave polarimetric (WindSat), 3) scatterometer (ERS, QuikSCAT, Midori-2 and NSCAT), 4) altimeter (ERS, Topex, Poseidon, GFO-1, Jason-1), 5) SAR (ERS, Envisat). The SAR wind maps were treated in S-WAsP developed by Risoe National Laboratory in cooperation with GRAS A/S in the innovative project SAT-WIND-SMV (Sagsnr. 2104-05-0084) in the years 2005 and 2006 in parallel with SAT-WIND. The results from the SAT-WIND project are presented. These include ocean wind statistics, offshore wind resource estimates and comparison results for wind-indexing. (au)

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 .

Burn injury reveals altered phenotype in mannan-binding lectin-deficient mice

DEFF Research Database (Denmark)

Møller-Kristensen, Mette; Hamblin, Michael R; Thiel, Steffen

2007-01-01

Burn injury destroys skin, the second largest innate immune organ in the body, and triggers chaotic immune and inflammatory responses. The pattern recognition molecule, mannan-binding lectin (MBL), plays an important role in the first-line host defense against infectious agents. MBL initiates...... the lectin complement pathway and acts as an opsonin. Recent studies suggest that MBL also modulates inflammatory responses. We report that local responses after burn in MBL null mice differ from those found in wild-type (WT) mice in the following important biological markers: spontaneous eschar separation......, thinned epidermis and dermis, upregulation of soluble factors including cytokines, chemokines, cell adhesion molecules, a growth factor-binding protein, and matrix metalloproteinases. Mice lacking C1q, C4, or C3 did not show the lack of eschar separation seen in MBL null-burn phenotype. These findings...

Bare Quantum Null Energy Condition.

Science.gov (United States)

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.

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

High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

Science.gov (United States)

Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

2015-11-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

A hybrid bit-encoding for SAT planning based on clique-partitioning

Science.gov (United States)

Tapia, Cristóbal; San Segundo, Pablo; Galán, Ramón

2017-09-01

Planning as satisfiability is one of the most efficient ways to solve classic automated planning problems. In SAT planning, the encoding used to convert the problem to a SAT formula is critical for the performance of the SAT solver. This paper presents a novel bit-encoding that reduces the number of bits required to represent actions in a SAT-based automated planning problem. To obtain such encoding we first build a conflict graph, which represents incompatibilities of pairs of actions, and bitwise encode the subsets of actions determined by a clique partition. This reduces the number of Boolean variables and clauses of the SAT encoding, while preserving the possibility of parallel execution of compatible (non-neighbor) actions. The article also describes an appropriate algorithm for selecting the clique partition for this application and compares the new encodings obtained over some standard planning problems.

Airborne campaigns for CryoSat pre-launch calibration and validation

DEFF Research Database (Denmark)

Hvidegaard, Sine Munk; Forsberg, René; Skourup, Henriette

2010-01-01

From 2003 to 2008 DTU Space together with ESA and several international partners carried out airborne and ground field campaigns in preparation for CryoSat validation; called CryoVEx: CryoSat Validation Experiments covering the main ice caps in Greenland, Canada and Svalbard and sea ice in the Ar......From 2003 to 2008 DTU Space together with ESA and several international partners carried out airborne and ground field campaigns in preparation for CryoSat validation; called CryoVEx: CryoSat Validation Experiments covering the main ice caps in Greenland, Canada and Svalbard and sea ice...... in the Arctic Ocean. The main goal of the airborne surveys was to acquire coincident scanning laser and CryoSat type radar elevation measurements of the surface; either sea ice or land ice. Selected lines have been surveyed along with detailed mapping of validation sites coordinated with insitu field work...... and helicopter electromagnetic surveying. This paper summarises the pre-launch campaigns and presents some of the result from the coincident measurement from airborne and ground observations....

Barron's SAT math workbook

CERN Document Server

Leff MS, Lawrence S

2016-01-01

This completely revised edition reflects all of the new questions and question types that will appear on the new SAT, scheduled to be administered in Spring 2016. Includes hundreds of revised math questions and answer explanations, math strategies, test-taking tips, and much more.

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.

AgSat Imagery Collection Footprints

Data.gov (United States)

Farm Service Agency, Department of Agriculture — The AgSat Imagery Collection Footprints map shows the imagery footprints which have been collected under the USDA satellite blanket purchase agreement. Click on a...

SAT, a flexible and optimized Web application for SSR marker development

Directory of Open Access Journals (Sweden)

Rami Jean-François

2007-11-01

Full Text Available Abstract Background Simple Sequence Repeats (SSRs, or microsatellites, are among the most powerful genetic markers known. A common method for the development of SSR markers is the construction of genomic DNA libraries enriched for SSR sequences, followed by DNA sequencing. However, designing optimal SSR markers from bulk sequence data is a laborious and time-consuming process. Results SAT (SSR Analysis Tool is a user-friendly Web application developed to minimize tedious manual operations and reduce errors. This tool facilitates the integration, analysis and display of sequence data from SSR-enriched libraries. SAT is designed to successively perform base calling and quality evaluation of chromatograms, eliminate cloning vector, adaptors and low quality sequences, detect chimera or partially digested sequences, search for SSR motifs, cluster and assemble the redundant sequences, and design SSR primer pairs. An additional virtual PCR step establishes primer specificity. Users may modify the different parameters of each step of the SAT analysis. Although certain steps are compulsory, such as SSR motifs search and sequence assembly, users do not have to run the entire pipeline, and they can choose selectively which steps to perform. A database allows users to store and query results, and to redo individual steps of the workflow. Conclusion The SAT Web application is available at http://sat.cirad.fr/sat, and a standalone command-line version is also freely downloadable. Users must send an email to the SAT administrator tropgene@cirad.fr to request a login and password.

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.

Cloud occurrences and cloud radiative effects (CREs) from CERES-CALIPSO-CloudSat-MODIS (CCCM) and CloudSat radar-lidar (RL) products

Science.gov (United States)

Ham, Seung-Hee; Kato, Seiji; Rose, Fred G.; Winker, David; L'Ecuyer, Tristan; Mace, Gerald G.; Painemal, David; Sun-Mack, Sunny; Chen, Yan; Miller, Walter F.

2017-08-01

Two kinds of cloud products obtained from Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO), CloudSat, and Moderate Resolution Imaging Spectroradiometer (MODIS) are compared and analyzed in this study: Clouds and the Earth's Radiant Energy System (CERES)-CALIPSO-CloudSat-MODIS (CCCM) product and CloudSat radar-lidar products such as GEOPROF-LIDAR and FLXHR-LIDAR. Compared to GEOPROF-LIDAR, low-level (40°). The difference occurs when hydrometeors are detected by CALIPSO lidar but are undetected by CloudSat radar. In the comparison of cloud radiative effects (CREs), global mean differences between CCCM and FLXHR-LIDAR are mostly smaller than 5 W m-2, while noticeable regional differences are found. For example, CCCM shortwave (SW) and longwave (LW) CREs are larger than FXLHR-LIDAR along the west coasts of Africa and America because the GEOPROF-LIDAR algorithm misses shallow marine boundary layer clouds. In addition, FLXHR-LIDAR SW CREs are larger than the CCCM counterpart over tropical oceans away from the west coasts of America. Over midlatitude storm-track regions, CCCM SW and LW CREs are larger than the FLXHR-LIDAR counterpart.

CubeSat constellations for disaster management in remote areas

Science.gov (United States)

Santilli, Giancarlo; Vendittozzi, Cristian; Cappelletti, Chantal; Battistini, Simone; Gessini, Paolo

2018-04-01

In recent years, CubeSats have considerably extended their range of possible applications, from a low cost means to train students and young researchers in space related activities up to possible complementary solutions to larger missions. Increasingly popular, whereas CubeSats are still not a solution for all types of missions, they offer the possibility of performing ambitious scientific experiments. Especially worth considering is the possibility of performing Distributed Space Missions, in which CubeSat systems can be used to increase observation sampling rates and resolutions, as well as to perform tasks that a single satellite is unable to handle. The cost of access to space for traditional Earth Observation (EO) missions is still quite high. Efficient architecture design would allow reducing mission costs by employing CubeSat systems, while maintaining a level of performance that, for some applications, could be close to that provided by larger platforms, and decreasing the time needed to design and deploy a fully functional constellation. For these reasons many countries, including developing nations, agencies and organizations are looking to CubeSat platforms to access space cheaply with, potentially, tens of remote sensing satellites. During disaster management, real-time, fast and continuous information broadcast is a fundamental requirement. In this sense, a constellation of small satellites can considerably decrease the revisit time (defined as the time elapsed between two consecutive observations of the same point on Earth by a satellite) over remote areas, by increasing the number of spacecraft properly distributed in orbit. This allows collecting as much data as possible for the use by Disaster Management Centers. This paper describes the characteristics of a constellation of CubeSats built to enable access over the most remote regions of Brazil, supporting an integrated system for mitigating environmental disasters in an attempt to prevent the

Introduction of the SAT based training programs at Paks NPP

International Nuclear Information System (INIS)

Kiss, I.

1998-01-01

An introduction of the SAT based training programs at Paks nuclear power plant is described in detail, including framework of project operation; project implementation; process of SAT applied at Paks NPP and the needs of its introduction

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

Science.gov (United States)

Hwang, M; Go, Y; Park, J-H; Shin, S-K; Song, S E; Oh, B-C; Im, S-S; Hwang, I; Jeon, Y H; Lee, I-K; Seino, S; Song, D-K

2017-02-01

The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic

AgSat Areas of Interest

Data.gov (United States)

Farm Service Agency, Department of Agriculture — The AgSat Areas of Interest map contains area polygons where satellite imagery will be collected for the Farm Service Agency (FSA) to provide imagery coverage for...

Forebrain deletion of αGDI in adult mice worsens the pre-synaptic deficit at cortico-lateral amygdala synaptic connections.

Directory of Open Access Journals (Sweden)

Veronica Bianchi

Full Text Available The GDI1 gene encodes αGDI, which retrieves inactive GDP-bound RAB from membranes to form a cytosolic pool awaiting vesicular release. Mutations in GDI1 are responsible for X-linked Intellectual Disability. Characterization of the Gdi1-null mice has revealed alterations in the total number and distribution of hippocampal and cortical synaptic vesicles, hippocampal short-term synaptic plasticity and specific short-term memory deficits in adult mice, which are possibly caused by alterations of different synaptic vesicle recycling pathways controlled by several RAB GTPases. However, interpretation of these studies is complicated by the complete ablation of Gdi1 in all cells in the brain throughout development. In this study, we generated conditionally gene-targeted mice in which the knockout of Gdi1 is restricted to the forebrain, hippocampus, cortex and amygdala and occurs only during postnatal development. Adult mutant mice reproduce the short-term memory deficit previously reported in Gdi1-null mice. Surprisingly, the delayed ablation of Gdi1 worsens the pre-synaptic phenotype at cortico-amygdala synaptic connections compared to Gdi1-null mice. These results suggest a pivotal role of αGDI via specific RAB GTPases acting specifically in forebrain regions at the pre-synaptic sites involved in memory formation.

COLD-SAT feasibility study safety analysis

Science.gov (United States)

Mchenry, Steven T.; Yost, James M.

1991-01-01

The Cryogenic On-orbit Liquid Depot-Storage, Acquisition, and Transfer (COLD-SAT) satellite presents some unique safety issues. The feasibility study conducted at NASA-Lewis desired a systems safety program that would be involved from the initial design in order to eliminate and/or control the inherent hazards. Because of this, a hazards analysis method was needed that: (1) identified issues that needed to be addressed for a feasibility assessment; and (2) identified all potential hazards that would need to be controlled and/or eliminated during the detailed design phases. The developed analysis method is presented as well as the results generated for the COLD-SAT system.

Sampling and sensitivity analyses tools (SaSAT for computational modelling

Directory of Open Access Journals (Sweden)

Wilson David P

2008-02-01

Full Text Available Abstract SaSAT (Sampling and Sensitivity Analysis Tools is a user-friendly software package for applying uncertainty and sensitivity analyses to mathematical and computational models of arbitrary complexity and context. The toolbox is built in Matlab®, a numerical mathematical software package, and utilises algorithms contained in the Matlab® Statistics Toolbox. However, Matlab® is not required to use SaSAT as the software package is provided as an executable file with all the necessary supplementary files. The SaSAT package is also designed to work seamlessly with Microsoft Excel but no functionality is forfeited if that software is not available. A comprehensive suite of tools is provided to enable the following tasks to be easily performed: efficient and equitable sampling of parameter space by various methodologies; calculation of correlation coefficients; regression analysis; factor prioritisation; and graphical output of results, including response surfaces, tornado plots, and scatterplots. Use of SaSAT is exemplified by application to a simple epidemic model. To our knowledge, a number of the methods available in SaSAT for performing sensitivity analyses have not previously been used in epidemiological modelling and their usefulness in this context is demonstrated.

Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

International Nuclear Information System (INIS)

Shan, Qiuli; Wang, Jing; Huang, Fengchen; Lv, Xiaowen; Ma, Min; Du, Yuguo

2014-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants found as complex mixtures in the environment throughout the world. Therefore, humans are ubiquitously and simultaneously exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to atherosclerosis. However, the effects of interactions or synergism between TCDD and PCBs on atherogenesis are unknown. We investigated the possible enhanced atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s) involved in this enhancement. Male ApoE −/− mice were exposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over six weeks of duration. Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone, developed atherosclerotic lesions. Moreover, we found that atherosclerotic disease was exacerbated to the greatest extent in mice co-exposed to TCDD and Aroclor1254. The enhanced lesions correlated with several pro-atherogenic changes, including a marked increase in the accumulation of the platelet-derived chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and Aroclor1254 markedly enhanced atherogenesis in ApoE −/− mice. Significantly, our observations suggest that combined exposure to TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies. - Highlights: • Augmented atherogenesis was found in ApoE −/− mice co-exposed to Aroclor1254 and TCDD. • Enhanced expression of PF4, MCP-1 and RIG-I correlated with augmented lesions. • POPs combination may be a greater cardiovascular health risk than individual POPs

Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

Energy Technology Data Exchange (ETDEWEB)

Shan, Qiuli [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Wang, Jing, E-mail: avaecn@gmail.com [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Huang, Fengchen [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Lv, Xiaowen [Feed Safety Reference Laboratory of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Zhongguancun South Street 12, Beijing 100081 (China); Ma, Min [Laboratory of Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Du, Yuguo [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)

2014-04-15

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants found as complex mixtures in the environment throughout the world. Therefore, humans are ubiquitously and simultaneously exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to atherosclerosis. However, the effects of interactions or synergism between TCDD and PCBs on atherogenesis are unknown. We investigated the possible enhanced atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s) involved in this enhancement. Male ApoE{sup −/−} mice were exposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over six weeks of duration. Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone, developed atherosclerotic lesions. Moreover, we found that atherosclerotic disease was exacerbated to the greatest extent in mice co-exposed to TCDD and Aroclor1254. The enhanced lesions correlated with several pro-atherogenic changes, including a marked increase in the accumulation of the platelet-derived chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and Aroclor1254 markedly enhanced atherogenesis in ApoE{sup −/−} mice. Significantly, our observations suggest that combined exposure to TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies. - Highlights: • Augmented atherogenesis was found in ApoE{sup −/−} mice co-exposed to Aroclor1254 and TCDD. • Enhanced expression of PF4, MCP-1 and RIG-I correlated with augmented lesions. • POPs combination may be a greater cardiovascular health risk than individual POPs.

CryoSat Data Quality Overview

Science.gov (United States)

Bouzinac, Catherine; Fornari, Marco; Mannan, Rubinder; Parrinello, Tommaso

2013-09-01

The main objective of CryoSat mission is the observation of ice thickness with SAR interferometry. CryoSat data are routinely controlled by ESA-ESRIN- SPPA office with various tools and with the support of the IDEAS industrial consortium. This presentation introduces to the different instrumental modes and processing levels, the available quality tools (Quality Checks and Monitoring Facility) and visualisation tools, and shows the main statistical results from the data acquired and processed with the new processing version (since February 2012). A major data quality improvement is obtained from this new release of the specialized processors for all instrument modes. These new processors are also used this year for a full reprocessing campaign. This presentation also details the main improvements expected from the next release of the specialized processors in 2013.

IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice.

Science.gov (United States)

Lynch, G S; Cuffe, S A; Plant, D R; Gregorevic, P

2001-04-01

Although insulin-like growth factor-I (IGF-I) has been proposed for use by patients suffering from muscle wasting conditions, few studies have investigated the functional properties of dystrophic skeletal muscle following IGF-I treatment. 129P1 ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer from a deficiency in the structural protein, laminin, and exhibit severe muscle wasting and weakness. We tested the hypothesis that 4 weeks of IGF-I treatment ( approximately 2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutaneously) would increase the mass and force producing capacity of skeletal muscles from dystrophic mice. IGF-I treatment increased the mass of the extensor digitorum longus (EDL) and soleus muscles of dystrophic mice by 20 and 29%, respectively, compared with untreated dystrophic mice (administered saline-vehicle only). Absolute maximum force (P(o)) of the EDL and soleus muscle was increased by 40 and 32%, respectively, following IGF-I treatment. Specific P(o) (sP(o)) was increased by 23% in the EDL muscles of treated compared with untreated mice, but in the soleus muscle sP(o) was unchanged. IGF-I treatment increased the proportion of type IIB and type IIA fibres and decreased the proportion of type I fibres in the EDL muscles of dystrophic mice. In the soleus muscles of dystrophic mice, IGF-I treatment increased the proportion of type IIA fibres and decreased the proportion of type I fibres. Average fibre cross-sectional area was increased in the EDL and soleus muscles of treated compared with untreated mice. We conclude that IGF-I treatment ameliorates muscle wasting and improves the functional properties of skeletal muscles of dystrophic mice. The findings have important implications for the role of IGF-I in ameliorating muscle wasting associated with the muscular dystrophies.

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.

Mothership - Affordable Exploration of Planetary Bodies through Individual Nano-Sats and Swarms

Science.gov (United States)

DiCorcia, James D.; Ernst, Sebastian M.; Grace, J. Mike; Gump, David P.; Lewis, John S.; Foulds, Craig F.; Faber, Daniel R.

2015-04-01

One concept to enable broad participation in the scientific exploration of small bodies is the Mothership mission architecture which delivers third-party nano-sats, experiments, and sensors to a near Earth asteroid or comet. Deep Space Industries' Mothership service includes delivery of nano-sats, communication to Earth, and visuals of the asteroid surface and surrounding area. It allows researchers to house their instruments in a low-cost nano-sat platform that does not require the high-performance propulsion or deep space communication capabilities that otherwise would be required for a solo asteroid mission. This enables organizations with relatively low operating budgets to closely examine an asteroid with highly specialized sensors of their own choosing, while the nano-sats can be built or commissioned by a variety of smaller institutions, companies, or agencies. In addition, the Mothership and its deployed nano-sats can offer a platform for instruments which need to be distributed over multiple spacecraft. The Mothership is designed to carry 10 to 12 nano-sats, based upon a variation of the Cubesat standard, with some flexibility on the specific geometry. The Deep Space Nano-Sat reference design is a 14.5 cm cube, which accomodates the same volume as a traditional 3U Cubesat. This design was found to be more favorable for deep space due to its thermal characteristics. The CubeSat standard was originally designed with operations in low Earth orbit in mind. By deliberately breaking the standard, Deep Space Nano-Sats offer better performance with less chance of a critical malfunction in the more hostile deep space environment. The first mission can launch as early as Q4 2017, with subsequent, regular launches through the 2020's.

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)

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.

NPS-SCAT: A CubeSat Communications System Design, Test, and Integration

Science.gov (United States)

2009-06-01

markets the system as a CubeSat Kit. Microhard Systems Inc. manufactures products that are complementary to the Pumpkin structure and the FM430 Flight...NPS CubeSats and leverage COTS technology during that process. With that philosophy in mind, the program chose the Pumpkin Inc. 1U CubeSat...Skeletonized Structure and the FM430 Flight Module that is already integrated within the Pumpkin structure ( Pumpkin Incorporated, 2005, p. 2). Pumpkin

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…

Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARgamma.

Science.gov (United States)

Evans, Nicholas P; Misyak, Sarah A; Schmelz, Eva M; Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-03-01

Conjugated linoleic acid (CLA) exerts a protective effect on experimental inflammatory bowel disease and shows promise as a chemopreventive agent against colorectal cancer (CRC) in mice, although the mechanisms by which it exerts its beneficial effects against malignancies in the gut are not completely understood. Mice lacking PPARgamma in immune and epithelial cells and PPARgamma-expressing littermates were fed either control or CLA-supplemented (1 g CLA/100 g) diets to determine the role of PPARgamma in inflammation-induced CRC. To induce tumor formation and colitis, mice were treated with azoxymethane and then challenged with 2% dextran sodium sulfate, respectively. Dietary CLA ameliorated disease activity, decreased colitis, and prevented adenocarcinoma formation in the PPARgamma-expressing floxed mice but not in the tissue-specific PPARgamma-null mice. Dietary CLA supplementation significantly decreased the percentages of macrophages in the mesenteric lymph nodes (MLN) regardless of the genotype and increased regulatory T cell numbers in MLN of PPARgamma-expressing, but not in the tissue-specific, PPARgamma-null mice. Colonic tumor necrosis factor-alpha mRNA expression was significantly suppressed in CLA-fed, PPARgamma-expressing mice. This study suggests CLA ameliorates colitis and prevents tumor formation in part through a PPARgamma-dependent mechanism.

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen.

Science.gov (United States)

Terajima, Masahiko; Taga, Yuki; Chen, Yulong; Cabral, Wayne A; Hou-Fu, Guo; Srisawasdi, Sirivimol; Nagasawa, Masako; Sumida, Noriko; Hattori, Shunji; Kurie, Jonathan M; Marini, Joan C; Yamauchi, Mitsuo

2016-04-29

Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet 10, e1004465). However, the extent of decrease appears to be tissue- and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. We found that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1-3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen*

Science.gov (United States)

Terajima, Masahiko; Taga, Yuki; Chen, Yulong; Cabral, Wayne A.; Hou-Fu, Guo; Srisawasdi, Sirivimol; Nagasawa, Masako; Sumida, Noriko; Hattori, Shunji; Kurie, Jonathan M.; Marini, Joan C.; Yamauchi, Mitsuo

2016-01-01

Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet. 10, e1004465). However, the extent of decrease appears to be tissue- and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. We found that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1–3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation. PMID:26934917

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...

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.

Distribution in pregnant mice of radioactivity after injection of 131I, and immunosuppressive effect by the whole body irradiation

International Nuclear Information System (INIS)

Sushida, Kiyo; Nakano, Hisao

1978-01-01

For the purpose of decreasing resistance to leprous bacilli, 100 μCi of 131 I was injected subcutaneously to 2-3 week pregnant, dd-strain mice. Internal distribution of 131 I was followed up by measuring radioactivity in each organ of parent mice (I-P) and fetal mice (I-F). 300 rad in all of 60 Co was irradiated to 2-3 week pregnant mice (R-P) in two directions from the dorsal side of the abdomen. Immunosuppressive effect of the irradiation was evaluated in the parent mice and their offsprings (R-F) and compared with that in the 131 I-treated mice using a skin graft method. It was shown that 131 I of parent mice stayed in the uterus and was transmitted to their fetus through the placenta, and clarified that 131 I which remained in parent mice was continually supplied to their infant mice through milk still after birth. These findings seem to explaine the result that I-F which had been affected continually by 131 I had higher sensitivity to leprous bacilli than I-P. Immunosuppressive effect on a skin graft disclosed that the chief mechanisms of 131 I are to decrease the function of the reticulo-endothelial system by iodine and to suppress cellular immunity by its radioactivity. The rejecting time for the mouse skin homograft in the untreated mouse was 8.8 days on the average, and the lymph node weight was 33 mg. The order of the duration in the graft survival was R-P>I-F>I-P>R-F> normal mice, while that of lymph node weights was completely inverse. Therefore, the immunosuppressive effect on I-P and I-F mice, when it is compared with normal mice, could be confirmed, and the I-F was said to be favorable further than to I-P when based on this immunity test by transplantation. (Ueda, J.)

The CryoSat Interferometer after 6 years in orbit: calibration and achievable performance

Science.gov (United States)

Scagliola, Michele; Fornari, Marco; De Bartolomei, Maurizio; Bouffard, Jerome; Parrinello, Tommaso

2016-04-01

The main payload of CryoSat is a Ku-band pulse width limited radar altimeter, called SIRAL (Synthetic interferometric radar altimeter). When commanded in SARIn (synthetic aperture radar interferometry) mode, through coherent along-track processing of the returns received from two antennas, the interferometric phase related to the first arrival of the echo is used to retrieve the angle of arrival of the scattering in the across-track direction. In fact, the across-track echo direction can be derived by exploiting the precise knowledge of the baseline vector (i.e. the vector between the two antennas centers of phase) and simple geometry. The end-to-end calibration strategy for the CryoSat interferometer consists on in-orbit calibration campaigns following the approach described in [1]. From the beginning of the CryoSat mission, about once a year the interferometer calibration campaigns have been periodically performed by rolling left and right the spacecraft of about ±0.4 deg. This abstract is aimed at presenting our analysis of the calibration parameters and of the achievable performance of the CryoSat interferometer over the 6 years of mission. Additionally, some further studies have been performed to assess the accuracy of the roll angle computed on ground as function of the aberration (the apparent displacement of a celestial object from its true position, caused by the relative motion of the observer and the object) correction applied to the attitude quaternions, provided by the Star Tracker mounted on-board. In fact, being the roll information crucial to obtain an accurate estimate of the angle of arrival, the data from interferometer calibration campaigns have been used to verify how the application of the aberration correction affects the roll information and, in turns, the measured angle of arrival. [1] Galin, N.; Wingham, D.J.; Cullen, R.; Fornari, M.; Smith, W.H.F.; Abdalla, S., "Calibration of the CryoSat-2 Interferometer and Measurement of Across

SAT Expo Europe 2010: EGNOS, GALILEO e politica geospaziale

Directory of Open Access Journals (Sweden)

Gianluca Pititto

2010-03-01

Full Text Available SatExpo Europe 2010The 2010 edition of SatExpo Europe has been held in Rome since the 6th until the 8th of february. The event focused on Navigation, Earth Observation and Advanced Telecommunications, with a special reference to the european market and the international colalborations between space agencies.

Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6

DEFF Research Database (Denmark)

Molinero, Amalia; Penkowa, Milena; Hernández, Joaquín

2003-01-01

in this report support the idea that the upregulation of MT-I observed in GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, GFAP-IL6 mice that were crossed with TgMTI transgenic mice (GFAP-IL6xTgMTI) and overexpressed MT-I in the brain showed a decreased upregulation of cytokines...... such as IL-6 and a diminished recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. The GFAP-IL6 mice showed clear evidence of increased oxidative stress, which was significantly decreased by MT-I overexpression. Interestingly, MT-I overexpression increased...

Peripheral mechanisms contributing to the glucocorticoid hypersensitivity in proopiomelanocortin null mice treated with corticosterone

Science.gov (United States)

Michailidou, Zoi; Coll, Anthony P; Kenyon, Christopher J; Morton, Nicholas M; O'Rahilly, Stephen; Seckl, Jonathan R; Chapman, Karen E

2007-01-01

Proopiomelanocortin (POMC) deficiency causes severe obesity through hyperphagia of hypothalamic origin. However, low glucocorticoid levels caused by adrenal insufficiency mitigate against insulin resistance, hyperphagia and fat accretion in Pomc−/− mice. Upon exogenous glucocorticoid replacement, corticosterone-supplemented (CORT) Pomc−/− mice show exaggerated responses, including excessive fat accumulation, hyperleptinaemia and insulin resistance. To investigate the peripheral mechanisms underlying this glucocorticoid hypersensitivity, we examined the expression levels of key determinants and targets of glucocorticoid action in adipose tissue and liver. Despite lower basal expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which generates active glucocorticoids within cells, CORT-mediated induction of 11β-HSD1 mRNA levels was more pronounced in adipose tissues of Pomc−/− mice. Similarly, CORT treatment increased lipoprotein lipase mRNA levels in all fat depots in Pomc−/− mice, consistent with exaggerated fat accumulation. Glucocorticoid receptor (GR) mRNA levels were selectively elevated in liver and retroperitoneal fat of Pomc−/− mice but were corrected by CORT in the latter depot. In liver, CORT increased phosphoenolpyruvate carboxykinase mRNA levels specifically in Pomc−/− mice, consistent with their insulin-resistant phenotype. Furthermore, CORT induced hypertension in Pomc−/− mice, independently of adipose or liver renin–angiotensin system activation. These data suggest that CORT-inducible 11β-HSD1 expression in fat contributes to the adverse cardiometabolic effects of CORT in POMC deficiency, whereas higher GR levels may be more important in liver. PMID:17592030

Cable y satélite: equipamiento del hogar y consumo televisivo

Directory of Open Access Journals (Sweden)

Lic. Emilio Fernández Peña

2000-01-01

Full Text Available Los servicios de difusión de canales de televisión de pago por satélite (Canal Satélite Digital y Vía Digital y cable son ya una realidad con importante presencia en el sistema televisivo español. Un millón cuatrocientos mil hogares reciben estos servicios con una preponderancia clara de los transmitidos por satélite respecto a los que usan el cable (1,2 millones.

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

The extracellular matrix metalloproteinase inducer EMMPRIN is a target of nitric oxide in myocardial ischemia/reperfusion.

Science.gov (United States)

Tarin, Carlos; Lavin, Begoña; Gomez, Monica; Saura, Marta; Diez-Juan, Antonio; Zaragoza, Carlos

2011-07-15

Nitric oxide (NO) is an important defense against myocardial ischemia/reperfusion (I/R) injury. Although matrix metalloproteinase (MMP)-mediated necrosis of cardiac myocytes is well characterized, the role of inducible NO synthase (iNOS)-derived NO in this process is poorly understood. I/R injury was increased in iNOS-deficient mice and in mice treated with 1400 W (a pharmacological iNOS inhibitor) and was associated with significantly increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and EMMPRIN-associated MMPs. Transcriptional activity of an EMMPRIN luciferase promoter reporter expressed in cardiac myocytes was inhibited by NO in a cGMP-dependent manner, and this transcriptional inhibition was abolished by mutation of a putative E2F site. Consistent with these findings, EMMPRIN null mice, in which iNOS is normally induced, are partially protected against I/R injury. Pharmacological inhibition of iNOS in EMMPRIN null mice had no additional protective effect, suggesting that EMMPRIN is a downstream target of NO. Administration of anti-EMMPRIN neutralizing antibodies partly reduced the excess heart damage and MMP-9 expression induced by I/R in iNOS null mice, indicating that regulation of EMMPRIN is an important mechanism of NO-mediated cardioprotection. Copyright © 2011 Elsevier Inc. All rights reserved.

The relationship of high school graduation exams to graduation rates and SAT scores.

Directory of Open Access Journals (Sweden)

Gregory J. Marchant

2005-01-01

Full Text Available The current study examined the effect of high school graduation exams on states' graduation rates, states' aggregated SAT scores, and individual students' SAT scores. Three data sources were used: One source identified states requiring a standardized test for graduation; the NCES provided state aggregated data on graduation rates for the class of 2002; and the College Board provided its 2001 SAT database for all test-takers. After controlling for students' demographic characteristics (e.g., race, family education and income, GPA and class rank, regression analyses revealed that states requiring graduation exams had lower graduation rates and lower SAT scores. Individually, students from states requiring a graduation exam performed more poorly on the SAT than did students from states not requiring an exam. The impact of high stakes tests' on students' motivation to stay in school and on the teaching of critical thinking skills (tested by the SAT are discussed.

Efficient and Reliable Solar Panels for Small CubeSat Picosatellites

Directory of Open Access Journals (Sweden)

Ivo Vertat

2014-01-01

Full Text Available CubeSat picosatellites have a limited area of walls for solar cells assembling and the available area has to be effectively shared with other parts, such as planar antennas, optical sensors, camera lens, and access port. With standard size of solar cell strings, it is not possible to construct a reliable solar panel for CubeSat with redundant strings interconnection. Typical solar panels for CubeSat consist of two solar cell strings serially wired with no redundancy in case of solar string failure. The loss of electric energy from one solar panel can cause a serious problem for most picosatellites due to minimum margin in the blueprints of the picosatellite subsystem power budget. In this paper, we propose a new architecture of solar panels for PilsenCUBE CubeSat with a high level of redundancy in the case of solar string failure or following switched power regulator failure. Our solar panels use a high efficiency triple junction GaInP2/GaAs/Ge in the form of small triangle strings from the Spectrolab Company. A suitable technology for precise solar cell assembling is also discussed, because CubeSat picosatellites are usually developed by small teams with limited access to high-end facilities.

SAT for NPP personnel training in Spain

International Nuclear Information System (INIS)

Gonzalez, M.

1995-01-01

The SAT process objectives as applied to Spanish NPPs are: Perform JTA for selected job positions at the NPPs; develop the associated training plans; develop training support media; prepare training instructors as teachers and as task analysts; develop a SAT database. A lesson-learned from the task assessments conducted at Spanish NPPs is that the final task list should be obtained with full participation of workers so that they feel the final training plan has been developed taking into account their own opinion and experience. The breakdown of the tasks into its elements and the concordant job performance measure was presented. The process of determining knowledge and skills associated with the task elements and the structure and use of the taxonomy codes (for component, system, and academic skills and knowledge) was shown and explained. Based on the Spanish experience, the average time devoted to analyze a complete task is 5.33 person-hours per task. This data has permitted training and plant management to allocate the NPP human resources to support the analysis phase of SAT (which can be very time-consuming)

Comparisons of Satellite-Deduced Overlapping Cloud Properties and CALIPSO CloudSat Data

Science.gov (United States)

Chang, Fu-Lung; Minnis, Patrick; Lin, Bing; Sun-Mack, Sunny

2010-01-01

Introduction to the overlapped cloud properties derived from polar-orbiting (MODIS) and geostationary (GOES-12, -13, Meteosat-8, -9, etc.) meteorological satellites, which are produced at the NASA Langley Research Center (LaRC) cloud research & development team (NASA lead scientist: Dr. Patrick Minnis). Comparison of the LaRC CERES MODIS Edition-3 overlapped cloud properties to the CALIPSO and the CloudSat active sensing data. High clouds and overlapped clouds occur frequently as deduced by CALIPSO (44 & 25%), CloudSat (25 & 4%), and MODIS (37 & 6%). Large fractions of optically-thin cirrus and overlapped clouds are deduced from CALIPSO, but much smaller fractions are from CloudSat and MODIS. For overlapped clouds, the averaged upper-layer CTHs are about 12.8 (CALIPSO), 10.9 (CloudSat) and 10 km (MODIS), and the averaged lower-layer CTHs are about 3.6 (CALIPSO), 3.2 (CloudSat) and 3.9 km (MODIS). Based on comparisons of upper and lower-layer cloud properties as deduced from the MODIS, CALIPSO and CloudSat data, more enhanced passive satellite methods for retrieving thin cirrus and overlapped cloud properties are needed and are under development.

Desacyl Ghrelin Decreases Anxiety-like Behavior in Male Mice.

Science.gov (United States)

Mahbod, Parinaz; Smith, Eric P; Fitzgerald, Maureen E; Morano, Rachel L; Packard, Benjamin A; Ghosal, Sriparna; Scheimann, Jessie R; Perez-Tilve, Diego; Herman, James P; Tong, Jenny

2018-01-01

Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism, and emotionality (stress, anxiety, and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or, in an acylated form, acyl ghrelin (AG), through the actions of ghrelin O-acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR) 1a. We investigated the role of endogenous AG, DAG, and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr stop-floxed (Ghsr null) mice. Behavioral and hormonal responses were tested in the elevated plus maze and light/dark (LD) box. Mice lacking both AG and DAG (Ghr KO) increased anxiety-like behaviors across tests, whereas anxiety reactions were attenuated in DAG-treated Ghr KO mice and in mice lacking AG (GOAT KO). Notably, loss of GHSR1a (Ghsr null) did not affect anxiety-like behavior in any test. Administration of AG and DAG to Ghr KO mice with lifelong ghrelin deficiency reduced anxiety-like behavior and decreased phospho-extracellular signal-regulated kinase phosphorylation in the Edinger-Westphal nucleus in wild-type mice, a site normally expressing GHSR1a and involved in stress- and anxiety-related behavior. Collectively, our data demonstrate distinct roles for endogenous AG and DAG in regulation of anxiety responses and suggest that the behavioral impact of ghrelin may be context dependent. Copyright © 2018 Endocrine Society.

CryoVEx 2011-12 Airborne Campaigns for CryoSat Validation

DEFF Research Database (Denmark)

Skourup, Henriette; Hvidegaard, Sine Munk; Forsberg, René

2013-01-01

After the successful launch of CryoSat-2 in April 2010, the first direct validation campaign of the satellite was carried out in the April-May 2011. Part of this was repeated in Spring 2012. DTU Space has been involved in ESA’s CryoSat Validation Experiment (CryoVEx) with airborne activities since...... 2003. To validate the performance of the CryoSat-2 radar altimeter (SIRAL), the aircraft is equipped with an airborne version of the SIRAL altimeter (ASIRAS) together with a laser scanner. Of particular interest is to study the penetration depth of SIRAL into both land- and sea ice. This can be done...... of Alert and sea ice around Svalbard in the Fram Strait. Selected tracks were planned to match CryoSat-2 passes and a few of them were flown in formation flight with the AlfredWegener Institute (AWI) Polar- 5 carrying an EM induction sounder. The paper presents an overview of the 2011-12 airborne campaigns...

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.

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

Impaired Hematopoiesis and Disrupted Monocyte/Macrophage Homeostasis in Mucopolysaccharidosis Type I Mice.

Science.gov (United States)

Viana, Gustavo Monteiro; Buri, Marcus Vinícius; Paredes-Gamero, Edgar Julian; Martins, Ana Maria; D'Almeida, Vânia

2016-03-01

Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disease caused by alpha-L-iduronidase deficiency in which heparan and dermatan sulfate degradation is compromised. Besides primary lysosomal glycosaminoglycan accumulation, further changes in cellular functions have also been described in several murine MPS models. Herein, we evaluated alterations in hematopoiesis and its implications on the production of mature progeny in a MPS I murine model. Despite the significant increase in hematopoietic stem cells, a reduction in common myeloid progenitors and granulocyte-macrophage progenitor cells was observed in Idua -/- mice bone marrow. Furthermore, no alterations in number, viability nor activation of cell death mechanisms were observed in Idua -/- mice mature macrophages but they presented higher sensitivity to apoptotic induction after staurosporine treatment. In addition, changes in Ca(2+) signaling and a reduction in phagocytosis ability were also found. In summary, our results revealed significant intracellular changes in mature Idua -/- macrophages related to alterations in Idua -/- mice hematopoiesis, revealing a disruption in cell homeostasis. These results provide new insights into physiopathology of MPS I. © 2015 Wiley Periodicals, Inc.

Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice

International Nuclear Information System (INIS)

Bix, M.; Nanshih Liao; Raulet, D.; Zijlstra, M.; Loring, J.; Jaenisch, R.

1991-01-01

Irradiated MHC-heterozygous mice often reject bone marrow cells transplanted from one of the homozygous parental strains, a phenomenon ('hybrid resistance') that appears to violate the laws of transplantation. Rejection of parental and allogeneic marrow cells also differs from conventional T cell-mediated rejection mechanisms as it is effected by NK1.1 + cells. To account for the unusual specificity of bone marrow rejection, it has been proposed that NK1.1 + cells destroy marrow cells that fail to express the full complement of self MHC class I (MHC-I) molecules. We show here that NK1.1 + cells in normal mice reject haemopoietic transplants from mice that are deficient for normal cell-surface MHC-I expression because of a targeted mutation in the β 2 -microglobulin gene. These findings demonstrate that deficient expression of MHC-I molecules renders marrow cells susceptible to rejection. (author)

Diminished thrombogenic responses by deletion of the Podocalyxin Gene in mouse megakaryocytes.

Directory of Open Access Journals (Sweden)

Miguel Pericacho

Full Text Available Podocalyxin (Podxl is a type I membrane sialoprotein of the CD34 family, originally described in the epithelial glomerular cells of the kidney (podocytes in which it plays an important function. Podxl can also be found in megakaryocytes and platelets among other extrarenal places. The surface exposure of Podxl upon platelet activation suggested it could play some physiological role. To elucidate the function of Podxl in platelets, we generated mice with restricted ablation of the podxl gene in megakaryocytes using the Cre-LoxP gene targeting methodology. Mice with Podxl-null megakaryocytes did not show any apparent phenotypical change and their rates of growth, life span and fertility did not differ from the floxed controls. However, Podxl-null mice showed prolonged bleeding time and decreased platelet aggregation in response to physiological agonists. The number, size-distribution and polyploidy of Podxl-null megakaryocytes were similar to the floxed controls. Podxl-null platelets showed normal content of surface receptors and normal activation by agonists. However, the mice bearing Podxl-null platelets showed a significant retardation in the ferric chloride-induced occlusion of the carotid artery. Moreover, acute thrombosis induced by the i.v. injection of sublethal doses of collagen and phenylephrine produced a smaller fall in the number of circulating platelets in Podxl-null mice than in control mice. In addition, perfusion of uncoagulated blood from Podxl-null mice in parallel flow chamber showed reduced adhesion of platelets and formation of aggregates under high shear stress. It is concluded that platelet Podxl is involved in the control of hemostasis acting as a platelet co-stimulator, likely due to its pro-adhesive properties.

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.

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

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)

NTC operator training program viewed from SAT-based training process

International Nuclear Information System (INIS)

Matsumoto, Yoshio

1996-01-01

The Nuclear Power Training Center Ltd. (NTC) was established in June 1972 to train PWR plant operators. Operator training was started in Apr. 1974. Presently we have three full-scope, control-room simulators. Recently IAEA recommended that its Systematic Approach to Training (SAT) be used for the training of NPP personnel. We thoroughly examined the SAT-based process and compared it against the NTC training program. As a result, we have recognized that the NTC training program satisfies the SAT-based training process. We now intend to improve the feedback step of the NTC training system. Our efforts continue to produce a relevant program at the forefront of our profession. (author)

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;.

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?’

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.

CryoSat/SIRAL Cal1 Calibration Orbits

Science.gov (United States)

Scagliola, Michele; Fornari, Marco; Bouffard, Jerome; Parrinello, Tommaso

2017-04-01

The main payload of CryoSat is a Ku band pulsewidth limited radar altimeter, called SIRAL (Synthetic interferometric radar altimeter), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for SAR processing. This allows to reach an along track resolution that is significantly improved with respect to traditional pulse-width limited altimeters. Due to the fact that SIRAL is a phase coherent pulse-width limited radar altimeter, a proper calibration approach has been developed. In fact, not only corrections for transfer function, gain and instrument path delay have to be computed (as in previous altimeters), but also corrections for phase (SAR/SARIn) and phase difference between the two receiving chains (SARIN only). Recalling that the CryoSat's orbit has a high inclination of 92° and it is non-sun-synchronous, the temperature of the SIRAL changes continuously along the orbit with a period of about 480 days and it is also function of the ascending/descending passes. By analysis of the CAL1 calibration corrections, it has been verified that the internal path delay and the instrument gain variation measured on the SIRAL are affected by the thermal status of the instrument and as a consequence they are expected to vary along the orbit. In order to gain knowledge on the calibration corrections (i.e. the instrument behavior) as function of latitude and temperature, it has been planned to command a few number of orbits where only CAL1 calibration acquisitions are continuously performed. The analysis of the CAL1 calibration corrections produced along the Calibration orbits can be also useful to verify whether the current calibration plan is able to provide sufficiently accurate corrections for the instrument acquisitions at any latitude. In 2016, the CryoSat/SIRAL Cal1 Calibration Orbits have been commanded two times, a first time the 20th of July 2016 and a second time the 24th of November 2016, and they

Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses

Science.gov (United States)

Opperman, Pamela A.; Rotherham, Lia S.; Esterhuysen, Jan; Charleston, Bryan; Juleff, Nicholas; Capozzo, Alejandra V.; Theron, Jacques

2014-01-01

ABSTRACT Monoclonal-antibody (MAb)-resistant mutants were used to map antigenic sites on foot-and-mouth disease virus (FMDV), which resulted in the identification of neutralizing epitopes in the flexible βG-βH loop in VP1. For FMDV SAT2 viruses, studies have shown that at least two antigenic sites exist. By use of an infectious SAT2 cDNA clone, 10 structurally exposed and highly variable loops were identified as putative antigenic sites on the VP1, VP2, and VP3 capsid proteins of SAT2/Zimbabwe (ZIM)/7/83 (topotype II) and replaced with the corresponding regions of SAT2/Kruger National Park (KNP)/19/89 (topotype I). Virus neutralization assays using convalescent-phase antisera raised against the parental virus, SAT2/ZIM/7/83, indicated that the mutant virus containing the TQQS-to-ETPV mutation in the N-terminal part of the βG-βH loop of VP1 showed not only a significant increase in the neutralization titer but also an increase in the index of avidity to the convalescent-phase antisera. Furthermore, antigenic profiling of the epitope-replaced and parental viruses with nonneutralizing SAT2-specific MAbs led to the identification of two nonneutralizing antigenic regions. Both regions were mapped to incorporate residues 71 to 72 of VP2 as the major contact point. The binding footprint of one of the antigenic regions encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 48 to 50 of VP1, and the second antigenic region encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 84 to 86 and 109 to 11 of VP1. This is the first time that antigenic regions encompassing residues 71 to 72 of VP2 have been identified on the capsid of a SAT2 FMDV. IMPORTANCE Monoclonal-antibody-resistant mutants have traditionally been used to map antigenic sites on foot-and-mouth disease virus (FMDV). However, for SAT2-type viruses, which are responsible for most of the FMD outbreaks in Africa and are the most varied of all seven serotypes, only two antigenic sites have been

Radioimmunoimaging of nude mice bearing human lung adenocarcinoma xenografts after injecting 131I-McAbs

International Nuclear Information System (INIS)

Liu Liang

1992-01-01

Monoclonal antibodies (Lc86a-C5, Lc86a-H8) directed against human lung adenocarcinoma cell line LTEP-a-2 and normal BALB/c IgG were labelled with iodine-131 by chloramine T. The 131 I-McAbs and 131 I-IgG were respectively injected into the peritoneal cavities of nude mice bearing transplanted human lung adenocarcinoma cell line LTEP-a-2. After 72 h, the tumor tissue in nude mice injected with 131 I-McAbs was distinguishable from normal tissues as a very clear image obtained during gamma scintigraphy. No difference was found between tumor and normal tissues in the nude mice injected with 131 I-IgG. The tumor: blood ration was 3.1:1 in nude injected with 131 I McAb(H8) and 0.9:1 in nude mice injected with 131 I-IgG respectively. This indicates that the tumor tissue image was the result of specific binding of the 131 I-McAbs, which have high specificity and affinity both in vitro and in vivo, to tumor cells, and these monoclonal antibodies may serve as potential agents in tumor diagnosis and treatment

Pi-Sat: A Low Cost Small Satellite and Distributed Spacecraft Mission System Test Platform

Science.gov (United States)

Cudmore, Alan

2015-01-01

Current technology and budget trends indicate a shift in satellite architectures from large, expensive single satellite missions, to small, low cost distributed spacecraft missions. At the center of this shift is the SmallSatCubesat architecture. The primary goal of the Pi-Sat project is to create a low cost, and easy to use Distributed Spacecraft Mission (DSM) test bed to facilitate the research and development of next-generation DSM technologies and concepts. This test bed also serves as a realistic software development platform for Small Satellite and Cubesat architectures. The Pi-Sat is based on the popular $35 Raspberry Pi single board computer featuring a 700Mhz ARM processor, 512MB of RAM, a flash memory card, and a wealth of IO options. The Raspberry Pi runs the Linux operating system and can easily run Code 582s Core Flight System flight software architecture. The low cost and high availability of the Raspberry Pi make it an ideal platform for a Distributed Spacecraft Mission and Cubesat software development. The Pi-Sat models currently include a Pi-Sat 1U Cube, a Pi-Sat Wireless Node, and a Pi-Sat Cubesat processor card.The Pi-Sat project takes advantage of many popular trends in the Maker community including low cost electronics, 3d printing, and rapid prototyping in order to provide a realistic platform for flight software testing, training, and technology development. The Pi-Sat has also provided fantastic hands on training opportunities for NASA summer interns and Pathways students.

Development of the severe accident management guidance module for the SATS training simulator

International Nuclear Information System (INIS)

Kim, K. R.; Park, S. H.; Kim, D. H.

2004-01-01

Recently KAERI has developed severe accident management guidance to establish Korea standard severe accident management system. On the other hand PC-based severe accident training simulator SATS has been developed, which uses MELCOR computing code as the simulation engine. SATS graphically displays and simulates the severe accident progression with interactive user inputs. The control capability of SATS makes a severe accident training course more interesting and effective. In this paper the development and functions of HyperKAMG module are explained. Furthermore easiness and effectiveness of the HyperKAMG-SATS system in severe accident management are described

NASA 3D Models: CloudSat

Data.gov (United States)

National Aeronautics and Space Administration — Launched in April 2006, CloudSat monitors the state of the Earth’s atmosphere and weather with a sophisticated radar system. The instrument, jointly developed with...

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.

Peptide mimetic of the S100A4 protein modulates peripheral nerve regeneration and attenuates the progression of neuropathy in myelin protein P0 null mice

DEFF Research Database (Denmark)

Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana

2013-01-01

and mimicked the S100A4-induced neuroprotection in brain trauma. Here, we investigated a possible function of S100A4 and its mimetics in the pathologies of the peripheral nervous system (PNS). We found that S100A4 was expressed in the injured PNS and that its peptide mimetic (H3) affected the regeneration......, these effects were attributed to the modulatory effect of H3 on initial axonal sprouting. In contrast to the modest effect of H3 on the time course of regeneration, H3 had a long-term neuroprotective effect in the myelin protein P0 null mice, a model of dysmyelinating neuropathy (Charcot-Marie-Tooth type 1...... disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss...

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;

Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses.

Science.gov (United States)

Ou, Yang; Wang, Shang-Jui; Li, Dawei; Chu, Bo; Gu, Wei

2016-11-01

Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N 1 -acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9-mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

Integration of CubeSat Systems with Europa Surface Exploration Missions

Science.gov (United States)

Erdoǧan, Enes; Inalhan, Gokhan; Kemal Üre, Nazım

2016-07-01

Recent studies show that there is a high probability that a liquid ocean exists under thick icy surface of Jupiter's Moon Europa. The findings also show that Europa has features that are similar to Earth, such as geological activities. As a result of these studies, Europa has promising environment of being habitable and currently there are many missions in both planning and execution level that target Europa. However, these missions usually involve extremely high budgets over extended periods of time. The objective of this talk is to argue that the mission costs can be reduced significantly by integrating CubeSat systems within Europa exploration missions. In particular, we introduce an integrated CubeSat-micro probe system, which can be used for measuring the size and depth of the hypothetical liquid ocean under the icy surface of Europa. The systems consist of an entry module that houses a CubeSat combined with driller measurement probes. Driller measurement probes deploy before the system hits the surface and penetrate the surface layers of Europa. Moreover, a micro laser probe could be used to examine the layers. This process enables investigation of the properties of the icy layer and the environment beneath the surface. Through examination of different scenarios and cost analysis of the components, we show that the proposed CubeSat systems has a significant potential to reduce the cost of the overall mission. Both subsystem requirements and launch prices of CubeSats are dramatically cheaper than currently used satellites. In addition, multiple CubeSats may be used to dominate wider area in space and they are expandable in face of potential failures. In this talk we discuss both the mission design and cost reduction aspects.

Experimental transmission of M. leprae in the testis of mice, born from 131I-injected females

International Nuclear Information System (INIS)

Sushida, Kiyo

1974-01-01

Six strains of M. leprae taken from lepromatous leprosy patients were inoculated into the testes of '' 131 I-F 1 '' mice, which were divided into two groups. The first group was born of females which had been subcutaneously injected with 131 I-100 μc during pregnancy; the second group was born of females which had been injected before pregnancy. The '' 131 I-F 1 '' mice which were born of females injected with 131 I-100 μc, during pregnancy were then inoculated with leprous bacilli described above, showed the presence of the so-called ''globi'' in the testes. When samples of leprous bacilli (LL28, LL32, LL33) taken from patients who had not been receiving anti-leprous drug treatments were injected into the 131 I-F 1 mice, globi were also found. When leprous bacilli from leproma removed from patients under treatment were injected into mice born from females which had been injected with 131 I-100 μc either during or before their pregnancy, no globi were found. Even though bacilli (LL32, LL33, LL34) from untreated patients were injected into mice born of females who were injected with 131 I-100 μc before pregnancy, no globi were found. (auth.)

DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents.

NARCIS (Netherlands)

B.J. Glassner (Brian); G. Weeda (Geert); J.M. Allan (James); J.L.M. Broekhof (Jose'); N.H.E. Carls (Nick); I. Donker (Ingrid); B.P. Engelward (Bevin); R.J. Hampson (Richard); R. Hersmus (Remko); M.J. Hickman (Mark); R.B. Roth (Richard); H.B. Warren (Henry); M.M. Wu (Mavis); J.H.J. Hoeijmakers (Jan); L.D. Samson (Leona)

1999-01-01

textabstractWe have generated mice deficient in O6-methylguanine DNA methyltransferase activity encoded by the murine Mgmt gene using homologous recombination to delete the region encoding the Mgmt active site cysteine. Tissues from Mgmt null mice displayed very low O6-methylguanine DNA

Combining Envisat and CryoSat-2 altimetry to inform hydrodynamic models

DEFF Research Database (Denmark)

Schneider, Raphael; Nygaard Godiksen, Peter; Ridler, Marc-Etienne

2016-01-01

fitted to the CryoSat-2 data: In a first step, the average simulated water levels along the river were calibrated to the CryoSat-2 data by adapting the hydrodynamic cross section datums. Subsequently the simulated water level amplitudes were fitted to those obtained from Envisat virtual station time......Remote sensing provides valuable data for parameterization and updating of hydrological models, for example water level measurements of inland water bodies from satellite radar altimeters. Many studies have used satellite altimetry data from repeat-orbit missions such as Envisat, ERS or Jason...... on Sentinel-3. CryoSat-2 SARIn level 2 data is used to improve a 1D hydrodynamic model of the Brahmaputra river basin in South Asia set up in the DHI MIKE 11 software. CryoSat-2 water levels were extracted over river masks derived from Landsat imagery. After discharge calibration, simulated water levels were...

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

Study of LEO-SAT microwave link for broad-band mobile satellite communication system

Science.gov (United States)

Fujise, Masayuki; Chujo, Wataru; Chiba, Isamu; Furuhama, Yoji; Kawabata, Kazuaki; Konishi, Yoshihiko

1993-01-01

In the field of mobile satellite communications, a system based on low-earth-orbit satellites (LEO-SAT's) such as the Iridium system has been proposed. The LEO-SAT system is able to offer mobile telecommunication services in high-latitude areas. Rain degradation, fading and shadowing are also expected to be decreased when the system is operated at a high elevation angle. Furthermore, the propagation delay generated in the LEO-SAT system is less pronounced than that in the geostationary orbit satellite (GEO-SAT) system and, in voice services, the effect of the delay is almost negligible. We proposed a concept of a broad-band mobile satellite communication system with LEO-SAT's and Optical ISL. In that system, a fixed L-band (1.6/1.5 GHz) multibeam is used to offer narrow band service to the mobile terminals in the entire area covered by a LEO-SAT and steerable Ka-band (30/20 GHz) spot beams are used for the wide band service. In this paper, we present results of a study of LEO-SAT microwave link between a satellite and a mobile terminal for a broad-band mobile satellite communication system. First, the results of link budget calculations are presented and the antennas mounted on satellites are shown. For a future mobile antenna technology, we also show digital beamforming (DBF) techniques. DBF, together with modulation and/or demodulation, is becoming a key technique for mobile antennas with advanced functions such as antenna pattern calibration, correction, and radio interference suppression. In this paper, efficient DBF techniques for transmitting and receiving are presented. Furthermore, an adaptive array antenna system suitable for this LEO-SAT is presented.

CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

Science.gov (United States)

Jain, Nidhi; Oswal, Neelam; Chawla, Amanpreet Singh; Agrawal, Tanvi; Biswas, Moanaro; Vrati, Sudhanshu; Rath, Satyajit; George, Anna; Bal, Vineeta; Medigeshi, Guruprasad R

2017-02-01

Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null) are highly susceptible and die over 10-18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function.

Directory of Open Access Journals (Sweden)

Nidhi Jain

2017-02-01

Full Text Available Following Japanese encephalitis virus (JEV infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β-T cells (TCRβ-null are highly susceptible and die over 10-18 day period as compared to the wild-type (WT mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB. Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.

Insulin and insulin-like growth factor-I (IGF-I) receptor phosphorylation in µ-calpain knockout mice

Science.gov (United States)

Numerous cellular processes are controlled by insulin and IGF-I signaling pathways. Due to previous work in our laboratories, we hypothesized that insulin (IR) and type 1 IGF-I (IGF-IR) receptor signaling is decreased due to increased protein tyrosine phosphatase 1B (PTP1B) activity. C57BL/6J mice...

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

Directory of Open Access Journals (Sweden)

Keisuke Nagao

Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

Science.gov (United States)

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Lunar and Lagrangian Point L1 L2 CubeSat Communication and Navigation Considerations

Science.gov (United States)

Schaire, Scott; Wong, Yen F.; Altunc, Serhat; Bussey, George; Shelton, Marta; Folta, Dave; Gramling, Cheryl; Celeste, Peter; Anderson, Mile; Perrotto, Trish;

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

SmallSat Common Electronics Board (SCEB)

Data.gov (United States)

National Aeronautics and Space Administration — We propose to design a low-power general-purpose SmallSat Common Electronics Board (SCEB).  The SCEB design will be based on input received from a group of...

Nfib hemizygous mice are protected from hyperoxic lung injury and death.

Science.gov (United States)

Kumar, Vasantha H S; Chaker El Khoury, Joseph; Gronostajski, Richard; Wang, Huamei; Nielsen, Lori; Ryan, Rita M

2017-08-01

Nuclear Factor I ( Nfi) genes encode transcription factors essential for the development of organ systems including the lung. Nfib null mice die at birth with immature lungs. Nfib hemizygous mice have reduced lung maturation with decreased survival. We therefore hypothesized that these mice would be more sensitive to lung injury and would have lower survival to hyperoxia. Adult Nfib hemizygous mice and their wild-type (Wt) littermates were exposed to 100% O 2 for 89, 80, 72 and 66 h for survival studies with lung outcome measurements at 66 h. Nfib hemizygous and Wt controls were also studied in RA at 66 h. Cell counts and cytokines were measured in bronchoalveolar lavage (BAL); lung sections examined by histopathology; lung angiogenic and oxidative stress gene expression assessed by real-time PCR Unexpectedly, Nfib hemizygous mice (0/14-0%) had significantly lower mortality compared to Wt mice (10/22-45%) at 80 h of hyperoxia ( P  mice exposed to hyperoxia. New vessel formation, edema, congestion, and alveolar hemorrhage were noted on histopathology at 72 and 80 h in wild-type mice. Nfib hemizygous lungs had significant downregulation of genes involved in redox signaling and inflammatory pathways. Adult Nfib hemizygous mice are relatively resistant to hyperoxia compared to wild-type littermates. Mechanisms contributing to this resistance are not clear; however, transcription factors such as Nfib may regulate cell survival and play a role in modulating postnatal lung development. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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.

Global gene expression profiles of MT knockout and wild-type mice in the condition of doxorubicin-induced cardiomyopathy.

Science.gov (United States)

Shuai, Yi; Guo, Jun; Dong, Yansheng; Zhong, Weijian; Xiao, Ping; Zhou, Tong; Zhang, Lishi; Peng, Shuangqing

2011-01-15

Increasing evidence from in vivo and in vitro studies has indicated that MT exerts protective effects against DOX-induced cardiotoxicity; however the underlying precise mechanisms still remain an enigma. Therefore, the present study was designed using MT knockout mice in concert with genomic approaches to explore the possible molecular and cellular mechanisms in terms of the genetic network changes. MT-I/II null (MT⁻/⁻) mice and corresponding wild-type mice (MT+/+) were administrated with a single dose of DOX (15 mg/kg, i.p.) or equal volume of saline. Animals were sacrificed on the 4th day after DOX administration and samples were collected for further analyses. Global gene expression profiles of cardiac mRNA from two genotype mice revealed that 381 characteristically MT-responsive genes were identified between MT+/+ mice and MT⁻/⁻ mice in response to DOX, including fos, ucp3, car3, atf3, map3k6, etc. Functional analysis implied MAPK signaling pathway, p53 signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway, Wnt signaling pathway, etc. might be involved to mediate the protection of DOX cardiomyopathy by MT. Results from the present study not only validated the previously reported possible mechanisms of MT protection against DOX toxicity, but also provided new clues into the molecular mechanisms involved in this process. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

On the Combinatorics of SAT and the Complexity of Planar Problems

DEFF Research Database (Denmark)

Talebanfard, Navid

In this thesis we study several problems arising in Boolean satisfiability ranging from lower bounds for SAT algorithms and proof systems to extremal properties of formulas. The first problem is about construction of hard instances for k-SAT algorithms. For PPSZ algorithm [40] we give the first...

Stack Characterization in CryoSat Level1b SAR/SARin Baseline C

Science.gov (United States)

Scagliola, Michele; Fornari, Marco; Di Giacinto, Andrea; Bouffard, Jerome; Féménias, Pierre; Parrinello, Tommaso

2015-04-01

CryoSat was launched on the 8th April 2010 and is the first European ice mission dedicated to the monitoring of precise changes in the thickness of polar ice sheets and floating sea ice. CryoSat is the first altimetry mission operating in SAR mode and it carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for azimuth processing. The current CryoSat IPF (Instrument Processing Facility), Baseline B, was released in operation in February 2012. After more than 2 years of development, the release in operations of the Baseline C is expected in the first half of 2015. It is worth recalling here that the CryoSat SAR/SARin IPF1 generates 20Hz waveforms in correspondence of an approximately equally spaced set of ground locations on the Earth surface, i.e. surface samples, and that a surface sample gathers a collection of single-look echoes coming from the processed bursts during the time of visibility. Thus, for a given surface sample, the stack can be defined as the collection of all the single-look echoes pointing to the current surface sample, after applying all the necessary range corrections. The L1B product contains the power average of all the single-look echoes in the stack: the multi-looked L1B waveform. This reduces the data volume, while removing some information contained in the single looks, useful for characterizing the surface and modelling the L1B waveform. To recover such information, a set of parameters has been added to the L1B product: the stack characterization or beam behaviour parameters. The stack characterization, already included in previous Baselines, has been reviewed and expanded in Baseline C. This poster describes all the stack characterization parameters, detailing what they represent and how they have been computed. In details, such parameters can be summarized in: - Stack

The Social Attribution Task-Multiple Choice (SAT-MC): A Psychometric and Equivalence Study of an Alternate Form.

Science.gov (United States)

Johannesen, Jason K; Lurie, Jessica B; Fiszdon, Joanna M; Bell, Morris D

2013-01-01

The Social Attribution Task-Multiple Choice (SAT-MC) uses a 64-second video of geometric shapes set in motion to portray themes of social relatedness and intentions. Considered a test of "Theory of Mind," the SAT-MC assesses implicit social attribution formation while reducing verbal and basic cognitive demands required of other common measures. We present a comparability analysis of the SAT-MC and the new SAT-MC-II, an alternate form created for repeat testing, in a university sample (n = 92). Score distributions and patterns of association with external validation measures were nearly identical between the two forms, with convergent and discriminant validity supported by association with affect recognition ability and lack of association with basic visual reasoning. Internal consistency of the SAT-MC-II was superior (alpha = .81) to the SAT-MC (alpha = .56). Results support the use of SAT-MC and new SAT-MC-II as equivalent test forms. Demonstrating relatively higher association to social cognitive than basic cognitive abilities, the SAT-MC may provide enhanced sensitivity as an outcome measure of social cognitive intervention trials.

Coastal Sea Level from CryoSat-2 SARIn Altimetry in Norway

DEFF Research Database (Denmark)

Idžanović, Martina; Ophaug, Vegard; Andersen, Ole Baltazar

2017-01-01

Conventional (pulse-limited) altimeters determine the sea surface height with an accuracy of a few centimeters over the open ocean. Sea surface heights and tide-gauge sea level serve as each other’s buddy check. However, in coastal areas, altimetry suffers from numerous effects, which degrade its...... conventional altimeters. In this study, we explore the potential of CryoSat-2 to provide valid observations in the Norwegian coastal zone. We do this by comparing time series of CryoSat-2 sea level anomalies with time series of in situ sea level at 22 tide gauges, where the CryoSat-2 sea level anomalies...... are averaged in a 45-km area around each tide gauge. For all tide gauges, CryoSat-2 shows standard deviations of differences and correlations of 16 cm and 61%, respectively. We further identify the ocean tide and inverted barometer geophysical corrections as the most crucial, and note that a large amount...

Integrated CubeSat ADACS with Reaction Wheels and Star Tracker, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The MAI-400SS Space Sextant is a precision attitude determination and control system for CubeSats and Nanosats. The MAI-400SS enables future CubeSat missions with...

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.

Life satisfaction after traumatic brain injury: comparison of ratings with the Life Satisfaction Questionnaire (LiSat-11) and the Satisfaction With Life Scale (SWLS).

Science.gov (United States)

Jacobsson, Lars; Lexell, Jan

2016-01-15

An optimal life satisfaction (LS) is considered an important long-term outcome after a traumatic brain injury (TBI). It is, however, not clear to what extent a single instrument captures all aspects of LS, and different instruments may be needed to comprehensively describe LS. The aim of this study was to compare self-ratings of life satisfaction after a TBI with two commonly used instruments. Life Satisfaction Questionnaire (LiSat-11), comprising eleven items and Satisfaction With Life Scale (SWLS), comprising five items, were administered to 67 individuals (51 men and 16 women). Secondary analysis of data collected as part of a survey of individuals with TBI 6 to 15 years post TBI. Item 1 in LiSat-11 ('Life as a whole') and the total SWLS score was strongly correlated (Spearman's rho = 0.66; p life' and 'Partner relationship', were moderately to strongly correlated with items in SWLS. The item 'Partner relationship' in LiSat-11 did not correlate with any of the items in SWLS or the total score. The item 'If I could live my life over, I would change nothing' in SWLS had the weakest correlations with items in LiSat-11. Items 'Vocation' and 'Leisure' in LISat-11 were most strongly correlated with items in SWLS, whereas the item 'ADL' in LiSat-11 was more weakly correlated with items in SWLS. The strength of the relationships implies that the two instruments assess similar but not identical aspects of LS and therefore complement each other when it is rated.

Design and Demonstration of a Constrained Control System for Maneuverable CubeSats

Data.gov (United States)

National Aeronautics and Space Administration — Picosatellites, such as CubeSats (less than 4 kg), have the potential to reduce the cost of conducting missions in space. Programs such as NASA Ames GeneSat and the...

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.

Mercury accumulation and its distribution to metallothionein in mouse brain after sub-chronic pulse exposure to mercury vapor

Energy Technology Data Exchange (ETDEWEB)

Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Sawada, M.; Shimada, A. [Department of Veterinary Pathology, Tottori University, 4-101 Koyamacho, Minami, Tottori 680-0945 (Japan); Satoh, M. [Department of Hygienics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585 (Japan); Tohyama, C. [Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)

2004-09-01

Previously we found that exposure to mercury vapor effectively induced metallothionein (MT) biosynthesis in rat brain. Although the induction of not only MT-I/II but also MT-III was evident, the induction rate of the latter was much lower than that of the former. The brain of an MT-null mouse lacks MT-I/II, but has MT-III. Here we examined the effects of sub-chronic pulse exposure to mercury vapor on the brain MT in MT-null mice and their wild type controls. MT-null and wild type mice were preliminarily exposed to mercury vapor for 2 weeks at 0.1 mg Hg/m{sup 3} for 1 h/day for 3 days a week, and then exposed for 11 weeks at 4.1 mg Hg/m{sup 3} for 30 min/day for 3 days a week. This exposure caused no toxic signs such as abnormal behavior or loss of body weight gain in the mice of either strain throughout the experimental period. Twenty-four hours after the termination of the exposure, mice were sacrificed and brain samples were subjected to mercury analysis, MT assay, and pathological examination. The MT-null mice showed lower accumulation of mercury in the brain than the wild type mice. Mercury exposure resulted in a 70% increase of brain MT in the wild type mice, which was mostly accounted for by the increase in MT-I/II. On the other hand, the brain MT in the MT-null mice increased by 19%, suggesting less reactivity of the MT-III gene to mercury vapor. Although histochemical examination revealed silver-mercury grains in the cytoplasm of nerve cells and glial cells throughout the brains of both strains, no significant difference was observed between the two strains. (orig.)

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.

In Bacillus subtilis, the SatA (Formerly YyaR) Acetyltransferase Detoxifies Streptothricin via Lysine Acetylation.

Science.gov (United States)

Burckhardt, Rachel M; Escalante-Semerena, Jorge C

2017-11-01

Soil is a complex niche, where survival of microorganisms is at risk due to the presence of antimicrobial agents. Many microbes chemically modify cytotoxic compounds to block their deleterious effects. Streptothricin is a broad-spectrum antibiotic produced by streptomycetes that affects Gram-positive and Gram-negative bacteria alike. Here we identify the SatA (for s treptothricin a ce t yltransferase A , formerly YyaR) enzyme of Bacillus subtilis as the mechanism used by this soil bacterium to detoxify streptothricin. B. subtilis strains lacking satA were susceptible to streptothricin. Ectopic expression of satA + restored streptothricin resistance to B. subtilis satA ( Bs SatA) strains. Purified Bs SatA acetylated streptothricin in vitro at the expense of acetyl-coenzyme A (acetyl-CoA). A single acetyl moiety transferred onto streptothricin by SatA blocked the toxic effects of the antibiotic. SatA bound streptothricin with high affinity ( K d [dissociation constant] = 1 μM), and did not bind acetyl-CoA in the absence of streptothricin. Expression of B. subtilis satA + in Salmonella enterica conferred streptothricin resistance, indicating that SatA was necessary and sufficient to detoxify streptothricin. Using this heterologous system, we showed that the SatA homologue from Bacillus anthracis also had streptothricin acetyltransferase activity. Our data highlight the physiological relevance of lysine acetylation for the survival of B. subtilis in the soil. IMPORTANCE Experimental support is provided for the functional assignment of gene products of the soil-dwelling bacilli Bacillus subtilis and Bacillus anthracis This study focuses on one enzyme that is necessary and sufficient to block the cytotoxic effects of a common soil antibiotic. The enzyme alluded to is a member of a family of proteins that are broadly distributed in all domains of life but poorly studied in B. subtilis and B. anthracis The initial characterization of the enzyme provides insights into its

PowerCube: Integrated Power, Propulsion, and Pointing for CubeSats, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The PowerCube is a 1U CubeSat module that provides integrated propulsion, power, and precision pointing to enable the low-cost CubeSat platform to be used to conduct...

Development of a Solar Array Drive Assembly for CubeSat

Science.gov (United States)

Passaretti, Mike; Hayes, Ron

2010-01-01

Small satellites and in particular CubeSats, have increasingly become more viable as platforms for payloads typically requiring much larger bus structures. As advances in technology make payloads and instruments for space missions smaller, lighter and more power efficient, a niche market is emerging from the university community to perform rapidly developed, low-cost missions on very small spacecraft - micro, nano, and picosatellites. In just the last few years, imaging, biological and new technology demonstration missions have been either proposed or have flown using variations of the CubeSat structure as a basis. As these missions have become more complex, and the CubeSat standard has increased in both size (number of cubes) and mass, available power has become an issue. Body-mounted solar cells provide a minimal amount of power; deployable arrays improve on that baseline but are still limited. To truly achieve maximum power, deployed tracked arrays are necessary. To this end, Honeybee Robotics Spacecraft Mechanisms Corporation, along with MMA of Nederland Colorado, has developed a solar array drive assembly (SADA) and deployable solar arrays specifically for CubeSat missions. In this paper, we discuss the development of the SADA.

Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

Energy Technology Data Exchange (ETDEWEB)

Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda; Ouyang, Honghai; Osaki, Mitsuhiko; Ito, Hisao; Nagasawa, Hatsumi; Little, John B.; Oshimura, Mitsuo; Li, Gloria C.; Chen, David J.

2002-04-15

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNEL staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.

Serological Detection of Foot and Mouth Disease Virus (Fmdv) Sat 1 ...

African Journals Online (AJOL)

The prevalence of Foot and Mouth Disease virus (FMDV) serotypes SAT 1 and SAT 2 antibodies among Nigerian cattle was determined using complement fixation (CF) and neutralization tests (NT) in 2000 cattle sera obtained from nine northern states. The two serological tests were very specific and sensitive enough to ...

Gum chewing improves adolescents’ math performance in an SAT preparatory course

Science.gov (United States)

The purpose of the current study was to determine the effect of gum chewing on students’ performance in a preparatory course for the Scholastic Aptitude Test (SAT). A total of 182 adolescents enrolled in an SAT preparatory class were randomized into one of two treatments: 1) gum chewing condition (G...

CloudSat Preps for Launch at Vandenberg Air Force Base, CA

Science.gov (United States)

2005-01-01

The CloudSat spacecraft sits encapsulated within its Boeing Delta launch vehicle dual payload attach fitting at Vandenberg Air Force Base, Calif. CloudSat will share its ride to orbit late next month with NASA's CALIPSO spacecraft. The two spacecraft are designed to reveal the secrets of clouds and aerosols.

Student Ranking Differences within Institutions Using Old and New SAT Scores

Science.gov (United States)

Marini, Jessica P.; Beard, Jonathan; Shaw, Emily J.

2018-01-01

Admission offices at colleges and universities often use SAT® scores to make decisions about applicants for their incoming class. Many institutions use prediction models to quantify a student's potential for success using various measures, including SAT scores (NACAC, 2016). In March 2016, the College Board introduced a redesigned SAT that better…

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.

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.

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.

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

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.

Interpreting force concept inventory scores: Normalized gain and SAT scores