Circulating CD4+CD28null and extra-thymic CD4+CD8+ double positive T cells are independently associated with disease damage in systemic lupus erythematosus patients.

PubMed

Ugarte-Gil, M F; Sánchez-Zúñiga, C; Gamboa-Cárdenas, R V; Aliaga-Zamudio, M; Zevallos, F; Tineo-Pozo, G; Cucho-Venegas, J M; Mosqueira-Riveros, A; Medina, M; Perich-Campos, R A; Alfaro-Lozano, J L; Rodriguez-Bellido, Z; Alarcón, G S; Pastor-Asurza, C A

2016-03-01

To determine whether circulating CD4+CD28null and extra-thymic CD4+CD8+ double positive (DP) T cells are independently associated with damage accrual in systemic lupus erythematosus (SLE) patients. This cross-sectional study was conducted between September 2013 and April 2014 in consecutive SLE patients from our Rheumatology Department. CD4+CD28null and CD4+CD8+ DP T-cell frequencies were analyzed by flow-cytometry. The association of damage (SLICC/ACR Damage Index, SDI) and CD4+CD28null and CD4+CD8+ DP T cells was examined by univariable and multivariable Poisson regression models, adjusting for possible confounders. All analyses were performed using SPSS 21.0. Patients' (n = 133) mean (SD) age at diagnosis was 35.5 (16.8) years, 124 (93.2%) were female; all were mestizo (mixed Caucasian and Amerindian ancestry). Disease duration was 7.4 (6.8) years. The SLE Disease Activity Index was 5.5 (4.2), and the SDI 0.9 (1.2). The percentages of CD4+CD28null and CD4+CD8+ DP T cells were 17.1 (14.4) and 0.4 (1.4), respectively. The percentage of CD4+CD28null and CD4+CD8+ DP T cells were positively associated with a higher SDI in both univariable (rate ratio (RR) 1.02, 95% confidence interval (CI): 1.01-1.03 and 1.17, 95% CI: 1.07-1.27, respectively; p < 0.001 for both) and multivariable analyses RR 1.02, 95% CI: 1.01-1.03, p = 0.001 for CD4+CD28null T cells and 1.28, 95% CI: 1.13-1.44, p < 0.001 for CD4+CD8+ DP T cells). Only the renal domain remained associated with CD4+CD28null in multivariable analyses (RR 1.023 (1.002-1.045); p = 0.034). In SLE patients, CD4+CD28null and CD4+CD8+ DP T cells are independently associated with disease damage. Longitudinal studies are warranted to determine the predictive value of these associations. © The Author(s) 2015.

Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide.

PubMed

Chaves, Guilherme Maranhão; da Silva, Walicyranison Plinio

2012-12-01

To cope with oxidative stress, Candida albicans possesses several enzymes involved in a number of biological processes, including superoxide dismutases (Sods) and glutaredoxins (Grxs). The resistance of C. albicans to reactive oxygen species is thought to act as a virulence factor. Genes such as SOD1 and GRX2, which encode for a Sod and Grx, respectively, in C. albicans are widely recognised to be important for pathogenesis. We generated a double mutant, Δgrx2/sod1, for both genes. This strain is very defective in hyphae formation and is susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, the double null mutant was susceptible to menadione and resistant to diamide. The reintegration of the SOD1 gene in the null mutant led to recovery in resistance to menadione, whereas reintegration of the GRX2 gene made the null mutant sensitive to diamide. Despite having two different roles in the responses to oxidative stress generated by chemical compounds, GRX2 and SOD1 are important for C. albicans pathogenesis because the double mutant Δgrx2/sod1 was very susceptible to neutrophil killing and was defective in hyphae formation in addition to having a lower virulence in an animal model of systemic infection.

Magnetic coherent population trapping in a single ion

NASA Astrophysics Data System (ADS)

Das, S.; Liu, P.; Grémaud, B.; Mukherjee, M.

2018-03-01

Magnetically induced coherent population trapping has been studied in a single trapped laser cooled ion. The magnetic-field-dependent narrow spectral feature is found to be a useful tool in determining the null point of magnetic field at the ion position. In particular, we use a double Λ scheme that allows us to measure the null magnetic-field point limited by the detector shot noise. We analyzed the system theoretically and found certain long-lived bright states as the dark state is generated under steady-state condition.

Semi-analytical study of the tokamak pedestal density profile in a single-null diverted plasma with puffing-recycling gas sources

NASA Astrophysics Data System (ADS)

Shi, Bingren

2010-10-01

The tokamak pedestal density structure is generally studied using a diffusion-dominant model. Recent investigations (Stacey and Groebner 2009 Phys. Plasmas 16 102504) from first principle based physics have shown a plausible existence of large inward convection in the pedestal region. The diffusion-convection equation with rapidly varying convection and diffusion coefficients in the near edge region and model puffing-recycling neutral particles is studied in this paper. A peculiar property of its solution for the existence of the large convection case is that the pedestal width of the density profile, qualitatively different from the diffusion-dominant case, depends mainly on the width of the inward convection and only weakly on the neutral penetration length and its injection position.

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

PubMed Central

Sapkota, Darshan; Chintala, Hemabindu; Wu, Fuguo; Fliesler, Steven J.; Hu, Zihua; Mu, Xiuqian

2014-01-01

Previously, we have shown that Onecut1 (Oc1) and Onecut2 (Oc2) are expressed in retinal progenitor cells, developing retinal ganglion cells (RGCs), and horizontal cells (HCs). However, in Oc1-null mice, we only observed an 80% reduction in HCs, but no defects in other cell types. We postulated that the lack of defects in other cell types in Oc1-null retinas was a result of redundancy with Oc2. To test this theory, we have generated Oc2-null mice and now show that their retinas also only have defects in HCs, with a 50% reduction in their numbers. However, when both Oc1 and Oc2 are knocked out, the retinas exhibit more profound defects in the development of all early retinal cell types, including completely failed genesis of HCs, compromised generation of cones, reduced production (by 30%) of RGCs, and absence of starburst amacrine cells. Cone subtype diversification and RGC subtype composition also were affected in the double-null retina. Using RNA-Seq expression profiling, we have identified downstream genes of Oc1 and Oc2, which not only confirms the redundancy between the two factors and renders a molecular explanation for the defects in the double-null retinas, but also shows that the onecut factors suppress the production of the late cell type, rods, indicating that the two factors contribute to the competence of retinal progenitor cells for the early retinal cell fates. Our results provide insight into how onecut factors regulate the creation of cellular diversity in the retina and, by extension, in the central nervous system in general. PMID:25228773

A symplectic map for trajectories of magnetic field lines in double-null divertor tokamaks

NASA Astrophysics Data System (ADS)

Crank, Willie; Ali, Halima; Punjabi, Alkesh

2009-11-01

The coordinates of the area-preserving map equations for integration of magnetic field line trajectories in tokamaks can be any coordinates for which a transformation to (ψ,θ,φ) coordinates exists [A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Lett. A 364, 140 (2007)]. ψ is toroidal magnetic flux, θ is poloidal angle, and φ is toroidal angle. This freedom is exploited to construct a map that represents the magnetic topology of double-null divertor tokamaks. For this purpose, the generating function of the simple map [A. Punjabi, A. Verma, and A. Boozer, Phys. Rev. Lett. 69, 3322 (1992)] is slightly modified. The resulting map equations for the double-null divertor tokamaks are: x1=x0-ky0(1-y0^2 ), y1=y0+kx1. k is the map parameter. It represents the generic topological effects of toroidal asymmetries. The O-point is at (0.0). The X-points are at (0,±1). The equilibrium magnetic surfaces are calculated. These surfaces are symmetric about the x- and y- axes. The widths of stochastic layer near the X-points in the principal plane, and the fractal dimensions of the magnetic footprints on the inboard and outboard side of upper and lower X-points are calculated from the map. This work is supported by US Department of Energy grants DE-FG02-07ER54937, DE-FG02-01ER54624 and DE-FG02-04ER54793.

Fabrication tolerant chalcogenide mid-infrared multimode interference coupler design with applications for Bracewell nulling interferometry.

PubMed

Goldsmith, Harry-Dean Kenchington; Cvetojevic, Nick; Ireland, Michael; Madden, Stephen

2017-02-20

Understanding exoplanet formation and finding potentially habitable exoplanets is vital to an enhanced understanding of the universe. The use of nulling interferometry to strongly attenuate the central star's light provides the opportunity to see objects closer to the star than ever before. Given that exoplanets are usually warm, the 4 µm Mid-Infrared region is advantageous for such observations. The key performance parameters for a nulling interferometer are the extinction ratio it can attain and how well that is maintained across the operational bandwidth. Both parameters depend on the design and fabrication accuracy of the subcomponents and their wavelength dependence. Via detailed simulation it is shown in this paper that a planar chalcogenide photonic chip, consisting of three highly fabrication tolerant multimode interference couplers, can exceed an extinction ratio of 60 dB in double nulling operation and up to 40 dB for a single nulling operation across a wavelength window of 3.9 to 4.2 µm. This provides a beam combiner with sufficient performance, in theory, to image exoplanets.

Destruction of Last Good Surface of The Simple Map For Single-null Divertor Tokamaks

NASA Astrophysics Data System (ADS)

Leach, Genese; Ali, Halima; Punjabi, Alkesh

2003-10-01

The Simple Map (SM) for a single-null diverted tokamak is given by x_n+1=x_n-ky_n(1-y_n) and y_n+1=y_n+kx_n+1, where the map parameter k represents the effects of toroidal asymmetries. Here we investigate what happens to the last good surface of SM with k= 0.6 when the value of k is increased. When k is in the region between .6 to .611, the good surface disappears and islands of different sizes and shapes start to appear. We find chaos when k is in the region between .6110 to 0.640. Some of these islands exhibit self-similarity. Self- Similarity can occur for a limitless number of times if one magnifies into this chaotic region. A Fortran code and TecPlot are used to visualize the data. Study of this phenomenon may contribute to the magnetic confinement problem through a better understanding of why and how the deterioration of the last good surface occurs. This work is jointly supported by NASA SHARP and US DOE Grant number DE-FG02-02ER54673. 1. Punjabi et al, Phys. Rev. Lett., 69, 3322 (1992), 2. Punjabi et al, Phys. Plasma, 4, 337 (1997)

Double gene deletion reveals the lack of cooperation between PPAR{alpha} and PPAR{beta} in skeletal muscle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bedu, E.; Desplanches, D.; Pequignot, J.

2007-06-15

The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPAR{alpha} and PPAR{beta} isotypes are known to regulate muscle fatty acid oxidation and a reciprocal compensation of their function has been proposed. Herein, we investigated muscle contractile and metabolic phenotypes in PPAR{alpha}-/-, PPAR{beta}-/-, and double PPAR{alpha}-/- {beta}-/- mice. Heart and soleus muscle analyses show that the deletion of PPAR{alpha} induces a decrease of the HAD activity ({beta}-oxidation) while soleus contractile phenotype remains unchanged. A PPAR{beta} deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensationmore » of PPAR{beta} and PPAR{alpha} functions since double gene deletion PPAR{alpha}-PPAR{beta} mostly reproduces the null PPAR{alpha}-mediated reduced {beta}-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPAR{beta} is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPAR{alpha} in PPAR{alpha} null mice.« less

Note of the methodological flaws in the paper entitled "GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis".

PubMed

Qiu, Mali; Wu, Xu; Qu, Xiaobing

2016-09-01

With great interest, we read the paper "GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis" (by Hu XY et al.), which has reached important conclusions that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response in breast cancer. The result is encouraging. Nevertheless, several methodological flaws in this meta-analysis are worth noticing.

The Simple Map for a Single-null Divertor Tokamak: How to Find the Footprint of Field lines

NASA Astrophysics Data System (ADS)

Figgins, Montoya; Ali, Halima; Punjabi, Alkesh

2000-10-01

We are working with the Simple Map^1 to find the footprint of field lines on the diverter plate in a single-null tokamak. Footprint of a field line is the position of the line when it escapes across the divertor plate. The Simple Map represents the magnetic field in a single-null divertor tokamak. The path of a field line is given by the equations: X_n+1=X_n-kY_n(1-Y_n) and Y_n+1=Y_n+kX_n+1. In order to find the footprint, we must first find the last good surface which is Y=0.997135768 and X=0. The value of k is fixed at 0.6. The starting values X0 are fixed at X_0=0. We use 10,000 points between the last good surface and the X-point. The X-point is located at (0,1). We also use the Continuous Analog of the Simple Map given by the equations: X(φ)=X_0-kY0 (1-Y_0)φ and Y(φ)=Y_0+kX(φ)φ. This will tell us what the (φ,X) is which represents the field lines crossing the divertor plate. The divertor plate is located at Y=1. When graphed, the footprint of field lines looks like the rings of Saturn. This work is supported by US DOES OFES. Ms. Montoya Figgins is HU CFRT Summer Fusion High School Scholar from E. E. Smith High School in North Carolina. She is supported by NASA under its NASA SHARP Plus Program. 1. Punjabi A, Verma A, and Boozer A, Phys Rev Lett, 69, 3322 (1992) and J Plasma Phys, 52, 91 (1994)

A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells.

PubMed

El-Hoss, Jad; Sullivan, Kate; Cheng, Tegan; Yu, Nicole Y C; Bobyn, Justin D; Peacock, Lauren; Mikulec, Kathy; Baldock, Paul; Alexander, Ian E; Schindeler, Aaron; Little, David G

2012-01-01

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue-specific lesions associated with local double-inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre-expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1(flox/flox) and Nf1(flox/-) mice. The effects of the presence of Nf1(null) cells were extensively examined. Cultured Nf1(null)-committed osteoprogenitors from neonatal calvaria failed to differentiate and express mature osteoblastic markers, even with recombinant bone morphogenetic protein-2 (rhBMP-2) treatment. Similarly, Nf1(null)-inducible osteoprogenitors obtained from Nf1 MyoDnull mouse muscle were also unresponsive to rhBMP-2. In both closed and open fracture models in Nf1(flox/flox) and Nf1(flox/-) mice, local AdCre injection significantly impaired bone healing, with fracture union being <50% that of wild type controls. No significant difference was seen between Nf1(flox/flox) and Nf1(flox/-) mice. Histological analyses showed invasion of the Nf1(null) fractures by fibrous and highly proliferative tissue. Mean amounts of fibrous tissue were increased upward of 10-fold in Nf1(null) fractures and bromodeoxyuridine (BrdU) staining in closed fractures showed increased numbers of proliferating cells. In Nf1(null) fractures, tartrate-resistant acid phosphatase-positive (TRAP+) cells were frequently observed within the fibrous tissue, not lining a bone surface. In summary, we report that local Nf1 deletion in a fracture callus is sufficient to impair bony union and recapitulate histological features of clinical CPT. Cell culture findings support the concept that Nf1 double inactivation impairs early osteoblastic differentiation. This model provides valuable insight into the pathobiology of the disease, and will be helpful for trialing therapeutic compounds. Copyright © 2012 American Society for Bone and Mineral Research.

Shadoo/PrP (Sprn0/0/Prnp0/0) double knockout mice

PubMed Central

Daude, Nathalie; Westaway, David

2012-01-01

Shadoo (Sho) is a brain glycoprotein with similarities to the unstructured region of PrPC. Frameshift alleles of the Sho gene, Sprn, are reported in variant Creutzfeldt-Jakob disease (vCJD) patients while Sprn mRNA knockdown in PrP-null (Prnp0/0) embryos produces lethality, advancing Sho as the hypothetical PrP-like “pi” protein. Also, Sho levels are reduced as misfolded PrP accumulates during prion infections. To penetrate these issues we created Sprn null alleles (Daude et al., Proc. Natl. Acad. Sci USA 2012; 109(23): 9035–40). Results from the challenge of Sprn null and TgSprn transgenic mice with rodent-adapted prions coalesce to define downregulation of Sho as a “tracer” for the formation of misfolded PrP. However, classical BSE and rodent-adapted BSE isolates may behave differently, as they do for other facets of the pathogenic process, and this intriguing variation warrants closer scrutiny. With regards to physiological function, double knockout mice (Sprn0/0/Prnp0/0) mice survived to over 600 d of age. This suggests that Sho is not pi, or, given the accumulating data for many activities for PrPC, that the pi hypothesis invoking a discrete signaling pathway to maintain neuronal viability is no longer tenable. PMID:22929230

Anomalous transport in discrete arcs and simulation of double layers in a model auroral circuit

NASA Technical Reports Server (NTRS)

Smith, Robert A.

1987-01-01

The evolution and long-time stability of a double layer (DL) in a discrete auroral arc requires that the parallel current in the arc, which may be considered uniform at the source, be diverted within the arc to charge the flanks of the U-shaped double layer potential structure. A simple model is presented in which this current redistribution is effected by anomalous transport based on electrostatic lower hybrid waves driven by the flank structure itself. This process provides the limiting constraint on the double layer potential. The flank charging may be represented as that of a nonlinear transmission line. A simplified model circuit, in which the transmission line is represented by a nonlinear impedance in parallel with a variable resistor, is incorporated in a one-dimensional simulation model to give the current density at the DL boundaries. Results are presented for the scaling of the DL potential as a function of the width of the arc and the saturation efficiency of the lower hybrid instability mechanism.

Anomalous transport in discrete arcs and simulation of double layers in a model auroral circuit

NASA Technical Reports Server (NTRS)

Smith, Robert A.

1987-01-01

The evolution and long-time stability of a double layer in a discrete auroral arc requires that the parallel current in the arc, which may be considered uniform at the source, be diverted within the arc to charge the flanks of the U-shaped double-layer potential structure. A simple model is presented in which this current re-distribution is effected by anomalous transport based on electrostatic lower hybrid waves driven by the flank structure itself. This process provides the limiting constraint on the double-layer potential. The flank charging may be represented as that of a nonlinear transmission. A simplified model circuit, in which the transmission line is represented by a nonlinear impedance in parallel with a variable resistor, is incorporated in a 1-d simulation model to give the current density at the DL boundaries. Results are presented for the scaling of the DL potential as a function of the width of the arc and the saturation efficiency of the lower hybrid instability mechanism.

Motion perception during variable-radius swing motion in darkness.

PubMed

Rader, A A; Oman, C M; Merfeld, D M

2009-10-01

Using a variable-radius roll swing motion paradigm, we examined the influence of interaural (y-axis) and dorsoventral (z-axis) force modulation on perceived tilt and translation by measuring perception of horizontal translation, roll tilt, and distance from center of rotation (radius) at 0.45 and 0.8 Hz using standard magnitude estimation techniques (primarily verbal reports) in darkness. Results show that motion perception was significantly influenced by both y- and z-axis forces. During constant radius trials, subjects' perceptions of tilt and translation were generally almost veridical. By selectively pairing radius (1.22 and 0.38 m) and frequency (0.45 and 0.8 Hz, respectively), the y-axis acceleration could be tailored in opposition to gravity so that the combined y-axis gravitoinertial force (GIF) variation at the subject's ears was reduced to approximately 0.035 m/s(2) - in effect, the y-axis GIF was "nulled" below putative perceptual threshold levels. With y-axis force nulling, subjects overestimated their tilt angle and underestimated their horizontal translation and radius. For some y-axis nulling trials, a radial linear acceleration at twice the tilt frequency (0.25 m/s(2) at 0.9 Hz, 0.13 m/s(2) at 1.6 Hz) was simultaneously applied to reduce the z-axis force variations caused by centripetal acceleration and by changes in the z-axis component of gravity during tilt. For other trials, the phase of this radial linear acceleration was altered to double the magnitude of the z-axis force variations. z-axis force nulling further increased the perceived tilt angle and further decreased perceived horizontal translation and radius relative to the y-axis nulling trials, while z-axis force doubling had the opposite effect. Subject reports were remarkably geometrically consistent; an observer model-based analysis suggests that perception was influenced by knowledge of swing geometry.

Physics Results from the National Spherical Torus Experiment

NASA Astrophysics Data System (ADS)

Kaye, S. M.

2000-10-01

The National Spherical Torus Experiment (NSTX) will produce plasmas with R/a=0.85/0.68 m 1.25, I_p= 1 MA, BT <=0.6 T, κ<=2.2, δ<=0.5, with 6 MW of High Harmonic Fast Wave (HHFW) heating and current drive, 5 MW of Neutral Beam Injection (NBI) and Co-axial Helicity Injection (CHI) for non-inductive startup to establish the physics principles of low aspect ratio. Outboard passive conducting plates aid vertical stability and suppression of low-n modes. During the initial set of physics experiments, studies of poloidal flux consumption indicated an optimal current ramp rate of 5 MA/sec, with higher ramp rates limited by m=2 oscillations and Internal Reconnection Events possibly related to impurity accumulation and double tearing modes. Flux consumption optimization and real-time plasma control led to the achievement of ohmic discharges with 1 MA plasma current and stored energies up to 48 kJ and βT 9%. Inboard limited and single and double-null diverted plasmas over a wide range of κ and δ were produced. The density limit, so far, is consistent with the Hugill limit, which is about 60% of the Greenwald limit, and it was characterized by growing and locking m=1 oscillations, followed by a series of Reconnection Events. The q-limit was manifest as growing and locking 2/1 perturbations leading to severe kinking of the plasma surface and subsequent discharge termination as q_cyl decreased below 2. Initial observations of edge turbulence indicated filamentary structures with λ_perp 10 cm. Up to 2 MW of HHFW power was coupled to the plasma, with increases in stored energy observed for waves with k_parallel=14 m-1, but not at higher phase velocity. CHI experiments on NSTX produced up to 130 kA of toroidal current for up to 100 msec. NBI heating is planned for late September 2000. This work has been supported at PPPL by U.S. DOE Contract # DE-AC02-76CH03073.

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients.

PubMed

Aly, Dalia Gamal; Salem, Samar Abdallah; Amr, Khalda Sayed; El-Hamid, Mahmoud Fawzy Abd

2018-01-01

The association of glutathione S-transferases M1/T1 (GSTM1/T1) null polymorphisms with vitiligo was proposed in several studies including two Egyptian studies with contradictory results. The aim here was to assess the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo in a larger sample of Egyptian patients with generalized vitiligo. This study included 122 vitiligo patients and 200 healthy controls that were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done using a multiplex polymerase chain reaction (PCR). Increased odds of generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1 polymorphisms (P<0.05). Controls with GSTM1 null/GSTT1+ heterozygosis presented with a 2.97 odds protection from having generalized vitiligo (OR=2.97, 95%CI=1.1-7.7) (P=0.02) compared with patients. Small sample size of patients. This study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a 2.97 odds protection from having generalized vitiligo compared with patients. It was is the first time, to our knowledge, that such an association has been reported.

Evidence for complete epistasis of null mutations in murine Fanconi anemia genes Fanca and Fancg.

PubMed

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.

Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors

PubMed Central

Fleming, Michael S; Vysochan, Anna; Paixão, Sόnia; Niu, Jingwen; Klein, Rüdiger; Savitt, Joseph M; Luo, Wenqin

2015-01-01

RET can be activated in cis or trans by its co-receptors and ligands in vitro, but the physiological roles of trans signaling are unclear. Rapidly adapting (RA) mechanoreceptors in dorsal root ganglia (DRGs) express Ret and the co-receptor Gfrα2 and depend on Ret for survival and central projection growth. Here, we show that Ret and Gfrα2 null mice display comparable early central projection deficits, but Gfrα2 null RA mechanoreceptors recover later. Loss of Gfrα1, the co-receptor implicated in activating RET in trans, causes no significant central projection or cell survival deficit, but Gfrα1;Gfrα2 double nulls phenocopy Ret nulls. Finally, we demonstrate that GFRα1 produced by neighboring DRG neurons activates RET in RA mechanoreceptors. Taken together, our results suggest that trans and cis RET signaling could function in the same developmental process and that the availability of both forms of activation likely enhances but not diversifies outcomes of RET signaling. DOI: http://dx.doi.org/10.7554/eLife.06828.001 PMID:25838128

Orexin Regulates Bone Remodeling via a Dominant Positive Central Action and a Subordinate Negative Peripheral Action

PubMed Central

Wei, Wei; Motoike, Toshiyuki; Krzeszinski, Jing Y.; Jin, Zixue; Xie, Xian-Jin; Dechow, Paul C.; Yanagisawa, Masashi; Wan, Yihong

2014-01-01

SUMMARY Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown. Here we show that orexin functions centrally through orexin receptor 2 (OX2R) in the brain to enhance bone formation. OX2R-null mice exhibit low-bone-mass owing to elevated circulating leptin; whereas central administration of an OX2R-selective agonist augments bone mass. Conversely, orexin also functions peripherally through orexin receptor 1 (OX1R) in the bone to suppress bone formation. OX1R-null mice exhibit high-bone-mass owing to a mesenchymal stem cell differentiation shift from adipocyte to osteoblast that results from higher osseous ghrelin expression. The central action is dominant over the peripheral action because bone mass is reduced in orexin-null and OX1R2R-double-null mice but enhanced in orexin over-expressing transgenic mice. These findings reveal orexin as a critical rheostat of skeletal homeostasis that exerts a yin-yang dual regulation, and highlight orexin as a therapeutic target for osteoporosis. PMID:24794976

Diverter assembly for radioactive material

DOEpatents

Andrews, Katherine M.; Starenchak, Robert W.

1989-01-01

A diverter assembly for diverting a pneumatically conveyed holder for a radioactive material between a central conveying tube and one of a plurality of radially offset conveying tubes includes an airtight container. A diverter tube having an offset end is suitably mounted in the container for rotation. A rotary seal seals one end of the diverter tube during and after rotation of the diverter tube while a spring biased seal seals the other end of the diverter tube which mvoes between various offset conveying tubes. An indexing device rotatably indexes the diverter tube and this indexing device is driven by a suitable drive. The indexing mechanism is preferably a geneva-type mechanism to provide a locking of the diverter tube in place.

Redundant role of protein kinase C delta and epsilon during mouse embryonic development.

PubMed

Carracedo, Sergio; Sacher, Frank; Brandes, Gudrun; Braun, Ursula; Leitges, Michael

2014-01-01

Protein Kinase C delta and epsilon are mediators of important cellular events, such as cell proliferation, migration or apoptosis. The formation of blood vessels, i.e., vasculo- and angiogenesis, is a process where these isoforms have also been shown to participate. However, mice deficient in either Protein Kinase C delta or epsilon are viable and therefore their individual contribution to the formation of the vasculature appeared so far dispensable. In this study, we show that double null mutation of Protein Kinase C delta and epsilon causes embryonic lethality at approximately E9.5. At this stage, whole mount staining of the endothelial marker CD31 in double null embryos revealed defective blood vessel formation. Moreover, culture of double deficient mouse allantois showed impaired endothelial cell organization, and analyses of double deficient embryo sections showed dilated vessels, decreased endothelial-specific adherent junctions, and decreased contact of endothelial cells with mural cells. Protein kinase C delta and epsilon also appeared essential for vascular smooth muscle cell differentiation, since α-smooth muscle actin, a classical marker for vascular smooth muscle cells, was almost undetectable in double deficient embryonic aorta at E9.5. Subsequent qPCR analyses showed decreased VE-cadherin, Vegfr2, Cd31, Cdh2, Ets1, and Fli-1, among other angiogenesis related transcripts in double deficient embryos. Taken together, these data suggest for the first time an in vivo redundant role between members of the novel Protein Kinase C subfamily that allows for mutual compensation during mouse embryonic development, with vasculogenesis/angiogenesis as an obvious common function of these two Protein Kinase Cs. Protein Kinase C delta and epsilon might therefore be useful targets for inhibiting vasculo- and/or angiogenesis.

Double-null divertor configuration discharge and disruptive heat flux simulation using TSC on EAST

NASA Astrophysics Data System (ADS)

Bo, SHI; Jinhong, YANG; Cheng, YANG; Desheng, CHENG; Hui, WANG; Hui, ZHANG; Haifei, DENG; Junli, QI; Xianzu, GONG; Weihua, WANG

2018-07-01

The tokamak simulation code (TSC) is employed to simulate the complete evolution of a disruptive discharge in the experimental advanced superconducting tokamak. The multiplication factor of the anomalous transport coefficient was adjusted to model the major disruptive discharge with double-null divertor configuration based on shot 61 916. The real-time feed-back control system for the plasma displacement was employed. Modeling results of the evolution of the poloidal field coil currents, the plasma current, the major radius, the plasma configuration all show agreement with experimental measurements. Results from the simulation show that during disruption, heat flux about 8 MW m‑2 flows to the upper divertor target plate and about 6 MW m‑2 flows to the lower divertor target plate. Computations predict that different amounts of heat fluxes on the divertor target plate could result by adjusting the multiplication factor of the anomalous transport coefficient. This shows that TSC has high flexibility and predictability.

Effects of glutathione s-transferase (GST) M1 and T1 polymorphisms on antioxidant vitamins and oxidative stress-related parameters in Korean subclinical hypertensive subjects after kale juice (Brassica oleracea acephala) supplementation.

PubMed

Lee, Hye-Jin; Han, Jeong-Hwa; Park, Yoo Kyoung; Kang, Myung-Hee

2018-04-01

Glutathione s-transferase ( GST ) is involved in the formation of a multigene family comprising phase II detoxification enzymes, involved in the detoxification of reactive oxygen species. This study evaluated whether daily supplementation with kale juice could modulate levels of plasma antioxidant vitamins and oxidative stress-related parameters. We further examined whether this modulation was affected by combined GSTM1 and T1 polymorphisms. Totally, 84 subclinical hypertensive patients having systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg, received 300 mL of kale juice daily for 6 weeks. Blood samples were drawn before start of study and after completion of 6 weeks. After supplementation, we observed significant decrease in DNA damage and increase in erythrocyte catalase activity in all genotypes. Plasma level of vitamin C was significantly increased in the wild/null and double null genotypes. The plasma levels of β-carotene, erythrocyte glutathione peroxidase activity, and nitric oxide were increased only in the wild/null genotype after kale juice supplementation. The effect of kale juice was significantly greater in the GSTM1 null genotype and wild/null genotype groups, suggesting possibility of personalized nutritional prescriptions based on personal genetics.

Influence of the renal artery ostium flow diverter on hemodynamics and atherogenesis.

PubMed

Albert, Scott; Balaban, Robert S; Neufeld, Edward B; Rossmann, Jenn Stroud

2014-05-07

The structure and function of the renal artery ostium flow diverter on the caudal side of the renal branch point were previously reported; in this study, we further evaluate the diverter׳s possible functions. The protrusion of this structure into the abdominal aorta suggests that the diverter may preferentially direct blood flow to the renal arteries, and that it may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution; depending on the diverter׳s position, the flow to the renal arteries may be increased or reduced. Calculated results also demonstrate the diverter׳s effect on the wall shear stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diverter assembly for radioactive material

DOEpatents

Andrews, K.M.; Starenchak, R.W.

1988-04-11

A diverter assembly for diverting a pneumatically conveyed holder for a radioactive material between a central conveying tube and one of a plurality of radially offset conveying tubes includes an airtight container. A diverter tube having an offset end is suitably mounted in the container for rotation. A rotary seal seals one end of the diverter tube during and after rotation of the diverter tube while a spring biased seal seals the other end of the diverter tube which moves between various offset conveying tubes. An indexing device rotatably indexes the diverter tube and this indexing device is driven by a suitable drive. The indexing mechanism is preferably a geneva-type mechanism to provide a locking of the diverter tube in place. 3 figs.

Role of Aquaporin-4 in Airspace-to-Capillary Water Permeability in Intact Mouse Lung Measured by a Novel Gravimetric Method

PubMed Central

Song, Yuanlin; Ma, Tonghui; Matthay, Michael A.; Verkman, A.S.

2000-01-01

The mammalian peripheral lung contains at least three aquaporin (AQP) water channels: AQP1 in microvascular endothelia, AQP4 in airway epithelia, and AQP5 in alveolar epithelia. In this study, we determined the role of AQP4 in airspace-to-capillary water transport by comparing water permeability in wild-type mice and transgenic null mice lacking AQP1, AQP4, or AQP1/AQP4 together. An apparatus was constructed to measure lung weight continuously during pulmonary artery perfusion of isolated mouse lungs. Osmotically induced water flux (Jv) between the airspace and capillary compartments was measured from the kinetics of lung weight change in saline-filled lungs in response to changes in perfusate osmolality. Jv in wild-type mice varied linearly with osmotic gradient size (4.4 × 10−5 cm3 s−1 mOsm−1) and was symmetric, independent of perfusate osmolyte size, weakly temperature dependent, and decreased 11-fold by AQP1 deletion. Transcapillary osmotic water permeability was greatly reduced by AQP1 deletion, as measured by the same method except that the airspace saline was replaced by an inert perfluorocarbon. Hydrostatically induced lung edema was characterized by lung weight changes in response to changes in pulmonary arterial inflow or pulmonary venous outflow pressure. At 5 cm H2O outflow pressure, the filtration coefficient was 4.7 cm3 s−1 mOsm−1 and reduced 1.4-fold by AQP1 deletion. To study the role of AQP4 in lung water transport, AQP1/AQP4 double knockout mice were generated by crossbreeding of AQP1 and AQP4 null mice. Jv were (cm3 s−1 mOsm−1 × 10−5, SEM, n = 7–12 mice): 3.8 ± 0.4 (wild type), 0.35 ± 0.02 (AQP1 null), 3.7 ± 0.4 (AQP4 null), and 0.25 ± 0.01 (AQP1/AQP4 null). The significant reduction in P f in AQP1 vs. AQP1/AQP4 null mice was confirmed by an independent pleural surface fluorescence method showing a 1.6 ± 0.2-fold (SEM, five mice) reduced P f in the AQP1/AQP4 double knockout mice vs. AQP1 null mice. These results establish a simple gravimetric method to quantify osmosis and filtration in intact mouse lung and provide direct evidence for a contribution of the distal airways to airspace-to-capillary water transport. PMID:10613915

Initial development of the DIII–D snowflake divertor control

NASA Astrophysics Data System (ADS)

Kolemen, E.; Vail, P. J.; Makowski, M. A.; Allen, S. L.; Bray, B. D.; Fenstermacher, M. E.; Humphreys, D. A.; Hyatt, A. W.; Lasnier, C. J.; Leonard, A. W.; McLean, A. G.; Maingi, R.; Nazikian, R.; Petrie, T. W.; Soukhanovskii, V. A.; Unterberg, E. A.

2018-06-01

Simultaneous control of two proximate magnetic field nulls in the divertor region is demonstrated on DIII–D to enable plasma operations in an advanced magnetic configuration known as the snowflake divertor (SFD). The SFD is characterized by a second-order poloidal field null, created by merging two first-order nulls of the standard divertor configuration. The snowflake configuration has many magnetic properties, such as high poloidal flux expansion, large plasma-wetted area, and additional strike points, that are advantageous for divertor heat flux management in future fusion reactors. However, the magnetic configuration of the SFD is highly-sensitive to changes in currents within the plasma and external coils and therefore requires complex magnetic control. The first real-time snowflake detection and control system on DIII–D has been implemented in order to stabilize the configuration. The control algorithm calculates the position of the two nulls in real-time by locally-expanding the Grad–Shafranov equation in the divertor region. A linear relation between variations in the poloidal field coil currents and changes in the null locations is then analytically derived. This formulation allows for simultaneous control of multiple coils to achieve a desired SFD configuration. It is shown that the control enabled various snowflake configurations on DIII–D in scenarios such as the double-null advanced tokamak. The SFD resulted in a 2.5×  reduction in the peak heat flux for many energy confinement times (2–3 s) without any adverse effects on core plasma performance.

Can one ever prove that neutrinos are Dirac particles?

NASA Astrophysics Data System (ADS)

Hirsch, Martin; Srivastava, Rahul; Valle, José W. F.

2018-06-01

According to the "Black Box" theorem the experimental confirmation of neutrinoless double beta decay (0 ν 2 β) would imply that at least one of the neutrinos is a Majorana particle. However, a null 0 ν 2 β signal cannot decide the nature of neutrinos, as it can be suppressed even for Majorana neutrinos. In this letter we argue that if the null 0 ν 2 β decay signal is accompanied by a 0 ν 4 β quadruple beta decay signal, then at least one neutrino should be a Dirac particle. This argument holds irrespective of the underlying processes leading to such decays.

Hypothalamic-pituitary cytokine network.

PubMed

Kariagina, Anastasia; Romanenko, Dmitry; Ren, Song-Guang; Chesnokova, Vera

2004-01-01

Cytokines expressed in the brain and involved in regulating the hypothalamus-pituitary-adrenal (HPA) axis contribute to the neuroendocrine interface. Leukemia inhibitory factor (LIF) and LIF receptors are expressed in human pituitary cells and murine hypothalamus and pituitary. LIF potently induces pituitary proopiomelanocortin (POMC) gene transcription and ACTH secretion and potentiates CRH induction of POMC. In vivo, LIF, along with CRH, enhances POMC expression and ACTH secretion in response to emotional and inflammatory stress. To further elucidate specific roles for both CRH and LIF in activating the inflammatory HPA response, double-knockout mice (CRH/LIFKO) were generated by breeding the null mutants for each respective single gene. Inflammation produced by ip injection of lipopolysaccharide (1 microg/mouse) to double CRH and LIF-deficient mice elicited pituitary POMC induction similar to wild type and markedly higher than in single null animals (P<0.0.01). Double-knockout mice also demonstrated robust corticosterone response to inflammation. High pituitary POMC mRNA levels may reflect abundant TNFalpha, IL-1beta, and IL-6 activation observed in the hypothalamus and pituitary of these animals. Our results suggest that increased central proinflammatory cytokine expression can compensate for the impaired HPA axis function and activates inflammatory ACTH and corticosterone responses in mice-deficient in both CRH and LIF.

Potential role of alpha-synuclein and metallothionein in lead-induced inclusion body formation.

PubMed

Zuo, Peijun; Qu, Wei; Cooper, Ryan N; Goyer, Robert A; Diwan, Bhalchandra A; Waalkes, Michael P

2009-09-01

Lead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knockout (MT-null) and parental wild-type (WT) cell lines to further explore the formation process of Pb-induced IBs. Unlike WT cells, MT-null cells did not form IBs after Pb exposure. Western blot of cytosol showed soluble MT protein in WT cells was lost during Pb exposure as IBs formed. Transfection of MT-I into MT-null cells allowed IBs formation after Pb exposure. Considering Pb-induced IBs may be like disease-related aggresomes, which often contain alpha-synuclein (Scna), we investigated Scna expression in cells capable (WT) and incapable (MT-null) of producing IBs after Pb exposure. Scna protein showed poor basal expression in MT-null cells. Pb exposure increased Scna expression only in WT cells. MT transfection increased Scna transcript to WT levels. In WT or MT-transfected MT-null cells, Pb-induced Scna expression rapidly increased and then decreased over 48 h as Pb-induced IBs were formed. A direct interaction between Scna and MT was confirmed ex vivo by antibody pulldown assay where the proteins coprecipitated with an antibody to MT. Pb exposure caused increased colocalization of MT and Scna proteins with time only in WT cells. In WT mice after chronic Pb exposure Scna was localized in renal cells containing forming IBs, whereas MT-null mice did not form IBs. Thus, Scna could be component of Pb-induced IBs and, with MT, may play a role in IBs formation.

30 CFR 250.430 - When must I install a diverter system?

Code of Federal Regulations, 2014 CFR

2014-07-01

... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling... diverter system before you drill a conductor or surface hole. The diverter system consists of a diverter... the diverter system to ensure proper diversion of gases, water, drilling fluid, and other materials...

30 CFR 250.430 - When must I install a diverter system?

Code of Federal Regulations, 2012 CFR

2012-07-01

... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling... diverter system before you drill a conductor or surface hole. The diverter system consists of a diverter... the diverter system to ensure proper diversion of gases, water, drilling fluid, and other materials...

30 CFR 250.430 - When must I install a diverter system?

Code of Federal Regulations, 2011 CFR

2011-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.430 When must I install a diverter system? You must install a diverter system before you drill a conductor or surface hole. The diverter system...

30 CFR 250.430 - When must I install a diverter system?

Code of Federal Regulations, 2013 CFR

2013-07-01

... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling... diverter system before you drill a conductor or surface hole. The diverter system consists of a diverter... the diverter system to ensure proper diversion of gases, water, drilling fluid, and other materials...

30 CFR 250.434 - What are the recordkeeping requirements for diverter actuations and tests?

Code of Federal Regulations, 2010 CFR

2010-07-01

... diverter actuations and tests? 250.434 Section 250.434 Mineral Resources MINERALS MANAGEMENT SERVICE... for diverter actuations and tests? You must record the time, date, and results of all diverter actuations and tests in the driller's report. In addition, you must: (a) Record the diverter pressure test on...

Effects of glutathione s-transferase (GST) M1 and T1 polymorphisms on antioxidant vitamins and oxidative stress-related parameters in Korean subclinical hypertensive subjects after kale juice (Brassica oleracea acephala) supplementation

PubMed Central

2018-01-01

BACKGROUND/OBJECTIVES Glutathione s-transferase (GST) is involved in the formation of a multigene family comprising phase II detoxification enzymes, involved in the detoxification of reactive oxygen species. This study evaluated whether daily supplementation with kale juice could modulate levels of plasma antioxidant vitamins and oxidative stress-related parameters. We further examined whether this modulation was affected by combined GSTM1 and T1 polymorphisms. SUBJECTS/METHODS Totally, 84 subclinical hypertensive patients having systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg, received 300 mL of kale juice daily for 6 weeks. Blood samples were drawn before start of study and after completion of 6 weeks. RESULTS After supplementation, we observed significant decrease in DNA damage and increase in erythrocyte catalase activity in all genotypes. Plasma level of vitamin C was significantly increased in the wild/null and double null genotypes. The plasma levels of β-carotene, erythrocyte glutathione peroxidase activity, and nitric oxide were increased only in the wild/null genotype after kale juice supplementation. CONCLUSIONS The effect of kale juice was significantly greater in the GSTM1 null genotype and wild/null genotype groups, suggesting possibility of personalized nutritional prescriptions based on personal genetics. PMID:29629028

Bile exclusion from the duodenum. Its effect on gastric and pancreatic function in the dog.

PubMed

Davies, H A; Wheeler, M H; Psaila, J; Rhodes, J; Newcombe, R G; Jones, J M; Procter, D; Adrian, T E; Bloom, S R

1985-10-01

The effect of diverting bile from the duodenum in four dogs with cholecystojejunostomy was studied using a double-marker perfusion technique. After the diversion procedure, a liquid meal increased acid secretion from 0.8 mmol H+/min to 1.48 mmol H+/min (P less than 0.05, paired t test); there was an associated rise in serum levels of gastrin 120 min after feeding (P less than 0.001, paired t test). Pancreatic secretion of trypsin decreased from 3.91 IU/min to 2.66 IU/min after bile diversion (P less than 0.01, paired t test), and the level of CCK was significantly lower 60 min after feeding (P less than 0.05, paired t test). There was no significant change in the rate of gastric emptying after bile diversion, but the pH of duodenal contents was lower in the later stages of digestion. These changes may explain the reported increase of peptic ulcer after diverting bile from the duodenum, and the procedure should not be considered unless the consequences of acid hypersecretion and pancreatic inhibition have been anticipated.

Initial development of the DIII–D snowflake divertor control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolemen, Egemen; Vail, P. J.; Makowski, M. A.

Simultaneous control of two proximate magnetic field nulls in the divertor region is demonstrated on DIII–D to enable plasma operations in an advanced magnetic configuration known as the snowflake divertor (SFD). The SFD is characterized by a second-order poloidal field null, created by merging two first-order nulls of the standard divertor configuration. The snowflake configuration has many magnetic properties, such as high poloidal flux expansion, large plasma-wetted area, and additional strike points, that are advantageous for divertor heat flux management in future fusion reactors. However, the magnetic configuration of the SFD is highly-sensitive to changes in currents within the plasmamore » and external coils and therefore requires complex magnetic control. The first real-time snowflake detection and control system on DIII–D has been implemented in order to stabilize the configuration. The control algorithm calculates the position of the two nulls in real-time by locally-expanding the Grad–Shafranov equation in the divertor region. A linear relation between variations in the poloidal field coil currents and changes in the null locations is then analytically derived. This formulation allows for simultaneous control of multiple coils to achieve a desired SFD configuration. It is shown that the control enabled various snowflake configurations on DIII–D in scenarios such as the double-null advanced tokamak. In conclusion, the SFD resulted in a 2.5×reduction in the peak heat flux for many energy confinement times (2–3s) without any adverse effects on core plasma performance.« less

Initial development of the DIII–D snowflake divertor control

DOE PAGES

Kolemen, Egemen; Vail, P. J.; Makowski, M. A.; ...

2018-04-11

Simultaneous control of two proximate magnetic field nulls in the divertor region is demonstrated on DIII–D to enable plasma operations in an advanced magnetic configuration known as the snowflake divertor (SFD). The SFD is characterized by a second-order poloidal field null, created by merging two first-order nulls of the standard divertor configuration. The snowflake configuration has many magnetic properties, such as high poloidal flux expansion, large plasma-wetted area, and additional strike points, that are advantageous for divertor heat flux management in future fusion reactors. However, the magnetic configuration of the SFD is highly-sensitive to changes in currents within the plasmamore » and external coils and therefore requires complex magnetic control. The first real-time snowflake detection and control system on DIII–D has been implemented in order to stabilize the configuration. The control algorithm calculates the position of the two nulls in real-time by locally-expanding the Grad–Shafranov equation in the divertor region. A linear relation between variations in the poloidal field coil currents and changes in the null locations is then analytically derived. This formulation allows for simultaneous control of multiple coils to achieve a desired SFD configuration. It is shown that the control enabled various snowflake configurations on DIII–D in scenarios such as the double-null advanced tokamak. In conclusion, the SFD resulted in a 2.5×reduction in the peak heat flux for many energy confinement times (2–3s) without any adverse effects on core plasma performance.« less

Mutations associated with base excision repair deficiency and methylation-induced genotoxic stress

PubMed Central

Sobol, Robert W.; Watson, David E.; Nakamura, Jun; Yakes, F. Michael; Hou, Esther; Horton, Julie K.; Ladapo, Joseph; Van Houten, Bennett; Swenberg, James A.; Tindall, Kenneth R.; Samson, Leona D.; Wilson, Samuel H.

2002-01-01

The long-term effect of exposure to DNA alkylating agents is entwined with the cell's genetic capacity for DNA repair and appropriate DNA damage responses. A unique combination of environmental exposure and deficiency in these responses can lead to genomic instability; this “gene–environment interaction” paradigm is a theme for research on chronic disease etiology. In the present study, we used mouse embryonic fibroblasts with a gene deletion in the base excision repair (BER) enzymes DNA β-polymerase (β-pol) and alkyladenine DNA glycosylase (AAG), along with exposure to methyl methanesulfonate (MMS) to study mutagenesis as a function of a particular gene–environment interaction. The β-pol null cells, defective in BER, exhibit a modest increase in spontaneous mutagenesis compared with wild-type cells. MMS exposure increases mutant frequency in β-pol null cells, but not in isogenic wild-type cells; UV light exposure or N-methyl-N′-nitro-N-nitrosoguanidine exposure increases mutant frequency similarly in both cell lines. The MMS-induced increase in mutant frequency in β-pol null cells appears to be caused by DNA lesions that are AAG substrates, because overexpression of AAG in β-pol null cells eliminates the effect. In contrast, β-pol/AAG double null cells are slightly more mutable than the β-pol null cells after MMS exposure. These results illustrate that BER plays a role in protecting mouse embryonic fibroblast cells against methylation-induced mutations and characterize the effect of a particular combination of BER gene defect and environmental exposure. PMID:11983862

Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks

PubMed Central

Stante, Maria; Minopoli, Giuseppina; Passaro, Fabiana; Raia, Maddalena; Vecchio, Luigi Del; Russo, Tommaso

2009-01-01

Fe65 is a binding partner of the Alzheimer's β-amyloid precursor protein APP. The possible involvement of this protein in the cellular response to DNA damage was suggested by the observation that Fe65 null mice are more sensitive to genotoxic stress than WT counterpart. Fe65 associated with chromatin under basal conditions and its involvement in DNA damage repair requires this association. A known partner of Fe65 is the histone acetyltransferase Tip60. Considering the crucial role of Tip60 in DNA repair, we explored the hypothesis that the phenotype of Fe65 null cells depended on its interaction with Tip60. We demonstrated that Fe65 knockdown impaired recruitment of Tip60-TRRAP complex to DNA double strand breaks and decreased histone H4 acetylation. Accordingly, the efficiency of DNA repair was decreased upon Fe65 suppression. To explore whether APP has a role in this mechanism, we analyzed a Fe65 mutant unable to bind to APP. This mutant failed to rescue the phenotypes of Fe65 null cells; furthermore, APP/APLP2 suppression results in the impairment of recruitment of Tip60-TRRAP complex to DNA double strand breaks, decreased histone H4 acetylation and repair efficiency. On these bases, we propose that Fe65 and its interaction with APP play an important role in the response to DNA damage by assisting the recruitment of Tip60-TRRAP to DNA damage sites. PMID:19282473

Doubling down on naturalness with a supersymmetric twin Higgs

NASA Astrophysics Data System (ADS)

Craig, Nathaniel; Howe, Kiel

2014-03-01

We show that naturalness of the weak scale can be comfortably reconciled with both LHC null results and observed Higgs properties provided the double protection of supersymmetry and the twin Higgs mechanism. This double protection radically alters conventional signs of naturalness at the LHC while respecting gauge coupling unification and precision electroweak limits. We find the measured Higgs mass, couplings, and percent-level naturalness of the weak scale are compatible with stops at ~ 3.5 TeV and higgsinos at ~ 1 TeV. The primary signs of naturalness in this scenario include modifications of Higgs couplings, a modest invisible Higgs width, resonant Higgs pair production, and an invisibly-decaying heavy Higgs.

Influence of injection speed on the effectiveness of incisive/mental nerve block: a randomized, controlled, double-blind study in adult volunteers.

PubMed

Whitworth, John Martin; Kanaa, Mohammad Dib; Corbett, Ian Porter; Meechan, John Gerald

2007-10-01

This randomized, double-blind trial tested the null hypothesis that speed of deposition has no influence on the injection discomfort, efficacy, distribution, and duration of pulp anesthesia after incisive/mental nerve block in adult volunteers. Thirty-eight subjects received incisive/mental nerve blocks of 2.0 mL lidocaine with 1:80,000 epinephrine slowly over 60 seconds or rapidly over 15 seconds at least 1 week apart. Pulp anesthesia was assessed electronically to 45 minutes after injection. Injection discomfort was self-recorded on visual analogue scales. Overall, 48.7% of volunteers developed pulp anesthesia in first molars, 81.8% in bicuspids, and 38.5% in lateral incisors. The mean duration of pulp anesthesia was 19.1 minutes for first molars, 28.5 minutes for bicuspids, and 19.0 minutes for lateral incisors. Speed of injection had no significant influence on anesthetic success or duration of anesthesia for individual teeth. Slow injection was significantly more comfortable than rapid injection (P < .001). The null hypothesis was supported, although slow injection was more comfortable.

Aeroelastic instability stoppers for wind tunnel models

NASA Technical Reports Server (NTRS)

Doggett, R. V., Jr.; Ricketts, R. H. (Inventor)

1981-01-01

A mechanism for diverting the flow in a wind tunnel from the wing of a tested model is described. The wing is mounted on the wall of a tunnel. A diverter plate is pivotally mounted on the tunnel wall ahead of the model. An actuator fixed to the tunnel is pivotably connected to the diverter plate, by plunger. When the model is about to become unstable during the test the actuator moves the diverter plate from the tunnel wall to divert maintaining stable model conditions. The diverter plate is then retracted to enable normal flow.

A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium.

PubMed

Lee, S; Parent, C A; Insall, R; Firtel, R A

1999-09-01

We have identified a novel Ras-interacting protein from Dictyostelium, RIP3, whose function is required for both chemotaxis and the synthesis and relay of the cyclic AMP (cAMP) chemoattractant signal. rip3 null cells are unable to aggregate and lack receptor activation of adenylyl cyclase but are able, in response to cAMP, to induce aggregation-stage, postaggregative, and cell-type-specific gene expression in suspension culture. In addition, rip3 null cells are unable to properly polarize in a cAMP gradient and chemotaxis is highly impaired. We demonstrate that cAMP stimulation of guanylyl cyclase, which is required for chemotaxis, is reduced approximately 60% in rip3 null cells. This reduced activation of guanylyl cyclase may account, in part, for the defect in chemotaxis. When cells are pulsed with cAMP for 5 h to mimic the endogenous cAMP oscillations that occur in wild-type strains, the cells will form aggregates, most of which, however, arrest at the mound stage. Unlike the response seen in wild-type strains, the rip3 null cell aggregates that form under these experimental conditions are very small, which is probably due to the rip3 null cell chemotaxis defect. Many of the phenotypes of the rip3 null cell, including the inability to activate adenylyl cyclase in response to cAMP and defects in chemotaxis, are very similar to those of strains carrying a disruption of the gene encoding the putative Ras exchange factor AleA. We demonstrate that aleA null cells also exhibit a defect in cAMP-mediated activation of guanylyl cyclase similar to that of rip3 null cells. A double-knockout mutant (rip3/aleA null cells) exhibits a further reduction in receptor activation of guanylyl cyclase, and these cells display almost no cell polarization or movement in cAMP gradients. As RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement, we propose that RIP3 and AleA are components of a Ras-regulated pathway involved in integrating chemotaxis and signal relay pathways that are essential for aggregation.

Is there an association between flow diverter fish mouthing and delayed-type hypersensitivity to metals?-a case-control study.

PubMed

Kocer, Naci; Mondel, Prabath Kumar; Yamac, Elif; Kavak, Ayse; Kizilkilic, Osman; Islak, Civan

2017-11-01

Flow diverters are increasingly used in the treatment of complex and giant intracranial aneurysms. However, they are associated with complications like late aneurysmal rupture. Additionally, flow diverters show focal structural decrease in luminal diameter without any intimal hyperplasia. This resembles a "fish mouth" when viewed en face. In this pilot study, we tested the hypothesis of a possible association between flow diverter fish-mouthing and delayed-type hypersensitivity to its metal constituents. We retrospectively reviewed patient records from our center between May 2010 and November 2015. A total of nine patients had flow diverter fish mouthing. A control group of 25 patients was selected. All study participants underwent prospective patch test to detect hypersensitivity to flow diverter metal constituents. Analysis was performed using logistic regression analysis and Wilcoxon sign rank sum test. Univariate and multivariate analyses were performed to test variables to predict flow diverter fish mouthing. The association between flow diverter fish mouthing and positive patch test was not statistically significant. In multivariate analysis, history of allergy and maximum aneurysm size category was associated with flow diverter fish mouthing. This was further confirmed on Wilcoxon sign rank sum test. The study showed statistically significant association between flow diverter fish mouthing and history of contact allergy and a small aneurysmal size. Further large-scale studies are needed to detect a statistically significant association between flow diverter fish mouthing and patch test. We recommend early and more frequent follow-up imaging in patients with contact allergy to detect flow diverter fish mouthing and its subsequent evolution.

Renal hemodynamics: the influence of the renal artery ostium flow diverter

NASA Astrophysics Data System (ADS)

Rossmann, Jenn Stroud; Albert, Scott; Balaban, Robert

2013-11-01

The recently identified renal artery ostium flow diverter may preferentially direct blood flow to the renal arteries, and may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution: depending on the diverter's position, the flow to the renal arteries may be increased or reduced. The results of simulations also show the diverter's effect on the Wall Shear Stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis.

Drosophila fragile X mental retardation protein and metabotropic glutamate receptor A convergently regulate the synaptic ratio of ionotropic glutamate receptor subclasses.

PubMed

Pan, Luyuan; Broadie, Kendal S

2007-11-07

A current hypothesis proposes that fragile X mental retardation protein (FMRP), an RNA-binding translational regulator, acts downstream of glutamatergic transmission, via metabotropic glutamate receptor (mGluR) G(q)-dependent signaling, to modulate protein synthesis critical for trafficking ionotropic glutamate receptors (iGluRs) at synapses. However, direct evidence linking FMRP and mGluR function with iGluR synaptic expression is limited. In this study, we use the Drosophila fragile X model to test this hypothesis at the well characterized glutamatergic neuromuscular junction (NMJ). Two iGluR classes reside at this synapse, each containing common GluRIIC (III), IID and IIE subunits, and variable GluRIIA (A-class) or GluRIIB (B-class) subunits. In Drosophila fragile X mental retardation 1 (dfmr1) null mutants, A-class GluRs accumulate and B-class GluRs are lost, whereas total GluR levels do not change, resulting in a striking change in GluR subclass ratio at individual synapses. The sole Drosophila mGluR, DmGluRA, is also expressed at the NMJ. In dmGluRA null mutants, both iGluR classes increase, resulting in an increase in total synaptic GluR content at individual synapses. Targeted postsynaptic dmGluRA overexpression causes the exact opposite GluR phenotype to the dfmr1 null, confirming postsynaptic GluR subtype-specific regulation. In dfmr1; dmGluRA double null mutants, there is an additive increase in A-class GluRs, and a similar additive impact on B-class GluRs, toward normal levels in the double mutants. These results show that both dFMRP and DmGluRA differentially regulate the abundance of different GluR subclasses in a convergent mechanism within individual postsynaptic domains.

Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function.

PubMed

Yan, C; Wang, P; DeMayo, J; DeMayo, F J; Elvin, J A; Carino, C; Prasad, S V; Skinner, S S; Dunbar, B S; Dube, J L; Celeste, A J; Matzuk, M M

2001-06-01

Knockout mouse technology has been used over the last decade to define the essential roles of ovarian-expressed genes and uncover genetic interactions. In particular, we have used this technology to study the function of multiple members of the transforming growth factor-beta superfamily including inhibins, activins, and growth differentiation factor 9 (GDF-9 or Gdf9). Knockout mice lacking GDF-9 are infertile due to a block in folliculogenesis at the primary follicle stage. In addition, recombinant GDF-9 regulates multiple cumulus granulosa cell functions in the periovulatory period including hyaluronic acid synthesis and cumulus expansion. We have also cloned an oocyte-specific homolog of GDF-9 from mice and humans, which is termed bone morphogenetic protein 15 (BMP-15 or Bmp15). To define the function of BMP-15 in mice, we generated embryonic stem cells and knockout mice, which have a null mutation in this X-linked gene. Male chimeric and Bmp15 null mice are normal and fertile. In contrast to Bmp15 null males and Gdf9 knockout females, Bmp15 null females (Bmp15(-/-)) are subfertile and usually have minimal ovarian histopathological defects, but demonstrate decreased ovulation and fertilization rates. To further decipher possible direct or indirect genetic interactions between GDF-9 and BMP-15, we have generated double mutant mice lacking one or both alleles of these related homologs. Double homozygote females (Bmp15(-/-)Gdf9(-/-)) display oocyte loss and cysts and resemble Gdf9(-/-) mutants. In contrast, Bmp15(-/-)Gdf9(+/-) female mice have more severe fertility defects than Bmp15(-/-) females, which appear to be due to abnormalities in ovarian folliculogenesis, cumulus cell physiology, and fertilization. Thus, the dosage of intact Bmp15 and Gdf9 alleles directly influences the destiny of the oocyte during folliculogenesis and in the periovulatory period. These studies have important implications for human fertility control and the maintenance of fertility and normal ovarian physiology.

Numerical study on AC loss reduction of stacked HTS tapes by optimal design of flux diverter

NASA Astrophysics Data System (ADS)

Liu, Guole; Zhang, Guomin; Jing, Liwei; Yu, Hui

2017-12-01

High temperature superconducting (HTS) coils are key parts of many AC applications, such as generators, superconducting magnetic energy storage and transformers. AC loss reduction in HTS coils is essential for the commercialization of these HTS devices. Magnetic material is generally used as the flux diverter in an effort to reduce the AC loss in HTS coils. To achieve the greatest reduction in the AC loss of the coils, the flux diverter should be made of a material with low loss and high saturated magnetic density, and the optimization of the geometric size and location of the flux diverter is required. In this paper, we chose Ni-alloy as the flux diverter, which can be processed into a specific shape and size. The influence of the shape and location of the flux diverter on the AC loss characteristics of stacked (RE)BCO tapes is investigated by use of a finite element method. Taking both the AC loss of the (RE)BCO coils and the ferromagnetic loss of the flux diverter into account, the optimal geometry of the flux diverter is obtained. It is found that when the applied current is at half the value of the critical current, the total loss of the HTS stack with the optimal flux diverter is only 18% of the original loss of the HTS stack without the flux diverter. Besides, the effect of the flux diverter on the critical current of the (RE)BCO stack is investigated.

Design of snowflake-diverted equilibria of CFETR

NASA Astrophysics Data System (ADS)

Hang, LI; Xiang, GAO; Guoqiang, LI; Zhengping, LUO; Damao, YAO; Yong, GUO

2018-03-01

The Chinese Fusion Engineering Test Reactor (CFETR) represents the next generation of full superconducting fusion reactors in China. Recently, CFETR was redesigned with a larger size and will be operated in two phases. To reduce the heat flux on the target plate, a snowflake (SF) divertor configuration is proposed. In this paper we show that by adding two dedicated poloidal field (PF) coils, the SF configuration can be achieved in both phases. The equilibria were calculated by TEQ code for a range of self-inductances l i3. The coil currents were calculated at some fiducial points in the flattop phase. The results indicate that the PF coil system has the ability to maintain a long flattop phase in 7.5 and 10 MA inductive scenarios for the single null divertor (SND) and SF divertor configurations. The properties of the SF configuration were also analyzed. The connection length and flux expansion of the SF divertor were both increased significantly over the SND.

Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

PubMed Central

POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

2015-01-01

Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

Yeast Genes Controlling Responses to Topogenic Signals in a Model Transmembrane Protein

PubMed Central

Tipper, Donald J.; Harley, Carol A

2002-01-01

Yeast protein insertion orientation (PIO) mutants were isolated by selecting for growth on sucrose in cells in which the only source of invertase is a C-terminal fusion to a transmembrane protein. Only the fraction with an exocellular C terminus can be processed to secreted invertase and this fraction is constrained to 2–3% by a strong charge difference signal. Identified pio mutants increased this to 9–12%. PIO1 is SPF1, encoding a P-type ATPase located in the endoplasmic reticulum (ER) or Golgi. spf1-null mutants are modestly sensitive to EGTA. Sensitivity is considerably greater in an spf1 pmr1 double mutant, although PIO is not further disturbed. Pmr1p is the Golgi Ca2+ ATPase and Spf1p may be the equivalent ER pump. PIO2 is STE24, a metalloprotease anchored in the ER membrane. Like Spf1p, Ste24p is expressed in all yeast cell types and belongs to a highly conserved protein family. The effects of ste24- and spf1-null mutations on invertase secretion are additive, cell generation time is increased 60%, and cells become sensitive to cold and to heat shock. Ste24p and Rce1p cleave the C-AAX bond of farnesylated CAAX box proteins. The closest paralog of SPF1 is YOR291w. Neither rce1-null nor yor291w-null mutations affected PIO or the phenotype of spf1- or ste24-null mutants. Mutations in PIO3 (unidentified) cause a weaker Pio phenotype, enhanced by a null mutation in BMH1, one of two yeast 14-3-3 proteins. PMID:11950929

Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer

PubMed Central

Yuan, Jian-Min; Chan, Kenneth K.; Coetzee, Gerhard A.; Castelao, J.Esteban; Watson, Mary A.; Bell, Douglas A.; Wang, Renwei; Yu, Mimi C.

2008-01-01

Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual’s susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case–control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19–48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19–1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12–1.81) and 1.71 (1.25–2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12–3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype. PMID:18544563

30 CFR 250.430 - When must I install a diverter system?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 250.430 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter... before you drill a conductor or surface hole. The diverter system consists of a diverter sealing element...

30 CFR 250.433 - What are the diverter actuation and testing requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.433 What are the diverter actuation and.... (a) For drilling operations with a surface wellhead configuration, you must actuate the diverter...

30 CFR 250.431 - What are the diverter design and installation requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.431 What are the diverter... wellhead configurations and at least 12 inches for floating drilling operations; (b) Use dual diverter...

30 CFR 250.433 - What are the diverter actuation and testing requirements?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.433 What are the diverter actuation and.... (a) For drilling operations with a surface wellhead configuration, you must actuate the diverter...

30 CFR 250.433 - What are the diverter actuation and testing requirements?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.433 What are the diverter actuation and.... (a) For drilling operations with a surface wellhead configuration, you must actuate the diverter...

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% andmore » 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.« less

30 CFR 250.431 - What are the diverter design and installation requirements?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.431 What are the diverter design and... configurations and at least 12 inches for floating drilling operations; (b) Use dual diverter lines arranged to...

30 CFR 250.431 - What are the diverter design and installation requirements?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.431 What are the diverter design and... configurations and at least 12 inches for floating drilling operations; (b) Use dual diverter lines arranged to...

30 CFR 250.431 - What are the diverter design and installation requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.431 What are the diverter design and... configurations and at least 12 inches for floating drilling operations; (b) Use dual diverter lines arranged to...

Smart-Divert Powered Descent Guidance to Avoid the Backshell Landing Dispersion Ellipse

NASA Technical Reports Server (NTRS)

Carson, John M.; Acikmese, Behcet

2013-01-01

A smart-divert capability has been added into the Powered Descent Guidance (PDG) software originally developed for Mars pinpoint and precision landing. The smart-divert algorithm accounts for the landing dispersions of the entry backshell, which separates from the lander vehicle at the end of the parachute descent phase and prior to powered descent. The smart-divert PDG algorithm utilizes the onboard fuel and vehicle thrust vectoring to mitigate landing error in an intelligent way: ensuring that the lander touches down with minimum- fuel usage at the minimum distance from the desired landing location that also avoids impact by the descending backshell. The smart-divert PDG software implements a computationally efficient, convex formulation of the powered-descent guidance problem to provide pinpoint or precision-landing guidance solutions that are fuel-optimal and satisfy physical thrust bound and pointing constraints, as well as position and speed constraints. The initial smart-divert implementation enforced a lateral-divert corridor parallel to the ground velocity vector; this was based on guidance requirements for MSL (Mars Science Laboratory) landings. This initial method was overly conservative since the divert corridor was infinite in the down-range direction despite the backshell landing inside a calculable dispersion ellipse. Basing the divert constraint instead on a local tangent to the backshell dispersion ellipse in the direction of the desired landing site provides a far less conservative constraint. The resulting enhanced smart-divert PDG algorithm avoids impact with the descending backshell and has reduced conservatism.

Drag measurements of an axisymmetric nacelle mounted on a flat plate at supersonic speeds

NASA Technical Reports Server (NTRS)

Flamm, Jeffrey D.; Wilcox, Floyd J., Jr.

1995-01-01

An experimental investigation was conducted to determine the effect of diverter wedge half-angle and nacelle lip height on the drag characteristics of an assembly consisting of a nacelle fore cowl from a typical high-speed civil transport (HSCT) and a diverter mounted on a flat plate. Data were obtained for diverter wedge half-angles of 4.0 deg, 6.0 deg, and 8.0 deg and ratios of the nacelle lip height above a flat plate to the boundary-layer thickness (h(sub n)/delta) of approximately 0.87 to 2.45. Limited drag data were also obtained on a complete nacelle/diverter configuration that included fore and aft cowls. Although the nacelle/diverter drag data were not corrected for base pressures or internal flow drag, the data are useful for comparing the relative drag of the configuration tested. The tests were conducted in the Langley Unitary Plan Wind Tunnel at Mach numbers of 1.50, 1.80, 2.10, and 2.40 and Reynolds numbers ranging from 2.00 x 10(exp 6) to 5.00 x 10(exp 6) per foot. The results of this investigation showed that the nacelle/diverter drag essentially increased linearly with increasing h(sub n)/delta except near 1.0 where the data showed a nonlinear behavior. This nonlinear behavior was probably caused by the interaction of the shock waves from the nacelle/diverter configuration with the flat-plate boundary layer. At the lowest h(sub n)/delta tested, the diverter wedge half-angle had virtually no effect on the nacelle/diverter drag. However, as h(sub n)/delta increased, the nacelle/diverter drag increased as diverter wedge half-angle increased.

Confinement & Stability in MAST

NASA Astrophysics Data System (ADS)

Akers, Rob

2001-10-01

Transition to H-mode has been achieved in the MAST spherical tokamak (ST) for both ohmically and neutral beam heated plasmas (P_NBI ~ 0.5-1.5MW), resulting in double-null diverted discharges containing both regular and irregular edge localised modes (ELMs). The observed L-H power threshold is ~10 times higher than predicted by established empirical scalings. L-H transition in MAST is accompanied by a sharp increase in edge density gradient, the efficient conversion of internal electron Bernstein waves into free space waves, the onset and saturation of edge poloidal rotation and a marked decrease in turbulence. During ELM free periods, a reduction in outboard power deposition width is observed using a Langmuir probe array. A novel divertor structure has been installed to counter the resulting increase in target heat-flux by applying a toroidally varying potential to the divertor plasma, theory suggesting that convective broadening of the scrape off layer will take place. Global confinement in H-mode is found to routinely exceed the international IPB(y,2) scaling, even for discharges approaching the Greenwald density. In an attempt to further extend the density range (densities in excess of Greenwald having been achieved for plasma currents up to 0.8MA) a multi-pellet injector has been installed at the low-field-side. In addition, high field side fuelling can be supplied via a gas-feed located at the centre-column mid-plane, this technique having been found to significantly enhance H-mode accessibility and quality. A range of stability issues will be discussed, including vertical displacement events, the rich variety of high frequency MHD seen in MAST and the physics of the Neoclassical Tearing Mode. This work was funded by the UK Department of Trade and Industry and by EURATOM. The NBI equipment is on loan from ORNL and the pellet injector was provided by FOM.

30 CFR 250.432 - How do I obtain a departure to diverter design and installation requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.432 How do I obtain a departure to diverter... diverter line for floating drilling operations on a dynamically positioned drillship Maintain an...

Symptomatic Post Endarterectomy Common Carotid Artery Pseudoaneurysm Treated with Combination of Flow Diverter Implantation and Carotid Stenting

PubMed Central

Imbarrato, Greg; Gordhan, Ajeet

2018-01-01

A 74-year-old male developed cervical carotid artery psuedoaneurysm 8 months after carotid endarterectomy. The patient was successfully managed with dual implantation of flow-diverter and conventional carotid stent. Flow-diverter was placed across the neck of pseudoaneurysm to provide flow diversion while carotid stent was implanted within the lumen of the expanded flow-diverter to approximate and hold the flow diverter proximal and distal to the pseudoaneurysm. Follow-up ultrasonography revealed complete resolution of the pseudoaneurysm. PMID:29535899

Examining Innovative Divertor and Main Chamber Options for a National Divertor Test Tokamak

NASA Astrophysics Data System (ADS)

Labombard, B.; Umansky, M.; Brunner, D.; Kuang, A. Q.; Marmar, E.; Wallace, G.; Whyte, D.; Wukitch, S.

2016-10-01

The US fusion community has identified a compelling need for a National Divertor Test Tokamak. The 2015 Community Planning Workshop on PMI called for a national working group to develop options. Important elements of a NDTT, adopted from the ADX concept, include the ability to explore long-leg divertor `solutions for power exhaust and particle control' (Priority Research Direction B) and to employ inside-launch RF actuators combined with double-null topologies as `plasma solution for main chamber wall components, including tools for controllable sustained operation' (PRD-C). Here we examine new information on these ideas. The projected performance of super-X and X-point target long-leg divertors is looking very promising; a stable fully-detached divertor condition handling an order-of-magnitude increase in power handling over conventional divertors may be possible. New experiments on Alcator C-Mod are addressing issues of high-field side versus low-field side heat flux sharing in double-null topologies and the screening of impurities that might originate from RF actuators placed in the high-field side - both with favorable results. Supported by USDoE Awards DE-FC02-99ER54512 and DE-AC52-07NA27344.

High Performance Double-null Plasma Operation Under Radiating Divertor Conditions

NASA Astrophysics Data System (ADS)

Petrie, T. W.; Osborne, T.; Leonard, A. W.; Luce, T. C.; Petty, C. C.; Fenstermacher, M. E.; Lasnier, C. J.; Turco, F.; Watkins, J. G.

2017-10-01

We report on heat flux reduction experiments in which deuterium/neon- or deuterium/argon-based radiating mantle/divertor approaches were applied to high performance double-null (DN) plasmas (H98 1.4-1.7,βN 4 , q 95 6) with a combined neutral beam and ECH power input PIN 15 MW. When the radial location of the ECH deposition is close to the magnetic axis (e.g., ρ <=0.20), the radial profiles of both injected and intrinsic impurities are flat to somewhat hollow. For deposition farther out (e.g., ρ=0.45), the impurity profiles are highly peaked on axis, which would make high performance DN operation with impurity injection more problematical. Comparison of neon with argon `seeding' with respect to core dilution, energy confinement, and heat flux reduction under these conditions favors argon. Conditions that lead to an improved τE as predicted previously from ELITE code analysis, i.e., very high PIN, proximity to magnetic balance, and higher q95, are largely consistent with this data. Work was supported by the US DOE under DE-FC02-04ER54698, DE-AC52-07NA27344, DE-FG02-04ER54761, and DE-AC04-94AL85000.

A Novel Ras-interacting Protein Required for Chemotaxis and Cyclic Adenosine Monophosphate Signal Relay in Dictyostelium

PubMed Central

Lee, Susan; Parent, Carole A.; Insall, Robert; Firtel, Richard A.

1999-01-01

We have identified a novel Ras-interacting protein from Dictyostelium, RIP3, whose function is required for both chemotaxis and the synthesis and relay of the cyclic AMP (cAMP) chemoattractant signal. rip3 null cells are unable to aggregate and lack receptor activation of adenylyl cyclase but are able, in response to cAMP, to induce aggregation-stage, postaggregative, and cell-type-specific gene expression in suspension culture. In addition, rip3 null cells are unable to properly polarize in a cAMP gradient and chemotaxis is highly impaired. We demonstrate that cAMP stimulation of guanylyl cyclase, which is required for chemotaxis, is reduced ∼60% in rip3 null cells. This reduced activation of guanylyl cyclase may account, in part, for the defect in chemotaxis. When cells are pulsed with cAMP for 5 h to mimic the endogenous cAMP oscillations that occur in wild-type strains, the cells will form aggregates, most of which, however, arrest at the mound stage. Unlike the response seen in wild-type strains, the rip3 null cell aggregates that form under these experimental conditions are very small, which is probably due to the rip3 null cell chemotaxis defect. Many of the phenotypes of the rip3 null cell, including the inability to activate adenylyl cyclase in response to cAMP and defects in chemotaxis, are very similar to those of strains carrying a disruption of the gene encoding the putative Ras exchange factor AleA. We demonstrate that aleA null cells also exhibit a defect in cAMP-mediated activation of guanylyl cyclase similar to that of rip3 null cells. A double-knockout mutant (rip3/aleA null cells) exhibits a further reduction in receptor activation of guanylyl cyclase, and these cells display almost no cell polarization or movement in cAMP gradients. As RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement, we propose that RIP3 and AleA are components of a Ras-regulated pathway involved in integrating chemotaxis and signal relay pathways that are essential for aggregation. PMID:10473630

Inactivation of Mre11 does not affect VSG gene duplication mediated by homologous recombination in Trypanosoma brucei.

PubMed

Robinson, Nicholas P; McCulloch, Richard; Conway, Colin; Browitt, Alison; Barry, J David

2002-07-19

We demonstrate, by gene deletion analysis, that Mre11 has a critical role in maintaining genomic integrity in Trypanosoma brucei. mre11(-/-) null mutant strains exhibited retarded growth but no delay or disruption of cell cycle progression. They showed also a weak hyporecombination phenotype and the accumulation of gross chromosomal rearrangements, which did not involve sequence translocation, telomere loss, or formation of new telomeres. The trypanosome mre11(-/-) strains were hypersensitive to phleomycin, a mutagen causing DNA double strand breaks (DSBs) but, in contrast to mre11(-/-) null mutants in other organisms and T. brucei rad51(-/-) null mutants, displayed no hypersensitivity to methyl methanesulfonate, which causes point mutations and DSBs. Mre11 therefore is important for the repair of chromosomal damage and DSBs in trypanosomes, although in this organism the intersection of repair pathways appears to differ from that in other organisms. Mre11 inactivation appears not to affect VSG gene switching during antigenic variation of a laboratory strain, which is perhaps surprising given the importance of homologous recombination during this process.

Trash Diverter Orientation Angle Optimization at Run-Off River Type Hydro-power Plant using CFD

NASA Astrophysics Data System (ADS)

Munisamy, Kannan M.; Kamal, Ahmad; Shuaib, Norshah Hafeez; Yusoff, Mohd. Zamri; Hasini, Hasril; Rashid, Azri Zainol; Thangaraju, Savithry K.; Hamid, Hazha

2010-06-01

Tenom Pangi Hydro Power Station in Tenom, Sabah is suffering from poor river quality with a lot of suspended trashes. This problem necessitates the need for a trash diverter to divert the trash away from the intake region. Previously, a trash diverter (called Trash Diverter I) was installed at the site but managed to survived for a short period of time due to an impact with huge log as a results of a heavy flood. In the current project, a second trash diverter structure is designed (called Trash Diverter II) with improved features compared to Trash Diverter I. The Computational Fluid Dynamics (CFD) analysis is done to evaluate the river flow interaction onto the trash diverter from the fluid flow point of view, Computational Fluids Dynamics is a numerical approach to solve fluid flow profile for different inlet conditions. In this work, the river geometry is modeled using commercial CFD code, FLUENT®. The computational model consists of Reynolds Averaged Navier-Stokes (RANS) equations coupled with other related models using the properties of the fluids under investigation. The model is validated with site-measurements done at Tenom Pangi Hydro Power Station. Different operating condition of river flow rate and weir opening is also considered. The optimum angle is determined in this simulation to further use the data for 3D simulation and structural analysis.

Accelerated Activation of SOCE Current in Myotubes from Two Mouse Models of Anesthetic- and Heat-Induced Sudden Death

PubMed Central

Yarotskyy, Viktor; Protasi, Feliciano; Dirksen, Robert T.

2013-01-01

Store-operated calcium entry (SOCE) channels play an important role in Ca2+ signaling. Recently, excessive SOCE was proposed to play a central role in the pathogenesis of malignant hyperthermia (MH), a pharmacogenic disorder of skeletal muscle. We tested this hypothesis by characterizing SOCE current (ISkCRAC) magnitude, voltage dependence, and rate of activation in myotubes derived from two mouse models of anesthetic- and heat-induced sudden death: 1) type 1 ryanodine receptor (RyR1) knock-in mice (Y524S/+) and 2) calsequestrin 1 and 2 double knock-out (dCasq-null) mice. ISkCRAC voltage dependence and magnitude at -80 mV were not significantly different in myotubes derived from wild type (WT), Y524S/+ and dCasq-null mice. However, the rate of ISkCRAC activation upon repetitive depolarization was significantly faster at room temperature in myotubes from Y524S/+ and dCasq-null mice. In addition, the maximum rate of ISkCRAC activation in dCasq-null myotubes was also faster than WT at more physiological temperatures (35-37°C). Azumolene (50 µM), a more water-soluble analog of dantrolene that is used to reverse MH crises, failed to alter ISkCRAC density or rate of activation. Together, these results indicate that while an increased rate of ISkCRAC activation is a common characteristic of myotubes derived from Y524S/+ and dCasq-null mice and that the protective effects of azumolene are not due to a direct inhibition of SOCE channels. PMID:24143248

Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes

PubMed Central

Schaetzlein, Sonja; Chahwan, Richard; Avdievich, Elena; Roa, Sergio; Wei, Kaichun; Eoff, Robert L.; Sellers, Rani S.; Clark, Alan B.; Kunkel, Thomas A.; Scharff, Matthew D.; Edelmann, Winfried

2013-01-01

Mammalian Exonuclease 1 (EXO1) is an evolutionarily conserved, multifunctional exonuclease involved in DNA damage repair, replication, immunoglobulin diversity, meiosis, and telomere maintenance. It has been assumed that EXO1 participates in these processes primarily through its exonuclease activity, but recent studies also suggest that EXO1 has a structural function in the assembly of higher-order protein complexes. To dissect the enzymatic and nonenzymatic roles of EXO1 in the different biological processes in vivo, we generated an EXO1-E109K knockin (Exo1EK) mouse expressing a stable exonuclease-deficient protein and, for comparison, a fully EXO1-deficient (Exo1null) mouse. In contrast to Exo1null/null mice, Exo1EK/EK mice retained mismatch repair activity and displayed normal class switch recombination and meiosis. However, both Exo1-mutant lines showed defects in DNA damage response including DNA double-strand break repair (DSBR) through DNA end resection, chromosomal stability, and tumor suppression, indicating that the enzymatic function is required for those processes. On a transformation-related protein 53 (Trp53)-null background, the DSBR defect caused by the E109K mutation altered the tumor spectrum but did not affect the overall survival as compared with p53-Exo1null mice, whose defects in both DSBR and mismatch repair also compromised survival. The separation of these functions demonstrates the differential requirement for the structural function and nuclease activity of mammalian EXO1 in distinct DNA repair processes and tumorigenesis in vivo. PMID:23754438

Flow Diverters for Intracranial Aneurysms

PubMed Central

Alderazi, Yazan J.; Kass-Hout, Tareq; Prestigiacomo, Charles J.; Gandhi, Chirag D.

2014-01-01

Flow diverters (pipeline embolization device, Silk flow diverter, and Surpass flow diverter) have been developed to treat intracranial aneurysms. These endovascular devices are placed within the parent artery rather than the aneurysm sac. They take advantage of altering hemodynamics at the aneurysm/parent vessel interface, resulting in gradual thrombosis of the aneurysm occurring over time. Subsequent inflammatory response, healing, and endothelial growth shrink the aneurysm and reconstruct the parent artery lumen while preserving perforators and side branches in most cases. Flow diverters have already allowed treatment of previously untreatable wide neck and giant aneurysms. There are risks with flow diverters including in-stent thrombosis, perianeurysmal edema, distant and delayed hemorrhages, and perforator occlusions. Comparative efficacy and safety against other therapies are being studied in ongoing trials. Antiplatelet therapy is mandatory with flow diverters, which has highlighted the need for better evidence for monitoring and tailoring antiplatelet therapy. In this paper we review the devices, their uses, associated complications, evidence base, and ongoing studies. PMID:24967131

Flow diverter value and flow diversion method

NASA Technical Reports Server (NTRS)

Arline, S. B.; Carlson, R. L. (Inventor)

1964-01-01

A flow diverter valve applicable to any fluid flow system requiring rapid bleed or bypass is disclosed. Examples of application of the flow diverter valve to a liquid rocket and a turbojet aircraft engine are given. Features of the valve include: (1) an independent fluid source is used to activate the flow diverter valve toward its closed position during its initial stage of travel; (2) the flow diverter port area and size is unlimited and the valve travel is unlimited; and (3) the valve housing is fabricated such that the valve can be a one step valve, a two step valve, or include as many steps as are found desirable.

Bath and Shower Diverter Notice of Intent

EPA Pesticide Factsheets

An often-overlooked source of wasted water, many bath and shower diverters continuously leak a small amount of water from the tub spout while they are engaged, and water is being diverted from the bathtub to the showerhead.

Using Simulation to Analyze Acoustic Environments

NASA Technical Reports Server (NTRS)

Wood, Eric J.

2016-01-01

One of the main projects that was worked on this semester was creating an acoustic model for the Advanced Space Suit in Comsol Multiphysics. The geometry tools built into the software were used to create an accurate model of the helmet and upper torso of the suit. After running the simulation, plots of the sound pressure level within the suit were produced, as seen below in Figure 1. These plots show significant nulls which should be avoided when placing microphones inside the suit. In the future, this model can be easily adapted to changes in the suit design to determine optimal microphone placements and other acoustic properties. Another major project was creating an acoustic diverter that will potentially be used to route audio into the Space Station's Node 1. The concept of the project was to create geometry to divert sound from a neighboring module, the US Lab, into Node 1. By doing this, no new audio equipment would need to be installed in Node 1. After creating an initial design for the diverter, analysis was performed in Comsol in order to determine how changes in geometry would affect acoustic performance, as shown in Figure 2. These results were used to produce a physical prototype diverter on a 3D printer. With the physical prototype, testing was conducted in an anechoic chamber to determine the true effectiveness of the design, as seen in Figure 3. The results from this testing have been compared to the Comsol simulation results to analyze how closely the Comsol results are to real-world performance. While the Comsol results do not seem to closely resemble the real world performance, this testing has provided valuable insight into how much trust can be placed in the results of Comsol simulations. A final project that was worked on during this tour was the Audio Interface Unit (AIU) design for the Orion program. The AIU is a small device that will be used for as an audio communication device both during launch and on-orbit. The unit will have functions including push-to-talk buttons and volume control. With this project, an existing design was modified based on prior feedback that had been received. With the modified design, I created a 3D printed prototype, shown in Figure 4, which was then used in suited evaluations performed by crew members. The feedback received from those evaluations will be utilized to help create the best possible Orion AIU. As a whole, a number of different interesting engineering projects were worked on over the course of this semester. For many of these projects, acoustic simulations provided valuable insight into how different environments would respond to sound. While work is still underway to verify the results of these simulations, the results are fascinating because of the interesting ways that sound waves interact with the environment. Going forward, it will be interesting to see how closely these results can be matched by real-world test data.

Oceanic Area System Improvement Study (OASIS). Volume IX. Flight Cost Model Description.

DTIC Science & Technology

1981-09-01

FUEL COST T.O.WT LAND.1%T .’n 8 SEA LGW 3105 3947 10.53 346249 24594 839249 493000 ND LK NXhD 6ND HI5 RHB HLI 6IT LVLTM Tj X61’ TEMP 471 -%050 578 2061...4000 101. Divert 60 nj (2 tracks) - 4000 102. Divert 90 ali (3 tracks) - 4000 103. Divert 120 nmi (4 tracks) - 4000 104 . Divert 150 nzi (5 tracks) - 4000

Influence of the renal artery ostium flow diverter on hemodynamics and atherogenesis

PubMed Central

Albert, Scott; Balaban, Robert S.; Neufeld, Edward B.; Rossmann, Jenn Stroud

2014-01-01

The structure and function of the renal artery ostium flow diverter on the caudal side of the renal branch point were previously reported; in this study, we further evaluate the diverter’s possible functions. The protrusion of this structure into the abdominal aorta suggests that the diverter may preferentially direct blood flow to the renal arteries, and that it may also influence flow patterns and recirculation known to be involved in atherogenesis. Three-dimensional computational fluid dynamics (CFD) simulations of steady and pulsatile blood flow are performed to investigate the influence of diverter size and position, and vascular geometry, on the flow patterns and fluid mechanical forces in the neighborhood of the diverter. CFD results show that the flow diverter does affect the blood distribution: depending on the diverter’s position, the flow to the renal arteries may be increased or reduced. Calculated results also demonstrate the diverter’s effect on the Wall Shear Stress (WSS) distribution, and suggest that the diverter contributes to an atherogenic environment in the abdominal aorta, while being atheroprotective in the renal arteries themselves. These results support previous clinical findings, and suggest directions for further clinical study. The results of this work have direct implications in understanding the physiological significance of the diverter, and its potential role in the pathophysiological development of atherosclerosis. PMID:24703300

DIVERT (during incidents vehicles exit to reduce time) : evaluation report

DOT National Transportation Integrated Search

1998-09-01

The goal of DIVERT is to provide management strategies during periods of freeway incidents by routing diverted traffic over city surface arterials in a planned, coordinated manner. Several detailed findings of the evaluation of this project are inclu...

Increased 4-hydroxynonenal protein adducts in male GSTA4–4/PPAR-alpha double knockout mice enhance injury during early stages of alcoholic liver disease

USDA-ARS?s Scientific Manuscript database

To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male wild type 129/SvJ mice, and glutathione S-transferase A4-4 null (GSTA4-/-) mice for 40 d. GSTA4-/- mice were also crossed with peroxisome proliferator-activated ...

Maize opaque5 Encodes Monogalactosyldiacylglycerol Synthase and Specifically Affects Galactolipids Necessary for Amyloplast and Chloroplast Function[C][W][OA

PubMed Central

Myers, Alan M.; James, Martha G.; Lin, Qiaohui; Yi, Gibum; Stinard, Philip S.; Hennen-Bierwagen, Tracie A.; Becraft, Philip W.

2011-01-01

The maize (Zea mays) opaque5 (o5) locus was shown to encode the monogalactosyldiacylglycerol synthase MGD1. Null and point mutations of o5 that affect the vitreous nature of mature endosperm engendered an allelic series of lines with stepwise reductions in gene function. C18:3/C18:2 galactolipid abundance in seedling leaves was reduced proportionally, without significant effects on total galactolipid content. This alteration in polar lipid composition disrupted the organization of thylakoid membranes into granal stacks. Total galactolipid abundance in endosperm was strongly reduced in o5- mutants, causing developmental defects and changes in starch production such that the normal simple granules were replaced with compound granules separated by amyloplast membrane. Complete loss of MGD1 function in a null mutant caused kernel lethality owing to failure in both endosperm and embryo development. The data demonstrate that low-abundance galactolipids with five double bonds serve functions in plastid membranes that are not replaced by the predominant species with six double bonds. Furthermore, the data identify a function of amyloplast membranes in the development of starch granules. Finally, the specific changes in lipid composition suggest that MGD1 can distinguish the constituency of acyl groups on its diacylglycerol substrate based upon the degree of desaturation. PMID:21685260

Adaptive mesh refinement for characteristic grids

NASA Astrophysics Data System (ADS)

Thornburg, Jonathan

2011-05-01

I consider techniques for Berger-Oliger adaptive mesh refinement (AMR) when numerically solving partial differential equations with wave-like solutions, using characteristic (double-null) grids. Such AMR algorithms are naturally recursive, and the best-known past Berger-Oliger characteristic AMR algorithm, that of Pretorius and Lehner (J Comp Phys 198:10, 2004), recurses on individual "diamond" characteristic grid cells. This leads to the use of fine-grained memory management, with individual grid cells kept in two-dimensional linked lists at each refinement level. This complicates the implementation and adds overhead in both space and time. Here I describe a Berger-Oliger characteristic AMR algorithm which instead recurses on null slices. This algorithm is very similar to the usual Cauchy Berger-Oliger algorithm, and uses relatively coarse-grained memory management, allowing entire null slices to be stored in contiguous arrays in memory. The algorithm is very efficient in both space and time. I describe discretizations yielding both second and fourth order global accuracy. My code implementing the algorithm described here is included in the electronic supplementary materials accompanying this paper, and is freely available to other researchers under the terms of the GNU general public license.

PTBP1 Is Required for Embryonic Development before Gastrulation

PubMed Central

Suckale, Jakob; Wendling, Olivia; Masjkur, Jimmy; Jäger, Melanie; Münster, Carla; Anastassiadis, Konstantinos; Stewart, A. Francis; Solimena, Michele

2011-01-01

Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures. PMID:21423341

PTBP1 is required for embryonic development before gastrulation.

PubMed

Suckale, Jakob; Wendling, Olivia; Masjkur, Jimmy; Jäger, Melanie; Münster, Carla; Anastassiadis, Konstantinos; Stewart, A Francis; Solimena, Michele

2011-02-17

Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures.

7 CFR 801.5 - Tolerance for diverter-type mechanical samplers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Tolerance for diverter-type mechanical samplers. 801.5 Section 801.5 Agriculture Regulations of the Department of Agriculture (Continued) GRAIN INSPECTION... mechanical samplers. The maintenance tolerance for diverter-type mechanical samplers (primary, or primary and...

30 CFR 250.433 - What are the diverter actuation and testing requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.433 What are the diverter...-test the vent lines. (a) For drilling operations with a surface wellhead configuration, you must...

30 CFR 250.1613 - Diverter systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) downstream of the spool outlet flange, and the radius of curvature of turns shall be as large as practicable... following shall apply: (1) If the diverter system utilizes only one spool outlet, branch lines shall be installed to provide downwind diversion capability, and (2) No spool outlet or diverter line internal...

Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

DTIC Science & Technology

2015-09-01

and PET images. Figure 2 highlights the dynamic uptake of TSPO as compared to muscle. Across 60 minutes the %ID/cc continues to increase which is...p53 double null mutant mouse model. Towards that end, we have successfully acquired anatomic MRI and PET data in orthotopic tumors within the Pten...castration resistant prostate cancer, MRI, PET , FDHT, image optimization 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES

Combined Effects of Flow Diverting Strategies and Parent Artery Curvature on Aneurysmal Hemodynamics: A CFD Study

PubMed Central

Yu, Ying; Lv, Nan; Wang, Shengzhang; Karmonik, Christof; Liu, Jian-Min; Huang, Qinghai

2015-01-01

Purpose Flow diverters (FD) are increasingly being considered for treating large or giant wide-neck aneurysms. Clinical outcome is highly variable and depends on the type of aneurysm, the flow diverting device and treatment strategies. The objective of this study was to analyze the effect of different flow diverting strategies together with parent artery curvature variations on altering intra-aneurysmal hemodynamics. Methods Four ideal intracranial aneurysm models with different parent artery curvature were constructed. Computational fluid dynamics (CFD) simulations of the hemodynamics before and after applying five types of flow diverting strategies (single FD, single FD with 5% and 10% packing density of coils, two FDs with 25% and 50% overlapping rate) were performed. Changes in pressure, wall shear stress (WSS), relative residence time (RRT), inflow velocity and inflow volume rate were calculated and compared. Results Each flow diverting strategy resulted in enhancement of RRT and reduction of normalized mean WSS, inflow volume rate and inflow velocity in various levels. Among them, 50% overlapped FD induced most effective hemodynamic changes in RRT and inflow volume rate. The mean pressure only slightly decreased after treatment. Regardless of the kind of implantation of FD, the mean pressure, inflow volume rate and inflow velocity increased and the RRT decreased as the curvature of the parent artery increased. Conclusions Of all flow diverting strategies, overlapping FDs induced most favorable hemodynamic changes. Hemodynamics alterations post treatment were substantially influenced by parent artery curvature. Our results indicate the need of an individualized flow diverting strategy that is tailored for a specific aneurysm. PMID:26398847

Rotary seal with enhanced lubrication and contaminant flushing

DOEpatents

Dietle, Lannie L.

2000-01-01

A resilient, ring shaped interference-type hydrodynamic rotary seal having waves on the lubricant side which provide increased film thickness and flushing action by creating contact pressure induced angulated restrictions formed by abrupt restrictive diverters. The angulated restrictions are defined by projecting ridges, corners at the trailing edge of the waves, or simply by use of a converging shape at the trailing edge of the waves which is more abrupt than the gently converging hydrodynamic inlet shape at the leading edge of the waves. The abrupt restrictive diverter performs two functions; a restricting function and a diverting function. The angulated restrictions cause a local film thickness restriction which produces a damming effect preventing a portion of the lubricant from leaking out of the dynamic sealing interface at the trailing edge of the wave, and results in a much thicker lubricant film thickness under the waves. This contributes to more film thickness in the remainder of the dynamic sealing interface toward the environment because film thickness tends to decay gradually rather than abruptly due to the relative stiffness of the seal material. Because of the angle of the abrupt restrictive diverter relative to the relative rotation direction, in conjunction with the restriction or damming effect, a strong diverting action is produced which pumps lubricant across the dynamic sealing interface toward the environment. The lubricant diversion is caused by the component of the rotational velocity tangent to the abrupt restrictive diverter. The component of rotational velocity normal to the abrupt restrictive diverter causes a portion of the lubricant film to be pumped past the abrupt restrictive diverter, thereby assuring adequate lubrication thereof.

30 CFR 250.431 - What are the diverter design and installation requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

... OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations... floating drilling operations; (b) Use dual diverter lines arranged to provide for downwind diversion capability; (c) Use at least two diverter control stations. One station must be on the drilling floor. The...

The study of flow diversion effects on aneurysm using multiple enterprise stents and two flow diverters

PubMed Central

Kojima, Masahiro; Irie, Keiko; Fukuda, Toshio; Arai, Fumihito; Hirose, Yuichi; Negoro, Makoto

2012-01-01

Background: Computer-based simulation is necessary to clarify the hemodynamics in brain aneurysm. Specifically for endovascular treatments, the effects of indwelling intravascular devices on blood stream need to be considered. The most recent technology used for cerebral aneurysm treatment is related to the use of flow diverters to reduce the amount of flow entering the aneurysm. To verify the differences of flow reduction, we analyzed multiple Enterprise stents and two kinds of flow diverters. Materials and Methods: In this research, we virtually modeled three kinds of commercial intracranial stents (Enterprise, Silk, and Pipeline) and mounted to fit into the vessel wall, and deployed across the neck of an IC-ophthalmic artery aneurysm. Also, we compared the differences among multiple Enterprise stents and two flow diverters in a standalone mode. Results: From the numerical results, the values of wall shear stress and pressure are reduced in proportion to the size of mesh, especially in the inflow area. However, the reduced velocity within the aneurysm sac by the multiple stents is not as significant as the flow diverters. Conclusions: This is the first study analyzing the flow alterations among multiple Enterprise stents and flow diverters. The placement of small meshed stents dramatically reduced the aneurysmal fluid movement. However, compared to the flow diverters, we did not observe the reduction of flow velocity within the aneurysm by the multiple stents. PMID:23559981

30 CFR 250.432 - How do I obtain a departure to diverter design and installation requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... MANAGEMENT, REGULATION, AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250... diameter of at least 8 inches. (d) Use a single diverter line for floating drilling operations on a...

30 CFR 250.432 - How do I obtain a departure to diverter design and installation requirements?

Code of Federal Regulations, 2013 CFR

2013-07-01

... ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.432 How do I obtain a... least 8 inches. (d) Use a single diverter line for floating drilling operations on a dynamically...

30 CFR 250.434 - What are the recordkeeping requirements for diverter actuations and tests?

Code of Federal Regulations, 2011 CFR

2011-07-01

..., REGULATION, AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.434 What are... diverter tests and actuations at the facility for the duration of drilling the well. [68 FR 8423, Feb. 20...

30 CFR 250.432 - How do I obtain a departure to diverter design and installation requirements?

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.432 How do I obtain a... least 8 inches. (d) Use a single diverter line for floating drilling operations on a dynamically...

30 CFR 250.432 - How do I obtain a departure to diverter design and installation requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... ENVIRONMENTAL ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.432 How do I obtain a... least 8 inches. (d) Use a single diverter line for floating drilling operations on a dynamically...

Improved confinement in highly powered high performance scenarios on DIII-D

NASA Astrophysics Data System (ADS)

Petrie, T. W.; Osborne, T.; Fenstermacher, M. E.; Ferron, J.; Groebner, R.; Grierson, B.; Holcomb, C.; Lasnier, C.; Leonard, A.; Luce, T.; Makowski, M.; Turco, F.; Solomon, W.; Victor, B.; Watkins, J.

2017-08-01

DIII-D has recently demonstrated improved energy confinement by injecting neutral deuterium gas into high performance near-double null divertor (DND) plasmas during high power operation. Representative parameters for these plasmas are: q 95  =  6, P IN up to 15 MW, H 98  =  1.4-1.8, and β N  =  2.5-4.0. The ion B   ×  \

Methylation of Gibberellins by Arabidopsis GAMT1 and GAMT2[W

PubMed Central

Varbanova, Marina; Yamaguchi, Shinjiro; Yang, Yue; McKelvey, Katherine; Hanada, Atsushi; Borochov, Roy; Yu, Fei; Jikumaru, Yusuke; Ross, Jeannine; Cortes, Diego; Ma, Choong Je; Noel, Joseph P.; Mander, Lew; Shulaev, Vladimir; Kamiya, Yuji; Rodermel, Steve; Weiss, David; Pichersky, Eran

2007-01-01

Arabidopsis thaliana GAMT1 and GAMT2 encode enzymes that catalyze formation of the methyl esters of gibberellins (GAs). Ectopic expression of GAMT1 or GAMT2 in Arabidopsis, tobacco (Nicotiana tabacum), and petunia (Petunia hybrida) resulted in plants with GA deficiency and typical GA deficiency phenotypes, such as dwarfism and reduced fertility. GAMT1 and GAMT2 are both expressed mainly in whole siliques (including seeds), with peak transcript levels from the middle until the end of silique development. Within whole siliques, GAMT2 was previously shown to be expressed mostly in developing seeds, and we show here that GAMT1 expression is also localized mostly to seed, suggesting a role in seed development. Siliques of null single GAMT1 and GAMT2 mutants accumulated high levels of various GAs, with particularly high levels of GA1 in the double mutant. Methylated GAs were not detected in wild-type siliques, suggesting that methylation of GAs by GAMT1 and GAMT2 serves to deactivate GAs and initiate their degradation as the seeds mature. Seeds of homozygous GAMT1 and GAMT2 null mutants showed reduced inhibition of germination, compared with the wild type, when placed on plates containing the GA biosynthesis inhibitor ancymidol, with the double mutant showing the least inhibition. These results suggest that the mature mutant seeds contained higher levels of active GAs than wild-type seeds. PMID:17220201

Disruption of insulin-like growth factor-II imprinting during embryonic development rescues the dwarf phenotype of mice null for pregnancy-associated plasma protein-A.

PubMed

Bale, Laurie K; Conover, Cheryl A

2005-08-01

Pregnancy-associated plasma protein-A (PAPP-A), an insulin-like growth factor-binding protein (IGFBP) protease, increases insulin-like growth factor (IGF) activity through cleavage of inhibitory IGFBP-4 and the consequent release of IGF peptide for receptor activation. Mice homozygous for targeted disruption of the PAPP-A gene are born as proportional dwarfs and exhibit retarded bone ossification during fetal development. Phenotype and in vitro data support a model in which decreased IGF-II bioavailability during embryogenesis results in growth retardation and reduction in overall body size. To test the hypothesis that an increase in IGF-II during embryogenesis would overcome the growth deficiencies, PAPP-A-null mice were crossed with DeltaH19 mutant mice, which have increased IGF-II expression and fetal overgrowth due to disruption of IgfII imprinting. DeltaH19 mutant mice were 126% and PAPP-A-null mice were 74% the size of controls at birth. These size differences were evident at embryonic day 16.5. Importantly, double mutants were indistinguishable from controls both in terms of size and skeletal development. Body size programmed during embryo development persisted post-natally. Thus, disruption of IgfII imprinting and consequent elevation in IGF-II during fetal development was associated with rescue of the dwarf phenotype and ossification defects of PAPP-A-null mice. These data provide strong genetic evidence that PAPP-A plays an essential role in determining IGF-II bioavailability for optimal fetal growth and development.

High internal inductance for steady-state operation in ITER and a reactor

DOE PAGES

Ferron, John R.; Holcomb, Christopher T.; Luce, Timothy C.; ...

2015-06-26

Increased confinement and ideal stability limits at relatively high values of the internal inductance (more » $${{\\ell}_{i}}$$ ) have enabled an attractive scenario for steady-state tokamak operation to be demonstrated in DIII-D. Normalized plasma pressure in the range appropriate for a reactor has been achieved in high elongation and triangularity double-null divertor discharges with $${{\\beta}_{\\text{N}}}\\approx 5$$ at $${{\\ell}_{i}}\\approx 1.3$$ , near the ideal $n=1$ kink stability limit calculated without the effect of a stabilizing vacuum vessel wall, with the ideal-wall limit still higher at $${{\\beta}_{\\text{N}}}>5.5$$ . Confinement is above the H-mode level with $${{H}_{98\\left(\\text{y},2\\right)}}\\approx 1.8$$ . At $${{q}_{95}}\\approx 7.5$$ , the current is overdriven, with bootstrap current fraction $${{f}_{\\text{BS}}}\\approx 0.8$$ , noninductive current fraction $${{f}_{\\text{NI}}}>1$$ and negative surface voltage. For ITER (which has a single-null divertor shape), operation at $${{\\ell}_{i}}\\approx 1$$ is a promising option with $${{f}_{\\text{BS}}}\\approx 0.5$$ and the remaining current driven externally near the axis where the electron cyclotron current drive efficiency is high. This scenario has been tested in the ITER shape in DIII-D at $${{q}_{95}}=4.8$$ , so far reaching $${{f}_{\\text{NI}}}=0.7$$ and $${{f}_{\\text{BS}}}=0.4$$ at $${{\\beta}_{\\text{N}}}\\approx 3.5$$ with performance appropriate for the ITER Q=5 mission, $${{H}_{89}}{{\\beta}_{\\text{N}}}/q_{95}^{2}\\approx 0.3$$ . Modeling studies explored how increased current drive power for DIII-D could be applied to maintain a stationary, fully noninductive high $${{\\ell}_{i}}$$ discharge. Lastly, stable solutions in the double-null shape are found without the vacuum vessel wall at $${{\\beta}_{\\text{N}}}=4$$ , $${{\\ell}_{i}}=1.07$$ and $${{f}_{\\text{BS}}}=0.5$$ , and at $${{\\beta}_{\\text{N}}}=5$$ with the vacuum vessel wall.« less

Magnetic Heat Pump Containing Flow Diverters

NASA Technical Reports Server (NTRS)

Howard, Frank S.

1995-01-01

Proposed magnetic heat pump contains flow diverters for suppression of undesired flows. If left unchecked, undesired flows mix substantial amounts of partially heated and partially cooled portions of working fluid, effectively causing leakage of heat from heated side to cooled side. By reducing leakage of heat, flow diverters increase energy efficiency of magnetic heat pump, potentially offering efficiency greater than compressor-driven refrigerator.

Overt orienting of spatial attention and corticospinal excitability during action observation are unrelated

PubMed Central

Betti, Sonia; Castiello, Umberto; Guerra, Silvia

2017-01-01

Observing moving body parts can automatically activate topographically corresponding motor representations in the primary motor cortex (M1), the so-called direct matching. Novel neurophysiological findings from social contexts are nonetheless proving that this process is not automatic as previously thought. The motor system can flexibly shift from imitative to incongruent motor preparation, when requested by a social gesture. In the present study we aim to bring an increase in the literature by assessing whether and how diverting overt spatial attention might affect motor preparation in contexts requiring interactive responses from the onlooker. Experiment 1 shows that overt attention—although anchored to an observed biological movement—can be captured by a target object as soon as a social request for it becomes evident. Experiment 2 reveals that the appearance of a short-lasting red dot in the contralateral space can divert attention from the target, but not from the biological movement. Nevertheless, transcranial magnetic stimulation (TMS) over M1 combined with electromyography (EMG) recordings (Experiment 3) indicates that attentional interference reduces corticospinal excitability related to the observed movement, but not motor preparation for a complementary action on the target. This work provides evidence that social motor preparation is impermeable to attentional interference and that a double dissociation is present between overt orienting of spatial attention and neurophysiological markers of action observation. PMID:28319191

Sialidases affect the host cell adherence and epsilon toxin-induced cytotoxicity of Clostridium perfringens type D strain CN3718.

PubMed

Li, Jihong; Sayeed, Sameera; Robertson, Susan; Chen, Jianming; McClane, Bruce A

2011-12-01

Clostridium perfringens type B or D isolates, which cause enterotoxemias or enteritis in livestock, produce epsilon toxin (ETX). ETX is exceptionally potent, earning it a listing as a CDC class B select toxin. Most C. perfringens strains also express up to three different sialidases, although the possible contributions of those enzymes to type B or D pathogenesis remain unclear. Type D isolate CN3718 was found to carry two genes (nanI and nanJ) encoding secreted sialidases and one gene (nanH) encoding a cytoplasmic sialidase. Construction in CN3718 of single nanI, nanJ and nanH null mutants, as well as a nanI/nanJ double null mutant and a triple sialidase null mutant, identified NanI as the major secreted sialidase of this strain. Pretreating MDCK cells with NanI sialidase, or with culture supernatants of BMC206 (an isogenic CN3718 etx null mutant that still produces sialidases) enhanced the subsequent binding and cytotoxic effects of purified ETX. Complementation of BMC207 (an etx/nanH/nanI/nanJ null mutant) showed this effect is mainly attributable to NanI production. Contact between BMC206 and certain mammalian cells (e.g., enterocyte-like Caco-2 cells) resulted in more rapid sialidase production and this effect involved increased transcription of BMC206 nanI gene. BMC206 was shown to adhere to some (e.g. Caco-2 cells), but not all mammalian cells, and this effect was dependent upon sialidase, particularly NanI, expression. Finally, the sialidase activity of NanI (but not NanJ or NanH) could be enhanced by trypsin. Collectively these in vitro findings suggest that, during type D disease originating in the intestines, trypsin may activate NanI, which (in turn) could contribute to intestinal colonization by C. perfringens type D isolates and also increase ETX action.

Water Relations of Obligate Riparian Plants as a Function of Streamflow Diversion on the Bishop Creek Watershed

Treesearch

Stanley D. Smith; Janet L. Nachlinger; A. Bruce Wellington; Carl A. Fox

1989-01-01

We investigated the water relations of obligate riparian plants on paired diverted and undiverted reaches on Bishop Creek, Eastern Sierra Nevada. Riparian plants on diverted reaches had reduced stomatal conductance and water potential compared to plants on undiverted reaches in a dry year, but not in a high runoff year. Juvenile plants on diverted reaches had reduced...

The application of improved flow diverter for first flush management.

PubMed

Mrowiec, M

2010-01-01

The paper presents the investigations on first flush phenomenon based on the total suspended solids (TSS) concentration measurement during selected rainfalls at central part of Czestochowa (Poland) and also the hydrodynamic model of the catchment. The model allows to present the conception of first flush management using an improved flow diverter Septurn. Flow diverters used in the separate sewer systems create a hybrid system called "semi-separate" sewage system, which allows to treat the first flush volume in the waste water treatment plant (WWTP). Proposed construction of the flow diverter makes possible to capture significant part of the pollutant load (TSS) and simultaneously to reduce volume discharges to WWTPs during wet weather.

The effects of resonant magnetic perturbations on fast ion confinement in the Mega Amp Spherical Tokamak

NASA Astrophysics Data System (ADS)

McClements, K. G.; Akers, R. J.; Boeglin, W. U.; Cecconello, M.; Keeling, D.; Jones, O. M.; Kirk, A.; Klimek, I.; Perez, R. V.; Shinohara, K.; Tani, K.

2015-07-01

The effects of resonant magnetic perturbations (RMPs) on the confinement of energetic (neutral beam) ions in the Mega Amp Spherical Tokamak (MAST) are assessed experimentally using measurements of neutrons, fusion protons and fast ion Dα (FIDA) light emission. In single null-diverted (SND) MAST pulses with relatively low plasma current (400 kA), the total neutron emission dropped by approximately a factor of two when RMPs with toroidal mode number n = 3 were applied. The measured neutron rate during RMPs was much lower than that calculated using the TRANSP plasma simulation code, even when non-classical (but axisymmetric) ad hoc fast ion transport was taken into account in the latter. Sharp drops in spatially-resolved neutron rates, fusion proton rates and FIDA emission were also observed. First principles-based simulations of RMP-induced fast ion transport in MAST, using the F3D-OFMC code, show similar losses for two alternative representations of the MAST first wall, with and without full orbit effects taken into account; for n = 6 RMPs in a 600 kA plasma, the additional loss of beam power due to the RMPs was found in the simulations to be approximately 11%.

Method and apparatus for cold gas reinjection in through-flow and reverse-flow wave rotors

NASA Technical Reports Server (NTRS)

Nalim, M. Razi (Inventor); Paxson, Daniel E. (Inventor)

1999-01-01

A method and apparatus for cold gas reinjection in through-flow and reverse-flow wave rotors having a plurality of channels formed around a periphery thereof. A first port injects a supply of cool air into the channels. A second port allows the supply of cool air to exit the channels and flow to a combustor. A third port injects a supply of hot gas from the combustor into the channels. A fourth port allows the supply of hot gas to exit the channels and flow to a turbine. A diverting port and a reinjection port are connected to the second and third ports, respectively. The diverting port diverts a portion of the cool air exiting through the second port as reinjection air. The diverting port is fluidly connected to the reinjection port which reinjects the reinjection air back into the channels. The reinjection air evacuates the channels of the hot gas resident therein and cools the channel walls, a pair of end walls of the rotor, ducts communicating with the rotor and subsequent downstream components. In a second embodiment, the second port receives all of the cool air exiting the channels and the diverting port diverts a portion of the cool air just prior to the cool air flowing to the combustor.

Is Diversion with Ileostomy Non-inferior to Hartmann Resection for Left-sided Colorectal Anastomotic Leak?

PubMed

Stafford, Caitlin; Francone, Todd D; Marcello, Peter W; Roberts, Patricia L; Ricciardi, Rocco

2018-03-01

Treatment of left-sided colorectal anastomotic leaks often requires fecal stream diversion for prevention of further septic complications. To manage anastomotic leak, it is unclear if diverting ileostomy provides similar outcomes to Hartmann resection with colostomy. We identified all patients who developed anastomotic leak following left-sided colorectal resections from 1/2012 through 12/2014 using the American College of Surgeons National Surgical Quality Improvement Program. Then, we examined the risk of mortality and abdominal reoperation in patients treated with diverting ileostomy as compared to Hartmann resection. There were 1745 patients who experienced an anastomotic leak in a cohort of 63,748 patients (3.7%). Two hundred thirty-five patients had a reoperation for anastomotic leak involving the formation of a diverting ileostomy (n = 77) or Hartmann resection (n = 158). There was no difference in mortality or abdominal reoperation in patients treated with diverting ileostomy (3.9, 7.8%) versus Hartmann resection (3.8, 6.3%) (p = 0.8). There was no difference in the outcomes of mortality or need for second abdominal reoperation in patients treated with diverting ileostomy as compared to Hartmann resection for left-sided colorectal anastomotic leak. Thus, select patients with left-sided colorectal anastomotic leaks may be safely managed with diverting ileostomy.

Both LOV1 and LOV2 domains of phototropin2 function as the photosensory domain for hypocotyl phototropic responses in Arabidopsis thaliana (Brassicaceae).

PubMed

Suetsugu, Noriyuki; Kong, Sam-Geun; Kasahara, Masahiro; Wada, Masamitsu

2013-01-01

Phototropins (phot) are blue light receptor proteins that mediate phototropism and control photomovement responses, such as chloroplast photorelocation movement and stomatal opening. Arabidopsis thaliana has two phototropins, phot1 and phot2. Although both phot1 and phot2 redundantly mediate photomovement responses, phot2 uniquely regulates phototropism and the chloroplast avoidance response under high-intensity blue light. However, compared to that of phot1, the mechanistic basis of phot2 function is poorly understood, and in particular, the importance of the LOV2 domain in phot2 function has not been clearly demonstrated. Indeed, photocycle-deficient LOV2 transgenic lines expressing phot2 in a phot1phot2 mutant background retained phototropism, although with less sensitivity than wild-type plants. We isolated 11 alleles of phot2 mutants and determined the molecular lesion in each allele. We analyzed hypocotyl phototropism, chloroplast photorelocation movement, and leaf flattening in the phot2 mutant and the respective phot1phot2 double mutant plants. We demonstrated that unlike the phot2 null mutant, the phot2-10 mutant, which has the defective phot2 LOV2 domain, retained the phototropic response and had unusual chloroplast movement. Mutants phot2-2 and phot2-6, which have a missense mutation in the kinase activation loop of phot2, had the phot2-null mutant phenotype. Furthermore, we convincingly demonstrated that the commonly used phot2-1 mutant allele is a phot2-null mutant. The analyses of the multiple phot2 mutant alleles provided strong evidence for the importance of both LOV domains and the kinase activation loop of phot2 in phototropism and other phot-dependent responses and also demonstrated that phot2-1 allele is a null mutant.

RNA interference can target pre-mRNA: consequences for gene expression in a Caenorhabditis elegans operon.

PubMed Central

Bosher, J M; Dufourcq, P; Sookhareea, S; Labouesse, M

1999-01-01

In nematodes, flies, trypanosomes, and planarians, introduction of double-stranded RNA results in sequence-specific inactivation of gene function, a process termed RNA interference (RNAi). We demonstrate that RNAi against the Caenorhabditis elegans gene lir-1, which is part of the lir-1/lin-26 operon, induced phenotypes very different from a newly isolated lir-1 null mutation. Specifically, lir-1(RNAi) induced embryonic lethality reminiscent of moderately strong lin-26 alleles, whereas the lir-1 null mutant was viable. We show that the lir-1(RNAi) phenotypes resulted from a severe loss of lin-26 gene expression. In addition, we found that RNAi directed against lir-1 or lin-26 introns induced similar phenotypes, so we conclude that lir-1(RNAi) targets the lir-1/lin-26 pre-mRNA. This provides direct evidence that RNA interference can prevent gene expression by targeting nuclear transcripts. Our results highlight that caution may be necessary when interpreting RNA interference without the benefit of mutant alleles. PMID:10545456

Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Nicastro, Holly L.; Dunn, Barbara K.

2013-01-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention. PMID:23552052

Relationship between aneurysm occlusion and flow diverting device oversizing in a rabbit model.

PubMed

Hodis, Simona; Ding, Yong-Hong; Dai, Daying; Lingineni, Ravi; Mut, Fernando; Cebral, Juan; Kallmes, David; Kadirvel, Ramanathan

2016-01-01

Implanted, actual flow diverter pore density is thought to be strongly influenced by proper matching between the device size and parent artery diameter. The objective of this study was to characterize the correlation between device sizing, metal coverage, and the resultant occlusion of aneurysms following flow diverter treatment in a rabbit model. Rabbit saccular aneurysms were treated with flow diverters (iso-sized to proximal parent artery, 0.5 mm oversized, or 1.0 mm oversized, respectively, n=6 for each group). Eight weeks after implantation, the angiographic degree of aneurysm occlusion was graded (complete, near-complete, or incomplete). The ostium of the explanted aneurysm covered with the flow diverter struts was photographed. Based on gross anatomic findings, the metal coverage and pore density at the ostium of the aneurysm were calculated and correlated with the degree of aneurysm occlusion. Angiographic results showed there were no statistically significant differences in aneurysm geometry and occlusion among groups. The mean parent artery diameter to flow diverter diameter ratio was higher in the 1.0 mm oversized group than in the other groups. Neither the percentage metal coverage nor the pore density showed statistically significant differences among groups. Aneurysm occlusion was inversely correlated with the ostium diameter, irrespective of the size of the device implanted. Device sizing alone does not predict resultant pore density or metal coverage following flow diverter implantation in the rabbit aneurysm model. Aneurysm occlusion was not impacted by either metal coverage or pore density, but was inversely correlated with the diameter of the ostium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Green Bank North Celestial Cap Pulsar Survey. III. 45 New Pulsar Timing Solutions

NASA Astrophysics Data System (ADS)

Lynch, Ryan S.; Swiggum, Joseph K.; Kondratiev, Vlad I.; Kaplan, David L.; Stovall, Kevin; Fonseca, Emmanuel; Roberts, Mallory S. E.; Levin, Lina; DeCesar, Megan E.; Cui, Bingyi; Cenko, S. Bradley; Gatkine, Pradip; Archibald, Anne M.; Banaszak, Shawn; Biwer, Christopher M.; Boyles, Jason; Chawla, Pragya; Dartez, Louis P.; Day, David; Ford, Anthony J.; Flanigan, Joseph; Hessels, Jason W. T.; Hinojosa, Jesus; Jenet, Fredrick A.; Karako-Argaman, Chen; Kaspi, Victoria M.; Leake, Sean; Lunsford, Grady; Martinez, José G.; Mata, Alberto; McLaughlin, Maura A.; Noori, Hind Al; Ransom, Scott M.; Rohr, Matthew D.; Siemens, Xavier; Spiewak, Renée; Stairs, Ingrid H.; van Leeuwen, Joeri; Walker, Arielle N.; Wells, Bradley L.

2018-06-01

We provide timing solutions for 45 radio pulsars discovered by the Robert C. Byrd Green Bank Telescope. These pulsars were found in the Green Bank North Celestial Cap pulsar survey, an all-GBT-sky survey being carried out at a frequency of 350 {MHz}. We include pulsar timing data from the Green Bank Telescope and Low Frequency Array. Our sample includes five fully recycled millisecond pulsars (MSPs, three of which are in a binary system), a new relativistic double neutron star system, an intermediate-mass binary pulsar, a mode-changing pulsar, a 138 ms pulsar with a very low magnetic field, and several nulling pulsars. We have measured two post-Keplerian parameters and thus the masses of both objects in the double neutron star system. We also report a tentative companion mass measurement via Shapiro delay in a binary MSP. Two of the MSPs can be timed with high precision and have been included in pulsar timing arrays being used to search for low-frequency gravitational waves, while a third MSP is a member of the black widow class of binaries. Proper motion is measurable in five pulsars, and we provide an estimate of their space velocity. We report on an optical counterpart to a new black widow system and provide constraints on the optical counterparts to other binary MSPs. We also present a preliminary analysis of nulling pulsars in our sample. These results demonstrate the scientific return of long timing campaigns on pulsars of all types.

Effects of shear on the magnetic footprint and stochastic layer in double-null divertor tokamak

NASA Astrophysics Data System (ADS)

Farhat, Hamidullah; Punjabi, Alkesh; Ali, Halima

2006-10-01

We have developed a new area-preserving map, called the Adjustable Shear Map, to calculate effects of shear on the magnetic footprint and stochastic layer in double-null divertor tokamak. The map is given by equationsxn+1=xn-kyn[(1-yn^2 )(1+syn)+sxn+1^2 ),yn+1=yn+kxn+1[1+s(xn+1^2 +yn^2 )]. k is the map parameter and s is the shear parameter. O-point of the map is (0, 0), and the X-points are (0, 1), and (0, -1). For s=0, k=0.6, the last good surface is y=0.9918 with q ˜3. Here we will report on the effects of shear on the stochastic layer and magnetic footprint as the shear parameter is varied from 0 to -1. Here we will report the preliminary results on the effect of shear on the magnetic foot print and the stochastic layer where the shear parameter s has values between -1 and 0. using method of maps [1-4]. This work is done under the DOE grant number DE-FG02-01ER54624. 1. A. Punjabi, A. Boozer, and A. Verma, Phys. Rev. lett., 69, 3322 (1992). 2. H. Ali, A. Punjabi, and A. Boozer, Phys. Plasmas 11, 4527 (2004). 3. A. Punjabi, H. Ali, and A. Boozer, Phys. Plasmas 10, 3992 (2003). 4. A. Punjabi, H. Ali, and A. Boozer, Phys. Plasmas 4, 337 (1997).

Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies

PubMed Central

Brydges, Susannah D.; Broderick, Lori; McGeough, Matthew D.; Pena, Carla A.; Mueller, James L.; Hoffman, Hal M.

2013-01-01

The inflammasome is a cytoplasmic multiprotein complex that promotes proinflammatory cytokine maturation in response to host- and pathogen-derived signals. Missense mutations in cryopyrin (NLRP3) result in a hyperactive inflammasome that drives overproduction of the proinflammatory cytokines IL-1β and IL-18, leading to the cryopyrin-associated periodic syndromes (CAPS) disease spectrum. Mouse lines harboring CAPS-associated mutations in Nlrp3 have elevated levels of IL-1β and IL-18 and closely mimic human disease. To examine the role of inflammasome-driven IL-18 in murine CAPS, we bred Nlrp3 mutations onto an Il18r-null background. Deletion of Il18r resulted in partial phenotypic rescue that abolished skin and visceral disease in young mice and normalized serum cytokines to a greater extent than breeding to Il1r-null mice. Significant systemic inflammation developed in aging Nlrp3 mutant Il18r-null mice, indicating that IL-1 and IL-18 drive pathology at different stages of the disease process. Ongoing inflammation in double-cytokine knockout CAPS mice implicated a role for caspase-1–mediated pyroptosis and confirmed that CAPS is inflammasome dependent. Our results have important implications for patients with CAPS and residual disease, emphasizing the need to explore other NLRP3-mediated pathways and the potential for inflammasome-targeted therapy. PMID:24084736

Cyclin A2 promotes DNA repair in the brain during both development and aging.

PubMed

Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

2016-07-01

Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.

Human dental pulp pluripotent-like stem cells promote wound healing and muscle regeneration.

PubMed

Martínez-Sarrà, Ester; Montori, Sheyla; Gil-Recio, Carlos; Núñez-Toldrà, Raquel; Costamagna, Domiziana; Rotini, Alessio; Atari, Maher; Luttun, Aernout; Sampaolesi, Maurilio

2017-07-27

Dental pulp represents an easily accessible autologous source of adult stem cells. A subset of these cells, named dental pulp pluripotent-like stem cells (DPPSC), shows high plasticity and can undergo multiple population doublings, making DPPSC an appealing tool for tissue repair or maintenance. DPPSC were harvested from the dental pulp of third molars extracted from young patients. Growth factors released by DPPSC were analysed using antibody arrays. Cells were cultured in specific differentiation media and their endothelial, smooth and skeletal muscle differentiation potential was evaluated. The therapeutic potential of DPPSC was tested in a wound healing mouse model and in two genetic mouse models of muscular dystrophy (Scid/mdx and Sgcb-null Rag2-null γc-null). DPPSC secreted several growth factors involved in angiogenesis and extracellular matrix deposition and improved vascularisation in all three murine models. Moreover, DPPSC stimulated re-epithelialisation and ameliorated collagen deposition and organisation in healing wounds. In dystrophic mice, DPPSC engrafted in the skeletal muscle of both dystrophic murine models and showed integration in muscular fibres and vessels. In addition, DPPSC treatment resulted in reduced fibrosis and collagen content, larger cross-sectional area of type II fast-glycolytic fibres and infiltration of higher numbers of proangiogenic CD206 + macrophages. Overall, DPPSC represent a potential source of stem cells to enhance the wound healing process and slow down dystrophic muscle degeneration.

NanI Sialidase, CcpA, and CodY Work Together To Regulate Epsilon Toxin Production by Clostridium perfringens Type D Strain CN3718.

PubMed

Li, Jihong; Freedman, John C; McClane, Bruce A

2015-10-01

Clostridium perfringens type D strains are usually associated with diseases of livestock, and their virulence requires the production of epsilon toxin (ETX). We previously showed (J. Li, S. Sayeed, S. Robertson, J. Chen, and B. A. McClane, PLoS Pathog 7:e1002429, 2011, http://dx.doi.org/10.1371/journal.ppat.1002429) that BMC202, a nanI null mutant of type D strain CN3718, produces less ETX than wild-type CN3718 does. The current study proved that the lower ETX production by strain BMC202 is due to nanI gene disruption, since both genetic and physical (NanI or sialic acid) complementation increased ETX production by BMC202. Furthermore, a sialidase inhibitor that interfered with NanI activity also reduced ETX production by wild-type CN3718. The NanI effect on ETX production was shown to involve reductions in codY and ccpA gene transcription levels in BMC202 versus wild-type CN3718. Similar to CodY, CcpA was found to positively control ETX production. A double codY ccpA null mutant produced even less ETX than a codY or ccpA single null mutant. CcpA bound directly to sequences upstream of the etx or codY start codon, and bioinformatics identified putative CcpA-binding cre sites immediately upstream of both the codY and etx start codons, suggesting possible direct CcpA regulatory effects. A ccpA mutation also decreased codY transcription, suggesting that CcpA effects on ETX production can be both direct and indirect, including effects on codY transcription. Collectively, these results suggest that NanI, CcpA, and CodY work together to regulate ETX production, with NanI-generated sialic acid from the intestines possibly signaling type D strains to upregulate their ETX production and induce disease. Clostridium perfringens NanI was previously shown to increase ETX binding to, and cytotoxicity for, MDCK host cells. The current study demonstrates that NanI also regulates ETX production via increased transcription of genes encoding the CodY and CcpA global regulators. Results obtained using single ccpA or codY null mutants and a ccpA codY double null mutant showed that codY and ccpA regulate ETX production independently of one another but that ccpA also affects codY transcription. Electrophoretic mobility shift assays and bioinformatic analyses suggest that both CodY and CcpA may directly regulate etx transcription. Collectively, results of this study suggest that sialic acid generated by NanI from intestinal sources signals ETX-producing C. perfringens strains, via CcpA and CodY, to upregulate ETX production and cause disease. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Study of an engine flow diverter system for a large scale ejector powered aircraft model

NASA Technical Reports Server (NTRS)

Springer, R. J.; Langley, B.; Plant, T.; Hunter, L.; Brock, O.

1981-01-01

Requirements were established for a conceptual design study to analyze and design an engine flow diverter system and to include accommodations for an ejector system in an existing 3/4 scale fighter model equipped with YJ-79 engines. Model constraints were identified and cost-effective limited modification was proposed to accept the ejectors, ducting and flow diverter valves. Complete system performance was calculated and a versatile computer program capable of analyzing any ejector system was developed.

New Variable Porosity Flow Diverter (VPOD) Stent Design for Treatment of Cerebrovascular Aneurysms

PubMed Central

Ionita, Ciprian; Baier, Robert; Rudin, Stephen

2012-01-01

Using flow diverting Stents for intracranial aneurysm repair has been an area of recent active research. While current commercial flow diverting stents rely on a dense mesh of braided coils for flow diversion, our group has been developing a method to selectively occlude the aneurysm neck, without endangering nearby perforator vessels. In this paper, we present a new method of fabricating the low porosity patch, a key element of such asymmetric vascular stents (AVS). PMID:22254507

Gas-Diverting Cup For Welding At An Angle

NASA Technical Reports Server (NTRS)

Dyer, G. E.

1988-01-01

Attachment makes automatic arc welders more versatile. Stainless-steel diverting cup slips over standard torch cup. Bent electrode inserted in torch. Assembly reaches weld joints inaccessible to straight welding torch.

Preparing for the Next Kamikaze Attack on the American Homeland

DTIC Science & Technology

2007-11-27

This paper presents a case for not diverting additional Transportation Security Administration (TSA) resources from Civil Aviation security to...divert additional resources from Civil Aviation security to General Aviation security .

Diverting Ileostomy for the Treatment of Severe, Refractory, Pediatric Inflammatory Bowel Disease.

PubMed

Maxwell, Elizabeth C; Dawany, Noor; Baldassano, Robert N; Mamula, Petar; Mattei, Peter; Albenberg, Lindsey; Kelsen, Judith R

2017-09-01

Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population. Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015. Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel. In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

Passive Localization of Underwater Acoustic Beacons

DTIC Science & Technology

1993-09-01

maxtime) TickCounto; aborto ; FSRead(gASerRefln,&numCharln,&addressBuf); TalkSail(’O); iistart the PTR’s data collecticn DrawString(w\\p: H) I display a...34); aborto ; EventLoopO; II main execution loop RAMSDClose(sPortA); HI must close the RAM Drivers before shutdown 193 free(gw); //must release the...kNumExp+l),sizeof(double)); if(wtrue ==NULL) DrawString("\\pCan’t allocate memory for data collection!!! ); aborto ; Nvmeas = calloc(3L*(kStep~kNumExp+l

Multiple-labelling immunoEM using different sizes of colloidal gold: alternative approaches to test for differential distribution and colocalization in subcellular structures.

PubMed

Mayhew, Terry M; Lucocq, John M

2011-03-01

Various methods for quantifying cellular immunogold labelling on transmission electron microscope thin sections are currently available. All rely on sound random sampling principles and are applicable to single immunolabelling across compartments within a given cell type or between different experimental groups of cells. Although methods are also available to test for colocalization in double/triple immunogold labelling studies, so far, these have relied on making multiple measurements of gold particle densities in defined areas or of inter-particle nearest neighbour distances. Here, we present alternative two-step approaches to codistribution and colocalization assessment that merely require raw counts of gold particles in distinct cellular compartments. For assessing codistribution over aggregate compartments, initial statistical evaluation involves combining contingency table and chi-squared analyses to provide predicted gold particle distributions. The observed and predicted distributions allow testing of the appropriate null hypothesis, namely, that there is no difference in the distribution patterns of proteins labelled by different sizes of gold particle. In short, the null hypothesis is that of colocalization. The approach for assessing colabelling recognises that, on thin sections, a compartment is made up of a set of sectional images (profiles) of cognate structures. The approach involves identifying two groups of compartmental profiles that are unlabelled and labelled for one gold marker size. The proportions in each group that are also labelled for the second gold marker size are then compared. Statistical analysis now uses a 2 × 2 contingency table combined with the Fisher exact probability test. Having identified double labelling, the profiles can be analysed further in order to identify characteristic features that might account for the double labelling. In each case, the approach is illustrated using synthetic and/or experimental datasets and can be refined to correct observed labelling patterns to specific labelling patterns. These simple and efficient approaches should be of more immediate utility to those interested in codistribution and colocalization in multiple immunogold labelling investigations.

The inability of Bacillus licheniformis perR mutant to grow is mainly due to the lack of PerR-mediated fur repression.

PubMed

Kim, Jung-Hoon; Yang, Yoon-Mo; Ji, Chang-Jun; Ryu, Su-Hyun; Won, Young-Bin; Ju, Shin-Yeong; Kwon, Yumi; Lee, Yeh-Eun; Youn, Hwan; Lee, Jin-Won

2017-06-01

PerR, a member of Fur family protein, is a metal-dependent H 2 O 2 sensing transcription factor that regulates genes involved in peroxide stress response. Industrially important bacterium Bacillus licheniformis contains three PerR-like proteins (PerR BL , PerR2, and PerR3) compared to its close relative Bacillus subtilis. Interestingly, unlike other bacteria including B. subtilis, no authentic perR BL null mutant could be established for B. licheniformis. Thus, we constructed a conditional perR BL mutant using a xylose-inducible promoter, and investigated the genes under the control of PerR BL . PerR BL regulon genes include katA, mrgA, ahpC, pfeT, hemA, fur, and perR as observed for PerR BS . However, there is some variation in the expression levels of fur and hemA genes between B. subtilis and B. licheniformis in the derepressed state. Furthermore, katA, mrgA, and ahpC are strongly induced, whereas the others are only weakly or not induced by H 2 O 2 treatment. In contrast to the B. subtilis perR null mutant which frequently gives rise to large colony phenotype mainly due to the loss of katA, the suppressors of B. licheniformis perR mutant, which can form colonies on LB agar, were all catalase-positive. Instead, many of the suppressors showed increased levels of siderophore production, suggesting that the suppressor mutation is linked to the fur gene. Consistent with this, perR fur double mutant could grow on LB agar without Fe supplementation, whereas perR katA double mutant could only grow on LB agar with Fe supplementation. Taken together, our data suggest that in B. licheniformis, despite the similarity in PerR BL and PerR BS regulon genes, perR is an essential gene required for growth and that the inability of perR null mutant to grow is mainly due to elevated expression of Fur.

Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase

PubMed Central

Siller, Saul S.; Broadie, Kendal

2011-01-01

SUMMARY Fragile X syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1) product (FMRP), is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP) inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1) null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ), clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP) in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity between the single dfmr1 mutants and controls. These results support minocycline as a promising potential FXS treatment and suggest that it might act via MMP inhibition. We conclude that FMRP and TIMP pathways interact in a reciprocal, bidirectional manner. PMID:21669931

Use of flow-diverting stents as salvage treatment following failed stent-assisted embolization of intracranial aneurysms.

PubMed

Heiferman, Daniel M; Billingsley, Joshua T; Kasliwal, Manish K; Johnson, Andrew K; Keigher, Kiffon M; Frudit, Michel E; Moftakhar, Roham; Lopes, Demetrius K

2016-07-01

Flow-diverting stents, including the Pipeline embolization device (PED) and Silk, have been beneficial in the treatment of aneurysms previously unable to be approached via endovascular techniques. Recurrent aneurysms for which stent-assisted embolization has failed are a therapeutic challenge, given the existing intraluminal construct with continued blood flow into the aneurysm. We report our experience using flow-diverting stents in the repair of 25 aneurysms for which stent-assisted embolization had failed. Nineteen (76%) of these aneurysms at the 12-month follow-up showed improved Raymond class occlusion, with 38% being completely occluded, and all aneurysms demonstrated decreased filling. One patient developed a moderate permanent neurologic deficit. Appropriate stent sizing, proximal and distal construct coverage, and preventing flow diverter deployment between the previously deployed stent struts are important considerations to ensure wall apposition and prevention of endoleak. Flow diverters are shown to be a reasonable option for treating previously stented recurrent cerebral aneurysms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Double muscling in cattle due to mutations in the myostatin gene

PubMed Central

McPherron, Alexandra C.; Lee, Se-Jin

1997-01-01

Myostatin (GDF-8) is a member of the transforming growth factor β superfamily of secreted growth and differentiation factors that is essential for proper regulation of skeletal muscle mass in mice. Here we report the myostatin sequences of nine other vertebrate species and the identification of mutations in the coding sequence of bovine myostatin in two breeds of double-muscled cattle, Belgian Blue and Piedmontese, which are known to have an increase in muscle mass relative to conventional cattle. The Belgian Blue myostatin sequence contains an 11-nucleotide deletion in the third exon which causes a frameshift that eliminates virtually all of the mature, active region of the molecule. The Piedmontese myostatin sequence contains a missense mutation in exon 3, resulting in a substitution of tyrosine for an invariant cysteine in the mature region of the protein. The similarity in phenotypes of double-muscled cattle and myostatin null mice suggests that myostatin performs the same biological function in these two species and is a potentially useful target for genetic manipulation in other farm animals. PMID:9356471

An automatic CFD-based flow diverter optimization principle for patient-specific intracranial aneurysms.

PubMed

Janiga, Gábor; Daróczy, László; Berg, Philipp; Thévenin, Dominique; Skalej, Martin; Beuing, Oliver

2015-11-05

The optimal treatment of intracranial aneurysms using flow diverting devices is a fundamental issue for neuroradiologists as well as neurosurgeons. Due to highly irregular manifold aneurysm shapes and locations, the choice of the stent and the patient-specific deployment strategy can be a very difficult decision. To support the therapy planning, a new method is introduced that combines a three-dimensional CFD-based optimization with a realistic deployment of a virtual flow diverting stent for a given aneurysm. To demonstrate the feasibility of this method, it was applied to a patient-specific intracranial giant aneurysm that was successfully treated using a commercial flow diverter. Eight treatment scenarios with different local compressions were considered in a fully automated simulation loop. The impact on the corresponding blood flow behavior was evaluated qualitatively as well as quantitatively, and the optimal configuration for this specific case was identified. The virtual deployment of an uncompressed flow diverter reduced the inflow into the aneurysm by 24.4% compared to the untreated case. Depending on the positioning of the local stent compression below the ostium, blood flow reduction could vary between 27.3% and 33.4%. Therefore, a broad range of potential treatment outcomes was identified, illustrating the variability of a given flow diverter deployment in general. This method represents a proof of concept to automatically identify the optimal treatment for a patient in a virtual study under certain assumptions. Hence, it contributes to the improvement of virtual stenting for intracranial aneurysms and can support physicians during therapy planning in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

FOXOs attenuate bone formation by suppressing Wnt signaling

PubMed Central

Iyer, Srividhya; Ambrogini, Elena; Bartell, Shoshana M.; Han, Li; Roberson, Paula K.; de Cabo, Rafael; Jilka, Robert L.; Weinstein, Robert S.; O’Brien, Charles A.; Manolagas, Stavros C.; Almeida, Maria

2013-01-01

Wnt/β-catenin/TCF signaling stimulates bone formation and suppresses adipogenesis. The hallmarks of skeletal involution with age, on the other hand, are decreased bone formation and increased bone marrow adiposity. These changes are associated with increased oxidative stress and decreased growth factor production, which activate members of the FOXO family of transcription factors. FOXOs in turn attenuate Wnt/β-catenin signaling by diverting β-catenin from TCF- to FOXO-mediated transcription. We show herein that mice lacking Foxo1, -3, and -4 in bipotential progenitors of osteoblast and adipocytes (expressing Osterix1) exhibited increased osteoblast number and high bone mass that was maintained in old age as well as decreased adiposity in the aged bone marrow. The increased bone mass in the Foxo-deficient mice was accounted for by increased proliferation of osteoprogenitor cells and bone formation resulting from upregulation of Wnt/β-catenin signaling and cyclin D1 expression, but not changes in redox balance. Consistent with this mechanism, β-catenin deletion in Foxo null cells abrogated both the increased cyclin D1 expression and proliferation. The elucidation of a restraining effect of FOXOs on Wnt signaling in bipotential progenitors suggests that FOXO activation by accumulation of age-associated cellular stressors may be a seminal pathogenetic mechanism in the development of involutional osteoporosis. PMID:23867625

Myosin Vs organize actin cables in fission yeast

PubMed Central

Lo Presti, Libera; Chang, Fred; Martin, Sophie G.

2012-01-01

Myosin V motors are believed to contribute to cell polarization by carrying cargoes along actin tracks. In Schizosaccharomyces pombe, Myosin Vs transport secretory vesicles along actin cables, which are dynamic actin bundles assembled by the formin For3 at cell poles. How these flexible structures are able to extend longitudinally in the cell through the dense cytoplasm is unknown. Here we show that in myosin V (myo52 myo51) null cells, actin cables are curled, bundled, and fail to extend into the cell interior. They also exhibit reduced retrograde flow, suggesting that formin-mediated actin assembly is impaired. Myo52 may contribute to actin cable organization by delivering actin regulators to cell poles, as myoV∆ defects are partially suppressed by diverting cargoes toward cell tips onto microtubules with a kinesin 7–Myo52 tail chimera. In addition, Myo52 motor activity may pull on cables to provide the tension necessary for their extension and efficient assembly, as artificially tethering actin cables to the nuclear envelope via a Myo52 motor domain restores actin cable extension and retrograde flow in myoV mutants. Together these in vivo data reveal elements of a self-organizing system in which the motors shape their own tracks by transporting cargoes and exerting physical pulling forces. PMID:23051734

Myosin Vs organize actin cables in fission yeast.

PubMed

Lo Presti, Libera; Chang, Fred; Martin, Sophie G

2012-12-01

Myosin V motors are believed to contribute to cell polarization by carrying cargoes along actin tracks. In Schizosaccharomyces pombe, Myosin Vs transport secretory vesicles along actin cables, which are dynamic actin bundles assembled by the formin For3 at cell poles. How these flexible structures are able to extend longitudinally in the cell through the dense cytoplasm is unknown. Here we show that in myosin V (myo52 myo51) null cells, actin cables are curled, bundled, and fail to extend into the cell interior. They also exhibit reduced retrograde flow, suggesting that formin-mediated actin assembly is impaired. Myo52 may contribute to actin cable organization by delivering actin regulators to cell poles, as myoV defects are partially suppressed by diverting cargoes toward cell tips onto microtubules with a kinesin 7-Myo52 tail chimera. In addition, Myo52 motor activity may pull on cables to provide the tension necessary for their extension and efficient assembly, as artificially tethering actin cables to the nuclear envelope via a Myo52 motor domain restores actin cable extension and retrograde flow in myoV mutants. Together these in vivo data reveal elements of a self-organizing system in which the motors shape their own tracks by transporting cargoes and exerting physical pulling forces.

Annealing of Complementary DNA Sequences During Double-Strand Break Repair in Drosophila Is Mediated by the Ortholog of SMARCAL1.

PubMed

Holsclaw, Julie Korda; Sekelsky, Jeff

2017-05-01

DNA double-strand breaks (DSBs) pose a serious threat to genomic integrity. If unrepaired, they can lead to chromosome fragmentation and cell death. If repaired incorrectly, they can cause mutations and chromosome rearrangements. DSBs are repaired using end-joining or homology-directed repair strategies, with the predominant form of homology-directed repair being synthesis-dependent strand annealing (SDSA). SDSA is the first defense against genomic rearrangements and information loss during DSB repair, making it a vital component of cell health and an attractive target for chemotherapeutic development. SDSA has also been proposed to be the primary mechanism for integration of large insertions during genome editing with CRISPR/Cas9. Despite the central role for SDSA in genome stability, little is known about the defining step: annealing. We hypothesized that annealing during SDSA is performed by the annealing helicase SMARCAL1, which can anneal RPA-coated single DNA strands during replication-associated DNA damage repair. We used unique genetic tools in Drosophila melanogaster to test whether the fly ortholog of SMARCAL1, Marcal1, mediates annealing during SDSA. Repair that requires annealing is significantly reduced in Marcal1 null mutants in both synthesis-dependent and synthesis-independent (single-strand annealing) assays. Elimination of the ATP-binding activity of Marcal1 also reduced annealing-dependent repair, suggesting that the annealing activity requires translocation along DNA. Unlike the null mutant, however, the ATP-binding defect mutant showed reduced end joining, shedding light on the interaction between SDSA and end-joining pathways. Copyright © 2017 by the Genetics Society of America.

Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent MLH1 hypermethylation and MSH2 somatic mutations.

PubMed

Wang, Tao; Stadler, Zsofia K; Zhang, Liying; Weiser, Martin R; Basturk, Olca; Hechtman, Jaclyn F; Vakiani, Efsevia; Saltz, Lenard B; Klimstra, David S; Shia, Jinru

2018-04-01

Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2). This led to subsequent MLH1 methylation testing and next generation sequencing which demonstrated that the loss of all MMR proteins was associated with concurrent promoter hypermethylation of MLH1 and double somatic truncating mutations in MSH2. These molecular findings, in conjunction with the patient's age being 80 years and the fact that the patient had no personal or family cancer history, indicated that the MMR deficiency was highly likely sporadic in nature. Thus, the stringent Lynch syndrome type surveillance programs were not recommended to the patient and her family members. This case illustrates a rare but important scenario where a null IHC phenotype signifies complex underlying molecular alternations that bear clinical management implications, highlighting the need for recognition and awareness of such unusual IHC staining patterns.

The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence

PubMed Central

Alves de Castro, Patrícia; dos Reis, Thaila Fernanda; Dolan, Stephen K.; Manfiolli, Adriana Oliveira; Brown, Neil Andrew; Jones, Gary W.; Doyle, Sean; Riaño-Pachón, Diego M.; Squina, Fábio Márcio; Caldana, Camila; Singh, Ashutosh; Del Poeta, Maurizio; Hagiwara, Daisuke; Silva-Rocha, Rafael; Goldman, Gustavo H.

2016-01-01

Summary The serine-threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP-dependent PKA, cGMP- dependent protein kinase G and phospholipid-dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism. The ΔschA null mutant showed increased phosphorylation of SakA, the A. fumigatus Hog1 homologue. The schA null mutant has increased and decreased trehalose and glycerol accumulation, respectively, suggesting SchA performs different roles for glycerol and trehalose accumulation during osmotic stress. The schA was transcriptionally regulated by osmotic stress and this response was dependent on SakA and MpkC. The double ΔschA ΔsakA and ΔschA ΔmpkC mutants were more sensitive to osmotic stress than the corresponding parental strains. Transcriptomics and proteomics identified direct and indirect targets of SchA post-exposure to hyperosmotic stress. Finally, ΔschA was avirulent in a low dose murine infection model. Our results suggest there is a complex network of interactions amongst the A. fumigatus TOR, SakA and SchA pathways. PMID:27538790

The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence.

PubMed

Alves de Castro, Patrícia; Dos Reis, Thaila Fernanda; Dolan, Stephen K; Oliveira Manfiolli, Adriana; Brown, Neil Andrew; Jones, Gary W; Doyle, Sean; Riaño-Pachón, Diego M; Squina, Fábio Márcio; Caldana, Camila; Singh, Ashutosh; Del Poeta, Maurizio; Hagiwara, Daisuke; Silva-Rocha, Rafael; Goldman, Gustavo H

2016-11-01

The serine-threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP-dependent PKA, cGMP- dependent protein kinase G and phospholipid-dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism. The ΔschA null mutant showed increased phosphorylation of SakA, the A. fumigatus Hog1 homologue. The schA null mutant has increased and decreased trehalose and glycerol accumulation, respectively, suggesting SchA performs different roles for glycerol and trehalose accumulation during osmotic stress. The schA was transcriptionally regulated by osmotic stress and this response was dependent on SakA and MpkC. The double ΔschA ΔsakA and ΔschA ΔmpkC mutants were more sensitive to osmotic stress than the corresponding parental strains. Transcriptomics and proteomics identified direct and indirect targets of SchA post-exposure to hyperosmotic stress. Finally, ΔschA was avirulent in a low dose murine infection model. Our results suggest there is a complex network of interactions amongst the A. fumigatus TOR, SakA and SchA pathways. © 2016 John Wiley & Sons Ltd.

The ultraviolet variations of iota Cas

NASA Technical Reports Server (NTRS)

Molnar, M. R.; Mallama, A. D.; Soskey, D. G.; Holm, A. V.

1976-01-01

The Ap variable star iota Cas was observed with the photometers on OAO-2 covering the spectral range 1430-4250 A. The ultraviolet light curves show a double wave with primary minimum and maximum at phase ? 0.00 and 0.35, respectively. Secondary minimum light is at phase ? 0.65 with secondary maximum at phase ? 0.85. The light curves longward of 3150 A vary in opposition to those shortward of this 'null region'. Ground-based coude spectra show that the Fe II and Cr II line strengths have a double-wave variation such that maximum strength occurs at minimum ultraviolet light. We suggest that the strong ultraviolet opacities due to photoionization and line blanketing by these metals may cause the observed photometric variations. We have also constructed an oblique-rotator model which shows iron and chromium lying in a great circle band rather than in circular spots.

Numerical investigation of disruption characteristics for the snowflake divertor configuration in HL-2M

NASA Astrophysics Data System (ADS)

Xue, L.; Duan, X. R.; Zheng, G. Y.; Liu, Y. Q.; Pan, Y. D.; Yan, S. L.; Dokuka, V. N.; Lukash, V. E.; Khayrutdinov, R. R.

2016-05-01

Cold and hot vertical displacement events (VDEs) are frequently related to the disruption of vertically-elongated tokamaks. The weak poloidal magnetic field around the null-points of a snowflake divertor configuration may influence the vertical displacement process. In this paper, the major disruption with a cold VDE and the vertical disruption in the HL-2M tokamak are investigated by the DINA code. In order to better illustrate the effect from the weak poloidal field, a double-null snowflake configuration is compared with the standard divertor (SD) configuration under the same plasma parameters. Computational results show that the weak poloidal magnetic field can be partly beneficial for mitigating the vertical instability of the plasma under small perturbations. For major disruption, the peak poloidal halo current fraction is almost the same between the snowflake and the SD configurations. However, this fraction becomes much larger for the snowflake in the event of a hot VDE. Furthermore, during the disruption for a snowflake configuration, the distribution of electromagnetic force on a vacuum vessel gets more non-uniform during the current quench.

Blood flow in intracranial aneurysms treated with Pipeline embolization devices: computational simulation and verification with Doppler ultrasonography on phantom models

PubMed Central

2015-01-01

Purpose: The aim of this study was to validate a computational fluid dynamics (CFD) simulation of flow-diverter treatment through Doppler ultrasonography measurements in patient-specific models of intracranial bifurcation and side-wall aneurysms. Methods: Computational and physical models of patient-specific bifurcation and sidewall aneurysms were constructed from computed tomography angiography with use of stereolithography, a three-dimensional printing technology. Flow dynamics parameters before and after flow-diverter treatment were measured with pulse-wave and color Doppler ultrasonography, and then compared with CFD simulations. Results: CFD simulations showed drastic flow reduction after flow-diverter treatment in both aneurysms. The mean volume flow rate decreased by 90% and 85% for the bifurcation aneurysm and the side-wall aneurysm, respectively. Velocity contour plots from computer simulations before and after flow diversion closely resembled the patterns obtained by color Doppler ultrasonography. Conclusion: The CFD estimation of flow reduction in aneurysms treated with a flow-diverting stent was verified by Doppler ultrasonography in patient-specific phantom models of bifurcation and side-wall aneurysms. The combination of CFD and ultrasonography may constitute a feasible and reliable technique in studying the treatment of intracranial aneurysms with flow-diverting stents. PMID:25754367

Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

PubMed Central

2015-01-01

Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo groups was −1.12 (80% CI −2.93 to 0.69) and the null hypothesis was rejected in favour of futility (p=0.09). Planned sensitivity analyses of the primary outcome, using last value carried forward (LVCF) to handle missing data and using the completers' only sample, suggested that the 15 mg dose is also futile (p=0.09 for LVCF, p=0.09 for completers) but failed to reject the null hypothesis for the 45 mg dose (p=0.12 for LVCF, p=0.19 for completers). Six serious adverse events occurred in the 15 mg group, nine in the 45 mg group, and three in the placebo group; none were thought to be definitely or probably related to the study interventions. Interpretation These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson's disease. Further study of pioglitazone in a larger trial in patients with Parkinson's disease is not recommended. Funding National Institute of Neurological Disorders and Stroke. PMID:26116315

Adaptive changes in translation initiation activities for rat pancreatic protein synthesis with feeding of a high-protein diet.

PubMed

Hashi, Masaru; Yoshizawa, Fumiaki; Onozuka, Emi; Ogata, Momoko; Hara, Hiroshi

2005-08-01

We have previously demonstrated that dietary protein induced pancreatic hypergrowth in pancreaticobiliary diverted (PBD) rats. Dietary protein and dietary amino acids stimulate protein synthesis by regulating translation initiation in the rat skeletal muscle and liver. The aim of the present study was to determine whether feeding a high-protein diet induces activation of translation initiation for protein synthesis in the rat pancreas. In PBD rats in which the bile-pancreatic juice was surgically diverted to the upper ileum for 11-13 days, pancreatic dry weight and protein content were doubled compared with those in sham rats and further increased with feeding of a high-protein diet (60% casein diet) for 2 days. These pancreatic growth parameters were maintained at high levels for the next 5 days and were much higher than those of sham rats fed a high-protein diet. In both sham and PBD rats, feeding of a high-protein diet for 2 days induced phosphorylation of eukaryotic initiation factor 4E-binding protein 1 and 70-kDa ribosomal protein S6 kinase, indicating the activation of the initiation phase of translation for pancreatic protein synthesis. However, this increased phosphorylation returned to normal levels on Day 7 in PBD but not in sham rats. We concluded that feeding a high-protein diet induced pancreatic growth with increases in the translation initiation activities for pancreatic protein synthesis within 2 days and that prolonged feeding of a high-protein diet changed the initiation activities differently in sham and PBD rats.

Gravimetric system using high-speed double switching valves for low liquid flow rates

NASA Astrophysics Data System (ADS)

Cheong, Kar-Hooi; Doihara, Ryouji; Shimada, Takashi; Terao, Yoshiya

2018-07-01

This paper presents a gravimetric system developed to perform the static weighing with flying-start-and-stop (SW-FSS) calibration method at low liquid flow rates using a pair of identical high-speed switching valves as a flow diverter. Features of the gravimetric system comprise three main components: a pair of switching valves that divert the working liquid between two symmetrical flow paths; a weighing vessel equipped with an overflow inner vessel and enclosed in a weighing chamber; and a liquid discharge mechanism comprising a discharge tube and a discharge pump, used with a multi-purpose bin. These are described with an explanation of the design considerations behind each feature. The overflow inner vessel is designed with a notch in its wall and is positioned so that it does not come into contact with the liquid surface of the accumulated liquid in the weighing vessel or the side wall of the weighing vessel to obtain a good repeatability of the interactive effects between the feeding tube and the submerging working liquid, thus ensuring a correct mass reading of the liquid collection. A performance test showed that, in terms of contribution to the overall uncertainty of the standard flow rate, the pair of switching valves is capable of performing SW-FSS satisfactorily with small relative timing errors within %. However, the mass loss due to evaporation is considered a major source of error of the gravimetric system, showing a maximum error of 0.011% under the most evaporative condition tested for the longest liquid collection time of the gravimetric system.

H-mode plasmas at very low aspect ratio on the Pegasus Toroidal Experiment

DOE PAGES

Thome, Kathleen E.; Bongard, Michael W.; Barr, Jayson L.; ...

2016-09-30

H-mode is obtained atmore » $$A\\sim 1.2$$ in the Pegasus Toroidal Experiment via Ohmic heating, high-field-side fueling, and low edge recycling in both limited and diverted magnetic topologies. These H-mode plasmas show the formation of edge current and pressure pedestals and a doubling of the energy confinement time to $${{H}_{98y,2}}\\sim 1$$ . The L–H power threshold $${{P}_{\\text{LH}}}$$ increases with density, and there is no $${{P}_{\\text{LH}}}$$ minimum observed in the attainable density space. The power threshold is equivalent in limited and diverted plasmas, consistent with the FM3 model. However, the measured $${{P}_{\\text{LH}}}$$ is $$\\sim 15\\,\\,\\times $$ higher than that predicted by conventional International Tokamak Physics Activity (ITPA) scalings, and $${{P}_{\\text{LH}}}/{{P}_{\\text{ITPA}08}}$$ increases as $$A\\to 1$$ . Small ELMs are present at low input power $${{P}_{\\text{IN}}}\\sim {{P}_{\\text{LH}}}$$ , with toroidal mode number $$n\\leqslant 4$$ . At $${{P}_{\\text{IN}}}\\gg {{P}_{\\text{LH}}}$$ , they transition to large ELMs with intermediate 5 < n < 15. The dominant-n component of a large ELM grows exponentially, while other components evolve nonlinearly and can damp prior to the crash. Direct measurements of the current profile in the pedestal region show that both ELM types exhibit a generation of a current-hole, followed by a pedestal recovery. Large ELMs are shown to further expel a current-carrying filament. Small ELM suppression via injection of low levels of helical current into the edge plasma region is also indicated.« less

Null result for violation of the equivalence principle with free-fall rotating gyroscopes

NASA Astrophysics Data System (ADS)

Luo, J.; Nie, Y. X.; Zhang, Y. Z.; Zhou, Z. B.

2002-02-01

The differential acceleration between a rotating mechanical gyroscope and a nonrotating one is directly measured by using a double free-fall interferometer, and no apparent differential acceleration has been observed at the relative level of 2×10-6. It means that the equivalence principle is still valid for rotating extended bodies, i.e., the spin-gravity interaction between the extended bodies has not been observed at this level. Also, to the limit of our experimental sensitivity, there is no observed asymmetrical effect or antigravity of the rotating gyroscopes as reported by Hayasaka et al.

Flatspace chiral supergravity

NASA Astrophysics Data System (ADS)

Bagchi, Arjun; Basu, Rudranil; Detournary, Stéphane; Parekh, Pulastya

2018-05-01

We propose a holographic duality between a 2 dimensional (2d) chiral superconformal field theory and a certain theory of supergravity in 3d with flatspace boundary conditions that is obtained as a double scaling limit of a parity breaking theory of supergravity. We show how the asymptotic symmetries of the bulk theory reduce from the "despotic" super Bondi-Metzner-Sachs algebra (or equivalently the inhomogeneous super Galilean conformal algebra) to a single copy of the super-Virasoro algebra in this limit and also reproduce the same reduction from a study of null vectors in the putative 2d dual field theory.

Influence of proximal end diverting colostomy on the healing of left-sided colonic anastomosis: an experimental study in rats.

PubMed

Bielecki, K; Grotowski, M; Kalczak, M

1995-01-01

The purpose of this study was to evaluate the healing of an experimental left-sided colonic anastomosis in rats protected by an end diverting proimal colostomy. The anastomoses were studied by radiological and biochemical examination and breaking strength was estimated. The results were compared with a non-operated group and with a group of rats having a non-defunctional anastomosis constructed in the same manner. In animals with an end diverting colostomy, anastomotic protein levels and enzymic activity were lower than in those with a colostomy, and the development of anastomotic strength was delayed compared with those not defunctioned.

AASHTO, 26 other groups urge lawmakers not to divert user fees in climate and energy legislation

DOT National Transportation Integrated Search

2010-04-01

In a letter to three senators who are crafting climate change legislation, the American Association of the State Highway and Transportation Officials along with 26 other groups urged the lawmakers to resist diverting funding derived from fuel taxes t...

LEE VINING INTAKE LOOKING NORTH. DIVERTED WATER FOR CITY OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

LEE VINING INTAKE LOOKING NORTH. DIVERTED WATER FOR CITY OF LOS ANGELES USED TO GO OUT VIA COVERED CONDUIT TO RIGHT OF PICTURE SPACE. SCORCHED SAGE IN FOREGROUND FROM RECENT FOREST FIRE - Los Angeles Aqueduct, Lee Vining Intake Structure, Los Angeles, Los Angeles County, CA

Flow-diverting Stent in the Treatment of Cervical Carotid Dissection and Pseudoaneurysm: Review of Literature and Case Report.

PubMed

Baptista-Sincos, Anna Paula Weinhardt; Simplício, Aline Bigatão; Sincos, Igor Rafael; Leaderman, Alex; Neto, Fernando Saliture; Moraes, Adjaldes; Aun, Ricardo

2018-01-01

The endovascular technique has been recommended over the past few years to extracranial carotid dissection and pseudoaneurysm with promising results, especially after medical therapy failure. Flow-diverting stents are an alternative for complex cases. These stents have proven to be effective treatment devices for intracranial aneurysms. The reference list of Pham's systematic review, published in 2011, and Seward's literature review, published in 2015, was considered, as well as all new articles with eligible features. Search was conducted on specific databases: MEDLINE and Literatura Latino-Americana e do Caribe em Ciências da Saúde. For carotid dissection and pseudoaneurysm, our review yielded 3 published articles including 12 patients. The technical success rate of flow-diverting stent was 100% with no procedural complication described. Mean clinical follow-up was 27.2 months (range 5-48), and in 5 months' angiographic follow-up, all lesions had healed. No new neurological events were reported during the clinical follow-up. Flow diverter stent use on intracranial and peripheral vascular surgery demonstrates satisfactory initial results, but it is still under investigation. There are very few cases treated till now and the initial results with flow-diverting stents to cervical carotid dissection are promising. In well-selected cases, where simple embolization or conventional stent is not appropriate, this technic may be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

The Diverted Dream Revisited.

ERIC Educational Resources Information Center

Clowes, Darrel

In their book, "The Diverted Dream," Brint and Karabel describe the growth of the American community college movement from 1900 to 1985 and claim that the colleges no longer act as stepping stones to four-year colleges and universities. Instead, the authors claim, the colleges are vocationalizing curricula and focusing on preparing…

30 CFR 250.1613 - Diverter systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... number of turns in the vent line(s) downstream of the spool outlet flange, and the radius of curvature of... utilizes only one spool outlet, branch lines shall be installed to provide downwind diversion capability, and (2) No spool outlet or diverter line internal diameter shall be less than 10 inches, except that...

30 CFR 250.1613 - Diverter systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... a minimum number of turns in the vent line(s) downstream of the spool outlet flange, and the radius... system utilizes only one spool outlet, branch lines shall be installed to provide downwind diversion capability, and (2) No spool outlet or diverter line internal diameter shall be less than 10 inches, except...

30 CFR 250.1613 - Diverter systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... number of turns in the vent line(s) downstream of the spool outlet flange, and the radius of curvature of... utilizes only one spool outlet, branch lines shall be installed to provide downwind diversion capability, and (2) No spool outlet or diverter line internal diameter shall be less than 10 inches, except that...

30 CFR 250.1613 - Diverter systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... number of turns in the vent line(s) downstream of the spool outlet flange, and the radius of curvature of... utilizes only one spool outlet, branch lines shall be installed to provide downwind diversion capability, and (2) No spool outlet or diverter line internal diameter shall be less than 10 inches, except that...

A second component of the SltA-dependent cation tolerance pathway in Aspergillus nidulans.

PubMed

Mellado, Laura; Calcagno-Pizarelli, Ana Maria; Lockington, Robin A; Cortese, Marc S; Kelly, Joan M; Arst, Herbert N; Espeso, Eduardo A

2015-09-01

The transcriptional response to alkali metal cation stress is mediated by the zinc finger transcription factor SltA in Aspergillus nidulans and probably in other fungi of the pezizomycotina subphylum. A second component of this pathway has been identified and characterized. SltB is a 1272 amino acid protein with at least two putative functional domains, a pseudo-kinase and a serine-endoprotease, involved in signaling to the transcription factor SltA. Absence of SltB activity results in nearly identical phenotypes to those observed for a null sltA mutant. Hypersensitivity to a variety of monovalent and divalent cations, and to medium alkalinization are among the phenotypes exhibited by a null sltB mutant. Calcium homeostasis is an exception and this cation improves growth of sltΔ mutants. Moreover, loss of kinase HalA in conjunction with loss-of-function sltA or sltB mutations leads to pronounced calcium auxotrophy. sltA sltB double null mutants display a cation stress sensitive phenotype indistinguishable from that of single slt mutants showing the close functional relationship between these two proteins. This functional relationship is reinforced by the fact that numerous mutations in both slt loci can be isolated as suppressors of poor colonial growth resulting from certain null vps (vacuolar protein sorting) mutations. In addition to allowing identification of sltB, our sltB missense mutations enabled prediction of functional regions in the SltB protein. Although the relationship between the Slt and Vps pathways remains enigmatic, absence of SltB, like that of SltA, leads to vacuolar hypertrophy. Importantly, the phenotypes of selected sltA and sltB mutations demonstrate that suppression of null vps mutations is not dependent on the inability to tolerate cation stress. Thus a specific role for both SltA and SltB in the VPS pathway seems likely. Finally, it is noteworthy that SltA and SltB have a similar, limited phylogenetic distribution, being restricted to the pezizomycotina subphylum. The relevance of the Slt regulatory pathway to cell structure, intracellular trafficking and cation homeostasis and its restricted phylogenetic distribution makes this pathway of general interest for future investigation and as a source of targets for antifungal drugs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Olfactory ability and object memory in three mouse models of varying body weight, metabolic hormones, and adiposity

PubMed Central

Tucker, Kristal R.; Godbey, Steven J.; Thiebaud, Nicolas; Fadool, Debra Ann

2012-01-01

Physiological and nutritional state can modify sensory ability and perception through hormone signaling. Obesity and related metabolic disorders present a chronic imbalance in hormonal signaling that could impact sensory systems. In the olfactory system, external chemical cues are transduced into electrical signals to encode information. It is becoming evident that this system can also detect internal chemical cues in the form of molecules of energy homeostasis and endocrine hormones, whereby neurons of the olfactory system are modulated to change animal behavior towards olfactory cues. We hypothesized that chronic imbalance in hormonal signaling and energy homeostasis due to obesity would thereby disrupt olfactory behaviors in mice. To test this idea, we utilized three mouse models of varying body weight, metabolic hormones, and visceral adiposity – 1) C57BL6/J mice maintained on a condensed-milk based, moderately high-fat diet (MHF) of 32% fat for 6 months as the diet-induced obesity model, 2) an obesity-resistant, lean line of mice due to a gene-targeted deletion of a voltage-dependent potassium channel (Kv1.3-null), and 3) a genetic model of obesity as a result of a gene-targeted deletion of the melanocortin 4 receptor (MC4R-null). Diet-induced obese (DIO) mice failed to find fatty-scented hidden peanut butter cracker, based solely on olfactory cues, any faster than an unscented hidden marble, initially suggesting general anosmia. However, when these DIO mice were challenged to find a sweet-scented hidden chocolate candy, they had no difficulty. Furthermore, DIO mice were able to discriminate between fatty acids that differ by a single double bond and are components of the MHF diet (linoleic and oleic acid) in a habituation-dishabituation paradigm. Obesity-resistant, Kv1.3-null mice exhibited no change in scented object retrieval when placed on the MHF-diet, nor did they perform differently than wild-type mice in parallel habituation-dishabituation paradigms of fatty food-related odor components. Genetically obese, MC4R-null mice successfully found hidden scented objects, but did so more slowly than lean, wild-type mice, in an object-dependent fashion. In habituation-dishabituation trials of general odorants, MC4R-null mice failed to discriminate a novel odor, but were able to distinguish two fatty acids. Object memory recognition tests for short- and long-term memory retention demonstrated that maintenance on the MHF diet did not modify ability to perform these tasks independent of whether mice became obese or were resistant to weight gain (Kv1.3-null), however, the genetically predisposed obese mice (MC4R-null) failed the long-term object memory recognition performed at 24 hours. These results demonstrate that even though both the DIO mice and genetically predisposed obese mice are obese, they vary in the degree to which they exhibit behavioral deficits in odor detection, odor discrimination, and long-term memory. PMID:22995978

Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

PubMed Central

Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard

2013-01-01

Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor. PMID:24459330

1α,25(OH)2-dihydroxyvitamin D3/VDR protects the skin from UVB-induced tumor formation by interacting with the β-catenin pathway.

PubMed

Jiang, Yan J; Teichert, Arnaud E; Fong, Frankie; Oda, Yuko; Bikle, Daniel D

2013-07-01

Ultra violet (UV) irradiation, in particular UVB, is the single most important carcinogen for skin tumor formation. UVB induces genetic mutations and immune suppression, which lead to abnormal cell proliferation and eventually tumor formation. Previously studies from our group and others demonstrated that both global and epidermal specific VDR knock out mice are predisposed to either chemical (DMBA)- or long-term UVB-induced skin tumor formation, paralleled by an increase in β-catenin signaling. Using primary cultured human keratinocytes, we further demonstrated that 1,25(OH)2-dihydroxyvitamin D3 (1,25(OH)2D3) suppresses cyclin D1 and Gli1 which are regulated by β-catenin/TCF signaling and have a critical role in epidermal carcinogenesis. Blockage of VDR by siRNA resulted in hyperproliferation of keratinocytes, and increased expression of cyclin D1 and Gli1. In addition, we also showed that 1,25(OH)2D3/VDR directly regulates transcriptional activity of β-catenin/TCF signaling using the -catenin reporter TopGlow. Using K14 driven tamoxifen-induced cre recombinase to delete both VDR and β-catenin in keratinocytes of mice following the first hair follicle cycle, we found that ablation of epidermal specific β-catenin cannot rescue VDR null mice from UVB-induced skin tumor formation. Further study using VDR or β-catenin single null mice is necessary to compare with the data from double null mice. This article is part of a Special Issue entitled 'Vitamin D Workshop'. Copyright © 2012 Elsevier Ltd. All rights reserved.

A rapid quantification of binocular misalignment without recording eye movements: Vertical and torsional alignment nulling.

PubMed

Beaton, Kara H; Shelhamer, Mark J; Roberts, Dale C; Schubert, Michael C

2017-05-01

Small, innate asymmetries between the left and right otolith organs can cause ocular misalignment with symptoms that include double vision and motion sickness. Additionally, ocular misalignment affects nearly 5% of the US population. We have developed a portable, non-invasive technology that uses subjective perception of binocular visual signals to estimate relative binocular alignment. The Vertical Alignment Nulling (VAN) and Torsional Alignment Nulling (TAN) tests ask subjects to view one red and one blue line on a tablet computer while looking through color-matched red and blue filters so that each eye sees only one of the lines. Subjects align the red and blue lines, which are initially vertically offset from one another during VAN or rotated relative to one another during TAN, until they perceive a single continuous line. Ocular misalignments are inferred from actual offsets in the final line positions. During testing, all binocular visual cues are eliminated by employing active-matrix organic light-emitting diode (AMOLED) technology and testing in darkness. VAN and TAN can accurately account for visual offsets induced by prisms, and test-retest reliability is excellent, with resolution better than many current standard clinical tests. VAN and TAN tests are similar to the clinical Lancaster red-green test. However, VAN and TAN employ inexpensive, hand-held hardware that can be self-administered with results that are quickly quantifiable. VAN and TAN provide simple, sensitive, and quantitative measures of binocular positioning alignment that may be useful for detecting subtle abnormalities in ocular positioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure.

PubMed

Hamblet, Natasha S; Lijam, Nardos; Ruiz-Lozano, Pilar; Wang, Jianbo; Yang, Yasheng; Luo, Zhenge; Mei, Lin; Chien, Kenneth R; Sussman, Daniel J; Wynshaw-Boris, Anthony

2002-12-01

The murine dishevelled 2 (Dvl2) gene is an ortholog of the Drosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway. Dvl2-deficient mice were produced to determine the role of Dvl2 in mammalian development. Mice containing null mutations in Dvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2(-/-) mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, approximately 90% of Dvl2(-/-) mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1 and Dvl2. Somite differentiation markers used to analyze Dvl2(-/-) and Dvl1(-/-);Dvl2(-/-) mutant embryos revealed mildly aberrant expression of Uncx4.1, delta 1 and myogenin, suggesting defects in somite segmentation. Finally, 2-3% of Dvl2(-/-) embryos displayed thoracic spina bifida, while virtually all Dvl1/2 double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis, somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes.

Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: a double-blind placebo-controlled trial.

PubMed

Del Fabbro, Egidio; Dev, Rony; Hui, David; Palmer, Lynn; Bruera, Eduardo

2013-04-01

Prior studies have suggested that melatonin, a frequently used integrative medicine, can attenuate weight loss, anorexia, and fatigue in patients with cancer. These studies were limited by a lack of blinding and absence of placebo controls. The primary purpose of this study was to compare melatonin with placebo for appetite improvement in patients with cancer cachexia. We performed a randomized, double-blind, 28-day trial of melatonin 20 mg versus placebo in patients with advanced lung or GI cancer, appetite scores ≥ 4 on a 0 to 10 scale (10 = worst appetite), and history of weight loss ≥ 5%. Assessments included weight, symptoms by the Edmonton Symptom Assessment Scale, and quality of life by the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire. Differences between groups from baseline to day 28 were analyzed using one-sided, two-sample t tests or Wilcoxon two-sample tests. Interim analysis halfway through the trial had a Lan-DeMets monitoring boundary with an O'Brien-Fleming stopping rule. Decision boundaries were to accept the null hypothesis of futility if the test statistic z < 0.39 (P ≥ .348) and reject the null hypothesis if z > 2.54 (P ≤ .0056). After interim analysis of 48 patients, the study was closed for futility. There were no significant differences between groups for appetite (P = .78) or other symptoms, weight (P = .17), FAACT score (P = .95), toxicity, or survival from baseline to day 28. In cachectic patients with advanced cancer, oral melatonin 20 mg at night did not improve appetite, weight, or quality of life compared with placebo.

Aberrant Muscle Antigen Exposure in Mice Is Sufficient to Cause Myositis in a Treg Cell–Deficient Milieu

PubMed Central

Young, Nicholas A; Sharma, Rahul; Friedman, Alexandra K; Kaffenberger, Benjamin H; Bolon, Brad; Jarjour, Wael N

2013-01-01

Objective Myositis is associated with muscle-targeted inflammation and is observed in some Treg cell–deficient mouse models. Because an autoimmune pathogenesis has been strongly implicated, the aim of this study was to investigate the hypothesis that abnormal exposure to muscle antigens, as observed in muscle injury, can induce autoimmune-mediated myositis in susceptible hosts. Methods FoxP3 mutant (scurfy) mice were mated to synaptotagmin VII (Syt VII) mutant mice, which resulted in a new mouse strain that combines impaired membrane resealing with Treg cell deficiency. Lymphocyte preparations from double-mutant mice were adoptively transferred intraperitoneally, with or without purified Treg cells, into recombination-activating gene 1 (RAG-1)–null recipients. Lymph node cells from mice with the FoxP3 mutation were transferred into RAG-1–null mice either 1) intraperitoneally in conjunction with muscle homogenate or purified myosin protein or 2) intramuscularly with or without cotransfer of purified Treg cells. Results FoxP3-deficient mouse lymph node cells transferred in conjunction with myosin protein or muscle homogenate induced robust skeletal muscle inflammation. The infiltrates consisted predominantly of CD4+ and CD8+ T cells, a limited number of macrophages, and no B cells. Significant inflammation was also seen in similar experiments using lymph node cells from FoxP3/Syt VII double-mutant mice but was absent in experiments using adoptive transfer of FoxP3 mutant mouse cells alone. The cotransfer of Treg cells completely suppressed myositis. Conclusion These data, derived from a new, reproducible model, demonstrate the critical roles of Treg cell deficiency and aberrant muscle antigen exposure in the priming of autoreactive cells to induce myositis. This mouse system has multifaceted potential for examining the interplay in vivo between tissue injury and autoimmunity. PMID:24022275

Dmc1 Functions in a Saccharomyces Cerevisiae Meiotic Pathway That Is Largely Independent of the Rad51 Pathway

PubMed Central

Dresser, M. E.; Ewing, D. J.; Conrad, M. N.; Dominguez, A. M.; Barstead, R.; Jiang, H.; Kodadek, T.

1997-01-01

Meiotic recombination in the yeast Saccharomyces cerevisiae requires two similar recA-like proteins, Dmc1p and Rad51p. A screen for dominant meiotic mutants provided DMC1-G126D, a dominant allele mutated in the conserved ATP-binding site (specifically, the A-loop motif) that confers a null phenotype. A recessive null allele, dmc1-K69E, was isolated as an intragenic suppressor of DMC1-G126D. Dmc1-K69Ep, unlike Dmc1p, does not interact homotypically in a two-hybrid assay, although it does interact with other fusion proteins identified by two-hybrid screen with Dmc1p. Dmc1p, unlike Rad51p, does not interact in the two-hybrid assay with Rad52p or Rad54p. However, Dmc1p does interact with Tid1p, a Rad54p homologue, with Tid4p, a Rad16p homologue, and with other fusion proteins that do not interact with Rad51p, suggesting that Dmc1p and Rad51p function in separate, though possibly overlapping, recombinational repair complexes. Epistasis analysis suggests that DMC1 and RAD51 function in separate pathways responsible for meiotic recombination. Taken together, our results are consistent with a requirement for DMC1 for meiosis-specific entry of DNA double-strand break ends into chromatin. Interestingly, the pattern on CHEF gels of chromosome fragments that result from meiotic DNA double-strand break formation is different in DMC1 mutant strains from that seen in rad50S strains. PMID:9335591

Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection

PubMed Central

Minandri, Fabrizia; Imperi, Francesco; Frangipani, Emanuela; Bonchi, Carlo; Visaggio, Daniela; Facchini, Marcella; Pasquali, Paolo; Bragonzi, Alessandra

2016-01-01

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. Iron is essential for bacterial growth, and P. aeruginosa expresses multiple iron uptake systems, whose role in lung infection deserves further investigation. P. aeruginosa Fe3+ uptake systems include the pyoverdine and pyochelin siderophores and two systems for heme uptake, all of which are dependent on the TonB energy transducer. P. aeruginosa also has the FeoB transporter for Fe2+ acquisition. To assess the roles of individual iron uptake systems in P. aeruginosa lung infection, single and double deletion mutants were generated in P. aeruginosa PAO1 and characterized in vitro, using iron-poor media and human serum, and in vivo, using a mouse model of lung infection. The iron uptake-null mutant (tonB1 feoB) and the Fe3+ transport mutant (tonB1) did not grow aerobically under low-iron conditions and were avirulent in the mouse model. Conversely, the wild type and the feoB, hasR phuR (heme uptake), and pchD (pyochelin) mutants grew in vitro and caused 60 to 90% mortality in mice. The pyoverdine mutant (pvdA) and the siderophore-null mutant (pvdA pchD) grew aerobically in iron-poor media but not in human serum, and they caused low mortality in mice (10 to 20%). To differentiate the roles of pyoverdine in iron uptake and virulence regulation, a pvdA fpvR double mutant defective in pyoverdine production but expressing wild-type levels of pyoverdine-regulated virulence factors was generated. Deletion of fpvR in the pvdA background partially restored the lethal phenotype, indicating that pyoverdine contributes to the pathogenesis of P. aeruginosa lung infection by combining iron transport and virulence-inducing capabilities. PMID:27271740

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, Nicholas A., E-mail: namurphy@cfa.harvard.edu; Parnell, Clare E.; Haynes, Andrew L.

2015-10-15

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

Sulfide Stress Cracking Behavior of a Martensitic Steel Controlled by Tempering Temperature

PubMed Central

Sun, Yu; Wang, Qian; Gu, Shunjie; He, Zaoneng; Wang, Qingfeng; Zhang, Fucheng

2018-01-01

A medium-carbon Cr–Mo–V martensitic steel was thermally processed by quenching (Q) at 890 °C and tempering (T) at increasing temperatures from 650 °C to 720 °C and the effect of tempering temperature, Tt, on sulfide stress cracking (SSC) behaviors was estimated mainly via double cantilever beam (DCB) and electrochemical hydrogen permeation (EHP) tests and microstructure characterization. The results indicate that the threshold stress intensity factor for SSC, KISSC, increased with increasing Tt. The overall and local H concentration around the inclusions decreased with increasing Tt, due to reductions in the amounts of solute atoms, grain boundaries and dislocations, which effectively prevented SSC initiation. Also, increasing Tt caused an increased fraction of high-angle boundaries, which evidently lowered the SSC propagation rate by more frequently diverting the propagating direction and accordingly restricted SSC propagation. The overall SSC resistance of this Q&T–treated steel was therefore significantly enhanced. PMID:29522494

On-site sanitation: a viable alternative to modern wastewater treatment plants.

PubMed

Lamichhane, K M

2007-01-01

Rapid population growth and urbanization are exerting excessive pressure on soil and water resources. To address these problems this paper proposes a cheap and sustainable alternative sanitation system, which accelerates nutrient recycling ("closing the loop"): ecological sanitation (ecosan) is a potential alternative to conventional sanitation systems that replenishes the organic matter and nutrients of the soil that are taken off as the crop harvest. A comparison is made of the environmental and the operation and maintenance costs between a modern wastewater treatment plant and on-site sanitation. An elevated double box urine diverting toilet ("ecotoilet") is proposed and its advantages and disadvantages over a system with a centrally controlled modern WWTP are discussed. Bagmati Area Sewerage Project in Kathmandu is taken as an example of modern WWTP and ecosan being practiced in a village in Nepal is taken as an example of ecotoilet for the comparison.

Heterologous Expression of Der Homologs in an Escherichia coli der Mutant and Their Functional Complementation

PubMed Central

Choi, Eunsil; Kang, Nalae; Jeon, Young; Pai, Hyun-Sook

2016-01-01

ABSTRACT The unique Escherichia coli GTPase Der (double Era-like GTPase), which contains tandemly repeated GTP-binding domains, has been shown to play an essential role in 50S ribosomal subunit biogenesis. The depletion of Der results in the accumulation of precursors of 50S ribosomal subunits that are structurally unstable at low Mg2+ concentrations. Der homologs are ubiquitously found in eubacteria. Conversely, very few are conserved in eukaryotes, and none is conserved in archaea. In the present study, to verify their conserved role in bacterial 50S ribosomal subunit biogenesis, we cloned Der homologs from two gammaproteobacteria, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium; two pathogenic bacteria, Staphylococcus aureus and Neisseria gonorrhoeae; and the extremophile Deinococcus radiodurans and then evaluated whether they could functionally complement the E. coli der-null phenotype. Only K. pneumoniae and S. Typhimurium Der proteins enabled the E. coli der-null strain to grow under nonpermissive conditions. Sucrose density gradient experiments revealed that the expression of K. pneumoniae and S. Typhimurium Der proteins rescued the structural instability of 50S ribosomal subunits, which was caused by E. coli Der depletion. To determine what allows their complementation, we constructed Der chimeras. We found that only Der chimeras harboring both the linker and long C-terminal regions could reverse the growth defects of the der-null strain. Our findings suggest that ubiquitously conserved essential GTPase Der is involved in 50S ribosomal subunit biosynthesis in various bacteria and that the linker and C-terminal regions may participate in species-specific recognition or interaction with the 50S ribosomal subunit. IMPORTANCE In Escherichia coli, Der (double Era-like GTPase) is an essential GTPase that is important for the production of mature 50S ribosomal subunits. However, to date, its precise role in ribosome biogenesis has not been clarified. In this study, we used five Der homologs from gammaproteobacteria, pathogenic bacteria, and an extremophile to elucidate their conserved function in 50S ribosomal subunit biogenesis. Among them, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium Der homologs implicated the participation of Der in ribosome assembly in E. coli. Our results show that the linker and C-terminal regions of Der homologs are correlated with its functional complementation in E. coli der mutants, suggesting that they are involved in species-specific recognition or interaction with 50S ribosomal subunits. PMID:27297882

Randomized sham-controlled, double-blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain.

PubMed

van Tilburg, C W J; Stronks, D L; Groeneweg, J G; Huygen, F J P M

2017-03-01

Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain. Randomized sham-controlled, double-blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0-10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. pain reduction. Secondary outcome measure: Global Perceived Effect. No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction. Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham-controlled, double-blind, multicenter clinical trial on the effect of radiofrequency at the ramus communicans for lumbar disc pain was conducted. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

EVALUATION OF DIVERSION AND COSTS FOR SELECTED DROP-OFF RECYCLING PROGRAMS - A MITE PROGRAM EVALUATION

EPA Science Inventory

This analysis was undertaken in 1993-94 to examine a sample of drop-off recycling programs in the United States and Canada to determine the quantities of recyclable materials diverted, the cost of diverting those materials, and the impact of a wide range of independent variables ...

30 CFR 250.434 - What are the recordkeeping requirements for diverter actuations and tests?

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.434 What are the recordkeeping... the facility for the duration of drilling the well. Blowout Preventer (BOP) System Requirements ...

30 CFR 250.434 - What are the recordkeeping requirements for diverter actuations and tests?

Code of Federal Regulations, 2013 CFR

2013-07-01

... ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.434 What are the recordkeeping... the facility for the duration of drilling the well. Blowout Preventer (BOP) System Requirements ...

30 CFR 250.434 - What are the recordkeeping requirements for diverter actuations and tests?

Code of Federal Regulations, 2012 CFR

2012-07-01

... ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Diverter System Requirements § 250.434 What are the recordkeeping... the facility for the duration of drilling the well. Blowout Preventer (BOP) System Requirements ...

76 FR 59664 - Notice of Intent To Prepare an Environmental Impact Statement For Divert Activities and Exercises...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... Mariana Islands. The proposed divert activities and exercises would involve airfield improvements designed... designed to support up to one tanker squadron of 12 KC-135 aircraft and its approximately 500 support... delivery capability; and associated pavement markings, lighting, security, and other related infrastructure...

Numerical simulation of helical flow in a cylindrical channel

NASA Astrophysics Data System (ADS)

Vasiliev, A.; Sukhanovskii, A.; Stepanov, R.

2017-06-01

Numerical simulation of the helical flow in a cylindrical channel with diverter was carried out using open-source software OpenFOAM Extend 4.0. The velocity, vorticity and helicity density distributions were analyzed. It was shown that azimithal contribution of helicity is negative near the wall and positive in the center. In opposite axial helicity contribution is negative in the center and positive near the wall. Analysis of helicity of non-axisymmetric part of the flow showed that it has substantial values near the diverter but than rapidly decreases with y (axial coordinate) and further downstream it can be neglected. Dependencies of integrated values of azimuthal Hϕ and axial Hy contributions of helicity density on y show a remarkable quantitative similarity. It was found that integral values of Hϕ and Hy are negative for all y. Magnitudes of Hϕ and Hy decrease after the diverter up to y ≈ 70 mm and after that monotonically increase. The flow behind the diverter is characterized by substantial amount of helicity and can be used as a helicity generator.

Simple Solutions for Space Station Audio Problems

NASA Technical Reports Server (NTRS)

Wood, Eric

2016-01-01

Throughout this summer, a number of different projects were supported relating to various NASA programs, including the International Space Station (ISS) and Orion. The primary project that was worked on was designing and testing an acoustic diverter which could be used on the ISS to increase sound pressure levels in Node 1, a module that does not have any Audio Terminal Units (ATUs) inside it. This acoustic diverter is not intended to be a permanent solution to providing audio to Node 1; it is simply intended to improve conditions while more permanent solutions are under development. One of the most exciting aspects of this project is that the acoustic diverter is designed to be 3D printed on the ISS, using the 3D printer that was set up earlier this year. Because of this, no new hardware needs to be sent up to the station, and no extensive hardware testing needs to be performed on the ground before sending it to the station. Instead, the 3D part file can simply be uploaded to the station's 3D printer, where the diverter will be made.

In-flight medical events and aircraft diversions: one airline's experience.

PubMed

Delaune, Eugene F; Lucas, Raymond H; Illig, Petra

2003-01-01

An aging population combined with the increasing mobility of people with acute and chronic illnesses could make an increase in the frequency of in-flight medical events aboard commercial aircraft likely. To determine the incidence of each type of in-flight medical complaint, the appropriateness of medical kit contents, which factors lead to aircraft diversion, and which factors effect the appropriateness of the decision to divert. Medical complaints reported aboard a sample airline from July 1, 1999 through June 30, 2000 were studied. The frequency of aircraft diversion was related to complaint and medical assistance provided. The appropriateness of the decision to divert was determined as a function of hospital admission rates. There was an incidence of 22.6 medical complaints per million passengers and 0.1 deaths per million passengers. There were 210 diversions per million flights with one of every 12.6 incidents resulting in a diversion. When a passenger volunteer was used, they opened the medical kit 62% of the time. When a physician participated in the decision to divert the hospital admission rate was 49% versus 15% with no physician input. Variations in incidence of medical complaints cited in previous studies demonstrate the need for an industry-wide standardized reporting method of in-flight medical events. All in-flight medical complaints could likely have been adequately treated with the contents of the FM's newly mandated medical kits. Physician participation in decisions to divert aircraft should be sought as it is associated with more appropriate divert decisions.

The treatment of pseudoaneurysms with flow diverters after malignant otitis externa.

PubMed

Németh, Tamás; Szakács, László; Bella, Zsolt; Majoros, Valéria; Barzó, Pál; Vörös, Erika

2017-12-01

Background We report a case of bilateral malignant otitis externa complicated with bilateral petrous internal carotid artery pseudoaneurysms and their successful treatment with a flow diverter. Case report A 68-year-old woman with serious complications of type II diabetes mellitus had malignant otitis externa on the right side. She was treated with combined antibiotic therapy and underwent mastoidectomy for mastoiditis. She presented at our hospital with acute hemorrhage from the right external auditory canal. The emergency computed tomography (CT) angiography revealed a multiobulated pseudoaneurysm at the petrous segment of the right internal carotid artery. The pseudoaneurysm was treated with a 5 × 40-mm Surpass flow diverter. Three months later, she developed a malignant external otitis on the left side. As the infection progressed, a left-sided mastoiditis, a brain abscess, and a pseudoaneurysm at the petrous segment of the left internal carotid artery developed. The pseudoaneurysm caused bleeding from the left ear, and was treated with a 5 × 50-mm Surpass flow diverter. No recurrent bleeding was observed. Four months later, a follow-up angiography showed complete occlusion of the pseudoaneurysm on the left side, but a residual aneurysm could be detected on the right side. One year after the first intervention, the follow-up CT and magnetic resonance angiography revealed the complete occlusion of the aneurysms bilaterally. Conclusion The use of a flow diverter appears to be an efficient and safe method to occlude carotid pseudoaneurysms even in an inflammatory milieu.

A Multicenter Cohort Comparison Study of the Safety, Efficacy, and Cost of Ticagrelor Compared to Clopidogrel in Aneurysm Flow Diverter Procedures.

PubMed

Moore, Justin M; Adeeb, Nimer; Shallwani, Hussain; Gupta, Raghav; Patel, Apar S; Griessenauer, Christoph J; Youn, Roy; Siddiqui, Adnan; Ogilvy, Christopher S; Thomas, Ajith J

2017-10-01

Thromboembolic and hemorrhagic complications are among the most feared adverse events in the endovascular treatment of aneurysms, and this is particularly the case for flow diverter devices. Dual antiplatelet therapy has become standard of care; however, the safety, efficacy, and cost profiles of newer antiplatelet agents are not well characterized in the neurovascular context. To compare the safety, efficacy, and cost of one of these newer agents, ticagrelor, to the most frequently used agent, clopidogrel. A multicenter, retrospective, cohort comparison study design of consecutively treated aneurysms with flow diverter embolization device and treated with either ticagrelor or clopidogrel was performed. Data were collected on patient demographics and risk factors, procedural details, antiplatelet treatment regime, complications, and angiographic and functional outcomes. Fifty patients undergoing flow diverter device deployment and treatment with ticagrelor were compared to 53 patients undergoing flow diversion and treatment with clopidogrel. The patients' age, sex, smoking status, aneurismal morphology and size, and procedural details did not differ between the 2 groups; neither did the rate of thromboembolic and hemorrhagic complications, angiographical, and functional outcomes. Ticagrelor was more expensive when compared to clopidogrel. Ticagrelor is a safe and effective agent for prevention of thromboembolic complications following flow diverter deployment when compared to clopidogrel. However, ticagrelor remains significantly more expensive than clopidogrel, and, thus, we would advise ticagrelor be reserved for patients who are hyporesponsive to clopidogrel. Copyright © 2017 by the Congress of Neurological Surgeons

Thermal performance of a customized multilayer insulation (MLI)

NASA Technical Reports Server (NTRS)

Leonhard, K. E.

1976-01-01

The thermal performance of a LH2 tank on a shroudless vehicle was investigated. The 1.52 m (60 in) tank was insulated with 2 MLI blankets consisting of 18 double aluminized Mylar radiation shields and 19 silk net spacers. The temperature of outer space was simulated by using a cryoshroud which was maintained at near liquid hydrogen temperature. The heating effects of a payload were simulated by utilizing a thermal payload simulator (TPS) viewing the tank. The test program consisted of three major test categories: (1) null testing, (2) thermal performance testing of the tank installed MLI system, and (3) thermal testing of a customized MLI configuration. TPS surface temperatures during the null test were maintained at near hydrogen temperature and during test categories 2 and 3 at 289 K (520R). The heat flow rate through the tank installed MLI at a tank/TPS spacing of 0.457 m was 1.204 watts with no MLI on the TPS and 0.059 watts through the customized MLI with three blankets on the TPS. Reducing the tank/TPS spacing from 0.457 m to 0.152 m the heat flow through the customized MLI increased by 10 percent.

Design, Analysis and R&D of the EAST In-Vessel Components

NASA Astrophysics Data System (ADS)

Yao, Damao; Bao, Liman; Li, Jiangang; Song, Yuntao; Chen, Wenge; Du, Shijun; Hu, Qingsheng; Wei, Jing; Xie, Han; Liu, Xufeng; Cao, Lei; Zhou, Zibo; Chen, Junling; Mao, Xinqiao; Wang, Shengming; Zhu, Ning; Weng, Peide; Wan, Yuanxi

2008-06-01

In-vessel components are important parts of the EAST superconducting tokamak. They include the plasma facing components, passive plates, cryo-pumps, in-vessel coils, etc. The structural design, analysis and related R&D have been completed. The divertor is designed in an up-down symmetric configuration to accommodate both double null and single null plasma operation. Passive plates are used for plasma movement control. In-vessel coils are used for the active control of plasma vertical movements. Each cryo-pump can provide an approximately 45 m3/s pumping rate at a pressure of 10-1 Pa for particle exhaust. Analysis shows that, when a plasma current of 1 MA disrupts in 3 ms, the EM loads caused by the eddy current and the halo current in a vertical displacement event (VDE) will not generate an unacceptable stress on the divertor structure. The bolted divertor thermal structure with an active cooling system can sustain a load of 2 MW/m2 up to a 60 s operation if the plasma facing surface temperature is limited to 1500 °C. Thermal testing and structural optimization testing were conducted to demonstrate the analysis results.

Results from core-edge experiments in high Power, high performance plasmas on DIII-D

DOE PAGES

Petrie, T. W.; Fenstermacher, M. E.; Holcomb, C. T.; ...

2016-12-24

Here, significant challenges to reducing divertor heat flux in highly powered near-double null divertor (DND) hybrid plasmas, while still maintaining both high performance metrics and low enough density for application of RF heating, are identified. For these DNDs on DIII-D, the scaling of the peak heat flux at the outer target (q ⊥ P) ∝ [P SOL x I P] 0.92 for P SOL = 8-19 MW and I P = 1.0–1.4 MA, and is consistent with standard ITPA scaling for single-null H-mode plasmas. Two divertor heat flux reduction methods were tested. First, applying the puff-and-pump radiating divertor to DIII-Dmore » plasmas may be problematical at high power and H98 (≥ 1.5) due to improvement in confinement time with deuterium gas puffing which can lead to unacceptably high core density under certain conditions. Second, q ⊥ P for these high performance DNDs was reduced by ≈35% when an open divertor is closed on the common flux side of the outer divertor target (“semi-slot”) but also that heating near the slot opening is a significant source for impurity contamination of the core.« less

Double-beta decay investigation with highly pure enriched $$^{82}$$Se for the LUCIFER experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beeman, J. W.; Bellini, F.; Benetti, P.

2015-12-13

The LUCIFER project aims at deploying the first array of enriched scintillating bolometers for the investigation of neutrinoless double-beta decay of 82Se. The matrix which embeds the source is an array of ZnSe crystals, where enriched 82Se is used as decay isotope. The radiopurity of the initial components employed for manufacturing crystals, that can be operated as bolometers, is crucial for achieving a null background level in the region of interest for double-beta decay investigations. In this work, we evaluated the radioactive content in 2.5 kg of 96.3 % enriched 82Se metal, measured with a high-purity germanium detector at themore » Gran Sasso deep underground laboratory. The limits on internal contaminations of primordial decay chain elements of 232Th, 238U and 235U are respectively: <61, <110 and <74 μBq/kg at 90 % C.L. The extremely low-background conditions in which the measurement was carried out and the high radiopurity of the 82Se allowed us to establish the most stringent lower limits on the half-lives of the double-beta decay of 82Se to 0+1, 2+2 and 2+1 excited states of 82Kr of 3.4•10 22, 1.3•10 22 and 1.0•10 22 y, respectively, with a 90 % C.L.« less

Water chemistry, seepage investigation, streamflow, reservoir storage, and annual availability of water for the San Juan-Chama Project, northern New Mexico, 1942-2010

USGS Publications Warehouse

McKean, Sarah E.; Anderholm, Scott K.

2014-01-01

The Albuquerque Bernalillo County Water Utility Authority supplements the municipal water supply for the Albuquerque metropolitan area, in central New Mexico, with surface water diverted from the Rio Grande. The U.S. Geological Survey, in cooperation with the Albuquerque Bernalillo County Water Utility Authority, undertook this study in which water-chemistry data and historical streamflow were compiled and new water-chemistry data were collected to characterize the water chemistry and streamflow of the San Juan-Chama Project (SJCP). Characterization of streamflow included analysis of the variability of annual streamflow and comparison of the theoretical amount of water that could have been diverted into the SJCP to the actual amount of water that was diverted for the SJCP. Additionally, a seepage investigation was conducted along the channel between Azotea Tunnel Outlet and the streamflow-gaging station at Willow Creek above Heron Reservoir to estimate the magnitude of the gain or loss in streamflow resulting from groundwater interaction over the approximately 10-mile reach. Generally, surface-water chemistry varied with streamflow throughout the year. Streamflow ranged from high flow to low flow on the basis of the quantity of water diverted from the Rio Blanco, Little Navajo River, and Navajo River for the SJCP. Vertical profiles of the water temperature over the depth of the water column at Heron Reservoir indicated that the reservoir is seasonally stratified. The results from the seepage investigations indicated a small amount of loss of streamflow along the channel. Annual variability in streamflow for the SJCP was an indication of the variation in the climate parameters that interact to contribute to streamflow in the Rio Blanco, Little Navajo River, Navajo River, and Willow Creek watersheds. For most years, streamflow at Azotea Tunnel Outlet started in March and continued for approximately 3 months until the middle of July. The majority of annual streamflow at Azotea Tunnel Outlet occurred from May through June, with a median duration of slightly longer than a month. Years with higher maximum daily streamflow generally are associated with higher annual streamflow than years with lower maximum daily streamflow. The amount of water that can be diverted for the SJCP is controlled by the availability of streamflow and is limited by several factors including legal limits for diversion, limits from the SJCP infrastructure including the size of the diversion dams and tunnels, the capacity of Heron Reservoir, and operational constraints that limit when water can be diverted. The average annual streamflow at Azotea Tunnel Outlet was 94,710 acre-feet, and the annual streamflow at Azotea Tunnel Outlet was approximately 75 percent of the annual streamflow available for the SJCP. The average annual percentage of available streamflow not diverted for the SJCP was 14 percent because of structural limitations of the capacity of infrastructure, 1 percent because of limitations of the reservoir storage capacity, and 29 percent because of the limitations from operations. For most years, the annual available streamflow not diverted for unknown reasons exceeded the sum of the water not diverted because of structural, capacity, and operational limitations.

9 CFR 325.18 - Diverting of shipments, breaking of seals, and reloading by carrier in emergency; reporting to...

Code of Federal Regulations, 2010 CFR

2010-01-01

... seals, and reloading by carrier in emergency; reporting to Regional Director. 325.18 Section 325.18... CERTIFICATION TRANSPORTATION § 325.18 Diverting of shipments, breaking of seals, and reloading by carrier in...) In case of wreck or similar extraordinary emergency, the Department seals on a railroad car or other...

9 CFR 325.18 - Diverting of shipments, breaking of seals, and reloading by carrier in emergency; reporting to...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Diverting of shipments, breaking of seals, and reloading by carrier in emergency; reporting to Regional Director. 325.18 Section 325.18 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY...

Characteristics of Adolescents and Young Adults with ADHD Who Divert or Misuse Their Prescribed Medications

ERIC Educational Resources Information Center

Wilens, Timothy E.; Gignac, Martin; Swezey, Allison; Monuteaux, Michael C.; Biederman, Joseph

2006-01-01

Objective: Little is known about the risks and characteristics of attention-deficit/hyperactivity disorder (ADHD) patients who misuse or divert their stimulant medications. As part of a 10-year longitudinal study of youths with ADHD, the authors evaluated medication diversion or misuse at the last follow-up period. Method: Structured psychiatric…

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

On the absence of radio haloes in clusters with double relics

NASA Astrophysics Data System (ADS)

Bonafede, A.; Cassano, R.; Brüggen, M.; Ogrean, G. A.; Riseley, C. J.; Cuciti, V.; de Gasperin, F.; Golovich, N.; Kale, R.; Venturi, T.; van Weeren, R. J.; Wik, D. R.; Wittman, D.

2017-09-01

Pairs of radio relics are believed to form during cluster mergers, and are best observed when the merger occurs in the plane of the sky. Mergers can also produce radio haloes, through complex processes likely linked to turbulent re-acceleration of cosmic ray electrons. However, only some clusters with double relics also show a radio halo. Here, we present a novel method to derive upper limits on the radio halo emission, and analyse archival X-ray Chandra data, as well as galaxy velocity dispersions and lensing data, in order to understand the key parameter that switches on radio halo emission. We place upper limits on the halo power below the P1.4 GHz-M500 correlation for some clusters, confirming that clusters with double relics have different radio properties. Computing X-ray morphological indicators, we find that clusters with double relics are associated with the most disturbed clusters. We also investigate the role of different mass-ratios and time-since-merger. Data do not indicate that the merger mass-ratio has an impact on the presence or absence of radio haloes (the null hypothesis that the clusters belong to the same group cannot be rejected). However, the data suggest that the absence of radio haloes could be associated with early and late mergers, but the sample is too small to perform a statistical test. Our study is limited by the small number of clusters with double relics. Future surveys with LOFAR, ASKAP, MeerKat and SKA will provide larger samples to better address this issue.

30 CFR 250.416 - What must I include in the diverter and BOP descriptions?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.416 What must I include in the diverter... the blind-shear rams installed in the BOP stack are capable of shearing any drill pipe (including...

30 CFR 250.416 - What must I include in the diverter and BOP descriptions?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.416 What must I include in the diverter... the blind-shear rams installed in the BOP stack are capable of shearing any drill pipe (including...

30 CFR 250.416 - What must I include in the diverter and BOP descriptions?

Code of Federal Regulations, 2010 CFR

2010-07-01

... OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.416 What must I include in the diverter and BOP descriptions? You must... rams installed in the BOP stack (both surface and subsea stacks) are capable of shearing the drill pipe...

30 CFR 250.416 - What must I include in the diverter and BOP descriptions?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.416 What must I include in the diverter... the blind-shear rams installed in the BOP stack are capable of shearing any drill pipe in the hole...

50 CFR 80.21 - What if a State diverts license revenue from the control of its fish and wildlife agency?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false What if a State diverts license revenue from the control of its fish and wildlife agency? 80.21 Section 80.21 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

50 CFR 80.21 - What if a State diverts license revenue from the control of its fish and wildlife agency?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false What if a State diverts license revenue from the control of its fish and wildlife agency? 80.21 Section 80.21 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

50 CFR 80.21 - What if a State diverts license revenue from the control of its fish and wildlife agency?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false What if a State diverts license revenue from the control of its fish and wildlife agency? 80.21 Section 80.21 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

50 CFR 80.21 - What if a State diverts license revenue from the control of its fish and wildlife agency?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false What if a State diverts license revenue from the control of its fish and wildlife agency? 80.21 Section 80.21 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE...

[An investigation for standardized diagnosis and treatment of idiopathic normal-pressure hydrocephalus].

PubMed

Jiang, H J; Zhang, J M; Fu, W M; Zheng, Z; Luo, W; Zheng, Y X; Zhu, J M

2016-06-07

To investigate some important issues for diagnosis and treatment of idiopathic normal-pressure hydrocephalus (iNPH), such as standardized pre-operative assessment, initial pressure value of diverter pump, and pressure regulation during follow-up. Twenty six iNPH patients (21 males) who treated in Department of Neurosurgery of 2nd Affiliated Hospital of Zhejiang University School of Medicine from 2011 to 2015 were analyzed retrospectively. The average age was 60.5 year. The analysis focused on the treatment process of iNPH, initial pressure value of diverter pump, choice of diverter pump, and pressure regulation during follow-up. As a result, 24 cases (92.3%) had a good prognosis based on their imaging and clinical manifestations. Based on the literature and their clinical experiences, this department established a diagnosis and treatment procedure of iNPH and a pressure regulation procedure for the follow-up of iNPH. Moreover, it is proposed that choosing an anti-gravity diverter pump and making an initial pressure value 20 mmH2O less than pre-surgical cerebrospinal pressure may be beneficial for the prognosis. This standardized diagnosis and treatment procedure for iNPH is practical and effective.

Microstructured Thin Film Nitinol for a Neurovascular Flow-Diverter

PubMed Central

Chen, Yanfei; Howe, Connor; Lee, Yongkuk; Cheon, Seongsik; Yeo, Woon-Hong; Chun, Youngjae

2016-01-01

A cerebral aneurysm occurs as a result of a weakened blood vessel, which allows blood to flow into a sac or a ballooned section. Recent advancement shows that a new device, ‘flow-diverter’, can divert blood flow away from the aneurysm sac. People found that a flow-diverter based on thin film nitinol (TFN), works very effectively, however there are no studies proving the mechanical safety in irregular, curved blood vessels. Here, we study the mechanical behaviors and structural safety of a novel microstructured TFN membrane through the computational and experimental studies, which establish the fundamental aspects of stretching and bending mechanics of the structure. The result shows a hyper-elastic behavior of the TFN with a negligible strain change up to 180° in bending and over 500% in radial stretching, which is ideal in the use in neurovascular curved arteries. The simulation determines the optimal joint locations between the TFN and stent frame. In vitro experimental test qualitatively demonstrates the mechanical flexibility of the flow-diverter with multi-modal bending. In vivo micro X-ray and histopathology study demonstrate that the TFN can be conformally deployed in the curved blood vessel of a swine model without any significant complications or abnormalities. PMID:27009500

Diverter bop system and method for a bottom supported offshore drilling rig

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roche, J. R.; Alexander, G. G.; Carbaugh, W. L.

1985-06-25

A system and method for installing a fluid flow controller and telescoping spools beneath an offshore bottom supported drilling rig rotary table is disclosed. Upper and lower telescoping spools are provided for initially connecting a Diverter/BOP convertible fluid flow controller between structural casing in the well and a permanent housing beneath the drilling rig rotary table. Clamp means are provided for clamping the rig vent line to an opening in the housing wall of the fluid flow controller during drilling of the borehole through the structural casing in preparation for setting and cementing the conductor casing. In that mode, themore » system is adapted as a diverter system. After the well is drilled for the conductor casing and the conductor casing is cemented and cut off at its top, a mandrel is fitted at the top of the conductor casing to which the lower end of the lower spool may be connected. The system may be used in this configuration as a diverter system, or after removal of the vent line and connection of a kill line to the housing outlet, the system may be used as a low pressure blowout preventer system.« less

Microstructured Thin Film Nitinol for a Neurovascular Flow-Diverter

NASA Astrophysics Data System (ADS)

Chen, Yanfei; Howe, Connor; Lee, Yongkuk; Cheon, Seongsik; Yeo, Woon-Hong; Chun, Youngjae

2016-03-01

A cerebral aneurysm occurs as a result of a weakened blood vessel, which allows blood to flow into a sac or a ballooned section. Recent advancement shows that a new device, ‘flow-diverter’, can divert blood flow away from the aneurysm sac. People found that a flow-diverter based on thin film nitinol (TFN), works very effectively, however there are no studies proving the mechanical safety in irregular, curved blood vessels. Here, we study the mechanical behaviors and structural safety of a novel microstructured TFN membrane through the computational and experimental studies, which establish the fundamental aspects of stretching and bending mechanics of the structure. The result shows a hyper-elastic behavior of the TFN with a negligible strain change up to 180° in bending and over 500% in radial stretching, which is ideal in the use in neurovascular curved arteries. The simulation determines the optimal joint locations between the TFN and stent frame. In vitro experimental test qualitatively demonstrates the mechanical flexibility of the flow-diverter with multi-modal bending. In vivo micro X-ray and histopathology study demonstrate that the TFN can be conformally deployed in the curved blood vessel of a swine model without any significant complications or abnormalities.

Immortalization and characterization of osteoblast cell lines generated from wild-type and Nmp4-null mouse bone marrow stromal cells using murine telomerase reverse transcriptase (mTERT).

PubMed

Alvarez, Marta B; Childress, Paul; Philip, Binu K; Gerard-O'Riley, Rita; Hanlon, Michael; Herbert, Brittney-Shea; Robling, Alexander G; Pavalko, Fredrick M; Bidwell, Joseph P

2012-05-01

Intermittent parathyroid hormone (PTH) adds new bone to the osteoporotic skeleton; the transcription factor Nmp4/CIZ represses PTH-induced bone formation in mice and as a consequence is a potential drug target for improving hormone clinical efficacy. To explore the impact of Nmp4/CIZ on osteoblast phenotype, we immortalized bone marrow stromal cells from wildtype (WT) and Nmp4-knockout (KO) mice using murine telomerase reverse transcriptase. Clonal lines were initially chosen based on their positive staining for alkaline phosphatase and capacity for mineralization. Disabling Nmp4/CIZ had no gross impact on osteoblast phenotype development. WT and KO clones exhibited identical sustained growth, reduced population doubling times, extended maintenance of the mature osteoblast phenotype, and competency for differentiating toward the osteoblast and adipocyte lineages. Additional screening of the immortalized cells for PTH-responsiveness permitted further studies with single WT and KO clones. We recently demonstrated that PTH-induced c-fos femoral mRNA expression is enhanced in Nmp4-KO mice and in the present study we observed that hormone stimulated either an equivalent or modestly enhanced increase in c-fos mRNA expression in both primary null and KO clone cells depending on PTH concentration. The null primary osteoblasts and KO clone cells exhibited a transiently enhanced response to bone morphogenetic protein 2 (BMP2). The clones exhibited lower and higher expressions of the PTH receptor (Pthr1) and the BMP2 receptor (Bmpr1a, Alk3), respectively, as compared to primary cells. These immortalized cell lines will provide a valuable tool for disentangling the complex functional roles underlying Nmp4/CIZ regulation of bone anabolism. Copyright © 2011 Wiley Periodicals, Inc.

Expression of the voltage-gated potassium channel KCNQ1 in mammalian taste bud cells and the effect of its null-mutation on taste preferences.

PubMed

Wang, Hong; Iguchi, Naoko; Rong, Qi; Zhou, Minliang; Ogunkorode, Martina; Inoue, Masashi; Pribitkin, Edmund A; Bachmanov, Alexander A; Margolskee, Robert F; Pfeifer, Karl; Huang, Liquan

2009-01-20

Vertebrate taste buds undergo continual cell turnover. To understand how the gustatory progenitor cells in the stratified lingual epithelium migrate and differentiate into different types of mature taste cells, we sought to identify genes that were selectively expressed in taste cells at different maturation stages. Here we report the expression of the voltage-gated potassium channel KCNQ1 in mammalian taste buds of mouse, rat, and human. Immunohistochemistry and nuclear staining showed that nearly all rodent and human taste cells express this channel. Double immunostaining with antibodies against type II and III taste cell markers validated the presence of KCNQ1 in these two types of cells. Co-localization studies with cytokeratin 14 indicated that KCNQ1 is also expressed in type IV basal precursor cells. Null mutation of the kcnq1 gene in mouse, however, did not alter the gross structure of taste buds or the expression of taste signaling molecules. Behavioral assays showed that the mutant mice display reduced preference to some umami substances, but not to any other taste compounds tested. Gustatory nerve recordings, however, were unable to detect any significant change in the integrated nerve responses of the mutant mice to umami stimuli. These results suggest that although it is expressed in nearly all taste bud cells, the function of KCNQ1 is not required for gross taste bud development or peripheral taste transduction pathways, and the reduced preference of kcnq1-null mice in the behavioral assays may be attributable to the deficiency in the central nervous system or other organs.

Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteins.

PubMed

O'Rourke, Thomas W; Doudican, Nicole A; Mackereth, Melinda D; Doetsch, Paul W; Shadel, Gerald S

2002-06-01

The mitochondrial genome is a significant target of exogenous and endogenous genotoxic agents; however, the determinants that govern this susceptibility and the pathways available to resist mitochondrial DNA (mtDNA) damage are not well characterized. Here we report that oxidative mtDNA damage is elevated in strains lacking Ntg1p, providing the first direct functional evidence that this mitochondrion-localized, base excision repair enzyme functions to protect mtDNA. However, ntg1 null strains did not exhibit a mitochondrial respiration-deficient (petite) phenotype, suggesting that mtDNA damage is negotiated by the cooperative actions of multiple damage resistance pathways. Null mutations in ABF2 or PIF1, two genes implicated in mtDNA maintenance and recombination, exhibit a synthetic-petite phenotype in combination with ntg1 null mutations that is accompanied by enhanced mtDNA point mutagenesis in the corresponding double-mutant strains. This phenotype was partially rescued by malonic acid, indicating that reactive oxygen species generated by the electron transport chain contribute to mitochondrial dysfunction in abf2 Delta strains. In contrast, when two other genes involved in mtDNA recombination, CCE1 and NUC1, were inactivated a strong synthetic-petite phenotype was not observed, suggesting that the effects mediated by Abf2p and Pif1p are due to novel activities of these proteins other than recombination. These results document the existence of recombination-independent mechanisms in addition to base excision repair to cope with oxidative mtDNA damage in Saccharomyces cerevisiae. Such systems are likely relevant to those operating in human cells where mtDNA recombination is less prevalent, validating yeast as a model system in which to study these important issues.

Epidermal Growth Factor Receptor Expression Modulates Antitumor Efficacy of Vandetanib or Cediranib Combined With Radiotherapy in Human Glioblastoma Xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wachsberger, Phyllis R., E-mail: Phyllis.wachsberger@jeffersonhospital.org; Lawrence, Yaacov R.; Liu Yi

2012-01-01

Purpose: The purpose of this study was to determine the ability of radiation therapy (RT) combined with the tyrosine kinase inhibitors (TKI) vandetanib (antiepidermal growth factor receptor [EGFR] plus antivascular endothelial growth factor receptor [anti-VEGFR]) and cediranib (anti-VEGFR) to inhibit glioblastoma multiforme (GBM) growth. A secondary aim was to investigate how this regimen is modulated by tumor EGFR expression. Methods and Materials: Radiosensitivity was assessed by clonogenic cell survival assay. VEGF secretion was quantified by enzyme-linked immunosorbent assay. GBM (U87MG wild-type EGFR [wtEGFR] and U87MG EGFR-null) xenografts were treated with vandetanib, cediranib, and RT, alone or in combinations. Excised tumormore » sections were stained for proliferative and survival biomarkers. Results: In vitro, U87MG wtEGFR and U87 EGFR-null cells had similar growth kinetics. Neither TKI affected clonogenic cell survival following RT. However, in vivo, exogenous overexpression of wtEGFR decreased tumor doubling time (T2x) in U87MG xenografts (2.70 vs. 4.41 days for U87MG wtEGFR vs. U87MG vector, respectively). In U87MG EGFR-null cells, TKI combined with radiation was no better than radiation therapy alone. In U87MG wtEGFR, RT in combination with vandetanib (but not with cediranib) significantly increased tumor T2x compared with RT alone (T2x, 10.4 days vs. 4.8 days; p < 0.001). In vivo, growth delay correlated with suppression of pAkt, survivin, and Ki67 expression in tumor samples. The presence of EGFR augmented RT-stimulated VEGF release; this effect was inhibited by vandetanib. Conclusions: EGFR expression promoted tumor growth in vivo but not in vitro, suggesting a microenvironmental effect. GBM xenografts expressing EGFR exhibited greater sensitivity to both cediranib and vandetanib than EGFR-null tumors. Hence EGFR status plays a major role in determining a tumor's in vivo response to radiation combined with TKI, supporting a 'personalized' approach to GBM management.« less

System and Method for Null-Lens Wavefront Sensing

NASA Technical Reports Server (NTRS)

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

2015-01-01

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

Adaptive jammer nulling in EHF communications satellites

NASA Astrophysics Data System (ADS)

Bhagwan, Jai; Kavanagh, Stephen; Yen, J. L.

A preliminary investigation is reviewed concerning adaptive null steering multibeam uplink receiving system concepts for future extremely high frequency communications satellites. Primary alternatives in the design of the uplink antenna, the multibeam adaptive nulling receiver, and the processing algorithm and optimization criterion are discussed. The alternatives are phased array, lens or reflector antennas, nulling at radio frequency or an intermediate frequency, wideband versus narrowband nulling, and various adaptive nulling algorithms. A primary determinant of the hardware complexity is the receiving system architecture, which is described for the alternative antenna and nulling concepts. The final concept chosen will be influenced by the nulling performance requirements, cost, and technological readiness.

Broken chiral symmetry on a null plane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beane, Silas R., E-mail: silas@physics.unh.edu

2013-10-15

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

Flight Testing of Terrain-Relative Navigation and Large-Divert Guidance on a VTVL Rocket

NASA Technical Reports Server (NTRS)

Trawny, Nikolas; Benito, Joel; Tweddle, Brent; Bergh, Charles F.; Khanoyan, Garen; Vaughan, Geoffrey M.; Zheng, Jason X.; Villalpando, Carlos Y.; Cheng, Yang; Scharf, Daniel P.;

Serial cooling of a combustor for a gas turbine engine

DOEpatents

Abreu, Mario E.; Kielczyk, Janusz J.

2001-01-01

A combustor for a gas turbine engine uses compressed air to cool a combustor liner and uses at least a portion of the same compressed air for combustion air. A flow diverting mechanism regulates compressed air flow entering a combustion air plenum feeding combustion air to a plurality of fuel nozzles. The flow diverting mechanism adjusts combustion air according to engine loading.

Newly invented biobased materials from low-carbon, diverted waste fibers: research methods, testing, and full-scale application in a case study structure

Treesearch

Julee A Herdt; John Hunt; Kellen Schauermann

2016-01-01

This project demonstrates newly invented, biobased construction materials developed by applying lowcarbon, biomass waste sources through the Authors’ engineered fiber processes and technology. If manufactured and applied large-scale the project inventions can divert large volumes of cellulose waste into high-performance, low embodied energy, environmental construction...

Analysis of Msx1; Msx2 double mutants reveals multiple roles for Msx genes in limb development.

PubMed

Lallemand, Yvan; Nicola, Marie-Anne; Ramos, Casto; Bach, Antoine; Cloment, Cécile Saint; Robert, Benoît

2005-07-01

The homeobox-containing genes Msx1 and Msx2 are highly expressed in the limb field from the earliest stages of limb formation and, subsequently, in both the apical ectodermal ridge and underlying mesenchyme. However, mice homozygous for a null mutation in either Msx1 or Msx2 do not display abnormalities in limb development. By contrast, Msx1; Msx2 double mutants exhibit a severe limb phenotype. Our analysis indicates that these genes play a role in crucial processes during limb morphogenesis along all three axes. Double mutant limbs are shorter and lack anterior skeletal elements (radius/tibia, thumb/hallux). Gene expression analysis confirms that there is no formation of regions with anterior identity. This correlates with the absence of dorsoventral boundary specification in the anterior ectoderm, which precludes apical ectodermal ridge formation anteriorly. As a result, anterior mesenchyme is not maintained, leading to oligodactyly. Paradoxically, polydactyly is also frequent and appears to be associated with extended Fgf activity in the apical ectodermal ridge, which is maintained up to 14.5 dpc. This results in a major outgrowth of the mesenchyme anteriorly, which nevertheless maintains a posterior identity, and leads to formation of extra digits. These defects are interpreted in the context of an impairment of Bmp signalling.

Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

PubMed

Lebin, Jacob A; Murphy, David L; Severtson, Stevan Geoffrey; Bau, Gabrielle E; Dasgupta, Nabarun; Dart, Richard C

2018-05-15

Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price. Copyright © 2018 John Wiley & Sons, Ltd.

Miniaturization design and implementation of magnetic field coupled RFID antenna

NASA Astrophysics Data System (ADS)

Hu, Tiling

2013-03-01

The development of internet of things has brought new opportunities and challenges to the application of RFID tags. Moreover, the Miniaturization application trend of tags at present has become the mainstream of development. In this paper, the double-layer design is to reduce the size of HF antenna, and the magnetic null point of magnetic reconnection region between the RLC resonant circuit and the reader provides sufficient energy to the miniaturization of antenna. The calculated and experimental results show that the miniaturization of HF antennas can meet the reading and writing requirement of the international standard ISO/IEC14443 standard. The results of this paper may make a positive contribution to the applications of RFID technology.

Cusp singularities in f(R) gravity: pros and cons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Pisin; Yeom, Dong-han

We investigate cusp singularities in f(R) gravity, especially for Starobinsky and Hu-Sawicki dark energy models. We illustrate that, by using double-null numerical simulations, a cusp singularity can be triggered by gravitational collapses. This singularity can be cured by adding a quadratic term, but this causes a Ricci scalar bump that can be observed by an observer outside the event horizon. Comparing with cosmological parameters, it seems that it would be difficult to see super-Planckian effects by astrophysical experiments. On the other hand, at once there exists a cusp singularity, it can be a mechanism to realize a horizon scale curvaturemore » singularity that can be interpreted by a firewall.« less

Is it really naked? On cosmic censorship in string theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frolov, Andrei V.

We investigate the possibility of cosmic censorship violation in string theory using a characteristic double-null code, which penetrates horizons and is capable of resolving the spacetime all the way to the singularity. We perform high-resolution numerical simulations of the evolution of negative mass initial scalar field profiles, which were argued to provide a counterexample to cosmic censorship conjecture for AdS-asymptotic spacetimes in five-dimensional supergravity. In no instances formation of naked singularity is seen. Instead, numerical evidence indicates that black holes form in the collapse. Our results are consistent with earlier numerical studies, and explicitly show where the 'no black hole'more » argument breaks.« less

Looking for a bulk point

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maldacena, Juan; Simmons-Duffin, David; Zhiboedov, Alexander

Here, we consider Lorentzian correlators of local operators. In perturbation theory, singularities occur when we can draw a position-space Landau diagram with null lines. In theories with gravity duals, we can also draw Landau diagrams in the bulk. We also argue that certain singularities can arise only from bulk diagrams, not from boundary diagrams. As has been previously observed, these singularities are a clear diagnostic of bulk locality. We analyze some properties of these perturbative singularities and discuss their relation to the OPE and the dimensions of double-trace operators. In the exact nonperturbative theory, we expect no singularity at thesemore » locations. Finally, we prove this statement in 1+1 dimensions by CFT methods.« less

Looking for a bulk point

DOE PAGES

Maldacena, Juan; Simmons-Duffin, David; Zhiboedov, Alexander

2017-01-03

Here, we consider Lorentzian correlators of local operators. In perturbation theory, singularities occur when we can draw a position-space Landau diagram with null lines. In theories with gravity duals, we can also draw Landau diagrams in the bulk. We also argue that certain singularities can arise only from bulk diagrams, not from boundary diagrams. As has been previously observed, these singularities are a clear diagnostic of bulk locality. We analyze some properties of these perturbative singularities and discuss their relation to the OPE and the dimensions of double-trace operators. In the exact nonperturbative theory, we expect no singularity at thesemore » locations. Finally, we prove this statement in 1+1 dimensions by CFT methods.« less

Numerical Studies of a Supersonic Fluidic Diverter Actuator for Flow Control

NASA Technical Reports Server (NTRS)

Gokoglu, Suleyman A.; Kuczmarski, Maria A.; Culley, Dennis e.; Raghu, Surya

2010-01-01

The analysis of the internal flow structure and performance of a specific fluidic diverter actuator, previously studied by time-dependent numerical computations for subsonic flow, is extended to include operation with supersonic actuator exit velocities. The understanding will aid in the development of fluidic diverters with minimum pressure losses and advanced designs of flow control actuators. The self-induced oscillatory behavior of the flow is successfully predicted and the calculated oscillation frequencies with respect to flow rate have excellent agreement with our experimental measurements. The oscillation frequency increases with Mach number, but its dependence on flow rate changes from subsonic to transonic to supersonic regimes. The delay time for the initiation of oscillations depends on the flow rate and the acoustic speed in the gaseous medium for subsonic flow, but is unaffected by the flow rate for supersonic conditions

Interactive display system having a digital micromirror imaging device

DOEpatents

Veligdan, James T.; DeSanto, Leonard; Kaull, Lisa; Brewster, Calvin

2006-04-11

A display system includes a waveguide optical panel having an inlet face and an opposite outlet face. A projector cooperates with a digital imaging device, e.g. a digital micromirror imaging device, for projecting an image through the panel for display on the outlet face. The imaging device includes an array of mirrors tiltable between opposite display and divert positions. The display positions reflect an image light beam from the projector through the panel for display on the outlet face. The divert positions divert the image light beam away from the panel, and are additionally used for reflecting a probe light beam through the panel toward the outlet face. Covering a spot on the panel, e.g. with a finger, reflects the probe light beam back through the panel toward the inlet face for detection thereat and providing interactive capability.

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

PubMed

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.

14. VIEW OF WESTERN CANAL AT THE SALT RIVER PROJECT'S ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. VIEW OF WESTERN CANAL AT THE SALT RIVER PROJECT'S KYRENE STEAM POWER PLANT, TEMPE. THE WESTERN CANAL BEGINS TO TURN NORTH AT THIS POINT, AND DIVERTS WATER TO THE HIGHLINE PUMP PLANT AND THE KYRENE LATERAL. THE KYRENE PLANT INLET (LEFT-CENTER) ALSO DIVERTS CANAL WATER FOR PLANT OPERATION AND COOLING. - Western Canal, South side of Salt River between Tempe, Phoenix & Mesa, Mesa, Maricopa County, AZ

The role of situation assessment and flight experience in pilots' decisions to continue visual flight rules flight into adverse weather.

PubMed

Wiegmann, Douglas A; Goh, Juliana; O'Hare, David

2002-01-01

Visual flight rules (VFR) flight into instrument meteorological conditions (IMC) is a major safety hazard in general aviation. In this study we examined pilots' decisions to continue or divert from a VFR flight into IMC during a dynamic simulation of a cross-country flight. Pilots encountered IMC either early or later into the flight, and the amount of time and distance pilots flew into the adverse weather prior to diverting was recorded. Results revealed that pilots who encountered the deteriorating weather earlier in the flight flew longer into the weather prior to diverting and had more optimistic estimates of weather conditions than did pilots who encountered the deteriorating weather later in the flight. Both the time and distance traveled into the weather prior to diverting were negatively correlated with pilots' previous flight experience. These findings suggest that VFR flight into IMC may be attributable, at least in part, to poor situation assessment and experience rather than to motivational judgment that induces risk-taking behavior as more time and effort are invested in a flight. Actual or potential applications of this research include the design of interventions that focus on improving weather evaluation skills in addition to addressing risk-taking attitudes.

Reduplication phenomena: body, mind and archetype.

PubMed

Garner, J

2000-09-01

The many biological and few psychodynamic explanations of reduplicative syndromes tend to have paralleled the dualism of the phenomenon with organic theories concentrating on form and dynamic theories emphasising content. This paper extends the contribution of psychoanalytic thinking to an elucidation of the form of the delusion. Literature on clinical and aetiological aspects of reduplicative phenomena is reviewed alongside a brief examination of psychoanalytic models not overtly related to these phenomena. The human experience of doubles as universal archetype is considered. There is an obvious aetiological role for brain lesions in delusional misidentifications, but psychological symptoms in an individual can rarely be reduced to an organic disorder. The splitting and doubling which occurs in the phenomena have resonances in cultural mythology and in theories from different schools of psychodynamic thought. For the individual patient and doctor, it is a diverting but potentially empty debate to endeavour to draw strict divisions between what is physical and what is psychological although both need to be investigated. Nevertheless, in patients in whom there is clear evidence of an organic contribution to aetiology a psychodynamic understanding may serve to illuminate the patient's experience. Organic brain disease or serious functional illness predispose to regression to earlier modes of archetypical and primitive thinking with concretization of the metaphorical and mythological world. Psychoanalytic models have a contribution in describing the form as well as the content of reduplicative phenomena.

Trypanosoma brucei (UMP synthase null mutants) are avirulent in mice, but recover virulence upon prolonged culture in vitro while retaining pyrimidine auxotrophy

PubMed Central

Ong, Han B; Sienkiewicz, Natasha; Wyllie, Susan; Patterson, Stephen; Fairlamb, Alan H

2013-01-01

African trypanosomes are capable of both de novo synthesis and salvage of pyrimidines. The last two steps in de novo synthesis are catalysed by UMP synthase (UMPS) – a bifunctional enzyme comprising orotate phosphoribosyl transferase (OPRT) and orotidine monophosphate decarboxylase (OMPDC). To investigate the essentiality of pyrimidine biosynthesis in Trypanosoma brucei, we generated a umps double knockout (DKO) line by gene replacement. The DKO was unable to grow in pyrimidine-depleted medium in vitro, unless supplemented with uracil, uridine, deoxyuridine or UMP. DKO parasites were completely resistant to 5-fluoroorotate and hypersensitive to 5-fluorouracil, consistent with loss of UMPS, but remained sensitive to pyrazofurin indicating that, unlike mammalian cells, the primary target of pyrazofurin is not OMPDC. The null mutant was unable to infect mice indicating that salvage of host pyrimidines is insufficient to support growth. However, following prolonged culture in vitro, parasites regained virulence in mice despite retaining pyrimidine auxotrophy. Unlike the wild-type, both pyrimidine auxotrophs secreted substantial quantities of orotate, significantly higher in the virulent DKO line. We propose that this may be responsible for the recovery of virulence in mice, due to host metabolism converting orotate to uridine, thereby bypassing the loss of UMPS in the parasite. PMID:23980694

ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells

PubMed Central

Pan, Ling; Deng, Min; Xie, Xiaoling; Gan, Lin

2009-01-01

SUMMARY LIM-homeodomain (HD) and POU-HD transcription factors play critical roles in neurogenesis. However, it remains largely unknown how they cooperate in this process and what downstream target genes they regulate. Here we show that ISL1, a LIM-HD protein, is co-expressed with BRN3B, a POU-HD factor, in nascent, post-mitotic retinal ganglion cells (RGCs). Similar to the Brn3b-null retinas, retina-specific deletion of Isl1 results in the apoptosis of a majority of RGCs and in RGC axon guidance defects. The Isl1 and Brn3b double null mice display more severe retinal abnormalities with a near complete loss of RGCs, indicating the synergistic functions of these two factors. Furthermore, we show that both Isl1 and Brn3b function downstream of Math5 to regulate the expression of a common set of RGC-specific genes. Whole retina chromatin immunoprecipitation and in vitro transactivation assays reveal that ISL1 and BRN3B concurrently bind to and synergistically regulate the expression of a common set of RGC-specific genes. Thus, our results uncover a novel regulatory mechanism of BRN3B and ISL1 in RGC differentiation. PMID:18434421

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, Rahul; Mitra, Dipanjan; Melikidze, George I., E-mail: rahulbasu.astro@gmail.com

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

MAGNETIC NULL POINTS IN KINETIC SIMULATIONS OF SPACE PLASMAS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olshevsky, Vyacheslav; Innocenti, Maria Elena; Cazzola, Emanuele

2016-03-01

We present a systematic attempt to study magnetic null points and the associated magnetic energy conversion in kinetic particle-in-cell simulations of various plasma configurations. We address three-dimensional simulations performed with the semi-implicit kinetic electromagnetic code iPic3D in different setups: variations of a Harris current sheet, dipolar and quadrupolar magnetospheres interacting with the solar wind, and a relaxing turbulent configuration with multiple null points. Spiral nulls are more likely created in space plasmas: in all our simulations except lunar magnetic anomaly (LMA) and quadrupolar mini-magnetosphere the number of spiral nulls prevails over the number of radial nulls by a factor of 3–9.more » 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.« less

Theoretical and experimental study of a thruster discharging a weight

NASA Astrophysics Data System (ADS)

Michaels, Dan; Gany, Alon

2014-06-01

An innovative concept for a rocket type thruster that can be beneficial for spacecraft trajectory corrections and station keeping was investigated both experimentally and theoretically. It may also be useful for divert and attitude control systems (DACS). The thruster is based on a combustion chamber discharging a weight through an exhaust tube. Calculations with granular double-base propellant and a solid ejected weight reveal that a specific impulse based on the propellant mass of well above 400 s can be obtained. An experimental thruster was built in order to demonstrate the new idea and validate the model. The thruster impulse was measured both directly with a load cell and indirectly by using a pressure transducer and high speed photography of the weight as it exits the tube, with both ways producing very similar total impulse measurement. The good correspondence between the computations and the measured data validates the model as a useful tool for studying and designing such a thruster.

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

NASA Astrophysics Data System (ADS)

Rodgers, J. Michael

2000-07-01

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

Moral distancing and the use of information technologies: The seven temptations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubin, R.

1994-12-31

There are many causes for unethical behavior among individuals who use information technologies. This article suggests that some of these reasons may be directly related to the characteristics of the technologies themselves. This is not to suggest that individuals are not responsible for their actions, but to identify factors about technology that may divert ethical attention. The diverting characteristics are identified as the {open_quote}Seven Temptations{open_quotes}.

Flow diversion in the treatment of carotid injury and carotid-cavernous fistula after transsphenoidal surgery

PubMed Central

Lum, Cheemum; Ahmed, Muhammad E; Glikstein, Rafael; dos Santos, Marlise P; Lesiuk, Howard; Labib, Mohamed; Kassam, Amin B

2015-01-01

We describe a case of iatrogenic carotid injury with secondary carotid-cavernous fistula (CCF) treated with a silk flow diverter stent placed within the injured internal carotid artery and coils placed within the cavernous sinus. Flow diverters may offer a simple and potentially safe vessel-sparing option in this rare complication of transsphenoidal surgery. The management options are discussed and the relevant literature is reviewed. PMID:26015526

Particle-Based Microfluidic Device for Providing High Magnetic Field Gradients

NASA Technical Reports Server (NTRS)

Wong, Tak S. (Inventor); Lin, Adam Y. (Inventor)

2013-01-01

A microfluidic device for manipulating particles in a fluid has a device body that defines a main channel therein, in which the main channel has an inlet and an outlet. The device body further defines a particulate diverting channel therein, the particulate diverting channel being in fluid connection with the main channel between the inlet and the outlet of the main channel and having a particulate outlet. The microfluidic device also has a plurality of microparticles arranged proximate or in the main channel between the inlet of the main channel and the fluid connection of the particulate diverting channel to the main channel. The plurality of microparticles each comprises a material in a composition thereof having a magnetic susceptibility suitable to cause concentration of magnetic field lines of an applied magnetic field while in operation. A microfluidic particle-manipulation system has a microfluidic particle-manipulation device and a magnet disposed proximate the microfluidic particle-manipulation device.

Numerical Studies of a Fluidic Diverter for Flow Control

NASA Technical Reports Server (NTRS)

Gokoglu, Suleyman A.; Kuczmarski, Maria A.; Culley, Dennis E.; Raghu, Surya

2009-01-01

The internal flow structure in a specific fluidic diverter is studied over a range from low subsonic to sonic inlet conditions by a time-dependent numerical analysis. The understanding will aid in the development of fluidic diverters with minimum pressure losses and advanced designs of flow control actuators. The velocity, temperature and pressure fields are calculated for subsonic conditions and the self-induced oscillatory behavior of the flow is successfully predicted. The results of our numerical studies have excellent agreement with our experimental measurements of oscillation frequencies. The acoustic speed in the gaseous medium is determined to be a key factor for up to sonic conditions in governing the mechanism of initiating the oscillations as well as determining its frequency. The feasibility of employing plasma actuation with a minimal perturbation level is demonstrated in steady-state calculations to also produce oscillation frequencies of our own choosing instead of being dependent on the fixed-geometry fluidic device.

Genetic metabolic complementation establishes a requirement for GDP-fucose in Leishmania.

PubMed

Guo, Hongjie; Novozhilova, Natalia M; Bandini, Giulia; Turco, Salvatore J; Ferguson, Michael A J; Beverley, Stephen M

2017-06-23

To survive in its sand fly vector, the trypanosomatid protozoan parasite Leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. In Leishmania major strain Friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (LPG). During differentiation to infective metacyclics, d-arabinopyranose (d-Ara p ) caps the LPG side-chain galactose residues, blocking interaction with the midgut lectin PpGalec, thereby leading to parasite detachment and transmission. Previously, we characterized two closely related L. major genes ( FKP40 and AFKP80 ) encoding bifunctional proteins with kinase/pyrophosphorylase activities required for salvage and conversion of l-fucose and/or d-Ara p into the nucleotide-sugar substrates required by glycosyltransferases. Whereas only AFKP80 yielded GDP-d-Ara p from exogenous d-Ara p , both proteins were able to salvage l-fucose to GDP-fucose. We now show that Δ afkp80 - null mutants ablated d-Ara p modifications of LPG as predicted, whereas Δ fkp40 - null mutants resembled wild type (WT). Fucoconjugates had not been reported previously in L. major , but unexpectedly, we were unable to generate fkp40 - / afkp80 - double mutants, unless one of the A/FKPs was expressed ectopically. To test whether GDP-fucose itself was essential for Leishmania viability, we employed "genetic metabolite complementation." First, the trypanosome de novo pathway enzymes GDP-mannose dehydratase (GMD) and GDP-fucose synthetase (GMER) were expressed ectopically; from these cells, the Δ fkp40 - /Δ afkp80 - double mutant was now readily obtained. As expected, the Δ fkp40 - /Δ afkp80 - /+ TbGMD-GMER line lacked the capacity to generate GDP-Ara p , while synthesizing abundant GDP-fucose. These results establish a requirement for GDP-fucose for L. major viability and predict the existence of an essential fucoconjugate(s). © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Aberrant muscle antigen exposure in mice is sufficient to cause myositis in a Treg cell-deficient milieu.

PubMed

Young, Nicholas A; Sharma, Rahul; Friedman, Alexandra K; Kaffenberger, Benjamin H; Bolon, Brad; Jarjour, Wael N

2013-12-01

Myositis is associated with muscle-targeted inflammation and is observed in some Treg cell-deficient mouse models. Because an autoimmune pathogenesis has been strongly implicated, the aim of this study was to investigate the hypothesis that abnormal exposure to muscle antigens, as observed in muscle injury, can induce autoimmune-mediated myositis in susceptible hosts. FoxP3 mutant (scurfy) mice were mated to synaptotagmin VII (Syt VII) mutant mice, which resulted in a new mouse strain that combines impaired membrane resealing with Treg cell deficiency. Lymphocyte preparations from double-mutant mice were adoptively transferred intraperitoneally, with or without purified Treg cells, into recombination-activating gene 1 (RAG-1)-null recipients. Lymph node cells from mice with the FoxP3 mutation were transferred into RAG-1-null mice either 1) intraperitoneally in conjunction with muscle homogenate or purified myosin protein or 2) intramuscularly with or without cotransfer of purified Treg cells. FoxP3-deficient mouse lymph node cells transferred in conjunction with myosin protein or muscle homogenate induced robust skeletal muscle inflammation. The infiltrates consisted predominantly of CD4+ and CD8+ T cells, a limited number of macrophages, and no B cells. Significant inflammation was also seen in similar experiments using lymph node cells from FoxP3/Syt VII double-mutant mice but was absent in experiments using adoptive transfer of FoxP3 mutant mouse cells alone. The cotransfer of Treg cells completely suppressed myositis. These data, derived from a new, reproducible model, demonstrate the critical roles of Treg cell deficiency and aberrant muscle antigen exposure in the priming of autoreactive cells to induce myositis. This mouse system has multifaceted potential for examining the interplay in vivo between tissue injury and autoimmunity. © 2013 The Authors. Arthritis & Rheumatism is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Genetic metabolic complementation establishes a requirement for GDP-fucose in Leishmania

PubMed Central

Novozhilova, Natalia M.; Turco, Salvatore J.

2017-01-01

To survive in its sand fly vector, the trypanosomatid protozoan parasite Leishmania first attaches to the midgut to avoid excretion, but eventually it must detach for transmission by the next bite. In Leishmania major strain Friedlin, this is controlled by modifications of the stage-specific adhesin lipophosphoglycan (LPG). During differentiation to infective metacyclics, d-arabinopyranose (d-Arap) caps the LPG side-chain galactose residues, blocking interaction with the midgut lectin PpGalec, thereby leading to parasite detachment and transmission. Previously, we characterized two closely related L. major genes (FKP40 and AFKP80) encoding bifunctional proteins with kinase/pyrophosphorylase activities required for salvage and conversion of l-fucose and/or d-Arap into the nucleotide-sugar substrates required by glycosyltransferases. Whereas only AFKP80 yielded GDP-d-Arap from exogenous d-Arap, both proteins were able to salvage l-fucose to GDP-fucose. We now show that Δafkp80− null mutants ablated d-Arap modifications of LPG as predicted, whereas Δfkp40− null mutants resembled wild type (WT). Fucoconjugates had not been reported previously in L. major, but unexpectedly, we were unable to generate fkp40−/afkp80− double mutants, unless one of the A/FKPs was expressed ectopically. To test whether GDP-fucose itself was essential for Leishmania viability, we employed “genetic metabolite complementation.” First, the trypanosome de novo pathway enzymes GDP-mannose dehydratase (GMD) and GDP-fucose synthetase (GMER) were expressed ectopically; from these cells, the Δfkp40−/Δafkp80− double mutant was now readily obtained. As expected, the Δfkp40−/Δafkp80−/+TbGMD-GMER line lacked the capacity to generate GDP-Arap, while synthesizing abundant GDP-fucose. These results establish a requirement for GDP-fucose for L. major viability and predict the existence of an essential fucoconjugate(s). PMID:28465349

Intermittent electron density and temperature fluctuations and associated fluxes in the Alcator C-Mod scrape-off layer

NASA Astrophysics Data System (ADS)

Kube, R.; Garcia, O. E.; Theodorsen, A.; Brunner, D.; Kuang, A. Q.; LaBombard, B.; Terry, J. L.

2018-06-01

The Alcator C-Mod mirror Langmuir probe system has been used to sample data time series of fluctuating plasma parameters in the outboard mid-plane far scrape-off layer. We present a statistical analysis of one second long time series of electron density, temperature, radial electric drift velocity and the corresponding particle and electron heat fluxes. These are sampled during stationary plasma conditions in an ohmically heated, lower single null diverted discharge. The electron density and temperature are strongly correlated and feature fluctuation statistics similar to the ion saturation current. Both electron density and temperature time series are dominated by intermittent, large-amplitude burst with an exponential distribution of both burst amplitudes and waiting times between them. The characteristic time scale of the large-amplitude bursts is approximately 15 μ {{s}}. Large-amplitude velocity fluctuations feature a slightly faster characteristic time scale and appear at a faster rate than electron density and temperature fluctuations. Describing these time series as a superposition of uncorrelated exponential pulses, we find that probability distribution functions, power spectral densities as well as auto-correlation functions of the data time series agree well with predictions from the stochastic model. The electron particle and heat fluxes present large-amplitude fluctuations. For this low-density plasma, the radial electron heat flux is dominated by convection, that is, correlations of fluctuations in the electron density and radial velocity. Hot and dense blobs contribute only a minute fraction of the total fluctuation driven heat flux.

The Metallothionein-Null Phenotype Is Associated with Heightened Sensitivity to Lead Toxicity and an Inability to Form Inclusion Bodies

PubMed Central

Qu, Wei; Diwan, Bhalchandra A.; Liu, Jie; Goyer, Robert A.; Dawson, Tammy; Horton, John L.; Cherian, M. George; Waalkes, Michael P.

2002-01-01

Susceptibility to lead toxicity in MT-null mice and cells, lacking the major forms of the metallothionein (MT) gene, was compared to wild-type (WT) mice or cells. Male MT-null and WT mice received lead in the drinking water (0 to 4000 ppm) for 10 to 20 weeks. Lead did not alter body weight in any group. Unlike WT mice, lead-treated MT-null mice showed dose-related nephromegaly. In addition, after lead exposure renal function was significantly diminished in MT-null mice in comparison to WT mice. MT-null mice accumulated less renal lead than WT mice and did not form lead inclusion bodies, which were present in the kidneys of WT mice. In gene array analysis, renal glutathione S-transferases were up-regulated after lead in MT-null mice only. In vitro studies on fibroblast cell lines derived from MT-null and WT mice showed that MT-null cells were much more sensitive to lead cytotoxicity. MT-null cells accumulated less lead and formed no inclusion bodies. The MT-null phenotype seems to preclude lead-induced inclusion body formation and increases lead toxicity at the organ and cellular level despite reducing lead accumulation. This study reveals important roles for MT in chronic lead toxicity, lead accumulation, and inclusion body formation. PMID:11891201

Adaptive Nulling for the Terrestrial Planet Finder Interferometer

NASA Technical Reports Server (NTRS)

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

2006-01-01

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

Implosive Collapse about Magnetic Null Points: A Quantitative Comparison between 2D and 3D Nulls

NASA Astrophysics Data System (ADS)

Thurgood, Jonathan O.; Pontin, David I.; McLaughlin, James A.

2018-03-01

Null collapse is an implosive process whereby MHD waves focus their energy in the vicinity of a null point, forming a current sheet and initiating magnetic reconnection. We consider, for the first time, the case of collapsing 3D magnetic null points in nonlinear, resistive MHD using numerical simulation, exploring key physical aspects of the system as well as performing a detailed parameter study. We find that within a particular plane containing the 3D null, the plasma and current density enhancements resulting from the collapse are quantitatively and qualitatively as per the 2D case in both the linear and nonlinear collapse regimes. However, the scaling with resistivity of the 3D reconnection rate—which is a global quantity—is found to be less favorable when the magnetic null point is more rotationally symmetric, due to the action of increased magnetic back-pressure. Furthermore, we find that, with increasing ambient plasma pressure, the collapse can be throttled, as is the case for 2D nulls. We discuss this pressure-limiting in the context of fast reconnection in the solar atmosphere and suggest mechanisms by which it may be overcome. We also discuss the implications of the results in the context of null collapse as a trigger mechanism of Oscillatory Reconnection, a time-dependent reconnection mechanism, and also within the wider subject of wave–null point interactions. We conclude that, in general, increasingly rotationally asymmetric nulls will be more favorable in terms of magnetic energy release via null collapse than their more symmetric counterparts.

Fermilab Education Office - Special Events for Students and Families

Science.gov Websites

students and families. These include: null Fermilab Outdoor Family Fair (K-12) null Wonders of Science (2-7 ) null Family Open House (3-12) null STEM Career Expo (9-12) Search Programs - Search Science Adventures

Cooling apparatus and method

DOEpatents

Mayes, James C [Sugar Land, TX

2009-05-05

A device and method provide for cooling of a system having an energy source, one or more devices that actively consume energy, and one or more devices that generate heat. The device may include one or more thermoelectric coolers ("TECs") in conductive engagement with at least one of the heat-generating devices, and an energy diverter for diverting at least a portion of the energy from the energy source that is not consumed by the active energy-consuming devices to the TECs.

Fiber optic monitoring device

DOEpatents

Samborsky, James K.

1993-01-01

A device for the purpose of monitoring light transmissions in optical fibers comprises a fiber optic tap that optically diverts a fraction of a transmitted optical signal without disrupting the integrity of the signal. The diverted signal is carried, preferably by the fiber optic tap, to a lens or lens system that disperses the light over a solid angle that facilitates viewing. The dispersed light indicates whether or not the monitored optical fiber or system of optical fibers is currently transmitting optical information.

Analysis of potential diverted of passenger car to the new toll road (case study: Cileunyi - Sumedang, West Java)

NASA Astrophysics Data System (ADS)

Prahara, Eduardi; Suangga, Made; Lutfi Ansori, Ahmad

2017-12-01

This study aims to determine of potential of passenger car divert from national road to on-construction Cisumdawu Toll Road. The study was conducted by traffic count survey and followed by a roadside interview survey. Stated Preference method was used in order to analyse trip forecasting value. Mode choice model of new trip mode plans (Cisumdawu Toll Road) and current intercity road for Cileunyi - Sumedang is (UJT -UJR ) = 0.1079-0.507726x 1-0.8953764x 2, while Sumedang - Cileunyi is (UJT -UJR ) = 0.0790-0.301341x 1-0.548446x 2. Multiple linear regression analysis was used to obtain the forecasting of private vehicle that diverts to the new toll road (Cisumdawu Toll Road). Trip characteristics such as trip origin and destination, types of trips, occupations, salary, and others become a motive for respondents to choose a new trip mode. Results of the new trip mode forecasting that prefer to divert to the toll road in terms of the value of cost and time for Cileunyi - Sumedang are 74.11% and 86.62% respectively, while for Sumedang - Cileunyi are 69.60% and 76.48% respectively. These results are relatively high compare to toll planning document. The impact of this results can be determined such as lower overall fuel consumption, lower pollution and more important is the maintenance cost of national road will be decrease.

Prescription Drug Diversion: Predictors of Illicit Acquisition and Redistribution in Three U.S. Metropolitan Areas.

PubMed

Harris, Shana; Nikulina, Valentina; Gelpí-Acosta, Camila; Morton, Cory; Newsome, Valerie; Gunn, Alana; Hoefinger, Heidi; Aikins, Ross; Smith, Vivian; Barry, Victoria; Downing, Martin J

2015-12-02

Prescription drug diversion, the transfer of prescription drugs from lawful to unlawful channels for distribution or use, is a problem in the United States. Despite the pervasiveness of diversion, there are gaps in the literature regarding characteristics of individuals who participate in the illicit trade of prescription drugs. This study examines a range of predictors (e.g., demographics, prescription insurance coverage, perceived risk associated with prescription drug diversion) of membership in three distinct diverter groups: individuals who illicitly acquire prescription drugs, those who redistribute them, and those who engage in both behaviors. Data were drawn from a cross-sectional Internet study ( N = 846) of prescription drug use and diversion patterns in New York City, South Florida, and Washington, D.C.. Participants were classified into diversion categories based on their self-reported involvement in the trade of prescription drugs. Group differences in background characteristics of diverter groups were assessed by Chi-Square tests and followed up with multivariate logistic regressions. While individuals in all diversion groups were more likely to be younger and have a licit prescription for any of the assessed drugs in the past year than those who did not divert, individuals who both acquire and redistribute are more likely to live in New York City, not have prescription insurance coverage, and perceive fewer legal risks of prescription drug diversion. Findings suggest that predictive characteristics vary according to diverter group.

A Gaussian Mixture Model for Nulling Pulsars

NASA Astrophysics Data System (ADS)

Kaplan, D. L.; Swiggum, J. K.; Fichtenbauer, T. D. J.; Vallisneri, M.

2018-03-01

The phenomenon of pulsar nulling—where pulsars occasionally turn off for one or more pulses—provides insight into pulsar-emission mechanisms and the processes by which pulsars turn off when they cross the “death line.” However, while ever more pulsars are found that exhibit nulling behavior, the statistical techniques used to measure nulling are biased, with limited utility and precision. In this paper, we introduce an improved algorithm, based on Gaussian mixture models, for measuring pulsar nulling behavior. We demonstrate this algorithm on a number of pulsars observed as part of a larger sample of nulling pulsars, and show that it performs considerably better than existing techniques, yielding better precision and no bias. We further validate our algorithm on simulated data. Our algorithm is widely applicable to a large number of pulsars even if they do not show obvious nulls. Moreover, it can be used to derive nulling probabilities of nulling for individual pulses, which can be used for in-depth studies.

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

NASA Astrophysics Data System (ADS)

Casini, Horacio; Testé, Eduardo; Torroba, Gonzalo

2017-09-01

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

An Experimental Evaluation of the Performance of Two Combination Pitot Pressure Probes

NASA Technical Reports Server (NTRS)

Arend, David J.; Saunders, John D.

2009-01-01

Experimental tests have been completed which recorded the ability of two combination steady state and high response time varying Pitot probe designs to accurately measure steady stagnation pressure at a single location in a flow field. Tests were conducted of double-barreled and coannular Prati probes in a 3.5 in. diameter free jet probe calibration facility from Mach 0.1 to 0.9. Geometric symmetry and pitch (-40 deg to 40 deg) and yaw (0 deg to 40 deg) angle actuation were used to fully evaluate the probes. These tests revealed that the double-barreled configuration induced error in its steady state measurement at zero incidence that increased consistently with jet Mach number to 1.1 percent at Mach 0.9. For all Mach numbers, the double-barreled probe nulled at a pitch angle of approximately 7.0 deg and provided inconsistent measurements when yawed. The double-barreled probe provided adequate measurements via both its steady state and high response tubes (within +/- 0.15 percent accuracy) over unacceptable ranges of biased pitch and inconsistent yaw angles which varied with Mach number. By comparison, the coannular probe provided accurate measurements (at zero incidence) for all jet Mach numbers as well as over a flow angularity range which varied from +/- 26.0 deg at Mach 0.3 deg to +/- 14.0 deg at Mach 0.9. Based on these results, the Prati probe is established as the preferred design. Further experimental tests are recommended to document the frequency response characteristics of the Prati probe.

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

NASA Astrophysics Data System (ADS)

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

2010-10-01

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

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

PubMed Central

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

2016-01-01

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

Cost Analysis of U.S. Navy Humanitarian Assistance and Disaster Relief Missions

DTIC Science & Technology

2014-12-01

93943–5000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING /MONITORING AGENCY NAME(S) AND ADDRESS(ES) N/ A 10. SPONSORING/MONITORING AGENCY...as a core competency to its maritime strategy. From 1970 to 2000, the Navy diverted vessels 366 times for HA/DR operations, as opposed to 22 times...Humanitarian Assistance and Disaster Relief as a core competency to its maritime strategy. From 1970 to 2000, the Navy diverted vessels 366 times for HA/DR

Performance characteristics of plane-wall venturi-like reverse flow diverters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, G.V.; Counce, R.M.

1984-02-01

The results of an analytical and experimental study of plane-wall venturi-like reverse flow diverters (RFD) are presented. In general, the flow characteristics of the RFD are reasonably well predicted by the mathematical model of the RFD, although a divergence between theory and data is observed for the output characteristics in the reverse flow mode as the output impedance is reduced. Overall, the performance of these devices indicates their usefulness in fluid control and fluid power systems, such as displacement pumping systems.

Performance characteristics of plane-wall venturi-like reverse flow diverters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, G.V.; Counce, R.M.

1982-01-01

The results of an analytical and experimental study of plane-wall venturi-like reverse flow diverters (RFD) are presented. In general, the flow characteristics of the RFD are reasonably well predicted by the mathematical model of the RFD, although a divergence between theory and data is observed for the output characteristics in the reverse flow mode as the output impedance is reduced. Overall, the performance of these devices indicates their usefulness in fluid control and fluid power systems, such as displacement pumping systems.

Hybrid indirect/direct contactor for thermal management of counter-current processes

DOEpatents

Hornbostel, Marc D.; Krishnan, Gopala N.; Sanjurjo, Angel

2018-03-20

The invention relates to contactors suitable for use, for example, in manufacturing and chemical refinement processes. In an aspect is a hybrid indirect/direct contactor for thermal management of counter-current processes, the contactor comprising a vertical reactor column, an array of interconnected heat transfer tubes within the reactor column, and a plurality of stream path diverters, wherein the tubes and diverters are configured to block all straight-line paths from the top to bottom ends of the reactor column.

Alterations in Taxol production in plant cell culture via manipulation of the phenylalanine ammonia lyase pathway.

PubMed

Brincat, Michelle C; Gibson, Donna M; Shuler, Michael L

2002-01-01

One approach to increasing secondary metabolite production in plant cell culture is to manipulate metabolic pathways to utilize more resources toward production of one desired compound or class of compounds, such as diverting carbon flux from competing secondary pathways. Since phenylalanine provides both the phenylisoserine side chain and the benzoyl moiety at C-2 of Taxol, we speculated that blockage of the phenylpropanoid pathway might divert phenylalanine into Taxol biosynthesis. We used specific enzyme inhibitors to target the first enzyme in the phenylpropanoid pathway, phenylalanine ammonia lyase (PAL), the critical control point for conversion of L-phenylalanine to trans-cinnamic acid. Cinnamic acid acted quickly in reducing PAL activity by 40-50%, without affecting total protein levels, but it generally inhibited the taxane pathway, reducing Taxol by 90% of control levels. Of the taxanes produced, 13-acetyl-9-dihydro-baccatin III and 9-dihydrobaccatin III doubled as a percentage of total taxanes in C93AD and CO93P cells treated with 0.20 and 0.25 mM cinnamic acid, when all other taxanes were lowered. The PAL inhibitor alpha-aminooxyacetic acid (AOA) almost entirely shut down Taxol production at both 0.5 and 1.5 mM, whereas L-alpha-aminooxy-beta-phenylpropionic acid (AOPP) had the opposite effect, slightly enhancing Taxol production at 1 microM but having no effect at 10 microM. The discrepancy in the effectiveness of AOA and AOPP and the lack of effect with addition of phenylalanine or benzoic acid derivatives further indicates that the impact of cinnamic acid on Taxol is related not to its effect on PAL but rather to a specific effect on the taxane pathway. On the basis of these results, a less direct route for inhibiting the phenylpropanoid pathway may be required to avoid unwanted side effects and potentially enhance Taxol production.

Toroidally symmetric plasma vortex at tokamak divertor null point

DOE PAGES

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

2016-03-09

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

Off-Axis Nulling Transfer Function Measurement: A First Assessment

NASA Technical Reports Server (NTRS)

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

The mitochondrial SIR2 related protein 2 (SIR2RP2) impacts Leishmania donovani growth and infectivity

PubMed Central

Mittal, Nimisha; Muthuswami, Rohini

2017-01-01

Background Leishmania donovani, a protozoan parasite is the major causative agent of visceral leishmaniasis. Increased toxicity and resistance to the existing repertoire of drugs has been reported. Hence, an urgent need exists for identifying newer drugs and drug targets. Previous reports have shown sirtuins (Silent Information Regulator) from kinetoplastids as promising drug targets. Leishmania species code for three SIR2 (Silent Information Regulator) related proteins. Here, we for the first time report the functional characterization of SIR2 related protein 2 (SIR2RP2) of L. donovani. Methodology Recombinant L. donovani SIR2RP2 was expressed in E. coli and purified. The enzymatic functions of SIR2RP2 were determined. The subcellular localization of LdSIR2RP2 was done by constructing C-terminal GFP-tagged full-length LdSIR2RP2. Deletion mutants of LdSIR2RP2 were generated in Leishmania by double targeted gene replacement methodology. These null mutants were tested for their proliferation, virulence, cell cycle defects, mitochondrial functioning and sensitivity to known SIR2 inhibitors. Conclusion Our data suggests that LdSIR2RP2 possesses NAD+-dependent ADP-ribosyltransferase activity. However, NAD+-dependent deacetylase and desuccinylase activities were not detected. The protein localises to the mitochondrion of the promastigotes. Gene deletion studies showed that ΔLdSIR2RP2 null mutants had restrictive growth phenotype associated with accumulation of cells in the G2/M phase and compromised mitochondrial functioning. The null mutants had attenuated infectivity. Deletion of LdSIR2RP2 resulted in increased sensitivity of the parasites to the known SIR2 inhibitors. The sirtuin inhibitors inhibited the ADP-ribosyltransferase activity of recombinant LdSIR2RP2. In conclusion, sirtuins could be used as potential new drug targets for visceral leishmaniasis. PMID:28493888

A Toxoplasma MORN1 Null Mutant Undergoes Repeated Divisions but Is Defective in Basal Assembly, Apicoplast Division and Cytokinesis

PubMed Central

Lorestani, Alexander; Sheiner, Lilach; Yang, Kevin; Robertson, Seth D.; Sahoo, Nivedita; Brooks, Carrie F.; Ferguson, David J. P.; Striepen, Boris; Gubbels, Marc-Jan

2010-01-01

The membrane occupation and recognition nexus protein 1 (MORN1) is highly conserved among apicomplexan parasites and is associated with several structures that have a role in cell division. Here we dissected the role of MORN1 using the relatively simple budding process of Toxoplasma gondii as a model. Ablation of MORN1 in a conditional null mutant resulted in pronounced defects suggesting a central role for MORN1 in apicoplast segregation and in daughter cell budding. Lack of MORN1 resulted in double-headed parasites. These Janus-headed parasites form two complete apical complexes but fail to assemble a basal complex. Moreover, these parasites were capable of undergoing several more budding rounds resulting in the formation of up to 16-headed parasites conjoined at the basal end. Despite this segregation defect, the mother's cytoskeleton was completely disassembled in every budding round. Overall this argues that successful completion of the budding is not required for cell cycle progression. None of the known basal complex components, including a set of recently identified inner membrane complex (IMC) proteins, localized correctly in these multi-headed parasites. These data suggest that MORN1 is essential for assembly of the basal complex, and that lack of the basal complex abolishes the contractile capacity assigned to the basal complex late in daughter formation. Consistent with this hypothesis we observe that MORN1 mutants fail to efficiently constrict and divide the apicoplast. We used the null background provided by the mutant to dissect the function of subdomains of the MORN1 protein. This demonstrated that deletion of a single MORN domain already prevented the function of MORN1 whereas a critical role for the short linker between MORN domains 6 and 7 was identified. In conclusion, MORN1 is required for basal complex assembly and loss of MORN1 results in defects in apicoplast division and daughter segregation. PMID:20808817

Tbx1 Regulates Progenitor Cell Proliferation in the Dental Epithelium by Modulating PITX2 Activation of p21

PubMed Central

Cao, Huojun; Florez, Sergio; Amen, Melanie; Huynh, Tuong; Skobe, Ziedonis; Baldini, Antonio; Amendt, Brad A.

2012-01-01

Tbx1−/− mice present with phenotypic effects observed in DiGeorge syndrome patients however, the molecular mechanisms of Tbx1 regulating craniofacial and tooth development are unclear. Analyses of the Tbx1 null mice reveal incisor microdontia, small cervical loops and BrdU labeling reveals a defect in epithelial cell proliferation. Furthermore, Tbx1 null mice molars are lacking normal cusp morphology. Interestingly, p21 (associated with cell cycle arrest) is up regulated in the dental epithelium of Tbx1−/− embryos. These data suggest that Tbx1 inhibits p21 expression to allow for cell proliferation in the dental epithelial cervical loop, however Tbx1 does not directly regulate p21 expression. A new molecular mechanism has been identified where Tbx1 inhibits Pitx2 transcriptional activity and decreases the expression of Pitx2 target genes, p21, Lef-1 and Pitx2c. p21 protein is increased in PITX2C transgenic mouse embryo fibroblasts (MEF) and chromatin immunoprecipitation assays demonstrate endogenous Pitx2 binding to the p21 promoter. Tbx1 attenuates PITX2 activation of endogenous p21 expression and Tbx1 null MEFs reveal increased Pitx2a and activation of Pitx2c isoform expression. Tbx1 physically interacts with the PITX2 C-terminus and represses PITX2 transcriptional activation of the p21, LEF-1, and Pitx2c promoters. Tbx1−/+/Pitx2−/+ double heterozygous mice present with an extra premolar-like tooth revealing a genetic interaction between these factors. The ability of Tbx1 to repress PITX2 activation of p21 may promote cell proliferation. In addition, PITX2 regulation of p21 reveals a new role for PITX2 in repressing cell proliferation. These data demonstrate new functional mechanisms for Tbx1 in tooth morphogenesis and provide a molecular basis for craniofacial defects in DiGeorge syndrome patients. PMID:20816801

Tbx1 regulates progenitor cell proliferation in the dental epithelium by modulating Pitx2 activation of p21.

PubMed

Cao, Huojun; Florez, Sergio; Amen, Melanie; Huynh, Tuong; Skobe, Ziedonis; Baldini, Antonio; Amendt, Brad A

2010-11-15

Tbx1(-/-) mice present with phenotypic effects observed in DiGeorge syndrome patients however, the molecular mechanisms of Tbx1 regulating craniofacial and tooth development are unclear. Analyses of the Tbx1 null mice reveal incisor microdontia, small cervical loops and BrdU labeling reveals a defect in epithelial cell proliferation. Furthermore, Tbx1 null mice molars are lacking normal cusp morphology. Interestingly, p21 (associated with cell cycle arrest) is up regulated in the dental epithelium of Tbx1(-/-) embryos. These data suggest that Tbx1 inhibits p21 expression to allow for cell proliferation in the dental epithelial cervical loop, however Tbx1 does not directly regulate p21 expression. A new molecular mechanism has been identified where Tbx1 inhibits Pitx2 transcriptional activity and decreases the expression of Pitx2 target genes, p21, Lef-1 and Pitx2c. p21 protein is increased in PITX2C transgenic mouse embryo fibroblasts (MEF) and chromatin immunoprecipitation assays demonstrate endogenous Pitx2 binding to the p21 promoter. Tbx1 attenuates PITX2 activation of endogenous p21 expression and Tbx1 null MEFs reveal increased Pitx2a and activation of Pitx2c isoform expression. Tbx1 physically interacts with the PITX2 C-terminus and represses PITX2 transcriptional activation of the p21, LEF-1, and Pitx2c promoters. Tbx1(-/+)/Pitx2(-/+) double heterozygous mice present with an extra premolar-like tooth revealing a genetic interaction between these factors. The ability of Tbx1 to repress PITX2 activation of p21 may promote cell proliferation. In addition, PITX2 regulation of p21 reveals a new role for PITX2 in repressing cell proliferation. These data demonstrate new functional mechanisms for Tbx1 in tooth morphogenesis and provide a molecular basis for craniofacial defects in DiGeorge syndrome patients. Copyright © 2010 Elsevier Inc. All rights reserved.

KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress.

PubMed

Choi, Shinkyu; Kim, Ji Aee; Li, Hai-Yan; Shin, Kyong-Oh; Oh, Goo Taeg; Lee, Yong-Moon; Oh, Seikwan; Pewzner-Jung, Yael; Futerman, Anthony H; Suh, Suk Hyo

2016-10-01

Endothelial oxidative stress develops with aging and reactive oxygen species impair endothelium-dependent relaxation (EDR) by decreasing nitric oxide (NO) availability. Endothelial KCa 3.1, which contributes to EDR, is upregulated by H2 O2 . We investigated whether KCa 3.1 upregulation compensates for diminished EDR to NO during aging-related oxidative stress. Previous studies identified that the levels of ceramide synthase 5 (CerS5), sphingosine, and sphingosine 1-phosphate were increased in aged wild-type and CerS2 mice. In primary mouse aortic endothelial cells (MAECs) from aged wild-type and CerS2 null mice, superoxide dismutase (SOD) was upregulated, and catalase and glutathione peroxidase 1 (GPX1) were downregulated, when compared to MAECs from young and age-matched wild-type mice. Increased H2 O2 levels induced Fyn and extracellular signal-regulated kinases (ERKs) phosphorylation and KCa 3.1 upregulation. Catalase/GPX1 double knockout (catalase(-/-) /GPX1(-/-) ) upregulated KCa 3.1 in MAECs. NO production was decreased in aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) MAECs. However, KCa 3.1 activation-induced, N(G) -nitro-l-arginine-, and indomethacin-resistant EDR was increased without a change in acetylcholine-induced EDR in aortic rings from aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) mice. CerS5 transfection or exogenous application of sphingosine or sphingosine 1-phosphate induced similar changes in levels of the antioxidant enzymes and upregulated KCa 3.1. Our findings suggest that, during aging-related oxidative stress, SOD upregulation and downregulation of catalase and GPX1, which occur upon altering the sphingolipid composition or acyl chain length, generate H2 O2 and thereby upregulate KCa 3.1 expression and function via a H2 O2 /Fyn-mediated pathway. Altogether, enhanced KCa 3.1 activity may compensate for decreased NO signaling during vascular aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Nonlinear Modeling of Radial Stellar Pulsations

NASA Astrophysics Data System (ADS)

Smolec, R.

2009-09-01

In this thesis, I present the results of my work concerning the nonlinear modeling of radial stellar pulsations. I will focus on classical Cepheids, particularly on the double-mode phenomenon. History of nonlinear modeling of radial stellar pulsations begins in the sixties of the previous century. At the beginning convection was disregarded in model equations. Qualitatively, almost all features of the radial pulsators were successfully modeled with purely radiative hydrocodes. Among problems that remained, the most disturbing was modeling of the double-mode phenomenon. This long-standing problem seemed to be finally solved with the inclusion of turbulent convection into the model equations (Kollath et al. 1998, Feuchtinger 1998). Although dynamical aspects of the double-mode behaviour were extensively studied, its origin, particularly the specific role played by convection, remained obscure. To study this and other problems of radial stellar pulsations, I implemented the convection into pulsation hydrocodes. The codes adopt the Kuhfuss (1986) convection model. In other codes, particularly in the Florida-Budapest hydrocode (e.g. Kollath et al. 2002), used in comput! ation of most of the published double-mode models, different approximations concerning e.g. eddy-viscous terms or treatment of convectively stable regions are adopted. Particularly the neglect of negative buoyancy effects in the Florida-Budapest code and its consequences, were never discussed in the literature. These consequences are severe. Concerning the single-mode pulsators, neglect of negative buoyancy leads to smaller pulsation amplitudes, in comparison to amplitudes computed with code including these effects. Particularly, neglect of negative buoyancy reduces the amplitude of the fundamental mode very strong. This property of the Florida-Budapest models is crucial in bringing up the stable non-resonant double-mode Cepheid pulsation involving fundamental and first overtone modes (F/1O). Such pulsation is not observed in models computed including negative buoyancy. As the neglect of negative buoyancy is physically not correct, so are the double-mode Cepheid models computed with the Florida-Budapest hydrocode. Extensive search for F/1O double-mode Cepheid pulsation with the codes including negative buoyancy effects yielded null result. Some resonant double-mode F/1O Cepheid models were found, but their occurrence was restricted to a very narrow domain in the Hertzsprung-Russel diagram. Model computations intended to model the double-overtone (1O/2O) Cepheids in the Large Magellanic Cloud, also revealed some stable double-mode pulsations, however, restricted to a narrow period range. Resonances are most likely conductive in bringing up the double-mode behaviour observed in these models. However, majority of the double-overtone LMC Cepheids cannot be reproduced with our codes. Hence, the modeling of double-overtone Cepheids with convective hydrocodes is not satisfactory, either. Double-mode pulsation still lacks satisfactory explanation, and problem of its modeling remains open.

Categorical clustering of the neural representation of color.

PubMed

Brouwer, Gijs Joost; Heeger, David J

2013-09-25

Cortical activity was measured with functional magnetic resonance imaging (fMRI) while human subjects viewed 12 stimulus colors and performed either a color-naming or diverted attention task. A forward model was used to extract lower dimensional neural color spaces from the high-dimensional fMRI responses. The neural color spaces in two visual areas, human ventral V4 (V4v) and VO1, exhibited clustering (greater similarity between activity patterns evoked by stimulus colors within a perceptual category, compared to between-category colors) for the color-naming task, but not for the diverted attention task. Response amplitudes and signal-to-noise ratios were higher in most visual cortical areas for color naming compared to diverted attention. But only in V4v and VO1 did the cortical representation of color change to a categorical color space. A model is presented that induces such a categorical representation by changing the response gains of subpopulations of color-selective neurons.

Diversion of ADHD Stimulants and Victimization Among Adolescents

PubMed Central

McCabe, Sean Esteban; Veliz, Philip T.; Stoddard, Sarah A.; Austic, Elizabeth A.; Boyd, Carol J.

2016-01-01

Objective To examine whether a recent prescription for stimulant medication is associated with peer victimization among youth with attention deficit/hyperactivity disorder (ADHD). Methods Data from 4,965 adolescents attending five public schools who completed an annual web survey over 4 years were used to examine recent stimulant medication prescription and self-reported frequent victimization. Results Adolescents with ADHD and recent stimulant prescription reported more victimization than those without ADHD, but similar to adolescents with ADHD and no recent prescription. Adolescents with ADHD and past 12-month diversion of their prescribed stimulants were at greatest risk of 12-month frequent victimization compared with adolescents without ADHD and adolescents with ADHD but no recent prescription. Youth approached to divert reported more victimization than youth not approached. Youth who diverted reported more victimization than those who did not divert. Conclusions Close parent–prescriber collaboration is needed to ensure effective medical treatment for ADHD without greater risk for victimization and treatment failure. PMID:26590265

Categorical Clustering of the Neural Representation of Color

PubMed Central

Heeger, David J.

2013-01-01

Cortical activity was measured with functional magnetic resonance imaging (fMRI) while human subjects viewed 12 stimulus colors and performed either a color-naming or diverted attention task. A forward model was used to extract lower dimensional neural color spaces from the high-dimensional fMRI responses. The neural color spaces in two visual areas, human ventral V4 (V4v) and VO1, exhibited clustering (greater similarity between activity patterns evoked by stimulus colors within a perceptual category, compared to between-category colors) for the color-naming task, but not for the diverted attention task. Response amplitudes and signal-to-noise ratios were higher in most visual cortical areas for color naming compared to diverted attention. But only in V4v and VO1 did the cortical representation of color change to a categorical color space. A model is presented that induces such a categorical representation by changing the response gains of subpopulations of color-selective neurons. PMID:24068814

Loss of Vitamin D Receptor Produces Polyuria by Increasing Thirst

PubMed Central

Kong, Juan; Zhang, Zhongyi; Li, Dongdong; Wong, Kari E.; Zhang, Yan; Szeto, Frances L.; Musch, Mark W.; Li, Yan Chun

2008-01-01

Vitamin D receptor (VDR)-null mice develop polyuria, but the underlying mechanism remains unknown. In this study, we investigated the relationship between vitamin D and homeostasis of water and electrolytes. VDR-null mice had polyuria, but the urine osmolarity was normal as a result of high salt excretion. The urinary responses to water restriction and to vasopressin were similar between wild-type and VDR-null mice, suggesting intact fluid-handling capacity in VDR-null mice. Compared with wild-type mice, however, renin and angiotensin II were dramatically upregulated in the kidney and brain of VDR-null mice, leading to a marked increase in water intake and salt appetite. Angiotensin II–mediated upregulation of intestinal NHE3 expression partially explained the increased salt absorption and excretion in VDR-null mice. In the brain of VDR-null mice, expression of c-Fos, which is known to associate with increased water intake, was increased in the hypothalamic paraventricular nucleus and the subfornical organ. Treatment with an angiotensin II type 1 receptor antagonist normalized water intake, urinary volume, and c-Fos expression in VDR-null mice. Furthermore, despite a salt-deficient diet to reduce intestinal salt absorption, VDR-null mice still maintained the increased water intake and urinary output. Together, these data indicate that the polyuria observed in VDR-null mice is not caused by impaired renal fluid handling or increased intestinal salt absorption but rather is the result of increased water intake induced by the increase in systemic and brain angiotensin II. PMID:18832438

Loss of vitamin D receptor produces polyuria by increasing thirst.

PubMed

Kong, Juan; Zhang, Zhongyi; Li, Dongdong; Wong, Kari E; Zhang, Yan; Szeto, Frances L; Musch, Mark W; Li, Yan Chun

2008-12-01

Vitamin D receptor (VDR)-null mice develop polyuria, but the underlying mechanism remains unknown. In this study, we investigated the relationship between vitamin D and homeostasis of water and electrolytes. VDR-null mice had polyuria, but the urine osmolarity was normal as a result of high salt excretion. The urinary responses to water restriction and to vasopressin were similar between wild-type and VDR-null mice, suggesting intact fluid-handling capacity in VDR-null mice. Compared with wild-type mice, however, renin and angiotensin II were dramatically upregulated in the kidney and brain of VDR-null mice, leading to a marked increase in water intake and salt appetite. Angiotensin II-mediated upregulation of intestinal NHE3 expression partially explained the increased salt absorption and excretion in VDR-null mice. In the brain of VDR-null mice, expression of c-Fos, which is known to associate with increased water intake, was increased in the hypothalamic paraventricular nucleus and the subfornical organ. Treatment with an angiotensin II type 1 receptor antagonist normalized water intake, urinary volume, and c-Fos expression in VDR-null mice. Furthermore, despite a salt-deficient diet to reduce intestinal salt absorption, VDR-null mice still maintained the increased water intake and urinary output. Together, these data indicate that the polyuria observed in VDR-null mice is not caused by impaired renal fluid handling or increased intestinal salt absorption but rather is the result of increased water intake induced by the increase in systemic and brain angiotensin II.

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

PubMed Central

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

2015-01-01

Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

Impaired hypothalamic regulation of endocrine function and delayed counterregulatory response to hypoglycemia in Magel2-null mice.

PubMed

Tennese, Alysa A; Wevrick, Rachel

2011-03-01

Hypothalamic dysfunction may underlie endocrine abnormalities in Prader-Willi syndrome (PWS), a genetic disorder that features GH deficiency, obesity, and infertility. One of the genes typically inactivated in PWS, MAGEL2, is highly expressed in the hypothalamus. Mice deficient for Magel2 are obese with increased fat mass and decreased lean mass and have blunted circadian rhythm. Here, we demonstrate that Magel2-null mice have abnormalities of hypothalamic endocrine axes that recapitulate phenotypes in PWS. Magel2-null mice had elevated basal corticosterone levels, and although male Magel2-null mice had an intact corticosterone response to restraint and to insulin-induced hypoglycemia, female Magel2-null mice failed to respond to hypoglycemia with increased corticosterone. After insulin-induced hypoglycemia, Magel2-null mice of both sexes became more profoundly hypoglycemic, and female mice were slower to recover euglycemia, suggesting an impaired hypothalamic counterregulatory response. GH insufficiency can produce abnormal body composition, such as that seen in PWS and in Magel2-null mice. Male Magel2-null mice had Igf-I levels similar to control littermates. Female Magel2-null mice had low Igf-I levels and reduced GH release in response to stimulation with ghrelin. Female Magel2-null mice did respond to GHRH, suggesting that their GH deficiency has a hypothalamic rather than pituitary origin. Female Magel2-null mice also had higher serum adiponectin than expected, considering their increased fat mass, and thyroid (T(4)) levels were low. Together, these findings strongly suggest that loss of MAGEL2 contributes to endocrine dysfunction of hypothalamic origin in individuals with PWS.

Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice.

PubMed

Tsuchiya, Hiroyuki; da Costa, Kerry-Ann; Lee, Sangmin; Renga, Barbara; Jaeschke, Hartmut; Yang, Zhihong; Orena, Stephen J; Goedken, Michael J; Zhang, Yuxia; Kong, Bo; Lebofsky, Margitta; Rudraiah, Swetha; Smalling, Rana; Guo, Grace; Fiorucci, Stefano; Zeisel, Steven H; Wang, Li

2015-05-01

Hyperhomocysteinemia is often associated with liver and metabolic diseases. We studied nuclear receptors that mediate oscillatory control of homocysteine homeostasis in mice. We studied mice with disruptions in Nr0b2 (called small heterodimer partner [SHP]-null mice), betaine-homocysteine S-methyltransferase (Bhmt), or both genes (BHMT-null/SHP-null mice), along with mice with wild-type copies of these genes (controls). Hyperhomocysteinemia was induced by feeding mice alcohol (National Institute on Alcohol Abuse and Alcoholism binge model) or chow diets along with water containing 0.18% DL-homocysteine. Some mice were placed on diets containing cholic acid (1%) or cholestyramine (2%) or high-fat diets (60%). Serum and livers were collected during a 24-hour light-dark cycle and analyzed by RNA-seq, metabolomic, and quantitative polymerase chain reaction, immunoblot, and chromatin immunoprecipitation assays. SHP-null mice had altered timing in expression of genes that regulate homocysteine metabolism compared with control mice. Oscillatory production of S-adenosylmethionine, betaine, choline, phosphocholine, glyceophosphocholine, cystathionine, cysteine, hydrogen sulfide, glutathione disulfide, and glutathione, differed between SHP-null mice and control mice. SHP inhibited transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1. Expression of Bhmt and cystathionine γ-lyase was decreased when mice were fed cholic acid but increased when they were placed on diets containing cholestyramine or high-fat content. Diets containing ethanol or homocysteine induced hyperhomocysteinemia and glucose intolerance in control, but not SHP-null, mice. In BHMT-null and BHMT-null/SHP-null mice fed a control liquid, lipid vacuoles were observed in livers. Ethanol feeding induced accumulation of macrovesicular lipid vacuoles to the greatest extent in BHMT-null and BHMT-null/SHP-null mice. Disruption of Shp in mice alters timing of expression of genes that regulate homocysteine metabolism and the liver responses to ethanol and homocysteine. SHP inhibits the transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice

PubMed Central

Kumar, Ramiya; Mota, Linda C.; Litoff, Elizabeth J.; Rooney, John P.; Boswell, W. Tyler; Courter, Elliott; Henderson, Charles M.; Hernandez, Juan P.; Corton, J. Christopher; Moore, David D.

2017-01-01

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16β-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and regulatory CYP changes followed the order CAR-null > Cyp3a-null > Cyp2b-null mice. PMID:28350814

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

PubMed Central

Keighren, Margaret A.; Flockhart, Jean H.

2016-01-01

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

Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice.

PubMed

Kumar, Ramiya; Mota, Linda C; Litoff, Elizabeth J; Rooney, John P; Boswell, W Tyler; Courter, Elliott; Henderson, Charles M; Hernandez, Juan P; Corton, J Christopher; Moore, David D; Baldwin, William S

2017-01-01

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16β-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and regulatory CYP changes followed the order CAR-null > Cyp3a-null > Cyp2b-null mice.

Analyses of Genetic Variations of Glutathione S-Transferase Mu1 and Theta1 Genes in Bangladeshi Tannery Workers and Healthy Controls.

PubMed

Akther, Jobaida; Ebihara, Akio; Nakagawa, Tsutomu; Islam, Laila N; Suzuki, Fumiaki; Hosen, Md Ismail; Hossain, Mahmud; Nabi, A H M Nurun

2016-01-01

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/-), 31.4% had GSTT1 (-/+) alleles, and 6.4% had null genotypes (-/-) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/-, 30.5% were -/+, and 8.4% were -/-. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes.

Trypanosoma brucei (UMP synthase null mutants) are avirulent in mice, but recover virulence upon prolonged culture in vitro while retaining pyrimidine auxotrophy.

PubMed

Ong, Han B; Sienkiewicz, Natasha; Wyllie, Susan; Patterson, Stephen; Fairlamb, Alan H

2013-10-01

African trypanosomes are capable of both de novo synthesis and salvage of pyrimidines. The last two steps in de novo synthesis are catalysed by UMP synthase (UMPS) - a bifunctional enzyme comprising orotate phosphoribosyl transferase (OPRT) and orotidine monophosphate decarboxylase (OMPDC). To investigate the essentiality of pyrimidine biosynthesis in Trypanosoma brucei, we generated a umps double knockout (DKO) line by gene replacement. The DKO was unable to grow in pyrimidine-depleted medium in vitro, unless supplemented with uracil, uridine, deoxyuridine or UMP. DKO parasites were completely resistant to 5-fluoroorotate and hypersensitive to 5-fluorouracil, consistent with loss of UMPS, but remained sensitive to pyrazofurin indicating that, unlike mammalian cells, the primary target of pyrazofurin is not OMPDC. The null mutant was unable to infect mice indicating that salvage of host pyrimidines is insufficient to support growth. However, following prolonged culture in vitro, parasites regained virulence in mice despite retaining pyrimidine auxotrophy. Unlike the wild-type, both pyrimidine auxotrophs secreted substantial quantities of orotate, significantly higher in the virulent DKO line. We propose that this may be responsible for the recovery of virulence in mice, due to host metabolism converting orotate to uridine, thereby bypassing the loss of UMPS in the parasite. © 2013 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells

PubMed Central

Burlison, Jared S.; Long, Qiaoming; Fujitani, Yoshio; Wright, Christopher V.E.; Magnuson, Mark A.

2008-01-01

The pancreas is derived from a pool of multipotent progenitor cells (MPCs) that co-express Pdx-1 and Ptf1a. To more precisely define how the individual and combined loss of Pdx-1 and Ptf1a affects pancreatic MPC specification and differentiation we derived and studied mice bearing a novel Ptf1aYFP allele. While the expression of Pdx-1 and Ptf1a in pancreatic MPCs coincides between E9.5–12.5 the developmental phenotypes of Pdx-1 null and Pdx-1; Ptf1a double null mice are indistinguishable, and an early pancreatic bud is formed in both cases. This finding indicates that Pdx-1 is required in the foregut endoderm prior to Ptf1a for pancreatic MPC specification. We also found that Ptf1a is neither required for specification of Ngn3-positive endocrine progenitors nor differentiation of mature β-cells. In the absence of Pdx-1 Ngn3-positive cells were not observed after E9.5. Thus, in contrast to the deletion of Ptf1a, the loss of Pdx-1 precludes the sustained Ngn3-based derivation of endocrine progenitors from pancreatic MPCs. Taken together, these studies indicate that Pdx-1 and Ptf1a have distinct but interdependent functions during pancreatic MPC specification. PMID:18294628

Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells.

PubMed

Burlison, Jared S; Long, Qiaoming; Fujitani, Yoshio; Wright, Christopher V E; Magnuson, Mark A

2008-04-01

The pancreas is derived from a pool of multipotent progenitor cells (MPCs) that co-express Pdx-1 and Ptf1a. To more precisely define how the individual and combined loss of Pdx-1 and Ptf1a affects pancreatic MPC specification and differentiation we derived and studied mice bearing a novel Ptf1a(YFP) allele. While the expression of Pdx-1 and Ptf1a in pancreatic MPCs coincides between E9.5 and 12.5 the developmental phenotypes of Pdx-1 null and Pdx-1; Ptf1a double null mice are indistinguishable, and an early pancreatic bud is formed in both cases. This finding indicates that Pdx-1 is required in the foregut endoderm prior to Ptf1a for pancreatic MPC specification. We also found that Ptf1a is neither required for specification of Ngn3-positive endocrine progenitors nor differentiation of mature beta-cells. In the absence of Pdx-1 Ngn3-positive cells were not observed after E9.5. Thus, in contrast to the deletion of Ptf1a, the loss of Pdx-1 precludes the sustained Ngn3-based derivation of endocrine progenitors from pancreatic MPCs. Taken together, these studies indicate that Pdx-1 and Ptf1a have distinct but interdependent functions during pancreatic MPC specification.

Clock genes and salt-sensitive hypertension: a new type of aldosterone-synthesizing enzyme controlled by the circadian clock and angiotensin II.

PubMed

Okamura, Hitoshi; Doi, Masao; Goto, Kaoru; Kojima, Rika

2016-10-01

With the current societal norm of shiftwork and long working hours, maintaining a stable daily life is becoming very difficult. An irregular lifestyle disrupts circadian rhythms, resulting in the malfunction of body physiology and ultimately leading to lifestyle-related diseases, including hypertension. By analyzing completely arrhythmic Cry1/Cry2 double-knockout (Cry-null) mice, we found salt-sensitive hypertension accompanied by hyperaldosteronism. On the basis of a DNA microarray analysis of the adrenal gland and subsequent biochemical analyses, we discovered that Hsd3b6/HSD3B1, a subtype of 3β-HSD, is markedly overexpressed in aldosterone-producing cells in the Cry-null adrenal cortex. In addition, we found that Hsd3b6/HSD3B1, which converts pregnenolone to progesterone, is a clock-controlled gene and might also be a key enzyme for the regulation of aldosterone biosynthesis, in addition to the previously established CYP11B2, which synthesizes aldosterone from deoxycorticosterone. Importantly, angiotensin II induces HSD3B1 via the transcription factor NGFIB in human adrenocortical H295R cells, similarly to CYP11B2. As HSD3B1 levels are abnormally high in the adrenal aldosterone-producing cells of idiopathic hyperaldosteronism (IHA), the temporal component of this system in the pathophysiology of IHA is a promising area for future research.

Mdm-2 binding and TAF(II)31 recruitment is regulated by hydrogen bond disruption between the p53 residues Thr18 and Asp21.

PubMed

Jabbur, James R; Tabor, Amy D; Cheng, Xiaodong; Wang, Hua; Uesugi, Motonari; Lozano, Guillermina; Zhang, Wei

2002-10-10

Analyses of five wild-type p53 containing cell lines revealed lineage specific differences in phosphorylation of Thr18 after treatment with ionizing (IR) or ultraviolet (UV) radiation. Importantly, Thr18 phosphorylation correlated with induction of the p53 downstream targets p21(Waf1/Cip1) (p21) and Mdm-2, suggesting a transactivation enhancing role. Thr18 phosphorylation has been shown to abolish side-chain hydrogen bonding between Thr18 and Asp21, an interaction necessary for stabilizing alpha-helical conformation within the transactivation domain. Mutagenesis-derived hydrogen bond disruption attenuated the interaction of p53 with the transactivation repressor Mdm-2 but had no direct effect on the interaction of p53 with the basal transcription factor TAF(II)31. However, prior incubation of p53 mutants with Mdm-2 modulated TAF(II)31 interaction with p53, suggesting Mdm-2 blocks the accessibility of p53 to TAF(II)31. Consistently, p53-null cells transfected with hydrogen bond disrupting p53 mutants demonstrated enhanced endogenous p21 expression, whereas p53/Mdm-2-double null cells exhibited no discernible differences in p21 expression. We conclude disruption of intramolecular hydrogen bonding between Thr18 and Asp21 enhances p53 transactivation by modulating Mdm-2 binding, facilitating TAF(II)31 recruitment.

The role of spatial and temporal heterogeneity and competition in structuring trematode communities in the great pond snail, Lymnaea stagnalis (L.)

USGS Publications Warehouse

Soldánová, Miroslava; Kuris, Armand M.; Scholz, Tomáš; Lafferty, Kevin D.

2012-01-01

We assessed how spatial and temporal heterogeneity and competition structure larval trematode communities in the pulmonate snail Lymnaea stagnalis. To postulate a dominance hierarchy, mark-release-recapture was used to monitor replacements of trematode species within snails over time. In addition, we sampled the trematode community in snails in different ponds in 3 consecutive years. A total of 7,623 snails (10,382 capture events) was sampled in 7 fishponds in the Jindřichův Hradec and Třeboň areas in South Bohemia (Czech Republic) from August 2006 to October 2008. Overall, 39% of snails were infected by a community of 14 trematode species; 7% of snails were infected with more than 1 trematode species (constituting 16 double- and 4 triple-species combinations). Results of the null-model analyses suggested that spatial heterogeneity in recruitment among ponds isolated trematode species from each other, whereas seasonal pulses in recruitment increased species interactions in some ponds. Competitive exclusion among trematodes led to a rarity of multiple infections compared to null-model expectations. Competitive relationships among trematode species were hypothesized as a dominance hierarchy based on direct evidence of replacement and invasion and on indirect evidence. Seven top dominant species with putatively similar competitive abilities (6 rediae and 1 sporocyst species) reduced the prevalence of the other trematode species developing in sporocysts only.

Bubble induced flow field modulation for pool boiling enhancement over a tubular surface

NASA Astrophysics Data System (ADS)

Raghupathi, P. A.; Joshi, I. M.; Jaikumar, A.; Emery, T. S.; Kandlikar, S. G.

2017-06-01

We demonstrate the efficacy of using a strategically placed enhancement feature to modify the trajectory of bubbles nucleating on a horizontal tubular surface to increase both the critical heat flux (CHF) and the heat transfer coefficient (HTC). The CHF on a plain tube is shown to be triggered by a local dryout at the bottom of the tube due to vapor agglomeration. To mitigate this effect and delay CHF, the nucleating bubble trajectory is modified by incorporating a bubble diverter placed axially at the bottom of the tube. The nucleating bubble at the base of the diverter experiences a tangential evaporation momentum force (EMF) which causes the bubble to grow sideways away from the tube and avoid localized bubble patches that are responsible for CHF initiation. High speed imaging confirmed the lateral displacement of the bubbles away from the diverter closely matched with the theoretical predictions using EMF and buoyancy forces. Since the EMF is stronger at higher heat fluxes, bubble displacement increases with heat flux and results in the formation of separate liquid-vapor pathways wherein the liquid enters almost unobstructed at the bottom and the vapor bubble leaves sideways. Experimental results yielded CHF and HTC enhancements of ˜60% and ˜75%, respectively, with the diverter configuration when compared to a plain tube. This work can be used for guidance in developing enhancement strategies to effectively modulate the liquid-vapor flow around the heater surface at various locations to enhance HTC and CHF.

A magnetic diverter for charged particle background rejection in the SIMBOL-X telescope

NASA Astrophysics Data System (ADS)

Spiga, D.; Fioretti, V.; Bulgarelli, A.; Dell'Orto, E.; Foschini, L.; Malaguti, G.; Pareschi, G.; Tagliaferri, G.; Tiengo, A.

2008-07-01

Minimization of charged particle background in X-ray telescopes is a well known issue. Charged particles (chiefly protons and electrons) naturally present in the cosmic environment constitute an important background source when they collide with the X-ray detector. Even worse, a serious degradation of spectroscopic performances of the X-ray detector was observed in Chandra and Newton-XMM, caused by soft protons with kinetic energies ranging between 100 keV and some MeV being collected by the grazing-incidence mirrors and funneled to the detector. For a focusing telescope like SIMBOL-X, the exposure of the soft X-ray detector to the proton flux can increase significantly the instrumental background, with a consequent loss of sensitivity. In the worst case, it can also seriously compromise the detector duration. A well-known countermeasure that can be adopted is the implementation of a properly-designed magnetic diverter, that should prevent high-energy particles from reaching the focal plane instruments of SIMBOL-X. Although Newton-XMM and Swift-XRT are equipped with magnetic diverters for electrons, the magnetic fields used are insufficient to effectively act on protons. In this paper, we simulate the behavior of a magnetic diverter for SIMBOL-X, consisting of commercially-available permanent magnets. The effects of SIMBOL-X optics is simulated through GEANT4 libraries, whereas the effect of the intense required magnetic fields is simulated along with specifically-written numerical codes in IDL.

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

ERIC Educational Resources Information Center

McCabe, Declan J.; Knight, Evelyn J.

2016-01-01

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

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

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Interpreting null results from measurements with uncertain correlations: an info-gap approach.

PubMed

Ben-Haim, Yakov

2011-01-01

Null events—not detecting a pernicious agent—are the basis for declaring the agent is absent. Repeated nulls strengthen confidence in the declaration. However, correlations between observations are difficult to assess in many situations and introduce uncertainty in interpreting repeated nulls. We quantify uncertain correlations using an info-gap model, which is an unbounded family of nested sets of possible probabilities. An info-gap model is nonprobabilistic and entails no assumption about a worst case. We then evaluate the robustness, to uncertain correlations, of estimates of the probability of a null event. This is then the basis for evaluating a nonprobabilistic robustness-based confidence interval for the probability of a null. © 2010 Society for Risk Analysis.

Flow-independent dynamics in aneurysm (FIDA): pressure measurements following partial and complete flow impairment in experimental aneurysm model

PubMed Central

Watanabe, Masaki; Chaudhry, Saqib A; Qureshi, Adnan I

2014-01-01

Background: There have been growing concerns regarding delayed aneurysm rupture subsequent to the flow-diverting stent deployment. Therefore, more investigations are needed regarding hemodynamic changes secondary to flow-diverting stent deployment. Objective: To study intra-aneurysmal and perianeurysmal pressures after partial and complete flow impairment into the aneurysm. Methods A silicone model of an 8-mm-sized aneurysm (neck diameter: 5 mm, vessel size: 4 mm) was used. The aneurysm wall was encapsulated and sealed within a 5 ml syringe filled with saline and a pressure sensor guide wire (ComboWire, Volcano Corp.) to detect pressure changes in the perivascular compartment (outer aneurysm wall). A second pressure sensor guide wire was advanced inside the aneurysm sac. Both pressure sensors were continuously measuring pressure inside and outside the aneurysm under pulsatile flow under the following conditions: 1) baseline (reference); 2) a 16 mm by 3.75 mm flow-diverting stent (ev3/Covidien Vascular, Mansfield, MA) deployed in front of the aneurysm; 3) two flow-diverting stents (16 mm by 3.5 mm) were deployed; and 4) a covered stent (4 mm by 16 mm VeriFlex coronary artery stent covered with rubber sheet) was deployed. Results: Mean (±SD) baseline pressures inside and outside the aneurysm were 53.9 (±2.4) mmHg (range 120–40 mmHg) and 15.4 (±0.7) mmHg (range 40–8mmHg), respectively. There was no change in pressure inside and outside the aneurysm after deploying the first and second flow-diverting stents (partial flow impairment) and it remained at 53.9 (±2.7) mmHg and 14.9 (±1) mmHg for the pressure inside and outside the aneurysm, respectively. The pressure recording from outside the aneurysm dropped from 15.4 (±0.7) mmHg to 0.3 (±0.7) mmHg after deploying the covered stent (complete flow impairment). There was no change in pressure inside the aneurysm after deploying the covered stent. Mean (±SD) pressure within the aneurysm was 55.1 (±1.7) mmHg and it remained 54.7 (±1.7) mmHg after covered stent deployment. Conclusion: Our findings suggest a major discordance between the pressures within the aneurysm and partial or complete flow impairment (flow independent). The outer wall pressure is reduced after covered stent placement. These finding may assist clinicians in better understanding of aneurysm hemodynamics and rupture after flow-diverting stent deployment. PMID:25298859

Level of Need, Divertibility, and Outcomes of Newly Admitted Nursing Home Residents.

PubMed

Tanuseputro, Peter; Hsu, Amy; Kuluski, Kerry; Chalifoux, Mathieu; Donskov, Melissa; Beach, Sarah; Walker, Peter

2017-07-01

To describe the level of need and divertibility of newly admitted nursing home residents, describe the factors that drive need, and describe the outcomes of residents across different levels of need. Retrospective cohort study. A total of 640 publicly funded nursing homes (also known as long-term care facilities) in Ontario, Canada. All newly admitted residents between January 1, 2010 and March 1, 2012. We categorized residents into 36 groups based on different levels of (1) cognitive impairment, (2) difficulty in activities of daily living (ADL), (3) difficulty in instrumental ADLs, and (4) whether or not they had a caregiver at home. Residents were then categorized as having low, intermediate, or high needs; applying results from previous "Balance of Care" studies, we also captured the proportion who could have been cost-effectively diverted into the community. We then contrasted the characteristics of residents across the needs and divertible groupings, and compared 4 outcomes among these groups: hospital admissions, emergency department visits, mortality, and return to home. A population-level cohort of 64,105 incident admissions was captured. About two-thirds had great difficulty performing ADLs (65%) and had mild to severe cognitive impairment (66%); over 90% had great difficulty with instrumental ADLs. Just less than 50% of the new admissions were considered to be residents with high care needs (cognitively impaired with great ADL difficulty), while only 4.5% (2880 residents) had low care needs (cognition and ADL intact). Those with dementia (71.0%) and previous stroke (21.5%) were over-represented in the high needs group. Those that cannot be divertible to anywhere else but an institution with 24 hour nursing care comprised 41.3% (n = 26,502) of residents. Only 5.4% (n = 3483), based on community resources available, could potentially be cost-effectively diverted to the community. Those at higher needs experienced higher rates of mortality, higher total cost across all health sectors, and lower rates of return to home. The majority of those admitted into nursing homes have high levels of need (driven largely by dementia and stroke) and could not have their needs met cost-effectively elsewhere, suggesting that the system is at capacity. Caring for the long-term care needs of the aging population should consider the balance of investments in institution and community settings. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking

PubMed Central

Abu-Amero, Khaled K; Al-Boudari, Olayan M; Mohamed, Gamal H; Dzimiri, Nduna

2006-01-01

Background The association of the deletion in GSTT1 and GSTM1 genes with coronary artery disease (CAD) among smokers is controversial. In addition, no such investigation has previously been conducted among Arabs. Methods We genotyped 1054 CAD patients and 762 controls for GSTT1 and GSTM1 deletion by multiplex polymerase chain reaction. Both CAD and controls were Saudi Arabs. Results In the control group (n = 762), 82.3% had the T wild M wildgenotype, 9% had the Twild M null, 2.4% had the Tnull M wild and 6.3% had the Tnull M null genotype. Among the CAD group (n = 1054), 29.5% had the Twild M wild genotype, 26.6% (p < .001) had the Twild M null, 8.3% (p < .001) had the Tnull M wild and 35.6% (p < .001) had the Tnull M null genotype, indicating a significant association of the Twild M null, Tnull M wild and Tnull M null genotypes with CAD. Univariate analysis also showed that smoking, age, hypercholesterolemia and hypertriglyceridemia, diabetes mellitus, family history of CAD, hypertension and obesity are all associated with CAD, whereas gender and myocardial infarction are not. Binary logistic regression for smoking and genotypes indicated that only M null and Tnullare interacting with smoking. However, further subgroup analysis stratifying the data by smoking status suggested that genotype-smoking interactions have no effect on the development of CAD. Conclusion GSTT1 and GSTM1 null-genotypes are risk factor for CAD independent of genotype-smoking interaction. PMID:16620396

Supermassive black hole binaries and transient radio events: studies in pulsar astronomy

NASA Astrophysics Data System (ADS)

Burke-Spolaor, S.

2011-06-01

The field of pulsar astronomy encompasses a rich breadth of astrophysical topics. The research in this thesis contributes to two particular subjects of pulsar astronomy: gravitational wave science, and identifying celestial sources of pulsed radio emission. We first investigated the detection of supermassive black hole (SMBH) binaries, which are the brightest expected source of gravitational waves for pulsar timing. We considered whether two electromagnetic SMBH tracers, velocity-resolved emission lines in active nuclei, and radio galactic nuclei with spatially-resolved, flat-spectrum cores, can reveal systems emitting gravitational waves in the pulsar timing band. We found that there are systems which may in principle be simultaneously detectable by both an electromagnetic signature and gravitational emission, however the probability of actually identifying such a system is low (they will represent much less than 1% of a randomly selected galactic nucleus sample). This study accents the fact that electromagnetic indicators may be used to explore binary populations down to the 'stalling radii' at which binary inspiral evolution may stall indefinitely at radii exceeding those which produce gravitational radiation in the pulsar timing band. We then performed a search for binary SMBH holes in archival Very Long Baseline Interferometry data for 3114 radio-luminous active galactic nuclei. One source was detected as a double nucleus. This result is interpreted in terms of post-merger timescales for SMBH centralisation, implications for 'stalling', and the relationship of radio activity in nuclei to mergers. Our analysis suggested that binary pair evolution of SMBHs (both of masses >108M circled bullet) spends less than 500Myr in progression from the merging of galactic stellar cores to within the purported stalling radius for SMBH pairs, giving no evidence for an excess of stalled binary systems at small separations. Circumstantial evidence showed that the relative state of radio emission between paired SMBHs is correlated within orbital separations of 2.5 kpc. We then searched for transient radio events in two archival pulsar surveys, and in the new High Time Resolution Universe (HTRU) Survey. We present the methodology employed for these searches, noting the novel addition of methods for single-event recognition, automatic interference mitigation, and data inspection. 27 new neutron stars were discovered. We discuss the relationship between "rotating radio transient" (RRAT) and pulsar populations, finding that the Galactic z-distribution of RRATs closely resembles the distribution of pulsars, and where measurable, RRAT pulse widths are similar to individual pulses from pulsars of similar period, implying a similar beaming fraction. We postulate that many RRATs may simply represent a tail of extreme-nulling pulsars that are "on" for less than a pulse period; this is supported by the fact that nulling pulsars and single-pulse discoveries exhibit a continuous distribution across null/activity timescales and nulling fractions. We found a drop-off in objects with emissivity cycles longer than 300 seconds at intermediate and low nulling fractions which is not readily explained by selection effects. The HTRU deep low-latitude survey (70-min. pointings at galactic latitudes |b| < 3.5 degrees and longitudes -80 degrees < l < 30 degrees) will be capable of exploring whether this deficit is natural or an effect of selection. The intriguing object PSR J0941-39 may represent an evolutionary link between nulling populations; discovered as an sparsely-pulsing RRAT, in follow-up observations it often appeared as a bright (10 mJy) pulsar with a low nulling fraction. It is therefore apparent that a neutron star can oscillate between nulling levels, much like mode-changing pulsars. Crucially, the RRAT and pulsar-mode emission sites are coincident, implying that the two emission mechanisms are linked. We estimate that the full HTRU survey will roughly quadruple the known deep-nulling pulsar population, allowing statistical studies to be made of extreme-nulling populations. HTRU's low-latitude survey will explore the neutron star population with null lengths lasting up to several hours. We lastly reported the discovery of 16 pulses, the bulk of which exhibit a frequency sweep with a shape and magnitude resembling the "Lorimer Burst" (Lorimer et al. 2007), which three years ago was reported as a solitary radio burst that was thought to be the first discovery of a rare, impulsive event of unknown extragalactic origin. However, the new events were of clearly terrestrial origin, with properties unlike any known sources of terrestrial broad-band radio emission. The new detections cast doubt on the extragalactic interpretation of the original burst, and call for further sophistication in radio-pulse survey techniques to identify the origin of the anomalous terrestrial signals and definitively distinguish future extragalactic pulse detections from local signals. The ambiguous origin of these seemingly dispersed, swept-frequency signals suggest that radio-pulse searches using multiple detectors will be the only experiments able to provide definitive information about the origin of new swept-frequency radio burst detections. Finally, we summarise our major findings and suggest future work which would expand on the work in this thesis.

Qualification of a Null Lens Using Image-Based Phase Retrieval

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

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

PubMed Central

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. PMID:24200853

Null conformal Killing-Yano tensors and Birkhoff theorem

NASA Astrophysics Data System (ADS)

Ferrando, Joan Josep; Sáez, Juan Antonio

2016-04-01

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

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

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

Transforming Growth Factor Beta (TGFβ1, TGFβ2 and TGFβ3) Null-Mutant Phenotypes in Embryonic Gonadal Development

PubMed Central

Memon, Mushtaq A.; Anway, Matthew D.; Covert, Trevor R.; Uzumcu, Mehmet; Skinner, Michael K.

2008-01-01

The role transforming growth factor beta (TGFb) isoforms TGFb1, TGFb2 and TGFb3 have in the regulation of embryonic gonadal development was investigated with the use of null-mutant (i.e. knockout) mice for each of the TGFb isoforms. Late embryonic gonadal development was investigated because homozygote TGFb null-mutant mice generally die around birth, with some embryonic loss as well. In the testis, the TGFb1 null-mutant mice had a decrease in the number of germ cells at birth, postnatal day 0 (P0). In the testis, the TGFb2 null-mutant mice had a decrease in the number of seminiferous cords at embryonic day 15 (E15). In the ovary, the TGFb2 null-mutant mice had an increase in the number of germ cells at P0. TGFb isoforms appear to have a role in gonadal development, but interactions between the isoforms is speculated to compensate in the different TGFb isoform null-mutant mice. PMID:18790002

Method and apparatus for preventing overspeed in a gas turbine

DOEpatents

Walker, William E.

1976-01-01

A method and apparatus for preventing overspeed in a gas turbine in response to the rapid loss of applied load is disclosed. The method involves diverting gas from the inlet of the turbine, bypassing the same around the turbine and thereafter injecting the diverted gas at the turbine exit in a direction toward or opposing the flow of gas through the turbine. The injected gas is mixed with the gas exiting the turbine to thereby minimize the thermal shock upon equipment downstream of the turbine exit.

Arabidopsis G-protein β subunit AGB1 interacts with NPH3 and is involved in phototropism.

PubMed

Kansup, Jeeraporn; Tsugama, Daisuke; Liu, Shenkui; Takano, Tetsuo

2014-02-28

Heterotrimeric G proteins (Gα, Gβ and Gγ) have pleiotropic roles in plants, but molecular mechanisms underlying them remain to be elucidated. Here we show that Arabidopsis Gβ (AGB1) interacts with NPH3, a regulator of phototropism. Yeast two-hybrid assays, in vitro pull-down assays and bimolecular fluorescence complementation assays showed that AGB1 and NPH3 physically interact. NPH3-null mutation (nph3) is known to completely abolish hypocotyl phototropism. Loss-of-function mutants of AGB1 (agb1-1 and agb1-2) showed decreased hypocotyl phototropism, and agb1/nph3 double mutants showed no hypocotyl phototropism. These results suggest that AGB1 is involved in the NPH3-mediated regulation of phototropism. Copyright © 2014 Elsevier Inc. All rights reserved.

Science Results From The ARCADE Open-Aperture Cryogenic Balloon Payload

NASA Technical Reports Server (NTRS)

Kogut, Alan J.

2010-01-01

The Absolute Radiometer for Cosmology, Astrophysics, and Diffuse Emission (ARCADE) is a balloon-borne instrument to measure the frequency spectrum of the cosmic microwave background and diffuse Galactic foregrounds at centimeter wavelengths. ARCADE greatly reduces measurement uncertainties compared to previous balloon-borne or ground-based instrument using a double-nulled design that features fully cryogenic optics with no windows between the atmosphere and the 2.7 K instrument. A four-hour flight in 2006 achieved sensitivity comparable to the COBE/FIRAS satellite measurement while providing new insights for emission ranging from spinning dust in the interstellar medium to an unexpectedly bright extragalactic radio background. I will discuss scientific results from the ARCADE program and implications of the ARCADE cold optics for millimeter and sub-mm astronomy.

Probing transcription-specific outputs of β-catenin in vivo

PubMed Central

Valenta, Tomas; Gay, Max; Steiner, Sarah; Draganova, Kalina; Zemke, Martina; Hoffmans, Raymond; Cinelli, Paolo; Aguet, Michel; Sommer, Lukas; Basler, Konrad

2011-01-01

β-Catenin, apart from playing a cell-adhesive role, is a key nuclear effector of Wnt signaling. Based on activity assays in Drosophila, we generated mouse strains where the endogenous β-catenin protein is replaced by mutant forms, which retain the cell adhesion function but lack either or both of the N- and the C-terminal transcriptional outputs. The C-terminal activity is essential for mesoderm formation and proper gastrulation, whereas N-terminal outputs are required later during embryonic development. By combining the double-mutant β-catenin with a conditional null allele and a Wnt1-Cre driver, we probed the role of Wnt/β-catenin signaling in dorsal neural tube development. While loss of β-catenin protein in the neural tube results in severe cell adhesion defects, the morphology of cells and tissues expressing the double-mutant form is normal. Surprisingly, Wnt/β-catenin signaling activity only moderately regulates cell proliferation, but is crucial for maintaining neural progenitor identity and for neuronal differentiation in the dorsal spinal cord. Our model animals thus allow dissecting signaling and structural functions of β-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. PMID:22190459

Magnetoacoustic Waves in a Stratified Atmosphere with a Magnetic Null Point

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tarr, Lucas A.; Linton, Mark; Leake, James, E-mail: lucas.tarr.ctr@nrl.navy.mil

2017-03-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, J. Q.; Yang, K.; Cheng, X.

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

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

PubMed

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 compositional null model. © 2017 John Wiley & Sons Ltd.

High frequency generation in the corona: Resonant cavities

NASA Astrophysics Data System (ADS)

Santamaria, I. C.; Van Doorsselaere, T.

2018-03-01

Aims: Null points are prominent magnetic field singularities in which the magnetic field strength strongly decreases in very small spatial scales. Around null points, predicted to be ubiquitous in the solar chromosphere and corona, the wave behavior changes considerably. Null points are also responsible for driving very energetic phenomena, and for contributing to chromospheric and coronal heating. In previous works we demonstrated that slow magneto-acoustic shock waves were generated in the chromosphere propagate through the null point, thereby producing a train of secondary shocks escaping along the field lines. A particular combination of the shock wave speeds generates waves at a frequency of 80 MHz. The present work aims to investigate this high frequency region around a coronal null point to give a plausible explanation to its generation at that particular frequency. Methods: We carried out a set of two-dimensional numerical simulations of wave propagation in the neighborhood of a null point located in the corona. We varied both the amplitude of the driver and the atmospheric properties to investigate the sensitivity of the high frequency waves to these parameters. Results: We demonstrate that the wave frequency is sensitive to the atmospheric parameters in the corona, but it is independent of the strength of the driver. Thus, the null point behaves as a resonant cavity generating waves at specific frequencies that depend on the background equilibrium model. Moreover, we conclude that the high frequency wave train generated at the null point is not necessarily a result of the interaction between the null point and a shock wave. This wave train can be also developed by the interaction between the null point and fast acoustic-like magneto-acoustic waves, that is, this interaction within the linear regime.

Austerity and its implications for immigrant health in France.

PubMed

Sargent, Carolyn; Kotobi, Laurence

2017-08-01

The ongoing economic crisis in France increasingly has affected immigrant rights, including access to health care. Consistent with a 2014 League Against Cancer survey, we identify the ways in which sickness produces a "double penalty" for immigrants with serious illness. Immigrants with chronic illnesses such as cancer, diabetes, and other debilitating conditions divert vital funds from daily needs to deal with sickness and loss of work while at the same time national austerity measures shred the state's traditional safety net of social services and support. We examine how immigrants strategize to manage financial exigencies, therapeutic itineraries and social relations in the face of these converging pressures. We base our findings on two studies related by this theme: an investigation of health inequalities in the Médoc region, in which 88 women, 44 of North African and Eastern European origin, were interviewed over a three-year period (2010-2013); and a three-year study (2014-2017) of West African immigrant women with breast cancer seeking treatment in the greater Paris region, 70 members of immigrant associations, and clinical personnel in three hospitals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Band 3 nullVIENNA , a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis.

PubMed

Kager, Leo; Bruce, Lesley J; Zeitlhofer, Petra; Flatt, Joanna F; Maia, Tabita M; Ribeiro, M Leticia; Fahrner, Bernhard; Fritsch, Gerhard; Boztug, Kaan; Haas, Oskar A

2017-03-01

We describe the second patient with anionic exchanger 1/band 3 null phenotype (band 3 null VIENNA ), which was caused by a novel nonsense mutation c.1430C>A (p.Ser477X) in exon 12 of SLC4A1. We also update on the previous band 3 null COIMBRA patient, thereby elucidating the physiological implications of total loss of AE1/band 3. Besides transfusion-dependent severe hemolytic anemia and complete distal renal tubular acidosis, dyserythropoiesis was identified in the band 3 null VIENNA patient, suggesting a role for band 3 in erythropoiesis. Moreover, we also, for the first time, report that long-term survival is possible in band 3 null patients. © 2016 Wiley Periodicals, Inc.

On the Penrose inequality along null hypersurfaces

NASA Astrophysics Data System (ADS)

Mars, Marc; Soria, Alberto

2016-06-01

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

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

PubMed

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olshevsky, Vyacheslav; Lapenta, Giovanni; Divin, Andrey

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 linesmore » 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.« less

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

PubMed

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.

Shocks and currents in stratified atmospheres with a magnetic null point

NASA Astrophysics Data System (ADS)

Tarr, Lucas A.; Linton, Mark

2017-08-01

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

Efficacy of loop colostomy construction for acute left-sided colonic obstructions: a cohort analysis.

PubMed

Amelung, Femke J; Mulder, Charlotte L J; Broeders, Ivo A M J; Consten, Esther C J; Draaisma, Werner A

2017-03-01

Acute primary resection as treatment for left-sided colonic obstruction (LSCO) is notorious for its high morbidity and mortality rates. Both stenting and loop colostomy construction can serve as a bridge to surgery, hereby avoiding the high morbidity and mortality rates associated with emergency resections. This study aims to investigate the safety of a loop colostomy in patients presenting with acute LSCO. Retrospective analysis of all patients that received a loop colostomy for LSCO between 2003 and 2015 was performed. Primary outcomes were mortality, major morbidity (Clavien-Dindo grades III-IV) and minor morbidity (Clavien-Dindo grades I-II). One hundred forty-six patients presenting with acute LSCO received a diverting colostomy. After colostomy construction, mortality occurred in four patients (2.7%) and major complications were reported in 20 patients (13.7%). In 61 patients, the diverting colostomy served as a palliative measure, because of metastatic disease or unfitness for major surgery. The remaining 85 patients all underwent delayed resection, resulting in an overall mortality, major morbidity and minor morbidity of 6.9% (n = 6), 14.0% (n = 12) and 26.7% (n = 23), respectively. Diverting colostomy construction is a minimally invasive and safe treatment option for LSCO. It can serve as a definite palliative measure, as well as a bridge to elective surgery. A diverting colostomy as a bridge to surgery might even be a valid alternative for emergency resections, since mortality and morbidity rates following colostomy construction and delayed resection appear lower than reported outcomes following primary resection.

Intraluminal irrigation with fibers improves mucosal inflammation and atrophy in diversion colitis.

PubMed

de Oliveira-Neto, Joaquim P; de Aguilar-Nascimento, José E

2004-02-01

We investigated the effect of irrigating the colorectal mucosa of patients with a colostomy using a solution of fibers. Eleven patients (10 male and 1 female; mean age, 34 y; age range, 16-49 y) with loop colostomy due to trauma underwent endoscopic evaluation of the rectum and the proximal and distal mucosa from the colostomy. An endoscopic score (range, 0-10) was used to quantify the intensity of the inflammation at the mucosa. Biopsies were taken from the colostomy border and from the rectum. The mean crypt depth of the five best-oriented glands was registered. Then the diverted colorectal segment was irrigated with a solution containing 5% fibers (10 g/d) for 7 d. The patients underwent repeated endoscopic and biopsy procedures, and then the colostomy was closed. The endoscopic score was higher (P < 0.01) at the distal border (2, 0-5) and the rectum (4, 1-10) when compared with the proximal border (0, 0-1). After treatment, the score at the diverted colon (1, 0-2) diminished (P = 0.03). The macroscopic score of the rectum also decreased after the infusion (4, 1-10, versus 3, 0-4; P = 0.03). Crypt depth at the proximal mucosa was higher than at the diverted mucosa (301 +/- 36 microm versus 205 +/- 76 microm; P < 0.01). After treatment, crypt depth at the diverted mucosa (280 +/- 64 microm) increased (P = 0.03). The rectum mucosa did not change before and after the treatment. Irrigation with fibers improves inflammation at the defunctionalized colon.

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Current progress on TPFI nulling architectures at Jet Propulsion Laboratory

NASA Technical Reports Server (NTRS)

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

2005-01-01

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

Simultaneous ablation of prmt-1 and prmt-5 abolishes asymmetric and symmetric arginine dimethylations in Caenorhabditis elegans.

PubMed

Hirota, Keiko; Shigekawa, Chihiro; Araoi, Sho; Sha, Liang; Inagawa, Takayuki; Kanou, Akihiko; Kako, Koichiro; Daitoku, Hiroaki; Fukamizu, Akiyoshi

2017-06-01

Protein arginine methyltransferases (PRMTs) catalyze the transfer of a methyl group from S-adenosylmethionine to arginine residues and are classified into two types: type I producing asymmetric dimethylarginine (ADMA) and type II producing symmetric dimethylarginine (SDMA). PRMTs have been shown to regulate many cellular processes, including signal transduction, transcriptional regulation and RNA processing. Since the loss-of-function mutation of PRMT1 and PRMT5, each of which is the predominant type I and II, respectively, causes embryonic lethality in mice, their physiological significance at the whole-body level remains largely unknown. Here, we show the morphological and functional phenotypes of single or double null alleles of prmt-1 and prmt-5 in Caenorhabditis elegans. The prmt-1;prmt-5 double mutants are viable, and exhibit short body length and small brood size compared to N2 and each of the single mutants. The liquid chromatography-tandem mass spectrometry analysis demonstrated that the levels of ADMA and SDMA were abolished in the prmt-1;prmt-5 double mutants. Both prmt-1 and prmt-5 were required for resistance to heat and oxidative stresses, whereas prmt-5 is not involved in lifespan regulation even when prmt-1 is ablated. This mutant strain would be a useful model animal for investigating the role of asymmetric and symmetric arginine dimethylation in vivo. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement.

PubMed

Weisleder, Noah; Soumaka, Elisavet; Abbasi, Shahrzad; Taegtmeyer, Heinrich; Capetanaki, Yassemi

2004-01-01

Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals. To determine whether altered capillary function or an intrinsic cardiomyocyte defect is responsible for desmin null DCM, transgenic mice were generated to rescue desmin expression specifically to cardiomyocytes. Desmin rescue mice display a wild-type cardiac phenotype with no fibrosis or calcification in the myocardium and normalization of coronary flow. Cardiomyocyte ultrastructure is also restored to normal. Markers of hypertrophy upregulated in desmin null hearts return to wild-type levels in desmin rescue mice. Working hearts were perfused to assess coronary flow and cardiac power. Restoration of a wild-type cardiac phenotype in a desmin null background by expression of desmin specifically within cardiomyocyte indicates that defects in the desmin null heart are due to an intrinsic cardiomyocytes defect rather than compromised coronary circulation.

Enterovaginal or Vesicovaginal Fistula Control Using a Silicone Cup.

PubMed

Russell, Katie W; Robinson, Ryan E; Mone, Mary C; Scaife, Courtney L

2016-12-01

An enterovaginal or vesicovaginal fistula is a complication resulting in vaginal discharge of succus, urine, or stool that can lead to significant complications. For low-volume fistulae, tampons or pads may be used. With high-volume fistulae, frequent product change can be painful and unpredictable in terms of efficacy. The psychologic distress is profound. Surgery may not be an option, making symptom control the priority. We report the use of a reusable menstrual silicone vaginal cup placed to divert and contain drainage. The menstrual cup provided significant symptom relief. Drainage is immediately diverted from tissue, unlike with tampon or pad use, which involves longer contact periods with caustic fluids. A system was created by adapting the end of the cup by adding silastic tubing and an external leg bag to provide long-term drainage control. Improvement in quality of life is of primary importance when dealing with fistula drainage. This simple and inexpensive device should be considered in those cases in which the drainage can be diverted as a viable option, especially in those who are symptomatic and awaiting surgical repair or in those for whom surgery cannot be performed.

Method and apparatus for reducing cold-phase emissions by utilizing oxygen-enriched intake air

DOEpatents

Poola, Ramesh B.; Sekar, Ramanujam R.; Stork, Kevin C.

1997-01-01

An oxygen-enriched air intake control system for an internal combustion engine includes air directing apparatus to control the air flow into the intake of the engine. During normal operation of the engine, ambient air flowing from an air filter of the engine flows through the air directing apparatus into the intake of the engine. In order to decrease the amount of carbon monoxide (CO) and hydrocarbon (HC) emissions that tend to be produced by the engine during a short period of time after the engine is started, the air directing apparatus diverts for a short period of time following the start up of the engine at least a portion of the ambient air from the air filter through a secondary path. The secondary path includes a selectively permeable membrane through which the diverted portion of the ambient air flows. The selectively permeable membrane separates nitrogen and oxygen from the diverted air so that oxygen enriched air containing from about 23% to 25% oxygen by volume is supplied to the intake of the engine.

Diverting lava flows in the lab

USGS Publications Warehouse

Dietterich, Hannah; Cashman, Katharine V.; Rust, Alison C.; Lev, Einat

2015-01-01

Recent volcanic eruptions in Hawai'i, Iceland and Cape Verde highlight the challenges of mitigating hazards when lava flows threaten infrastructure. Diversion barriers are the most common form of intervention, but historical attempts to divert lava flows have met with mixed success and there has been little systematic analysis of optimal barrier design. We examine the interaction of viscous flows of syrup and molten basalt with barriers in the laboratory. We find that flows thicken immediately upslope of an obstacle, forming a localized bow wave that can overtop barriers. Larger bow waves are generated by faster flows and by obstacles oriented at a high angle to the flow direction. The geometry of barriers also influences flow behaviour. Barriers designed to split or dam flows will slow flow advance, but cause the flow to widen, whereas oblique barriers can effectively divert flows, but may also accelerate flow advance. We argue that to be successful, mitigation of lava-flow hazards must incorporate the dynamics of lava flow–obstacle interactions into barrier design. The same generalizations apply to the effect of natural topographic features on flow geometry and advance rates.

Background Rejection of Charged Particles in the Simbol-X Telescope: Preliminary Study of Protons Scattering

NASA Astrophysics Data System (ADS)

Dell'Orto, E.; Barbera, M.; Bulgarelli, A.; Fioretti, V.; Malaguti, G.; Mineo, T.; Pareschi, G.; Rigato, V.; Spiga, D.; Tagliaferri, G.

2009-05-01

X-ray telescopes equipped with focusing optics in high eccentric orbit, as e.g. Newton-XMM and Chandra, showed a degradation of the detector performance and an important increase of the noise due to soft protons with energy between a few tens of keV and a few MeV, that are focused on the detector through the mirror module. It should be noted that the focusing of the protons by Wolter optics was an unexpected phenomenon. In Simbol-X a magnetic diverter will be implemented to deflect protons, in order to reduce the flux of charged particles impinging upon the focal plane. Obviously the design of the diverter should take into consideration the protons distribution at the exit of the mirror module; for this reason a detailed simulation about the interaction of particles with the mirror surface is necessary. Here we will present the scattering protons models currently under consideration, suggesting a preliminary solution for the design of the magnetic diverter. We will also discuss an ad hoc experiment to study this problem.

Specifications for Managed Strings, Second Edition

DTIC Science & Technology

2010-05-01

const char * cstr , const size_t maxsize, const char *charset); 10 | CMU/SEI-2010-TR-018 Runtime-Constraints s shall not be a null pointer...strcreate_m function creates a managed string, referenced by s, given a conventional string cstr (which may be null or empty). maxsize specifies the...characters to those in the null-terminated byte string cstr (which may be empty). If charset is a null pointer, no restricted character set is defined. If

An omnibus test for the global null hypothesis.

PubMed

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.

Continuous development of current sheets near and away from magnetic nulls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Sanjay; Bhattacharyya, R.

2016-04-15

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

Experimental evaluation of achromatic phase shifters for mid-infrared starlight suppression.

PubMed

Gappinger, Robert O; Diaz, Rosemary T; Ksendzov, Alexander; Lawson, Peter R; Lay, Oliver P; Liewer, Kurt M; Loya, Frank M; Martin, Stefan R; Serabyn, Eugene; Wallace, James K

2009-02-10

Phase shifters are a key component of nulling interferometry, one of the potential routes to enabling the measurement of faint exoplanet spectra. Here, three different achromatic phase shifters are evaluated experimentally in the mid-infrared, where such nulling interferometers may someday operate. The methods evaluated include the use of dispersive glasses, a through-focus field inversion, and field reversals on reflection from antisymmetric flat-mirror periscopes. All three approaches yielded deep, broadband, mid-infrared nulls, but the deepest broadband nulls were obtained with the periscope architecture. In the periscope system, average null depths of 4x10(-5) were obtained with a 25% bandwidth, and 2x10(-5) with a 20% bandwidth, at a central wavelength of 9.5 mum. The best short term nulls at 20% bandwidth were approximately 9x10(-6), in line with error budget predictions and the limits of the current generation of hardware.

The Importance of Proving the Null

PubMed Central

Gallistel, C. R.

2010-01-01

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 favored. A general solution is a sensitivity analysis: Compute the odds for or against the null as a function of the limit(s) on the vagueness of the alternative. If the odds on the null approach 1 from above as the hypothesized maximum size of the possible effect approaches 0, then the data favor the null over any vaguer alternative to it. The simple computations and the intuitive graphic representation of the analysis are illustrated by the analysis of diverse examples from the current literature. They pose 3 common experimental questions: (a) Are 2 means the same? (b) Is performance at chance? (c) Are factors additive? PMID:19348549

Light cone structure near null infinity of the Kerr metric

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai Shan; Shang Yu; Graduate School of Chinese Academy of Sciences, Beijing, 100080

2007-02-15

Motivated by our attempt to understand the question of angular momentum of a relativistic rotating source carried away by gravitational waves, in the asymptotic regime near future null infinity of the Kerr metric, a family of null hypersurfaces intersecting null infinity in shearfree (good) cuts are constructed by means of asymptotic expansion of the eikonal equation. The geometry of the null hypersurfaces as well as the asymptotic structure of the Kerr metric near null infinity are studied. To the lowest order in angular momentum, the Bondi-Sachs form of the Kerr metric is worked out. The Newman-Unti formalism is then furthermore » developed, with which the Newman-Penrose constants of the Kerr metric are computed and shown to be zero. Possible physical implications of the vanishing of the Newman-Penrose constants of the Kerr metric are also briefly discussed.« less

Evidence that the Dictyostelium Dd-STATa protein is a repressor that regulates commitment to stalk cell differentiation and is also required for efficient chemotaxis.

PubMed

Mohanty, S; Jermyn, K A; Early, A; Kawata, T; Aubry, L; Ceccarelli, A; Schaap, P; Williams, J G; Firtel, R A

1999-08-01

Dd-STATa is a structural and functional homologue of the metazoan STAT (Signal Transducer and Activator of Transcription) proteins. We show that Dd-STATa null cells exhibit several distinct developmental phenotypes. The aggregation of Dd-STATa null cells is delayed and they chemotax slowly to a cyclic AMP source, suggesting a role for Dd-STATa in these early processes. In Dd-STATa null strains, slug-like structures are formed but they have an aberrant pattern of gene expression. In such slugs, ecmB/lacZ, a marker that is normally specific for cells on the stalk cell differentiation pathway, is expressed throughout the prestalk region. Stalk cell differentiation in Dictyostelium has been proposed to be under negative control, mediated by repressor elements present in the promoters of stalk cell-specific genes. Dd-STATa binds these repressor elements in vitro and the ectopic expression of ecmB/lacZ in the null strain provides in vivo evidence that Dd-STATa is the repressor protein that regulates commitment to stalk cell differentiation. Dd-STATa null cells display aberrant behavior in a monolayer assay wherein stalk cell differentiation is induced using the stalk cell morphogen DIF. The ecmB gene, a general marker for stalk cell differentiation, is greatly overinduced by DIF in Dd-STATa null cells. Also, Dd-STATa null cells are hypersensitive to DIF for expression of ST/lacZ, a marker for the earliest stages in the differentiation of one of the stalk cell sub-types. We suggest that both these manifestations of DIF hypersensitivity in the null strain result from the balance between activation and repression of the promoter elements being tipped in favor of activation when the repressor is absent. Paradoxically, although Dd-STATa null cells are hypersensitive to the inducing effects of DIF and readily form stalk cells in monolayer assay, the Dd-STATa null cells show little or no terminal stalk cell differentiation within the slug. Dd-STATa null slugs remain developmentally arrested for several days before forming very small spore masses supported by a column of apparently undifferentiated cells. Thus, complete stalk cell differentiation appears to require at least two events: a commitment step, whereby the repression exerted by Dd-STATa is lifted, and a second step that is blocked in a Dd-STATa null organism. This latter step may involve extracellular cAMP, a known repressor of stalk cell differentiation, because Dd-STATa null cells are abnormally sensitive to the inhibitory effects of extracellular cyclic AMP.

Discovery of stationary operation of quiescent H-mode plasmas with net-zero neutral beam injection torque and high energy confinement on DIII-D [Discovery of stationary operation of quiescent H-mode plasmas with Net-Zero NBI torque and high energy confinement on DIII-D

DOE PAGES

Burrell, Keith H.; Barada, Kshitish; Chen, Xi; ...

2016-03-11

Here, recent experiments in DIII-D have led to the discovery of a means of modifying edge turbulence to achieve stationary, high confinement operation without Edge Localized Mode (ELM) instabilities and with no net external torque input. Eliminating the ELM-induced heat bursts and controlling plasma stability at low rotation represent two of the great challenges for fusion energy. By exploiting edge turbulence in a novel manner, we achieved excellent tokamak performance, well above the H 98y2 international tokamak energy confinement scaling (H 98y2=1.25), thus meeting an additional confinement challenge that is usually difficult at low torque. The new regime is triggeredmore » in double null plasmas by ramping the injected torque to zero and then maintaining it there. This lowers ExB rotation shear in the plasma edge, allowing low-k, broadband, electromagnetic turbulence to increase. In the H-mode edge, a narrow transport barrier usually grows until MHD instability (a peeling ballooning mode) leads to the ELM heat burst. However, the increased turbulence reduces the pressure gradient, allowing the development of a broader and thus higher transport barrier. A 60% increase in pedestal pressure and 40% increase in energy confinement result. An increase in the ExB shearing rate inside of the edge pedestal is a key factor in the confinement increase. Strong double-null plasma shaping raises the threshold for the ELM instability, allowing the plasma to reach a transport-limited state near but below the explosive ELM stability boundary. The resulting plasmas have burning-plasma-relevant β N=1.6-1.8 and run without the need for extra torque from 3D magnetic fields. To date, stationary conditions have been produced for 2 s or 12 energy confinement times, limited only by external hardware constraints. Stationary operation with improved pedestal conditions is highly significant for future burning plasma devices, since operation without ELMs at low rotation and good confinement is key for fusion energy production.« less

Discovery of stationary operation of quiescent H-mode plasmas with net-zero neutral beam injection torque and high energy confinement on DIII-D [Discovery of stationary operation of quiescent H-mode plasmas with Net-Zero NBI torque and high energy confinement on DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burrell, Keith H.; Barada, Kshitish; Chen, Xi

Here, recent experiments in DIII-D have led to the discovery of a means of modifying edge turbulence to achieve stationary, high confinement operation without Edge Localized Mode (ELM) instabilities and with no net external torque input. Eliminating the ELM-induced heat bursts and controlling plasma stability at low rotation represent two of the great challenges for fusion energy. By exploiting edge turbulence in a novel manner, we achieved excellent tokamak performance, well above the H 98y2 international tokamak energy confinement scaling (H 98y2=1.25), thus meeting an additional confinement challenge that is usually difficult at low torque. The new regime is triggeredmore » in double null plasmas by ramping the injected torque to zero and then maintaining it there. This lowers ExB rotation shear in the plasma edge, allowing low-k, broadband, electromagnetic turbulence to increase. In the H-mode edge, a narrow transport barrier usually grows until MHD instability (a peeling ballooning mode) leads to the ELM heat burst. However, the increased turbulence reduces the pressure gradient, allowing the development of a broader and thus higher transport barrier. A 60% increase in pedestal pressure and 40% increase in energy confinement result. An increase in the ExB shearing rate inside of the edge pedestal is a key factor in the confinement increase. Strong double-null plasma shaping raises the threshold for the ELM instability, allowing the plasma to reach a transport-limited state near but below the explosive ELM stability boundary. The resulting plasmas have burning-plasma-relevant β N=1.6-1.8 and run without the need for extra torque from 3D magnetic fields. To date, stationary conditions have been produced for 2 s or 12 energy confinement times, limited only by external hardware constraints. Stationary operation with improved pedestal conditions is highly significant for future burning plasma devices, since operation without ELMs at low rotation and good confinement is key for fusion energy production.« less

AtrbohD and AtrbohF negatively regulate lateral root development by changing the localized accumulation of superoxide in primary roots of Arabidopsis.

PubMed

Li, Ning; Sun, Lirong; Zhang, Liyue; Song, Yalin; Hu, Panpan; Li, Cui; Hao, Fu Shun

2015-03-01

NADPH oxidase AtrbohD an d AtrbohF negatively modulate lateral root development by changing the peroxidase activity and increasing the local generation of superoxide in primary roots of Arabidopsis in an auxin-independent manner. NADPH oxidase subunits AtrbohD and AtrbohF play pivotal roles in regulating growth, development and stress responses in Arabidopsis. However, whether they modulate lateral root (LR) formation has not yet been addressed, and the detailed mechanisms underlying the process remain unanswered. Here, we show that two null double mutants atrbohD1/F1 and atrbohD2/F2, in which both AtrbohD and AtrbohF genes are disrupted, had remarkably higher LR density than wild-type (WT), or the single mutant atrbohD1 and atrbohF1. Compared to WT, the double mutants exhibited early emerged LRs and enhanced density of lateral root primordia (LRP). Unexpectedly, the production of superoxide (O2 (-)), but not hydrogen peroxide, in the mature area of the primary root containing LRs significantly increased in the double mutants relative to that in WT. Further experiments revealed that the local accumulation of O2 (-) led to the enhancement of LR density in the double mutants. Moreover, the deficiency of AtrbohD and AtrbohF caused a marked increase in peroxidase activity in the mature root zone, which contributed to the localized accumulation of O2 (-) and the elevated LR density in the double mutants. Furthermore, the double mutants were not sensitive to exogenous auxin naphthalene acetic acid or auxin transport inhibitor 1-N-naphthylphthalamic acid in terms of LR formation. The auxin response of LRP in vivo in atrbohD1/F1 was also similar to that in WT. Taken together, these results suggest that AtrbohD and AtrbohF negatively modulate LR development by controlling the local generation of superoxide in an auxin-independent manner. These findings provide new insights into the mechanisms of NADPH oxidase-mediated regulation of LR branching in Arabidopsis.

Gas only nozzle

DOEpatents

Bechtel, William Theodore; Fitts, David Orus; DeLeonardo, Guy Wayne

2002-01-01

A diffusion flame nozzle gas tip is provided to convert a dual fuel nozzle to a gas only nozzle. The nozzle tip diverts compressor discharge air from the passage feeding the diffusion nozzle air swirl vanes to a region vacated by removal of the dual fuel components, so that the diverted compressor discharge air can flow to and through effusion holes in the end cap plate of the nozzle tip. In a preferred embodiment, the nozzle gas tip defines a cavity for receiving the compressor discharge air from a peripheral passage of the nozzle for flow through the effusion openings defined in the end cap plate.

Gas only nozzle fuel tip

DOEpatents

Bechtel, William Theodore; Fitts, David Orus; DeLeonardo, Guy Wayne

2002-01-01

A diffusion flame nozzle gas tip is provided to convert a dual fuel nozzle to a gas only nozzle. The nozzle tip diverts compressor discharge air from the passage feeding the diffusion nozzle air swirl vanes to a region vacated by removal of the dual fuel components, so that the diverted compressor discharge air can flow to and through effusion holes in the end cap plate of the nozzle tip. In a preferred embodiment, the nozzle gas tip defines a cavity for receiving the compressor discharge air from a peripheral passage of the nozzle for flow through the effusion openings defined in the end cap plate.

The origin of nulls mode changes and timing noise in pulsars

NASA Astrophysics Data System (ADS)

Jones, P. B.

A solvable polar cap model obtained previously has normal states which may be associated with radio emission and null states. The solutions cannot be time-independent; the neutron star surface temperature T and mean surface nuclear charge Z are both functions of time. The normal and null states, and the transitions between them, form closed cycles in the T-Z plane. Normal-null transitions can occur inside a fraction of the area on the neutron star surface intersected by open magnetic flux lines. The fraction increases with pulsar period and becomes unity when the pulsar nears extinction. Frequency noise, mode changes, and pulse nulls have a common explanation in the transitions.

The origin of nulls, mode changes and timing noise in pulsars

NASA Astrophysics Data System (ADS)

Jones, P. B.

1982-09-01

A solvable polar cap model obtained previously has normal states which may be associated with radio emission, and null states. The solutions cannot be time-independent; the neutron star surface temperature T and mean surface nuclear charge Z are both functions of time. The normal and null states and the transitions between them, form closed cycles in the T-Z plane. Normal-null transitions can occur inside a fraction of the area of the neutron star surface intersected by open magnetic flux lines. The fraction increases with pulsar period and becomes unity when the pulsar nears extinction. Frequency noise, mode changes and pulse nulls have a common explanation in the transitions.

Peripheral Frequency of CD4+ CD28− Cells in Acute Ischemic Stroke

PubMed Central

Tuttolomondo, Antonino; Pecoraro, Rosaria; Casuccio, Alessandra; Di Raimondo, Domenico; Buttà, Carmelo; Clemente, Giuseppe; Corte, Vittoriano della; Guggino, Giuliana; Arnao, Valentina; Maida, Carlo; Simonetta, Irene; Maugeri, Rosario; Squatrito, Rosario; Pinto, Antonio

2015-01-01

Abstract CD4+ CD28− T cells also called CD28 null cells have been reported as increased in the clinical setting of acute coronary syndrome. Only 2 studies previously analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic stroke but, to our knowledge, peripheral frequency of CD28 null cells in each TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that CD4+ cells and, in particular, the CD28 null cell subset could show a different degree of peripheral percentage in subjects with acute ischemic stroke in relation to clinical subtype and severity of ischemic stroke. The aim of our study was to analyze peripheral frequency of CD28 null cells in subjects with acute ischemic stroke in relation to TOAST diagnostic subtype, and to evaluate their relationship with scores of clinical severity of acute ischemic stroke, and their predictive role in the diagnosis of acute ischemic stroke and diagnostic subtype We enrolled 98 consecutive subjects admitted to our recruitment wards with a diagnosis of ischemic stroke. As controls we enrolled 66 hospitalized patients without a diagnosis of acute ischemic stroke. Peripheral frequency of CD4+ and CD28 null cells has been evaluated with a FACS Calibur flow cytometer. Subjects with acute ischemic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to control subjects without acute ischemic stroke. Subjects with cardioembolic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to subjects with other TOAST subtypes. We observed a significant relationship between CD28 null cells peripheral percentage and Scandinavian Stroke Scale and NIHSS scores. ROC curve analysis showed that CD28 null cell percentage may be useful to differentiate between stroke subtypes. These findings seem suggest a possible role for a T-cell component also in acute ischemic stroke clinical setting showing a different peripheral frequency of CD28 null cells in relation of each TOAST subtype of stroke. PMID:25997053

Measurement Via Optical Near-Nulling and Subaperture Stitching

NASA Technical Reports Server (NTRS)

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

2012-01-01

A subaperture stitching interferometer system provides near-nulling of a subaperture wavefront reflected from an object of interest over a portion of a surface of the object. A variable optical element located in the radiation path adjustably provides near-nulling to facilitate stitching of subaperture interferograms, creating an interferogram representative of the entire surface of interest. This enables testing of aspheric surfaces without null optics customized for each surface prescription. The surface shapes of objects such as lenses and other precision components are often measured with interferometry. However, interferometers have a limited capture range, and thus the test wavefront cannot be too different from the reference or the interference cannot be analyzed. Furthermore, the performance of the interferometer is usually best when the test and reference wavefronts are nearly identical (referred to as a null condition). Thus, it is necessary when performing such measurements to correct for known variations in shape to ensure that unintended variations are within the capture range of the interferometer and accurately measured. This invention is a system for nearnulling within a subaperture stitching interferometer, although in principle, the concept can be employed by wavefront measuring gauges other than interferometers. The system employs a light source for providing coherent radiation of a subaperture extent. An object of interest is placed to modify the radiation (e.g., to reflect or pass the radiation), and a variable optical element is located to interact with, and nearly null, the affected radiation. A detector or imaging device is situated to obtain interference patterns in the modified radiation. Multiple subaperture interferograms are taken and are stitched, or joined, to provide an interferogram representative of the entire surface of the object of interest. The primary aspect of the invention is the use of adjustable corrective optics in the context of subaperture stitching near-nulling interferometry, wherein a complex surface is analyzed via multiple, separate, overlapping interferograms. For complex surfaces, the problem of managing the identification and placement of corrective optics becomes even more pronounced, to the extent that in most cases the null corrector optics are specific to the particular asphere prescription and no others (i.e. another asphere requires completely different null correction optics). In principle, the near-nulling technique does not require subaperture stitching at all. Building a near-null system that is practically useful relies on two key features: simplicity and universality. If the system is too complex, it will be difficult to calibrate and model its manufacturing errors, rendering it useless as a precision metrology tool and/or prohibitively expensive. If the system is not applicable to a wide range of test parts, then it does not provide significant value over conventional null-correction technology. Subaperture stitching enables simpler and more universal near-null systems to be effective, because a fraction of a surface is necessarily less complex than the whole surface (excepting the extreme case of a fractal surface description). The technique of near-nulling can significantly enhance aspheric subaperture stitching capability by allowing the interferometer to capture a wider range of aspheres. More over, subaperture stitching is essential to a truly effective near-nulling system, since looking at a fraction of the surface keeps the wavefront complexity within the capability of a relatively simple nearnull apparatus. Furthermore, by reducing the subaperture size, the complexity of the measured wavefront can be reduced until it is within the capability of the near-null design.

Analyses of Genetic Variations of Glutathione S-Transferase Mu1 and Theta1 Genes in Bangladeshi Tannery Workers and Healthy Controls

PubMed Central

Akther, Jobaida; Ebihara, Akio; Nakagawa, Tsutomu; Islam, Laila N.; Suzuki, Fumiaki; Hosen, Md. Ismail; Hossain, Mahmud; Nabi, A. H. M. Nurun

2016-01-01

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/−), 31.4% had GSTT1 (−/+) alleles, and 6.4% had null genotypes (−/−) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/−, 30.5% were −/+, and 8.4% were −/−. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes. PMID:27294127

Genetic characterization of p27(kip1) and stathmin in controlling cell proliferation in vivo.

PubMed

Berton, Stefania; Pellizzari, Ilenia; Fabris, Linda; D'Andrea, Sara; Segatto, Ilenia; Canzonieri, Vincenzo; Marconi, Daniela; Schiappacassi, Monica; Benevol, Sara; Gattei, Valter; Colombatti, Alfonso; Belletti, Barbara; Baldassarre, Gustavo

2014-01-01

The CDK inhibitor p27(kip1) is a critical regulator of cell cycle progression, but the mechanisms by which p27(kip1) controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27(kip1) binding partner. To get more insights into the in vivo significance of this interaction, we generated p27(kip1) and stathmin double knock-out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27(kip1) null mice linked to the hyper-proliferative behavior, such as the increased body and organ weight, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27(kip1) null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profiling of mouse thymuses confirmed the phenotypes observed in vivo, showing that DKO clustered with WT more than with p27 knock-out tissue. Taken together, our results demonstrate that stathmin cooperates with p27(kip1) to control the early phase of G1 to S phase transition and that this function may be of particular relevance in the context of tumor progression.

Drosophila Growth and Development in the Absence of dMyc and dMnt

PubMed Central

Pierce, Sarah B.; Yost, Cynthia; Anderson, Sarah A. R.; Flynn, Erin M.; Delrow, Jeffrey; Eisenman, Robert N.

2008-01-01

Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in dm results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMyc leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the dm null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt. PMID:18241851

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

PubMed Central

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

Foxa1 and Foxa2 are required for formation of the intervertebral discs.

PubMed

Maier, Jennifer A; Lo, YinTing; Harfe, Brian D

2013-01-01

The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2)), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-);Foxa2(c/c);ShhcreER(T2) double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.

Foxa1 and Foxa2 Are Required for Formation of the Intervertebral Discs

PubMed Central

Maier, Jennifer A.; Lo, YinTing; Harfe, Brian D.

2013-01-01

The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreERT2), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1−/−;Foxa2c/c;ShhcreERT2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord. PMID:23383217

pKAMA-ITACHI Vectors for Highly Efficient CRISPR/Cas9-Mediated Gene Knockout in Arabidopsis thaliana

PubMed Central

2017-01-01

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) system is widely used as a tool for genome engineering in various organisms. A complex consisting of Cas9 and single guide RNA (sgRNA) induces a DNA double-strand break in a sequence-specific manner, resulting in knockout. Some binary vectors for CRISPR/Cas9 in plants have been reported, but there is a problem with low efficiency. Here, we present a newly developed, highly efficient CRISPR/Cas9 vector for Arabidopsis thaliana, pKAMA-ITACHI Red (pKIR), harboring the RIBOSOMAL PROTEIN S5 A (RPS5A) promoter to drive Cas9. The RPS5A promoter maintains high constitutive expression at all developmental stages starting from the egg cell and including meristematic cells. Even in the T1 generation, pKIR induced null phenotypes in some genes: PHYTOENE DESATURASE 3 (PDS3), AGAMOUS (AG) and DUO POLLEN 1 (DUO1). Mutations induced by pKIR were carried in the germ cell line of the T1 generation. Surprisingly, in some lines, 100% of the T2 plants had the adh1 (ALCOHOL DEHYDROGENASE 1) null phenotype, indicating that pKIR strongly induced heritable mutations. Cas9-free T2 mutant plants were obtained by removing T2 seeds expressing a fluorescent marker in pKIR. Our results suggest that the pKIR system is a powerful molecular tool for genome engineering in Arabidopsis. PMID:27856772

Important Functional Roles of Basigin in Thymocyte Development and T cell Activation

PubMed Central

Yao, Hui; Teng, Yan; Sun, Qian; Xu, Jing; Chen, Ya-Tong; Hou, Ning; Cheng, Xuan; Yang, Xiao; Chen, Zhi-Nan

2014-01-01

Basigin is a highly glycosylated transmembrane protein that is expressed in a broad range of tissues and is involved in a number of physiological and pathological processes. However, the in vivo role of basigin remains unknown. To better understand the physiological and pathological functions of basigin in vivo, we generated a conditional null allele by introducing two loxP sites flanking exons 2 and 7 of the basigin gene (Bsg). Bsgfl/fl mice were born at the expected Mendelian ratio and showed a similar growth rate compared with wildtype mice. After crossing these mice with Lck-Cre transgenic mice, basigin expression was specifically inactivated in T cells in the resulting Lck-Cre; Bsgfl/fl mice. Although the birth and growth rate of Lck-Cre; Bsgfl/fl mice were similar to control mice, thymus development was partially arrested in Lck-Cre; Bsgfl/fl mice, specifically at the CD4+CD8+ double-positive (DP) and CD4 single-positive (CD4+CD8-, CD4SP) stages. In addition, CD4+ T cell activation was enhanced upon Concanavalin A (Con A) or anti-CD3/anti-CD28 stimulation but not upon PMA/Ionomycin stimulation in the absence of basigin. Overall, this study provided the first in vivo evidence for the function of basigin in thymus development. Moreover, the successful generation of the conditional null basigin allele provides a useful tool for the study of distinct physiological or pathological functions of basigin in different tissues at different development stages. PMID:24391450

Genetic characterization of p27kip1 and stathmin in controlling cell proliferation in vivo

PubMed Central

Berton, Stefania; Pellizzari, Ilenia; Fabris, Linda; D'Andrea, Sara; Segatto, Ilenia; Canzonieri, Vincenzo; Marconi, Daniela; Schiappacassi, Monica; Benevol, Sara; Gattei, Valter; Colombatti, Alfonso; Belletti, Barbara; Baldassarre, Gustavo

2014-01-01

The CDK inhibitor p27kip1 is a critical regulator of cell cycle progression, but the mechanisms by which p27kip1 controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27kip1 binding partner. To get more insights into the in vivo significance of this interaction, we generated p27kip1 and stathmin double knock-out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27kip1 null mice linked to the hyper-proliferative behavior, such as the increased body and organ weight, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27kip1 null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profiling of mouse thymuses confirmed the phenotypes observed in vivo, showing that DKO clustered with WT more than with p27 knock-out tissue. Taken together, our results demonstrate that stathmin cooperates with p27kip1 to control the early phase of G1 to S phase transition and that this function may be of particular relevance in the context of tumor progression. PMID:25486569

A Defect in DNA Ligase4 Enhances the Frequency of TALEN-Mediated Targeted Mutagenesis in Rice1[OPEN

PubMed Central

Cermak, Tomas; Sugimoto, Kazuhiko; Saika, Hiroaki; Mori, Akiko; Osakabe, Keishi; Hamada, Masao; Katayose, Yuichi; Voytas, Daniel F.

2016-01-01

We have established methods for site-directed mutagenesis via transcription activator-like effector nucleases (TALENs) in the endogenous rice (Oryza sativa) waxy gene and demonstrated stable inheritance of TALEN-induced somatic mutations to the progeny. To analyze the role of classical nonhomologous end joining (cNHEJ) and alternative nonhomologous end joining (altNHEJ) pathways in TALEN-induced mutagenesis in plant cells, we investigated whether a lack of DNA Ligase4 (Lig4) affects the kinetics of TALEN-induced double-strand break repair in rice cells. Deep-sequencing analysis revealed that the frequency of all types of mutations, namely deletion, insertion, combination of insertion with deletion, and substitution, in lig4 null mutant calli was higher than that in a lig4 heterozygous mutant or the wild type. In addition, the ratio of large deletions (greater than 10 bp) and deletions repaired by microhomology-mediated end joining (MMEJ) to total deletion mutations in lig4 null mutant calli was higher than that in the lig4 heterozygous mutant or wild type. Furthermore, almost all insertions (2 bp or greater) were shown to be processed via copy and paste of one or more regions around the TALENs cleavage site and rejoined via MMEJ regardless of genetic background. Taken together, our findings indicate that the dysfunction of cNHEJ leads to a shift in the repair pathway from cNHEJ to altNHEJ or synthesis-dependent strand annealing. PMID:26668331

Trigger Factor can antagonize both SecB and DnaK/DnaJ chaperone functions in Escherichia coli

PubMed Central

Ullers, Ronald S.; Ang, Debbie; Schwager, Françoise; Georgopoulos, Costa; Genevaux, Pierre

2007-01-01

Polypeptides emerging from the ribosome are assisted by a pool of molecular chaperones and targeting factors, which enable them to efficiently partition as cytoplasmic, integral membrane, or exported proteins. In Escherichia coli, the chaperones SecB, Trigger Factor (TF), and DnaK are key players in this process. Here, we report that, as with dnaK or dnaJ mutants, a secB null strain exhibits a strong cold-sensitive (Cs) phenotype. Through suppressor analyses, we found that inactivating mutations in the tig gene encoding TF fully relieve both the Cs phenotype and protein aggregation observed in the absence of SecB. This antagonistic effect of TF depends on its ribosome-binding and chaperone activities but unrelated to its peptidyl-prolyl cis/trans isomerase (PPIase) activity. Furthermore, in contrast to the previously known synergistic action of TF and DnaK/DnaJ above 30°C, a tig null mutation partially suppresses the Cs phenotype exhibited by a compromised DnaK/DnaJ chaperone machine. The antagonistic role of TF is further exemplified by the fact that the secB dnaJ double mutant is viable only in the absence of TF. Finally, we show that, in the absence of TF, more SecA and ribosomes are associated with the inner membrane, suggesting that the presence of TF directly or indirectly interferes with the process of cotranslational protein targeting to the Sec translocon. PMID:17360615

Bayes factor and posterior probability: Complementary statistical evidence to p-value.

PubMed

Lin, Ruitao; Yin, Guosheng

2015-09-01

As a convention, a p-value is often computed in hypothesis testing and compared with the nominal level of 0.05 to determine whether to reject the null hypothesis. Although the smaller the p-value, the more significant the statistical test, it is difficult to perceive the p-value in a probability scale and quantify it as the strength of the data against the null hypothesis. In contrast, the Bayesian posterior probability of the null hypothesis has an explicit interpretation of how strong the data support the null. We make a comparison of the p-value and the posterior probability by considering a recent clinical trial. The results show that even when we reject the null hypothesis, there is still a substantial probability (around 20%) that the null is true. Not only should we examine whether the data would have rarely occurred under the null hypothesis, but we also need to know whether the data would be rare under the alternative. As a result, the p-value only provides one side of the information, for which the Bayes factor and posterior probability may offer complementary evidence. Copyright © 2015 Elsevier Inc. All rights reserved.

Terrestrial Planet Finder Interferometer Technology Status and Plans

NASA Technical Reports Server (NTRS)

Lawson, Perter R.; Ahmed, A.; Gappinger, R. O.; Ksendzov, A.; Lay, O. P.; Martin, S. R.; Peters, R. D.; Scharf, D. P.; Wallace, J. K.; Ware, B.

2006-01-01

A viewgraph presentation on the technology status and plans for Terrestrial Planet Finder Interferometer is shown. The topics include: 1) The Navigator Program; 2) TPF-I Project Overview; 3) Project Organization; 4) Technology Plan for TPF-I; 5) TPF-I Testbeds; 6) Nulling Error Budget; 7) Nulling Testbeds; 8) Nulling Requirements; 9) Achromatic Nulling Testbed; 10) Single Mode Spatial Filter Technology; 11) Adaptive Nuller Testbed; 12) TPF-I: Planet Detection Testbed (PDT); 13) Planet Detection Testbed Phase Modulation Experiment; and 14) Formation Control Testbed.

Surfactant-Associated Protein A Provides Critical Immunoprotection in Neonatal Mice▿

PubMed Central

George, Caroline L. S.; Goss, Kelli L.; Meyerholz, David K.; Lamb, Fred S.; Snyder, Jeanne M.

2008-01-01

The collectins surfactant-associated protein A (SP-A) and SP-D are components of innate immunity that are present before birth. Both proteins bind pathogens and assist in clearing infection. The significance of SP-A and SP-D as components of the neonatal immune system has not been investigated. To determine the role of SP-A and SP-D in neonatal immunity, wild-type, SP-A null, and SP-D null mice were bred in a bacterium-laden environment (corn dust bedding) or in a semisterile environment (cellulose fiber bedding). When reared in the corn dust bedding, SP-A null pups had significant mortality (P < 0.001) compared to both wild-type and SP-D null pups exposed to the same environment. The mortality of the SP-A null pups was associated with significant gastrointestinal tract pathology but little lung pathology. Moribund SP-A null newborn mice exhibited Bacillus sp. and Enterococcus sp. peritonitis. When the mother or newborn produced SP-A, newborn survival was significantly improved (P < 0.05) compared to the results when there was a complete absence of SP-A in both the mother and the pup. Significant sources of SP-A likely to protect a newborn include the neonatal lung and gastrointestinal tract but not the lactating mammary tissue of the mother. Furthermore, exogenous SP-A delivered by mouth to newborn SP-A null pups with SP-A null mothers improved newborn survival in the corn dust environment. Therefore, a lack of SP-D did not affect newborn survival, while SP-A produced by either the mother or the pup or oral exogenous SP-A significantly reduced newborn mortality associated with environmentally induced infection in SP-A null newborns. PMID:17967856

P value and the theory of hypothesis testing: an explanation for new researchers.

PubMed

Biau, David Jean; Jolles, Brigitte M; Porcher, Raphaël

2010-03-01

In the 1920s, Ronald Fisher developed the theory behind the p value and Jerzy Neyman and Egon Pearson developed the theory of hypothesis testing. These distinct theories have provided researchers important quantitative tools to confirm or refute their hypotheses. The p value is the probability to obtain an effect equal to or more extreme than the one observed presuming the null hypothesis of no effect is true; it gives researchers a measure of the strength of evidence against the null hypothesis. As commonly used, investigators will select a threshold p value below which they will reject the null hypothesis. The theory of hypothesis testing allows researchers to reject a null hypothesis in favor of an alternative hypothesis of some effect. As commonly used, investigators choose Type I error (rejecting the null hypothesis when it is true) and Type II error (accepting the null hypothesis when it is false) levels and determine some critical region. If the test statistic falls into that critical region, the null hypothesis is rejected in favor of the alternative hypothesis. Despite similarities between the two, the p value and the theory of hypothesis testing are different theories that often are misunderstood and confused, leading researchers to improper conclusions. Perhaps the most common misconception is to consider the p value as the probability that the null hypothesis is true rather than the probability of obtaining the difference observed, or one that is more extreme, considering the null is true. Another concern is the risk that an important proportion of statistically significant results are falsely significant. Researchers should have a minimum understanding of these two theories so that they are better able to plan, conduct, interpret, and report scientific experiments.

Sf29 Gene of Spodoptera frugiperda Multiple Nucleopolyhedrovirus Is a Viral Factor That Determines the Number of Virions in Occlusion Bodies▿

PubMed Central

Simón, Oihane; Williams, Trevor; Asensio, Aaron C.; Ros, Sarhay; Gaya, Andrea; Caballero, Primitivo; Possee, Robert D.

2008-01-01

The genome of Spodoptera frugiperda multiple nucleopolyhedrovirus (NPV) was inserted into a bacmid (Sfbac) and used to produce a mutant lacking open reading frame 29 (Sf29null). Sf29null bacmid DNA was able to generate an infection in S. frugiperda. Approximately six times less DNA was present in occlusion bodies (OBs) produced by the Sf29null bacmid in comparison to viruses containing this gene. This reduction in DNA content was consistent with fewer virus particles being packaged within Sf29null bacmid OBs, as determined by fractionation of dissolved polyhedra and comparison of occlusion-derived virus (ODV) infectivity in cell culture. DNA from Sfbac, Sf29null, or Sf29null-repair, in which the gene deletion had been repaired, were equally infectious when used to transfect S. frugiperda. All three viruses produced similar numbers of OBs, although those from Sf29null were 10-fold less infectious than viruses with the gene. Insects infected with Sf29null bacmid died ∼24 h later than positive controls, consistent with the reduced virus particle content of Sf29null OBs. Transcripts from Sf29 were detected in infected insects 12 h prior to those from the polyhedrin gene. Homologs to Sf29 were present in other group II NPVs, and similar sequences were present in entomopoxviruses. Analysis of the Sf29 predicted protein sequence revealed signal peptide and transmembrane domains, but the presence of 12 potential N-glycosylation sites suggest that it is not an ODV envelope protein. Other motifs, including zinc-binding and threonine-rich regions, suggest degradation and adhesion functions. We conclude that Sf29 is a viral factor that determines the number of ODVs occluded in each OB. PMID:18550678

Constitutive Androgen Receptor-Null Mice Are Sensitive to the Toxic Effects of Parathion: Association with Reduced Cytochrome P450-Mediated Parathion MetabolismS⃞

PubMed Central

Mota, Linda C.; Hernandez, Juan P.

2010-01-01

Constitutive androgen receptor (CAR) is activated by several chemicals and in turn regulates multiple detoxification genes. Our research demonstrates that parathion is one of the most potent, environmentally relevant CAR activators with an EC50 of 1.43 μM. Therefore, animal studies were conducted to determine whether CAR was activated by parathion in vivo. Surprisingly, CAR-null mice, but not wild-type (WT) mice, showed significant parathion-induced toxicity. However, parathion did not induce Cyp2b expression, suggesting that parathion is not a CAR activator in vivo, presumably because of its short half-life. CAR expression is also associated with the expression of several drug-metabolizing cytochromes P450 (P450). CAR-null mice demonstrate lower expression of Cyp2b9, Cyp2b10, Cyp2c29, and Cyp3a11 primarily, but not exclusively in males. Therefore, we incubated microsomes from untreated WT and CAR-null mice with parathion in the presence of esterase inhibitors to determine whether CAR-null mice show perturbed P450-mediated parathion metabolism compared with that in WT mice. The metabolism of parathion to paraoxon and p-nitrophenol (PNP) was reduced in CAR-null mice with male CAR-null mice showing reduced production of both paraoxon and PNP, and female CAR-null mice showing reduced production of only PNP. Overall, the data indicate that CAR-null mice metabolize parathion slower than WT mice. These results provide a potential mechanism for increased sensitivity of individuals with lower CAR activity such as newborns to parathion and potentially other chemicals due to decreased metabolic capacity. PMID:20573718

Delayed complications after flow-diverter stenting: reactive in-stent stenosis and creeping stents.

PubMed

Cohen, José E; Gomori, John Moshe; Moscovici, Samuel; Leker, Ronen R; Itshayek, Eyal

2014-07-01

We assessed the frequency and severity of changes in stent configuration and location after the treatment of intracranial aneurysms, and patterns of in-stent stenosis. We retrospectively reviewed data for consecutive aneurysm patients managed with endovascular implantation of flow-diverter stents (Silk Flow Diverter [Balt Extrusion, Montmorency, France] and Pipeline Embolization Device [ev3/Coviden, Minneapolis, MN, USA]) from October 2011 to July 2012. Routine 2, 6, 9-12, and 16-20 month follow-up angiograms were compared, with a focus on changes in stent configuration and location from immediately after deployment to angiographic follow-up, and the incidence and development of in-stent stenosis. Thirty-four patients with 42 aneurysms met inclusion criteria. The Silk device was implanted in 16 patients (47%, single device in 15), the Pipeline device in 18 (53%, single device in 16). On first follow-up angiography, in-stent stenosis was observed in 38% of Silk devices and 39% of Pipeline devices. In-stent stenosis was asymptomatic in 12 of 13 patients. One woman presented with transient ischemic attacks and required stent angioplasty due to end tapering and mild, diffuse in-stent stenosis. Configuration and location changes, including stent creeping and end tapering were seen in 2/16 patients (13%) with Silk devices, and 0/18 patients with Pipeline devices. We describe stent creeping and end tapering as unusual findings with the potential for delayed clinical complications. In-stent stenosis, with a unique behavior, is a frequent angiographic finding observed after flow-diverter stent implant. The stenosis is usually asymptomatic; however, close clinical and angiographic monitoring is mandatory for individualized management. Copyright © 2013 Elsevier Ltd. All rights reserved.

Risk Factors of Anastomotic Leakage and Long-Term Survival After Colorectal Surgery

PubMed Central

Park, Jong Seob; Huh, Jung Wook; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

2016-01-01

Abstract Anastomotic leakage (AL) is one of the most serious complications of colorectal surgery. It can affect long-term oncologic outcomes, but the impact on long-term survival remains uncertain. The aim of this study is to evaluate the operative characteristics of leakage and no leakage groups and to analyze long-term oncologic outcomes. We prospectively enrolled 10,477 patients from 2000 to 2011 and retrospectively reviewed the data. Male sex (odds ratio [OR], 3.90; P < 0.001), intraoperative transfusion (OR, 2.31; P = 0.042), and operative time (OR, 1.73; P = 0.032) were independent risk factors of AL in the colon. In the rectum, male sex (OR, 2.37; P < 0.001), neoadjuvant chemoradiotherapy (OR, 2.26; P < 0.001), and regional lymph node metastasis (OR, 1.43; P = 0.012) were independent risk factors of AL, and diverting stoma (OR, 0.24; P < 0.001) was associated with a deceased risk of AL. AL in the rectum without a diverting stoma was associated with disease-free survival (DFS, OR, 1.47; P = 0.037). Colonic leakage was not associated with 5-year DFS (leakage group vs nonleakage group, 72.4% vs 80.9%, P = 0.084); however, in patients undergoing rectal resection, there was a significant difference in 5-year DFS (67.0% vs 76.6%, P = 0.005, respectively). AL in the rectum is associated with worse long-term DFS and overall survival. A diverting stoma was shown to protect against this effect and was associated with long-term survival in rectal surgery. Therefore, creating a diverting stoma should be considered in high-risk patients undergoing rectal surgery. PMID:26937928

RANS Analyses of Turbofan Nozzles with Internal Wedge Deflectors for Noise Reduction

NASA Technical Reports Server (NTRS)

DeBonis, James R.

2009-01-01

Computational fluid dynamics (CFD) was used to evaluate the flow field and thrust performance of a promising concept for reducing the noise at take-off of dual-stream turbofan nozzles. The concept, offset stream technology, reduces the jet noise observed on the ground by diverting (offsetting) a portion of the fan flow below the core flow, thickening and lengthening this layer between the high-velocity core flow and the ground observers. In this study a wedge placed in the internal fan stream is used as the diverter. Wind, a Reynolds averaged Navier-Stokes (RANS) code, was used to analyze the flow field of the exhaust plume and to calculate nozzle performance. Results showed that the wedge diverts all of the fan flow to the lower side of the nozzle, and the turbulent kinetic energy on the observer side of the nozzle is reduced. This reduction in turbulent kinetic energy should correspond to a reduction in noise. However, because all of the fan flow is diverted, the upper portion of the core flow is exposed to the freestream, and the turbulent kinetic energy on the upper side of the nozzle is increased, creating an unintended noise source. The blockage due to the wedge reduces the fan mass flow proportional to its blockage, and the overall thrust is consequently reduced. The CFD predictions are in very good agreement with experimental flow field data, demonstrating that RANS CFD can accurately predict the velocity and turbulent kinetic energy fields. While this initial design of a large scale wedge nozzle did not meet noise reduction or thrust goals, this study identified areas for improvement and demonstrated that RANS CFD can be used to improve the concept.

Early signal of diverted use of tropicamide eye drops in France.

PubMed

Ponté, Camille; Pi, Christian; Palmaro, Aurore; Jouanjus, Emilie; Lapeyre-Mestre, Maryse

2017-08-01

Tropicamide is a mydriatic drug used as eye-drops for diagnostic or therapeutic purposes. From 2013, a diverted use by intravenous route has been suspected in Eastern Europe in opioids users. To date, no signal of misuse has been identified in France. The aims of this study were to investigate any early signals of a diverted use of tropicamide eye drops and to collect information regarding motives for the misuse and tropicamide-induced effects. Information was obtained at three levels: (1) at regional level (Midi-Pyrénées area), from reimbursement data and pharmacists' reports on suspicious requests; (2) at national level: from reimbursement data and prescriptions suggesting possible abuse from the OSIAP (Ordonnances Suspectes, Indicateur d'Abus Possible) survey; and (3) at international level: from VigiBase ® reports and Web sources. Beta-blocker eye-drops were used as comparators. In France, in 2014-2015, 17 (0.91%, 95% CI [0.53-1.46%]) falsified prescriptions involving tropicamide were identified in the OSIAP survey (compared with 0%, 95% CI [0-0.19%] for beta-blockers). Moreover, 37 other suspicious prescriptions were presented in 2015 (notified in 2016). In Midi-Pyrénées, seven patients aged 35-49 were reimbursed for 19-45 vials of 10 ml, in a year. Since September 2014, the regional Addictovigilance Centre has received 91 notifications of suspicious requests to obtain tropicamide. In VigiBase ® , two cases were identified but none in France. An increased interest in tropicamide-related Internet searches was observed from Russia and Ukraine. These results represent the first early warnings of a tropicamide diverted use in France. Tropicamide abusers would seek euphoria or hallucinations. The high doses involved in intravenous administration could lead to serious complications. © 2017 The British Pharmacological Society.

A New Flow-Diverter (the FloWise): In-Vivo Evaluation in an Elastase-Induced Rabbit Aneurysm Model.

PubMed

Kim, Byung Moon; Kim, Dong Joon; Kim, Dong Ik

2016-01-01

We aimed to evaluate the efficacy and safety of a newly developed, partially retrievable flow-diverter (the FloWise) in an elastase-induced rabbit aneurysm model. We developed a partially retrievable flow diverter composed of 48 strands of Nitinol and platinum wire. The FloWise is compatible with any microcatheter of 0.027-inch inner diameter, and is retrievable up to 70% deployment. The efficacy and safety of the FloWise were evaluated in the elastase-induced rabbit aneurysm model. The rate of technical success (full coverage of aneurysm neck) and assessment of aneurysm occlusion and stent patency was conducted by angiograms and histologic examinations at the 1-month, 3-month, and 6-month follow-up. The patency of small arterial branches (intercostal or lumbar arteries) covered by the FloWise were also assessed in the 5 subjects. We attempted FloWise insertion in a total of 32 aneurysm models. FloWise placement was successful in 31 subjects (96.9%). Two stents (6.2%) were occluded at the 3-month follow-up, but there was no evidence of in-stent stenosis in other subjects. All stented aneurysms showed progressive occlusion: grade I (complete aneurysm occlusion) in 44.4% and grade II (aneurysm occlusion > 90%) in 55.6% at 1 month; grade I in 90% and II in 10% at 3 months; and grade I in 90% and II in 10% at 6 months. All small arterial branches covered by the FloWise remained patent. A newly developed, partially retrievable flow-diverter seems to be a safe and effective tool of aneurysm occlusion, as evaluated in the rabbit aneurysm model.

Experimental Evaluation of the Effect of Angle-of-attack on the External Aerodynamics and Mass Capture of a Symmetric Three-engine Air-breathing Launch Vehicle Configuration at Supersonic Speeds

NASA Technical Reports Server (NTRS)

Kim, Hyun D.; Frate, Franco C.

2001-01-01

A subscale aerodynamic model of the GTX air-breathing launch vehicle was tested at NASA Glenn Research Center's 10- by 10-Foot Supersonic Wind Tunnel from Mach 2.0 to 3.5 at various angles-of-attack. The objective of the test was to investigate the effect of angle-of-attack on inlet mass capture, inlet diverter effectiveness, and the flowfield at the cowl lip plane. The flow-through inlets were tested with and without boundary-layer diverters. Quantitative measurements such as inlet mass flow rates and pitot-pressure distributions in the cowl lip plane are presented. At a 3deg angle-of-attack, the flow rates for the top and side inlets were within 8 percent of the zero angle-of-attack value, and little distortion was evident at the cowl lip plane. Surface oil flow patterns showing the shock/boundary-layer interaction caused by the inlet spikes are shown. In addition to inlet data, vehicle forebody static pressure distributions, boundary-layer profiles, and temperature-sensitive paint images to evaluate the boundary-layer transition are presented. Three-dimensional parabolized Navier-Stokes computational fluid dynamics calculations of the forebody flowfield are presented and show good agreement with the experimental static pressure distributions and boundary-layer profiles. With the boundary-layer diverters installed, no adverse aerodynamic phenomena were found that would prevent the inlets from operating at the required angles-of-attack. We recommend that phase 2 of the test program be initiated, where inlet contraction ratio and diverter geometry variations will be tested.

Current Structure and Nonideal Behavior at Magnetic Null Points in the Turbulent Magnetosheath

NASA Technical Reports Server (NTRS)

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

2013-01-01

The Poincaré index indicates that the Cluster spacecraft tetrahedron entraps a number of 3-D magnetic nulls during an encounter with the turbulent magnetosheath. Previous researchers have found evidence for reconnection at one of the many filamentary current layers observed by Cluster in this region. We find that many of the entrained nulls are also associated with strong currents. We dissect the current structure of a pair of spiral nulls that may be topologically connected. At both nulls, we find a strong current along the spine, accompanied by a somewhat more modest current perpendicular to the spine that tilts the fan toward the axis of the spine. The current along the fan is comparable to the that along the spine. At least one of the nulls manifests a rotational flow pattern in the fan plane that is consistent with torsional spine reconnection as predicted by theory. These results emphasize the importance of examining the magnetic topology in interpreting the nature of currents and reconnection in 3-D turbulence.

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

PubMed

Manfroi, Silvia; Scarcello, Antonio; Pagliaro, Pasqualepaolo

2015-10-01

Molecular genetic studies on Duffy blood group antigens have identified mutations underlying rare FY*Null and FY*X alleles. FY*Null has a high frequency in Blacks, especially from sub-Saharan Africa, while its frequency is not defined in Caucasians. FY*X allele, associated with Fy(a-b+w) phenotype, has a frequency of 2-3.5% in Caucasian people while it is absent in Blacks. During the project of extensive blood group genotyping in patients affected by hemoglobinopathies, we identified FY*X/FY*Null and FY*A/FY*Null genotypes in a Caucasian thalassemic family from Sardinia. We speculate on the frequency of FY*X and FY*Null alleles in Caucasian and Black people; further, we focused on the association of FY*X allele with weak Fyb antigen expression on red blood cells and its identification performing high sensitivity serological typing methods or genotyping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Position sensor for a fuel injection element in an internal combustion engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fulkerson, D.E.; Geske, M.L.

1987-08-18

This patent describes an electronic circuit for dynamically sensing and processing signals representative of changes in a magnet field, the circuit comprising: means for sensing a change in a magnetic field external to the circuit and providing an output representative of the change; circuit means electronically coupled with the output of the sensing means for providing an output indicating the presence of the magnetic field change; and a nulling circuit coupled with the output of the sensing means and across the indicating circuit means for nulling the electronic circuit responsive to the sensing means output, to thereby avoid ambient magneticmore » fields temperature and process variations, and wherein the nulling circuit comprises a capacitor coupled to the output of the nulling circuit, means for charging and discharging the capacitor responsive to any imbalance in the input to the nulling circuit, and circuit means coupling the capacitor with the output of the sensing means for nulling any imbalance during the charging or discharging of the capacitor.« less

Naked singularity resolution in cylindrical collapse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurita, Yasunari; Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto, 606-8502; Nakao, Ken-ichi

In this paper, we study the gravitational collapse of null dust in cylindrically symmetric spacetime. The naked singularity necessarily forms at the symmetry axis. We consider the situation in which null dust is emitted again from the naked singularity formed by the collapsed null dust and investigate the backreaction by this emission for the naked singularity. We show a very peculiar but physically important case in which the same amount of null dust as that of the collapsed one is emitted from the naked singularity as soon as the ingoing null dust hits the symmetry axis and forms the nakedmore » singularity. In this case, although this naked singularity satisfies the strong curvature condition by Krolak (limiting focusing condition), geodesics which hit the singularity can be extended uniquely across the singularity. Therefore, we may say that the collapsing null dust passes through the singularity formed by itself and then leaves for infinity. Finally, the singularity completely disappears and the flat spacetime remains.« less

Evaluation of null-point detection methods on simulation data

NASA Astrophysics Data System (ADS)

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.

The importance of proving the null.

PubMed

Gallistel, C R

2009-04-01

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 favored. A general solution is a sensitivity analysis: Compute the odds for or against the null as a function of the limit(s) on the vagueness of the alternative. If the odds on the null approach 1 from above as the hypothesized maximum size of the possible effect approaches 0, then the data favor the null over any vaguer alternative to it. The simple computations and the intuitive graphic representation of the analysis are illustrated by the analysis of diverse examples from the current literature. They pose 3 common experimental questions: (a) Are 2 means the same? (b) Is performance at chance? (c) Are factors additive? (c) 2009 APA, all rights reserved

Independently variable phase and stroke control for a double acting Stirling engine

DOEpatents

Berchowitz, David M.

1983-01-01

A phase and stroke control apparatus for the pistons of a Stirling engine includes a ring on the end of each piston rod in which a pair of eccentrics is arranged in series, torque transmitting relationship. The outer eccentric is rotatably mounted in the ring and is rotated by the orbiting ring; the inner eccentric is mounted on an output shaft. The two eccentrics are mounted for rotation together within the ring during normal operation. A device is provided for rotating one eccentric with respect to another to change the effective eccentricity of the pair of eccentrics. A separately controlled phase adjustment is provided to null the phase change introduced by the change in the orientation of the outer eccentric, and also to enable the phase of the pistons to be changed independently of the stroke change.

Direct Search for Dark Matter with DarkSide

NASA Astrophysics Data System (ADS)

Agnes, P.; Alexander, T.; Alton, A.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Brigatti, A.; Brodsky, J.; Budano, F.; Cadonati, L.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; Cocco, A. G.; Crippa, L.; D'Angelo, D.; D'Incecco, M.; Davini, S.; De Deo, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Goretti, A.; Grandi, L.; Gromov, M.; Guan, M. Y.; Guardincerri, Y.; Hackett, B.; Herner, K.; Hungerford, E. V.; Ianni, Al; Ianni, An; Jollet, C.; Keeter, K.; Kendziora, C.; Kidner, S.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kurlej, A.; Li, P. X.; Loer, B.; Lombardi, P.; Love, C.; Ludhova, L.; Luitz, S.; Ma, Y. Q.; Machulin, I.; Mandarano, A.; Mari, S.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meroni, E.; Meyers, P. D.; Milincic, R.; Montanari, D.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B.; Muratova, V.; Musico, P.; Nelson, A.; Odrowski, S.; Okounkova, M.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Papp, L.; Parmeggiano, S.; Parsells, R.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; Pugachev, D.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Renshaw, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Segreto, E.; Semenov, D.; Shields, E.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Unzhakov, E.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A.; Westerdale, S.; Wojcik, M.; Wright, A.; Xiang, X.; Xu, J.; Yang, C. G.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhu, C.; Zuzel, G.

2015-11-01

The DarkSide experiment is designed for the direct detection of Dark Matter with a double phase liquid Argon TPC operating underground at Laboratori Nazionali del Gran Sasso. The TPC is placed inside a 30 tons liquid organic scintillator sphere, acting as a neutron veto, which is in turn installed inside a 1 kt water Cherenkov detector. The current detector is running since November 2013 with a 50 kg atmospheric Argon fill and we report here the first null results of a Dark Matter search for a (1422 ± 67) kg.d exposure. This result correspond to a 90% CL upper limit on the WIMP-nucleon cross section of 6.1 × 10-44 cm2 (for a WIMP mass of 100 GeV/c2) and it's currently the most sensitive limit obtained with an Argon target.

Hierarchy of Certain Types of DNA Splicing Systems

NASA Astrophysics Data System (ADS)

Yusof, Yuhani; Sarmin, Nor Haniza; Goode, T. Elizabeth; Mahmud, Mazri; Heng, Fong Wan

A Head splicing system (H-system)consists of a finite set of strings (words) written over a finite alphabet, along with a finite set of rules that acts on the strings by iterated cutting and pasting to create a splicing language. Any interpretation that is aligned with Tom Head's original idea is one in which the strings represent double-stranded deoxyribonucleic acid (dsDNA) and the rules represent the cutting and pasting action of restriction enzymes and ligase, respectively. A new way of writing the rule sets is adopted so as to make the biological interpretation transparent. This approach is used in a formal language- theoretic analysis of the hierarchy of certain classes of splicing systems, namely simple, semi-simple and semi-null splicing systems. The relations between such systems and their associated languages are given as theorems, corollaries and counterexamples.

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

PubMed Central

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

2016-01-01

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. PMID:26481005

Pronouns in Catalan: Information, Discourse and Strategy

ERIC Educational Resources Information Center

Mayol, Laia

2009-01-01

This thesis investigates the variation between null and overt pronouns in subject position in Catalan, a null subject language. I argue that null and overt subject pronouns are two resources that speakers efficiently deploy to signal their intended interpretation regarding antecedent choice or semantic meaning, and that communicative agents…

The Importance of Proving the Null

ERIC Educational Resources Information Center

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…

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

EPA Science Inventory

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

Complex Fuzzy Set-Valued Complex Fuzzy Measures and Their Properties

PubMed Central

Ma, Shengquan; Li, Shenggang

2014-01-01

Let F*(K) be the set of all fuzzy complex numbers. In this paper some classical and measure-theoretical notions are extended to the case of complex fuzzy sets. They are fuzzy complex number-valued distance on F*(K), fuzzy complex number-valued measure on F*(K), and some related notions, such as null-additivity, pseudo-null-additivity, null-subtraction, pseudo-null-subtraction, autocontionuous from above, autocontionuous from below, and autocontinuity of the defined fuzzy complex number-valued measures. Properties of fuzzy complex number-valued measures are studied in detail. PMID:25093202

Comparison null imaging ellipsometry using polarization rotator

NASA Astrophysics Data System (ADS)

Park, Sungmo; Kim, Eunsung; Kim, Jiwon; An, Ilsin

2018-05-01

In this study, two-reflection imaging ellipsometry is carried out to compare the changes in polarization states between two samples. By using a polarization rotator, the parallel and perpendicular components of polarization are easily switched between the two samples being compared. This leads to an intensity image consisting of null and off-null points depending on the difference in optical characteristics between the two samples. This technique does not require any movement of optical elements for nulling and can be used to detect defects or surface contamination for quality control of samples.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pontin, D. I.; Priest, E. R.; Galsgaard, K., E-mail: dpontin@maths.dundee.ac.uk

2013-09-10

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

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

NASA Astrophysics Data System (ADS)

Konoplya, R. A.; Stuchlík, Z.

2017-08-01

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

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

NASA Astrophysics Data System (ADS)

Zhang, Zhiwei; Wang, Zhenyu

2017-10-01

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

The relationship of the local food environment with obesity: A systematic review of methods, study quality, and results.

PubMed

Cobb, Laura K; Appel, Lawrence J; Franco, Manuel; Jones-Smith, Jessica C; Nur, Alana; Anderson, Cheryl A M

2015-07-01

To examine the relationship between local food environments and obesity and assess the quality of studies reviewed. Systematic keyword searches identified studies from US and Canada that assessed the relationship of obesity to local food environments. We applied a quality metric based on design, exposure and outcome measurement, and analysis. We identified 71 studies representing 65 cohorts. Overall, study quality was low; 60 studies were cross-sectional. Associations between food outlet availability and obesity were predominantly null. Among non-null associations, we saw a trend toward inverse associations between supermarket availability and obesity (22 negative, 4 positive, 67 null) and direct associations between fast food and obesity (29 positive, 6 negative, 71 null) in adults. We saw direct associations between fast food availability and obesity in lower income children (12 positive, 7 null). Indices including multiple food outlets were most consistently associated with obesity in adults (18 expected, 1 not expected, 17 null). Limiting to higher quality studies did not affect results. Despite the large number of studies, we found limited evidence for associations between local food environments and obesity. The predominantly null associations should be interpreted cautiously due to the low quality of available studies. © 2015 The Obesity Society.

The Lande-Kirkpatrick mechanism is the null model of evolution by intersexual selection: implications for meaning, honesty, and design in intersexual signals.

PubMed

Prum, Richard O

2010-11-01

The Fisher-inspired, arbitrary intersexual selection models of Lande (1981) and Kirkpatrick (1982), including both stable and unstable equilibrium conditions, provide the appropriate null model for the evolution of traits and preferences by intersexual selection. Like the Hardy–Weinberg equilibrium, the Lande–Kirkpatrick (LK) mechanism arises as an intrinsic consequence of genetic variation in trait and preference in the absence of other evolutionary forces. The LK mechanism is equivalent to other intersexual selection mechanisms in the absence of additional selection on preference and with additional trait-viability and preference-viability correlations equal to zero. The LK null model predicts the evolution of arbitrary display traits that are neither honest nor dishonest, indicate nothing other than mating availability, and lack any meaning or design other than their potential to correspond to mating preferences. The current standard for demonstrating an arbitrary trait is impossible to meet because it requires proof of the null hypothesis. The LK null model makes distinct predictions about the evolvability of traits and preferences. Examples of recent intersexual selection research document the confirmationist pitfalls of lacking a null model. Incorporation of the LK null into intersexual selection will contribute to serious examination of the extent to which natural selection on preferences shapes signals.

Viewing condition dependence of the gaze-evoked nystagmus in Arnold Chiari type 1 malformation.

PubMed

Ghasia, Fatema F; Gulati, Deepak; Westbrook, Edward L; Shaikh, Aasef G

2014-04-15

Saccadic eye movements rapidly shift gaze to the target of interest. Once the eyes reach a given target, the brainstem ocular motor integrator utilizes feedback from various sources to assure steady gaze. One of such sources is cerebellum whose lesion can impair neural integration leading to gaze-evoked nystagmus. The gaze evoked nystagmus is characterized by drifts moving the eyes away from the target and a null position where the drifts are absent. The extent of impairment in the neural integration for two opposite eccentricities might determine the location of the null position. Eye in the orbit position might also determine the location of the null. We report this phenomenon in a patient with Arnold Chiari type 1 malformation who had intermittent esotropia and horizontal gaze-evoked nystagmus with a shift in the null position. During binocular viewing, the null was shifted to the right. During monocular viewing, when the eye under cover drifted nasally (secondary to the esotropia), the null of the gaze-evoked nystagmus reorganized toward the center. We speculate that the output of the neural integrator is altered from the bilateral conflicting eye in the orbit position secondary to the strabismus. This could possibly explain the reorganization of the location of the null position. Copyright © 2014 Elsevier B.V. All rights reserved.

Sachs' free data in real connection variables

NASA Astrophysics Data System (ADS)

De Paoli, Elena; Speziale, Simone

2017-11-01

We discuss the Hamiltonian dynamics of general relativity with real connection variables on a null foliation, and use the Newman-Penrose formalism to shed light on the geometric meaning of the various constraints. We identify the equivalent of Sachs' constraint-free initial data as projections of connection components related to null rotations, i.e. the translational part of the ISO(2) group stabilising the internal null direction soldered to the hypersurface. A pair of second-class constraints reduces these connection components to the shear of a null geodesic congruence, thus establishing equivalence with the second-order formalism, which we show in details at the level of symplectic potentials. A special feature of the first-order formulation is that Sachs' propagating equations for the shear, away from the initial hypersurface, are turned into tertiary constraints; their role is to preserve the relation between connection and shear under retarded time evolution. The conversion of wave-like propagating equations into constraints is possible thanks to an algebraic Bianchi identity; the same one that allows one to describe the radiative data at future null infinity in terms of a shear of a (non-geodesic) asymptotic null vector field in the physical spacetime. Finally, we compute the modification to the spin coefficients and the null congruence in the presence of torsion.

The relationship of the local food environment with obesity: A systematic review of methods, study quality and results

PubMed Central

Cobb, Laura K; Appel, Lawrence J; Franco, Manuel; Jones-Smith, Jessica C; Nur, Alana; Anderson, Cheryl AM

2015-01-01

Objective To examine the relationship between local food environments and obesity and assess the quality of studies reviewed. Methods Systematic keyword searches identified studies from US and Canada that assessed the relationship of obesity to local food environments. We applied a quality metric based on design, exposure and outcome measurement, and analysis. Results We identified 71 studies representing 65 cohorts. Overall, study quality was low; 60 studies were cross-sectional. Associations between food outlet availability and obesity were predominantly null. Among non-null associations, we saw a trend toward inverse associations between supermarket availability and obesity (22 negative, 4 positive, 67 null) and direct associations between fast food and obesity (29 positive, 6 negative, 71 null) in adults. We saw direct associations between fast food availability and obesity in lower income children (12 positive, 7 null). Indices including multiple food outlets were most consistently associated with obesity in adults (18 expected, 1 not expected, 17 null). Limiting to higher quality studies did not affect results. Conclusions Despite the large number of studies, we found limited evidence for associations between local food environments and obesity. The predominantly null associations should be interpreted cautiously due to the low quality of available studies. PMID:26096983

Fiscal Shenanigans, Targeted Federal Health Care Funds, and Patient Mortality

PubMed Central

Baicker, Katherine; Staiger, Douglas

2007-01-01

We explore the effectiveness of matching grants when lower levels of government can expropriate some of the funds for other uses. Using data on the Medicaid Disproportionate Share program, we identify states that were most able to expropriate funds. Payments to public hospitals in these states were systematically diverted and had no significant impact on patient mortality. Payments that were not expropriated were associated with significant declines in patient mortality. Overall, subsidies were an effective mechanism for improving outcomes for the poor, but the impact was limited by the ability of state and local governments to divert the targeted funds. PMID:18084627

Method of cooling gas only nozzle fuel tip

DOEpatents

Bechtel, William Theodore; Fitts, David Orus; DeLeonardo, Guy Wayne

2002-01-01

A diffusion flame nozzle gas tip is provided to convert a dual fuel nozzle to a gas only nozzle. The nozle tip diverts compressor discharge air from the passage feeding the diffusion nozzle air swirl vanes to a region vacated by removal of the dual fuel components, so that the diverted compressor discharge air can flow to and through effusion holes in the end cap plate of the nozzle tip. In a preferred embodiment, the nozzle gas tip defines a cavity for receiving the compressor discharge air from a peripheral passage of the nozzle for flow through the effusion openings defined in the end cap plate.

Diverter AI based decision aid, phases 1 and 2

NASA Technical Reports Server (NTRS)

Sexton, George A.; Bayles, Scott J.; Patterson, Robert W.; Schulke, Duane A.; Williams, Deborah C.

1989-01-01

It was determined that a system to incorporate artificial intelligence (AI) into airborne flight management computers is feasible. The AI functions that would be most useful to the pilot are to perform situational assessment, evaluate outside influences on the contemplated rerouting, perform flight planning/replanning, and perform maneuver planning. A study of the software architecture and software tools capable of demonstrating Diverter was also made. A skeletal planner known as the Knowledge Acquisition Development Tool (KADET), which is a combination script-based and rule-based system, was used to implement the system. A prototype system was developed which demonstrates advanced in-flight planning/replanning capabilities.

Application of Chimera Navier-Stokes Code for High Speed Flows

NASA Technical Reports Server (NTRS)

Ajmani, Kumud

1997-01-01

The primary task for this year was performed in support of the "Trailblazer" project. The purpose of the task was to perform an extensive CFD study of the shock boundary-layer interaction between the engine-diverters and the primary body surfaces of the Trailblazer vehicle. Information gathered from this study would be used to determine the effectiveness of the diverters in preventing the boundary-layer coming off of the vehicle forebody from entering the main engines. The PEGSUS code was used to define the "holes" and "boundaries" for each grid. Two sets of CFD calculations were performed.Extensive post-processing of the results was performed.

Analysis of results from wind tunnel tests of inlets for an advanced turboprop nacelle installation

NASA Technical Reports Server (NTRS)

Hancock, J. P.; Lyman, V.; Pennock, A. P.

1986-01-01

Inlets for tractor installations of advanced turboprop propulsion systems were tested in three phases, covering a period from November, 1982 to January, 1984. Nacelle inlet configuration types included single scoop, twin scoop, and annular arrangements. Tests were performed with and without boundary layer diverters and several different diverter heights were tested for the single scoop inlet. This same inlet was also tested at two different axial positions. Test Mach numbers ranged from Mach 0.20 to 0.80. Types of data taken were: (1) internal and external pressures, including inlet throat recoveries; (2) balance forces, including thrust-minus-drag; and (3) propellar blade stresses.

PH adjustment of power plant cooling water with flue gas/fly ash

DOEpatents

Brady, Patrick V.; Krumhansl, James L.

2015-09-22

A system including a vessel including a heat source and a flue; a turbine; a condenser; a fluid conduit circuit disposed between the vessel, the turbine and the condenser; and a diverter coupled to the flue to direct a portion of an exhaust from the flue to contact with a cooling medium for the condenser water. A method including diverting a portion of exhaust from a flue of a vessel; modifying the pH of a cooling medium for a condenser with the portion of exhaust; and condensing heated fluid from the vessel with the pH modified cooling medium.

Parachuting: a dangerous trend in recreational psychoactive substance delivery.

PubMed

Boels, David; Grall-Bronnec, Marie; Guerlais, Marylène; Le Roux, Gael; Spiers, Andrew; Gerardin, Marie; Lomenech, Hélène; Bretaudeau-Deguigne, Marie; Daveluy, Amélie; Turcant, Alain; Jolliet, Pascale; Victorri-Vigneau, Caroline

2017-04-01

Medicine diversion for recreational use is a constant concern for health authorities. Parachuting, also refered to as bombing, is used in order to increase the expected effect, to accelerate time-to-onset and to create mixtures of medicines and substances. Aeras covered: Firstly, we analyzed all available scientific literature (PRISMA) and internet forums without any limiting timeframe. Secondly, we collected cases of parachuting reported in the west of France by the addictovigilance and poison control centres. Our study confirms the reality of this emerging issue associated with a higher medical risk (60% of intoxication cases were moderate-to-severe in our study). The substances involved in parachuting were primarily stimulants, with a majority of MDMA, although the use of diverted medication and psychotropes is also of concern. Expert opinion: Parachuting is a dangerous way of using substances and of diverting medicines. This type of administration gives users a certain pharmacokinetic latitude to 'play' with respect to substances and medicines. Medicine abuse deterrent formulations do not seem to be sufficient in preventing diversions. This dangerous method of using substances and of diverting medicines should drive pharmaceutical companies to innovate in the interest of public health and safety.

Flow assignment model for quantitative analysis of diverting bulk freight from road to railway

PubMed Central

Liu, Chang; Wang, Jiaxi; Xiao, Jie; Liu, Siqi; Wu, Jianping; Li, Jian

2017-01-01

Since railway transport possesses the advantage of high volume and low carbon emissions, diverting some freight from road to railway will help reduce the negative environmental impacts associated with transport. This paper develops a flow assignment model for quantitative analysis of diverting truck freight to railway. First, a general network which considers road transportation, railway transportation, handling and transferring is established according to all the steps in the whole transportation process. Then general functions which embody the factors which the shippers will pay attention to when choosing mode and path are formulated. The general functions contain the congestion cost on road, the capacity constraints of railways and freight stations. Based on the general network and general cost function, a user equilibrium flow assignment model is developed to simulate the flow distribution on the general network under the condition that all shippers choose transportation mode and path independently. Since the model is nonlinear and challenging, we adopt a method that uses tangent lines to constitute envelope curve to linearize it. Finally, a numerical example is presented to test the model and show the method of making quantitative analysis of bulk freight modal shift between road and railway. PMID:28771536

Dispersion and transport of hypersaline gravity currents in the presence of internal waves at a pycnocline

NASA Astrophysics Data System (ADS)

Hogg, C. A. R.; Pietrasz, V. B.; Ouellette, N. T.; Koseff, J. R.

2015-12-01

Desalination of seawater offers a source of potable water in arid regions and during drought. However, hypersaline discharge from desalination facilities presents environmental risks, particularly to benthic organisms. The risks posed by salt levels and chemical additives, which can be toxic to local ecosystems, are typically mitigated by ensuring high levels of dilution close to the source. We report on laboratory flume experiments examining how internal waves at the pycnocline of a layered ambient density stratification influence the transport of hypersaline effluent moving as a gravity current down the slope. We found that some of the hypersaline fluid from the gravity current was diverted away from the slope into an intrusion along the pycnocline. A parametric study investigated how varying the energy of the internal wave altered the amount of dense fluid that was diverted into the pycnocline intrusion. The results are compared to an analytical framework that compares the incident energy in the internal wave to potential energy used in diluting the gravity current. These results are significant for desalination effluents because fluid diverted into the intrusion avoids the ecologically sensitive benthic layer and disperses more quickly than if it had continued to propagate along the bed.

Influence of internal waves on the dispersion and transport of inclined gravity currents

NASA Astrophysics Data System (ADS)

Hogg, C. A. R.; Pietrasz, V. B.; Ouellette, N. T.; Koseff, J. R.

2016-02-01

Brine discharge from desalination facilities presents environmental risks, particularly to benthic organisms. High concentrations of salt and chemical additives, which can be toxic to local ecosystems, are typically mitigated by dilution close to the source. Our laboratory experiments investigate how breaking internal tides can help to dilute gravity currents caused by desalination effluents and direct them away from the benthic layer. In laboratory experiments, internal waves at the pycnocline of an ambient stratification were directed towards a sloping shelf, down which ran a gravity current. The breaking internal waves were seen to increase the proportion of the fluid from the gravity current diverted away from the slope into an intrusion along the pycnocline. In a parametric study, increasing the amplitude of the internal wave was seen to increase the amount of dense fluid in the pycnocline intrusion. The amplitude required to divert the gravity current into the intrusion compares well with an analytical theory that equates the incident energy in the internal wave to the potential energy required to dilute the gravity current. These experimental results suggest that sites of breaking internal waves may be good sites for effluent disposal. Effluent diverted into the intrusion avoids the ecologically sensitive benthic layer.

RANS Analyses of Turbofan Nozzles with Wedge Deflectors for Noise Reduction

NASA Technical Reports Server (NTRS)

DeBonis, James R.

2008-01-01

Computational fluid dynamics (CFD) was used to evaluate a promising concept for reducing the noise at take-off of dual-stream, turbofan nozzles. The concept, offset stream technology, reduces the jet noise observed on the ground by diverting (offsetting) the majority of the fan flow below the core flow, thickening this layer between the high velocity core flow and the ground observers. In this study a wedge placed in the internal fan stream is used as the diverter. Wind, a Reynolds Averaged Navier-Stokes (RANS) code, was used to analyze the flowfield of the exhaust plume and to calculate nozzle performance. Results showed that the wedge effectively diverts the fan flow and the turbulent kinetic energy on the observer side of the nozzle is reduced. The reduction in turbulent kinetic energy should correspond to a reduction in noise. The blockage due to the wedge reduces the fan massflow proportional to its blockage and the overall thrust is consequently reduced. The CFD predictions are in very good agreement with experimental data. This noise reduction concept shows promise for reduced jet noise at a small reduction in thrust. It has been demonstrated that RANS CFD can be used to optimize this concept.

Constituents of smoke from cigarettes made from diverted nicotine replacement therapy patches.

PubMed

Morrissey, Hana; Ball, Patrick; Boland, Martin; Hefler, Marita; Thomas, David P

2016-03-01

Anecdotes of nicotine replacement therapy patch misuse associated with the introduction of smoke-free prisons have been reported by media internationally, including Canada in 2006, New Zealand in 2011 and Australia in 2014. This study identifies chemical compounds released through diverted nicotine replacement therapy patches when they are smoked. Two samples were produced: (i) shredded 21 mg nicotine replacement therapy patches rolled with tea leaves into a cigarette; and (ii) patches boiled in water and tea leaves, and then dried tea leaves rolled into a cigarette. The smoke was tested for nicotine, caffeine and toxins. High-performance liquid chromatography, mass spectrometry and spectrophotometry were used to detect the presence and quantity of nicotine and caffeine. A specialised laboratory was contracted to test the presence of toxins. Nicotine was liberated when the two samples were burnt but not if the nicotine replacement therapy patches were boiled in water alone. High concentrations of formaldehyde, acetaldehyde, acrolein, toluene, xylene and heavy metals were also released. Nicotine is released when diverted nicotine replacement therapy patches are smoked, as are caffeine and harmful toxins. These toxins have the potential to cause short- and long-term health damage. © 2015 Australasian Professional Society on Alcohol and other Drugs.

SPECTROSCOPIC ONLINE MONITORING FOR PROCESS CONTROL AND SAFEGUARDING OF RADIOCHEMICAL STREAMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryan, Samuel A.; Levitskaia, Tatiana G.

2013-09-29

There is a renewed interest worldwide to promote the use of nuclear power and close the nuclear fuel cycle. The long term successful use of nuclear power is critically dependent upon adequate and safe processing and disposition of the used nuclear fuel. Liquid-liquid extraction is a separation technique commonly employed for the processing of the dissolved used nuclear fuel. The instrumentation used to monitor these processes must be robust, require little or no maintenance, and be able to withstand harsh environments such as high radiation fields and aggressive chemical matrices. This paper summarizes application of the absorption and vibrational spectroscopicmore » techniques supplemented by physicochemical measurements for radiochemical process monitoring. In this context, our team experimentally assessed the potential of Raman and spectrophotometric techniques for online real-time monitoring of the U(VI)/nitrate ion/nitric acid and Pu(IV)/Np(V)/Nd(III), respectively, in solutions relevant to spent fuel reprocessing. These techniques demonstrate robust performance in the repetitive batch measurements of each analyte in a wide concentration range using simulant and commercial dissolved spent fuel solutions. Spectroscopic measurements served as training sets for the multivariate data analysis to obtain partial least squares predictive models, which were validated using on-line centrifugal contactor extraction tests. Satisfactory prediction of the analytes concentrations in these preliminary experiments warrants further development of the spectroscopy-based methods for radiochemical process control and safeguarding. Additionally, the ability to identify material intentionally diverted from a liquid-liquid extraction contactor system was successfully tested using on-line process monitoring as a means to detect the amount of material diverted. A chemical diversion and detection from a liquid-liquid extraction scheme was demonstrated using a centrifugal contactor system operating with the simulant PUREX extraction system of Nd(NO3)3/nitric acid aqueous phase and TBP/n-dodecane organic phase. During a continuous extraction experiment, a portion of the feed from a counter-current extraction system was diverted while the spectroscopic on-line process monitoring system was simultaneously measuring the feed, raffinate and organic products streams. The amount observed to be diverted by on-line spectroscopic process monitoring was in excellent agreement with values based from the known mass of sample directly taken (diverted) from system feed solution.« less

Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India.

PubMed

Mastana, Sarabjit S; Kaur, Antarpreet; Hale, Rachel; Lindley, Martin R

2013-12-01

Glutathione S-transferases (GSTs) belong to a group of multigene and multifunctional detoxification enzymes, which defend cells against a wide variety of toxic insults and oxidative stress. Oxidative stress leads to cellular dysfunction which contributes to the pathophysiology of diseases such as cancer, atherosclerosis, and diabetes mellitus. It is important to assess whether the glutathione S-Transferase (GSTT1, GSTM1 and GSTP1) genotypes are associated with type 2 diabetes mellitus as deletion polymorphisms have an impaired capability to counteract the oxidative stress which is a feature of diabetes. GSTT1, GSTM1 and GSTP1 gene polymorphisms were analysed in 321 patients and 309 healthy controls from an endogamous population from north India. An association analysis was carried out at two levels (a) individual genes and (b) their double and triple combinations. The proportion of GSTT1 and GSTM1 null genotypes was higher in diabetics compared to controls (GSTT1 30.8 vs. 21.0 %; GSTM1 49.5 vs. 27.2 %). The frequency of the null genotype at both loci was higher in diabetics (19.6 vs. 7.8 %) leading to an odds ratio of 2.90 (CI 1.76-4.78, P < 0.0001). At GSTP1locus, patients had a higher frequency of the V/V genotype (15.6 vs. 7.5 %) and significant susceptible odds ratio (2.56, CI 1.47-4.48, P < 0.001). A combination of null genotypes at GSTT1 and GSTM1 loci and V/V genotype of GSTP1 locus showed highest odds ratio (9.64, CI 1.53-60.63, P < 0.01). Overall this study highlights that GST genes may play an important role in the pathogenesis of type 2 diabetes. The risk is higher in individuals carrying more than one susceptible genotype at these loci. The potential role of GST polymorphisms as markers of susceptibility to type 2 diabetes needs further investigations in a larger number of patients and populations.

Predictive uncertainty analysis of a saltwater intrusion model using null-space Monte Carlo

USGS Publications Warehouse

Herckenrath, Daan; Langevin, Christian D.; Doherty, John

2011-01-01

Because of the extensive computational burden and perhaps a lack of awareness of existing methods, rigorous uncertainty analyses are rarely conducted for variable-density flow and transport models. For this reason, a recently developed null-space Monte Carlo (NSMC) method for quantifying prediction uncertainty was tested for a synthetic saltwater intrusion model patterned after the Henry problem. Saltwater intrusion caused by a reduction in fresh groundwater discharge was simulated for 1000 randomly generated hydraulic conductivity distributions, representing a mildly heterogeneous aquifer. From these 1000 simulations, the hydraulic conductivity distribution giving rise to the most extreme case of saltwater intrusion was selected and was assumed to represent the "true" system. Head and salinity values from this true model were then extracted and used as observations for subsequent model calibration. Random noise was added to the observations to approximate realistic field conditions. The NSMC method was used to calculate 1000 calibration-constrained parameter fields. If the dimensionality of the solution space was set appropriately, the estimated uncertainty range from the NSMC analysis encompassed the truth. Several variants of the method were implemented to investigate their effect on the efficiency of the NSMC method. Reducing the dimensionality of the null-space for the processing of the random parameter sets did not result in any significant gains in efficiency and compromised the ability of the NSMC method to encompass the true prediction value. The addition of intrapilot point heterogeneity to the NSMC process was also tested. According to a variogram comparison, this provided the same scale of heterogeneity that was used to generate the truth. However, incorporation of intrapilot point variability did not make a noticeable difference to the uncertainty of the prediction. With this higher level of heterogeneity, however, the computational burden of generating calibration-constrained parameter fields approximately doubled. Predictive uncertainty variance computed through the NSMC method was compared with that computed through linear analysis. The results were in good agreement, with the NSMC method estimate showing a slightly smaller range of prediction uncertainty than was calculated by the linear method. Copyright 2011 by the American Geophysical Union.

"Null-E" magnetic bearings

NASA Astrophysics Data System (ADS)

Filatov, Alexei Vladimirovich

2002-09-01

Using electromagnetic forces to suspend rotating objects (rotors) without mechanical contact is often an appealing technical solution. Magnetic suspensions are typically required to have adequate load capacity and stiffness, and low rotational loss. Other desired features include low price, high reliability and manufacturability. With recent advances in permanent-magnet materials, the required forces can often be obtained by simply using the interaction between permanent magnets. While a magnetic bearing based entirely on permanent magnets could be expected to be inexpensive, reliable and easy to manufacture, a fundamental physical principle known as Earnshaw's theorem maintains that this type of suspension cannot be statically stable. Therefore, some other physical mechanisms must be included. One such mechanism employs the interaction between a conductor and a nonuniform magnetic field in relative motion. Its advantages include simplicity, reliability, wide range of operating temperature and system autonomy (no external wiring and power supplies are required). The disadvantages of the earlier embodiments were high rotational loss, low stiffness and load capacity. This dissertation proposes a novel type of magnetic bearing stabilized by the field-conductor interaction. One of the advantages of this bearing is that no electric field, E, develops in the conductor during the rotor rotation when the system is in no-load equilibrium. Because of this we refer to it as the Null-E Bearing. Null-E Bearings have potential for lower rotational loss and higher load capacity and stiffness than other bearings utilizing the field-conductor interaction. Their performance is highly insensitive to manufacturing inaccuracies. The Null-E Bearing in its basic form can be augmented with supplementary electronics to improve its performance. Depending on the degree of the electronics involvement, a variety of magnetic bearings can be developed ranging from a completely passive to an active magnetic bearing of a novel type. This dissertation contains theoretical analysis of the Null-E Bearing operation, including derivation of the stability conditions and estimation of some of the rotational losses. The validity of the theoretical conclusions has been demonstrated by building and testing a prototype in which non-contact suspension of a 3.2-kg rotor is achieved at spin speeds above 18 Hz.

Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease.

PubMed

Dai, Mei; Liou, Benjamin; Swope, Brittany; Wang, Xiaohong; Zhang, Wujuan; Inskeep, Venette; Grabowski, Gregory A; Sun, Ying; Pan, Dao

2016-01-01

To study the neuronal deficits in neuronopathic Gaucher Disease (nGD), the chronological behavioral profiles and the age of onset of brain abnormalities were characterized in a chronic nGD mouse model (9V/null). Progressive accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) in the brain of 9V/null mice were observed at as early as 6 and 3 months of age for GC and GS, respectively. Abnormal accumulation of α-synuclein was present in the 9V/null brain as detected by immunofluorescence and Western blot analysis. In a repeated open-field test, the 9V/null mice (9 months and older) displayed significantly less environmental habituation and spent more time exploring the open-field than age-matched WT group, indicating the onset of short-term spatial memory deficits. In the marble burying test, the 9V/null group had a shorter latency to initiate burying activity at 3 months of age, whereas the latency increased significantly at ≥12 months of age; 9V/null females buried significantly more marbles to completion than the WT group, suggesting an abnormal response to the instinctive behavior and an abnormal activity in non-associative anxiety-like behavior. In the conditional fear test, only the 9V/null males exhibited a significant decrease in response to contextual fear, but both genders showed less response to auditory-cued fear compared to age- and gender-matched WT at 12 months of age. These results indicate hippocampus-related emotional memory defects. Abnormal gait emerged in 9V/null mice with wider front-paw and hind-paw widths, as well as longer stride in a gender-dependent manner with different ages of onset. Significantly higher liver- and spleen-to-body weight ratios were detected in 9V/null mice with different ages of onsets. These data provide temporal evaluation of neurobehavioral dysfunctions and brain pathology in 9V/null mice that can be used for experimental designs to evaluate novel therapies for nGD.

Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease

PubMed Central

Dai, Mei; Liou, Benjamin; Swope, Brittany; Wang, Xiaohong; Zhang, Wujuan; Inskeep, Venette; Grabowski, Gregory A.; Sun, Ying; Pan, Dao

2016-01-01

To study the neuronal deficits in neuronopathic Gaucher Disease (nGD), the chronological behavioral profiles and the age of onset of brain abnormalities were characterized in a chronic nGD mouse model (9V/null). Progressive accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) in the brain of 9V/null mice were observed at as early as 6 and 3 months of age for GC and GS, respectively. Abnormal accumulation of α-synuclein was present in the 9V/null brain as detected by immunofluorescence and Western blot analysis. In a repeated open-field test, the 9V/null mice (9 months and older) displayed significantly less environmental habituation and spent more time exploring the open-field than age-matched WT group, indicating the onset of short-term spatial memory deficits. In the marble burying test, the 9V/null group had a shorter latency to initiate burying activity at 3 months of age, whereas the latency increased significantly at ≥12 months of age; 9V/null females buried significantly more marbles to completion than the WT group, suggesting an abnormal response to the instinctive behavior and an abnormal activity in non-associative anxiety-like behavior. In the conditional fear test, only the 9V/null males exhibited a significant decrease in response to contextual fear, but both genders showed less response to auditory-cued fear compared to age- and gender-matched WT at 12 months of age. These results indicate hippocampus-related emotional memory defects. Abnormal gait emerged in 9V/null mice with wider front-paw and hind-paw widths, as well as longer stride in a gender-dependent manner with different ages of onset. Significantly higher liver- and spleen-to-body weight ratios were detected in 9V/null mice with different ages of onsets. These data provide temporal evaluation of neurobehavioral dysfunctions and brain pathology in 9V/null mice that can be used for experimental designs to evaluate novel therapies for nGD. PMID:27598339

Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

PubMed

ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

2018-06-20

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

Influence of Choice of Null Network on Small-World Parameters of Structural Correlation Networks

PubMed Central

Hosseini, S. M. Hadi; Kesler, Shelli R.

2013-01-01

In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures. PMID:23840672

Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse

PubMed Central

Braun, Anne; Zhang, Songwen; Miettinen, Helena E.; Ebrahim, Shamsah; Holm, Teresa M.; Vasile, Eliza; Post, Mark J.; Yoerger, Danita M.; Picard, Michael H.; Krieger, Joshua L.; Andrews, Nancy C.; Simons, Michael; Krieger, Monty

2003-01-01

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5–6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between ≈3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease. PMID:12771386

Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers

PubMed Central

Fukada, So-ichiro; Yamaguchi, Masahiko; Kokubo, Hiroki; Ogawa, Ryo; Uezumi, Akiyoshi; Yoneda, Tomohiro; Matev, Miroslav M.; Motohashi, Norio; Ito, Takahito; Zolkiewska, Anna; Johnson, Randy L.; Saga, Yumiko; Miyagoe-Suzuki, Yuko; Tsujikawa, Kazutake; Takeda, Shin’ichi; Yamamoto, Hiroshi

2011-01-01

Satellite cells, which are skeletal muscle stem cells, divide to provide new myonuclei to growing muscle fibers during postnatal development, and then are maintained in an undifferentiated quiescent state in adult skeletal muscle. This state is considered to be essential for the maintenance of satellite cells, but their molecular regulation is unknown. We show that Hesr1 (Hey1) and Hesr3 (Heyl) (which are known Notch target genes) are expressed simultaneously in skeletal muscle only in satellite cells. In Hesr1 and Hesr3 single-knockout mice, no obvious abnormalities of satellite cells or muscle regenerative potentials are observed. However, the generation of undifferentiated quiescent satellite cells is impaired during postnatal development in Hesr1/3 double-knockout mice. As a result, myogenic (MyoD and myogenin) and proliferative (Ki67) proteins are expressed in adult satellite cells. Consistent with the in vivo results, Hesr1/3-null myoblasts generate very few Pax7+ MyoD– undifferentiated cells in vitro. Furthermore, the satellite cell number gradually decreases in Hesr1/3 double-knockout mice even after it has stabilized in control mice, and an age-dependent regeneration defect is observed. In vivo results suggest that premature differentiation, but not cell death, is the reason for the reduced number of satellite cells in Hesr1/3 double-knockout mice. These results indicate that Hesr1 and Hesr3 are essential for the generation of adult satellite cells and for the maintenance of skeletal muscle homeostasis. PMID:21989910

DNA recombination-initiation plays a role in the extremely biased inheritance of yeast [rho-] mitochondrial DNA that contains the replication origin ori5.

PubMed

Ling, Feng; Hori, Akiko; Shibata, Takehiko

2007-02-01

Hypersuppressiveness, as observed in Saccharomyces cerevisiae, is an extremely biased inheritance of a small mitochondrial DNA (mtDNA) fragment that contains a replication origin (HS [rho(-)] mtDNA). Our previous studies showed that concatemers (linear head-to-tail multimers) are obligatory intermediates for mtDNA partitioning and are primarily formed by rolling-circle replication mediated by Mhr1, a protein required for homologous mtDNA recombination. In this study, we found that Mhr1 is required for the hypersuppressiveness of HS [ori5] [rho(-)] mtDNA harboring ori5, one of the replication origins of normal ([rho(+)]) mtDNA. In addition, we detected an Ntg1-stimulated double-strand break at the ori5 locus. Purified Ntg1, a base excision repair enzyme, introduced a double-stranded break by itself into HS [ori5] [rho(-)] mtDNA at ori5 isolated from yeast cells. Both hypersuppressiveness and concatemer formation of HS [ori5] [rho(-)] mtDNA are simultaneously suppressed by the ntg1 null mutation. These results support a model in which, like homologous recombination, rolling-circle HS [ori5] [rho(-)] mtDNA replication is initiated by double-stranded breakage in ori5, followed by Mhr1-mediated homologous pairing of the processed nascent DNA ends with circular mtDNA. The hypersuppressiveness of HS [ori5] [rho(-)] mtDNA depends on a replication advantage furnished by the higher density of ori5 sequences and on a segregation advantage furnished by the higher genome copy number on transmitted concatemers.

Arabidopsis Chloroplast Mini-Ribonuclease III Participates in rRNA Maturation and Intron Recycling

PubMed Central

Hotto, Amber M.; Castandet, Benoît; Gilet, Laetitia; Higdon, Andrea; Condon, Ciarán; Stern, David B.

2015-01-01

RNase III proteins recognize double-stranded RNA structures and catalyze endoribonucleolytic cleavages that often regulate gene expression. Here, we characterize the functions of RNC3 and RNC4, two Arabidopsis thaliana chloroplast Mini-RNase III-like enzymes sharing 75% amino acid sequence identity. Whereas rnc3 and rnc4 null mutants have no visible phenotype, rnc3/rnc4 (rnc3/4) double mutants are slightly smaller and chlorotic compared with the wild type. In Bacillus subtilis, the RNase Mini-III is integral to 23S rRNA maturation. In Arabidopsis, we observed imprecise maturation of 23S rRNA in the rnc3/4 double mutant, suggesting that exoribonucleases generated staggered ends in the absence of specific Mini-III-catalyzed cleavages. A similar phenotype was found at the 3′ end of the 16S rRNA, and the primary 4.5S rRNA transcript contained 3′ extensions, suggesting that Mini-III catalyzes several processing events of the polycistronic rRNA precursor. The rnc3/4 mutant showed overaccumulation of a noncoding RNA complementary to the 4.5S-5S rRNA intergenic region, and its presence correlated with that of the extended 4.5S rRNA precursor. Finally, we found rnc3/4-specific intron degradation intermediates that are probable substrates for Mini-III and show that B. subtilis Mini-III is also involved in intron regulation. Overall, this study extends our knowledge of the key role of Mini-III in intron and noncoding RNA regulation and provides important insight into plastid rRNA maturation. PMID:25724636

Probing transcription-specific outputs of β-catenin in vivo.

PubMed

Valenta, Tomas; Gay, Max; Steiner, Sarah; Draganova, Kalina; Zemke, Martina; Hoffmans, Raymond; Cinelli, Paolo; Aguet, Michel; Sommer, Lukas; Basler, Konrad

2011-12-15

β-Catenin, apart from playing a cell-adhesive role, is a key nuclear effector of Wnt signaling. Based on activity assays in Drosophila, we generated mouse strains where the endogenous β-catenin protein is replaced by mutant forms, which retain the cell adhesion function but lack either or both of the N- and the C-terminal transcriptional outputs. The C-terminal activity is essential for mesoderm formation and proper gastrulation, whereas N-terminal outputs are required later during embryonic development. By combining the double-mutant β-catenin with a conditional null allele and a Wnt1-Cre driver, we probed the role of Wnt/β-catenin signaling in dorsal neural tube development. While loss of β-catenin protein in the neural tube results in severe cell adhesion defects, the morphology of cells and tissues expressing the double-mutant form is normal. Surprisingly, Wnt/β-catenin signaling activity only moderately regulates cell proliferation, but is crucial for maintaining neural progenitor identity and for neuronal differentiation in the dorsal spinal cord. Our model animals thus allow dissecting signaling and structural functions of β-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. © 2011 by Cold Spring Harbor Laboratory Press

Differential Requirements for c-Myc in Chronic Hematopoietic Hyperplasia and Acute Hematopoietic Malignancies in Pten-null Mice

PubMed Central

Zhang, Jun; Xiao, Yechen; Guo, Yinshi; Breslin, Peter; Zhang, Shubin; Wei, Wei; Zhang, Zhou; Zhang, Jiwang

2011-01-01

Myeloproliferative disorders (MPDs), lymphoproliferative disorders (LPDs), acute T-lymphocytic or myeloid leukemia and T-lymphocytic lymphoma were developed in inducible Pten-knockout (Pten−/−) mice. The appearance of these multiple diseases in one animal model provides an opportunity to study the pathogenesis of multiple diseases simultaneously. To study whether Myc function is required for the development of these hematopoietic disorders in Pten−/− mice, we generated inducible Pten/Myc double-knockout mice (Pten−/−/Myc−/−). By comparing the hematopoietic phenotypes of these double-knockout mice with those of Pten−/− mice, we found that both sets of animals developed MPDs and LPDs. However, none of the compound-mutant mice developed acute leukemia or lymphoma. Interestingly, in contrast to the MPDs which developed in Pten−/− mice which are dominated by granulocytes, megakaryocytes predominate in the MPDs of Pten−/−/Myc−/− mice. Our study suggests that the deregulation of PI3K/Akt signaling in Pten−/− hematopoietic cells protects these cells from apoptotic cell death, resulting in chronic proliferative disorders. But due to the differential requirement for Myc in granulocyte as compared to megakaryocyte proliferation, Myc deletion converts Pten−/− MPDs from granulocyte-dominated to megakaryocyte-dominated conditions. Myc is absolutely required for the development of acute hematopoietic malignancies. PMID:21926961

Visual and Plastic Arts in Teaching Literacy: Null Curricula?

ERIC Educational Resources Information Center

Wakeland, Robin Gay

2010-01-01

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

A Critique of One-Tailed Hypothesis Test Procedures in Business and Economics Statistics Textbooks.

ERIC Educational Resources Information Center

Liu, Tung; Stone, Courtenay C.

1999-01-01

Surveys introductory business and economics statistics textbooks and finds that they differ over the best way to explain one-tailed hypothesis tests: the simple null-hypothesis approach or the composite null-hypothesis approach. Argues that the composite null-hypothesis approach contains methodological shortcomings that make it more difficult for…

Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice

EPA Science Inventory

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we ...

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

NASA Astrophysics Data System (ADS)

Shibata, Tsuyoshi; Murakami, Toshiyuki

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

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

PubMed

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.

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

PubMed Central

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

2016-01-01

To investigate the role of synaptic zinc in the ASD pathogenesis, we examined zinc transporter 3 (ZnT3) null mice. At 4–5 weeks of age, male but not female ZnT3 null mice exhibited autistic-like behaviors. Cortical volume and neurite density were significantly greater in male ZnT3 null mice than in WT mice. In male ZnT3 null mice, consistent with enhanced neurotrophic stimuli, the level of BDNF as well as activity of MMP-9 was increased. Consistent with known roles for MMPs in BDNF upregulation, 2.5-week treatment with minocycline, an MMP inhibitor, significantly attenuated BDNF levels as well as megalencephaly and autistic-like behaviors. Although the ZnT3 null state removed synaptic zinc, it rather increased free zinc in the cytosol of brain cells, which appeared to increase MMP-9 activity and BDNF levels. The present results suggest that zinc dyshomeostasis during the critical period of brain development may be a possible contributing mechanism for ASD. PMID:27352957

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

PubMed

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

2016-06-29

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

Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

PubMed

Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

2004-04-01

Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (P<0.0001). This effect was reproduced in control subjects who had depressed leucine levels when treated with sodium phenylacetate/benzoate (P<0.0001). Our studies suggest that this therapeutic modality has a substantial impact on the metabolism of branched chain amino acids in urea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

Divertor with a third-order null of the poloidal field

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2013-09-15

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

Both genetic deletion and pharmacological blockade of lysophosphatidic acid LPA1 receptor results in increased alcohol consumption.

PubMed

Castilla-Ortega, Estela; Pavón, Francisco Javier; Sánchez-Marín, Laura; Estivill-Torrús, Guillermo; Pedraza, Carmen; Blanco, Eduardo; Suárez, Juan; Santín, Luis; Rodríguez de Fonseca, Fernando; Serrano, Antonia

2016-04-01

Lysophosphatidic acid species (LPA) are lipid bioactive signaling molecules that have been recently implicated in the modulation of emotional and motivational behaviors. The present study investigates the consequences of either genetic deletion or pharmacological blockade of lysophosphatidic acid receptor-1 (LPA1) in alcohol consumption. The experiments were performed in alcohol-drinking animals by using LPA1-null mice and administering the LPA1 receptor antagonist Ki16425 in both mice and rats. In the two-bottle free choice paradigm, the LPA1-null mice preferred the alcohol more than their wild-type counterparts. Whereas the male LPA1-null mice displayed this higher preference at all doses tested, the female LPA1-null mice only consumed more alcohol at 6% concentration. The male LPA1-null mice were then further characterized, showing a notably increased ethanol drinking after a deprivation period and a reduced sleep time after acute ethanol administration. In addition, LPA1-null mice were more anxious than the wild-type mice in the elevated plus maze test. For the pharmacological experiments, the acute administration of the antagonist Ki16425 consistently increased ethanol consumption in both wild-type mice and rats; while it did not modulate alcohol drinking in the LPA1-null mice and lacked intrinsic rewarding properties and locomotor effects in a conditioned place preference paradigm. In addition, LPA1-null mice exhibited a marked reduction on the expression of glutamate-transmission-related genes in the prefrontal cortex similar to those described in alcohol-exposed rodents. Results suggest a relevant role for the LPA/LPA1 signaling system in alcoholism. In addition, the LPA1-null mice emerge as a new model for genetic vulnerability to excessive alcohol drinking. The pharmacological manipulation of LPA1 receptor arises as a new target for the study and treatment of alcoholism. Copyright © 2015 Elsevier Ltd. All rights reserved.

On Nulling, Drifting, and Their Interactions in PSRs J1741-0840 and J1840-0840

NASA Astrophysics Data System (ADS)

Gajjar, V.; Yuan, J. P.; Yuen, R.; Wen, Z. G.; Liu, Z. Y.; Wang, N.

2017-12-01

We report detailed investigation of nulling and drifting behavior of two pulsars PSRs J1741-0840 and J1840-0840 observed from the Giant Meterwave Radio Telescope at 625 MHz. PSR J1741-0840 was found to show a nulling fraction (NF) of around 30% ± 5% while PSR J1840-0840 was shown to have an NF of around 50% ± 6%. We measured drifting behavior from different profile components in PSR J1840-0840 for the first time with the leading component showing drifting with 13.5 ± 0.7 periods while the weak trailing component showed drifting of around 18 ± 1 periods. Large nulling hampers accuracy of these quantities derived using standard Fourier techniques. A more accurate comparison was drawn from driftband slopes, measured after sub-pulse modeling. These measurements revealed interesting sporadic and irregular drifting behavior in both pulsars. We conclude that the previously reported different drifting periodicities in the trailing component of PSR J1741-0840 is likely due to the spread in these driftband slopes. We also find that both components of PSR J1840-0840 show similar driftband slopes within the uncertainties. Unique nulling-drifting interaction is identified in PSR J1840-0840 where, on most occasions, the pulsar tends to start nulling after what appears to be the end of a driftband. Similarly, when the pulsar switches back to an emission phase, on most occasions it starts at the beginning of a new driftband in both components. Such behaviors have not been detected in any other pulsars to our knowledge. We also found that PSR J1741-0840 seems to have no memory of its previous burst phase while PSR J1840-0840 clearly exhibits memory of its previous state even after longer nulls for both components. We discuss possible explanations for these intriguing nulling-drifting interactions seen in both pulsars based on various pulsar nulling models.

Apolipoprotein AI Deficiency Inhibits Serum Opacity Factor Activity against Plasma High Density Lipoprotein via a Stabilization Mechanism

PubMed Central

Rosales, Corina; Patel, Niket; Gillard, Baiba K.; Yelamanchili, Dedipya; Yang, Yaliu; Courtney, Harry S.; Santos, Raul D.; Gotto, Antonio M.; Pownall, Henry J.

2016-01-01

The reaction of Streptococcal serum opacity factor (SOF) against plasma high-density lipoproteins (HDL) produces a large cholesteryl ester-rich microemulsion (CERM), a smaller neo HDL that is apolipoprotein (apo) AI-poor, and lipid-free apo AI. SOF is active vs. both human and mouse plasma HDL. In vivo injection of SOF into mice reduces plasma cholesterol ~40% in 3 hours while forming the same products observed in vitro, but at different ratios. Previous studies supported the hypothesis that labile apo AI is required for the SOF reaction vs. HDL. Here we further tested that hypothesis by studies of SOF against HDL from apo AI-null mice. When injected into apo AI-null mice, SOF reduced plasma cholesterol ~35% in three hours. The reaction of SOF vs. apo AI-null HDL in vitro produced a CERM and neo HDL, but no lipid-free apo. Moreover, according to the rate of CERM formation, the extent and rate of the SOF reaction vs. apo AI-null mouse HDL was less than that against wild-type (WT) mouse HDL. Chaotropic perturbation studies using guanidine hydrochloride showed that apo AI-null HDL was more stable than WT HDL. Human apo AI added to apo AI-null HDL was quantitatively incorporated, giving reconstituted HDL. Both SOF and guanidine hydrochloride displaced apo AI from the reconstituted HDL. These results support the conclusion that apo AI-null HDL is more stable than WT HDL because it lacks apo AI, a labile protein that is readily displaced by physico-chemical and biochemical perturbations. Thus, apo AI-null HDL is less SOF-reactive than WT HDL. The properties of apo AI-null HDL can be partially restored to those of WT HDL by the spontaneous incorporation of human apo AI. It remains to be determined what other HDL functions are affected by apo AI deletion. PMID:25790332

Adaptive Nulling for Interferometric Detection of Planets

NASA Technical Reports Server (NTRS)

Lay, Oliver P.; Peters, Robert D.

2010-01-01

An adaptive-nulling method has been proposed to augment the nulling-optical- interferometry method of detection of Earth-like planets around distant stars. The method is intended to reduce the cost of building and aligning the highly precise optical components and assemblies needed for nulling. Typically, at the mid-infrared wavelengths used for detecting planets orbiting distant stars, a star is millions of times brighter than an Earth-sized planet. In order to directly detect the light from the planet, it is necessary to remove most of the light coming from the star. Nulling interferometry is one way to suppress the light from the star without appreciably suppressing the light from the planet. In nulling interferometry in its simplest form, one uses two nominally identical telescopes aimed in the same direction and separated laterally by a suitable distance. The light collected by the two telescopes is processed through optical trains and combined on a detector. The optical trains are designed such that the electric fields produced by an on-axis source (the star) are in anti-phase at the detector while the electric fields from the planet, which is slightly off-axis, combine in phase, so that the contrast ratio between the star and the planet is greatly decreased. If the electric fields from the star are exactly equal in amplitude and opposite in phase, then the star is effectively nulled out. Nulling is effective only if it is complete in the sense that it occurs simultaneously in both polarization states and at all wavelengths of interest. The need to ensure complete nulling translates to extremely tight demands upon the design and fabrication of the complex optical trains: The two telescopes must be highly symmetric, the reflectivities of the many mirrors in the telescopes and other optics must be carefully tailored, the optical coatings must be extremely uniform, sources of contamination must be minimized, optical surfaces must be nearly ideal, and alignments must be extremely precise. Satisfaction of all of these requirements entails substantial cost.

Cruciferous Vegetables Have Variable Effects on Biomarkers of Systemic Inflammation in a Randomized Controlled Trial in Healthy Young Adults12

PubMed Central

Navarro, Sandi L.; Schwarz, Yvonne; Song, Xiaoling; Wang, Ching-Yun; Chen, Chu; Trudo, Sabrina P.; Kristal, Alan R.; Kratz, Mario; Eaton, David L.; Lampe, Johanna W.

2014-01-01

Background: Isothiocyanates in cruciferous vegetables modulate signaling pathways critical to carcinogenesis, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of inflammation. Glutathione S-transferase (GST) M1 and GSTT1 metabolize isothiocyanates; genetic variants may result in differences in biologic response. Objective: The objective of this study was to test whether consumption of cruciferous or cruciferous plus apiaceous vegetables altered serum concentrations of interleukin (IL)-6, IL-8, C-reactive protein (CRP), tumor necrosis factor (TNF) α, and soluble TNF receptor (sTNFR) I and II, and whether this response was GSTM1/GSTT1 genotype dependent. Methods: In a randomized crossover trial, healthy men (n = 32) and women (n = 31) aged 20–40 y consumed 4 14-d controlled diets: basal (vegetable-free), single-dose cruciferous (1xC) [7 g vegetables/kg body weight (BW)], double-dose cruciferous (2xC) (14 g/kg BW), and cruciferous plus apiaceous (carrot family) (1xC+A) vegetables (7 and 4 g/kg BW, respectively), with a 21-d washout period between each intervention. Urinary isothiocyanate excretion was also evaluated as a marker of systemic isothiocyanate exposure. Fasting morning blood and urine samples were collected on days 0 and 14 and analyzed. Results: IL-6 concentrations were significantly lower on day 14 of the 2xC and 1xC+A diets than with the basal diet [−19% (95% CI: −30%, −0.1%) and −20% (95% CI: −31%, -0.7%), respectively]. IL-8 concentrations were higher after the 1xC+A diet (+16%; 95% CI: 4.2%, 35.2%) than after the basal diet. There were no effects of diet on CRP, TNF-α, or sTNFRI or II. There were significant differences between GSTM1-null/GSTT1+ individuals for several biomarkers in response to 1xC+A compared with basal diets (CRP: −37.8%; 95% CI: −58.0%, −7.4%; IL-6: −48.6%; 95% CI: −49.6%, −12.0%; IL-8: 16.3%; 95% CI: 6.7%, 57.7%) and with the 2xC diet compared with the basal diet (IL-8: −33.2%; 95% CI: −43.0%, −1.4%; sTNFRI: −7.5%; 95% CI: −12.7%, −2.3%). There were no significant reductions in biomarker concentrations in response to diet among GSTM1+/GSTT1+ or GSTM1-null/GSTT1-null individuals. Twenty-four-hour urinary isothiocyanate excretion was not associated with any of the inflammation markers overall; however, IL-6 was inversely associated with total isothiocyanate excretion in GSTM1-null/GSTT1-null individuals (β = −0.12; 95% CI: −0.19, −0.05). Conclusions: In this young, healthy population, consumption of cruciferous and apiaceous vegetables reduced circulating IL-6; however, results for other biomarkers of inflammation were not consistent. PMID:25165394

Regional and Large-Scale Climate Influences on Tree-Ring Reconstructed Null Zone Position in San Francisco Bay

NASA Astrophysics Data System (ADS)

Stahle, D.; Griffin, D.; Cleaveland, M.; Fye, F.; Meko, D.; Cayan, D.; Dettinger, M.; Redmond, K.

2007-05-01

A new network of 36 moisture sensitive tree-ring chronologies has been developed in and near the drainage basins of the Sacramento and San Joaquin Rivers. The network is based entirely on blue oak (Quercus douglasii), which is a California endemic found from the lower forest border up into the mixed conifer zone in the Coast Ranges, Sierra Nevada, and Cascades. These blue oak tree-ring chronologies are highly correlated with winter-spring precipitation totals, Sacramento and San Joaquin streamflow, and with seasonal variations in salinity and null zone position in San Francisco Bay. Null zone is the non-tidal bottom water location where density-driven salinity and river-driven freshwater currents balance (zero flow). It is the area of highest turbidity, water residence time, sediment accumulation, and net primary productivity in the estuary. Null zone position is measured by the distance from the Golden Gate of the 2 per mil bottom water isohaline and is primarily controlled by discharge from the Sacramento and San Joaquin Rivers (and ultimately by winter-spring precipitation). The location of the null zone is an estuarine habitat indicator, a policy variable used for ecosystem management, and can have a major impact on biological resources in the San Francisco estuary. Precipitation-sensitive blue oak chronologies can be used to estimate null zone position based on the strong biogeophysical interaction among terrestrial, aquatic, and estuarine ecosystems, orchestrated by precipitation. The null zone reconstruction is 626-years long and provides a unique long term perspective on the interannual to decadal variability of this important estuarine habitat indicator. Consecutive two-year droughts (or longer) allow the null zone to shrink into the confined upper reaches of Suisun Bay, causing a dramatic reduction in phytoplankton production and favoring colonization of the estuary by marine biota. The reconstruction indicates an approximate 10 year recurrence interval between these consecutive two-year droughts and null zone maxima. Composite analyses of the Palmer drought index over North America indicate that the drought and wetness regimes associated with maxima and minima in reconstructed null zone position are largely restricted to the California sector. Composite analyses of the 20th century global sea surface temperature (SST) field indicate that wet years over central California with good oak growth, high flows, and a seaward position for the null zone (minima) are associated with warm El Nino conditions and a "Pineapple Express" SST pattern. The composite SST pattern is not as strong during dry years with poor growth, low flows, and a landward position of the null zone (maxima), but the composite warm SST anomaly in the eastern North Pacific during maxima would be consistent with a persistent ridge and drought over western North America.

Identification of Noninvasive Biomarkers for Alcohol-Induced Liver Disease Using Urinary Metabolomics and the Ppara-null Mouse

PubMed Central

Manna, Soumen K.; Patterson, Andrew D.; Yang, Qian; Krausz, Kristopher W.; Li, Henghong; Idle, Jeffrey R.; Fornace, Albert J.; Gonzalez, Frank J.

2010-01-01

Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively non-specific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study the metabolic changes associated with alcohol-induced liver disease were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-β-D-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model. PMID:20540569

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

NASA Astrophysics Data System (ADS)

White, J.; Brakefield, L. K.

2015-12-01

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

Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population.

PubMed

Abbas, Shania; Raza, Syed Tasleem; Chandra, Anu; Rizvi, Saliha; Ahmed, Faisal; Eba, Ale; Mahdi, Farzana

2015-01-01

Hypertension has a multi-factorial background based on genetic and environmental interactive factors. ACE, FABP2 and GST genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. The present study was carried out to investigate the association of ACE (rs4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism with essential HTN cases and controls. This study includes 138 essential hypertension (HTN) patients and 116 age-, sex- and ethnicity-matched control subjects. GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphisms were evaluated by multiplex PCR, ACE (rs4646994) gene polymorphisms by PCR and FABP2 (rs1799883) gene polymorphisms by PCR-RFLP method. Significant differences were obtained in the frequencies of ACE DD, II genotype (p = 0.006, 0.003), GSTT1 null, GSTM1 positive genotype (p = 0.048, 0.010) and FABP2 Ala54/Ala54 genotype (p = 0.049) between essential HTN cases and controls. It is concluded that ACE (rs 4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism are associated with HTN. Further investigation with a larger sample size may be required to validate this study.

FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly

PubMed Central

Jurak Begonja, Antonija; Hoffmeister, Karin M.; Hartwig, John H.

2011-01-01

Filamin A (FlnA) is a large cytoplasmic protein that crosslinks actin filaments and anchors membrane receptors and signaling intermediates. FlnAloxP PF4-Cre mice that lack FlnA in the megakaryocyte (MK) lineage have a severe macrothrombocytopenia because of accelerated platelet clearance. Macrophage ablation by injection of clodronate-encapsulated liposomes increases blood platelet counts in FlnAloxP PF4-Cre mice and reveals the desintegration of FlnA-null platelets into microvesicles, a process that occurs spontaneously during storage. FlnAloxP PF4-Cre bone marrows and spleens have a 2.5- to 5-fold increase in MK numbers, indicating increased thrombopoiesis in vivo. Analysis of platelet production in vitro reveals that FlnA-null MKs prematurely convert their cytoplasm into large CD61+ platelet-sized particles, reminiscent of the large platelets observed in vivo. FlnA stabilizes the platelet von Willebrand factor receptor, as surface expression of von Willebrand factor receptor components is normal on FlnA-null MKs but decreased on FlnA-null platelets. Further, FlnA-null platelets contain multiple GPIbα degradation products and have increased expression of the ADAM17 and MMP9 metalloproteinases. Together, the findings indicate that FlnA-null MKs prematurely release large and fragile platelets that are removed rapidly from the circulation by macrophages. PMID:21652675

31 CFR 536.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... a specially designated narcotics trafficker has or has had an interest since such date, is null and... which otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any person with whom such property was...

31 CFR 585.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... authorization hereunder and involves any property or interest in property blocked pursuant to § 585.201 is null... hereunder. (d) Transfers of property which otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any...

Null Effects and Publication Bias in Special Education Research

ERIC Educational Resources Information Center

Cook, Bryan G.; Therrien, William J.

2017-01-01

Researchers sometimes conduct a study and find that the predicted relation between variables did not exist or that the intervention did not have a positive impact on student outcomes; these are referred to as null findings because they fail to disconfirm the null hypothesis. Rather than consider such studies as failures and disregard the null…

A Short Term Real Time Study in Syntactic Change.

ERIC Educational Resources Information Center

Duarte, Maria Eugenia Lamoglia

Recent research has shown that Brazilian Portuguese is undergoing a change regarding the null subject parameter, evolving from a null subject to a non-null subject language. This paper presents the results of a short term, real time study of speakers of Brazilian Portuguese with low and mid levels of formal education. The study was based on…

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

PubMed

Singh, Navneet; Chakrabarty, Subhas

2013-11-15

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

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

PubMed

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.

Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

PubMed Central

Milner, Derek J.; Mavroidis, Manolis; Weisleder, Noah; Capetanaki, Yassemi

2000-01-01

Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K m) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant role in mitochondrial positioning and respiratory function in cardiac and skeletal muscle. PMID:10995435

The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.

PubMed

Barberi, Theresa J; Dunkle, Alexis; He, You-Wen; Racioppi, Luigi; Means, Anthony R

2012-01-01

Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that potently activate naïve T cells, thereby bridging innate and adaptive immune responses. When challenged with LPS, Pin1-null mice failed to accumulate spleen conventional dendritic cells (cDC). Analysis of steady-state spleen DC populations revealed that Pin1-null mice had fewer CD8+ cDC. This defect was recapitulated by culturing Pin1-null bone marrow with the DC-instructive cytokine Flt3 Ligand. Additionally, injection of Flt3 Ligand for 9 days failed to induce robust expansion of CD8+ cDC in Pin1-null mice. Upon infection with Listeria monocytogenes, Pin1-null mice were defective in stimulating proliferation of adoptively transferred WT CD8+ T cells, suggesting that decreases in Pin1 null CD8+ cDC may affect T cell responses to infection in vivo. Finally, upon analyzing expression of proteins involved in DC development, elevated expression of PU.1 was detected in Pin1-null cells, which resulted from an increase in PU.1 protein half-life. We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity.

Hepatic effects of a methionine-choline-deficient diet in hepatocyte RXRalpha-null mice.

PubMed

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

2009-01-15

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

Altered Anterior Segment Biometric Parameters in Mice Deficient in SPARC.

PubMed

Ho, Henrietta; Htoon, Hla M; Yam, Gary Hin-Fai; Toh, Li Zhen; Lwin, Nyein Chan; Chu, Stephanie; Lee, Ying Shi; Wong, Tina T; Seet, Li-Fong

2017-01-01

Secreted protein acidic and rich in cysteine (SPARC) and Hevin are structurally related matricellular proteins involved in extracellular matrix assembly. In this study, we compared the anterior chamber biometric parameters and iris collagen properties in SPARC-, Hevin- and SPARC-/Hevin-null with wild-type (WT) mice. The right eyes of 53 WT, 35 SPARC-, 56 Hevin-, and 63 SPARC-/Hevin-null mice were imaged using the RTVue-100 Fourier-domain optical coherence tomography system. The parameters measured were anterior chamber depth (ACD), trabecular-iris space area (TISA), angle opening distance (AOD), and pupil diameter. Biometric data were analyzed using analysis of covariance and adjusted for age, sex, and pupil diameter. Expression of Col1a1, Col8a1, and Col8a2 transcripts in the irises was measured by quantitative polymerase chain reaction. Collagen fibril thickness was evaluated by transmission electron microscopy. Mice that were SPARC- and SPARC-/Hevin-null had 1.28- and 1.25-fold deeper ACD, 1.45- and 1.53-fold larger TISA, as well as 1.42- and 1.51-fold wider AOD than WT, respectively. These measurements were not significantly different between SPARC- and SPARC-/Hevin-null mice. The SPARC-null iris expressed lower Col1a1, but higher Col8a1 and Col8a2 transcripts compared with WT. Collagen fibrils in the SPARC- and SPARC-/Hevin-null irises were 1.5- and 1.7-fold thinner than WT, respectively. The Hevin-null iris did not differ from WT in these collagen properties. SPARC-null mice have deeper anterior chamber as well as wider drainage angles compared with WT. Therefore, SPARC plays a key role in influencing the spatial organization of the anterior segment, potentially via modulation of collagen properties, while Hevin is not likely to be involved.

Characterization of CpSte11, a MAPKKK gene of Cryphonectria parasitica, and initial evidence of its involvement in the pheromone response pathway.

PubMed

Park, Jin-Ah; Kim, Jung-Mi; Park, Seung-Moon; Kim, Dae-Hyuk

2012-04-01

The gene CpSte11 of Cryphonectria parasitica, which encodes a yeast Ste11 homologue, was cloned and characterized. Gene replacement analysis revealed a high frequency of CpSte11 null mutants. When compared with the wild-type parent strain, CpSte11 null mutants showed no difference in terms of growth rate or pigmentation. However, CpSte11 null mutants showed a marked decrease in both the number and size of stromal pustules on chestnut twigs. The virulence test showed that, in comparison with those of the wild-type and virus-infected hypovirulent strains, CpSte11 null mutants produced necrotic areas of intermediate size. Disruption of the CpSte11 gene also resulted in defects in female fertility. Down-regulation of transcripts for the mating pheromone precursor gene, Mf2/2, and mating response transcription factors, such as cpst12 and pro1, was observed in CpSte11 null mutants. The down-regulation of Mf2/2, cpst12 and pro1 was also observed in the mutant phenotype of Cpmk2, a mating response Fus3-like mitogen-activated protein kinase (MAPK) gene, but not in the mutant of Cpmk1, a high-osmolarity glycerol Hog1-like MAPK gene. These results indicate that the cloned CpSte11 gene is functionally involved in the mating response pathway and acts through downstream targets, including Cpmk2, cpst12, pro1 and Mf2/2. However, the characteristics of the CpSte11 null mutant were fully phenocopied only in the cpst12 null mutant, but not in other studied null mutants of components of the putative mating response pathway. © 2011 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2011 BSPP AND BLACKWELL PUBLISHING LTD.

Subpulse drifting, nulling, and mode changing in PSR J1822-2256

NASA Astrophysics Data System (ADS)

Basu, Rahul; Mitra, Dipanjan

2018-05-01

We report a detailed observational study of the single pulses from the pulsar J1822-2256. The pulsar shows the presence of subpulse drifting, nulling as well as multiple emission modes. During these observations the pulsar existed primarily in two modes; mode A with prominent drift bands and mode B which was more disorderly without any clear subpulse drifting. A third mode C was also seen for a short duration with a different drifting periodicity compared to mode A. The nulls were present throughout the observations but were more frequent during the disorderly B mode. The nulling also exhibited periodicity with a clear peak in the fluctuation spectra. Before the transition from mode A to nulling the pulsar switched to a third drifting state with periodicity different from both mode A and C. The diversity seen in the single pulse behaviour from the pulsar J1822-2256 provides an unique window into the emission physics.

Association of PTSD symptoms with asthma attacks among hurricane Katrina survivors.

PubMed

Arcaya, Mariana C; Lowe, Sarah R; Rhodes, Jean E; Waters, Mary C; Subramanian, S V

2014-12-01

The relationship between posttraumatic stress disorder (PTSD) and asthma in the wake of natural disasters is poorly understood. Using pre- and postdisaster data (N = 405) from the Resilience in Survivors of Katrina (RISK) project, we examined associations between PTSD symptoms, measured by the Impact of Event Scale-Revised (IES-R), and self-reported postdisaster asthma attacks. A 1-point increase in the IES-R avoidance score, which corresponded to one standard deviation change in this sample, was associated with double the odds of reporting an asthma attack or episode since the hurricane, 95% CI Revise spacing among characters: [1.22, 4.16]. Association with hyperarousal and intrusion symptoms was null. Further research using objective measures of asthma morbidity is needed; nevertheless, these findings may help inform postdisaster health services delivery and predisaster mitigation planning. Copyright © 2014 International Society for Traumatic Stress Studies.

The effect of safety factor profile on transport in steady-state, high-performance scenarios

DOE PAGES

Holcomb, C. T.; Ferron, J. R.; Luce, T. C.; ...

2012-03-09

In this study, an analysis of the dependence of transport on the safety factor profile in high-performance, steady-state scenario discharges is presented. This is based on experimental scans of q 95 and q min taken with fixed β N, toroidal field, double-null plasma shape, divertor pumping, and electron cyclotron current drive input. The temperature and thermal diffusivity profiles were found to vary considerably with the q-profile, and these variations were significantly different for electrons and ions. With fixed q 95, both temperature profiles increase and broaden as q min is increased and the magnetic shear becomes low or negative inmore » the inner half radius, but these temperature profile changes are stronger for the electrons. Power balance calculations show the peak in the ion thermal diffusivity (χ i) at ρ – 0.6 – 0.8 increases with q 95 or q min.« less

Thermally driven spin-Seebeck transport in chiral dsDNA-based molecular devices

NASA Astrophysics Data System (ADS)

Nian, L. L.; Zhang, Rong; Tang, F. R.; Tang, Jun; Bai, Long

2018-03-01

By employing the nonequilibrium Green's function technique, we study the thermal-induced spin-Seebeck transport through a chiral double-stranded DNA (dsDNA) connected to a normal-metal and a ferromagnetic lead. How the main parameters of the dsDNA-based system influence the spin-Seebeck transport is analyzed at length, and the thermally created charge (spin-related) current displays the rectification effect and the negative differential thermal conductance feature. More importantly, the spin current exhibits the rectification behavior of the spin-Seebeck effect; even the perfect spin-Seebeck effect can be obtained with the null charge current. Thus, the chiral dsDNA-based system can act as a spin(charge)-Seebeck diode, spin(charge)-Seebeck switch, and spin(charge)-Seebeck transistor. Our results provide new ways to design spin caloritronic devices based on dsDNA or other organic molecules.

The Green Bank North Celestial Cap Pulsar Survey: New Pulsars and Future Prospects

NASA Astrophysics Data System (ADS)

Lynch, Ryan S.; Swiggum, Joe; Stovall, Kevin; Chawla, Pragya; DeCesar, Megan E.; Fonseca, Emmanuel; Levin, Lina; Cui, Bingyi; Kondratiev, Vlad; Archibald, Anne; Boyles, Jason; Hessels, Jason W. T.; Jenet, Fredrick; Kaplan, David; Karako-Argaman, Chen; Kaspi, Victoria; Martinez, Jose; McLaughlin, Maura; Ransom, Scott M.; Roberts, Mallory; Siemens, Xavier; Spiewak, Renee; Stairs, Ingrid; van Leeuwn, Joeri; Green Bank North Celestial Cap Survey Collaboration

2018-01-01

The Green Bank North Celestial Cap pulsar survey is the most successful low frequency pulsar survey ever. GBNCC uses the Green Bank telescope to cover the full visible sky at 350 MHz. With the survey over 70% complete, we have discovered over 150 pulsars, including 20 MSPs and 11 RRATs. I will report on the current status of the survey and plans for its completion in the coming years. I will also report on several discoveries including: timing solutions for dozens of new pulsars; new high precision MSPs and their suitability for inclusion in pulsar timing arrays; a new relativistic double neutron star system; new pulsar mass measurements; proper motion measurements for several MSPs; a new mode changing pulsar; interesting new MSP binaries; nulling fraction analyses; and possible implications of the lack of any fast radio bursts in the survey so far.

Direct search for dark matter with DarkSide

DOE PAGES

Agnes, P.

2015-11-16

Here, the DarkSide experiment is designed for the direct detection of Dark Matter with a double phase liquid Argon TPC operating underground at Laboratori Nazionali del Gran Sasso. The TPC is placed inside a 30 tons liquid organic scintillator sphere, acting as a neutron veto, which is in turn installed inside a 1 kt water Cherenkov detector. The current detector is running since November 2013 with a 50 kg atmospheric Argon fill and we report here the first null results of a Dark Matter search for a (1422 ± 67) kg.d exposure. This result correspond to a 90% CL uppermore » limit on the WIMP-nucleon cross section of 6.1 × 10 -44 cm 2 (for a WIMP mass of 100 GeV/c 2) and it's currently the most sensitive limit obtained with an Argon target.« less

A simplified technique for a totally diverting transverse loop colostomy and distal irrigation.

PubMed

Rose, D; Koniges, F; Frazier, T G

1985-12-01

This technique of totally diverting loop colostomy may be performed as an independent procedure or with exploratory laparotomy and surgical treatment on the distal part of the colon. Either a transverse or sigmoid loop colostomy can be used for diversion without the risk of fecal contamination of the peritoneal cavity, particularly when working with unprepared intestine. When distal irrigation is desired to purge the intestine of fecal material, either intraoperatively or as part of a subsequent intestinal preparation, it can easily be accomplished by placing an irrigating catheter distal to the staple line. In addition, the use of a small rubber suspension bar facilitates application of standard colostomy appliances for the stoma.

Solids feed nozzle for fluidized bed

DOEpatents

Zielinski, Edward A.

1982-01-01

The vertical fuel pipe of a fluidized bed extends up through the perforated support structure of the bed to discharge granulated solid fuel into the expanded bed. A cap, as a deflecting structure, is supported above the discharge of the fuel pipe and is shaped and arranged to divert the carrier fluid and granulated fuel into the combusting bed. The diverter structure is spaced above the end of the fuel pipe and provided with a configuration on its underside to form a venturi section which generates a low pressure in the stream into which the granules of solid fuel are drawn to lengthen their residence time in the combustion zone of the bed adjacent the fuel pipe.

Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.

PubMed

Steele, Andrew D; Keohane, Colleen E; Knouse, Kyle W; Rossiter, Sean E; Williams, Sierra J; Wuest, William M

2016-05-11

Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere.

Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity

PubMed Central

Steele, Andrew D.; Keohane, Colleen E.; Knouse, Kyle W.; Rossiter, Sean E.; Williams, Sierra J.; Wuest, William M.

2016-01-01

Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere. PMID:27096543

Magnetic switch for reactor control rod. [LMFBR

DOEpatents

Germer, J.H.

1982-09-30

A magnetic reed switch assembly is described for activating an electromagnetic grapple utilized to hold a control rod in position above a reactor core. In normal operation the magnetic field of a permanent magnet is short-circuited by a magnetic shunt, diverting the magnetic field away from the reed switch. The magnetic shunt is made of a material having a Curie-point at the desired release temperature. Above that temperature the material loses its ferromagnetic properties, and the magnetic path is diverted to the reed switch which closes and short-circuits the control circuit for the control rod electro-magnetic grapple which allows the control rod to drop into the reactor core for controlling the reactivity of the core.

Magnetic switch for reactor control rod

DOEpatents

Germer, John H.

1986-01-01

A magnetic reed switch assembly for activating an electromagnetic grapple utilized to hold a control rod in position above a reactor core. In normal operation the magnetic field of a permanent magnet is short-circuited by a magnetic shunt, diverting the magnetic field away from the reed switch. The magnetic shunt is made of a material having a Curie-point at the desired release temperature. Above that temperature the material loses its ferromagnetic properties, and the magnetic path is diverted to the reed switch which closes and short-circuits the control circuit for the control rod electromagnetic grapple which allows the control rod to drop into the reactor core for controlling the reactivity of the core.

MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice

PubMed Central

Risal, Sanjiv; Zhang, Jingjing; Adhikari, Deepak; Liu, Xiaoman; Shao, Jingchen; Hu, Mengwen; Busayavalasa, Kiran; Tu, Zhaowei; Chen, Zijiang; Kaldis, Philipp; Liu, Kui

2017-01-01

In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75–8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs. We generated a mouse model where we specifically deleted Mastl in PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion of Mastl in PGCs did not prevent mitotic entry, but led to a failure of the cells to proceed beyond metaphase-like stage, indicating that MASTL-mediated molecular events are indispensable for anaphase entry in PGCs. These mitotic defects further led to the death of Mastl-null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in the Mastl-null PGCs was rescued by simultaneous deletion of Ppp2r1a (α subunit of PP2A). Thus, our results demonstrate that MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis. PMID:28224044

pKAMA-ITACHI Vectors for Highly Efficient CRISPR/Cas9-Mediated Gene Knockout in Arabidopsis thaliana.

PubMed

Tsutsui, Hiroki; Higashiyama, Tetsuya

2017-01-01

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) system is widely used as a tool for genome engineering in various organisms. A complex consisting of Cas9 and single guide RNA (sgRNA) induces a DNA double-strand break in a sequence-specific manner, resulting in knockout. Some binary vectors for CRISPR/Cas9 in plants have been reported, but there is a problem with low efficiency. Here, we present a newly developed, highly efficient CRISPR/Cas9 vector for Arabidopsis thaliana, pKAMA-ITACHI Red (pKIR), harboring the RIBOSOMAL PROTEIN S5 A (RPS5A) promoter to drive Cas9. The RPS5A promoter maintains high constitutive expression at all developmental stages starting from the egg cell and including meristematic cells. Even in the T1 generation, pKIR induced null phenotypes in some genes: PHYTOENE DESATURASE 3 (PDS3), AGAMOUS (AG) and DUO POLLEN 1 (DUO1). Mutations induced by pKIR were carried in the germ cell line of the T1 generation. Surprisingly, in some lines, 100% of the T2 plants had the adh1 (ALCOHOL DEHYDROGENASE 1) null phenotype, indicating that pKIR strongly induced heritable mutations. Cas9-free T2 mutant plants were obtained by removing T2 seeds expressing a fluorescent marker in pKIR. Our results suggest that the pKIR system is a powerful molecular tool for genome engineering in Arabidopsis. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

Regulation of ciaXRH Operon Expression and Identification of the CiaR Regulon in Streptococcus mutans▿

PubMed Central

Wu, Chenggang; Ayala, Eduardo A.; Downey, Jennifer S.; Merritt, Justin; Goodman, Steven D.; Qi, Fengxia

2010-01-01

The ciaRH operon in Streptococcus mutans contains 3 contiguous genes, ciaXRH. Unlike the CiaRH system in other streptococci, only the ciaH-null mutant displays defective phenotypes, while the ciaR-null mutant behaves like the wild type. The objective of this study was to determine the mechanism of this unusual property. We demonstrate that the ciaH mutation caused a >20-fold increase in ciaR transcript synthesis. A ciaRH double deletion reversed the ciaH phenotype, suggesting that overexpressed ciaR might be responsible for the observed ciaH phenotypes. When ciaR was forced to be overexpressed by a transcriptional fusion to the ldh promoter in the wild-type background, the same ciaH phenotypes were restored, confirming the involvement of overexpressed ciaR in the ciaH phenotypes. The ciaH mutation and ciaR overexpression also caused transcriptional alterations in 100 genes, with 15 genes upregulated >5-fold. Bioinformatics analysis identified a putative CiaR regulon consisting of 8 genes/operons, including the ciaXRH operon itself, all of which were upregulated. In vitro footprinting on 4 of the 8 promoters revealed a protected region of 26 to 28 bp encompassing two direct repeats, NTTAAG-n5-WTTAAG, 10 bp upstream of the −10 region, indicating direct binding of the CiaR protein to these promoters. Taken together, we conclude that overexpressed CiaR, as a result of either ciaH deletion or forced expression from a constitutive promoter, is a mediator in the CiaH-regulated phenotypes. PMID:20639331

Drosophila caspases involved in developmentally regulated programmed cell death of peptidergic neurons during early metamorphosis.

PubMed

Lee, Gyunghee; Wang, Zixing; Sehgal, Ritika; Chen, Chun-Hong; Kikuno, Keiko; Hay, Bruce; Park, Jae H

2011-01-01

A great number of obsolete larval neurons in the Drosophila central nervous system are eliminated by developmentally programmed cell death (PCD) during early metamorphosis. To elucidate the mechanisms of neuronal PCD occurring during this period, we undertook genetic dissection of seven currently known Drosophila caspases in the PCD of a group of interneurons (vCrz) that produce corazonin (Crz) neuropeptide in the ventral nerve cord. The molecular death program in the vCrz neurons initiates within 1 hour after pupariation, as demonstrated by the cytological signs of cell death and caspase activation. PCD was significantly suppressed in dronc-null mutants, but not in null mutants of either dredd or strica. A double mutation lacking both dronc and strica impaired PCD phenotype more severely than did a dronc mutation alone, but comparably to a triple dredd/strica/dronc mutation, indicating that dronc is a main initiator caspase, while strica plays a minor role that overlaps with dronc's. As for effector caspases, vCrz PCD requires both ice and dcp-1 functions, as they work cooperatively for a timely removal of the vCrz neurons. Interestingly, the activation of the Ice and Dcp-1 is not solely dependent on Dronc and Strica, implying an alternative pathway to activate the effectors. Two remaining effector caspase genes, decay and damm, found no apparent functions in the neuronal PCD, at least during early metamorphosis. Overall, our work revealed that vCrz PCD utilizes dronc, strica, dcp-1, and ice wherein the activation of Ice and Dcp-1 requires a novel pathway in addition to the initiator caspases.

"WhatsApp"ening in orthopedic care: a concise report from a 300-bedded tertiary care teaching center.

PubMed

Khanna, Vishesh; Sambandam, Senthil N; Gul, Arif; Mounasamy, Varatharaj

2015-07-01

Smartphones have emerged as essential tools providing assistance in patient care, monitoring, rehabilitation, communication, diagnosis, teaching, research and reference. Among innumerable communication apps, WhatsApp has been widely popular and cost effective. The aim of our study was to report the impact of introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool on (1) awareness of patient-related information, (2) efficiency of the handover process and (3) duration of traditional morning handovers among orthopedic residents in a 300-bedded tertiary care teaching center. Written handovers and paging used for communication at our center led to occasional inefficiencies among residents. Widespread use, low cost, availability and double password protection (phone lock and WhatsApp lock) made WhatsApp's group conversation feature an ideal tool for intradepartmental patient-related communication. Twenty-five consecutive admissions before and after WhatsApp (BW, AW) were included in the study. Eight orthopedic residents attempted fifty randomly arranged questions based on the twenty-five patients in each study period. A null hypothesis that introduction of WhatsApp group would neither increase the awareness of patient-related information nor improve the efficiency of the handovers among residents was assumed. A significant improvement observed in scores obtained by residents in the AW group led to rejection of the null hypothesis. The residents also reported swifter and efficient handovers after the introduction of WhatsApp. Our results indicate that the introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool can bring about an improvement in patient-related awareness, communication and handovers among orthopedic residents.

The Green Bank Northern Celestial Cap Pulsar Survey. II. The Discovery and Timing of 10 Pulsars

NASA Astrophysics Data System (ADS)

Kawash, A. M.; McLaughlin, M. A.; Kaplan, D. L.; DeCesar, M. E.; Levin, L.; Lorimer, D. R.; Lynch, R. S.; Stovall, K.; Swiggum, J. K.; Fonseca, E.; Archibald, A. M.; Banaszak, S.; Biwer, C. M.; Boyles, J.; Cui, B.; Dartez, L. P.; Day, D.; Ernst, S.; Ford, A. J.; Flanigan, J.; Heatherly, S. A.; Hessels, J. W. T.; Hinojosa, J.; Jenet, F. A.; Karako-Argaman, C.; Kaspi, V. M.; Kondratiev, V. I.; Leake, S.; Lunsford, G.; Martinez, J. G.; Mata, A.; Matheny, T. D.; Mcewen, A. E.; Mingyar, M. G.; Orsini, A. L.; Ransom, S. M.; Roberts, M. S. E.; Rohr, M. D.; Siemens, X.; Spiewak, R.; Stairs, I. H.; van Leeuwen, J.; Walker, A. N.; Wells, B. L.

2018-04-01

We present timing solutions for 10 pulsars discovered in 350 MHz searches with the Green Bank Telescope. Nine of these were discovered in the Green Bank Northern Celestial Cap survey and one was discovered by students in the Pulsar Search Collaboratory program during an analysis of drift-scan data. Following the discovery and confirmation with the Green Bank Telescope, timing has yielded phase-connected solutions with high-precision measurements of rotational and astrometric parameters. Eight of the pulsars are slow and isolated, including PSR J0930‑2301, a pulsar with a nulling fraction lower limit of ∼30% and a nulling timescale of seconds to minutes. This pulsar also shows evidence of mode changing. The remaining two pulsars have undergone recycling, accreting material from binary companions, resulting in higher spin frequencies. PSR J0557‑2948 is an isolated, 44 ms pulsar that has been partially recycled and is likely a former member of a binary system that was disrupted by a second supernova. The paucity of such so-called “disrupted binary pulsars” (DRPs) compared to double neutron star (DNS) binaries can be used to test current evolutionary scenarios, especially the kicks imparted on the neutron stars in the second supernova. There is some evidence that DRPs have larger space velocities, which could explain their small numbers. PSR J1806+2819 is a 15 ms pulsar in a 44-day orbit with a low-mass white dwarf companion. We did not detect the companion in archival optical data, indicating that it must be older than 1200 Myr.

Ku must load directly onto the chromosome end in order to mediate its telomeric functions.

PubMed

Lopez, Christopher R; Ribes-Zamora, Albert; Indiviglio, Sandra M; Williams, Christopher L; Haricharan, Svasti; Bertuch, Alison A

2011-08-01

The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where it impacts several aspects of telomere structure and function. Although Ku avidly binds DNA ends via a preformed channel, its ability to associate with telomeres via this mechanism could be challenged by factors known to bind directly to the chromosome terminus. This has led to uncertainty as to whether Ku itself binds directly to telomeric ends and whether end association is crucial for Ku's telomeric functions. To address these questions, we constructed DNA end binding-defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that were predicted to contact DNA. These mutants continued to associate with their known telomere-related partners, such as Sir4, a factor required for telomeric silencing, and TLC1, the RNA component of telomerase. Despite these interactions, we found that the Ku mutants had markedly reduced association with telomeric chromatin and null-like deficiencies for telomere end protection, length regulation, and silencing functions. In contrast to Ku null strains, the DNA end binding defective Ku mutants resulted in increased, rather than markedly decreased, imprecise end-joining proficiency at an induced double-strand break. This result further supports that it was the specific loss of Ku's telomere end binding that resulted in telomeric defects rather than global loss of Ku's functions. The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance.

Ku Must Load Directly onto the Chromosome End in Order to Mediate Its Telomeric Functions

PubMed Central

Lopez, Christopher R.; Ribes-Zamora, Albert; Indiviglio, Sandra M.; Williams, Christopher L.; Haricharan, Svasti; Bertuch, Alison A.

2011-01-01

The Ku heterodimer associates with the Saccharomyces cerevisiae telomere, where it impacts several aspects of telomere structure and function. Although Ku avidly binds DNA ends via a preformed channel, its ability to associate with telomeres via this mechanism could be challenged by factors known to bind directly to the chromosome terminus. This has led to uncertainty as to whether Ku itself binds directly to telomeric ends and whether end association is crucial for Ku's telomeric functions. To address these questions, we constructed DNA end binding–defective Ku heterodimers by altering amino acid residues in Ku70 and Ku80 that were predicted to contact DNA. These mutants continued to associate with their known telomere-related partners, such as Sir4, a factor required for telomeric silencing, and TLC1, the RNA component of telomerase. Despite these interactions, we found that the Ku mutants had markedly reduced association with telomeric chromatin and null-like deficiencies for telomere end protection, length regulation, and silencing functions. In contrast to Ku null strains, the DNA end binding defective Ku mutants resulted in increased, rather than markedly decreased, imprecise end-joining proficiency at an induced double-strand break. This result further supports that it was the specific loss of Ku's telomere end binding that resulted in telomeric defects rather than global loss of Ku's functions. The extensive telomere defects observed in these mutants lead us to propose that Ku is an integral component of the terminal telomeric cap, where it promotes a specific architecture that is central to telomere function and maintenance. PMID:21852961

15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis.

PubMed

Myung, Seung-Jae; Rerko, Ronald M; Yan, Min; Platzer, Petra; Guda, Kishore; Dotson, Angela; Lawrence, Earl; Dannenberg, Andrew J; Lovgren, Alysia Kern; Luo, Guangbin; Pretlow, Theresa P; Newman, Robert A; Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D

2006-08-08

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin-degrading enzyme that is highly expressed in normal colon mucosa but is ubiquitously lost in human colon cancers. Herein, we demonstrate that 15-PGDH is active in vivo as a highly potent suppressor of colon neoplasia development and acts in the colon as a required physiologic antagonist of the prostaglandin-synthesizing activity of the cyclooxygenase 2 (COX-2) oncogene. We first show that 15-PGDH gene knockout induces a marked 7.6-fold increase in colon tumors arising in the Min (multiple intestinal neoplasia) mouse model. Furthermore, 15-PGDH gene knockout abrogates the normal resistance of C57BL/6J mice to colon tumor induction by the carcinogen azoxymethane (AOM), conferring susceptibility to AOM-induced adenomas and carcinomas in situ. Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E(2) in 15-PGDH null colonic mucosa. A parallel role for 15-PGDH loss in promoting the earliest steps of colon neoplasia in humans is supported by our finding of a universal loss of 15-PGDH expression in microscopic colon adenomas recovered from patients with familial adenomatous polyposis, including adenomas as small as a single crypt. These models thus delineate the in vivo significance of 15-PGDH-mediated negative regulation of the COX-2 pathway and moreover reveal the particular importance of 15-PGDH in opposing the neoplastic progression of colonic aberrant crypt foci.

New Methods of Entanglement with Spatial Modes of Light

DTIC Science & Technology

2014-02-01

Poincare beam by state nulling. ....................................... 15 Figure 13: Poincare patterns measured by imaging polarimetry ...perform imaging polarimetry . This entails taking six single photon images, pixel by pixel, after the passage through six different polarization filters...state nulling [21,22] and by imaging polarimetry [24]. Figure 12 shows the result of state nulling measurements in diagnosing the mode of a Poincare

Using the Coefficient of Confidence to Make the Philosophical Switch from a Posteriori to a Priori Inferential Statistics

ERIC Educational Resources Information Center

Trafimow, David

2017-01-01

There has been much controversy over the null hypothesis significance testing procedure, with much of the criticism centered on the problem of inverse inference. Specifically, p gives the probability of the finding (or one more extreme) given the null hypothesis, whereas the null hypothesis significance testing procedure involves drawing a…

31 CFR 588.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any property or interest in property blocked pursuant to § 588.201(a), is null and void and shall not... part. (d) Transfers of property that otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any person with...

31 CFR 594.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any property or interest in property blocked pursuant to § 594.201(a), is null and void and shall not... property that otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any person with whom such property was...

31 CFR 543.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any property or interest in property blocked pursuant to § 543.201(a), is null and void and shall not..., instruction, or license issued pursuant to this part. (d) Transfers of property that otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null...

31 CFR 548.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... interest in property blocked pursuant to § 548.201(a), is null and void and shall not be the basis for the..., instruction, or license issued pursuant to this part. (d) Transfers of property that otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null...

31 CFR 538.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... property or interest in property blocked pursuant to § 538.201 is null and void and shall not be the basis... be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any person with whom such property was held or maintained...

31 CFR 545.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., and that involves any property or interest in property blocked pursuant to § 545.201(a), is null and... property that otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any person with whom such property was...

31 CFR 541.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any property or interest in property blocked pursuant to § 541.201(a), is null and void and shall not... part. (d) Transfers of property that otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any person with...

31 CFR 597.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... such date, is null and void and shall not be the basis for the assertion or recognition of any interest... assets which otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or unenforceable as to any financial institution with whom...

31 CFR 587.202 - Effect of transfers violating the provisions of this part.

Code of Federal Regulations, 2010 CFR

2010-07-01

... blocked pursuant to § 587.201(a), is null and void and shall not be the basis for the assertion or... issued pursuant to this part. (d) Transfers of property that otherwise would be null and void or unenforceable by virtue of the provisions of this section shall not be deemed to be null and void or...

A statistical test to show negligible trend

Treesearch

Philip M. Dixon; Joseph H.K. Pechmann

2005-01-01

The usual statistical tests of trend are inappropriate for demonstrating the absence of trend. This is because failure to reject the null hypothesis of no trend does not prove that null hypothesis. The appropriate statistical method is based on an equivalence test. The null hypothesis is that the trend is not zero, i.e., outside an a priori specified equivalence region...

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

ERIC Educational Resources Information Center

Park, H.

2004-01-01

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