Patterns in the English language: phonological networks, percolation and assembly models

NASA Astrophysics Data System (ADS)

Stella, Massimo; Brede, Markus

2015-05-01

In this paper we provide a quantitative framework for the study of phonological networks (PNs) for the English language by carrying out principled comparisons to null models, either based on site percolation, randomization techniques, or network growth models. In contrast to previous work, we mainly focus on null models that reproduce lower order characteristics of the empirical data. We find that artificial networks matching connectivity properties of the English PN are exceedingly rare: this leads to the hypothesis that the word repertoire might have been assembled over time by preferentially introducing new words which are small modifications of old words. Our null models are able to explain the ‘power-law-like’ part of the degree distributions and generally retrieve qualitative features of the PN such as high clustering, high assortativity coefficient and small-world characteristics. However, the detailed comparison to expectations from null models also points out significant differences, suggesting the presence of additional constraints in word assembly. Key constraints we identify are the avoidance of large degrees, the avoidance of triadic closure and the avoidance of large non-percolating clusters.

Multidirectional hybrid algorithm for the split common fixed point problem and application to the split common null point problem.

PubMed

Li, Xia; Guo, Meifang; Su, Yongfu

2016-01-01

In this article, a new multidirectional monotone hybrid iteration algorithm for finding a solution to the split common fixed point problem is presented for two countable families of quasi-nonexpansive mappings in Banach spaces. Strong convergence theorems are proved. The application of the result is to consider the split common null point problem of maximal monotone operators in Banach spaces. Strong convergence theorems for finding a solution of the split common null point problem are derived. This iteration algorithm can accelerate the convergence speed of iterative sequence. The results of this paper improve and extend the recent results of Takahashi and Yao (Fixed Point Theory Appl 2015:87, 2015) and many others .

Exposures of tungsten nanostructures to divertor plasmas in DIII-D

DOE PAGES

Rudakov, D. L.; Wong, C. P. C.; Doerner, R. P.; ...

2016-01-22

Tungsten nanostructures (W-fuzz) prepared in the PISCES-A linear device have been found to survive direct exposure to divertor plasmas in DIII-D. W-fuzz was exposed in the lower divertor of DIII-D using the divertor material evaluation system. Two samples were exposed in lower single null (LSN) deuterium H-mode plasmas. The first sample was exposed in three discharges terminated by vertical displacement event disruptions, and the second in two discharges near the lowered X-point. More recently, three samples were exposed near the lower outer strike point in predominantly helium H-mode LSN plasmas. In all cases, the W-fuzz survived plasma exposure with littlemore » obvious damage except in the areas where unipolar arcing occurred. In conclusion, arcing is effective in W-fuzz removal, and it appears that surfaces covered with W-fuzz can be more prone to arcing than smooth W surfaces.« less

On the Measure and the Structure of the Free Boundary of the Lower Dimensional Obstacle Problem

NASA Astrophysics Data System (ADS)

Focardi, Matteo; Spadaro, Emanuele

2018-04-01

We provide a thorough description of the free boundary for the lower dimensional obstacle problem in R^{n+1} up to sets of null H^{n-1} measure. In particular, we prove (i) local finiteness of the (n-1)-dimensional Hausdorff measure of the free boundary, (ii) H^{n-1}-rectifiability of the free boundary, (iii) classification of the frequencies up to a set of Hausdorff dimension at most (n-2) and classification of the blow-ups at H^{n-1} almost every free boundary point.

Dynamic topology and flux rope evolution during non-linear tearing of 3D null point current sheets

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

Wyper, P. F., E-mail: peterw@maths.dundee.ac.uk; Pontin, D. I., E-mail: dpontin@maths.dundee.ac.uk

2014-10-15

In this work, the dynamic magnetic field within a tearing-unstable three-dimensional current sheet about a magnetic null point is described in detail. We focus on the evolution of the magnetic null points and flux ropes that are formed during the tearing process. Generally, we find that both magnetic structures are created prolifically within the layer and are non-trivially related. We examine how nulls are created and annihilated during bifurcation processes, and describe how they evolve within the current layer. The type of null bifurcation first observed is associated with the formation of pairs of flux ropes within the current layer.more » We also find that new nulls form within these flux ropes, both following internal reconnection and as adjacent flux ropes interact. The flux ropes exhibit a complex evolution, driven by a combination of ideal kinking and their interaction with the outflow jets from the main layer. The finite size of the unstable layer also allows us to consider the wider effects of flux rope generation. We find that the unstable current layer acts as a source of torsional magnetohydrodynamic waves and dynamic braiding of magnetic fields. The implications of these results to several areas of heliophysics are discussed.« less

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.

ELECTRIC CURRENT FILAMENTATION AT A NON-POTENTIAL MAGNETIC NULL-POINT DUE TO PRESSURE PERTURBATION

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

Jelínek, P.; Karlický, M.; Murawski, K., E-mail: pjelinek@prf.jcu.cz

2015-10-20

An increase of electric current densities due to filamentation is an important process in any flare. We show that the pressure perturbation, followed by an entropy wave, triggers such a filamentation in the non-potential magnetic null-point. In the two-dimensional (2D), non-potential magnetic null-point, we generate the entropy wave by a negative or positive pressure pulse that is launched initially. Then, we study its evolution under the influence of the gravity field. We solve the full set of 2D time dependent, ideal magnetohydrodynamic equations numerically, making use of the FLASH code. The negative pulse leads to an entropy wave with amore » plasma density greater than in the ambient atmosphere and thus this wave falls down in the solar atmosphere, attracted by the gravity force. In the case of the positive pressure pulse, the plasma becomes evacuated and the entropy wave propagates upward. However, in both cases, owing to the Rayleigh–Taylor instability, the electric current in a non-potential magnetic null-point is rapidly filamented and at some locations the electric current density is strongly enhanced in comparison to its initial value. Using numerical simulations, we find that entropy waves initiated either by positive or negative pulses result in an increase of electric current densities close to the magnetic null-point and thus the energy accumulated here can be released as nanoflares or even flares.« less

Magnetic topological analysis of coronal bright points

NASA Astrophysics Data System (ADS)

Galsgaard, K.; Madjarska, M. S.; Moreno-Insertis, F.; Huang, Z.; Wiegelmann, T.

2017-10-01

Context. We report on the first of a series of studies on coronal bright points which investigate the physical mechanism that generates these phenomena. Aims: The aim of this paper is to understand the magnetic-field structure that hosts the bright points. Methods: We use longitudinal magnetograms taken by the Solar Optical Telescope with the Narrowband Filter Imager. For a single case, magnetograms from the Helioseismic and Magnetic Imager were added to the analysis. The longitudinal magnetic field component is used to derive the potential magnetic fields of the large regions around the bright points. A magneto-static field extrapolation method is tested to verify the accuracy of the potential field modelling. The three dimensional magnetic fields are investigated for the presence of magnetic null points and their influence on the local magnetic domain. Results: In nine out of ten cases the bright point resides in areas where the coronal magnetic field contains an opposite polarity intrusion defining a magnetic null point above it. We find that X-ray bright points reside, in these nine cases, in a limited part of the projected fan-dome area, either fully inside the dome or expanding over a limited area below which typically a dominant flux concentration resides. The tenth bright point is located in a bipolar loop system without an overlying null point. Conclusions: All bright points in coronal holes and two out of three bright points in quiet Sun regions are seen to reside in regions containing a magnetic null point. An as yet unidentified process(es) generates the brigh points in specific regions of the fan-dome structure. The movies are available at http://www.aanda.org

A Magnetohydrodynamic Simulation of Magnetic Null-point Reconnections in NOAA AR 12192, Initiated with an Extrapolated Non-force-free Field

NASA Astrophysics Data System (ADS)

Prasad, A.; Bhattacharyya, R.; Hu, Qiang; Kumar, Sanjay; Nayak, Sushree S.

2018-06-01

The magnetohydrodynamics of the solar corona is simulated numerically. The simulation is initialized with an extrapolated non-force-free magnetic field using the vector magnetogram of the active region NOAA 12192, which was obtained from the solar photosphere. Particularly, we focus on the magnetic reconnections (MRs) occurring close to a magnetic null point that resulted in the appearance of circular chromospheric flare ribbons on 2014 October 24 around 21:21 UT, after the peak of an X3.1 flare. The extrapolated field lines show the presence of the three-dimensional (3D) null near one of the polarity-inversion lines—where the flare was observed. In the subsequent numerical simulation, we find MRs occurring near the null point, where the magnetic field lines from the fan plane of the 3D null form a X-type configuration with underlying arcade field lines. The footpoints of the dome-shaped field lines, inherent to the 3D null, show high gradients of the squashing factor. We find slipping reconnections at these quasi-separatrix layers, which are co-located with the post-flare circular brightening observed at chromospheric heights. This demonstrates the viability of the initial non-force-free field, along with the dynamics it initiates. Moreover, the initial field and its simulated evolution are found to be devoid of any flux rope, which is congruent with the confined nature of the flare.

Current singularities at quasi-separatrix layers and three-dimensional magnetic nulls

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

Craig, I. J. D.; Effenberger, Frederic, E-mail: feffen@waikato.ac.nz

2014-11-10

The open problem of how singular current structures form in line-tied, three-dimensional magnetic fields is addressed. A Lagrangian magneto-frictional relaxation method is employed to model the field evolution toward the final near-singular state. Our starting point is an exact force-free solution of the governing magnetohydrodynamic equations that is sufficiently general to allow for topological features like magnetic nulls to be inside or outside the computational domain, depending on a simple set of parameters. Quasi-separatrix layers (QSLs) are present in these structures and, together with the magnetic nulls, they significantly influence the accumulation of current. It is shown that perturbations affectingmore » the lateral boundaries of the configuration lead not only to collapse around the magnetic null but also to significant QSL currents. Our results show that once a magnetic null is present, the developing currents are always attracted to that specific location and show a much stronger scaling with resolution than the currents that form along the QSL. In particular, the null-point scalings can be consistent with models of 'fast' reconnection. The QSL currents also appear to be unbounded but give rise to weaker singularities, independent of the perturbation amplitude.« less

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.

Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

PubMed Central

Ye, Ling-li; Zhang, Guang-hui; Huang, Jing-wen; Li, Yong; Zheng, Guo-qiao; Zhang, De-ting; Zhou, Li-fang; Tao, Xi-dan; Zhang, Jing; Ye, Yun-jie; Sun, Pin; Frank, Arthur; Xia, Zhao-lin

2015-01-01

Background: Genetic variations in metabolic enzyme genes may enhance hematotoxicity in benzene-exposed populations. Objective: To investigate the association between polymorphisms of metabolism genes and white blood cells (WBCs). Methods: Three hundred and eighty-five benzene-exposed workers and 220 unexposed indoor workers were recruited in China. We explored the relationship between metabolic enzymes polymorphisms [glutathione S-transferase T1/M1 (GSTT1/M1) null, glutathione S-transferase P1 (GSTP1)rs1695, Cytochrome P450 2E1 (CYP2E1) rs3813867, rs2031920, rs6413432, microsomal epoxide hydrolase (mEH) rs1051740, rs2234922] by polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) analysis and WBC. Results: The exposed group had lower WBC counts (P<0.001) than the unexposed group. Increased susceptibility to hematotoxicity, as evidenced by lower WBC counts, was found in workers with null-GSTT1 (P = 0.045), null-GSTM1 (P = 0.030), rs2031920 (P = 0.020), and rs3813867 (P = 0.014) genotypes. White blood cell counts were also lower in workers with null-GSTT1 and null-GSTM after adjusting for age, gender, smoking, and alcohol consumption. Conclusion: Null-GSTT1 and null-GSTM1 genotypes and Cytochrome P4502E1 (CYP2E1: rs2031920, rs3813867) may support the hematotoxicity of benzene-exposed workers in China, and we can make use of it to select susceptible population. PMID:26179485

High-frequency waves in the corona due to null points

NASA Astrophysics Data System (ADS)

Santamaria, I. C.; Khomenko, E.; Collados, M.; de Vicente, A.

2017-06-01

This work aims to understand the behavior of non-linear waves in the vicinity of a coronal null point. In previous works we have shown that high-frequency waves are generated in such a magnetic configuration. This paper studies those waves in detail in order to provide a plausible explanation of their generation. We demonstrate that slow magneto-acoustic shock waves generated in the chromosphere propagate through the null point and produce a train of secondary shocks that escape along the field lines. A particular combination of the shock wave speeds generates waves at a frequency of 80 mHz. We speculate that this frequency may be sensitive to the atmospheric parameters in the corona and therefore can be used to probe the structure of this solar layer. Movies attached to Figs 2 and 4 are available at http://www.aanda.org

Design and tolerance analysis of two null corrector designs for the Space Telescope fine guidance aspheric collimating mirror

NASA Technical Reports Server (NTRS)

Friedman, I.; Casas, R. E.

1982-01-01

The collimating mirror within the Fine Guidance Subsystem of the Space Telescope's Pointing Control System is aspherized in order to correct the pupil aberration. A null corrector is needed to test the collimating mirror in autocollimation. Triplet and doublet null corrector designs are subjected to tolerance sensitivity analyses, and the doublet design is chosen despite its more restricted tolerances because of its compactness and simplicity.

ON THE 2012 OCTOBER 23 CIRCULAR RIBBON FLARE: EMISSION FEATURES AND MAGNETIC TOPOLOGY

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

Yang, Kai; Guo, Yang; Ding, M. D., E-mail: guoyang@nju.edu.cn, E-mail: dmd@nju.edu.cn

2015-06-20

Circular ribbon flares are usually related to spine-fan type magnetic topology containing null points. In this paper, we investigate an X-class circular ribbon flare on 2012 October 23, using the multiwavelength data from the Solar Dynamics Observatory, Hinode, and RHESSI. In Ca ii H emission, the flare showed three ribbons with two highly elongated ones inside and outside a quasi-circular one, respectively. A hot channel was displayed in the extreme-ultraviolet emissions that infers the existence of a magnetic flux rope. Two hard X-ray (HXR) sources in the 12–25 keV energy band were located at the footpoints of this hot channel. Using amore » nonlinear force-free magnetic field extrapolation, we identify three topological structures: (1) a three-dimensional null point, (2) a flux rope below the fan of the null point, and (3) a large-scale quasi-separatrix layer (QSL) induced by the quadrupolar-like magnetic field of the active region. We find that the null point is embedded within the large-scale QSL. In our case, all three identified topological structures must be considered to explain all the emission features associated with the observed flare. Besides, the HXR sources are regarded as the consequence of the reconnection within or near the border of the flux rope.« less

Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation

PubMed Central

Dedeoglu, Burç; Meijers, Ruud W. J.; Klepper, Mariska; Hesselink, Dennis A.; Baan, Carla C.; Litjens, Nicolle H. R.; Betjes, Michiel G. H.

2016-01-01

Background End-stage renal disease patients have a dysfunctional, prematurely aged peripheral T-cell system. Here we hypothesized that the degree of premature T-cell ageing before kidney transplantation predicts the risk for early acute allograft rejection (EAR). Methods 222 living donor kidney transplant recipients were prospectively analyzed. EAR was defined as biopsy proven acute allograft rejection within 3 months after kidney transplantation. The differentiation status of circulating T cells, the relative telomere length and the number of CD31+ naive T cells were determined as T-cell ageing parameters. Results Of the 222 patients analyzed, 30 (14%) developed an EAR. The donor age and the historical panel reactive antibody score were significantly higher (p = 0.024 and p = 0.039 respectively) and the number of related donor kidney transplantation was significantly lower (p = 0.018) in the EAR group. EAR-patients showed lower CD4+CD28null T-cell numbers (p<0.01) and the same trend was observed for CD8+CD28null T-cell numbers (p = 0.08). No differences regarding the other ageing parameters were found. A multivariate Cox regression analysis showed that higher CD4+CD28null T-cell numbers was associated with a lower risk for EAR (HR: 0.65, p = 0.028). In vitro, a significant lower percentage of alloreactive T cells was observed within CD28null T cells (p<0.001). Conclusion Immunological ageing-related expansion of highly differentiated CD28null T cells is associated with a lower risk for EAR. PMID:26950734

Multi-transmitter multi-receiver null coupled systems for inductive detection and characterization of metallic objects

NASA Astrophysics Data System (ADS)

Smith, J. Torquil; Morrison, H. Frank; Doolittle, Lawrence R.; Tseng, Hung-Wen

2007-03-01

Equivalent dipole polarizabilities are a succinct way to summarize the inductive response of an isolated conductive body at distances greater than the scale of the body. Their estimation requires measurement of secondary magnetic fields due to currents induced in the body by time varying magnetic fields in at least three linearly independent (e.g., orthogonal) directions. Secondary fields due to an object are typically orders of magnitude smaller than the primary inducing fields near the primary field sources (transmitters). Receiver coils may be oriented orthogonal to primary fields from one or two transmitters, nulling their response to those fields, but simultaneously nulling to fields of additional transmitters is problematic. If transmitter coils are constructed symmetrically with respect to inversion in a point, their magnetic fields are symmetric with respect to that point. If receiver coils are operated in pairs symmetric with respect to inversion in the same point, then their differenced output is insensitive to the primary fields of any symmetrically constructed transmitters, allowing nulling to three (or more) transmitters. With a sufficient number of receivers pairs, object equivalent dipole polarizabilities can be estimated in situ from measurements at a single instrument sitting, eliminating effects of inaccurate instrument location on polarizability estimates. The method is illustrated with data from a multi-transmitter multi-receiver system with primary field nulling through differenced receiver pairs, interpreted in terms of principal equivalent dipole polarizabilities as a function of time.

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

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.

Frequency-Tracking CW Doppler Radar Solving Small-Angle Approximation and Null Point Issues in Non-Contact Vital Signs Monitoring.

PubMed

Mercuri, Marco; Liu, Yao-Hong; Lorato, Ilde; Torfs, Tom; Bourdoux, Andre; Van Hoof, Chris

2017-06-01

A Doppler radar operating as a Phase-Locked-Loop (PLL) in frequency demodulator configuration is presented and discussed. The proposed radar presents a unique architecture, using a single channel mixer, and allows to detect contactless vital signs parameters while solving the null point issue and without requiring the small angle approximation condition. Spectral analysis, simulations, and experimental results are presented and detailed to demonstrate the feasibility and the operational principle of the proposed radar architecture.

Impurity screening behavior of the high-field side scrape-off layer in near-double-null configurations: prospect for mitigating plasma-material interactions on RF actuators and first-wall components

NASA Astrophysics Data System (ADS)

LaBombard, B.; Kuang, A. Q.; Brunner, D.; Faust, I.; Mumgaard, R.; Reinke, M. L.; Terry, J. L.; Howard, N.; Hughes, J. W.; Chilenski, M.; Lin, Y.; Marmar, E.; Rice, J. E.; Rodriguez-Fernandez, P.; Wallace, G.; Whyte, D. G.; Wolfe, S.; Wukitch, S.

2017-07-01

The impurity screening response of the high-field side (HFS) scrape-off layer (SOL) to localized nitrogen injection is investigated on Alcator C-Mod for magnetic equilibria spanning lower-single-null, double-null and upper-single-null configurations under otherwise identical plasma conditions. L-mode, EDA H-mode and I-mode discharges are investigated. HFS impurity screening is found to depend on magnetic flux balance and the direction of B  ×  \

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

Whistler mode refraction in highly nonuniform magnetic fields

NASA Astrophysics Data System (ADS)

Urrutia, J. M.; Stenzel, R.

2016-12-01

In a large laboratory plasma the propagation of whistler modes is measured in highly nonuniform magnetic fields created by a current-carrying wires. Ray tracing is not applicable since the wavelength and gradient scale length are comparable. The waves are excited with a loop antenna near the wire. The antenna launches an m=1 helicon mode in a uniform plasma. The total magnetic field consists of a weak uniform background field and a nearly circular field of a straight wire across the background field. A circular loop produces 3D null points and a 2D null line. The whistler wave propagation will be shown. It is relevant to whistler mode propagation in space plasmas near magnetic null-points, small flux ropes, lunar crustal magnetic fields and active wave injection experiments.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Comparison of Heat Flux Gages for High Enthalpy Flows - NASA Ames and IRS

NASA Technical Reports Server (NTRS)

Loehle, Stefan; Nawaz, Anuscheh; Herdrich, Georg; Fasoulas, Stefanos; Martinez, Edward; Raiche, George

2016-01-01

This article is a companion to a paper on heat flux measurements as initiated under a Space Act Agreement in 2011. The current focus of this collaboration between the Institute of Space Systems (IRS) of the University of Stuttgart and NASA Ames Research Center is the comparison and refinement of diagnostic measurements. A first experimental campaign to test different heat flux gages in the NASA Interaction Heating Facility (IHF) and the Plasmawindkanaele (PWK) at IRS was established. This paper focuses on the results of the measurements conducted at IRS. The tested gages included a at face and hemispherical probe head, a 4" hemispherical slug calorimeter, a null-point calorimeter from Ames and a null-point calorimeter developed for this purpose at IRS. The Ames null-point calorimeter was unfortunately defective upon arrival. The measured heat fluxes agree fairly well with each other. The reason for discrepancies can be attributed to signal-to-noise levels and the probe geometry.

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.

Compression of auditory space during forward self-motion.

PubMed

Teramoto, Wataru; Sakamoto, Shuichi; Furune, Fumimasa; Gyoba, Jiro; Suzuki, Yôiti

2012-01-01

Spatial inputs from the auditory periphery can be changed with movements of the head or whole body relative to the sound source. Nevertheless, humans can perceive a stable auditory environment and appropriately react to a sound source. This suggests that the inputs are reinterpreted in the brain, while being integrated with information on the movements. Little is known, however, about how these movements modulate auditory perceptual processing. Here, we investigate the effect of the linear acceleration on auditory space representation. Participants were passively transported forward/backward at constant accelerations using a robotic wheelchair. An array of loudspeakers was aligned parallel to the motion direction along a wall to the right of the listener. A short noise burst was presented during the self-motion from one of the loudspeakers when the listener's physical coronal plane reached the location of one of the speakers (null point). In Experiments 1 and 2, the participants indicated which direction the sound was presented, forward or backward relative to their subjective coronal plane. The results showed that the sound position aligned with the subjective coronal plane was displaced ahead of the null point only during forward self-motion and that the magnitude of the displacement increased with increasing the acceleration. Experiment 3 investigated the structure of the auditory space in the traveling direction during forward self-motion. The sounds were presented at various distances from the null point. The participants indicated the perceived sound location by pointing a rod. All the sounds that were actually located in the traveling direction were perceived as being biased towards the null point. These results suggest a distortion of the auditory space in the direction of movement during forward self-motion. The underlying mechanism might involve anticipatory spatial shifts in the auditory receptive field locations driven by afferent signals from vestibular system.

MUTYH mediates the toxicity of combined DNA 6-thioguanine and UVA radiation.

PubMed

Grasso, Francesca; Ruggieri, Vitalba; De Luca, Gabriele; Leopardi, Paola; Mancuso, Maria Teresa; Casorelli, Ida; Pichierri, Pietro; Karran, Peter; Bignami, Margherita

2015-04-10

The therapeutic thiopurines, including the immunosuppressant azathioprine (Aza) cause the accumulation of the UVA photosensitizer 6-thioguanine (6-TG) in the DNA of the patients' cells. DNA 6-TG and UVA are synergistically cytotoxic and their interaction causes oxidative damage. The MUTYH DNA glycosylase participates in the base excision repair of oxidized DNA bases. Using Mutyh-nullmouse fibroblasts (MEFs) we examined whether MUTYH provides protection against the lethal effects of combined DNA 6-TG/UVA. Surprisingly, Mutyh-null MEFs were more resistant than wild-type MEFs, despite accumulating higher levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG).Their enhanced 6-TG/UVA resistance reflected the absence of the MUTYH protein and MEFs expressing enzymatically-dead human variants were as sensitive as wild-type cells. Consistent with their enhanced resistance, Mutyh-null cells sustained fewer DNA strand breaks and lower levels of chromosomal damage after 6-TG/UVA. Although 6-TG/UVA treatment caused early checkpoint activation irrespective of the MUTYH status, Mutyh-null cells failed to arrest in S-phase at late time points. MUTYH-dependent toxicity was also apparent in vivo. Mutyh-/- mice survived better than wild-type during a 12-month chronicexposure to Aza/UVA treatments that significantly increased levels of skin DNA 8-oxoG. Two squamous cell skin carcinomas arose in Aza/UVA treated Mutyh-/- mice whereas similarly treated wild-type animals remained tumor-free.

The impact of p53 protein core domain structural alteration on ovarian cancer survival.

PubMed

Rose, Stephen L; Robertson, Andrew D; Goodheart, Michael J; Smith, Brian J; DeYoung, Barry R; Buller, Richard E

2003-09-15

Although survival with a p53 missense mutation is highly variable, p53-null mutation is an independent adverse prognostic factor for advanced stage ovarian cancer. By evaluating ovarian cancer survival based upon a structure function analysis of the p53 protein, we tested the hypothesis that not all missense mutations are equivalent. The p53 gene was sequenced from 267 consecutive ovarian cancers. The effect of individual missense mutations on p53 structure was analyzed using the International Agency for Research on Cancer p53 Mutational Database, which specifies the effects of p53 mutations on p53 core domain structure. Mutations in the p53 core domain were classified as either explained or not explained in structural or functional terms by their predicted effects on protein folding, protein-DNA contacts, or mutation in highly conserved residues. Null mutations were classified by their mechanism of origin. Mutations were sequenced from 125 tumors. Effects of 62 of the 82 missense mutations (76%) could be explained by alterations in the p53 protein. Twenty-three (28%) of the explained mutations occurred in highly conserved regions of the p53 core protein. Twenty-two nonsense point mutations and 21 frameshift null mutations were sequenced. Survival was independent of missense mutation type and mechanism of null mutation. The hypothesis that not all missense mutations are equivalent is, therefore, rejected. Furthermore, p53 core domain structural alteration secondary to missense point mutation is not functionally equivalent to a p53-null mutation. The poor prognosis associated with p53-null mutation is independent of the mutation mechanism.

High heat flux measurements and experimental calibrations/characterizations

NASA Technical Reports Server (NTRS)

Kidd, Carl T.

1992-01-01

Recent progress in techniques employed in the measurement of very high heat-transfer rates in reentry-type facilities at the Arnold Engineering Development Center (AEDC) is described. These advances include thermal analyses applied to transducer concepts used to make these measurements; improved heat-flux sensor fabrication methods, equipment, and procedures for determining the experimental time response of individual sensors; performance of absolute heat-flux calibrations at levels above 2,000 Btu/cu ft-sec (2.27 kW/cu cm); and innovative methods of performing in-situ run-to-run characterizations of heat-flux probes installed in the test facility. Graphical illustrations of the results of extensive thermal analyses of the null-point calorimeter and coaxial surface thermocouple concepts with application to measurements in aerothermal test environments are presented. Results of time response experiments and absolute calibrations of null-point calorimeters and coaxial thermocouples performed in the laboratory at intermediate to high heat-flux levels are shown. Typical AEDC high-enthalpy arc heater heat-flux data recently obtained with a Calspan-fabricated null-point probe model are included.

Blob dynamics in TORPEX poloidal null configurations

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

On the trajectories of null and timelike geodesics in different wormhole geometries

NASA Astrophysics Data System (ADS)

Mishra, Anuj; Chakraborty, Subenoy

2018-05-01

The paper deals with an extensive study of null and timelike geodesics in the background of wormhole geometries. Starting with a spherically symmetric spacetime, null geodesics are analyzed for the Morris-Thorne wormhole (WH) and photon spheres are examined in WH geometries. Both bounded and unbounded orbits are discussed for timelike geodesics. A similar analysis has been done for trajectories in a dynamic spherically symmetric WH and for a rotating WH. Finally, the invariant angle method of Rindler and Ishak has been used to calculate the angle between radial and tangential vectors at any point on the photon's trajectory.

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

PubMed

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

2010-04-01

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

Reconnection at three dimensional magnetic null points: Effect of current sheet asymmetry

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

Wyper, P. F.; Jain, Rekha

2013-05-15

Asymmetric current sheets are likely to be prevalent in both astrophysical and laboratory plasmas with complex three dimensional (3D) magnetic topologies. This work presents kinematic analytical models for spine and fan reconnection at a radially symmetric 3D null (i.e., a null where the eigenvalues associated with the fan plane are equal) with asymmetric current sheets. Asymmetric fan reconnection is characterized by an asymmetric reconnection of flux past each spine line and a bulk flow of plasma across the null point. In contrast, asymmetric spine reconnection is characterized by the reconnection of an equal quantity of flux across the fan planemore » in both directions. The higher modes of spine reconnection also include localized wedges of vortical flux transport in each half of the fan. In this situation, two definitions for reconnection rate become appropriate: a local reconnection rate quantifying how much flux is genuinely reconnected across the fan plane and a global rate associated with the net flux driven across each semi-plane. Through a scaling analysis, it is shown that when the ohmic dissipation in the layer is assumed to be constant, the increase in the local rate bleeds from the global rate as the sheet deformation is increased. Both models suggest that asymmetry in the current sheet dimensions will have a profound effect on the reconnection rate and manner of flux transport in reconnection involving 3D nulls.« less

Null boundary controllability of a one-dimensional heat equation with an internal point mass and variable coefficients

NASA Astrophysics Data System (ADS)

Ben Amara, Jamel; Bouzidi, Hedi

2018-01-01

In this paper, we consider a linear hybrid system which is composed by two non-homogeneous rods connected by a point mass with Dirichlet boundary conditions on the left end and a boundary control acts on the right end. We prove that this system is null controllable with Dirichlet or Neumann boundary controls. Our approach is mainly based on a detailed spectral analysis together with the moment method. In particular, we show that the associated spectral gap in both cases (Dirichlet or Neumann boundary controls) is positive without further conditions on the coefficients other than the regularities.

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.

Influence of pinches on magnetic reconnection in turbulent space plasmas

NASA Astrophysics Data System (ADS)

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

A generally accepted scenario of magnetic reconnection in space plasmas is the breakage of magnetic field lines in X-points. In laboratory, reconnection is widely studied in pinches, current channels embedded into twisted magnetic fields. No model of magnetic reconnection in space plasmas considers both null-points and pinches as peers. We have performed a particle-in-cell simulation of magnetic reconnection in a three-dimensional configuration where null-points are present nitially, and Z-pinches are formed during the simulation. The X-points are relatively stable, and no substantial energy dissipation is associated with them. On contrary, turbulent magnetic reconnection in the pinches causes the magnetic energy to decay at a rate of approximately 1.5 percent per ion gyro period. Current channels and twisted magnetic fields are ubiquitous in turbulent space plasmas, so pinches can be responsible for the observed high magnetic reconnection rates.

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

Thurgood, Jonathan O.; McLaughlin, James A.; Pontin, David I., E-mail: jonathan.thurgood@northumbria.ac.uk

Here we detail the dynamic evolution of localized reconnection regions about 3D magnetic null points using numerical simulation. We demonstrate for the first time that reconnection triggered by the localized collapse of a 3D null point that is due to an external magnetohydrodynamic (MHD) wave involves a self-generated oscillation, whereby the current sheet and outflow jets undergo a reconnection reversal process during which back-pressure formation at the jet heads acts to prise open the collapsed field before overshooting the equilibrium into an opposite-polarity configuration. The discovery that reconnection at fully 3D nulls can proceed naturally in a time-dependent and periodicmore » fashion suggests that oscillatory reconnection mechanisms may play a role in explaining periodicity in astrophysical phenomena associated with magnetic reconnection, such as the observed quasi-periodicity of solar and stellar flare emission. Furthermore, we find that a consequence of oscillatory reconnection is the generation of a plethora of freely propagating MHD waves that escape the vicinity of the reconnection region.« less

MUTYH mediates the toxicity of combined DNA 6-thioguanine and UVA radiation

PubMed Central

De Luca, Gabriele; Leopardi, Paola; Mancuso, Maria Teresa; Casorelli, Ida; Pichierri, Pietro; Karran, Peter; Bignami, Margherita

2015-01-01

The therapeutic thiopurines, including the immunosuppressant azathioprine (Aza) cause the accumulation of the UVA photosensitizer 6-thioguanine (6-TG) in the DNA of the patients' cells. DNA 6-TG and UVA are synergistically cytotoxic and their interaction causes oxidative damage. The MUTYH DNA glycosylase participates in the base excision repair of oxidized DNA bases. Using Mutyh-nullmouse fibroblasts (MEFs) we examined whether MUTYH provides protection against the lethal effects of combined DNA 6-TG/UVA. Surprisingly, Mutyh-null MEFs were more resistant than wild-type MEFs, despite accumulating higher levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG). Their enhanced 6-TG/UVA resistance reflected the absence of the MUTYH protein and MEFs expressing enzymatically-dead human variants were as sensitive as wild-type cells. Consistent with their enhanced resistance, Mutyh-null cells sustained fewer DNA strand breaks and lower levels of chromosomal damage after 6-TG/UVA. Although 6-TG/UVA treatment caused early checkpoint activation irrespective of the MUTYH status, Mutyh-null cells failed to arrest in S-phase at late time points. MUTYH-dependent toxicity was also apparent in vivo. Mutyh−/−mice survived better than wild-type during a 12-month chronicexposure to Aza/UVA treatments that significantly increased levels of skin DNA 8-oxoG. Two squamous cell skin carcinomas arose in Aza/UVA treated Mutyh−/− mice whereas similarly treated wild-type animals remained tumor-free. PMID:25638157

A simplified filterless photonic frequency octupling scheme based on cascaded modulators

NASA Astrophysics Data System (ADS)

Zhang, Wu; Wen, Aijun; Gao, Yongsheng; Zheng, Hanxiao; Chen, Wei; He, Hongye

2017-04-01

A simplified filterless frequency octupling scheme by connecting an intensity modulator (IM) with a dual-parallel Mach-Zehnder (DPMZM) in series is proposed in this paper. The LO signal is distributed into two parts, and one part is used to drive the IM and the other part is applied to drive the DPMZM's upper sub-modulator, both at the peak point. The lower sub-modulator is only driven by dc bias, and the parent modulator works at null point. By properly adjusting dc bias of the lower sub-modulator, only ±4th-order optical sidebands dominate at the output of the DPMZM. The approach is verified by experiments, and 32-GHz and 40-GHz millimetre waves (mm-waves) are generated using 4-GHz and 5-GHz LO signals, respectively. We acquire a 15-dB electrical spurious suppression ratio (ESSR) and a relatively good phase noise of the signal. Compared with other schemes, the scheme is simple in configuration because only an IM and a DPMZM are needed. What's more, the scheme is tunable in frequency as no filter is used.

The quantum null energy condition in curved space

NASA Astrophysics Data System (ADS)

Fu, Zicao; Koeller, Jason; Marolf, Donald

2017-11-01

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

[Liver cirrhosis patogenetics: polymorphism of glutation S-transferase genes].

PubMed

Goncharova, I A; Rachkovskiĭ, M I; Beloborodova, E V; Gamal' Abd El'-Aziz Nasar, Kh; Puzyrev, V P

2010-01-01

Association of deletion polymorphism in GSTT1 and GSTM1 genes and polymorphic variant A313G of GSTP1 gene with cirrhosis diseases and 4-year survival rate for the Tomsk region (West Siberia) patients were tested. Homozygous deletion of GSTM1 gene (null genotype) was a protective factor for alcoholic and mixed (HCV, HBV and alcohol) liver cirrhosis development. The patients from the joint group (all etiology forms) as well as having alcoholic and mixed cirrhosis had lower frequency of GSTM1 null genotype (39.2, 39.0, and 34.2%, respectively) in comparison with the control group (64.6%). The GSTM1 null genotype and GSTP1 gene A313G polymorphic variant correlated with the patients' survival rate. The patients survived in comparison with the dead had higher frequency of a GSTM1 null genotype (46.6 vs. 30.2%) and GSTP1 AA genotype (63.1 vs. 40.5%), and lower frequency of GSTP1 AG (A313G) genotype (31.1 vs. 51.2%). A survival rate was 2.5 times higher for patients having GSTP1 AA genotype in comparison with the GG and AG genotype carriers and 2 times higher for patients having GSTM1 null genotype than the gene carriers. A 4-year fatal case probability was 2.3 times higher among the patients having heterozygous AG GSTP1 genotype in comparison with homozygous AA and GG genotype carriers.

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

Strehl ratio: a tool for optimizing optical nulls and singularities.

PubMed

Hénault, François

2015-07-01

In this paper a set of radial and azimuthal phase functions are reviewed that have a null Strehl ratio, which is equivalent to generating a central extinction in the image plane of an optical system. The study is conducted in the framework of Fraunhofer scalar diffraction, and is oriented toward practical cases where optical nulls or singularities are produced by deformable mirrors or phase plates. The identified solutions reveal unexpected links with the zeros of type-J Bessel functions of integer order. They include linear azimuthal phase ramps giving birth to an optical vortex, azimuthally modulated phase functions, and circular phase gratings (CPGs). It is found in particular that the CPG radiometric efficiency could be significantly improved by the null Strehl ratio condition. Simple design rules for rescaling and combining the different phase functions are also defined. Finally, the described analytical solutions could also serve as starting points for an automated searching software tool.

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.

La place de la negation syntaxique en francais (The Place of Syntactic Negation in French). Montreal Working Papers in Linguistics, Vol. 2.

ERIC Educational Resources Information Center

Paradis, Michel

This paper is a syntactic analysis of standard French negation. The following expressions are described in detail: (1)ne...pas(point), (2)nullement (aucunement), (3)plus, (4)jamais, (5)pas encore, (6)guere, (7)rien, (8)personne, (9)aucun(e), (10)nul(le), (11)ni...ni..., (12)nulle part, (13)que, (14)pas un(e), (15)nul. The negative expressions are…

Analyses of Simulated Reconnection-Driven Solar Polar Jets

NASA Astrophysics Data System (ADS)

Roberts, M. A.; Uritsky, V. M.; Karpen, J. T.; DeVore, C. R.

2014-12-01

Solar polar jets are observed to originate in regions within the open field of solar coronal holes. These so called "anemone" regions are generally accepted to be regions of opposite polarity, and are associated with an embedded dipole topology, consisting of a fan-separatrix and a spine line emanating from a null point occurring at the top of the dome shaped fan surface. Previous analysis of these jets (Pariat et al. 2009,2010) modeled using the Adaptively Refined Magnetohydrodynamics Solver (ARMS) has supported the claim that magnetic reconnection across current sheets formed at the null point between the highly twisted closed field of the dipole and open field lines surrounding it releases the energy necessary to drive these jets. However, these initial simulations assumed a "static" environment for the jets, neglecting effects due to gravity, solar wind and the expanding spherical geometry. A new set of ARMS simulations taking into account these additional physical processes was recently performed. Initial results are qualitatively consistent with the earlier Cartesian studies, demonstrating the robustness of the underlying ideal and resistive mechanisms. We focus on density and velocity fluctuations within a narrow radial slit aligned with the direction of the spine of the jet, as well as other physical properties, in order to identify and refine their signatures in the lower heliosphere. These refined signatures can be used as parameters by which plasma processes initiated by these jets may be identified in situ by future missions such as Solar Orbiter and Solar Probe Plus.

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 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

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

PubMed

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

2008-02-01

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

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

PubMed Central

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

2012-01-01

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild type mice, whereas Tas1r3 null mice were not different from wild-type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in conditioned taste aversion to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol. PMID:17376151

Lovelock vacua with a recurrent null vector field

NASA Astrophysics Data System (ADS)

Ortaggio, Marcello

2018-02-01

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

Hypothesis testing of a change point during cognitive decline among Alzheimer's disease patients.

PubMed

Ji, Ming; Xiong, Chengjie; Grundman, Michael

2003-10-01

In this paper, we present a statistical hypothesis test for detecting a change point over the course of cognitive decline among Alzheimer's disease patients. The model under the null hypothesis assumes a constant rate of cognitive decline over time and the model under the alternative hypothesis is a general bilinear model with an unknown change point. When the change point is unknown, however, the null distribution of the test statistics is not analytically tractable and has to be simulated by parametric bootstrap. When the alternative hypothesis that a change point exists is accepted, we propose an estimate of its location based on the Akaike's Information Criterion. We applied our method to a data set from the Neuropsychological Database Initiative by implementing our hypothesis testing method to analyze Mini Mental Status Exam scores based on a random-slope and random-intercept model with a bilinear fixed effect. Our result shows that despite large amount of missing data, accelerated decline did occur for MMSE among AD patients. Our finding supports the clinical belief of the existence of a change point during cognitive decline among AD patients and suggests the use of change point models for the longitudinal modeling of cognitive decline in AD research.

Effect of Power Point Enhanced Teaching (Visual Input) on Iranian Intermediate EFL Learners' Listening Comprehension Ability

ERIC Educational Resources Information Center

Sehati, Samira; Khodabandehlou, Morteza

2017-01-01

The present investigation was an attempt to study on the effect of power point enhanced teaching (visual input) on Iranian Intermediate EFL learners' listening comprehension ability. To that end, a null hypothesis was formulated as power point enhanced teaching (visual input) has no effect on Iranian Intermediate EFL learners' listening…

Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

PubMed Central

Gokhin, David S.; Lewis, Raymond A.; McKeown, Caroline R.; Nowak, Roberta B.; Kim, Nancy E.; Littlefield, Ryan S.; Lieber, Richard L.

2010-01-01

During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology. PMID:20368620

The Role of Superior Oblique Posterior Tenectomy Along With Inferior Rectus Recessions for the Treatment of Chin-up Head Positioning in Patients With Nystagmus.

PubMed

Escuder, Anna G; Ranka, Milan P; Lee, Kathy; Nam, Julie N; Steele, Mark A

2018-05-29

To evaluate the clinical outcomes of bilateral superior oblique posterior 7/8th tenectomy with inferior rectus recession on improving chin-up head positioning in patients with horizontal nystagmus. Medical records were reviewed from 2007 to 2017 for patients with nystagmus and chin-up positioning of 15° or more who underwent combined bilateral superior oblique posterior 7/8th tenectomy with an inferior rectus recession of at least 5 mm. Thirteen patients (9 males and 4 females) were included, with an average age of 7.3 years (range: 1.8 to 15 years). Chin-up positioning ranged from 15° to 45° degrees (average: 30°). Three patients had prior horizontal muscle surgeries, 1 for esotropia and 2 for horizontal null zones causing anomalous face turns. Ten patients underwent other concomitant eye muscle surgery: 3 had esotropia, 1 had exotropia, and 2 had biplanar nystagmus null point requiring a horizontal Anderson procedure. Four patients underwent simultaneous bilateral medial rectus tenotomy and reattachment. All patients had improved chin-up positioning. Eight patients had complete resolution, whereas 5 had minimal residual chin-up positioning. Three patients developed an eccentric horizontal gaze null point with compensatory anomalous face turn with onset 2 weeks, 2 years, and 3 years postoperatively. Average follow-up was 42.7 months. No postoperative pattern deviations, cyclodeviations, or inferior oblique overaction were seen. No surgical complications were noted. Bilateral superior oblique posterior 7/8th tenectomy in conjunction with bilateral inferior rectus recession is a safe and effective procedure for improving chin-up head positioning in patients with horizontal nystagmus with a down gaze null point. [J Pediatr Ophthalmol Strabismus. 201X;XX(X):XX-XX.]. Copyright 2018, SLACK Incorporated.

Non-linear tearing of 3D null point current sheets

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

Wyper, P. F., E-mail: peterw@maths.dundee.ac.uk; Pontin, D. I., E-mail: dpontin@maths.dundee.ac.uk

2014-08-15

The manner in which the rate of magnetic reconnection scales with the Lundquist number in realistic three-dimensional (3D) geometries is still an unsolved problem. It has been demonstrated that in 2D rapid non-linear tearing allows the reconnection rate to become almost independent of the Lundquist number (the “plasmoid instability”). Here, we present the first study of an analogous instability in a fully 3D geometry, defined by a magnetic null point. The 3D null current layer is found to be susceptible to an analogous instability but is marginally more stable than an equivalent 2D Sweet-Parker-like layer. Tearing of the sheet createsmore » a thin boundary layer around the separatrix surface, contained within a flux envelope with a hyperbolic structure that mimics a spine-fan topology. Efficient mixing of flux between the two topological domains occurs as the flux rope structures created during the tearing process evolve within this envelope. This leads to a substantial increase in the rate of reconnection between the two domains.« less

Prolonged mechanical noise restores tactile sense in diabetic neuropathic patients.

PubMed

Cloutier, Rachel; Horr, Samuel; Niemi, James B; D'Andrea, Susan; Lima, Christina; Harry, Jason D; Veves, Aristidis

2009-03-01

Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 +/- 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 +/- 11.9) compared with both baseline (P = .018) and off position (P = .045). The 60 minutes VPT with active SR (28.7 +/- 11.1) reached significance comparing the baseline when one outlier was removed from the analysis (P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Long-term application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function.

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

Balloon Exoplanet Nulling Interferometer (BENI)

NASA Technical Reports Server (NTRS)

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

2009-01-01

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

The importance of topographically corrected null models for analyzing ecological point processes.

PubMed

McDowall, Philip; Lynch, Heather J

2017-07-01

Analyses of point process patterns and related techniques (e.g., MaxEnt) make use of the expected number of occurrences per unit area and second-order statistics based on the distance between occurrences. Ecologists working with point process data often assume that points exist on a two-dimensional x-y plane or within a three-dimensional volume, when in fact many observed point patterns are generated on a two-dimensional surface existing within three-dimensional space. For many surfaces, however, such as the topography of landscapes, the projection from the surface to the x-y plane preserves neither area nor distance. As such, when these point patterns are implicitly projected to and analyzed in the x-y plane, our expectations of the point pattern's statistical properties may not be met. When used in hypothesis testing, we find that the failure to account for the topography of the generating surface may bias statistical tests that incorrectly identify clustering and, furthermore, may bias coefficients in inhomogeneous point process models that incorporate slope as a covariate. We demonstrate the circumstances under which this bias is significant, and present simple methods that allow point processes to be simulated with corrections for topography. These point patterns can then be used to generate "topographically corrected" null models against which observed point processes can be compared. © 2017 by the Ecological Society of America.

Accounting for independent nondifferential misclassification does not increase certainty that an observed association is in the correct direction.

PubMed

Greenland, Sander; Gustafson, Paul

2006-07-01

Researchers sometimes argue that their exposure-measurement errors are independent of other errors and are nondifferential with respect to disease, resulting in estimation bias toward the null. Among well-known problems with such arguments are that independence and nondifferentiality are harder to satisfy than ordinarily appreciated (e.g., because of correlation of errors in questionnaire items, and because of uncontrolled covariate effects on error rates); small violations of independence or nondifferentiality may lead to bias away from the null; and, if exposure is polytomous, the bias produced by independent nondifferential error is not always toward the null. The authors add to this list by showing that, in a 2 x 2 table (for which independent nondifferential error produces bias toward the null), accounting for independent nondifferential error does not reduce the p value even though it increases the point estimate. Thus, such accounting should not increase certainty that an association is present.

Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women.

PubMed

Arking, Dan E; Fallin, Daniele M; Fried, Linda P; Li, Tao; Beamer, Brock A; Xue, Qian Li; Chakravarti, Aravinda; Walston, Jeremy

2006-05-01

To determine whether genetic variants in the ciliary neurotrophic factor (CNTF) gene are associated with muscle strength in older women. Cross-sectional analysis of baseline data from the Women's Health and Aging Studies I (1992) and II (1994), complementary population-based studies. Twelve contiguous ZIP code areas in Baltimore, Maryland. Three hundred sixty-three Caucasian, community-dwelling women aged 70 to 79. Participants were genotyped at the CNTF locus for eight single nucleotide polymorphisms (SNPs), including the null allele rs1800169. The dependent variables were grip strength and the frailty syndrome, identified as presence of three or more of five frailty indicators (weakness, slowness, weight loss, low physical activity, exhaustion). In addition to genotypes, independent variables of body mass index (BMI) and osteoarthritis of the hands were included. Using multivariate linear regression, single SNP analysis identified five SNPs significantly associated with grip strength (P<.05), after adjusting for age, BMI, and osteoarthritis. Haplotype analysis was performed, and a single haplotype associated with grip strength was identified (P<.01). The rs1800169 null allele fully explained the association between this haplotype and grip strength under a recessive model, with individuals homozygous for the null allele exhibiting a 3.80-kg lower (95% confidence interval=1.01-6.58) grip strength. No association was seen between the CNTF null allele and frailty. Individuals homozygous for the CNTF null allele had significantly lower grip strength but did not exhibit overt frailty. Larger prospective studies are needed to confirm this finding and extend it to additional populations.

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.

Enabling low-noise null-point scanning thermal microscopy by the optimization of scanning thermal microscope probe through a rigorous theory of quantitative measurement.

PubMed

Hwang, Gwangseok; Chung, Jaehun; Kwon, Ohmyoung

2014-11-01

The application of conventional scanning thermal microscopy (SThM) is severely limited by three major problems: (i) distortion of the measured signal due to heat transfer through the air, (ii) the unknown and variable value of the tip-sample thermal contact resistance, and (iii) perturbation of the sample temperature due to the heat flux through the tip-sample thermal contact. Recently, we proposed null-point scanning thermal microscopy (NP SThM) as a way of overcoming these problems in principle by tracking the thermal equilibrium between the end of the SThM tip and the sample surface. However, in order to obtain high spatial resolution, which is the primary motivation for SThM, NP SThM requires an extremely sensitive SThM probe that can trace the vanishingly small heat flux through the tip-sample nano-thermal contact. Herein, we derive a relation between the spatial resolution and the design parameters of a SThM probe, optimize the thermal and electrical design, and develop a batch-fabrication process. We also quantitatively demonstrate significantly improved sensitivity, lower measurement noise, and higher spatial resolution of the fabricated SThM probes. By utilizing the exceptional performance of these fabricated probes, we show that NP SThM can be used to obtain a quantitative temperature profile with nanoscale resolution independent of the changing tip-sample thermal contact resistance and without perturbation of the sample temperature or distortion due to the heat transfer through the air.

Removal of the local geomagnetic field affects reproductive growth in Arabidopsis.

PubMed

Xu, Chunxiao; Wei, Shufeng; Lu, Yan; Zhang, Yuxia; Chen, Chuanfang; Song, Tao

2013-09-01

The influence of the geomagnetic field-removed environment on Arabidopsis growth was investigated by cultivation of the plants in a near-null magnetic field and local geomagnetic field (45 µT) for the whole growth period under laboratory conditions. The biomass accumulation of plants in the near-null magnetic field was significantly suppressed at the time when plants were switching from vegetative growth to reproductive growth compared with that of plants grown in the local geomagnetic field, which was caused by a delay in the flowering of plants in the near-null magnetic field. At the early or later growth stage, no significant difference was shown in the biomass accumulation between the plants in the near-null magnetic field and local geomagnetic field. The average number of siliques and the production of seeds per plant in the near-null magnetic field was significantly lower by about 22% and 19%, respectively, than those of control plants. These resulted in a significant reduction of about 20% in the harvest index of plants in the near-null magnetic field compared with that of the controls. These results suggest that the removal of the local geomagnetic field negatively affects the reproductive growth of Arabidopsis, which thus affects the yield and harvest index. Copyright © 2013 Wiley Periodicals, Inc.

Flux rope, hyperbolic flux tube, and late extreme ultraviolet phases in a non-eruptive circular-ribbon flare

NASA Astrophysics Data System (ADS)

Masson, Sophie; Pariat, Étienne; Valori, Gherardo; Deng, Na; Liu, Chang; Wang, Haimin; Reid, Hamish

2017-08-01

Context. The dynamics of ultraviolet (UV) emissions during solar flares provides constraints on the physical mechanisms involved in the trigger and the evolution of flares. In particular it provides some information on the location of the reconnection sites and the associated magnetic fluxes. In this respect, confined flares are far less understood than eruptive flares generating coronal mass ejections. Aims: We present a detailed study of a confined circular flare dynamics associated with three UV late phases in order to understand more precisely which topological elements are present and how they constrain the dynamics of the flare. Methods: We perform a non-linear force-free field extrapolation of the confined flare observed with the Helioseismic and Magnetic Imager (HMI) and Atmospheric Imaging Assembly (AIA) instruments on board Solar Dynamics Observatory (SDO). From the 3D magnetic field we compute the squashing factor and we analyse its distribution. Conjointly, we analyse the AIA extreme ultraviolet (EUV) light curves and images in order to identify the post-flare loops, and their temporal and thermal evolution. By combining the two analyses we are able to propose a detailed scenario that explains the dynamics of the flare. Results: Our topological analysis shows that in addition to a null-point topology with the fan separatrix, the spine lines and its surrounding quasi-separatix layer (QSL) halo (typical for a circular flare), a flux rope and its hyperbolic flux tube (HFT) are enclosed below the null. By comparing the magnetic field topology and the EUV post-flare loops we obtain an almost perfect match between the footpoints of the separatrices and the EUV 1600 Å ribbons and between the HFT field line footpoints and bright spots observed inside the circular ribbons. We show, for the first time in a confined flare, that magnetic reconnection occurred initially at the HFT below the flux rope. Reconnection at the null point between the flux rope and the overlying field is only initiated in a second phase. In addition, we showed that the EUV late phase observed after the main flare episode is caused by the cooling loops of different length which have all reconnected at the null point during the impulsive phase. Conclusions: Our analysis shows in one example that flux ropes are present in null-point topology not only for eruptive and jet events, but also for confined flares. This allows us to conjecture on the analogies between conditions that govern the generation of jets, confined flares or eruptive flares. A movie is available at http://www.aanda.org

Spine-fan reconnection. The influence of temporal and spatial variation in the driver

NASA Astrophysics Data System (ADS)

Wyper, P. F.; Jain, R.; Pontin, D. I.

2012-09-01

Context. From observations, the atmosphere of the Sun has been shown to be highly dynamic with perturbations of the magnetic field often lacking temporal or spatial symmetry. Despite this, studies of the spine-fan reconnection mode at 3D nulls have so far focused on the very idealised case with symmetric driving of a fixed spatial extent. Aims: We investigate the spine-fan reconnection process for less idealised cases, focusing on asymmetric driving and drivers with different length scales. We look at the initial current sheet formation and whether the scalings developed in the idealised models are robust in more realistic situations. Methods: The investigation was carried out by numerically solving the resistive compressible 3D magnetohydrodynamic equations in a Cartesian box containing a linear null point. The spine-fan collapse was driven at the null through tangential boundary driving of the spine foot points. Results: We find significant differences in the initial current sheet formation with asymmetric driving. Notable is the displacement of the null point position as a function of driving velocity and resistivity (η). However, the scaling relations developed in the idealised case are found to be robust (albeit at reduced amplitudes) despite this extra complexity. Lastly, the spatial variation is also shown to play an important role in the initial current sheet formation through controlling the displacement of the spine foot points. Conclusions: We conclude that during the early stages of spine-fan reconnection both the temporal and spatial nature of the driving play important roles, with the idealised symmetrically driven case giving a "best case" for the rate of current development and connectivity change. As the most interesting eruptive events occur in relatively short time frames this work clearly shows the need for high temporal and spatial knowledge of the flows for accurate interpretation of the reconnection scenario. Lastly, since the scalings developed in the idealised case remain robust with more complex driving we can be more confident of their use in interpreting reconnection in complex magnetic field structures.

Mathematical Capture of Human Data for Computer Model Building and Validation

DTIC Science & Technology

2014-04-03

weapon. The Projectile, the VDE , and the IDE weapons had effects of financial loss for the targeted participant, while the MRAD yielded its own...for LE, Centroid and TE for the baseline and The VDE weapon conditions since p-values exceeded α. All other conditions rejected the null...hypothesis except the LE for VDE weapon. The K-S Statistics were correspondingly lower for the measures that failed to reject the null hypothesis. The CDF

Divertor scenario development for NSTX Upgrade

NASA Astrophysics Data System (ADS)

Soukhanovskii, V. A.; McLean, A. G.; Meier, E. T.; Rognlien, T. D.; Ryutov, D. D.; Bell, R. E.; Diallo, A.; Gerhardt, S. P.; Kaita, R.; Kolemen, E.; Leblanc, B. P.; Menard, J. E.; Podesta, M.; Scotti, F.

2012-10-01

In the NSTX-U tokamak, initial plans for divertor plasma-facing components (PFCs) include lithium and boron coated graphite, with a staged transition to molybdenum. Steady-state peak divertor heat fluxes are projected to reach 20-30 MW/m^2 in 2 MA, 12 MW NBI-heated discharges of up to 5 s duration, thus challenging PFC thermal limits. Based on the recent NSTX divertor experiments and modeling with edge transport code UEDGE, a favorable basis for divertor power handling in NSTX-U is developed. The snowflake divertor geometry and feedback-controlled divertor impurity seeding applied to the lower and upper divertors are presently envisioned. In the NSTX snowflake experiments with lithium-coated graphite PFCs, the peak divertor heat fluxes from Type I ELMs and between ELMs were significantly reduced due to geometry effects, increased volumetric losses and null-point convective redistribution between strike points. H-mode core confinement was maintained at H98(y,2)<=1 albeit the radiative detachment. Additional CD4 seeding demonstrated potential for a further increase of divertor radiation.

Identification of the sequence variations of 15 autosomal STR loci in a Chinese population.

PubMed

Chen, Wenjing; Cheng, Jianding; Ou, Xueling; Chen, Yong; Tong, Dayue; Sun, Hongyu

2014-01-01

DNA sequence variation including base(s) changes and insertion or deletion in the primer binding region may cause a null allele and, if this changes the length of the amplified fragment out of the allelic ladder, off-ladder (OL) alleles may be detected. In order to provide accurate and reliable DNA evidence for forensic DNA analysis, it is essential to clarify sequence variations in prevalently used STR loci. Suspected null alleles and OL alleles of PlowerPlex16® System from 21,934 unrelated Chinese individuals were verified by alternative systems and sequenced. A total of 17 cases with null alleles were identified, including 12 kinds of point mutations in 16 cases and a 19-base deletion in one case. The total frequency of null alleles was 7.751 × 10(-4). Eight hundred and forty-four OL alleles classified as being of 97 different kinds were observed at 15 STR loci of the PowerPlex®16 system except vWA. All the frequencies of OL alleles were under 0.01. Null alleles should be confirmed by alternative primers and OL alleles should be named appropriately. Particular attention should be paid to sequence variation, since incorrect designation could lead to false conclusions.

Two-sample binary phase 2 trials with low type I error and low sample size

PubMed Central

Litwin, Samuel; Basickes, Stanley; Ross, Eric A.

2017-01-01

Summary We address design of two-stage clinical trials comparing experimental and control patients. Our end-point is success or failure, however measured, with null hypothesis that the chance of success in both arms is p0 and alternative that it is p0 among controls and p1 > p0 among experimental patients. Standard rules will have the null hypothesis rejected when the number of successes in the (E)xperimental arm, E, sufficiently exceeds C, that among (C)ontrols. Here, we combine one-sample rejection decision rules, E ≥ m, with two-sample rules of the form E – C > r to achieve two-sample tests with low sample number and low type I error. We find designs with sample numbers not far from the minimum possible using standard two-sample rules, but with type I error of 5% rather than 15% or 20% associated with them, and of equal power. This level of type I error is achieved locally, near the stated null, and increases to 15% or 20% when the null is significantly higher than specified. We increase the attractiveness of these designs to patients by using 2:1 randomization. Examples of the application of this new design covering both high and low success rates under the null hypothesis are provided. PMID:28118686

Circumpulsar Asteroids: Inferences from Nulling Statistics and High Energy Correlations

NASA Astrophysics Data System (ADS)

Shannon, Ryan; Cordes, J. M.

2006-12-01

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

The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities.

PubMed

Sarac, Miroslav S; Zieske, Arthur W; Lindberg, Iris

2002-06-01

The neuroendocrine-specific protein 7B2, which serves as a molecular escort for proPC2 in the secretory pathway, promotes the production of enzymatically active PC2 and may have non-PC2 related endocrine roles. Mice null for 7B2 exhibit a lethal phenotype with a complex Cushing's-like pathology, which develops from intermediate lobe ACTH hypersecretion as a consequences of interruption of PC2-mediated peptide processing as well as undefined consequences of the loss of 7B2. In this study we investigated the endocrine and metabolic alterations of 7B2 null mice from pathological and biochemical points of view. Our results show that 7B2 nulls exhibit a multisystem disorder that includes severe pathoanatomical and histopathologic alterations of vital organs, including the heart and spleen but most notably the liver, in which massive steatosis and necrosis are observed. Metabolic derangements in glucose metabolism result in glycogen and fat deposition in liver under conditions of chronic hypoglycemia. Liver failure is also likely to contribute to abnormalities in blood coagulation and blood chemistry, such as lactic acidosis. A hypoglycemic crisis coupled with respiratory distress and intensive internal thrombosis most likely results in rapid deterioration and death of the 7B2 null.

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.

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.

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.

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

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

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

Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione andmore » exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gst{alpha}1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.« less

Loss of REDD1 augments the rate of the overload-induced increase in muscle mass

PubMed Central

Liu, Chang; Steiner, Jennifer L.; Nader, Gustavo A.; Jefferson, Leonard S.; Kimball, Scot R.

2016-01-01

The overload-induced increase in muscle mass is accompanied by protein accretion; however, the initiating events are poorly understood. Regulated in Development and DNA Damage 1 (REDD1), a repressor of the mechanistic target of rapamycin in complex 1 (mTORC1), blunts the elevation in protein synthesis induced by acute muscle contractions. Therefore, this study was designed to determine whether REDD1 alters the rate of the overload-induced increase in muscle mass. Wild-type (WT) and REDD1-null mice underwent unilateral functional overload (OV) of the plantaris, while the contralateral sham leg served as a control. After 3 and 5 days of OV, puromycin incorporation was used as a measurement of protein synthesis. The percent increase in plantaris wet weight and protein content was greater in REDD1-null mice after 3, 5, and 10 days OV. The overload-stimulated rate of protein synthesis in the plantaris was similar between genotypes after 3 days OV, but translational capacity was lower in REDD1-null mice, indicating elevated translational efficiency. This was likely due to elevated absolute mTORC1 signaling [phosphorylation of p70S6K1 (Thr-389) and 4E-BP1 (Ser-65)]. By 5 days of OV, the rate of protein synthesis in REDD1-null mice was lower than WT mice with no difference in absolute mTORC1 signaling. Additionally, markers of autophagy (LC3II/I ratio and p62 protein) were decreased to a greater absolute extent after 3 days OV in REDD1-null mice. These data suggest that loss of REDD1 augments the rate of the OV-induced increase in muscle mass by altering multiple protein balance pathways. PMID:27465734

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

PubMed

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

2010-06-15

Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gstalpha1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities. Copyright 2010. Published by Elsevier Inc.

Requirements Formulation and Dynamic Jitter Analysis for Fourier-Kelvin Stellar Interferometer

NASA Technical Reports Server (NTRS)

Liu, Kuo-Chia; Hyde, Tristram; Blaurock, Carl; Bolognese, Jeff; Howard, Joseph; Danchi, William

2004-01-01

The Fourier-Kelvin Stellar Interferometer (FKSI) has been proposed to detect and characterize extra solar giant planets. The baseline configuration for FKSI is a two- aperture, structurally connected nulling interferometer, capable of providing null depth less than lo4 in the infrared. The objective of this paper is to summarize the process for setting the top level requirements and the jitter analysis performed on FKSI to date. The first part of the paper discusses the derivation of dynamic stability requirements, necessary for meeting the FKSI nulling demands. An integrated model including structures, optics, and control systems has been developed to support dynamic jitter analysis and requirements verification. The second part of the paper describes how the integrated model is used to investigate the effects of reaction wheel disturbances on pointing and optical path difference stabilities.

Attenuated progression of diet-induced steatohepatitis in glutathione-deficient mice

PubMed Central

Haque, Jamil A; McMahan, Ryan S; Campbell, Jean S; Shimizu-Albergine, Masami; Wilson, Angela M; Botta, Dianne; Bammler, Theo K; Beyer, Richard P; Montine, Thomas J; Yeh, Matthew M; Kavanagh, Terrance J; Fausto, Nelson

2011-01-01

In nonalcoholic fatty liver disease (NAFLD), depletion of hepatic antioxidants may contribute to the progression of steatosis to nonalcoholic steatohepatitis (NASH) by increasing oxidative stress that produces lipid peroxidation, inflammation, and fibrosis. We investigated whether depletion of glutathione (GSH) increases NASH-associated hepatic pathology in mice fed a diet deficient in methionine and choline (MCD diet). Wild-type (wt) mice and genetically GSH-deficient mice lacking the modifier subunit of glutamate cysteine ligase (Gclm null mice), the rate-limiting enzyme for de novo synthesis of GSH, were fed the MCD diet, a methionine/choline-sufficient diet, or standard chow for 21 days. We assessed NASH-associated hepatic pathology, including steatosis, fibrosis, inflammation, and hepatocyte ballooning, and used the NAFLD Scoring System to evaluate the extent of changes. We measured triglyceride levels, determined the level of lipid peroxidation products, and measured by qPCR the expression of mRNAs for several proteins associated with lipid metabolism, oxidative stress, and fibrosis. MCD-fed GSH-deficient Gclm null mice were to a large extent protected from MCD diet-induced excessive fat accumulation, hepatocyte injury, inflammation, and fibrosis. Compared with wt animals, MCD-fed Gclm null mice had much lower levels of F2-isoprostanes, lower expression of acyl-CoA oxidase, carnitine palmitoyltransferase 1a, uncoupling protein-2, stearoyl-coenzyme A desaturase-1, transforming growth factor-β, and plas-minogen activator inhibitor-1 mRNAs, and higher activity of catalase, indicative of low oxidative stress, inhibition of triglyceride synthesis, and lower expression of profibrotic proteins. Global gene analysis of hepatic RNA showed that compared with wt mice, the livers of Gclm null mice have a high capacity to metabolize endogenous and exogenous compounds, have lower levels of lipogenic proteins, and increased antioxidant activity. Thus, metabolic adaptations resulting from severe GSH deficiency seem to protect against the development of steatohepatitis. PMID:20548286

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

Liu Ke; Li Yanqiu; Wang Hai

Characterization of measurement accuracy of the phase-shifting point diffraction interferometer (PS/PDI) is usually performed by two-pinhole null test. In this procedure, the geometrical coma and detector tilt astigmatism systematic errors are almost one or two magnitude higher than the desired accuracy of PS/PDI. These errors must be accurately removed from the null test result to achieve high accuracy. Published calibration methods, which can remove the geometrical coma error successfully, have some limitations in calibrating the astigmatism error. In this paper, we propose a method to simultaneously calibrate the geometrical coma and detector tilt astigmatism errors in PS/PDI null test. Basedmore » on the measurement results obtained from two pinhole pairs in orthogonal directions, the method utilizes the orthogonal and rotational symmetry properties of Zernike polynomials over unit circle to calculate the systematic errors introduced in null test of PS/PDI. The experiment using PS/PDI operated at visible light is performed to verify the method. The results show that the method is effective in isolating the systematic errors of PS/PDI and the measurement accuracy of the calibrated PS/PDI is 0.0088{lambda} rms ({lambda}= 632.8 nm).« less

PERSEE: a nulling interferometer with dynamic correction of external perturbations

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Diverse effects of Glut 4 ablation on glucose uptake and glycogen synthesis in red and white skeletal muscle.

PubMed

Stenbit, A E; Burcelin, R; Katz, E B; Tsao, T S; Gautier, N; Charron, M J; Le Marchand-Brustel, Y

1996-08-01

The ability of muscles from Glut 4-null mice to take up and metabolize glucose has been studied in the isolated white EDL and red soleus muscles. In EDL muscles from male or female Glut 4-null mice, basal deoxyglucose uptake was lower than in control muscles and was not stimulated by insulin. In parallel, glycogen synthesis and content were decreased. Soleus muscles from male Glut 4-null mice took up twice more deoxyglucose in the absence of insulin than control muscles, but did not respond to insulin. In females, soleus deoxyglucose uptake measured in the absence of hormone was similar in Glut 4-null mice and in control mice. This uptake was stimulated twofold in Glut 4-null mice and threefold in control mice. Basal glycogen synthesis was increased by 4- and 2.2-fold in male and female null mice, respectively, compared to controls, and insulin had no or small (20% stimulation over basal) effect. These results indicate that while EDL muscles behaved as expected, soleus muscles were able to take up a large amount of glucose in the absence (males) or the presence of insulin (females). Whether this is due to a change in Glut 1 intrinsic activity or targeting and/or to the appearance of another glucose transporter remains to be determined.

A no-short scalar hair theorem for rotating Kerr black holes

NASA Astrophysics Data System (ADS)

Hod, Shahar

2016-06-01

If a black hole has hair, how short can this hair be? A partial answer to this intriguing question was recently provided by the ‘no-short hair’ theorem which asserts that the external fields of a spherically symmetric electrically neutral hairy black-hole configuration must extend beyond the null circular geodesic which characterizes the corresponding black-hole spacetime. One naturally wonders whether the no-short hair inequality {r}{hair}\\gt {r}{null} is a generic property of all electrically neutral hairy black-hole spacetimes. In this paper we provide evidence that the answer to this interesting question may be positive. In particular, we prove that the recently discovered cloudy Kerr black-hole spacetimes—non-spherically symmetric non-static black holes which support linearized massive scalar fields in their exterior regions—also respect this no-short hair lower bound. Specifically, we analytically derive the lower bound {r}{field}/{r}+\\gt {r}+/{r}- on the effective lengths of the external bound-state massive scalar clouds (here {r}{field} is the peak location of the stationary bound-state scalar fields and r ± are the horizon radii of the black hole). Remarkably, this lower bound is universal in the sense that it is independent of the physical parameters (proper mass and angular harmonic indices) of the exterior scalar fields. Our results suggest that the lower bound {r}{hair}\\gt {r}{null} may be a general property of asymptotically flat electrically neutral hairy black-hole configurations.

A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection.

PubMed

Pollin, Toni I; Damcott, Coleen M; Shen, Haiqing; Ott, Sandra H; Shelton, John; Horenstein, Richard B; Post, Wendy; McLenithan, John C; Bielak, Lawrence F; Peyser, Patricia A; Mitchell, Braxton D; Miller, Michael; O'Connell, Jeffrey R; Shuldiner, Alan R

2008-12-12

Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.

Approaches to highly parameterized inversion: Pilot-point theory, guidelines, and research directions

USGS Publications Warehouse

Doherty, John E.; Fienen, Michael N.; Hunt, Randall J.

2011-01-01

Pilot points have been used in geophysics and hydrogeology for at least 30 years as a means to bridge the gap between estimating a parameter value in every cell of a model and subdividing models into a small number of homogeneous zones. Pilot points serve as surrogate parameters at which values are estimated in the inverse-modeling process, and their values are interpolated onto the modeling domain in such a way that heterogeneity can be represented at a much lower computational cost than trying to estimate parameters in every cell of a model. Although the use of pilot points is increasingly common, there are few works documenting the mathematical implications of their use and even fewer sources of guidelines for their implementation in hydrogeologic modeling studies. This report describes the mathematics of pilot-point use, provides guidelines for their use in the parameter-estimation software suite (PEST), and outlines several research directions. Two key attributes for pilot-point definitions are highlighted. First, the difference between the information contained in the every-cell parameter field and the surrogate parameter field created using pilot points should be in the realm of parameters which are not informed by the observed data (the null space). Second, the interpolation scheme for projecting pilot-point values onto model cells ideally should be orthogonal. These attributes are informed by the mathematics and have important ramifications for both the guidelines and suggestions for future research.

"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.

Event and Apparent Horizon Finders for 3 + 1 Numerical Relativity.

PubMed

Thornburg, Jonathan

2007-01-01

Event and apparent horizons are key diagnostics for the presence and properties of black holes. In this article I review numerical algorithms and codes for finding event and apparent horizons in numerically-computed spacetimes, focusing on calculations done using the 3 + 1 ADM formalism. The event horizon of an asymptotically-flat spacetime is the boundary between those events from which a future-pointing null geodesic can reach future null infinity and those events from which no such geodesic exists. The event horizon is a (continuous) null surface in spacetime. The event horizon is defined nonlocally in time : it is a global property of the entire spacetime and must be found in a separate post-processing phase after all (or at least the nonstationary part) of spacetime has been numerically computed. There are three basic algorithms for finding event horizons, based on integrating null geodesics forwards in time, integrating null geodesics backwards in time, and integrating null surfaces backwards in time. The last of these is generally the most efficient and accurate. In contrast to an event horizon, an apparent horizon is defined locally in time in a spacelike slice and depends only on data in that slice, so it can be (and usually is) found during the numerical computation of a spacetime. A marginally outer trapped surface (MOTS) in a slice is a smooth closed 2-surface whose future-pointing outgoing null geodesics have zero expansion Θ. An apparent horizon is then defined as a MOTS not contained in any other MOTS. The MOTS condition is a nonlinear elliptic partial differential equation (PDE) for the surface shape, containing the ADM 3-metric, its spatial derivatives, and the extrinsic curvature as coefficients. Most "apparent horizon" finders actually find MOTSs. There are a large number of apparent horizon finding algorithms, with differing trade-offs between speed, robustness, accuracy, and ease of programming. In axisymmetry, shooting algorithms work well and are fairly easy to program. In slices with no continuous symmetries, spectral integral-iteration algorithms and elliptic-PDE algorithms are fast and accurate, but require good initial guesses to converge. In many cases, Schnetter's "pretracking" algorithm can greatly improve an elliptic-PDE algorithm's robustness. Flow algorithms are generally quite slow but can be very robust in their convergence. Minimization methods are slow and relatively inaccurate in the context of a finite differencing simulation, but in a spectral code they can be relatively faster and more robust.

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

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

Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie

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

The appearance and propagation of filaments in the private flux region in Mega Amp Spherical Tokamak

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

Harrison, J. R.; Fishpool, G. M.; Thornton, A. J.

2015-09-15

The transport of particles via intermittent filamentary structures in the private flux region (PFR) of plasmas in the MAST tokamak has been investigated using a fast framing camera recording visible light emission from the volume of the lower divertor, as well as Langmuir probes and IR thermography monitoring particle and power fluxes to plasma-facing surfaces in the divertor. The visible camera data suggest that, in the divertor volume, fluctuations in light emission above the X-point are strongest in the scrape-off layer (SOL). Conversely, in the region below the X-point, it is found that these fluctuations are strongest in the PFRmore » of the inner divertor leg. Detailed analysis of the appearance of these filaments in the camera data suggests that they are approximately circular, around 1–2 cm in diameter, but appear more elongated near the divertor target. The most probable toroidal quasi-mode number is between 2 and 3. These filaments eject plasma deeper into the private flux region, sometimes by the production of secondary filaments, moving at a speed of 0.5–1.0 km/s. Probe measurements at the inner divertor target suggest that the fluctuations in the particle flux to the inner target are strongest in the private flux region, and that the amplitude and distribution of these fluctuations are insensitive to the electron density of the core plasma, auxiliary heating and whether the plasma is single-null or double-null. It is found that the e-folding width of the time-average particle flux in the PFR decreases with increasing plasma current, but the fluctuations appear to be unaffected. At the outer divertor target, the fluctuations in particle and power fluxes are strongest in the SOL.« less

Quasi-static three-dimensional magnetic field evolution in solar active region NOAA 11166 associated with an X1.5 flare

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

Vemareddy, P.; Wiegelmann, T., E-mail: vema@prl.res.in, E-mail: wiegelmann@mps.mpg.de

We study the quasi-static evolution of coronal magnetic fields constructed from the non-linear force-free field (NLFFF) approximation aiming to understand the relation between the magnetic field topology and ribbon emission during an X1.5 flare in active region (AR) NOAA 11166. The flare with a quasi-elliptical and two remote ribbons occurred on 2011 March 9 at 23:13 UT over a positive flux region surrounded by negative flux at the center of the bipolar AR. Our analysis of the coronal magnetic structure with potential and NLFFF solutions unveiled the existence of a single magnetic null point associated with a fan-spine topology andmore » is co-spatial with the hard X-ray source. The footpoints of the fan separatrix surface agree with the inner edge of the quasi-elliptical ribbon and the outer spine is linked to one of the remote ribbons. During the evolution, the slow footpoint motions stressed the field lines along the polarity inversion line and caused electric current layers in the corona around the fan separatrix surface. These current layers trigger magnetic reconnection as a consequence of dissipating currents, which are visible as cusp-shaped structures at lower heights. The reconnection process reorganized the magnetic field topology whose signatures are observed at the separatrices/quasi-separatrix layer structure in both the photosphere and the corona during the pre-to-post flare evolution. In agreement with previous numerical studies, our results suggest that the line-tied footpoint motions perturb the fan-spine system and cause null point reconnection, which eventually causes the flare emission at the footpoints of the field lines.« less

Manufacturing of the 1070mm F/1.5 ellipsoid mirror

NASA Astrophysics Data System (ADS)

Guo, Peiji; Yu, Jingchi; Zhang, Yaoming; Qiu, Gufeng

2009-05-01

The manufacturing procedure of a φ1070mm in diameter F/1.5 ellipsoid mirror is introduced in detail. For testing the rough-ground surface, guiding shaping and fine grinding, a three dimension X-θ-Z profilometer is developed, the instrument measures surface profiles with 1μm accuracy and the biggest mirror being tested is φ1200mm in diameter. During polishing and fine figuring, we chose null test by null corrector with point source at infinity, the designed null corrector includes two piece of lenses and the designed residual wave front aberration is less than 0.008λ(λ=0.6328μm)PV. For avoiding the influence of gravity deformation during polishing and testing, a kind of support system with multipoint unequal support force is developed by applying FEA-based optimization. The mirror was finally figured to the shape accuracy of 0.016λRMS.

Revisiting self-regulatory techniques to promote physical activity in older adults: null-findings from a randomised controlled trial.

PubMed

Warner, Lisa M; Wolff, Julia K; Ziegelmann, Jochen P; Schwarzer, Ralf; Wurm, Susanne

2016-10-01

A randomised controlled trial (RCT) was conducted to evaluate a three-hour face-to-face physical activity (PA) intervention in community-dwelling older German adults with four groups: The intervention group (IG) received behaviour change techniques (BCTs) based on the health action process approach plus a views-on-ageing component to increase PA. The second intervention group 'planning' (IGpl) contained the same BCTs, only substituted the views-on-ageing component against an additional planning task. An active control group received the same BCTs, however, targeting volunteering instead of PA. A passive control group (PCG) received no intervention. The RCT comprised 5 time-points over 14 months in N = 310 participants aged 64+. Self-reported as well as accelerometer-assessed PA. Neither PA measure increased in the IG as compared to the other groups at any point in time. Bayes analyses supported these null-effects. A possible explanation for this null-finding in line with a recent meta-analysis is that some self-regulatory BCTs may be ineffective or even negatively associated with PA in interventions for older adults as they are assumed to be less acceptable for older adults. This interpretation was supported by observed reluctance to participate in self-regulatory BCTs in the current study.

Where Else Is Null the Gravitational Field between Two Massive Spheres?

ERIC Educational Resources Information Center

Lima, F. M. S.

2009-01-01

To find the point between two massive spherical bodies at which their gravitational fields cancel is an apparently simple problem usually found in introductory physics textbooks. However, by noting that such a point does not exist when the distance between the spheres is small and one of the masses is much smaller than the other--e.g., between the…

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

Akers, Chris; Bousso, Raphael; Halpern, Illan F.

We prove that the boundary of the future of a surface K consists precisely of the points p that lie on a null geodesic orthogonal to K such that between K and p there are no points conjugate to K nor intersections with another such geodesic. Our theorem has applications to holographic screens and their associated light sheets and in particular enters the proof that holographic screens satisfy an area law.

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

BMS in cosmology

NASA Astrophysics Data System (ADS)

Kehagias, A.; Riotto, A.

2016-05-01

Symmetries play an interesting role in cosmology. They are useful in characterizing the cosmological perturbations generated during inflation and lead to consistency relations involving the soft limit of the statistical correlators of large-scale structure dark matter and galaxies overdensities. On the other hand, in observational cosmology the carriers of the information about these large-scale statistical distributions are light rays traveling on null geodesics. Motivated by this simple consideration, we study the structure of null infinity and the associated BMS symmetry in a cosmological setting. For decelerating Friedmann-Robertson-Walker backgrounds, for which future null infinity exists, we find that the BMS transformations which leaves the asymptotic metric invariant to leading order. Contrary to the asymptotic flat case, the BMS transformations in cosmology generate Goldstone modes corresponding to scalar, vector and tensor degrees of freedom which may exist at null infinity and perturb the asymptotic data. Therefore, BMS transformations generate physically inequivalent vacua as they populate the universe at null infinity with these physical degrees of freedom. We also discuss the gravitational memory effect when cosmological expansion is taken into account. In this case, there are extra contribution to the gravitational memory due to the tail of the retarded Green functions which are supported not only on the light-cone, but also in its interior. The gravitational memory effect can be understood also from an asymptotic point of view as a transition among cosmological BMS-related vacua.

Two-sample binary phase 2 trials with low type I error and low sample size.

PubMed

Litwin, Samuel; Basickes, Stanley; Ross, Eric A

2017-04-30

We address design of two-stage clinical trials comparing experimental and control patients. Our end point is success or failure, however measured, with null hypothesis that the chance of success in both arms is p 0 and alternative that it is p 0 among controls and p 1  > p 0 among experimental patients. Standard rules will have the null hypothesis rejected when the number of successes in the (E)xperimental arm, E, sufficiently exceeds C, that among (C)ontrols. Here, we combine one-sample rejection decision rules, E⩾m, with two-sample rules of the form E - C > r to achieve two-sample tests with low sample number and low type I error. We find designs with sample numbers not far from the minimum possible using standard two-sample rules, but with type I error of 5% rather than 15% or 20% associated with them, and of equal power. This level of type I error is achieved locally, near the stated null, and increases to 15% or 20% when the null is significantly higher than specified. We increase the attractiveness of these designs to patients by using 2:1 randomization. Examples of the application of this new design covering both high and low success rates under the null hypothesis are provided. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

BMS in cosmology

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

Kehagias, A.; Riotto, A.; Center for Astroparticle Physics

Symmetries play an interesting role in cosmology. They are useful in characterizing the cosmological perturbations generated during inflation and lead to consistency relations involving the soft limit of the statistical correlators of large-scale structure dark matter and galaxies overdensities. On the other hand, in observational cosmology the carriers of the information about these large-scale statistical distributions are light rays traveling on null geodesics. Motivated by this simple consideration, we study the structure of null infinity and the associated BMS symmetry in a cosmological setting. For decelerating Friedmann-Robertson-Walker backgrounds, for which future null infinity exists, we find that the BMS transformationsmore » which leaves the asymptotic metric invariant to leading order. Contrary to the asymptotic flat case, the BMS transformations in cosmology generate Goldstone modes corresponding to scalar, vector and tensor degrees of freedom which may exist at null infinity and perturb the asymptotic data. Therefore, BMS transformations generate physically inequivalent vacua as they populate the universe at null infinity with these physical degrees of freedom. We also discuss the gravitational memory effect when cosmological expansion is taken into account. In this case, there are extra contribution to the gravitational memory due to the tail of the retarded Green functions which are supported not only on the light-cone, but also in its interior. The gravitational memory effect can be understood also from an asymptotic point of view as a transition among cosmological BMS-related vacua.« less

Social science. Publication bias in the social sciences: unlocking the file drawer.

PubMed

Franco, Annie; Malhotra, Neil; Simonovits, Gabor

2014-09-19

We studied publication bias in the social sciences by analyzing a known population of conducted studies--221 in total--in which there is a full accounting of what is published and unpublished. We leveraged Time-sharing Experiments in the Social Sciences (TESS), a National Science Foundation-sponsored program in which researchers propose survey-based experiments to be run on representative samples of American adults. Because TESS proposals undergo rigorous peer review, the studies in the sample all exceed a substantial quality threshold. Strong results are 40 percentage points more likely to be published than are null results and 60 percentage points more likely to be written up. We provide direct evidence of publication bias and identify the stage of research production at which publication bias occurs: Authors do not write up and submit null findings. Copyright © 2014, American Association for the Advancement of Science.

Solar Coronal Loop Dynamics Near the Null Point Above Active Region NOAA 2666

NASA Astrophysics Data System (ADS)

Filippov, B.

2018-06-01

We analyse observations of a saddle-like structure in the corona above the western limb of the Sun on 2017 July 18. The structure was clearly outlined by coronal loops with typical coronal temperature no more than 1 MK. The dynamics of loops showed convergence towards the centre of the saddle in the vertical direction and divergence in the horizontal direction. The event is a clear example of smooth coronal magnetic field reconnection. No heating manifestations in the reconnection region or magnetically connected areas were observed. Potential magnetic field calculations, which use as the boundary condition the SDO/HMI magnetogram taken on July 14, showed the presence of a null point at the height of 122 arcsec above the photosphere just at the centre of the saddle structure. The shape of field lines fits the fan-spine magnetic configuration above NOAA 2666.

Slow-Mode MHD Wave Penetration into a Coronal Null Point due to the Mode Transmission

NASA Astrophysics Data System (ADS)

Afanasyev, Andrey N.; Uralov, Arkadiy M.

2016-11-01

Recent observations of magnetohydrodynamic oscillations and waves in solar active regions revealed their close link to quasi-periodic pulsations in flaring light curves. The nature of that link has not yet been understood in detail. In our analytical modelling we investigate propagation of slow magnetoacoustic waves in a solar active region, taking into account wave refraction and transmission of the slow magnetoacoustic mode into the fast one. The wave propagation is analysed in the geometrical acoustics approximation. Special attention is paid to the penetration of waves in the vicinity of a magnetic null point. The modelling has shown that the interaction of slow magnetoacoustic waves with the magnetic reconnection site is possible due to the mode transmission at the equipartition level where the sound speed is equal to the Alfvén speed. The efficiency of the transmission is also calculated.

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

PubMed

Lukong, Kiven E; Richard, Stéphane

2008-06-03

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

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

PubMed

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

2017-08-01

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

Nod-Like Receptor Protein-3 Inflammasome Plays an Important Role during Early Stages of Wound Healing

PubMed Central

Weinheimer-Haus, Eileen M.; Mirza, Rita E.; Koh, Timothy J.

2015-01-01

The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing. PMID:25793779

Observation of a 3D Magnetic Null Point

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

Romano, P.; Falco, M.; Guglielmino, S. L.

2017-03-10

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

Existence and stability of circular orbits in static and axisymmetric spacetimes

NASA Astrophysics Data System (ADS)

Jia, Junji; Pang, Xiankai; Yang, Nan

2018-04-01

The existence and stability of timelike and null circular orbits (COs) in the equatorial plane of general static and axisymmetric (SAS) spacetime are investigated in this work. Using the fixed point approach, we first obtained a necessary and sufficient condition for the non-existence of timelike COs. It is then proven that there will always exist timelike COs at large ρ in an asymptotically flat SAS spacetime with a positive ADM mass and moreover, these timelike COs are stable. Some other sufficient conditions on the stability of timelike COs are also solved. We then found the necessary and sufficient condition on the existence of null COs. It is generally shown that the existence of timelike COs in SAS spacetime does not imply the existence of null COs, and vice-versa, regardless whether the spacetime is asymptotically flat or the ADM mass is positive or not. These results are then used to show the existence of timelike COs and their stability in an SAS Einstein-Yang-Mills-Dilaton spacetimes whose metric is not completely known. We also used the theorems to deduce the existence of timelike and null COs in some known SAS spacetimes.

DETECTING UNSPECIFIED STRUCTURE IN LOW-COUNT IMAGES

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

Stein, Nathan M.; Dyk, David A. van; Kashyap, Vinay L.

Unexpected structure in images of astronomical sources often presents itself upon visual inspection of the image, but such apparent structure may either correspond to true features in the source or be due to noise in the data. This paper presents a method for testing whether inferred structure in an image with Poisson noise represents a significant departure from a baseline (null) model of the image. To infer image structure, we conduct a Bayesian analysis of a full model that uses a multiscale component to allow flexible departures from the posited null model. As a test statistic, we use a tailmore » probability of the posterior distribution under the full model. This choice of test statistic allows us to estimate a computationally efficient upper bound on a p-value that enables us to draw strong conclusions even when there are limited computational resources that can be devoted to simulations under the null model. We demonstrate the statistical performance of our method on simulated images. Applying our method to an X-ray image of the quasar 0730+257, we find significant evidence against the null model of a single point source and uniform background, lending support to the claim of an X-ray jet.« less

How to talk about protein‐level false discovery rates in shotgun proteomics

PubMed Central

The, Matthew; Tasnim, Ayesha

2016-01-01

A frequently sought output from a shotgun proteomics experiment is a list of proteins that we believe to have been present in the analyzed sample before proteolytic digestion. The standard technique to control for errors in such lists is to enforce a preset threshold for the false discovery rate (FDR). Many consider protein‐level FDRs a difficult and vague concept, as the measurement entities, spectra, are manifestations of peptides and not proteins. Here, we argue that this confusion is unnecessary and provide a framework on how to think about protein‐level FDRs, starting from its basic principle: the null hypothesis. Specifically, we point out that two competing null hypotheses are used concurrently in today's protein inference methods, which has gone unnoticed by many. Using simulations of a shotgun proteomics experiment, we show how confusing one null hypothesis for the other can lead to serious discrepancies in the FDR. Furthermore, we demonstrate how the same simulations can be used to verify FDR estimates of protein inference methods. In particular, we show that, for a simple protein inference method, decoy models can be used to accurately estimate protein‐level FDRs for both competing null hypotheses. PMID:27503675

Optical Properties of Blow-Off Particulates.

DTIC Science & Technology

1984-02-29

examination of the SEM data in Sec- tion 3, for the particulates vary greatly in size, structure and melting points . Table 4. Refractive indices of minerals...of the balance. With no dc field applied the particle oscillates about a point below the midplane of the balance. When a dc field is applied to offset...electric field near the null point (midplane) of the balance is given by V dc Edc,z x- (11) where C is a geometrical constant which takes into account the

Testing for a Debt-Threshold Effect on Output Growth.

PubMed

Lee, Sokbae; Park, Hyunmin; Seo, Myung Hwan; Shin, Youngki

2017-12-01

Using the Reinhart-Rogoff dataset, we find a debt threshold not around 90 per cent but around 30 per cent, above which the median real gross domestic product (GDP) growth falls abruptly. Our work is the first to formally test for threshold effects in the relationship between public debt and median real GDP growth. The null hypothesis of no threshold effect is rejected at the 5 per cent significance level for most cases. While we find no evidence of a threshold around 90 per cent, our findings from the post-war sample suggest that the debt threshold for economic growth may exist around a relatively small debt-to-GDP ratio of 30 per cent. Furthermore, countries with debt-to-GDP ratios above 30 per cent have GDP growth that is 1 percentage point lower at the median.

Testing for a Debt‐Threshold Effect on Output Growth†

PubMed Central

Lee, Sokbae; Park, Hyunmin; Seo, Myung Hwan; Shin, Youngki

2017-01-01

Abstract Using the Reinhart–Rogoff dataset, we find a debt threshold not around 90 per cent but around 30 per cent, above which the median real gross domestic product (GDP) growth falls abruptly. Our work is the first to formally test for threshold effects in the relationship between public debt and median real GDP growth. The null hypothesis of no threshold effect is rejected at the 5 per cent significance level for most cases. While we find no evidence of a threshold around 90 per cent, our findings from the post‐war sample suggest that the debt threshold for economic growth may exist around a relatively small debt‐to‐GDP ratio of 30 per cent. Furthermore, countries with debt‐to‐GDP ratios above 30 per cent have GDP growth that is 1 percentage point lower at the median. PMID:29263562

3D Magnetic Reconnection

NASA Astrophysics Data System (ADS)

Parnell, Clare E.; Maclean, Rhona C.; Haynes, Andrew L.; Galsgaard, Klaus

2011-08-01

Magnetic reconnection is an important process that is prevalent in a wide range of astrophysical bodies. It is the mechanism that permits magnetic fields to relax to a lower energy state through the global restructuring of the magnetic field and is thus associated with a range of dynamic phenomena such as solar flares and CMEs. The characteristics of three-dimensional reconnection are reviewed revealing how much more diverse it is than reconnection in two dimensions. For instance, three-dimensional reconnection can occur both in the vicinity of null points, as well as in the absence of them. It occurs continuously and continually throughout a diffusion volume, as opposed to at a single point, as it does in two dimensions. This means that in three-dimensions field lines do not reconnect in pairs of lines making the visualisation and interpretation of three-dimensional reconnection difficult. By considering particular numerical 3D magnetohydrodynamic models of reconnection, we consider how magnetic reconnection can lead to complex magnetic topologies and current sheet formation. Indeed, it has been found that even simple interactions, such as the emergence of a flux tube, can naturally give rise to `turbulent-like' reconnection regions.

Thioredoxin-interacting protein (Txnip) is a critical regulator of hepatic glucose production.

PubMed

Chutkow, William A; Patwari, Parth; Yoshioka, Jun; Lee, Richard T

2008-01-25

Thioredoxin-interacting protein (Txnip) has been recently described as a possible link between cellular redox state and metabolism; Txnip binds thioredoxin and inhibits its disulfide reductase activity in vitro, while a naturally occurring strain of Txnip-deficient mice has hyperlipidemia, hypoglycemia, and ketosis exacerbated by fasting. We generated Txnip-null mice to investigate the role of Txnip in glucose homeostasis. Txnip-null mice were hypoglycemic, hypoinsulinemic, and had blunted glucose production following a glucagon challenge, consistent with a central liver glucose-handling defect. Glucose release from isolated Txnip-null hepatocytes was 2-fold lower than wild-type hepatocytes, whereas beta-hydroxybutyrate release was increased 2-fold, supporting an intrinsic defect in hepatocyte glucose metabolism. While hepatocyte-specific gene deletion of Txnip did not alter glucose clearance compared with littermate controls, Txnip expression in the liver was required for maintaining normal fasting glycemia and glucose production. In addition, hepatic overexpression of a Txnip transgene in wild-type mice resulted in elevated serum glucose levels and decreased ketone levels. Liver homogenates from Txnip-null mice had no significant differences in the glutathione oxidation state or in the amount of available thioredoxin. However, overexpression of wild-type Txnip in Txnip-null hepatocytes rescued cellular glucose production, whereas overexpression of a C247S mutant Txnip, which does not bind thioredoxin, had no effect. These data demonstrate that Txnip is required for normal glucose homeostasis in the liver. While available thioredoxin is not changed in Txnip-null mice, the effects of Txnip on glucose homeostasis are abolished by a single cysteine mutation that inhibits binding to thioredoxin.

Nrf2 activation prevents cadmium-induced acute liver injury

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

Wu, Kai C.; Liu, Jie J.; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu

2012-08-15

Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-nullmore » mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice were resistant to cadmium-induced liver injury. ► Cadmium increased ROS in hepatocytes isolated from Nrf2-null and wild-type mice. ► Mt-1 and Mt‐2 were induced over 200-fold in both Nrf2-null and Nrf2-enhanced mice. ► Gclc, Gpx2, and Srxn-1 were induced in Nrf2-enhanced mice, not in Nrf2-null mice.« less

Kinetic titration with differential thermometric determination of the end-point.

PubMed

Sajó, I

1968-06-01

A method has been described for the determination of concentrations below 10(-4)M by applying catalytic reactions and using thermometric end-point determination. A reference solution, identical with the sample solution except for catalyst, is titrated with catalyst solution until the rates of reaction become the same, as shown by a null deflection on a galvanometer connected via bridge circuits to two opposed thermistors placed in the solutions.

Boundary of the future of a surface

DOE PAGES

Akers, Chris; Bousso, Raphael; Halpern, Illan F.; ...

2018-01-12

We prove that the boundary of the future of a surface K consists precisely of the points p that lie on a null geodesic orthogonal to K such that between K and p there are no points conjugate to K nor intersections with another such geodesic. Our theorem has applications to holographic screens and their associated light sheets and in particular enters the proof that holographic screens satisfy an area law.

Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice

PubMed Central

Niewiadomski, Julie; Zhou, James Q.; Roman, Heather B.; Liu, Xiaojing; Hirschberger, Lawrence L.; Locasale, Jason W.; Stipanuk, Martha H.

2016-01-01

To gain further insights into the effect of elevated cysteine levels on energy metabolism and the possible mechanisms by which cysteine may have these effects, we conducted studies in cysteine dioxygenase (Cdo1)–null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression holds in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggested impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2S production and impairments in energy metabolism suggest that H2S signaling could be involved. PMID:26995761

Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice.

PubMed

Niewiadomski, Julie; Zhou, James Q; Roman, Heather B; Liu, Xiaojing; Hirschberger, Lawrence L; Locasale, Jason W; Stipanuk, Martha H

2016-01-01

To gain further insights into the effects of elevated cysteine levels on energy metabolism and the possible mechanisms underlying these effects, we conducted studies in cysteine dioxygenase (Cdo1)-null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression are also seen in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggests impaired mitochondrial β-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2 S production and impairments in energy metabolism suggest that H2 S signaling could be involved. © 2016 New York Academy of Sciences.

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

PubMed

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

2016-10-01

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

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.

Minimal Phenotype of Mice Homozygous for a Null Mutation in the Forkhead/Winged Helix Gene, Mf2

PubMed Central

Kume, Tsutomu; Deng, Keyu; Hogan, Brigid L. M.

2000-01-01

Mf2 (mesoderm/mesenchyme forkhead 2) encodes a forkhead/winged helix transcription factor expressed in numerous tissues of the mouse embryo, including paraxial mesoderm, somites, branchial arches, vibrissae, developing central nervous system, and developing kidney. We have generated mice homozygous for a null mutation in the Mf2 gene (Mf2lacZ) to examine its role during embryonic development. The lacZ allele also allows monitoring of Mf2 gene expression. Homozygous null mutants are viable and fertile and have no major developmental defects. Some mutants show renal abnormalities, including kidney hypoplasia and hydroureter, but the penetrance of this phenotype is only 40% or lower, depending on the genetic background. These data suggest that Mf2 can play a unique role in kidney development, but there is functional redundancy in this organ and other tissues with other forkhead/winged helix genes. PMID:10648626

Minimal phenotype of mice homozygous for a null mutation in the forkhead/winged helix gene, Mf2.

PubMed

Kume, T; Deng, K; Hogan, B L

2000-02-01

Mf2 (mesoderm/mesenchyme forkhead 2) encodes a forkhead/winged helix transcription factor expressed in numerous tissues of the mouse embryo, including paraxial mesoderm, somites, branchial arches, vibrissae, developing central nervous system, and developing kidney. We have generated mice homozygous for a null mutation in the Mf2 gene (Mf2(lacZ)) to examine its role during embryonic development. The lacZ allele also allows monitoring of Mf2 gene expression. Homozygous null mutants are viable and fertile and have no major developmental defects. Some mutants show renal abnormalities, including kidney hypoplasia and hydroureter, but the penetrance of this phenotype is only 40% or lower, depending on the genetic background. These data suggest that Mf2 can play a unique role in kidney development, but there is functional redundancy in this organ and other tissues with other forkhead/winged helix genes.

Electromagnetic dissipation during asymmetric reconnection with a moderate guide field

NASA Astrophysics Data System (ADS)

Genestreti, Kevin; Burch, James; Cassak, Paul; Torbert, Roy; Phan, Tai; Ergun, Robert; Giles, Barbara; Russell, Chris; Wang, Shan; Akhavan-Tafti, Mojtaba; Varsani, Ali

2017-04-01

We calculate the work done on the plasma by the electromagnetic (EM) field, ⃗Jṡ⃗E', and analyze the related electron currents and electric fields, focusing on a single asymmetric guide field electron diffusion region (EDR) event observed by MMS on 8 December 2015. For this event, each of the four MMS spacecraft observed dissipation of EM energy at the in-plane magnetic null point, though large-scale generation/dissipation was observed inconsistently on the magnetospheric side of the boundary. The current at the null was carried by a beam-like population of magnetosheath electrons traveling anti-parallel to the guide field, whereas the current on the Earthward side of the boundary was carried by crescent-shaped electron distributions. We also analyze the terms in Ohm's law, finding a large residual electric field throughout the EDR, inertial and pressure divergence fields at the null, and pressure divergence fields at the magnetosphere-side EDR. Our analysis of the terms in Ohm's law suggests that the EDR had significant three-dimensional structure.

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

Evidence of 3-D Reconnection at Null Point from the Observations of Circular Flares and Homologous Jets

NASA Astrophysics Data System (ADS)

Wang, Haimin; Liu, C.

2012-05-01

In recent studies by Pariat, Antiochos and DeVore (2009, 2010), fan-separatrix topology and magnetic reconnection at the null-point were simulated and found to produce homologous jets. This motivates us to search for axisymmetric magnetic structure and associated flaring/jetting activity. Using high-resolution ( 0.15" per pixel) and high-cadence ( 15 s) H-alpha center/offband observations obtained from the recently digitized films of Big Bear Solar Observatory, we were able to identify five large circular flares with associated surges. All the events exhibit a central parasite magnetic field surrounded by opposite polarity, forming a circular polarity inversion line (PIL). Consequently, a compact flare kernel at the center is surrounded by a circular ribbon, and together with the upward ejecting dark surge, these seem to depict a dome-like magnetic structure. Very interestingly, (1) the circular ribbon brightens sequentially rather than simultaneously, (2) the central compact flare kernel shows obvious motion, and (3) a remote elongated, co-temporal flare ribbon at a region with the same polarity as the central parasite site is seen in the series of four homologous events on 1991 March 17 and 18. The remote ribbon is 120" away from the jet location. Moreover, magnetic reconnection across the circular PIL is evident from the magnetic flux cancellation. These rarely observed homologous surges with circular as well as central and remote flare ribbons provide valuable evidence concerning the dynamics of magnetic reconnection in a null-point topology. This study is dedicated to Professor Hal Zirin, the founder of Big Bear Solar Observatory, who passed away on January 3, 2012.

3D Solar Null Point Reconnection MHD Simulations

NASA Astrophysics Data System (ADS)

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

2013-06-01

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

Dynamics of charged particle motion in the vicinity of three dimensional magnetic null points: Energization and chaos

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

Gascoyne, Andrew, E-mail: a.d.gascoyne@sheffield.ac.uk

2015-03-15

Using a full orbit test particle approach, we analyse the motion of a single proton in the vicinity of magnetic null point configurations which are solutions to the kinematic, steady state, resistive magnetohydrodynamics equations. We consider two magnetic configurations, namely, the sheared and torsional spine reconnection regimes [E. R. Priest and D. I. Pontin, Phys. Plasmas 16, 122101 (2009); P. Wyper and R. Jain, Phys. Plasmas 17, 092902 (2010)]; each produce an associated electric field and thus the possibility of accelerating charged particles to high energy levels, i.e., > MeV, as observed in solar flares [R. P. Lin, Space Sci. Rev. 124,more » 233 (2006)]. The particle's energy gain is strongly dependent on the location of injection and is characterised by the angle of approach β, with optimum angle of approach β{sub opt} as the value of β which produces the maximum energy gain. We examine the topological features of each regime and analyse the effect on the energy gain of the proton. We also calculate the complete Lyapunov spectrum for the considered dynamical systems in order to correctly quantify the chaotic nature of the particle orbits. We find that the sheared model is a good candidate for the acceleration of particles, and for increased shear, we expect a larger population to be accelerated to higher energy levels. In the strong electric field regime (E{sub 0}=1500 V/m), the torsional model produces chaotic particle orbits quantified by the calculation of multiple positive Lyapunov exponents in the spectrum, whereas the sheared model produces chaotic orbits only in the neighbourhood of the null point.« less

Interchange Slip-Running Reconnection and Sweeping SEP-Beams

NASA Technical Reports Server (NTRS)

Masson, S.; Aulanier, G.; Pariat, E.; Klein, K.-L.

2011-01-01

We present a new model to explain how particles, accelerated at a reconnection site that is not magnetically connected to the Earth, could eventually propagate along the well-connected open flux tube. Our model is based on the results of a low-beta resistive magnetohydrodynamics simulation of a three-dimensional line-tied and initially current-free bipole, that is embedded in a non-uniform open potential field. The topology of this configuration is that of an asymmetric coronal null-point, with a closed fan surface and an open outer spine. When driven by slow photospheric shearing motions, field lines, initially fully anchored below the fan dome, reconnect at the null point, and jump to the open magnetic domain. This is the standard interchange mode as sketched and calculated in 2D. The key result in 3D is that, reconnected open field lines located in the vicinity of the outer spine, keep reconnecting continuously, across an open quasi-separatrix layer, as previously identified for non-open-null-point reconnection. The apparent slipping motion of these field lines leads to form an extended narrow magnetic flux tube at high altitude. Because of the slip-running reconnection, we conjecture that if energetic particles would be travelling through, or be accelerated inside, the diffusion region, they would be successively injected along continuously reconnecting field lines that are connected farther and farther from the spine. At the scale of the full Sun, owing to the super-radial expansion of field lines below 3 solar radius, such energetic particles could easily be injected in field lines slipping over significant distances, and could eventually reach the distant flux tube that is well-connected to the Earth.

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)

The maintenance of elevated active chlorine levels in the Antarctic lower stratosphere through HCl null cycles

NASA Astrophysics Data System (ADS)

Müller, Rolf; Grooß, Jens-Uwe; Mannan Zafar, Abdul; Robrecht, Sabine; Lehmann, Ralph

2018-03-01

The Antarctic ozone hole arises from ozone destruction driven by elevated levels of ozone destroying (active) chlorine in Antarctic spring. These elevated levels of active chlorine have to be formed first and then maintained throughout the period of ozone destruction. It is a matter of debate how this maintenance of active chlorine is brought about in Antarctic spring, when the rate of formation of HCl (considered to be the main chlorine deactivation mechanism in Antarctica) is extremely high. Here we show that in the heart of the ozone hole (16-18 km or 85-55 hPa, in the core of the vortex), high levels of active chlorine are maintained by effective chemical cycles (referred to as HCl null cycles hereafter). In these cycles, the formation of HCl is balanced by immediate reactivation, i.e. by immediate reformation of active chlorine. Under these conditions, polar stratospheric clouds sequester HNO3 and thereby cause NO2 concentrations to be low. These HCl null cycles allow active chlorine levels to be maintained in the Antarctic lower stratosphere and thus rapid ozone destruction to occur. For the observed almost complete activation of stratospheric chlorine in the lower stratosphere, the heterogeneous reaction HCl + HOCl is essential; the production of HOCl occurs via HO2 + ClO, with the HO2 resulting from CH2O photolysis. These results are important for assessing the impact of changes of the future stratospheric composition on the recovery of the ozone hole. Our simulations indicate that, in the lower stratosphere, future increased methane concentrations will not lead to enhanced chlorine deactivation (through the reaction CH4 + Cl → HCl + CH3) and that extreme ozone destruction to levels below ≈ 0.1 ppm will occur until mid-century.

Null test fourier domain alignment technique for phase-shifting point diffraction interferometer

DOEpatents

Naulleau, Patrick; Goldberg, Kenneth Alan

2000-01-01

Alignment technique for calibrating a phase-shifting point diffraction interferometer involves three independent steps where the first two steps independently align the image points and pinholes in rotation and separation to a fixed reference coordinate system, e.g, CCD. Once the two sub-elements have been properly aligned to the reference in two parameters (separation and orientation), the third step is to align the two sub-element coordinate systems to each other in the two remaining parameters (x,y) using standard methods of locating the pinholes relative to some easy to find reference point.

Shear nulling after PSF Gaussianisation: Moment-based weak lensing measurements with subpercent noise bias

NASA Astrophysics Data System (ADS)

Herbonnet, Ricardo; Buddendiek, Axel; Kuijken, Konrad

2017-03-01

Context. Current optical imaging surveys for cosmology cover large areas of sky. Exploiting the statistical power of these surveys for weak lensing measurements requires shape measurement methods with subpercent systematic errors. Aims: We introduce a new weak lensing shear measurement algorithm, shear nulling after PSF Gaussianisation (SNAPG), designed to avoid the noise biases that affect most other methods. Methods: SNAPG operates on images that have been convolved with a kernel that renders the point spread function (PSF) a circular Gaussian, and uses weighted second moments of the sources. The response of such second moments to a shear of the pre-seeing galaxy image can be predicted analytically, allowing us to construct a shear nulling scheme that finds the shear parameters for which the observed galaxies are consistent with an unsheared, isotropically oriented population of sources. The inverse of this nulling shear is then an estimate of the gravitational lensing shear. Results: We identify the uncertainty of the estimated centre of each galaxy as the source of noise bias, and incorporate an approximate estimate of the centroid covariance into the scheme. We test the method on extensive suites of simulated galaxies of increasing complexity, and find that it is capable of shear measurements with multiplicative bias below 0.5 percent.

How to talk about protein-level false discovery rates in shotgun proteomics.

PubMed

The, Matthew; Tasnim, Ayesha; Käll, Lukas

2016-09-01

A frequently sought output from a shotgun proteomics experiment is a list of proteins that we believe to have been present in the analyzed sample before proteolytic digestion. The standard technique to control for errors in such lists is to enforce a preset threshold for the false discovery rate (FDR). Many consider protein-level FDRs a difficult and vague concept, as the measurement entities, spectra, are manifestations of peptides and not proteins. Here, we argue that this confusion is unnecessary and provide a framework on how to think about protein-level FDRs, starting from its basic principle: the null hypothesis. Specifically, we point out that two competing null hypotheses are used concurrently in today's protein inference methods, which has gone unnoticed by many. Using simulations of a shotgun proteomics experiment, we show how confusing one null hypothesis for the other can lead to serious discrepancies in the FDR. Furthermore, we demonstrate how the same simulations can be used to verify FDR estimates of protein inference methods. In particular, we show that, for a simple protein inference method, decoy models can be used to accurately estimate protein-level FDRs for both competing null hypotheses. © 2016 The Authors. Proteomics Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conical twist fields and null polygonal Wilson loops

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis.

PubMed

Wang, Lai; Tian, Fang; Arias, Ana; Yang, Mingjie; Sharifi, Behrooz G; Shah, Prediman K

2016-05-01

Apolipoprotein A-1 (Apo A-I) Milano, a naturally occurring Arg173to Cys mutant of Apo A-1, has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. We have shown the superior atheroprotective effects of Apo A-I Milano (Apo A-IM) gene compared to wild-type Apo A-I gene using transplantation of retrovirally transduced bone marrow in Apo A-I/Apo E null mice. In this study, we compared the effect of dietary lipid lowering versus lipid lowering plus Apo A-IM gene transfer using recombinant adeno-associated virus (rAAV) 8 as vectors on atherosclerosis regression in Apo A-I/Apo E null mice. All mice were fed a high-cholesterol diet from age of 6 weeks until week 20, and at 20 weeks, 10 mice were euthanized to determine the extent of atherosclerosis. After 20 weeks, an additional 20 mice were placed on either a low-cholesterol diet plus empty rAAV (n = 10) to serve as controls or low-cholesterol diet plus 1 single intravenous injection of 1.2 × 10(12)vector genomes of adeno-associated virus (AAV) 8 vectors expressing Apo A-IM (n = 10). At the 40 week time point, intravenous AAV8 Apo A-IM recipients showed a significant regression of atherosclerosis in the whole aorta (P< .01), aortic sinuses (P< .05), and brachiocephalic arteries (P< .05) compared to 20-week-old mice, whereas low-cholesterol diet plus empty vector control group showed no significant regression in lesion size. Immunostaining showed that compared to the 20-week-old mice, there was a significantly reduced macrophage content in the brachiocephalic (P< .05) and aortic sinus plaques (P< .05) of AAV8 Apo A-IM recipients. These data show that although dietary-mediated cholesterol lowering halts progression of atherosclerosis, it does not induce regression, whereas combination of low-cholesterol diet and AAV8 mediated Apo A-I Milano gene therapy induces rapid and significant regression of atherosclerosis in mice. These data provide support for the potential feasibility of this approach for atherosclerosis regression. © The Author(s) 2015.

Divertor heat flux mitigation in the National Spherical Torus Experimenta)

NASA Astrophysics Data System (ADS)

Soukhanovskii, V. A.; Maingi, R.; Gates, D. A.; Menard, J. E.; Paul, S. F.; Raman, R.; Roquemore, A. L.; Bell, M. G.; Bell, R. E.; Boedo, J. A.; Bush, C. E.; Kaita, R.; Kugel, H. W.; Leblanc, B. P.; Mueller, D.; NSTX Team

2009-02-01

Steady-state handling of divertor heat flux is a critical issue for both ITER and spherical torus-based devices with compact high power density divertors. Significant reduction of heat flux to the divertor plate has been achieved simultaneously with favorable core and pedestal confinement and stability properties in a highly shaped lower single null configuration in the National Spherical Torus Experiment (NSTX) [M. Ono et al., Nucl. Fusion 40, 557 2000] using high magnetic flux expansion at the divertor strike point and the radiative divertor technique. A partial detachment of the outer strike point was achieved with divertor deuterium injection leading to peak flux reduction from 4-6MWm-2to0.5-2MWm-2 in small-ELM 0.8-1.0MA, 4-6MW neutral beam injection-heated H-mode discharges. A self-consistent picture of the outer strike point partial detachment was evident from divertor heat flux profiles and recombination, particle flux and neutral pressure measurements. Analytic scrape-off layer parallel transport models were used for interpretation of NSTX detachment experiments. The modeling showed that the observed peak heat flux reduction and detachment are possible with high radiated power and momentum loss fractions, achievable with divertor gas injection, and nearly impossible to achieve with main electron density, divertor neutral density or recombination increases alone.

VizieR Online Data Catalog: GUViCS. Ultraviolet Source Catalogs (Voyer+, 2014)

NASA Astrophysics Data System (ADS)

Voyer, E. N.; Boselli, A.; Boissier, S.; Heinis, S.; Cortese, L.; Ferrarese, L.; Cote, P.; Cuillandre, J.-C.; Gwyn, S. D. J.; Peng, E. W.; Zhang, H.; Liu, C.

2014-07-01

These catalogs are based on GALEX NUV and FUV source detections in and behind the Virgo Cluster. The detections are split into catalogs of extended sources and point-like sources. The UV Virgo Cluster Extended Source catalog (UV_VES.fit) provides the deepest and most extensive UV photometric data of extended galaxies in Virgo to date. If certain data is not available for a given source then a null value is entered (e.g. -999, -99). UV point-like sources are matched with SDSS, NGVS, and NED and the relevant photometry and further data from these databases/catalogs are provided in this compilation of catalogs. The primary GUViCS UV Virgo Cluster Point-Like Source catalog is UV_VPS.fit. This catalog provides the most useful GALEX pipeline NUV and FUV photometric parameters, and categorizes sources as stars, Virgo members, and background sources, when possible. It also provides identifiers for optical matches in the SDSS and NED, and indicates if a match exists in the NGVS, only if GUViCS-optical matches are one-to-one. NED spectroscopic redshifts are also listed for GUViCS-NED one-to-one matches. If certain data is not available for a given source a null value is entered. Additionally, the catalog is useful for quick access to optical data on one-to-one GUViCS-SDSS matches.The only parameter available in the catalog for UV sources that have multiple SDSS matches is the total number of multiple matches, i.e. SDSSNUMMTCHS. Multiple GUViCS sources matched to the same SDSS source are also flagged given a total number of matches, SDSSNUMMTCHS, of one. All other fields for multiple matches are set to a null value of -99. In order to obtain full optical SDSS data for multiply matched UV sources in both scenarios, the user can cross-correlate the GUViCS ID of the sources of interest with the full GUViCS-SDSS matched catalog in GUV_SDSS.fit. The GUViCS-SDSS matched catalog, GUV_SDSS.fit, provides the most relevant SDSS data on all GUViCS-SDSS matches, including one-to-one matches and multiply matched sources. The catalog gives full SDSS identification information, complete SDSS photometric measurements in multiple aperture types, and complete redshift information (photometric and spectroscopic). It is ideal for large statistical studies of galaxy populations at multiple wavelengths in the background of the Virgo Cluster. The catalog can also be used as a starting point to study and search for previously unknown UV-bright point-like objects within the Virgo Cluster. If certain data is not available for a given source that field is given a null value. (6 data files).

The Impact Literacy Coaches Have on Mississippi's Lower-Performing Schools

ERIC Educational Resources Information Center

Trivelli-Bowen, Barbara

2017-01-01

The purpose of this study was to explore the impact literacy coaches had on Mississippi's lower-performing schools. To guide the study, the researcher developed four research questions and four null hypotheses. The population of this study was derived from a sample of Mississippi students in Grades K-3 who were administered the Early Literacy STAR…

Effects of sounds generated by a dental turbine and a stream on regional cerebral blood flow and cardiovascular responses.

PubMed

Mishima, Riho; Kudo, Takumu; Tsunetsugu, Yuko; Miyazaki, Yoshifumi; Yamamura, Chie; Yamada, Yoshiaki

2004-09-01

Effects of sound generated by a dental turbine and a small stream (murmur) and the effects of no sound (null, control) on heart rate, systolic and diastolic blood pressure, and hemodynamic changes (oxygenated, deoxygenated, and total hemoglobin concentrations) in the frontal cortex were measured in 18 young volunteers. Questionnaires completed by the volunteers were also evaluated. Near-infrared spectroscopy and the Finapres technique were employed to measure hemodynamic and vascular responses, respectively. The subjects assessed the murmur, null, and turbine sounds as "pleasant," "natural," and "unpleasant," respectively. Blood pressures changed in response to the murmur, null, and turbine sound stimuli as expected: lower than the control level, unchanged, and higher than the control level, respectively. Mean blood pressure values tended to increase gradually over the recording time even during the null sound stimulation, possibly because of the recording environment. Oxygenated hemoglobin concentrations decreased drastically in response to the dental turbine sound, while deoxygenated hemoglobin concentrations remained unchanged and thus total hemoglobin concentrations decreased (due to the decreased oxygenated hemoglobin concentrations). Hemodynamic responses to the murmuring sound and the null sound were slight or unchanged, respectively. Surprisingly, heart rate measurements remained fairly stable in response to the stimulatory noises. In conclusion, we demonstrate here that sound generated by a dental turbine may affect cerebral blood flow and metabolism as well as autonomic responses. Copyright 2004 The Society of the Nippon Dental University

Filaggrin haploinsufficiency is highly penetrant and is associated with increased severity of eczema: further delineation of the skin phenotype in a prospective epidemiological study of 792 school children

PubMed Central

Brown, SJ; Relton, CL; Liao, H; Zhao, Y; Sandilands, A; McLean, WHI; Cordell, HJ; Reynolds, NJ

2009-01-01

Background Null mutations within the filaggrin gene (FLG) cause ichthyosis vulgaris and are associated with atopic eczema. However, the dermatological features of filaggrin haploinsufficiency have not been clearly defined. Objectives This study investigated the genotype–phenotype association between detailed skin phenotype and FLG genotype data in a population-based cohort of children. Methods Children (n= 792) aged 7–9 years were examined by a dermatologist. Features of ichthyosis vulgaris, atopic eczema and xerosis were recorded and eczema severity graded using the Three Item Severity score. Each child was genotyped for the six most prevalent FLG null mutations (R501X, 2282del4, R2447X, S3247X, 3702delG, 3673delC). Fisher’s exact test was used to compare genotype frequencies in phenotype groups; logistic regression analysis was used to estimate odds ratios and penetrance of the FLG null genotype and a permutation test performed to investigate eczema severity in different genotype groups. Results Ten children in this cohort had ichthyosis vulgaris, of whom five had mild–moderate eczema. The penetrance of FLG null mutations with respect to flexural eczema was 55·6% in individuals with two mutations, 16·3% in individuals with one mutation and 14·2% in wild-type individuals. Summating skin features known to be associated with FLG null mutations (ichthyosis, keratosis pilaris, palmar hyperlinearity and flexural eczema) showed a penetrance of 100% in children with two FLG mutations, 87·8% in children with one FLG mutation and 46·5% in wild-type individuals (P< 0·0001, Fisher exact test). FLG null mutations were associated with more severe eczema (P= 0·0042) but the mean difference was only 1–2 points in severity score. Three distinct patterns of palmar hyperlinearity were observed and these are reported for the first time. Conclusions Filaggrin haploinsufficiency appears to be highly penetrant when all relevant skin features are included in the analysis. FLG null mutations are associated with more severe eczema, but the effect size is small in a population setting. PMID:19681860

Radiant Temperature Nulling Radiometer

NASA Technical Reports Server (NTRS)

Ryan, Robert (Inventor)

2003-01-01

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

Fine Guidance Sensing for Coronagraphic Observatories

NASA Technical Reports Server (NTRS)

Brugarolas, Paul; Alexander, James W.; Trauger, John T.; Moody, Dwight C.

2011-01-01

Three options have been developed for Fine Guidance Sensing (FGS) for coronagraphic observatories using a Fine Guidance Camera within a coronagraphic instrument. Coronagraphic observatories require very fine precision pointing in order to image faint objects at very small distances from a target star. The Fine Guidance Camera measures the direction to the target star. The first option, referred to as Spot, was to collect all of the light reflected from a coronagraph occulter onto a focal plane, producing an Airy-type point spread function (PSF). This would allow almost all of the starlight from the central star to be used for centroiding. The second approach, referred to as Punctured Disk, collects the light that bypasses a central obscuration, producing a PSF with a punctured central disk. The final approach, referred to as Lyot, collects light after passing through the occulter at the Lyot stop. The study includes generation of representative images for each option by the science team, followed by an engineering evaluation of a centroiding or a photometric algorithm for each option. After the alignment of the coronagraph to the fine guidance system, a "nulling" point on the FGS focal point is determined by calibration. This alignment is implemented by a fine alignment mechanism that is part of the fine guidance camera selection mirror. If the star images meet the modeling assumptions, and the star "centroid" can be driven to that nulling point, the contrast for the coronagraph will be maximized.

Singularities and the geometry of spacetime

NASA Astrophysics Data System (ADS)

Hawking, Stephen

2014-11-01

The aim of this essay is to investigate certain aspects of the geometry of the spacetime manifold in the General Theory of Relativity with particular reference to the occurrence of singularities in cosmological solutions and their relation with other global properties. Section 2 gives a brief outline of Riemannian geometry. In Section 3, the General Theory of Relativity is presented in the form of two postulates and two requirements which are common to it and to the Special Theory of Relativity, and a third requirement, the Einstein field equations, which distinguish it from the Special Theory. There does not seem to be any alternative set of field equations which would not have some undeseriable features. Some exact solutions are described. In Section 4, the physical significance of curvature is investigated using the deviation equation for timelike and null curves. The Riemann tensor is decomposed into the Ricci tensor which represents the gravitational effect at a point of matter at that point and the Welyl tensor which represents the effect at a point of gravitational radiation and matter at other points. The two tensors are related by the Bianchi identities which are presented in a form analogous to the Maxwell equations. Some lemmas are given for the occurrence of conjugate points on timelike and null geodesics and their relation with the variation of timelike and null curves is established. Section 5 is concerned with properties of causal relations between points of spacetime. It is shown that these could be used to determine physically the manifold structure of spacetime if the strong causality assumption held. The concepts of a null horizon and a partial Cauchy surface are introduced and are used to prove a number of lemmas relating to the existence of a timelike curve of maximum length between two sets. In Section 6, the definition of a singularity of spacetime is given in terms of geodesic incompleteness. The various energy assumptions needed to prove the occurrence of singularities are discussed and then a number of theorems are presented which prove the occurrence of singularities in most cosmological solutions. A procedure is given which could be used to describe and classify the singularites and their expected nature is discussed. Sections 2 and 3 are reviews of standard work. In Section 4, the deviation equation is standard but the matrix method used to analyse it is the author's own as is the decomposition given of the Bianchi identities (this was also obtained independently by Trümper). Variation of curves and conjugate points are standard in a positive-definite metric but this seems to be the first full account for timelike and null curves in a Lorentz metric. Except where otherwise indicated in the text, Sections 5 and 6 are the work of the author who, however, apologises if through ignorance or inadvertance he has failed to make acknowledgements where due. Some of this work has been described in [Hawking S.W. 1965b. Occurrence of singularities in open universes. Phys. Rev. Lett. 15: 689-690; Hawking S.W. and G.F.R. Ellis. 1965c. Singularities in homogeneous world models. Phys. Rev. Lett. 17: 246-247; Hawking S.W. 1966a. Singularities in the universe. Phys. Rev. Lett. 17: 444-445; Hawking S.W. 1966c. The occurrence of singularities in cosmology. Proc. Roy. Soc. Lond. A 294: 511-521]. Undoubtedly, the most important results are the theorems in Section 6 on the occurrence of singularities. These seem to imply either that the General Theory of Relativity breaks down or that there could be particles whose histories did not exist before (or after) a certain time. The author's own opinion is that the theory probably does break down, but only when quantum gravitational effects become important. This would not be expected to happen until the radius of curvature of spacetime became about 10-14 cm.

Design concepts using ring lasers for frequency stabilization

NASA Technical Reports Server (NTRS)

Mocker, H.

1967-01-01

Laser frequency stabilization methods are based on a frequency discriminant which generates an unambiguous deviation signal used for automatic stabilization. Closed-loop control stabilizes cavity length at a null point. Some systems have a stabilized ring laser using a piezoelectric dither and others use a Doppler gain tube.

On the Transition from Reconsolidation to Extinction of Contextual Fear Memories

ERIC Educational Resources Information Center

Cassini, Lindsey F.; Flavell, Charlotte R.; Amaral, Olavo B.; Lee, Jonathan L. C.

2017-01-01

Retrieval of an associative memory can lead to different phenomena. Brief reexposure sessions tend to trigger reconsolidation, whereas more extended ones trigger extinction. In appetitive and fear cued Pavlovian memories, an intermediate "null point" period has been observed where neither process seems to be engaged. Here we investigated…

Why Might Relative Fit Indices Differ between Estimators?

ERIC Educational Resources Information Center

Weng, Li-Jen; Cheng, Chung-Ping

1997-01-01

Relative fit indices using the null model as the reference point in computation may differ across estimation methods, as this article illustrates by comparing maximum likelihood, ordinary least squares, and generalized least squares estimation in structural equation modeling. The illustration uses a covariance matrix for six observed variables…

M3D-C1 simulations of the plasma response to RMPs in NSTX-U single-null and snowflake divertor configurations

DOE PAGES

Canal, G. P.; Ferraro, N. M.; Evans, T. E.; ...

2017-04-20

Here in this work, single- and two-fluid resistive magnetohydrodynamic calculations of the plasma response to n = 3 magnetic perturbations in single-null (SN) and snowflake (SF) divertor configurations are compared with those based on the vacuum approach. The calculations are performed using the code M3D-C 1 and are based on simulated NSTX-U plasmas. Significantly different plasma responses were found from these calculations, with the difference between the single- and two-fluid plasma responses being caused mainly by the different screening mechanism intrinsic to each of these models. Although different plasma responses were obtained from these different plasma models, no significant differencemore » between the SN and SF plasma responses were found. However, due to their different equilibrium properties, magnetic perturbations cause the SF configuration to develop additional and longer magnetic lobes in the null-point region than the SN, regardless of the plasma model used. The intersection of these longer and additional lobes with the divertor plates are expected to cause more striations in the particle and heat flux target profiles. In addition, the results indicate that the size of the magnetic lobes, in both single-null and snowflake configurations, are more sensitive to resonant magnetic perturbations than to non-resonant magnetic perturbations.« less

Averaged null energy condition from causality

DOE PAGES

Hartman, Thomas; Kundu, Sandipan; Tajdini, Amirhossein

2017-07-14

Unitary, Lorentz-invariant quantum field theories in at spacetime obey mi-crocausality: commutators vanish at spacelike separation. For interacting theories in more than two dimensions, we show that this implies that the averaged null energy,more » $$\\int$$duT uu, must be non-negative. This non-local operator appears in the operator product expansion of local operators in the lightcone limit, and therefore contributes to n-point functions. We derive a sum rule that isolates this contribution and is manifestly positive. The argument also applies to certain higher spin operators other than the stress tensor, generating an infinite family of new constraints of the form RduX uuu∙∙∙u ≥ 0. These lead to new inequalities for the coupling constants of spinning operators in conformal field theory, which include as special cases (but are generally stronger than) the existing constraints from the lightcone bootstrap, deep inelastic scattering, conformal collider methods, and relative entropy. We also comment on the relation to the recent derivation of the averaged null energy condition from relative entropy, and suggest a more general connection between causality and information-theoretic inequalities in QFT.« less

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

DOE PAGES

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

2016-09-08

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

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

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

PubMed

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

2012-08-06

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

Testing Small Variance Priors Using Prior-Posterior Predictive p Values.

PubMed

Hoijtink, Herbert; van de Schoot, Rens

2017-04-03

Muthén and Asparouhov (2012) propose to evaluate model fit in structural equation models based on approximate (using small variance priors) instead of exact equality of (combinations of) parameters to zero. This is an important development that adequately addresses Cohen's (1994) The Earth is Round (p < .05), which stresses that point null-hypotheses are so precise that small and irrelevant differences from the null-hypothesis may lead to their rejection. It is tempting to evaluate small variance priors using readily available approaches like the posterior predictive p value and the DIC. However, as will be shown, both are not suited for the evaluation of models based on small variance priors. In this article, a well behaving alternative, the prior-posterior predictive p value, will be introduced. It will be shown that it is consistent, the distributions under the null and alternative hypotheses will be elaborated, and it will be applied to testing whether the difference between 2 means and the size of a correlation are relevantly different from zero. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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.

Averaged null energy condition from causality

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

Hartman, Thomas; Kundu, Sandipan; Tajdini, Amirhossein

Unitary, Lorentz-invariant quantum field theories in at spacetime obey mi-crocausality: commutators vanish at spacelike separation. For interacting theories in more than two dimensions, we show that this implies that the averaged null energy,more » $$\\int$$duT uu, must be non-negative. This non-local operator appears in the operator product expansion of local operators in the lightcone limit, and therefore contributes to n-point functions. We derive a sum rule that isolates this contribution and is manifestly positive. The argument also applies to certain higher spin operators other than the stress tensor, generating an infinite family of new constraints of the form RduX uuu∙∙∙u ≥ 0. These lead to new inequalities for the coupling constants of spinning operators in conformal field theory, which include as special cases (but are generally stronger than) the existing constraints from the lightcone bootstrap, deep inelastic scattering, conformal collider methods, and relative entropy. We also comment on the relation to the recent derivation of the averaged null energy condition from relative entropy, and suggest a more general connection between causality and information-theoretic inequalities in QFT.« less

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

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

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

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

Analysis of nulling phase functions suitable to image plane coronagraphy

NASA Astrophysics Data System (ADS)

Hénault, François; Carlotti, Alexis; Vérinaud, Christophe

2016-07-01

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

Averaged null energy condition from causality

NASA Astrophysics Data System (ADS)

Hartman, Thomas; Kundu, Sandipan; Tajdini, Amirhossein

2017-07-01

Unitary, Lorentz-invariant quantum field theories in flat spacetime obey mi-crocausality: commutators vanish at spacelike separation. For interacting theories in more than two dimensions, we show that this implies that the averaged null energy, ∫ duT uu , must be non-negative. This non-local operator appears in the operator product expansion of local operators in the lightcone limit, and therefore contributes to n-point functions. We derive a sum rule that isolates this contribution and is manifestly positive. The argument also applies to certain higher spin operators other than the stress tensor, generating an infinite family of new constraints of the form ∫ duX uuu··· u ≥ 0. These lead to new inequalities for the coupling constants of spinning operators in conformal field theory, which include as special cases (but are generally stronger than) the existing constraints from the lightcone bootstrap, deep inelastic scattering, conformal collider methods, and relative entropy. We also comment on the relation to the recent derivation of the averaged null energy condition from relative entropy, and suggest a more general connection between causality and information-theoretic inequalities in QFT.

The ExtraSolar Planetary Imaging Coronagraph

NASA Astrophysics Data System (ADS)

Clampin, M.; Lyon, R.

2010-10-01

The Extrasolar Planetary Imaging Coronagraph (EPIC) is a 1.65-m telescope employing a visible nulling coronagraph (VNC) to deliver high-contrast images of extrasolar system architectures. EPIC will survey the architectures of exosolar systems, and investigate the physical nature of planets in these solar systems. EPIC will employ a Visible Nulling Coronagraph (VNC), featuring an inner working angle of ≤2λ/D, and offers the ideal balance between performance and feasibility of implementation, while not sacrificing science return. The VNC does not demand unrealistic thermal stability from its telescope optics, achieving its primary mirror surface figure requires no new technology, and pointing stability is within state of the art. The EPIC mission will be launched into a drift-away orbit with a five-year mission lifetime.

Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells

NASA Technical Reports Server (NTRS)

Smilenov, L. B.; Brenner, D. J.; Hall, E. J.

2001-01-01

Subpopulations that are genetically predisposed to radiation-induced cancer could have significant public health consequences. Individuals homozygous for null mutations at the ataxia telangiectasia gene are indeed highly radiosensitive, but their numbers are very small. Ataxia Telangiectasia heterozygotes (1-2% of the population) have been associated with somewhat increased radiosensitivity for some end points, but none directly related to carcinogenesis. Here, intralitter comparisons between wild-type mouse embryo fibroblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitive to radiation oncogenesis than their normal, litter-matched, counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally-significant radiosensitive human subpopulation.

On the null trajectories in conformal Weyl gravity

NASA Astrophysics Data System (ADS)

Villanueva, J. R.; Olivares, Marco

2013-06-01

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

Reduced alcohol consumption in mice lacking preprodynorphin.

PubMed Central

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

2007-01-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the κ-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 hours) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest thath this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability). PMID:17307643

Reduced alcohol consumption in mice lacking preprodynorphin.

PubMed

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

2006-10-01

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

Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion

PubMed Central

Tong, Xuemei; Coulombe, Pierre A.

2006-01-01

Mammalian hair follicles cycle between stages of rapid growth (anagen) and metabolic quiescence (telogen) throughout life. Transition from anagen to telogen involves an intermediate stage, catagen, consisting of a swift, apoptosis-driven involution of the lower half of the follicle. How catagen is coordinated, and spares the progenitor cells needed for anagen re-entry, is poorly understood. Keratin 17 (K17)-null mice develop alopecia in the first week post-birth, correlating with hair shaft fragility and untimely apoptosis in the hair bulb. Here we show that this abnormal apoptosis reflects premature entry into catagen. Of the proapoptotic challenges tested, K17-null skin keratinocytes in primary culture are selectively more sensitive to TNFα. K17 interacts with TNF receptor 1 (TNFR1)-associated death domain protein (TRADD), a death adaptor essential for TNFR1-dependent signal relay, suggesting a functional link between this keratin and TNFα signaling. The activity of NF-κB, a downstream target of TNFα, is increased in K17-null skin. We also find that TNFα is required for a timely anagen–catagen transition in mouse pelage follicles, and that its ablation partially rescues the hair cycling defect of K17-null mice. These findings identify K17 and TNFα as two novel and interdependent regulators of hair cycling. PMID:16702408

Analysis of a Spatial Point Pattern: Examining the Damage to Pavement and Pipes in Santa Clara Valley Resulting from the Loma Prieta Earthquake

USGS Publications Warehouse

Phelps, G.A.

2008-01-01

This report describes some simple spatial statistical methods to explore the relationships of scattered points to geologic or other features, represented by points, lines, or areas. It also describes statistical methods to search for linear trends and clustered patterns within the scattered point data. Scattered points are often contained within irregularly shaped study areas, necessitating the use of methods largely unexplored in the point pattern literature. The methods take advantage of the power of modern GIS toolkits to numerically approximate the null hypothesis of randomly located data within an irregular study area. Observed distributions can then be compared with the null distribution of a set of randomly located points. The methods are non-parametric and are applicable to irregularly shaped study areas. Patterns within the point data are examined by comparing the distribution of the orientation of the set of vectors defined by each pair of points within the data with the equivalent distribution for a random set of points within the study area. A simple model is proposed to describe linear or clustered structure within scattered data. A scattered data set of damage to pavement and pipes, recorded after the 1989 Loma Prieta earthquake, is used as an example to demonstrate the analytical techniques. The damage is found to be preferentially located nearer a set of mapped lineaments than randomly scattered damage, suggesting range-front faulting along the base of the Santa Cruz Mountains is related to both the earthquake damage and the mapped lineaments. The damage also exhibit two non-random patterns: a single cluster of damage centered in the town of Los Gatos, California, and a linear alignment of damage along the range front of the Santa Cruz Mountains, California. The linear alignment of damage is strongest between 45? and 50? northwest. This agrees well with the mean trend of the mapped lineaments, measured as 49? northwest.

The effect of AM noise on correlation phase-noise measurements.

PubMed

Rubiola, Enrico; Boudot, Rodolphe

2007-05-01

We analyze the phase-noise measurement methods in which correlation and averaging is used to reject the background noise of the instrument. All the known methods make use of a mixer, used either as a saturated-phase detector or as a linear-synchronous detector. Unifortunately, AM noise is taken in through the power-to-dc-offset conversion mechanism that results from the mixer asymmetry. The measurement of some mixers indicates that the unwanted amplitude-to-voltage gain is of the order of 5-50 mV, which is 12-35 dB lower than the phase-to-voltage gain of the mixer. In addition, the trick of setting the mixer at a sweet point--off the quadrature condition--where the sensitivity to AM nulls, works only with microwave mixers. The HF-VHF mixers do not have this sweet point. Moreover, we prove that if the AM noise comes from the oscillator under test, it cannot be rejected by correlation. At least not with the schemes currently used. An example shows that at some critical frequencies the unwanted effect of AM noise is of the same order-if not greater--than the phase noise. Thus, experimental mistakes are around the corner.

Process Optimization for Solid Extraction, Flavor Improvement and Fat Removal in the Production of Soymilk From Full Fat Soy Flakes

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

Prawiradjaja, Stanley

Traditionally soymilk has been made with whole soybeans; however, there are other alternative raw ingredients for making soymilk, such as soy flour or full-fat soy flakes. US markets prefer soymilk with little or no beany flavor. modifying the process or using lipoxygenase-free soybeans can be used to achieve this. Unlike the dairy industry, fat reduction in soymilk has been done through formula modification instead of by conventional fat removal (skimming). This project reports the process optimization for solids and protein extraction, flavor improvement and fat removal in the production of 5, 8 and 12 °Brix soymilk from full fat soymore » flakes and whole soybeans using the Takai soymilk machine. Proximate analyses, and color measurement were conducted in 5, 8 and 12 °Brix soymilk. Descriptive analyses with trained panelists (n = 9) were conducted using 8 and 12 °Brix lipoxygenase-free and high protein blend soy flake soymilks. Rehydration of soy flakes is necessary to prevent agglomeration during processing and increase extractability. As the rehydration temperature increases from 15 to 50 to 85 C, the hexanal concentration was reduced. Enzyme inactivation in soy flakes milk production (measured by hexanal levels) is similar to previous reports with whole soybeans milk production; however, shorter rehydration times can be achieved with soy flakes (5 to 10 minutes) compared to whole beans (8 to 12 hours). Optimum rehydration conditions for a 5, 8 and 12 °Brix soymilk are 50 C for 5 minutes, 85 C for 5 minutes and 85 C for 10 minutes, respectively. In the flavor improvement study of soymilk, the hexanal date showed differences between undeodorized HPSF in contrast to triple null soymilk and no differences between deodorized HPSF in contrast to deodorized triple null. The panelists could not differentiate between the beany, cereal, and painty flavors. However, the panelists responded that the overall aroma of deodorized 8 °Brix triple null and HPSF soymilk are lower than the undeodorized triple null and HPSF soymilk. The triple null soymilk was perceived to be more bitter than the HPSF soymilk by the sensory panel due to oxidation on the triple null soy flakes. This oxidation may produce other aroma that was not analyzed using the GC but noticed by the panelists. The sensory evaluation results did show that the deodorizer was able to reduce the soymilk aroma in HPSF soymilk so it would be similar to triple null soymilk at 8 °Brix level. Regardless of skimming method and solids levels, the fat from the whole soybean milk was removed less efficiently than soy flake milk (7 to 30% fat extraction in contrast to 50 to 80% fat extraction respectively). In soy flake milk, less fat was removed as the % solid increases regardless of the processing method. In whole soybean milk, the fat was removed less efficiently at lower solids level milk using the commercial dairy skimmer and more efficient at lower solids level using the centrifuge-decant method. Based on the Hunter L, a, b measurement, the color of the reduced fat soy flake milk yielded a darker, greener and less yellow colored milk than whole soymilk (α < 0.05), whereas no differences were noticed in reduced fat soybean milk (α < 0.05). Color comparison of whole and skim cow's milk showed the same the same trend as in the soymilk.« less

Vortex motion in doubly connected domains

NASA Astrophysics Data System (ADS)

Zannetti, L.; Gallizio, F.; Ottino, G. M.

The unsteady two-dimensional rotational flow past doubly connected domains is analytically addressed. By concentrating the vorticity in point vortices, the flow is modelled as a potential flow with point singularities. The dependence of the complex potential on time is defined according to the Kelvin theorem. The general case of non-null circulations around the solid bodies is discussed. Vortex shedding and time evolution of the circulation past a two-element airfoil and past a two-bladed Darrieus turbine are presented as physically coherent examples.

INTERACTION OF TWO FILAMENT CHANNELS OF DIFFERENT CHIRALITIES

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

Joshi, Navin Chandra; Magara, Tetsuya; Moon, Yong-Jae

2016-07-10

We present observations of the interactions between the two filament channels of different chiralities and associated dynamics that occurred during 2014 April 18–20. While two flux ropes of different helicity with parallel axial magnetic fields can only undergo a bounce interaction when they are brought together, the observations at first glance show that the heated plasma is moving from one filament channel to the other. The SDO /AIA 171 Å observations and the potential-field source-surface magnetic field extrapolation reveal the presence of a fan-spine magnetic configuration over the filament channels with a null point located above them. Three different eventsmore » of filament activations, partial eruptions, and associated filament channel interactions have been observed. The activation initiated in one filament channel seems to propagate along the neighboring filament channel. We believe that the activation and partial eruption of the filaments brings the field lines of flux ropes containing them closer to the null point and triggers the magnetic reconnection between them and the fan-spine magnetic configuration. As a result, the hot plasma moves along the outer spine line toward the remote point. Utilizing the present observations, for the first time we have discussed how two different-chirality filament channels can interact and show interrelation.« less

A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice

PubMed Central

Gerard-O'Riley, Rita L.; Acton, Dena; McQueen, Amie K.; Strobel, Isabel E.; Witcher, Phillip C.; Feng, Jian Q.; Econs, Michael J.

2017-01-01

Mutations in the dentin matrix protein 1 (DMP1) gene cause autosomal recessive hypophosphatemic rickets (ARHR). Hypophosphatemia in ARHR results from increased circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Similarly, elevated FGF23, caused by mutations in the PHEX gene, is responsible for the hypophosphatemia in X-linked hypophosphatemic rickets (XLH). Previously, we demonstrated that a Phex mutation in mice creates a lower set point for extracellular phosphate, where an increment in phosphorus further stimulates Fgf23 production to maintain low serum phosphorus levels. To test the presence of the similar set point defect in ARHR, we generated 4- and 12-week-old Dmp1/Galnt3 double knockout mice and controls, including Dmp1 knockout mice (a murine model of ARHR), Galnt3 knockout mice (a murine model of familial tumoral calcinosis), and phenotypically normal double heterozygous mice. Galnt3 knockout mice had increased proteolytic cleavage of Fgf23, leading to low circulating intact Fgf23 levels with consequent hyperphosphatemia. In contrast, Dmp1 knockout mice had little Fgf23 cleavage and increased femoral Fgf23 expression, resulting in hypophosphatemia and low femoral bone mineral density (BMD). However, introduction of the Galnt3 null allele to Dmp1 knockout mice resulted in a significant increase in serum phosphorus and normalization of BMD. This increased serum phosphorus was accompanied by markedly elevated Fgf23 expression and circulating Fgf23 levels, an attempt to reduce serum phosphorus in the face of improving phosphorus levels. These data indicate that a Dmp1 mutation creates a lower set point for extracellular phosphate and maintains it through the regulation of Fgf23 cleavage and expression. PMID:28005411

A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice.

PubMed

Ichikawa, Shoji; Gerard-O'Riley, Rita L; Acton, Dena; McQueen, Amie K; Strobel, Isabel E; Witcher, Phillip C; Feng, Jian Q; Econs, Michael J

2017-03-01

Mutations in the dentin matrix protein 1 (DMP1) gene cause autosomal recessive hypophosphatemic rickets (ARHR). Hypophosphatemia in ARHR results from increased circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Similarly, elevated FGF23, caused by mutations in the PHEX gene, is responsible for the hypophosphatemia in X-linked hypophosphatemic rickets (XLH). Previously, we demonstrated that a Phex mutation in mice creates a lower set point for extracellular phosphate, where an increment in phosphorus further stimulates Fgf23 production to maintain low serum phosphorus levels. To test the presence of the similar set point defect in ARHR, we generated 4- and 12-week-old Dmp1/Galnt3 double knockout mice and controls, including Dmp1 knockout mice (a murine model of ARHR), Galnt3 knockout mice (a murine model of familial tumoral calcinosis), and phenotypically normal double heterozygous mice. Galnt3 knockout mice had increased proteolytic cleavage of Fgf23, leading to low circulating intact Fgf23 levels with consequent hyperphosphatemia. In contrast, Dmp1 knockout mice had little Fgf23 cleavage and increased femoral Fgf23 expression, resulting in hypophosphatemia and low femoral bone mineral density (BMD). However, introduction of the Galnt3 null allele to Dmp1 knockout mice resulted in a significant increase in serum phosphorus and normalization of BMD. This increased serum phosphorus was accompanied by markedly elevated Fgf23 expression and circulating Fgf23 levels, an attempt to reduce serum phosphorus in the face of improving phosphorus levels. These data indicate that a Dmp1 mutation creates a lower set point for extracellular phosphate and maintains it through the regulation of Fgf23 cleavage and expression. Copyright © 2017 by the Endocrine Society.

Confidence Intervals for Effect Sizes: Applying Bootstrap Resampling

ERIC Educational Resources Information Center

Banjanovic, Erin S.; Osborne, Jason W.

2016-01-01

Confidence intervals for effect sizes (CIES) provide readers with an estimate of the strength of a reported statistic as well as the relative precision of the point estimate. These statistics offer more information and context than null hypothesis statistic testing. Although confidence intervals have been recommended by scholars for many years,…

Formation of a rotating jet during the filament eruption on 2013 April 10-11

NASA Astrophysics Data System (ADS)

Filippov, B.; Srivastava, A. K.; Dwivedi, B. N.; Masson, S.; Aulanier, G.; Joshi, N. C.; Uddin, W.

2015-07-01

We analyse multiwavelength and multiviewpoint observations of a helically twisted plasma jet formed during a confined filament eruption on 2013 April 10-11. Given a rather large-scale event with its high spatial and temporal resolution observations, it allows us to clearly understand some new physical details about the formation and triggering mechanism of twisting jet. We identify a pre-existing flux rope associated with a sinistral filament, which was observed several days before the event. The confined eruption of the filament within a null-point topology, also known as an Eiffel tower (or inverted-Y) magnetic field configuration results in the formation of a twisted jet after the magnetic reconnection near a null point. The sign of helicity in the jet is found to be the same as that of the sign of helicity in the filament. Untwisting motion of the reconnected magnetic field lines gives rise to the accelerating plasma along the jet axis. The event clearly shows the twist injection from the pre-eruptive magnetic field to the jet.

A Model for Solar Polar Jets

NASA Technical Reports Server (NTRS)

Pariat, E.; Antiochos, S. K.; DeVore, C. R.

2008-01-01

We propose a model for the jetting activity that is commonly observed in the Sun's corona, especially in the open-field regions of polar coronal holes. Magnetic reconnection is the process driving the jets and a relevant magnetic configuration is the well-known null point and fan separatrix topology. The primary challenge in explaining the observations is that reconnection must occur in a short-duration energetic burst rather than quasi-continuously as is implied by the observations of long-lived structures in coronal holes, such as polar plumes, for example. The key idea underlying our model for jets is that reconnection is forbidden for an axisymmetric null-point topology. Consequently, by imposing a twisting motion that maintains the axisymmetry, magnetic stress can be built up to large levels until an ideal instability breaks the symmetry and leads to an explosive release of energy via reconnection. Using 3D MHD simulations we demonstrate that this mechanism does produce jets with high speed and mass, driven by nonlinear Alfven waves. We discuss the implications of our results for observations of the solar corona.

Severe changes in colon epithelium in the Mecp2-null mouse model of Rett syndrome.

PubMed

Millar-Büchner, Pamela; Philp, Amber R; Gutierrez, Noemí; Villanueva, Sandra; Kerr, Bredford; Flores, Carlos A

2016-12-01

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice. Mecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples. First we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice. In summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in the Mecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease.

Habitat classification modeling with incomplete data: Pushing the habitat envelope

USGS Publications Warehouse

Zarnetske, P.L.; Edwards, T.C.; Moisen, Gretchen G.

2007-01-01

Habitat classification models (HCMs) are invaluable tools for species conservation, land-use planning, reserve design, and metapopulation assessments, particularly at broad spatial scales. However, species occurrence data are often lacking and typically limited to presence points at broad scales. This lack of absence data precludes the use of many statistical techniques for HCMs. One option is to generate pseudo-absence points so that the many available statistical modeling tools can be used. Traditional techniques generate pseudoabsence points at random across broadly defined species ranges, often failing to include biological knowledge concerning the species-habitat relationship. We incorporated biological knowledge of the species-habitat relationship into pseudo-absence points by creating habitat envelopes that constrain the region from which points were randomly selected. We define a habitat envelope as an ecological representation of a species, or species feature's (e.g., nest) observed distribution (i.e., realized niche) based on a single attribute, or the spatial intersection of multiple attributes. We created HCMs for Northern Goshawk (Accipiter gentilis atricapillus) nest habitat during the breeding season across Utah forests with extant nest presence points and ecologically based pseudo-absence points using logistic regression. Predictor variables were derived from 30-m USDA Landfire and 250-m Forest Inventory and Analysis (FIA) map products. These habitat-envelope-based models were then compared to null envelope models which use traditional practices for generating pseudo-absences. Models were assessed for fit and predictive capability using metrics such as kappa, thresholdindependent receiver operating characteristic (ROC) plots, adjusted deviance (Dadj2), and cross-validation, and were also assessed for ecological relevance. For all cases, habitat envelope-based models outperformed null envelope models and were more ecologically relevant, suggesting that incorporating biological knowledge into pseudo-absence point generation is a powerful tool for species habitat assessments. Furthermore, given some a priori knowledge of the species-habitat relationship, ecologically based pseudo-absence points can be applied to any species, ecosystem, data resolution, and spatial extent. ?? 2007 by the Ecological Society of America.

THE EFFECT OF RECONNECTION ON THE STRUCTURE OF THE SUN’S OPEN–CLOSED FLUX BOUNDARY

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

Pontin, D. I.; Wyper, P. F., E-mail: dpontin@maths.dundee.ac.uk, E-mail: peter.f.wyper@nasa.gov

2015-05-20

Global magnetic field extrapolations are now revealing the huge complexity of the Sun's corona, and in particular the structure of the boundary between open and closed magnetic flux. Moreover, recent developments indicate that magnetic reconnection in the corona likely occurs in highly fragmented current layers, and that this typically leads to a dramatic increase in the topological complexity beyond that of the equilibrium field. In this paper we use static models to investigate the consequences of reconnection at the open–closed flux boundary (“interchange reconnection”) in a fragmented current layer. We demonstrate that it leads to efficient mixing of magnetic fluxmore » (and therefore plasma) from open and closed field regions. This corresponds to an increase in the length and complexity of the open–closed boundary. Thus, whenever reconnection occurs at a null point or separator of this open–closed boundary, the associated separatrix arc of the so-called S-web in the high corona becomes not a single line but a band of finite thickness within which the open–closed boundary is highly structured. This has significant implications for the acceleration of the slow solar wind, for which the interaction of open and closed field is thought to be important, and may also explain the coronal origins of certain solar energetic particles. The topological structures examined contain magnetic null points, separatrices and separators, and include a model for a pseudo-streamer. The potential for understanding both the large scale morphology and fine structure observed in flare ribbons associated with coronal nulls is also discussed.« less

Radiation patterns of interfacial dipole antennas

NASA Technical Reports Server (NTRS)

Engheta, N.; Papas, C. H.; Elachi, C.

1982-01-01

The radiation pattern of an infinitesimal electric dipole is calculated for the case where the dipole is vertically located on the plane interface of two dielectric half spaces and for the case where the dipole is lying horizontally along the interface. For the vertical case, it is found that the radiation pattern has nulls at the interface and along the dipole axis. For the horizontal case, it is found that the pattern has a null at the interface; that the pattern in the upper half space, whose index of refraction is taken to be less than that of the lower half space, has a single lobe whose maximum is normal to the interface; and that in the lower half space, in the plane normal to the interface and containing the dipole, the pattern has three lobes, whereas in the plane normal to the interface and normally bisecting the dipole, the pattern has two maxima located symmetrically about a minimum. Interpretation of these results in terms of the Cerenkov effect is given.

A Novel Defensive Mechanism against Acetaminophen Toxicity in the Mouse Lateral Nasal Gland: Role of CYP2A5-Mediated Regulation of Testosterone Homeostasis and Salivary Androgen-Binding Protein Expression

PubMed Central

Zhou, Xin; Wei, Yuan; Xie, Fang; Laukaitis, Christina M.; Karn, Robert C.; Kluetzman, Kerri; Gu, Jun; Zhang, Qing-Yu; Roberts, Dean W.

2011-01-01

To identify novel factors or mechanisms that are important for the resistance of tissues to chemical toxicity, we have determined the mechanisms underlying the previously observed increases in resistance to acetaminophen (APAP) toxicity in the lateral nasal gland (LNG) of the male Cyp2g1-null/Cyp2a5-low mouse. Initial studies established that Cyp2a5-null mice, but not a newly generated strain of Cyp2g1-null mice, were resistant to APAP toxicity in the LNG; therefore, subsequent studies were focused on the Cyp2a5-null mice. Compared with the wild-type (WT) male mouse, the Cyp2a5-null male mouse had intact capability to metabolize APAP to reactive intermediates in the LNG, as well as unaltered circulating levels of APAP, APAP-GSH, APAP-glucuronide, and APAP-sulfate. However, it displayed reduced tissue levels of APAP and APAP-GSH and increased tissue levels of testosterone and salivary androgen-binding protein (ABP) in the LNG. Furthermore, we found that ABP was able to compete with GSH and cellular proteins for adduction with reactive metabolites of APAP in vitro. The amounts of APAP-ABP adducts formed in vivo were greater, whereas the amounts of APAP adducts formed with other cellular proteins were substantially lower, in the LNG of APAP-treated male Cyp2a5-null mice compared with the LNG of APAP-treated male WT mice. We propose that through its critical role in testosterone metabolism, CYP2A5 regulates 1) the bioavailability of APAP and APAP-GSH (presumably through modulation of the rates of xenobiotic excretion from the LNG) and 2) the expression of ABP, which can quench reactive APAP metabolites and thereby spare critical cellular proteins from inactivation. PMID:21252290

Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse

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

Siddens, Lisbeth K.; Superfund Research Center, Oregon State University, Corvallis, OR 97331; Bunde, Kristi L.

FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8 h post-initiation. A significant reduction in levels of Cyp 1a1,more » Nqo1 at 8 h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4 h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8 h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. - Highlights: • Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE. • Cyp1b1 expression impacts expression of other PAH metabolizing enzymes. • cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver • Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.« less

Mutations in Prickle Orthologs Cause Seizures in Flies, Mice, and Humans

PubMed Central

Tao, Hirotaka; Manak, J. Robert; Sowers, Levi; Mei, Xue; Kiyonari, Hiroshi; Abe, Takaya; Dahdaleh, Nader S.; Yang, Tian; Wu, Shu; Chen, Shan; Fox, Mark H.; Gurnett, Christina; Montine, Thomas; Bird, Thomas; Shaffer, Lisa G.; Rosenfeld, Jill A.; McConnell, Juliann; Madan-Khetarpal, Suneeta; Berry-Kravis, Elizabeth; Griesbach, Hilary; Saneto, Russell P.; Scott, Matthew P.; Antic, Dragana; Reed, Jordan; Boland, Riley; Ehaideb, Salleh N.; El-Shanti, Hatem; Mahajan, Vinit B.; Ferguson, Polly J.; Axelrod, Jeffrey D.; Lehesjoki, Anna-Elina; Fritzsch, Bernd; Slusarski, Diane C.; Wemmie, John; Ueno, Naoto; Bassuk, Alexander G.

2011-01-01

Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution. PMID:21276947

MAGNETOMETER

DOEpatents

Leavitt, M.A.

1958-11-18

A magnetometer ls described, partlcularly to a device which accurately indicates the polarity and intensity of a magnetlc field. The main feature of the invention is a unique probe construction in combinatlon wlth a magnetic fleld detector system. The probe comprises two coils connected in series opposition for energization with an a-c voltage. The voltage lnduced in a third coll on the probe, a pick-up coil, is distorted by the presence of an external field to produce even harmonic voltages. A controlled d-c current is passed through the energized coils to counter the dlstortlon and reduce tbe even harmonic content to a null. When the null point is reached, the d-c current is a measure of the external magnetic field strength, and the phase of the pickup coil voltage indicates tbe field polarlty.

High Impact = High Statistical Standards? Not Necessarily So

PubMed Central

Tressoldi, Patrizio E.; Giofré, David; Sella, Francesco; Cumming, Geoff

2013-01-01

What are the statistical practices of articles published in journals with a high impact factor? Are there differences compared with articles published in journals with a somewhat lower impact factor that have adopted editorial policies to reduce the impact of limitations of Null Hypothesis Significance Testing? To investigate these questions, the current study analyzed all articles related to psychological, neuropsychological and medical issues, published in 2011 in four journals with high impact factors: Science, Nature, The New England Journal of Medicine and The Lancet, and three journals with relatively lower impact factors: Neuropsychology, Journal of Experimental Psychology-Applied and the American Journal of Public Health. Results show that Null Hypothesis Significance Testing without any use of confidence intervals, effect size, prospective power and model estimation, is the prevalent statistical practice used in articles published in Nature, 89%, followed by articles published in Science, 42%. By contrast, in all other journals, both with high and lower impact factors, most articles report confidence intervals and/or effect size measures. We interpreted these differences as consequences of the editorial policies adopted by the journal editors, which are probably the most effective means to improve the statistical practices in journals with high or low impact factors. PMID:23418533

High impact  =  high statistical standards? Not necessarily so.

PubMed

Tressoldi, Patrizio E; Giofré, David; Sella, Francesco; Cumming, Geoff

2013-01-01

What are the statistical practices of articles published in journals with a high impact factor? Are there differences compared with articles published in journals with a somewhat lower impact factor that have adopted editorial policies to reduce the impact of limitations of Null Hypothesis Significance Testing? To investigate these questions, the current study analyzed all articles related to psychological, neuropsychological and medical issues, published in 2011 in four journals with high impact factors: Science, Nature, The New England Journal of Medicine and The Lancet, and three journals with relatively lower impact factors: Neuropsychology, Journal of Experimental Psychology-Applied and the American Journal of Public Health. Results show that Null Hypothesis Significance Testing without any use of confidence intervals, effect size, prospective power and model estimation, is the prevalent statistical practice used in articles published in Nature, 89%, followed by articles published in Science, 42%. By contrast, in all other journals, both with high and lower impact factors, most articles report confidence intervals and/or effect size measures. We interpreted these differences as consequences of the editorial policies adopted by the journal editors, which are probably the most effective means to improve the statistical practices in journals with high or low impact factors.

Influence of primary care professionals on early detection of breast cancer: different perception between family physicians and nursing professionals.

PubMed

Esteban-Vasallo, María D; Aerny-Perreten, Nicole; García-Riolobos, Carmen; López Rubio, Aranzazu; Domínguez-Berjón, Felicitas

2017-01-01

The aim of this study was to assess the level of self-perceived influence on early detection of breast cancer among nurses and family physicians (FP) working in primary care and to identify the factors associated with a lower perception in each group. In the Autonomous Community of Madrid, an online questionnaire on cancer prevention was sent to a random sample of primary care professionals (3586 FP and nurses). The data included sex, age, profession, years in primary care, specific postgraduate training, and opinions and attitudes toward cancer prevention. A descriptive analysis was carried out. Factors associated with a low/null self-perceived influence on early detection of breast cancer were analyzed separately for FP and nurses with multivariate logistic regression models. In all, 76.4% of the participants considered that their influence on the early detection of breast cancer was enough/high. FP attributed to themselves a higher influence than nurses (enough/high: 86.0 vs. 64.6%, P<0.01), and a lower perception was associated with a low/null perceived utility of their individual intervention [odds ratio (OR): 6.42, 95% confidence interval (CI) 2.77-14.85]. Among nurses, also associated with this low/null perceived utility [adjusted odds ratio (aOR): 2.81, 95% CI 1.37-5.77] were the absence of postgraduate training in the matter (aOR: 2.56, 95% CI 1.05-6.25), and a low/null perception of feasibility of prevention programs in their centers (aOR: 1.93, 95% CI 1.25-2.98). Primary care professionals perceive their activity in the early detection of breast cancer as relevant, especially FP. To increase knowledge of the utility of individual interventions, specific training and improvement of the feasibility of these programs could enhance this perception.

Evidence that the Dictyostelium STAT protein Dd-STATa plays a role in the differentiation of inner basal disc cells and identification of a promoter element essential for expression in these cells.

PubMed

Shimada, Nao; Maruo, Toshinari; Maeda, Mineko; Urushihara, Hideko; Kawata, Takefumi

2005-02-01

Dd-STATa, a Dictyostelium homolog of the metazoan STAT (signal transducers and activators of transcription) proteins, is necessary in the slug for correct entry into culmination. Dd-STATa-null mutant fails to culminate and its phenotype correlates with the loss of a funnel-shaped core region, the pstAB core region, which expresses both the ecmA and ecmB genes. To understand how the differentiation of pstAB core cells is regulated, we identified an EST that is expressed in the core cells of normal slugs but down-regulated in the Dd-STATa-null mutant. This EST, SSK348, encodes a close homolog of the Dictyostelium acetyl-CoA synthetase (ACS). A promoter fragment of the cognate gene, aslA (acetyl-CoA synthetase-like A), was fused to a lacZ reporter and the expression pattern determined. As expected from the behavior of the endogenous aslA gene, the aslA::lacZ fusion gene is not expressed in Dd-STATa-null slugs. In parental cells, the aslA promoter is first activated in the funnel-shaped core cells located at the slug anterior, the "pstAB core." During culmination, the pstAB core cells move down, through the prespore cells, to form the inner part of the basal disc. As the spore mass climbs the stalk, the aslA gene comes to be expressed in cells of the upper and lower cups, structures that cradle the spore head. Deletion and point mutation analyses of the promoter identified an AT-rich sequence that is necessary for expression in the pstAB core. This acts in combination with repressor regions that prevent ectopic aslA expression in the pre-stalk regions of slugs and the stalks of culminants. Thus, this study confirms that Dd-STATa is necessary for the differentiation of pstAB core cells, by showing that it is needed for the activation of the aslA gene. It also identifies aslA promoter elements that are likely to be regulated, directly or indirectly, by Dd-STATa.

Alternative Derivations for the Poisson Integral Formula

ERIC Educational Resources Information Center

Chen, J. T.; Wu, C. S.

2006-01-01

Poisson integral formula is revisited. The kernel in the Poisson integral formula can be derived in a series form through the direct BEM free of the concept of image point by using the null-field integral equation in conjunction with the degenerate kernels. The degenerate kernels for the closed-form Green's function and the series form of Poisson…

Negative, Null and Beneficial Effects of Drinking Water on Energy Intake, Energy Expenditure, Fat Oxidation and Weight Change in Randomized Trials: A Qualitative Review

PubMed Central

Stookey, Jodi J. D.

2016-01-01

Drinking water has heterogeneous effects on energy intake (EI), energy expenditure (EE), fat oxidation (FO) and weight change in randomized controlled trials (RCTs) involving adults and/or children. The aim of this qualitative review of RCTs was to identify conditions associated with negative, null and beneficial effects of drinking water on EI, EE, FO and weight, to generate hypotheses about ways to optimize drinking water interventions for weight management. RCT conditions that are associated with negative or null effects of drinking water on EI, EE and/or FO in the short term are associated with negative or null effects on weight over the longer term. RCT conditions that are associated with lower EI, increased EE and/or increased FO in the short term are associated with less weight gain or greater weight loss over time. Drinking water instead of caloric beverages decreases EI when food intake is ad libitum. Drinking water increases EE in metabolically-inflexible, obese individuals. Drinking water increases FO when blood carbohydrate and/or insulin concentrations are not elevated and when it is consumed instead of caloric beverages or in volumes that alter hydration status. Further research is needed to confirm the observed associations and to determine if/what specific conditions optimize drinking water interventions for weight management. PMID:26729162

Negative, Null and Beneficial Effects of Drinking Water on Energy Intake, Energy Expenditure, Fat Oxidation and Weight Change in Randomized Trials: A Qualitative Review.

PubMed

Stookey, Jodi J D

2016-01-02

Drinking water has heterogeneous effects on energy intake (EI), energy expenditure (EE), fat oxidation (FO) and weight change in randomized controlled trials (RCTs) involving adults and/or children. The aim of this qualitative review of RCTs was to identify conditions associated with negative, null and beneficial effects of drinking water on EI, EE, FO and weight, to generate hypotheses about ways to optimize drinking water interventions for weight management. RCT conditions that are associated with negative or null effects of drinking water on EI, EE and/or FO in the short term are associated with negative or null effects on weight over the longer term. RCT conditions that are associated with lower EI, increased EE and/or increased FO in the short term are associated with less weight gain or greater weight loss over time. Drinking water instead of caloric beverages decreases EI when food intake is ad libitum. Drinking water increases EE in metabolically-inflexible, obese individuals. Drinking water increases FO when blood carbohydrate and/or insulin concentrations are not elevated and when it is consumed instead of caloric beverages or in volumes that alter hydration status. Further research is needed to confirm the observed associations and to determine if/what specific conditions optimize drinking water interventions for weight management.

Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models.

PubMed

Shannon, Harlan E; Yang, Lijuan

2004-01-01

Neuropeptide Y (NPY) administered exogenously is anticonvulsant, and, NPY null mutant mice are more susceptible to kainate-induced seizures. In order to better understand the potential role of NPY in epileptogenesis, the present studies investigated the development of amygdala kindling, post-kindling seizure thresholds, and anticonvulsant effects of carbamazepine and levetiracetam in 129S6/SvEv NPY(+/+) and NPY(-/-) mice. In addition, susceptibility to pilocarpine- and kainate-induced seizures was compared in NPY(+/+) and (-/-) mice. The rate of amygdala kindling development did not differ in the NPY(-/-) and NPY(+/+) mice either when kindling stimuli were presented once daily for at least 20 days, or, 12 times daily for 2 days. However, during kindling development, the NPY(-/-) mice had higher seizure severity scores and longer afterdischarge durations than the NPY(+/+) mice. Post-kindling, the NPY(-/-) mice had markedly lower afterdischarge thresholds and longer afterdischarge durations than NPY (+/+) mice. Carbamazepine and levetiracetam increased the seizure thresholds of both NPY (-/-) and (+/+) mice. In addition, NPY (-/-) mice had lower thresholds for both kainate- and pilocarpine-induced seizures. The present results in amygdala kindling and chemical seizure models suggest that NPY may play a more prominent role in determining seizure thresholds and severity of seizures than in events leading to epileptogenesis. In addition, a lack of NPY does not appear to confer drug-resistance in that carbamazepine and levetiracetam were anticonvulsant in both wild type (WT) and NPY null mutant mice.

Deficiency of aldose reductase exacerbates early pressure overload-induced cardiac dysfunction and autophagy in mice.

PubMed

Baba, Shahid P; Zhang, Deqing; Singh, Mahavir; Dassanayaka, Sujith; Xie, Zhengzhi; Jagatheesan, Ganapathy; Zhao, Jingjing; Schmidtke, Virginia K; Brittian, Kenneth R; Merchant, Michael L; Conklin, Daniel J; Jones, Steven P; Bhatnagar, Aruni

2018-05-01

Pathological cardiac hypertrophy is associated with the accumulation of lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) and acrolein in the heart. These aldehydes are metabolized via several pathways, of which aldose reductase (AR) represents a broad-specificity route for their elimination. We tested the hypothesis that by preventing aldehyde removal, AR deficiency accentuates the pathological effects of transverse aortic constriction (TAC). We found that the levels of AR in the heart were increased in mice subjected to TAC for 2 weeks. In comparison with wild-type (WT), AR-null mice showed lower ejection fraction, which was exacerbated 2 weeks after TAC. Levels of atrial natriuretic peptide and myosin heavy chain were higher in AR-null than in WT TAC hearts. Deficiency of AR decreased urinary levels of the acrolein metabolite, 3-hydroxypropylmercapturic acid. Deletion of AR did not affect the levels of the other aldehyde-metabolizing enzyme - aldehyde dehydrogenase 2 in the heart, or its urinary product - (N-Acetyl-S-(2-carboxyethyl)-l-cystiene). AR-null hearts subjected to TAC showed increased accumulation of HNE- and acrolein-modified proteins, as well as increased AMPK phosphorylation and autophagy. Superfusion with HNE led to a greater increase in p62, LC3II formation, and GFP-LC3-II punctae formation in AR-null than WT cardiac myocytes. Pharmacological inactivation of JNK decreased HNE-induced autophagy in AR-null cardiac myocytes. Collectively, these results suggest that during hypertrophy the accumulation of lipid peroxidation derived aldehydes promotes pathological remodeling via excessive autophagy, and that metabolic detoxification of these aldehydes by AR may be essential for maintaining cardiac function during early stages of pressure overload. Published by Elsevier Ltd.

Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.

PubMed

Espitia-Pérez, Lyda; Sosa, Milton Quintana; Salcedo-Arteaga, Shirley; León-Mejía, Grethel; Hoyos-Giraldo, Luz Stella; Brango, Hugo; Kvitko, Katia; da Silva, Juliana; Henriques, João A P

2016-09-15

Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms. This modulation may involve specific and differentiated pathways in different tissues that also may cause a differential sensitivity related to differential induction of some enzymes. Copyright © 2016 Elsevier B.V. All rights reserved.

KiDS-i-800: comparing weak gravitational lensing measurements from same-sky surveys

NASA Astrophysics Data System (ADS)

Amon, A.; Heymans, C.; Klaes, D.; Erben, T.; Blake, C.; Hildebrandt, H.; Hoekstra, H.; Kuijken, K.; Miller, L.; Morrison, C. B.; Choi, A.; de Jong, J. T. A.; Glazebrook, K.; Irisarri, N.; Joachimi, B.; Joudaki, S.; Kannawadi, A.; Lidman, C.; Napolitano, N.; Parkinson, D.; Schneider, P.; van Uitert, E.; Viola, M.; Wolf, C.

2018-07-01

We present a weak gravitational lensing analysis of 815 deg2 of i-band imaging from the Kilo-Degree Survey (KiDS-i-800). In contrast to the deep r-band observations, which take priority during excellent seeing conditions and form the primary KiDS data set (KiDS-r-450), the complementary yet shallower KiDS-i-800 spans a wide range of observing conditions. The overlapping KiDS-i-800 and KiDS-r-450 imaging therefore provides a unique opportunity to assess the robustness of weak lensing measurements. In our analysis we introduce two new `null' tests. The `nulled' two-point shear correlation function uses a matched catalogue to show that the calibrated KiDS-i-800 and KiDS-r-450 shear measurements agree at the level of 1 ± 4 per cent. We use five galaxy lens samples to determine a `nulled' galaxy-galaxy lensing signal from the full KiDS-i-800 and KiDS-r-450 surveys and find that the measurements agree to 7 ± 5 per cent when the KiDS-i-800 source redshift distribution is calibrated using either spectroscopic redshifts, or the 30-band photometric redshifts from the COSMOS survey.

Light-Ring Stability for Ultracompact Objects.

PubMed

Cunha, Pedro V P; Berti, Emanuele; Herdeiro, Carlos A R

2017-12-22

We prove the following theorem: axisymmetric, stationary solutions of the Einstein field equations formed from classical gravitational collapse of matter obeying the null energy condition, that are everywhere smooth and ultracompact (i.e., they have a light ring) must have at least two light rings, and one of them is stable. It has been argued that stable light rings generally lead to nonlinear spacetime instabilities. Our result implies that smooth, physically and dynamically reasonable ultracompact objects are not viable as observational alternatives to black holes whenever these instabilities occur on astrophysically short time scales. The proof of the theorem has two parts: (i) We show that light rings always come in pairs, one being a saddle point and the other a local extremum of an effective potential. This result follows from a topological argument based on the Brouwer degree of a continuous map, with no assumptions on the spacetime dynamics, and, hence, it is applicable to any metric gravity theory where photons follow null geodesics. (ii) Assuming Einstein's equations, we show that the extremum is a local minimum of the potential (i.e., a stable light ring) if the energy-momentum tensor satisfies the null energy condition.

Existence and stability of circular orbits in general static and spherically symmetric spacetimes

NASA Astrophysics Data System (ADS)

Jia, Junji; Liu, Jiawei; Liu, Xionghui; Mo, Zhongyou; Pang, Xiankai; Wang, Yaoguang; Yang, Nan

2018-02-01

The existence and stability of circular orbits (CO) in static and spherically symmetric (SSS) spacetime are important because of their practical and potential usefulness. In this paper, using the fixed point method, we first prove a necessary and sufficient condition on the metric function for the existence of timelike COs in SSS spacetimes. After analyzing the asymptotic behavior of the metric, we then show that asymptotic flat SSS spacetime that corresponds to a negative Newtonian potential at large r will always allow the existence of CO. The stability of the CO in a general SSS spacetime is then studied using the Lyapunov exponent method. Two sufficient conditions on the (in)stability of the COs are obtained. For null geodesics, a sufficient condition on the metric function for the (in)stability of null CO is also obtained. We then illustrate one powerful application of these results by showing that three SSS spacetimes whose metric function is not completely known will allow the existence of timelike and/or null COs. We also used our results to assert the existence and (in)stabilities of a number of known SSS metrics.

KiDS-i-800: Comparing weak gravitational lensing measurements from same-sky surveys

NASA Astrophysics Data System (ADS)

Amon, A.; Heymans, C.; Klaes, D.; Erben, T.; Blake, C.; Hildebrandt, H.; Hoekstra, H.; Kuijken, K.; Miller, L.; Morrison, C. B.; Choi, A.; de Jong, J. T. A.; Glazebrook, K.; Irisarri, N.; Joachimi, B.; Joudaki, S.; Kannawadi, A.; Lidman, C.; Napolitano, N.; Parkinson, D.; Schneider, P.; van Uitert, E.; Viola, M.; Wolf, C.

2018-04-01

We present a weak gravitational lensing analysis of 815deg2 of i-band imaging from the Kilo-Degree Survey (KiDS-i-800). In contrast to the deep r-band observations, which take priority during excellent seeing conditions and form the primary KiDS dataset (KiDS-r-450), the complementary yet shallower KiDS-i-800 spans a wide range of observing conditions. The overlapping KiDS-i-800 and KiDS-r-450 imaging therefore provides a unique opportunity to assess the robustness of weak lensing measurements. In our analysis we introduce two new `null' tests. The `nulled' two-point shear correlation function uses a matched catalogue to show that the calibrated KiDS-i-800 and KiDS-r-450 shear measurements agree at the level of 1 ± 4%. We use five galaxy lens samples to determine a `nulled' galaxy-galaxy lensing signal from the full KiDS-i-800 and KiDS-r-450 surveys and find that the measurements agree to 7 ± 5% when the KiDS-i-800 source redshift distribution is calibrated using either spectroscopic redshifts, or the 30-band photometric redshifts from the COSMOS survey.

Light-Ring Stability for Ultracompact Objects

NASA Astrophysics Data System (ADS)

Cunha, Pedro V. P.; Berti, Emanuele; Herdeiro, Carlos A. R.

2017-12-01

We prove the following theorem: axisymmetric, stationary solutions of the Einstein field equations formed from classical gravitational collapse of matter obeying the null energy condition, that are everywhere smooth and ultracompact (i.e., they have a light ring) must have at least two light rings, and one of them is stable. It has been argued that stable light rings generally lead to nonlinear spacetime instabilities. Our result implies that smooth, physically and dynamically reasonable ultracompact objects are not viable as observational alternatives to black holes whenever these instabilities occur on astrophysically short time scales. The proof of the theorem has two parts: (i) We show that light rings always come in pairs, one being a saddle point and the other a local extremum of an effective potential. This result follows from a topological argument based on the Brouwer degree of a continuous map, with no assumptions on the spacetime dynamics, and, hence, it is applicable to any metric gravity theory where photons follow null geodesics. (ii) Assuming Einstein's equations, we show that the extremum is a local minimum of the potential (i.e., a stable light ring) if the energy-momentum tensor satisfies the null energy condition.

Parameter estimation uncertainty: Comparing apples and apples?

NASA Astrophysics Data System (ADS)

Hart, D.; Yoon, H.; McKenna, S. A.

2012-12-01

Given a highly parameterized ground water model in which the conceptual model of the heterogeneity is stochastic, an ensemble of inverse calibrations from multiple starting points (MSP) provides an ensemble of calibrated parameters and follow-on transport predictions. However, the multiple calibrations are computationally expensive. Parameter estimation uncertainty can also be modeled by decomposing the parameterization into a solution space and a null space. From a single calibration (single starting point) a single set of parameters defining the solution space can be extracted. The solution space is held constant while Monte Carlo sampling of the parameter set covering the null space creates an ensemble of the null space parameter set. A recently developed null-space Monte Carlo (NSMC) method combines the calibration solution space parameters with the ensemble of null space parameters, creating sets of calibration-constrained parameters for input to the follow-on transport predictions. Here, we examine the consistency between probabilistic ensembles of parameter estimates and predictions using the MSP calibration and the NSMC approaches. A highly parameterized model of the Culebra dolomite previously developed for the WIPP project in New Mexico is used as the test case. A total of 100 estimated fields are retained from the MSP approach and the ensemble of results defining the model fit to the data, the reproduction of the variogram model and prediction of an advective travel time are compared to the same results obtained using NSMC. We demonstrate that the NSMC fields based on a single calibration model can be significantly constrained by the calibrated solution space and the resulting distribution of advective travel times is biased toward the travel time from the single calibrated field. To overcome this, newly proposed strategies to employ a multiple calibration-constrained NSMC approach (M-NSMC) are evaluated. Comparison of the M-NSMC and MSP methods suggests that M-NSMC can provide a computationally efficient and practical solution for predictive uncertainty analysis in highly nonlinear and complex subsurface flow and transport models. This material is based upon work supported as part of the Center for Frontiers of Subsurface Energy Security, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Award Number DE-SC0001114. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

USDA-ARS?s Scientific Manuscript database

The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CA...

Cosmic shear measurements with Dark Energy Survey Science Verification data

DOE PAGES

Becker, M. R.

2016-07-06

Here, we present measurements of weak gravitational lensing cosmic shear two-point statistics using Dark Energy Survey Science Verification data. We demonstrate that our results are robust to the choice of shear measurement pipeline, either ngmix or im3shape, and robust to the choice of two-point statistic, including both real and Fourier-space statistics. Our results pass a suite of null tests including tests for B-mode contamination and direct tests for any dependence of the two-point functions on a set of 16 observing conditions and galaxy properties, such as seeing, airmass, galaxy color, galaxy magnitude, etc. We use a large suite of simulationsmore » to compute the covariance matrix of the cosmic shear measurements and assign statistical significance to our null tests. We find that our covariance matrix is consistent with the halo model prediction, indicating that it has the appropriate level of halo sample variance. We also compare the same jackknife procedure applied to the data and the simulations in order to search for additional sources of noise not captured by the simulations. We find no statistically significant extra sources of noise in the data. The overall detection significance with tomography for our highest source density catalog is 9.7σ. Cosmological constraints from the measurements in this work are presented in a companion paper.« less

Statistical reporting inconsistencies in experimental philosophy

PubMed Central

Colombo, Matteo; Duev, Georgi; Nuijten, Michèle B.; Sprenger, Jan

2018-01-01

Experimental philosophy (x-phi) is a young field of research in the intersection of philosophy and psychology. It aims to make progress on philosophical questions by using experimental methods traditionally associated with the psychological and behavioral sciences, such as null hypothesis significance testing (NHST). Motivated by recent discussions about a methodological crisis in the behavioral sciences, questions have been raised about the methodological standards of x-phi. Here, we focus on one aspect of this question, namely the rate of inconsistencies in statistical reporting. Previous research has examined the extent to which published articles in psychology and other behavioral sciences present statistical inconsistencies in reporting the results of NHST. In this study, we used the R package statcheck to detect statistical inconsistencies in x-phi, and compared rates of inconsistencies in psychology and philosophy. We found that rates of inconsistencies in x-phi are lower than in the psychological and behavioral sciences. From the point of view of statistical reporting consistency, x-phi seems to do no worse, and perhaps even better, than psychological science. PMID:29649220

Performance of the primary mirror center-of-curvature optical metrology system during cryogenic testing of the JWST Pathfinder telescope

NASA Astrophysics Data System (ADS)

Hadaway, James B.; Wells, Conrad; Olczak, Gene; Waldman, Mark; Whitman, Tony; Cosentino, Joseph; Connolly, Mark; Chaney, David; Telfer, Randal

2016-07-01

The James Webb Space Telescope (JWST) primary mirror (PM) is 6.6 m in diameter and consists of 18 hexagonal segments, each 1.5 m point-to-point. Each segment has a six degree-of-freedom hexapod actuation system and a radius of-curvature (RoC) actuation system. The full telescope will be tested at its cryogenic operating temperature at Johnson Space Center. This testing will include center-of-curvature measurements of the PM, using the Center-of-Curvature Optical Assembly (COCOA) and the Absolute Distance Meter Assembly (ADMA). The COCOA includes an interferometer, a reflective null, an interferometer-null calibration system, coarse and fine alignment systems, and two displacement measuring interferometer systems. A multiple-wavelength interferometer (MWIF) is used for alignment and phasing of the PM segments. The ADMA is used to measure, and set, the spacing between the PM and the focus of the COCOA null (i.e. the PM center-of-curvature) for determination of the ROC. The performance of these metrology systems was assessed during two cryogenic tests at JSC. This testing was performed using the JWST Pathfinder telescope, consisting mostly of engineering development and spare hardware. The Pathfinder PM consists of two spare segments. These tests provided the opportunity to assess how well the center-of-curvature optical metrology hardware, along with the software and procedures, performed using real JWST telescope hardware. This paper will describe the test setup, the testing performed, and the resulting metrology system performance. The knowledge gained and the lessons learned during this testing will be of great benefit to the accurate and efficient cryogenic testing of the JWST flight telescope.

Performance of the Primary Mirror Center-of-curvature Optical Metrology System During Cryogenic Testing of the JWST Pathfinder Telescope

NASA Technical Reports Server (NTRS)

Hadaway, James B.; Wells, Conrad; Olczak, Gene; Waldman, Mark; Whitman, Tony; Cosentino, Joseph; Connolly, Mark; Chaney, David; Telfer, Randal

2016-01-01

The James Webb Space Telescope (JWST) primary mirror (PM) is 6.6 m in diameter and consists of 18 hexagonal segments, each 1.5 m point-to-point. Each segment has a six degree-of-freedom hexapod actuation system and a radius-of-curvature (RoC) actuation system. The full telescope will be tested at its cryogenic operating temperature at Johnson Space Center. This testing will include center-of-curvature measurements of the PM, using the Center-of-Curvature Optical Assembly (COCOA) and the Absolute Distance Meter Assembly (ADMA). The COCOA includes an interferometer, a reflective null, an interferometer-null calibration system, coarse & fine alignment systems, and two displacement measuring interferometer systems. A multiple-wavelength interferometer (MWIF) is used for alignment & phasing of the PM segments. The ADMA is used to measure, and set, the spacing between the PM and the focus of the COCOA null (i.e. the PM center-of-curvature) for determination of the ROC. The performance of these metrology systems was assessed during two cryogenic tests at JSC. This testing was performed using the JWST Pathfinder telescope, consisting mostly of engineering development & spare hardware. The Pathfinder PM consists of two spare segments. These tests provided the opportunity to assess how well the center-of-curvature optical metrology hardware, along with the software & procedures, performed using real JWST telescope hardware. This paper will describe the test setup, the testing performed, and the resulting metrology system performance. The knowledge gained and the lessons learned during this testing will be of great benefit to the accurate & efficient cryogenic testing of the JWST flight telescope.

Effects of hypo-O-GlcNAcylation on Drosophila development.

PubMed

Mariappa, Daniel; Ferenbach, Andrew T; van Aalten, Daan M F

2018-05-11

Post-translational modification of serine/threonine residues in nucleocytoplasmic proteins with GlcNAc ( O -GlcNAcylation) is an essential regulatory mechanism in many cellular processes. In Drosophila , null mutants of the Polycomb gene O -GlcNAc transferase ( OGT ; also known as super sex combs ( sxc )) display homeotic phenotypes. To dissect the requirement for O -GlcNAc signaling in Drosophila development, we used CRISPR/Cas9 gene editing to generate rationally designed sxc catalytically hypomorphic or null point mutants. Of the fertile males derived from embryos injected with the CRISPR/Cas9 reagents, 25% produced progeny carrying precise point mutations with no detectable off-target effects. One of these mutants, the catalytically inactive sxc K872M , was recessive lethal, whereas a second mutant, the hypomorphic sxc H537A , was homozygous viable. We observed that reduced total protein O -GlcNAcylation in the sxc H537A mutant is associated with a wing vein phenotype and temperature-dependent lethality. Genetic interaction between sxc H537A and a null allele of Drosophila host cell factor ( dHcf ), encoding an extensively O -GlcNAcylated transcriptional coactivator, resulted in abnormal scutellar bristle numbers. A similar phenotype was also observed in sxc H537A flies lacking a copy of skuld ( skd ), a Mediator complex gene known to affect scutellar bristle formation. Interestingly, this phenotype was independent of OGT Polycomb function or dHcf downstream targets. In conclusion, the generation of the endogenous OGT hypomorphic mutant sxc H537A enabled us to identify pleiotropic effects of globally reduced protein O -GlcNAc during Drosophila development. The mutants generated and phenotypes observed in this study provide a platform for discovery of OGT substrates that are critical for Drosophila development. © 2018 Mariappa et al.

The Effect of Magnetic Topology on the Escape of Flare Particles

NASA Technical Reports Server (NTRS)

Antiochos, S. K.; Masson, S.; DeVore, C. R.

2012-01-01

Magnetic reconnection in the solar atmosphere is believed to be the driver of most solar explosive phenomena. Therefore, the topology of the coronal magnetic field is central to understanding the solar drivers of space weather. Of particular importance to space weather are the impulsive Solar Energetic particles that are associated with some CME/eruptive flare events. Observationally, the magnetic configuration of active regions where solar eruptions originate appears to agree with the standard eruptive flare model. According to this model, particles accelerated at the flare reconnection site should remain trapped in the corona and the ejected plasmoid. However, flare-accelerated particles frequently reach the Earth long before the CME does. We present a model that may account for the injection of energetic particles onto open magnetic flux tubes connecting to the Earth. Our model is based on the well-known 2.5D breakout topology, which has a coronal null point (null line) and a four-flux system. A key new addition, however, is that we include an isothermal solar wind with open-flux regions. Depending on the location of the open flux with respect to the null point, we find that the flare reconnection can consist of two distinct phases. At first, the flare reconnection involves only closed field, but if the eruption occurs close to the open field, we find a second phase involving interchange reconnection between open and closed. We argue that this second reconnection episode is responsible for the injection of flare-accelerated particles into the interplanetary medium. We will report on our recent work toward understanding how flare particles escape to the heliosphere. This work uses high-resolution 2.5D MHD numerical simulations performed with the Adaptively Refined MHD Solver (ARMS).

A predictive approach to selecting the size of a clinical trial, based on subjective clinical opinion.

PubMed

Spiegelhalter, D J; Freedman, L S

1986-01-01

The 'textbook' approach to determining sample size in a clinical trial has some fundamental weaknesses which we discuss. We describe a new predictive method which takes account of prior clinical opinion about the treatment difference. The method adopts the point of clinical equivalence (determined by interviewing the clinical participants) as the null hypothesis. Decision rules at the end of the study are based on whether the interval estimate of the treatment difference (classical or Bayesian) includes the null hypothesis. The prior distribution is used to predict the probabilities of making the decisions to use one or other treatment or to reserve final judgement. It is recommended that sample size be chosen to control the predicted probability of the last of these decisions. An example is given from a multi-centre trial of superficial bladder cancer.

Hazard analysis of Clostridium perfringens in the Skylab Food System

NASA Technical Reports Server (NTRS)

Bourland, C. T.; Huber, C. S.; Kiser, P. R.; Heidelbaugh, N. D.; Rowley, D. B.

1974-01-01

The Skylab Food System presented unique microbiological problems because food was warmed in null-gravity and because the heat source was limited to 69.4 C (to prevent boiling in null-gravity). For these reasons, the foods were manufactured using critical control point techniques of quality control coupled with appropriate hazard analyses. One of these hazard analyses evaluated the threat from Clostridium perfringens. Samples of food were inoculated with C. perfringens and incubated for 2 h at temperatures ranging from 25 to 55 C. Generation times were determined for the foods at various temperatures. Results of these tests were evaluated taking into consideration: food-borne disease epidemiology, the Skylab food manufacturing procedures, and the performance requirements of the Skylab Food System. Based on this hazard analysis, a limit for C. perfringens of 100/g was established for Skylab foods.

Lower bound on the compactness of isotropic ultracompact objects

NASA Astrophysics Data System (ADS)

Hod, Shahar

2018-04-01

Horizonless spacetimes describing spatially regular ultracompact objects which, like black-hole spacetimes, possess closed null circular geodesics (light rings) have recently attracted much attention from physicists and mathematicians. In the present paper we raise the following physically intriguing question: how compact is an ultracompact object? Using analytical techniques, we prove that ultracompact isotropic matter configurations with light rings are characterized by the dimensionless lower bound maxr{2 m (r )/r }>7 /12 on their global compactness parameter.

Accentuated Osteoclastic Response to Parathyroid Hormone Undermines Bone Mass Acquisition in Osteonectin-null Mice

PubMed Central

do Reis, Luciene Machado; Kessler, Catherine B.; Adams, Douglas J.; Lorenzo, Joseph; Jorgetti, Vanda; Delany, Anne M.

2008-01-01

Matricellular proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone. In the absence of osteonectin, mice develop progressive low turnover osteopenia, particularly affecting trabecular bone. Polymorphisms in a regulatory region of the osteonectin gene are associated with bone mass in a subset of idiopathic osteoporosis patients, and these polymorphisms likely regulate osteonectin expression. Thus it is important to determine how osteonectin gene dosage affects skeletal function. Moreover, intermittent administration of parathyroid hormone (PTH) (1-34) is the only anabolic therapy approved for the treatment of osteoporosis, and it is critical to understand how modulators of bone remodeling, such as osteonectin, affect skeletal response to anabolic agents. In this study, 10 week old female wild type, osteonectin-haploinsufficient, and osteonectin-null mice (C57Bl/6 genetic background) were given 80 μg/kg body weight/day PTH(1-34) for 4 weeks. Osteonectin gene dosage had a profound effect on bone microarchitecture. The connectivity density of trabecular bone in osteonectin-haploinsufficient mice was substantially decreased compared with that of wild type mice, suggesting compromised mechanical properties. Whereas mice of each genotype had a similar osteoblastic response to PTH treatment, the osteoclastic response was accentuated in osteonectin-haploinsufficient and osteonectin-null mice. Eroded surface and osteoclast number were significantly higher in PTH-treated osteonectin-null mice, as was endosteal area. In vitro studies confirmed that PTH induced the formation of more osteoclast-like cells in marrow from osteonectin-null mice compared with wild type. PTH treated osteonectin-null bone marrow cells expressed more RANKL mRNA compared with wild type. However, the ratio of RANKL:OPG mRNA was somewhat lower in PTH treated osteonectin-null cultures. Increased expression of RANKL in response to PTH could contribute to the accentuated osteoclastic response in osteonectin-/- mice, but other mechanisms are also likely to be involved. The molecular mechanisms by which PTH elicits bone anabolic vs. bone catabolic effects remain poorly understood. Our results imply that osteonectin levels may play a role in modulating the balance of bone formation and resorption in response to PTH. PMID:18499553

Thermal Entanglement in XXZ Heisenberg Model for Coupled Spin-Half and Spin-One Triangular Cell

NASA Astrophysics Data System (ADS)

Najarbashi, Ghader; Balazadeh, Leila; Tavana, Ali

2018-01-01

In this paper, we investigate the thermal entanglement of two-spin subsystems in an ensemble of coupled spin-half and spin-one triangular cells, (1/2, 1/2, 1/2), (1/2, 1, 1/2), (1, 1/2, 1) and (1, 1, 1) with the XXZ anisotropic Heisenberg model subjected to an external homogeneous magnetic field. We adopt the generalized concurrence as the measure of entanglement which is a good indicator of the thermal entanglement and the critical points in the mixed higher dimensional spin systems. We observe that in the near vicinity of the absolute zero, the concurrence measure is symmetric with respect to zero magnetic field and changes abruptly from a non-null to null value for a critical magnetic field that can be signature of a quantum phase transition at finite temperature. The analysis of concurrence versus temperature shows that there exists a critical temperature, that depends on the type of the interaction, i.e. ferromagnetic or antiferromagnetic, the anisotropy parameter and the strength of the magnetic field. Results show that the pairwise thermal entanglement depends on the third spin which affects the maximum value of the concurrence at absolute zero and at quantum critical points.

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.

Yeast hnRNP-related proteins contribute to the maintenance of telomeres

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

Lee-Soety, Julia Y., E-mail: jlee04@sju.edu; Jones, Jennifer; MacGibeny, Margaret A.

Highlights: Black-Right-Pointing-Pointer Yeast hnRNP-related proteins are able to prevent faster senescence in telomerase-null cells. Black-Right-Pointing-Pointer The conserved RRMs in Npl3 are important for telomere maintenance. Black-Right-Pointing-Pointer Human hnRNP A1 is unable to complement the lack of NPL3 in yeast. Black-Right-Pointing-Pointer Npl3 and Cbc2 may work as telomere capping proteins. -- Abstract: Telomeres protect the ends of linear chromosomes, which if eroded to a critical length can become uncapped and lead to replicative senescence. Telomerase maintains telomere length in some cells, but inappropriate expression facilitates the immortality of cancer cells. Recently, proteins involved in RNA processing and ribosome assembly, such asmore » hnRNP (heterogeneous nuclear ribonucleoprotein) A1, have been found to participate in telomere maintenance in mammals. The Saccharomyces cerevisiae protein Npl3 shares significant amino acid sequence similarities with hnRNP A1. We found that deleting NPL3 accelerated the senescence of telomerase null cells. The highly conserved RNA recognition motifs (RRM) in Npl3 appear to be important for preventing faster senescence. Npl3 preferentially binds telomere sequences in vitro, suggesting that Npl3 may affect telomeres directly. Despite similarities between the two proteins, human hnRNP A1 is unable to complement the lack of Npl3 to rescue accelerated senescence in tlc1 npl3 cells. Deletion of CBC2, which encodes another hnRNP-related protein that associates with Npl3, also accelerates senescence. Potential mechanisms by which hnRNP-related proteins maintain telomeres are discussed.« less

Role of RhAG and AQP1 in NH3 and CO2 gas transport in red cell ghosts: a stopped-flow analysis.

PubMed

Ripoche, P; Goossens, D; Devuyst, O; Gane, P; Colin, Y; Verkman, A S; Cartron, J-P

2006-01-01

To clarify the potential role Rh/RhAG and AQP1 proteins in erythrocyte gas transport, NH3 and CO2 transport was measured in erythrocyte ghost membrane vesicles from rare human variants (Rh(null), CO(null),) and knockout mice (homozygous AQP1-/-, Rh-/- and Rhag-/-) exhibiting well-characterized protein defects. Transport was measured from intracellular pH (pHi) changes in a stopped-flow fluorimeter. NH3 transport was measured in chloride-free conditions with ghosts exposed to 20 mM inwardly directed gradients of gluconate salts of ammonium, hydrazine and methylammonium at 15 degrees C. Alkalinization rates of control samples were 6.5+/-0.3, 4.03+/-0.17, 0.95+/-0.08 s(-1) for each solute, respectively, but were significantly reduced for Rh(null) and CO(null) samples that are deficient in RhAG and AQP1 proteins, respectively. Alkalinization rates of Rh(null) ghosts were about 60%, 83% and 94% lower than that in control ghosts, respectively, for each solute. In CO(null) ghosts, the lack of AQP1 resulted in about 30% reduction of the alkalinization rates as compared to controls, but the transport selectivity of RhAG for the three solutes was preserved. Similar observations were made with ghosts from KO mice Rhag-/- and AQP1-/-. These results confirm the major contribution of RhAG/Rhag in the NH3 conductance of erythrocytes and suggest that the reduction of transport rates in the absence of AQP1 would be better explained by a direct or indirect effect on RhAG/Rhag-mediated transport. When ghosts were preloaded with carbonic anhydrase and exposed to a 25 mM CO2/HCO3- gradient at 6 degrees C, an extremely rapid kinetics of acidification corresponding to CO2 influx was observed. The rate constants were not significantly different between controls and human variants (125+/-6 s(-1)), or between wild-type and KO mice, suggesting no major role of RhAG or AQP1 in CO2 transport, at least in our experimental conditions.

Advances in understanding quiescent H-mode plasmas in DIII-Da)

NASA Astrophysics Data System (ADS)

Burrell, K. H.; West, W. P.; Doyle, E. J.; Austin, M. E.; Casper, T. A.; Gohil, P.; Greenfield, C. M.; Groebner, R. J.; Hyatt, A. W.; Jayakumar, R. J.; Kaplan, D. H.; Lao, L. L.; Leonard, A. W.; Makowski, M. A.; McKee, G. R.; Osborne, T. H.; Snyder, P. B.; Solomon, W. M.; Thomas, D. M.; Rhodes, T. L.; Strait, E. J.; Wade, M. R.; Wang, G.; Zeng, L.

2005-05-01

Recent QH-mode research on DIII-D [J. L. Luxon et al., Plasma Physics and Controlled Nuclear Fusion Research 1996 (International Atomic Energy Agency, Vienna, 1987), Vol. I, p. 159] has used the peeling-ballooning modes model of edge magnetohydrodynamic stability as a working hypothesis to organize the data; several predictions of this theory are consistent with the experimental results. Current ramping results indicate that QH modes operate near the edge current limit set by peeling modes. This operating point explains why QH mode is easier to get at lower plasma currents. Power scans have shown a saturation of edge pressure with increasing power input. This allows QH-mode plasmas to remain stable to edge localized modes (ELMs) to the highest powers used in DIII-D. At present, the mechanism for this saturation is unknown; if the edge harmonic oscillation (EHO) is playing a role here, the physics is not a simple amplitude dependence. The increase in edge stability with plasma triangularity predicted by the peeling-ballooning theory is consistent with the substantial improvement in pedestal pressure achieved by changing the plasma shape from a single null divertor to a high triangularity double null. Detailed ELITE calculations for the high triangularity plasmas have demonstrated that the plasma operating point is marginally stable to peeling-ballooning modes. Comparison of ELMing, coinjected and quiescent, counterinjected discharges with the same shape, current, toroidal field, electron density, and electron temperature indicates that the edge radial electric field or the edge toroidal rotation are also playing a role in edge stability. The EHO produces electron, main ion, and impurity particle transport at the plasma edge which is more rapid than that produced by ELMs under similar conditions. The EHO also decreases the edge rotation while producing little change in the edge electron and ion temperatures. Other edge electromagnetic modes also produce particle transport; this includes the incoherent, broadband activity seen at high triangularity. Pedestal values of ν* and βT bracketing, those required for International Experimental Thermonuclear Reactor [Nucl. Fusion 39, 2137 (1999)] have been achieved in DIII-D, demonstrating the QH-mode edge densities are sufficient for future devices.

Advances in understanding quiescent H-mode plasmas in DIII-D

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

Burrell, K.H.; West, W.P.; Gohil, P.

2005-05-15

Recent QH-mode research on DIII-D [J. L. Luxon et al., Plasma Physics and Controlled Nuclear Fusion Research 1996 (International Atomic Energy Agency, Vienna, 1987), Vol. I, p. 159] has used the peeling-ballooning modes model of edge magnetohydrodynamic stability as a working hypothesis to organize the data; several predictions of this theory are consistent with the experimental results. Current ramping results indicate that QH modes operate near the edge current limit set by peeling modes. This operating point explains why QH mode is easier to get at lower plasma currents. Power scans have shown a saturation of edge pressure with increasingmore » power input. This allows QH-mode plasmas to remain stable to edge localized modes (ELMs) to the highest powers used in DIII-D. At present, the mechanism for this saturation is unknown; if the edge harmonic oscillation (EHO) is playing a role here, the physics is not a simple amplitude dependence. The increase in edge stability with plasma triangularity predicted by the peeling-ballooning theory is consistent with the substantial improvement in pedestal pressure achieved by changing the plasma shape from a single null divertor to a high triangularity double null. Detailed ELITE calculations for the high triangularity plasmas have demonstrated that the plasma operating point is marginally stable to peeling-ballooning modes. Comparison of ELMing, coinjected and quiescent, counterinjected discharges with the same shape, current, toroidal field, electron density, and electron temperature indicates that the edge radial electric field or the edge toroidal rotation are also playing a role in edge stability. The EHO produces electron, main ion, and impurity particle transport at the plasma edge which is more rapid than that produced by ELMs under similar conditions. The EHO also decreases the edge rotation while producing little change in the edge electron and ion temperatures. Other edge electromagnetic modes also produce particle transport; this includes the incoherent, broadband activity seen at high triangularity. Pedestal values of {nu}{sub *} and {beta}{sub T} bracketing, those required for International Experimental Thermonuclear Reactor [Nucl. Fusion 39, 2137 (1999)] have been achieved in DIII-D, demonstrating the QH-mode edge densities are sufficient for future devices.« less

SOL effects on the pedestal structure in DIII-D discharges

DOE PAGES

Sontag, Aaron C.; Chen, Xi; Canik, John; ...

2017-05-24

SOLPS analysis explains the differences in pedestal structure associated with different ion ∇B drift directions in DIII-D. Core transport models predict that fusion power scales roughly as the square of the pressure at the top of the pedestal, so understanding the effects that determine pedestal structure in steady-state operational scenarios is important to projecting scenarios developed in DIII-D to ITER and other devices. Both experiments and modeling indicate that scrape off layer (SOL) conditions are important in optimizing the pedestal structure for high-beta steady-state scenarios. The SOLPS code is used to provide interpretive analysis of the pedestal and SOL tomore » examine the nature of flows and fueling on the pedestal structure including the effects of drifts in the fluid model. This analysis shows that flows driven by the ion ∇B drift are outward when this drift is toward the x-point in a single-null divertor configuration (favorable ∇B direction for reduced H-mode power threshold), and inward when the drift is away from the x-point (unfavorable ∇B direction). It is hypothesized that these flows decrease the density gradient in the pedestal in the favorable direction, thereby stabilizing the kinetic ballooning mode (KBM) and increasing the pedestal width. Comparisons of pedestal structures in similarly shaped DIII-D steady-state plasmas confirm this change, showing increased density pedestal width and lower peak density and lower separatrix density with the favorable drift direction. The pedestal temperature is higher in the lower density case, resulting in an increased pedestal pressure, which indicates that the increased particle flux does not significantly degrade energy confinement. Modeling of cases with constant ∇B drift direction but changing between the more open lower divertor and more closed upper divertor show that there is increased fueling inside the pedestal with the more open geometry. As a result, the pedestal fueling rate for both attached and detached cases is always lower with more closed divertor geometry than in any cases with more open geometry.« less

SOL effects on the pedestal structure in DIII-D discharges

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

Sontag, Aaron C.; Chen, Xi; Canik, John

SOLPS analysis explains the differences in pedestal structure associated with different ion ∇B drift directions in DIII-D. Core transport models predict that fusion power scales roughly as the square of the pressure at the top of the pedestal, so understanding the effects that determine pedestal structure in steady-state operational scenarios is important to projecting scenarios developed in DIII-D to ITER and other devices. Both experiments and modeling indicate that scrape off layer (SOL) conditions are important in optimizing the pedestal structure for high-beta steady-state scenarios. The SOLPS code is used to provide interpretive analysis of the pedestal and SOL tomore » examine the nature of flows and fueling on the pedestal structure including the effects of drifts in the fluid model. This analysis shows that flows driven by the ion ∇B drift are outward when this drift is toward the x-point in a single-null divertor configuration (favorable ∇B direction for reduced H-mode power threshold), and inward when the drift is away from the x-point (unfavorable ∇B direction). It is hypothesized that these flows decrease the density gradient in the pedestal in the favorable direction, thereby stabilizing the kinetic ballooning mode (KBM) and increasing the pedestal width. Comparisons of pedestal structures in similarly shaped DIII-D steady-state plasmas confirm this change, showing increased density pedestal width and lower peak density and lower separatrix density with the favorable drift direction. The pedestal temperature is higher in the lower density case, resulting in an increased pedestal pressure, which indicates that the increased particle flux does not significantly degrade energy confinement. Modeling of cases with constant ∇B drift direction but changing between the more open lower divertor and more closed upper divertor show that there is increased fueling inside the pedestal with the more open geometry. As a result, the pedestal fueling rate for both attached and detached cases is always lower with more closed divertor geometry than in any cases with more open geometry.« 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

Multi-arm group sequential designs with a simultaneous stopping rule.

PubMed

Urach, S; Posch, M

2016-12-30

Multi-arm group sequential clinical trials are efficient designs to compare multiple treatments to a control. They allow one to test for treatment effects already in interim analyses and can have a lower average sample number than fixed sample designs. Their operating characteristics depend on the stopping rule: We consider simultaneous stopping, where the whole trial is stopped as soon as for any of the arms the null hypothesis of no treatment effect can be rejected, and separate stopping, where only recruitment to arms for which a significant treatment effect could be demonstrated is stopped, but the other arms are continued. For both stopping rules, the family-wise error rate can be controlled by the closed testing procedure applied to group sequential tests of intersection and elementary hypotheses. The group sequential boundaries for the separate stopping rule also control the family-wise error rate if the simultaneous stopping rule is applied. However, we show that for the simultaneous stopping rule, one can apply improved, less conservative stopping boundaries for local tests of elementary hypotheses. We derive corresponding improved Pocock and O'Brien type boundaries as well as optimized boundaries to maximize the power or average sample number and investigate the operating characteristics and small sample properties of the resulting designs. To control the power to reject at least one null hypothesis, the simultaneous stopping rule requires a lower average sample number than the separate stopping rule. This comes at the cost of a lower power to reject all null hypotheses. Some of this loss in power can be regained by applying the improved stopping boundaries for the simultaneous stopping rule. The procedures are illustrated with clinical trials in systemic sclerosis and narcolepsy. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model

PubMed Central

Araki, Susumu; Imai, Shinji; Ishigaki, Hirohito; Mimura, Tomohiro; Nishizawa, Kazuya; Ueba, Hiroaki; Kumagai, Kousuke; Kubo, Mitsuhiko; Mori, Kanji; Ogasawara, Kazumasa; Matsusue, Yoshitaka

2015-01-01

Background and purpose Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. Methods Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). Results The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. Interpretation Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice. PMID:25175660

Smoothness of the future and past trapped sets in Kerr–Newman–Taub-NUT spacetimes

NASA Astrophysics Data System (ADS)

Paganini, Claudio F.; Oancea, Marius A.

2018-03-01

We consider the sets of future/past trapped null geodesics in the exterior region of a sub-extremal Kerr–Newman–Taub-NUT spacetime. We show that from the point of view of any timelike observer outside of such a black hole, trapping can be understood as two smooth sets of spacelike directions on the celestial sphere of the observer.

The Implicit Function Theorem and Non-Existence of Limit of Functions of Several Variables

ERIC Educational Resources Information Center

dos Santos, A. L. C.; da Silva, P. N.

2008-01-01

We use the Implicit Function Theorem to establish a result of non-existence of limit to a certain class of functions of several variables. We consider functions given by quotients such that both the numerator and denominator functions are null at the limit point. We show that the non-existence of the limit of such function is related with the…

Optimal trajectory planning of free-floating space manipulator using differential evolution algorithm

NASA Astrophysics Data System (ADS)

Wang, Mingming; Luo, Jianjun; Fang, Jing; Yuan, Jianping

2018-03-01

The existence of the path dependent dynamic singularities limits the volume of available workspace of free-floating space robot and induces enormous joint velocities when such singularities are met. In order to overcome this demerit, this paper presents an optimal joint trajectory planning method using forward kinematics equations of free-floating space robot, while joint motion laws are delineated with application of the concept of reaction null-space. Bézier curve, in conjunction with the null-space column vectors, are applied to describe the joint trajectories. Considering the forward kinematics equations of the free-floating space robot, the trajectory planning issue is consequently transferred to an optimization issue while the control points to construct the Bézier curve are the design variables. A constrained differential evolution (DE) scheme with premature handling strategy is implemented to find the optimal solution of the design variables while specific objectives and imposed constraints are satisfied. Differ from traditional methods, we synthesize null-space and specialized curve to provide a novel viewpoint for trajectory planning of free-floating space robot. Simulation results are presented for trajectory planning of 7 degree-of-freedom (DOF) kinematically redundant manipulator mounted on a free-floating spacecraft and demonstrate the feasibility and effectiveness of the proposed method.

A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells.

PubMed

Kwiatkowski, David J; Zhang, Hongbing; Bandura, Jennifer L; Heiberger, Kristina M; Glogauer, Michael; el-Hashemite, Nisreen; Onda, Hiroaki

2002-03-01

Tuberous sclerosis (TSC) is a autosomal dominant genetic disorder caused by mutations in either TSC1 or TSC2, and characterized by benign hamartoma growth. We developed a murine model of Tsc1 disease by gene targeting. Tsc1 null embryos die at mid-gestation from a failure of liver development. Tsc1 heterozygotes develop kidney cystadenomas and liver hemangiomas at high frequency, but the incidence of kidney tumors is somewhat lower than in Tsc2 heterozygote mice. Liver hemangiomas were more common, more severe and caused higher mortality in female than in male Tsc1 heterozygotes. Tsc1 null embryo fibroblast lines have persistent phosphorylation of the p70S6K (S6K) and its substrate S6, that is sensitive to treatment with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin. Hyperphosphorylation of S6 is also seen in kidney tumors in the heterozygote mice, suggesting that inhibition of this pathway may have benefit in control of TSC hamartomas.

EFFECTS OF FIELD-LINE TOPOLOGY ON ENERGY PROPAGATION IN THE CORONA

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

Candelaresi, S.; Pontin, D. I.; Hornig, G.

We study the effect of photospheric footpoint motions on magnetic field structures containing magnetic nulls. The footpoint motions are prescribed on the photospheric boundary as a velocity field that entangles the magnetic field. We investigate the propagation of the injected energy, the conversion of energy, emergence of current layers, and other consequences of the nontrivial magnetic field topology in this situation. These boundary motions lead initially to an increase in magnetic and kinetic energy. Following this, the energy input from the photosphere is partially dissipated and partially transported out of the domain through the Poynting flux. The presence of separatrixmore » layers and magnetic null points fundamentally alters the propagation behavior of disturbances from the photosphere into the corona. Depending on the field-line topology close to the photosphere, the energy is either trapped or free to propagate into the corona.« less

Aspects of QCD current algebra on a null plane

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

New method for analyzing dark matter direct detection data

NASA Astrophysics Data System (ADS)

Davis, Jonathan H.; Enßlin, Torsten; BÅ`hm, Céline

2014-02-01

The experimental situation of dark matter direct detection has reached an exciting crossroads, with potential hints of a discovery of dark matter (DM) from the CDMS, CoGeNT, CRESST-II and DAMA experiments in tension with null results from xenon-based experiments such as XENON100 and LUX. Given the present controversial experimental status, it is important that the analytical method used to search for DM in direct detection experiments is both robust and flexible enough to deal with data for which the distinction between signal and background points is difficult, and hence where the choice between setting a limit or defining a discovery region is debatable. In this article we propose a novel (Bayesian) analytical method, which can be applied to all direct detection experiments and which extracts the maximum amount of information from the data. We apply our method to the XENON100 experiment data as a worked example, and show that firstly our exclusion limit at 90% confidence is in agreement with their own for the 225 live days data, but is several times stronger for the 100 live days data. Secondly we find that, due to the two points at low values of S1 and S2 in the 225 days data set, our analysis points to either weak consistency with low-mass dark matter or the possible presence of an unknown background. Given the null result from LUX, the latter scenario seems the more plausible.

Temperature is better than precipitation as a predictor of plant community assembly across a dryland region

USGS Publications Warehouse

Butterfield, Bradley J.; Munson, Seth M.

2016-01-01

QuestionHow closely do plant communities track climate? Research suggests that plant species converge toward similar environmental tolerances relative to the environments that they experience. Whether these patterns apply to severe environments or scale up to plant community-level patterns of relative climatic tolerances is poorly understood. Using estimates of species' climatic tolerances acquired from occurrence records, we determined the contributions of individual species' climatic niche breadths and environmental filtering to the relationships between community-average climatic tolerances and the local climates experienced by those communities.LocationSouthwestern United States drylands.MethodsInterspecific variation in niche breadth was assessed as a function of species' climatic optima (median climatic niche value). The relationships between climatic optima and tolerances were used as null expectations for the relationship between abundance-weighted mean climatic tolerances of communities and the local climate of that community. Deviations from this null expectation indicate that species with greater or lesser climatic tolerances are favoured relative to co-occurring species. The intensity of environmental filtering was estimated by comparing the range of climatic tolerances within each community to a null distribution generated from a random assembly algorithm.ResultsThe temperature niches of species were consistently symmetrical and of similar breadths, regardless of their temperature optima. In contrast, precipitation niches were skewed toward wetter conditions, and niche breadth increased with increasing precipitation optima. At the community level, relationships with climate were much stronger for temperature than for precipitation. Furthermore, cold and heat were stronger assembly filters than drought or precipitation, with the intensity of environmental filtering increasing at both ends of climatic gradients. Community-average climatic tolerances did deviate significantly from null expectations, indicating that species with higher or lower relative climatic tolerances were favoured under certain conditions.ConclusionsDespite strong water limitation of plant performance in dryland ecosystems, communities tracked variation in temperature much more closely, intimating strong responses to anticipated temperature increases. Furthermore, abundance distributions were biased toward species with higher or lower relative climatic tolerances under different climatic conditions, but predictably so, indicating the need for assembly models that include processes other than simple environmental filtering.

The Development of Anaphora Resolution at the Syntax-Discourse Interface: Pronominal Subjects in Greek Learners of Spanish

ERIC Educational Resources Information Center

Lozano, Cristóbal

2018-01-01

This study explores the development of anaphora resolution (AR) in late sequential bilinguals, namely, adult Greek learners of Spanish at three proficiency levels (intermediate, lower advanced, upper advanced). The use of an overt/null pronominal subject anaphor is investigated in three discourse contexts: topic-continuity (a single antecedent…

Natural disease history of mouse models for limb girdle muscular dystrophy types 2D and 2F

PubMed Central

Putker, K.; Tanganyika-de Winter, C. L.; Boertje-van der Meulen, J. W.; van Vliet, L.; Overzier, M.; Plomp, J. J.; Aartsma-Rus, A.; van Putten, M.

2017-01-01

Limb-girdle muscular dystrophy types 2D and 2F (LGMD 2D and 2F) are autosomal recessive disorders caused by mutations in the alpha- and delta sarcoglycan genes, respectively, leading to severe muscle weakness and degeneration. The cause of the disease has been well characterized and a number of animal models are available for pre-clinical studies to test potential therapeutic interventions. To facilitate transition from drug discovery to clinical trials, standardized procedures and natural disease history data were collected for these mouse models. Implementing the TREAD-NMD standardized operating procedures, we here subjected LGMD2D (SGCA-null), LGMD2F (SGCD-null) and wild type (C57BL/6J) mice to five functional tests from the age of 4 to 32 weeks. To assess whether the functional test regime interfered with disease pathology, sedentary groups were taken along. Muscle physiology testing of tibialis anterior muscle was performed at the age of 34 weeks. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Muscle histopathology and gene expression was analysed in skeletal muscles and heart. Mice successfully accomplished the functional tests, which did not interfere with disease pathology. Muscle function of SGCA- and SGCD-null mice was impaired and declined over time. Interestingly, female SGCD-null mice outperformed males in the two and four limb hanging tests, which proved the most suitable non-invasive tests to assess muscle function. Muscle physiology testing of tibialis anterior muscle revealed lower specific force and higher susceptibility to eccentric-induced damage in LGMD mice. Analyzing muscle histopathology and gene expression, we identified the diaphragm as the most affected muscle in LGMD strains. Cardiac fibrosis was found in SGCD-null mice, being more severe in males than in females. Our study offers a comprehensive natural history dataset which will be useful to design standardized tests and future pre-clinical studies in LGMD2D and 2F mice. PMID:28797108

Interactions of Seedborne Bacterial Pathogens with Host and Non-Host Plants in Relation to Seed Infestation and Seedling Transmission

PubMed Central

Dutta, Bhabesh; Gitaitis, Ronald; Smith, Samuel; Langston, David

2014-01-01

The ability of seed-borne bacterial pathogens (Acidovorax citrulli, Clavibacter michiganensis subsp. michiganensis, Pseudomonas syringae pv. tomato, Xanthomonas euvesicatoria, and Pseudomonas syringae pv. glycinea) to infest seeds of host and non-host plants (watermelon, tomato, pepper, and soybean) and subsequent pathogen transmission to seedlings was investigated. A non-pathogenic, pigmented strain of Serratia marcescens was also included to assess a null-interacting situation with the same plant species. Flowers of host and non-host plants were inoculated with 1×106 colony forming units (CFUs)/flower for each bacterial species and allowed to develop into fruits or umbels (in case of onion). Seeds harvested from each host/non-host bacterial species combination were assayed for respective bacteria by plating on semi-selective media. Additionally, seedlots for each host/non-host bacterial species combination were also assayed for pathogen transmission by seedling grow-out (SGO) assays under greenhouse conditions. The mean percentage of seedlots infested with compatible and incompatible pathogens was 31.7 and 30.9% (by plating), respectively and they were not significantly different (P = 0.67). The percentage of seedlots infested with null-interacting bacterial species was 16.8% (by plating) and it was significantly lower than the infested lots generated with compatible and incompatible bacterial pathogens (P = 0.03). None of the seedlots with incompatible/null-interacting bacteria developed symptoms on seedlings; however, when seedlings were assayed for epiphytic bacterial presence, 19.5 and 9.4% of the lots were positive, respectively. These results indicate that the seeds of non-host plants can become infested with incompatible and null-interacting bacterial species through flower colonization and they can be transmitted via epiphytic colonization of seedlings. In addition, it was also observed that flowers and seeds of non-host plants can be colonized by compatible/incompatible/null-interacting bacteria to higher populations; however, the level of colonization differed significantly depending on the type of bacterial species used. PMID:24936863

Primordial power spectrum features and consequences

NASA Astrophysics Data System (ADS)

Goswami, G.

2014-03-01

The present Cosmic Microwave Background (CMB) temperature and polarization anisotropy data is consistent with not only a power law scalar primordial power spectrum (PPS) with a small running but also with the scalar PPS having very sharp features. This has motivated inflationary models with such sharp features. Recently, even the possibility of having nulls in the power spectrum (at certain scales) has been considered. The existence of these nulls has been shown in linear perturbation theory. What shall be the effect of higher order corrections on such nulls? Inspired by this question, we have attempted to calculate quantum radiative corrections to the Fourier transform of the 2-point function in a toy field theory and address the issue of how these corrections to the power spectrum behave in models in which the tree-level power spectrum has a sharp dip (but not a null). In particular, we have considered the possibility of the relative enhancement of radiative corrections in a model in which the tree-level spectrum goes through a dip in power at a certain scale. The mode functions of the field (whose power spectrum is to be evaluated) are chosen such that they undergo the kind of dynamics that leads to a sharp dip in the tree level power spectrum. Next, we have considered the situation in which this field has quartic self interactions, and found one loop correction in a suitably chosen renormalization scheme. Thus, we have attempted to answer the following key question in the context of this toy model (which is as important in the realistic case): In the chosen renormalization scheme, can quantum radiative corrections be enhanced relative to tree-level power spectrum at scales, at which sharp dips appear in the tree-level spectrum?

[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.

Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals

PubMed Central

Prajapati, Saumya; Tao, Jinhui; Ruan, Qichao; De Yoreo, James J.; Moradian-Oldak, Janet

2015-01-01

Reconstruction of enamel-like materials is a central topic of research in dentistry and material sciences. The importance of precise proteolytic mechanisms in amelogenesis to form a hard tissue with more than 95% mineral content has already been reported. A mutation in the Matrix Metalloproteinase-20 (MMP-20) gene results in hypomineralized enamel that is thin, disorganized and breaks from the underlying dentin. We hypothesized that the absence of MMP-20 during amelogenesis results in the occlusion of amelogenin in the enamel hydroxyapatite crystals. We used spectroscopy and electron microscopy techniques to qualitatively and quantitatively analyze occluded proteins within the isolated enamel crystals from MMP-20 null and Wild type (WT) mice. Our results showed that the isolated enamel crystals of MMP-20 null mice had more organic macromolecules occluded inside them than enamel crystals from the WT. The crystal lattice arrangements of MMP-20 null enamel crystals analyzed by High Resolution Transmission Electron Microscopy (HRTEM) were found to be significantly different from those of the WT. Raman studies indicated that the crystallinity of the MMP-20 null enamel crystals was lower than that of the WT. In conclusion, we present a novel functional mechanism of MMP-20, specifically prevention of unwanted organic material entrapped in the forming enamel crystals, which occurs as the result of precise amelogenin cleavage. MMP-20 action guides the growth morphology of the forming hydroxyapatite crystals and enhances their crystallinity. Elucidating such molecular mechanisms can be applied in the design of novel biomaterials for future clinical applications in dental restoration or repair. PMID:26513418

Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals.

PubMed

Prajapati, Saumya; Tao, Jinhui; Ruan, Qichao; De Yoreo, James J; Moradian-Oldak, Janet

2016-01-01

Reconstruction of enamel-like materials is a central topic of research in dentistry and material sciences. The importance of precise proteolytic mechanisms in amelogenesis to form a hard tissue with more than 95% mineral content has already been reported. A mutation in the Matrix Metalloproteinase-20 (MMP-20) gene results in hypomineralized enamel that is thin, disorganized and breaks from the underlying dentin. We hypothesized that the absence of MMP-20 during amelogenesis results in the occlusion of amelogenin in the enamel hydroxyapatite crystals. We used spectroscopy and electron microscopy techniques to qualitatively and quantitatively analyze occluded proteins within the isolated enamel crystals from MMP-20 null and Wild type (WT) mice. Our results showed that the isolated enamel crystals of MMP-20 null mice had more organic macromolecules occluded inside them than enamel crystals from the WT. The crystal lattice arrangements of MMP-20 null enamel crystals analyzed by High Resolution Transmission Electron Microscopy (HRTEM) were found to be significantly different from those of the WT. Raman studies indicated that the crystallinity of the MMP-20 null enamel crystals was lower than that of the WT. In conclusion, we present a novel functional mechanism of MMP-20, specifically prevention of unwanted organic material entrapped in the forming enamel crystals, which occurs as the result of precise amelogenin cleavage. MMP-20 action guides the growth morphology of the forming hydroxyapatite crystals and enhances their crystallinity. Elucidating such molecular mechanisms can be applied in the design of novel biomaterials for future clinical applications in dental restoration or repair. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Bassuk, James; Lendvay, Thomas S.; Sweet, Robert

Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functionalmore » protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.« less

Vegetarianism and colorectal cancer risk in a low-selenium environment: effect modification by selenium status? A possible factor contributing to the null results in British vegetarians.

PubMed

Sobiecki, Jakub G

2017-08-01

Despite the consistent findings of lower total cancer incidence in vegetarians than in meat-eaters in the UK, the results of studies of colorectal cancer (CRC) risk in British vegetarians have largely been null. This was in contrast to the hypothesis of a decreased risk of CRC in this population due to null intake of red and processed meats and increased intake of fibre. Although the data are inconsistent, it has been suggested that selenium (Se) status may influence CRC risk. A literature review was performed of studies on CRC risk in vegetarians, Se intakes and status in vegetarians, and changes of Se intakes and status in the UK throughout the follow-up periods of studies on CRC risk in British vegetarians. Vegetarians in the UK and other low-Se areas were found to have low Se intakes and status compared to non-vegetarians. There was some evidence of a reverse J-shaped curve of Se intakes and status in the UK throughout the last three decades. These presumed patterns were followed by the changes in CRC mortality or incidence in British vegetarians during this period. Available data on Se intake and status in British vegetarians, as well as the relationship between their secular changes in the UK and changes in CRC risk in this dietary group, are compatible with the hypothesis that low Se status may contribute to the largely null results of studies of CRC risk in vegetarians in the UK.

Green's function and Bloch theory for the analysis of the dynamic response of a periodically supported beam to a moving load

NASA Astrophysics Data System (ADS)

Lassoued, R.; Lecheheb, M.; Bonnet, G.

2012-08-01

This paper describes an analytical method for the wave field induced by a moving load on a periodically supported beam. The Green's function for an Euler beam without support is evaluated by using the direct integration. Afterwards, it introduces the supports into the model established by using the superposition principle which states that the response from all the sleeper points and from the external point force add up linearly to give a total response. The periodicity of the supports is described by Bloch's theorem. The homogeneous system thus obtained represents a linear differential equation which governs rail response. It is initially solved in the homogeneous case, and it admits a no null solution if its determinant is null, this permits the establishment the dispersion equation to Bloch waves and wave bands. The Bloch waves and dispersion curves contain all the physics of the dynamic problem and the wave field induced by a dynamic load applied to the system is finally obtained by decomposition into Bloch waves, similarly to the usual decomposition into dynamic modes on a finite structure. The method is applied to obtain the field induced by a load moving at constant velocity on a thin beam supported by periodic elastic supports.

Limits on the cosmological abundance of supermassive compact objects from a millilensing search in gamma-ray burst data.

PubMed

Nemiroff, R J; Marani, G F; Norris, J P; Bonnell, J T

2001-01-22

A new search for the gravitational lens effects of a significant cosmological density of supermassive compact objects (SCOs) on gamma-ray bursts (GRBs) has yielded a null result. We inspected the timing data of 774 BATSE-triggered GRBs for evidence of millilensing: repeated peaks similar in light-curve shape and spectra. Our null detection leads us to conclude that, in all candidate universes simulated, Omega(SCO)<0.1 is favored for SCO masses in the range 10(5)

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

An innovative small angle slot divertor concept for long pulse advanced tokamaks

NASA Astrophysics Data System (ADS)

Guo, Houyang

2017-10-01

A new Small Angle Slot (SAS) divertor is being developed in DIII-D to address the challenge of efficient divertor heat dispersal at the relatively low plasma density required for non-inductive current drive in future advanced tokamaks. SAS features a small incident angle near the plasma strike point on the divertor target plate with a progressively opening slot. SOLPS (B2-Eirene) edge code analysis finds that SAS can achieve strong plasma cooling when the strike point is placed near the small angle target plate in the slot, leading to low electron temperature Te across the entire divertor target. This is enabled by strong coupling between a gas tight slot and directed neutral recycling by the small angle target to enhance neutral buildup near the target. SOLPS analysis reveals a strong correlation between Te and D2 density at the target for various divertor configurations including the flat target, slanted target, and lower single null divertor. The strong correlation suggests that achievement of low Te may reduce essentially to identifying the divertor baffle geometry that achieves the highest target gas density at a given upstream condition. The SAS divertor concept has recently been tested in DIII-D for a range of plasma configurations and conditions with precise control of slot strike point location. In confirmation of SOLPS predictions, a sharp transition is observed when the strike point is moved to the critical outer corner of SAS. A set of Langmuir probes imbedded in SAS show that the Te radial profile, which is peaked at the strike point when it is located away from the SAS corner, becomes low across the target when the strike point is located near the corner. With further increase in density, deep-slot detachment occurs with Te 1 eV, measured by the unique DIII-D divertor Thomson Scattering diagnostic. Work supported by US DOE under DE-FC02-04ER54698.

Computational tools for calculating alternative muscle force patterns during motion: a comparison of possible solutions.

PubMed

Martelli, Saulo; Calvetti, Daniela; Somersalo, Erkki; Viceconti, Marco; Taddei, Fulvia

2013-08-09

Comparing the available electromyography (EMG) and the related uncertainties with the space of muscle forces potentially driving the same motion can provide insights into understanding human motion in healthy and pathological neuromotor conditions. However, it is not clear how effective the available computational tools are in completely sample the possible muscle forces. In this study, we compared the effectiveness of Metabolica and the Null-Space algorithm at generating a comprehensive spectrum of possible muscle forces for a representative motion frame. The hip force peak during a selected walking trial was identified using a lower-limb musculoskeletal model. The joint moments, the muscle lever arms, and the muscle force constraints extracted from the model constituted the indeterminate equilibrium equation at the joints. Two spectra, each containing 200,000 muscle force samples, were calculated using Metabolica and the Null-Space algorithm. The full hip force range was calculated using optimization and compared with the hip force ranges derived from the Metabolica and the Null-Space spectra. The Metabolica spectrum spanned a much larger force range than the NS spectrum, reaching 811N difference for the gluteus maximus intermediate bundle. The Metabolica hip force range exhibited a 0.3-0.4 BW error on the upper and lower boundaries of the full hip force range (3.4-11.3 BW), whereas the full range was imposed in the NS spectrum. The results suggest that Metabolica is well suited for exhaustively sample the spectrum of possible muscle recruitment strategy. Future studies will investigate the muscle force range in healthy and pathological neuromotor conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recognition deficits in mice carrying mutations of genes encoding BLOC-1 subunits pallidin or dysbindin.

PubMed

Spiegel, S; Chiu, A; James, A S; Jentsch, J D; Karlsgodt, K H

2015-11-01

Numerous studies have implicated DTNBP1, the gene encoding dystrobrevin-binding protein or dysbindin, as a candidate risk gene for schizophrenia, though this relationship remains somewhat controversial. Variation in dysbindin, and its location on chromosome 6p, has been associated with cognitive processes, including those relying on a complex system of glutamatergic and dopaminergic interactions. Dysbindin is one of the seven protein subunits that comprise the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Dysbindin protein levels are lower in mice with null mutations in pallidin, another gene in the BLOC-1, and pallidin levels are lower in mice with null mutations in the dysbindin gene, suggesting that multiple subunit proteins must be present to form a functional oligomeric complex. Furthermore, pallidin and dysbindin have similar distribution patterns in a mouse and human brain. Here, we investigated whether the apparent correspondence of pallid and dysbindin at the level of gene expression is also found at the level of behavior. Hypothesizing a mutation leading to underexpression of either of these proteins should show similar phenotypic effects, we studied recognition memory in both strains using the novel object recognition task (NORT) and social novelty recognition task (SNRT). We found that mice with a null mutation in either gene are impaired on SNRT and NORT when compared with wild-type controls. These results support the conclusion that deficits consistent with recognition memory impairment, a cognitive function that is impaired in schizophrenia, result from either pallidin or dysbindin mutations, possibly through degradation of BLOC-1 expression and/or function. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Eddy current-nulled convex optimized diffusion encoding (EN-CODE) for distortion-free diffusion tensor imaging with short echo times.

PubMed

Aliotta, Eric; Moulin, Kévin; Ennis, Daniel B

2018-02-01

To design and evaluate eddy current-nulled convex optimized diffusion encoding (EN-CODE) gradient waveforms for efficient diffusion tensor imaging (DTI) that is free of eddy current-induced image distortions. The EN-CODE framework was used to generate diffusion-encoding waveforms that are eddy current-compensated. The EN-CODE DTI waveform was compared with the existing eddy current-nulled twice refocused spin echo (TRSE) sequence as well as monopolar (MONO) and non-eddy current-compensated CODE in terms of echo time (TE) and image distortions. Comparisons were made in simulations, phantom experiments, and neuro imaging in 10 healthy volunteers. The EN-CODE sequence achieved eddy current compensation with a significantly shorter TE than TRSE (78 versus 96 ms) and a slightly shorter TE than MONO (78 versus 80 ms). Intravoxel signal variance was lower in phantoms with EN-CODE than with MONO (13.6 ± 11.6 versus 37.4 ± 25.8) and not different from TRSE (15.1 ± 11.6), indicating good robustness to eddy current-induced image distortions. Mean fractional anisotropy values in brain edges were also significantly lower with EN-CODE than with MONO (0.16 ± 0.01 versus 0.24 ± 0.02, P < 1 x 10 -5 ) and not different from TRSE (0.16 ± 0.01 versus 0.16 ± 0.01, P = nonsignificant). The EN-CODE sequence eliminated eddy current-induced image distortions in DTI with a TE comparable to MONO and substantially shorter than TRSE. Magn Reson Med 79:663-672, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Why We Should Not Be Indifferent to Specification Choices for Difference-in-Differences.

PubMed

Ryan, Andrew M; Burgess, James F; Dimick, Justin B

2015-08-01

To evaluate the effects of specification choices on the accuracy of estimates in difference-in-differences (DID) models. Process-of-care quality data from Hospital Compare between 2003 and 2009. We performed a Monte Carlo simulation experiment to estimate the effect of an imaginary policy on quality. The experiment was performed for three different scenarios in which the probability of treatment was (1) unrelated to pre-intervention performance; (2) positively correlated with pre-intervention levels of performance; and (3) positively correlated with pre-intervention trends in performance. We estimated alternative DID models that varied with respect to the choice of data intervals, the comparison group, and the method of obtaining inference. We assessed estimator bias as the mean absolute deviation between estimated program effects and their true value. We evaluated the accuracy of inferences through statistical power and rates of false rejection of the null hypothesis. Performance of alternative specifications varied dramatically when the probability of treatment was correlated with pre-intervention levels or trends. In these cases, propensity score matching resulted in much more accurate point estimates. The use of permutation tests resulted in lower false rejection rates for the highly biased estimators, but the use of clustered standard errors resulted in slightly lower false rejection rates for the matching estimators. When treatment and comparison groups differed on pre-intervention levels or trends, our results supported specifications for DID models that include matching for more accurate point estimates and models using clustered standard errors or permutation tests for better inference. Based on our findings, we propose a checklist for DID analysis. © Health Research and Educational Trust.

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.

High-sensitivity observations of 28 pulsars

NASA Technical Reports Server (NTRS)

Weisberg, J. M.; Armstrong, B. K.; Backus, P. R.; Cordes, J. M.; Boriakoff, V.

1986-01-01

Average 430-MHz pulse profiles and, where possible, modulation indices and pulse-nulling fractions are computed for 28 pulsars. Morphological classifications are determined for most of the pulsars. It is found that core emission components tend to have lower modulation indices than conal components, and that pulsars having only a core component never exhibit pulse pulling. PSR 1612 + 07 is shown to undergo mode changes.

The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis.

PubMed

Starrett, Gabriel J; Luengas, Elizabeth M; McCann, Jennifer L; Ebrahimi, Diako; Temiz, Nuri A; Love, Robin P; Feng, Yuqing; Adolph, Madison B; Chelico, Linda; Law, Emily K; Carpenter, Michael A; Harris, Reuben S

2016-09-21

Cytosine mutations within TCA/T motifs are common in cancer. A likely cause is the DNA cytosine deaminase APOBEC3B (A3B). However, A3B-null breast tumours still have this mutational bias. Here we show that APOBEC3H haplotype I (A3H-I) provides a likely solution to this paradox. A3B-null tumours with this mutational bias have at least one copy of A3H-I despite little genetic linkage between these genes. Although deemed inactive previously, A3H-I has robust activity in biochemical and cellular assays, similar to A3H-II after compensation for lower protein expression levels. Gly105 in A3H-I (versus Arg105 in A3H-II) results in lower protein expression levels and increased nuclear localization, providing a mechanism for accessing genomic DNA. A3H-I also associates with clonal TCA/T-biased mutations in lung adenocarcinoma suggesting this enzyme makes broader contributions to cancer mutagenesis. These studies combine to suggest that A3B and A3H-I, together, explain the bulk of 'APOBEC signature' mutations in cancer.

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.

The Simple Map for a Single-null Divertor Tokamak: How to Find the Last Good Surface

NASA Astrophysics Data System (ADS)

Phan, Huong; Ali, Halima; Punjabi, Alkesh

2000-10-01

The Simple Map^1 is a representation of the magnetic field inside a single-null divertor tokamak. It is given by the equations: X_n+1=X_n kYn (1-Y_n), Y_n+1= Y_n+kX_n+1. These equations mimic the motion of the magnetic field lines in a single-null divertor tokamak. The fixed stable point is (0,0) and the unstable fixed oint is (0,1). k is fixed at 0.60. In our work, the starting values of Y in the map is kept in the interval of 0 to 1, and the starting value of X is 0. Using the successive bifurcation method, we first run these equations for 10^6 iterations to find the approximate value of Y when chaos occurs. We examine the neighborhood of this Y value to find the exact value of Y for the last good surface. We call this value Y_lgs. We find Y_lgs to be 0.997135768 for k=0.60 and X=0. This work is supported by US DOE OFES. Ms. Huong Phan is a HU CFRT Summer Fusion High School Workshop Scholar from Andrew P. Hill High School in California. She is supported by 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)

Systemic PPARγ deletion causes severe disturbance in fluid homeostasis in mice

PubMed Central

Zhou, Li; Panasiuk, Alexandra; Downton, Maicy; Zhao, Daqiang; Yang, Baoxue; Jia, Zhanjun

2015-01-01

The pharmacological action of peroxisome proliferator-activated receptor (PPAR)γ in promoting sodium and water retention is well documented as highlighted by the major side-effect of body weight gain and edema associated with thiazolidinedione use. However, a possible physiological role of PPARγ in regulation of fluid metabolism has not been reported by previous studies. Here we analyzed fluid metabolism in inducible whole-body PPARγ knockout mice. The null mice developed severe polydipsia and polyuria, reduced urine osmolality, and modest hyperphagia. The phenomenon persisted during 3 days of pair feeding and pair drinking, accompanied by progressive weight loss. After 24 h water deprivation, the null mice had a lower urine osmolality, a higher urine volume, a greater weight loss, and a greater rise in hematocrit than the floxed control. Urinary vasopressin (AVP) excretion was not different between the genotypes under basal condition or after WD. The response of urine osmolality to acute and chronic 1-desamino-8-d-arginine vasopressin treatment was attenuated in the null mice, but the total abundance or phosphorylation of aquaporin 2 (AQP2) in the kidney or AVP-induced cAMP production in inner medullary collecting duct suspensions was unaffected. Overall, PPARγ participates in physiological control of fluid homeostasis through an unknown mechanism involving cAMP/AQP2-independent enhancement of AVP response. PMID:26330489

Trust in Leadership DEOCS 4.1 Construct Validity Summary

DTIC Science & Technology

2017-08-01

Item Corrected Item- Total Correlation Cronbach’s Alpha if Item Deleted Four-point Scale Items I can depend on my immediate supervisor to meet...1974) were used to assess the fit between the data and the factor. The BTS hypothesizes that the correlation matrix is an identity matrix. The...to reject the null hypothesis that the correlation matrix is an identity, and to conclude that the factor analysis is an appropriate method to

CPU Performance Counter-Based Problem Diagnosis for Software Systems

DTIC Science & Technology

2009-09-01

application servers and implementation techniques), this thesis only used the Enterprise Java Bean (EJB) SessionBean version of RUBiS. The PHP and Servlet ...collection statistics at the Java Virtual Machine (JVM) level can be reused for any Java application. Other examples of gray-box instrumentation include path...used gray-box approaches. For example, PinPoint [11, 14] and [29] use request tracing to diagnose Java exceptions, endless calls, and null calls in

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

Using a plenoptic sensor to reconstruct vortex phase structures.

PubMed

Wu, Chensheng; Ko, Jonathan; Davis, Christopher C

2016-07-15

A branch point problem and its solution commonly involve recognizing and reconstructing a vortex phase structure around a singular point. In laser beam propagation through random media, the destructive phase contributions from various parts of a vortex phase structure will cause a dark area in the center of the beam's intensity profile. This null of intensity can, in turn, prevent the vortex phase structure from being recognized. In this Letter, we show how to use a plenoptic sensor to transform the light field of a vortex beam so that a simple and direct reconstruction algorithm can be applied to reveal the vortex phase structure. As a result, we show that the plenoptic sensor is effective in detecting branch points and can be used to reconstruct phase distortion in a beam in a wide sense.

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.

Regulator of G protein signaling-12 modulates the dopamine transporter in ventral striatum and locomotor responses to psychostimulants.

PubMed

Gross, Joshua D; Kaski, Shane W; Schroer, Adam B; Wix, Kimberley A; Siderovski, David P; Setola, Vincent

2018-02-01

Regulators of G protein signaling are proteins that accelerate the termination of effector stimulation after G protein-coupled receptor activation. Many regulators of G protein signaling proteins are highly expressed in the brain and therefore considered potential drug discovery targets for central nervous system pathologies; for example, here we show that RGS12 is highly expressed in microdissected mouse ventral striatum. Given a role for the ventral striatum in psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss significantly decreased hyperlocomotion to lower doses of both amphetamine and cocaine; however, other outcomes of administration (sensitization and conditioned place preference) were unaffected, suggesting that RGS12 does not function in support of the rewarding properties of these psychostimulants. To test whether observed response changes upon RGS12 loss were caused by changes to dopamine transporter expression and/or function, we prepared crude membranes from the brains of wild-type and RGS12-null mice and measured dopamine transporter-selective [ 3 H]WIN 35428 binding, revealing an increase in dopamine transporter levels in the ventral-but not dorsal-striatum of RGS12-null mice. To address dopamine transporter function, we prepared striatal synaptosomes and measured [ 3 H]dopamine uptake. Consistent with increased [ 3 H]WIN 35428 binding, dopamine transporter-specific [ 3 H]dopamine uptake in RGS12-null ventral striatal synaptosomes was found to be increased. Decreased amphetamine-induced locomotor activity and increased [ 3 H]WIN 35428 binding were recapitulated with an independent RGS12-null mouse strain. Thus, we propose that RGS12 regulates dopamine transporter expression and function in the ventral striatum, affecting amphetamine- and cocaine-induced increases in dopamine levels that specifically elicit acute hyperlocomotor responses.

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function

PubMed Central

Chaudhary, Ketul R.; Batchu, Sri Nagarjun; Das, Dipankar; Suresh, Mavanur R.; Falck, John R.; Graves, Joan P.; Zeldin, Darryl C.; Seubert, John M.

2009-01-01

Aims This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null). Methods and results Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C ε and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3β was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts. Conclusion Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events. PMID:19401302

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

PubMed Central

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

2015-01-01

Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2–59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. PMID:26282580

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

Chung, Chi-Jung; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Huang, Chao-Yuan

Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain riskmore » factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.« less

Prolonged QT interval and lipid alterations beyond β-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts

PubMed Central

Gélinas, Roselle; Thompson-Legault, Julie; Bouchard, Bertrand; Daneault, Caroline; Mansour, Asmaa; Gillis, Marc-Antoine; Charron, Guy; Gavino, Victor; Labarthe, François

2011-01-01

Patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency frequently present cardiomyopathy and heartbeat disorders. However, the underlying factors, which may be of cardiac or extra cardiac origins, remain to be elucidated. In this study, we tested for metabolic and functional alterations in the heart from 3- and 7-mo-old VLCAD null mice and their littermate counterparts, using validated experimental paradigms, namely, 1) ex vivo perfusion in working mode, with concomitant evaluation of myocardial contractility and metabolic fluxes using 13C-labeled substrates under various conditions; as well as 2) in vivo targeted lipidomics, gene expression analysis as well as electrocardiogram monitoring by telemetry in mice fed various diets. Unexpectedly, when perfused ex vivo, working VLCAD null mouse hearts maintained values similar to those of the controls for functional parameters and for the contribution of exogenous palmitate to β-oxidation (energy production), even at high palmitate concentration (1 mM) and increased energy demand (with 1 μM epinephrine) or after fasting. However, in vivo, these hearts displayed a prolonged rate-corrected QT (QTc) interval under all conditions examined, as well as the following lipid alterations: 1) age- and condition-dependent accumulation of triglycerides, and 2) 20% lower docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) in membrane phospholipids. The latter was independent of liver but affected by feeding a diet enriched in saturated fat (exacerbated) or fish oil (attenuated). Our finding of a longer QTc interval in VLCAD null mice appears to be most relevant given that such condition increases the risk of sudden cardiac death. PMID:21685264

Candida albicans Iff11, a secreted protein required for cell wall structure and virulence.

PubMed

Bates, Steven; de la Rosa, José M; MacCallum, Donna M; Brown, Alistair J P; Gow, Neil A R; Odds, Frank C

2007-06-01

The Candida albicans cell wall is the immediate point of contact with the host and is implicated in the host-fungal interaction and virulence. To date, a number of cell wall proteins have been identified and associated with virulence. Analysis of the C. albicans genome has identified the IFF gene family as encoding the largest family of cell wall-related proteins. This family is also conserved in a range of other Candida species. Iff11 differs from other family members in lacking a GPI anchor, and we have demonstrated it to be O glycosylated and secreted in C. albicans. A null mutant lacking IFF11 was hypersensitive to cell wall-damaging agents, suggesting a role in cell wall organization. In a murine model of systemic infection the null mutant was highly attenuated in virulence, and survival-standardized infections suggest it is required to establish an infection. This work provides the first evidence of the importance of this gene family in the host-fungal interaction and virulence.

Design Optimization for a Maglev System Employing Flux Eliminating Coils

NASA Technical Reports Server (NTRS)

Davey, Kent R.

1996-01-01

Flux eliminating coils have received no little attention over the past thirty years as an alternative for realizing lift in a MAGLEV system. When the magnets on board the vehicle are displaced from the equilibrium or null flux point of these coils, they induce current in those coils which act to restore the coil to its null flux or centerline position. The question being addressed in this paper is that of how to choose the best coil for a given system. What appears at first glance to be an innocent question is in fact one that is actually quite involved, encompassing both the global economics and physics of the system. The real key in analyzing that question is to derive an optimization index or functional which represents the cost of the system subject to constraints, the primary constraint being that the vehicle lift itself at a certain threshold speed. Outlined in this paper is one scenario for realizing a total system design which uses sequential quadratic programming techniques.

TMJ symptoms reduce chewing amplitude and velocity, and increase variability.

PubMed

Radke, John C; Kamyszek, Greg J; Kull, Robert S; Velasco, Gerardo R

2017-09-04

The null hypothesis was that mandibular amplitude, velocity, and variability during gum chewing are not altered in subjects with temporomandibular joint (TMJ) internal derangements (ID). Thirty symptomatic subjects with confirmed ID consented to chew gum on their left and right sides while being tracked by an incisor-point jaw tracker. A gender and age matched control group (p > 0.67) volunteered to be likewise recorded. Student's t-test compared the ID group's mean values to the control group. The control group opened wider (p < 0.05) and chewed faster (p < 0.05) than the ID group. The mean cycle time of the ID group (0.929 s) was longer than the control group (0.751 s; p < 0.05) and more variable (p < 0.05). The ID group exhibited reduced amplitude and velocity but increased variability during chewing. The null hypothesis was rejected. Further study of adaptation to ID by patients should be pursued.

Who Was Walking on the Beach? Anaphora Resolution in Spanish Heritage Speakers and Adult Second Language Learners

ERIC Educational Resources Information Center

Keating, Gregory D.; VanPatten, Bill; Jegerski, Jill

2011-01-01

The position of antecedent strategy (Carminati, 2002) claims that speakers of null-subject languages prefer to resolve intrasentential anaphora by linking pro to an antecedent in the specifier of the inflection phrase and the overt pronoun to an antecedent lower in the clause. The present study has two aims: (a) to determine whether adult early…

Flow convergence caused by a salinity minimum in a tidal channel

USGS Publications Warehouse

Warner, John C.; Schoellhamer, David H.; Burau, Jon R.; Schladow, S. Geoffrey

2006-01-01

Residence times of dissolved substances and sedimentation rates in tidal channels are affected by residual (tidally averaged) circulation patterns. One influence on these circulation patterns is the longitudinal density gradient. In most estuaries the longitudinal density gradient typically maintains a constant direction. However, a junction of tidal channels can create a local reversal (change in sign) of the density gradient. This can occur due to a difference in the phase of tidal currents in each channel. In San Francisco Bay, the phasing of the currents at the junction of Mare Island Strait and Carquinez Strait produces a local salinity minimum in Mare Island Strait. At the location of a local salinity minimum the longitudinal density gradient reverses direction. This paper presents four numerical models that were used to investigate the circulation caused by the salinity minimum: (1) A simple one-dimensional (1D) finite difference model demonstrates that a local salinity minimum is advected into Mare Island Strait from the junction with Carquinez Strait during flood tide. (2) A three-dimensional (3D) hydrodynamic finite element model is used to compute the tidally averaged circulation in a channel that contains a salinity minimum (a change in the sign of the longitudinal density gradient) and compares that to a channel that contains a longitudinal density gradient in a constant direction. The tidally averaged circulation produced by the salinity minimum is characterized by converging flow at the bed and diverging flow at the surface, whereas the circulation produced by the constant direction gradient is characterized by converging flow at the bed and downstream surface currents. These velocity fields are used to drive both a particle tracking and a sediment transport model. (3) A particle tracking model demonstrates a 30 percent increase in the residence time of neutrally buoyant particles transported through the salinity minimum, as compared to transport through a constant direction density gradient. (4) A sediment transport model demonstrates increased deposition at the near-bed null point of the salinity minimum, as compared to the constant direction gradient null point. These results are corroborated by historically noted large sedimentation rates and a local maximum of selenium accumulation in clams at the null point in Mare Island Strait.

Compact solar UV burst triggered in a magnetic field with a fan-spine topology

NASA Astrophysics Data System (ADS)

Chitta, L. P.; Peter, H.; Young, P. R.; Huang, Y.-M.

2017-09-01

Context. Solar ultraviolet (UV) bursts are small-scale features that exhibit intermittent brightenings that are thought to be due to magnetic reconnection. They are observed abundantly in the chromosphere and transition region, in particular in active regions. Aims: We investigate in detail a UV burst related to a magnetic feature that is advected by the moat flow from a sunspot towards a pore. The moving feature is parasitic in that its magnetic polarity is opposite to that of the spot and the pore. This comparably simple photospheric magnetic field distribution allows for an unambiguous interpretation of the magnetic geometry leading to the onset of the observed UV burst. Methods: We used UV spectroscopic and slit-jaw observations from the Interface Region Imaging Spectrograph (IRIS) to identify and study chromospheric and transition region spectral signatures of said UV burst. To investigate the magnetic topology surrounding the UV burst, we used a two-hour-long time sequence of simultaneous line-of-sight magnetograms from the Helioseismic and Magnetic Imager (HMI) and performed data-driven 3D magnetic field extrapolations by means of a magnetofrictional relaxation technique. We can connect UV burst signatures to the overlying extreme UV (EUV) coronal loops observed by the Atmospheric Imaging Assembly (AIA). Results: The UV burst shows a variety of extremely broad line profiles indicating plasma flows in excess of ±200 km s-1 at times. The whole structure is divided into two spatially distinct zones of predominantly up- and downflows. The magnetic field extrapolations show a persistent fan-spine magnetic topology at the UV burst. The associated 3D magnetic null point exists at a height of about 500 km above the photosphere and evolves co-spatially with the observed UV burst. The EUV emission at the footpoints of coronal loops is correlated with the evolution of the underlying UV burst. Conclusions: The magnetic field around the null point is sheared by photospheric motions, triggering magnetic reconnection that ultimately powers the observed UV burst and energises the overlying coronal loops. The location of the null point suggests that the burst is triggered low in the solar chromosphere. Movies associated to Figs. 2 and 4 are available at http://www.aanda.org

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

The impact of glutathione s-transferase M1 and cytochrome P450 1A1 genotypes on white-blood-cell polycyclic aromatic hydrocarbon-DNA adduct levels in humans.

PubMed

Rothman, N; Shields, P G; Poirier, M C; Harrington, A M; Ford, D P; Strickland, P T

1995-09-01

Carcinogenic polycyclic aromatic hydrocarbons (PAHs) form DNA adducts via a complex metabolic activation pathway that includes cytochrome P450 (CYP) 1A1, whereas intermediate metabolites can be detoxified by conjugation through pathways including glutathione s-transferase M1 (GSTM1). PAH-DNA adducts can be measured in peripheral white blood cells (WBCs) and should reflect the net effect of competing activation and detoxification pathways and DNA repair as well as exposure. We have previously shown that WBC PAH-DNA adducts measured by an enzyme-linked immunosorbent assay (ELISA) were associated with recent, frequent consumption of charbroiled food among 47 nonsmoking wildland fire-fighters who provided two blood samples 8 wk apart. In the investigation reported here, which was performed in the same population, we measured the association between the GSTM1 null genotype, which results in loss of enzyme activity, and PAH-DNA adduct levels, hypothesizing that subjects with this genotype would have higher levels of DNA adducts because of their decreased ability to detoxify PAH metabolites. However, PAH-DNA adduct levels were nonsignificantly lower in subjects with the GSTM1 null genotype (n = 28) compared with other subjects (n = 19) (median 0.04 fmol/microgram DNA vs 0.07 fmol/microgram DNA, respectively, P = 0.45, Wilcoxon rank-sum test). Adduct levels were also lower in the nine subjects heterozygous or homozygous for the CYP1A1 exon 7 polymorphism (which codes for a valine rather than isoleucine and is thought to be associated with greater CYP1A1 activity) compared with the 38 wild-type subjects (P = 0.12). In the entire group, there was a positive association between consuming charbroiled food and PAH-DNA adduct formation (r = 0.24, P = 0.02, Spearman rank-order correlation). This association was weaker in the subgroup of subjects with the GSTM1 null genotype (r = 0.03, P = 0.84) and stronger among the remaining subjects (r = 0.57, P = 0.0002). These results suggest that the GSTM1 null genotype and CYP1A1 exon 7 polymorphism are not associated with increased susceptibility for PAH-DNA adduct formation in peripheral WBCs measured by ELISA in nonsmoking populations.

Large gauge transformations and little group for soft photons

NASA Astrophysics Data System (ADS)

Hamada, Yuta; Seo, Min-Seok; Shiu, Gary

2017-11-01

Recently, large gauge transformation (LGT), the residual gauge symmetry after gauge fixing that survives at null infinity, has drawn much attention concerning soft theorems and the memory effect. We point out that LGT charges in quantum electrodynamics are in fact one of noncompact generators of the two dimensional Euclidean group. Moreover, by comparing two equivalent descriptions of gauge transformation, we suggest that LGT is simply another way of describing the gauged little group for massless soft photons.

Targeting SRC Family Kinases and HSP90 in Lung Cancer

DTIC Science & Technology

2016-12-01

inhalation of Adeno-Cre, followed by MRI imaging at regular intervals to detect tumor initiation and growth, followed by euthanasia and processing of...experimental endpoint. 10 mice were used per time point Representative MRI data describing tumor volume (TV) are shown in Figure 1. Quantification of data is...dasatinib, we were able to make several conclusions. Figure 1. Representative MRI images from Nedd9wt or Nedd9 null Kras mutant mice, treated with

Flight demonstration of a milliarcsecond pointing system for direct exoplanet imaging.

PubMed

Mendillo, Christopher B; Chakrabarti, Supriya; Cook, Timothy A; Hicks, Brian A; Lane, Benjamin F

2012-10-10

We present flight results from the optical pointing control system onboard the Planetary Imaging Concept Testbed Using a Rocket Experiment (PICTURE) sounding rocket. PICTURE (NASA mission number: 36.225 UG) was launched on 8 October 2011, from White Sands Missile Range. It attempted to directly image the exozodiacal dust disk of ϵ Eridani (K2V, 3.22 pc) down to an inner radius of 1.5 AU using a visible nulling coronagraph. The rocket attitude control system (ACS) provided 627 milliarcsecond (mas) RMS body pointing (~2'' peak-to-valley). The PICTURE fine pointing system (FPS) successfully stabilized the telescope beam to 5.1 mas (0.02λ/D) RMS using an angle tracker camera and fast steering mirror. This level of pointing stability is comparable to that of the Hubble Space Telescope. We present the hardware design of the FPS, a description of the limiting noise sources and a power spectral density analysis of the FPS and rocket ACS in-flight performance.

Magnetic Topology of Coronal Hole Linkages

NASA Technical Reports Server (NTRS)

Titov, V. S.; Mikic, Z.; Linker, J. A.; Lionello, R.; Antiochos, S. K.

2010-01-01

In recent work, Antiochos and coworkers argued that the boundary between the open and closed field regions on the Sun can be extremely complex with narrow corridors of open ux connecting seemingly disconnected coronal holes from the main polar holes, and that these corridors may be the sources of the slow solar wind. We examine, in detail, the topology of such magnetic configurations using an analytical source surface model that allows for analysis of the eld with arbitrary resolution. Our analysis reveals three important new results: First, a coronal hole boundary can join stably to the separatrix boundary of a parasitic polarity region. Second, a single parasitic polarity region can produce multiple null points in the corona and, more important, separator lines connecting these points. Such topologies are extremely favorable for magnetic reconnection, because it can now occur over the entire length of the separators rather than being con ned to a small region around the nulls. Finally, the coronal holes are not connected by an open- eld corridor of finite width, but instead are linked by a singular line that coincides with the separatrix footprint of the parasitic polarity. We investigate how the topological features described above evolve in response to motion of the parasitic polarity region. The implications of our results for the sources of the slow solar wind and for coronal and heliospheric observations are discussed.

Oscillations in solar jets observed with the SOT of Hinode: viscous effects during reconnection

NASA Astrophysics Data System (ADS)

Tavabi, E.; Koutchmy, S.

2014-07-01

Transverse oscillatory motions and recurrence behavior in the chromospheric jets observed by Hinode/SOT are studied. A comparison is considered with the behavior that was noticed in coronal X-ray jets observed by Hinode/XRT. A jet like bundle observed at the limb in Ca II H line appears to show a magnetic topology that is similar to X-ray jets (i.e., the Eiffel tower shape). The appearance of such magnetic topology is usually assumed to be caused by magnetic reconnection near a null point. Transverse motions of the jet axis are recorded but no clear evidence of twist is appearing from the highly processed movie. The aim is to investigate the dynamical behavior of an incompressible magnetic X-point occurring during the magnetic reconnection in the jet formation region. The viscous effect is specially considered in the closed line-tied magnetic X-shape nulls. We perform the MHD numerical simulation in 2-D by solving the visco-resistive MHD equations with the tracing of velocity and magnetic field. A qualitative agreement with Hinode observations is found for the oscillatory and non-oscillatory behaviors of the observed solar jets in both the chromosphere and the corona. Our results suggest that the viscous effect contributes to the excitation of the magnetic reconnection by generating oscillations that we observed at least inside this Ca II H line cool solar jet bundle.

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

PubMed Central

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

2014-01-01

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

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.;

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.

What is the relationship between free flow and pressure flow studies in women?

PubMed

Duckett, Jonathan; Cheema, Katherine; Patil, Avanti; Basu, Maya; Beale, Sian; Wise, Brian

2013-03-01

The relationship between free flow (FFS) and pressure flow (PFS) voiding studies remains uncertain and the effect of a urethral catheter on flow rates has not been determined. The relationship between residuals obtained at FF and PFS has yet to be established. This was a prospective cohort study based on 474 consecutive women undergoing cystometry using different sized urethral catheters at different centres. FFS and PFS data were compared for different conditions and the relationship of residuals analysed for FFS and PFS. The null hypothesis was that urethral catheters do not produce an alteration in maximum flow rates for PFS and FF studies. Urethral catheterisation results in lower flow rates (p < 0.01) and this finding is confirmed when flows are corrected for voided volume (p < 0.01). FFS and PFS maximum flow rates are lower in women with DO than USI (p < 0.01). A 6-F urethral catheter does not have a significantly greater effect than a 4.5-F urethral catheter. A mathematical model can be applied to transform FFS to PFS flow rates and vice versa. There was no significant difference between the mean residuals of the two groups (FFS vs PFS-two-tailed t = 0.54, p = 0.59). Positive residuals in FFS showed a good association with positive residuals in the PFS (r = 0.53, p < 0.01) Urethral catheterisation results in lower maximum flow rates. The relationship can be compared mathematically. The null hypothesis can be rejected.

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.

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.

Targeting Th17-IL-17 pathway in prevention of micro-invasive prostate cancer in a mouse model

PubMed Central

Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Cunningham, David M.; Huang, Feng; Ma, Lin; Burris, Thomas P.; You, Zongbing

2017-01-01

Background Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model. Methods The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected i.p. twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected i.v. once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10-week-old. All mice were analyzed for the prostate phenotypes at 12 weeks of age. Results We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates. Conclusions These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice. PMID:28240383

Motion versus position in the perception of head-centred movement.

PubMed

Freeman, Tom C A; Sumnall, Jane H

2002-01-01

Abstract. Observers can recover motion with respect to the head during an eye movement by comparing signals encoding retinal motion and the velocity of pursuit. Evidently there is a mismatch between these signals because perceived head-centred motion is not always veridical. One example is the Filehne illusion, in which a stationary object appears to move in the opposite direction to pursuit. Like the motion aftereffect, the phenomenal experience of the Filehne illusion is one in which the stimulus moves but does not seem to go anywhere. This raises problems when measuring the illusion by motion nulling because the more traditional technique confounds perceived motion with changes in perceived position. We devised a new nulling technique using global-motion stimuli that degraded familiar position cues but preserved cues to motion. Stimuli consisted of random-dot patterns comprising signal and noise dots that moved at the same retinal 'base' speed. Noise moved in random directions. In an eye-stationary speed-matching experiment we found noise slowed perceived retinal speed as 'coherence strength' (ie percentage of signal) was reduced. The effect occurred over the two-octave range of base speeds studied and well above direction threshold. When the same stimuli were combined with pursuit, observers were able to null the Filehne illusion by adjusting coherence. A power law relating coherence to retinal base speed fit the data well with a negative exponent. Eye-movement recordings showed that pursuit was quite accurate. We then tested the hypothesis that the stimuli found at the null-points appeared to move at the same retinal speed. Two observers supported the hypothesis, a third partially, and a fourth showed a small linear trend. In addition, the retinal speed found by the traditional Filehne technique was similar to the matches obtained with the global-motion stimuli. The results provide support for the idea that speed is the critical cue in head-centred motion perception.

HD CAG-correlated gene expression changes support a simple dominant gain of function

PubMed Central

Jacobsen, Jessie C.; Gregory, Gillian C.; Woda, Juliana M.; Thompson, Morgan N.; Coser, Kathryn R.; Murthy, Vidya; Kohane, Isaac S.; Gusella, James F.; Seong, Ihn Sik; MacDonald, Marcy E.; Shioda, Toshi; Lee, Jong-Min

2011-01-01

Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size. The mechanism could involve a simple gain of function or a more complex gain of function coupled to a loss of function (e.g. dominant negative-graded loss of function). To distinguish these alternatives, we compared genome-wide gene expression changes correlated with CAG size across an allelic series of heterozygous CAG knock-in mouse embryonic stem (ES) cell lines (HdhQ20/7, HdhQ50/7, HdhQ91/7, HdhQ111/7), to genes differentially expressed between Hdhex4/5/ex4/5 huntingtin null and wild-type (HdhQ7/7) parental ES cells. The set of 73 genes whose expression varied continuously with CAG length had minimal overlap with the 754-member huntingtin-null gene set but the two were not completely unconnected. Rather, the 172 CAG length-correlated pathways and 238 huntingtin-null significant pathways clustered into 13 shared categories at the network level. A closer examination of the energy metabolism and the lipid/sterol/lipoprotein metabolism categories revealed that CAG length-correlated genes and huntingtin-null-altered genes either were different members of the same pathways or were in unique, but interconnected pathways. Thus, varying the polyglutamine size in full-length huntingtin produced gene expression changes that were distinct from, but related to, the effects of lack of huntingtin. These findings support a simple gain-of-function mechanism acting through a property of the full-length huntingtin protein and point to CAG-correlative approaches to discover its effects. Moreover, for therapeutic strategies based on huntingtin suppression, our data highlight processes that may be more sensitive to the disease trigger than to decreased huntingtin levels. PMID:21536587

Targeting Th17-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model.

PubMed

Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Cunningham, David M; Huang, Feng; Ma, Lin; Burris, Thomas P; You, Zongbing

2017-06-01

Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model. The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected intraperitoneally (i.p.) twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected intravenously (i.v.) once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10 weeks old. All mice were analyzed for the prostate phenotypes at 12 weeks of age. We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates. These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice. Prostate 77:888-899, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The study of heat flux for disruption on experimental advanced superconducting tokamak

NASA Astrophysics Data System (ADS)

Yang, Zhendong; Fang, Jianan; Gong, Xianzu; Gan, Kaifu; Luo, Jiarong; Zhao, Hailin; Cui, Zhixue; Zhang, Bin; Chen, Meiwen

2016-05-01

Disruption of the plasma is one of the most dangerous instabilities in tokamak. During the disruption, most of the plasma thermal energy is lost, which causes damages to the plasma facing components. Infrared (IR) camera is an effective tool to detect the temperature distribution on the first wall, and the energy deposited on the first wall can be calculated from the surface temperature profile measured by the IR camera. This paper concentrates on the characteristics of heat flux distribution onto the first wall under different disruptions, including the minor disruption and the vertical displacement events (VDE) disruption. Several minor disruptions have been observed before the major disruption under the high plasma density in experimental advanced superconducting tokamak. During the minor disruption, the heat fluxes are mainly deposited on the upper/lower divertors. The magnetic configuration prior to the minor disruption is a lower single null with the radial distance between the two separatrices in the outer midplane dRsep = -2 cm, while it changes to upper single null (dRsep = 1.4 cm) during the minor disruption. As for the VDE disruption, the spatial distribution of heat flux exhibits strong toroidal and radial nonuniformity, and the maximum heat flux received on the dome plate can be up to 11 MW/m2.

The δ isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload

PubMed Central

Backs, Johannes; Backs, Thea; Neef, Stefan; Kreusser, Michael M.; Lehmann, Lorenz H.; Patrick, David M.; Grueter, Chad E.; Qi, Xiaoxia; Richardson, James A.; Hill, Joseph A.; Katus, Hugo A.; Bassel-Duby, Rhonda; Maier, Lars S.; Olson, Eric N.

2009-01-01

Acute and chronic injuries to the heart result in perturbation of intracellular calcium signaling, which leads to pathological cardiac hypertrophy and remodeling. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transduction of calcium signals in the heart, but the specific isoforms of CaMKII that mediate pathological cardiac signaling have not been fully defined. To investigate the potential involvement in heart disease of CaMKIIδ, the major CaMKII isoform expressed in the heart, we generated CaMKIIδ-null mice. These mice are viable and display no overt abnormalities in cardiac structure or function in the absence of stress. However, pathological cardiac hypertrophy and remodeling are attenuated in response to pressure overload in these animals. Cardiac extracts from CaMKIIδ-null mice showed diminished kinase activity toward histone deacetylase 4 (HDAC4), a substrate of stress-responsive protein kinases and suppressor of stress-dependent cardiac remodeling. In contrast, phosphorylation of the closely related HDAC5 was unaffected in hearts of CaMKIIδ-null mice, underscoring the specificity of the CaMKIIδ signaling pathway for HDAC4 phosphorylation. We conclude that CaMKIIδ functions as an important transducer of stress stimuli involved in pathological cardiac remodeling in vivo, which is mediated, at least in part, by the phosphorylation of HDAC4. These findings point to CaMKIIδ as a potential therapeutic target for the maintenance of cardiac function in the setting of pressure overload. PMID:19179290

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.

Aberrant Bone Density in Aging Mice Lacking the Adenosine Transporter ENT1

PubMed Central

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

2014-01-01

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

CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men

PubMed Central

Hamachi, Tadamichi; Tajima, Osamu; Uezono, Kousaku; Tabata, Shinji; Abe, Hiroshi; Ohnaka, Keizo; Kono, Suminori

2013-01-01

AIM: To investigate the role of functional genetic polymorphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas. METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied were CYP1A1*2A (rs 4646903), CYP1A1*2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other lifestyle factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test. RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1. A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1 (P = 0.051). The OR associated with CYP1A1*2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1*2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1*2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1*2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There was no measurable effect modification of smoking even regarding the combination of the genetic polymorphisms of the phase I and phase II enzymes. CONCLUSION: Combination of the CYP1A1*2C and NQO1 609CC genotypes was associated with a decreased risk of colorectal adenomas regardless of smoking status. PMID:23840148

The vitamin D receptor functions as a transcription regulator in the absence of 1,25-dihydroxyvitamin D3.

PubMed

Lee, Seong Min; Pike, J Wesley

2016-11-01

The vitamin D receptor (VDR) is a critical mediator of the biological actions of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). As a nuclear receptor, ligand activation of the VDR leads to the protein's binding to specific sites on the genome that results in the modulation of target gene expression. The VDR is also known to play a role in the hair cycle, an action that appears to be 1,25(OH) 2 D 3 -independent. Indeed, in the absence of the VDR as in hereditary 1,25-dihydroxyvitamin D resistant rickets (HVDRR) both skin defects and alopecia emerge. Recently, we generated a mouse model of HVDRR without alopecia wherein a mutant human VDR lacking 1,25(OH) 2 D 3 -binding activity was expressed in the absence of endogenous mouse VDR. While 1,25(OH) 2 D 3 failed to induce gene expression in these mice, resulting in an extensive skeletal phenotype, the receptor was capable of restoring normal hair cycling. We also noted a level of secondary hyperparathyroidism that was much higher than that seen in the VDR null mouse and was associated with an exaggerated bone phenotype as well. This suggested that the VDR might play a role in parathyroid hormone (PTH) regulation independent of 1,25(OH) 2 D 3 . To evaluate this hypothesis further, we contrasted PTH levels in the HVDRR mouse model with those seen in Cyp27b1 null mice where the VDR was present but the hormone was absent. The data revealed that PTH was indeed higher in Cyp27b1 null mice compared to VDR null mice. To evaluate the mechanism of action underlying such a hypothesis, we measured the expression levels of a number of VDR target genes in the duodena of wildtype mice and in transgenic mice expressing either normal or hormone-binding deficient mutant VDRs. We also compared expression levels of these genes between VDR null mice and Cyp27b1 null mice. In a subset of cases, the expression of VDR target genes was lower in mice containing the VDR as opposed to mice that did not. We suggest that the VDR may function as a selective suppressor/de-repressor of gene expression in the absence of 1,25(OH) 2 D 3 . Copyright © 2015 Elsevier Ltd. 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

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

Global Stability and Control Analysis of Aircraft at High Angles-of-Attack.

DTIC Science & Technology

1977-06-30

500 deg/sec to 500 deg/sec and com - puting the eigenvalues of the linearized system around different equilibrium points for 6e = 2°. It is noticed...SYSTEMS, INC. 0" -114- 2 Ä»" • + + + + + _+ + + + + + + + + M I o o o a i i 8 8 in 8 8 XNXX * x x» x x x< x...history com - parisons show significant improvement in dynamic response and performance using the BACTM ARI gain, as opposed to nulling the rudder

PRMT1-Mediated Translation Regulation is a Crucial Vulnerability of Cancer | Office of Cancer Genomics

Cancer.gov

Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control.

Second level semi-degenerate fields in W_3 Toda theory: matrix element and differential equation

NASA Astrophysics Data System (ADS)

Belavin, Vladimir; Cao, Xiangyu; Estienne, Benoit; Santachiara, Raoul

2017-03-01

In a recent study we considered W_3 Toda 4-point functions that involve matrix elements of a primary field with the highest-weight in the adjoint representation of sl_3 . We generalize this result by considering a semi-degenerate primary field, which has one null vector at level two. We obtain a sixth-order Fuchsian differential equation for the conformal blocks. We discuss the presence of multiplicities, the matrix elements and the fusion rules.

The Cytoplasmic C-Tail of the Mouse Cytomegalovirus 7 Transmembrane Receptor Homologue, M78, Regulates Endocytosis of the Receptor and Modulates Virus Replication in Different Cell Types

PubMed Central

2016-01-01

Virus homologues of seven-transmembrane receptors (7TMR) are encoded by all beta- and gammaherpesviruses, suggesting important functional roles. M78 of mouse cytomegalovirus (MCMV) is representative of a family of 7TMR conserved in all betaherpesviruses. M78 family members have been found to exhibit cell-type specific effects upon virus replication in tissue culture and to affect virus pathogenesis in vivo. We reported previously that M78, for which no ligands are known, undergoes rapid, constitutive endocytosis. In this study, we have investigated the role of the M78 cytoplasmic C-tail in mediating endocytosis and consequences of C-tail deletion upon replication and pathogenesis. Mutations of M78 (C-tail truncations or point mutations) and CCR5-M78 chimeras identified two distinct regions affecting endocytosis. The first was a classical acidic di-leucine motif (DDxxxLL), located close to the C-terminus. The second region, the activity of which was suppressed by downstream sequences, included the putative 8th helix, located close to the 7th transmembrane domain. A recombinant MCMV expressing an endocytosis-deficient M78, lacking most of the C-tail (M78_CΔ155), had a cell-type specific replication phenotype. M78_CΔ155 had restricted replication in bone marrow macrophages, indistinguishable from an M78-null recombinant. In contrast, M78_CΔ155 replicated normally or with enhanced titres to wild type virus in other tested cell-types, whereas M78-null was attenuated. Distinct phenotypes for M78_CΔ155 and M78-null suggest that the C-tail deletion resulted in M78 dysfunction, rather than complete loss of function; furthermore, they highlight a cell-type specific role of M78 during replication. Infection of mice (intranasal) demonstrated that M78_CΔ155, similar to M78-null, was cleared more rapidly from the lungs than wild type virus and was severely attenuated for replication in salivary glands. It may be speculated that attenuation of both M78_CΔ155 and M78-null for replication in macrophages may have contributed to their similar pathogenic phenotypes. PMID:27760189

Mutations reducing replication from R-loops suppress the defects of growth, chromosome segregation and DNA supercoiling in cells lacking topoisomerase I and RNase HI activity.

PubMed

Usongo, Valentine; Martel, Makisha; Balleydier, Aurélien; Drolet, Marc

2016-04-01

R-loop formation occurs when the nascent RNA hybridizes with the template DNA strand behind the RNA polymerase. R-loops affect a wide range of cellular processes and their use as origins of replication was the first function attributed to them. In Escherichia coli, R-loop formation is promoted by the ATP-dependent negative supercoiling activity of gyrase (gyrA and gyrB) and is inhibited by topoisomerase (topo) I (topA) relaxing transcription-induced negative supercoiling. RNase HI (rnhA) degrades the RNA moiety of R-loops. The depletion of RNase HI activity in topA null mutants was previously shown to lead to extensive DNA relaxation, due to DNA gyrase inhibition, and to severe growth and chromosome segregation defects that were partially corrected by overproducing topo III (topB). Here, DNA gyrase assays in crude cell extracts showed that the ATP-dependent activity (supercoiling) of gyrase but not its ATP-independent activity (relaxation) was inhibited in topA null cells lacking RNase HI. To characterize the cellular event(s) triggered by the absence of RNase HI, we performed a genetic screen for suppressors of the growth defect of topA rnhA null cells. Suppressors affecting genes in replication (holC2::aph and dnaT18::aph) nucleotide metabolism (dcd49::aph), RNA degradation (rne59::aph) and fimbriae synthesis (fimD22::aph) were found to reduce replication from R-loops and to restore supercoiling, thus pointing to a correlation between R-loop-dependent replication in topA rnhA mutants and the inhibition of gyrase activity and growth. Interestingly, the position of fimD on the E. coli chromosome corresponds to the site of one of the five main putative origins of replication from R-loops in rnhA null cells recently identified by next-generation sequencing, thus suggesting that the fimD22::aph mutation inactivated one of these origins. Furthermore, we show that topo III overproduction is unable to complement the growth defect of topA rnhA null mutants at low temperatures that stabilizes hyper-negatively supercoiled DNA. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

PubMed Central

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

2015-01-01

Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp-/- mice. PMID:26130257

Development and evaluation of spatial point process models for epidermal nerve fibers.

PubMed

Olsbo, Viktor; Myllymäki, Mari; Waller, Lance A; Särkkä, Aila

2013-06-01

We propose two spatial point process models for the spatial structure of epidermal nerve fibers (ENFs) across human skin. The models derive from two point processes, Φb and Φe, describing the locations of the base and end points of the fibers. Each point of Φe (the end point process) is connected to a unique point in Φb (the base point process). In the first model, both Φe and Φb are Poisson processes, yielding a null model of uniform coverage of the skin by end points and general baseline results and reference values for moments of key physiologic indicators. The second model provides a mechanistic model to generate end points for each base, and we model the branching structure more directly by defining Φe as a cluster process conditioned on the realization of Φb as its parent points. In both cases, we derive distributional properties for observable quantities of direct interest to neurologists such as the number of fibers per base, and the direction and range of fibers on the skin. We contrast both models by fitting them to data from skin blister biopsy images of ENFs and provide inference regarding physiological properties of ENFs. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging

PubMed Central

Salehpour, F.; Ghanian, Z.; Yang, C.; Zheleznova, N. N.; Kurth, T.; Dash, R. K.; Cowley, A. W.

2015-01-01

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67phox subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67phox was rendered functionally inactive by zinc finger nuclease mutation of the gene (SSp67phox-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SSp67phox-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SSp67phox-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SSp67phox rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67phox subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. PMID:26062875

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging.

PubMed

Salehpour, F; Ghanian, Z; Yang, C; Zheleznova, N N; Kurth, T; Dash, R K; Cowley, A W; Ranji, M

2015-08-15

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. Copyright © 2015 the American Physiological Society.

Divertor Heat Flux Reduction and Detachment in the National Spherical Torus eXperiment.

NASA Astrophysics Data System (ADS)

Soukhanovskii, Vsevolod

2007-11-01

Steady-state handling of the heat flux is a critical divertor issue for both the International Thermonuclear Experimental Reactor and spherical torus (ST) devices. Because of an inherently compact divertor, it was thought that ST-based devices might not be able to fully utilize radiative and dissipative divertor techniques based on induced power and momentum loss. However, initial experiments conducted in the National Spherical Torus Experiment in an open geometry horizontal carbon plate divertor using 0.8 MA 2-6 MW NBI-heated lower single null H-mode plasmas at the lower end of elongations κ=1.8-2.4 and triangularities δ=0.45-0.75 demonstrated that high divertor peak heat fluxes, up to 6-10 MW/ m^2, could be reduced by 50-75% using a high-recycling radiative divertor regime with D2 injection. Furthermore, similar reduction was obtained with a partially detached divertor (PDD) at high D2 injection rates, however, it was accompanied by an X-point MARFE that quickly led to confinement degradation. Another approach takes advantage of the ST relation between strong shaping and high performance, and utilizes the poloidal magnetic flux expansion in the divertor region. Up to 60 % reduction in divertor peak heat flux was achieved at similar levels of scrape-off layer power by varying plasma shaping and thereby increasing the outer strike point (OSP) poloidal flux expansion from 4-6 to 18-22. In recent experiments conducted in highly-shaped 1.0-1.2 MA 6 MW NBI heated H-mode plasmas with divertor D2 injection at rates up to 10^22 s-1, a PDD regime with OSP peak heat flux 0.5-1.5 MW/m^2 was obtained without noticeable confinement degradation. Calculations based on a two point scrape-off layer model with parameterized power and momentum losses show that the short parallel connection length at the OSP sets the upper limit on the radiative exhaust channel, and both the impurity radiation and large momentum sink achievable only at high divertor neutral pressures are required for detachment.

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.

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.

Applications of conformal field theory to problems in 2D percolation

NASA Astrophysics Data System (ADS)

Simmons, Jacob Joseph Harris

This thesis explores critical two-dimensional percolation in bounded regions in the continuum limit. The main method which we employ is conformal field theory (CFT). Our specific results follow from the null-vector structure of the c = 0 CFT that applies to critical two-dimensional percolation. We also make use of the duality symmetry obeyed at the percolation point, and the fact that percolation may be understood as the q-state Potts model in the limit q → 1. Our first results describe the correlations between points in the bulk and boundary intervals or points, i.e. the probability that the various points or intervals are in the same percolation cluster. These quantities correspond to order-parameter profiles under the given conditions, or cluster connection probabilities. We consider two specific cases: an anchoring interval, and two anchoring points. We derive results for these and related geometries using the CFT null-vectors for the corresponding boundary condition changing (bcc) operators. In addition, we exhibit several exact relationships between these probabilities. These relations between the various bulk-boundary connection probabilities involve parameters of the CFT called operator product expansion (OPE) coefficients. We then compute several of these OPE coefficients, including those arising in our new probability relations. Beginning with the familiar CFT operator φ1,2, which corresponds to a free-fixed spin boundary change in the q-state Potts model, we then develop physical interpretations of the bcc operators. We argue that, when properly normalized, higher-order bcc operators correspond to successive fusions of multiple φ1,2, operators. Finally, by identifying the derivative of φ1,2 with the operator φ1,4, we derive several new quantities called first crossing densities. These new results are then combined and integrated to obtain the three previously known crossing quantities in a rectangle: the probability of a horizontal crossing cluster, the probability of a cluster crossing both horizontally and vertically, and the expected number of horizontal crossing clusters. These three results were known to be solutions to a certain fifth-order differential equation, but until now no physically meaningful explanation had appeared. This differential equation arises naturally in our derivation.

Photon orbits and thermodynamic phase transition of d -dimensional charged AdS black holes

NASA Astrophysics Data System (ADS)

Wei, Shao-Wen; Liu, Yu-Xiao

2018-05-01

We study the relationship between the null geodesics and thermodynamic phase transition for the charged AdS black hole. In the reduced parameter space, we find that there exist nonmonotonic behaviors of the photon sphere radius and the minimum impact parameter for the pressure below its critical value. The study also shows that the changes of the photon sphere radius and the minimum impact parameter can serve as order parameters for the small-large black hole phase transition. In particular, these changes have an universal exponent of 1/2 near the critical point for any dimension d of spacetime. These results imply that there may exist universal critical behavior of gravity near the thermodynamic critical point of the black hole system.

Interface extinction and subsurface peaking of the radiation pattern of a line source

NASA Technical Reports Server (NTRS)

Engheta, N.; Papas, C. H.; Elachi, C.

1981-01-01

The radiation pattern of a line source lying along the plane interface of two dielectric half-spaces is calculated. It is found that the pattern at the interface has a null (interface extinction); that the pattern in the upper half-space, whose index of refraction is taken to be less than that of the lower half-space, has a single lobe with a maximum normal to the interface; and that the pattern in the lower half-space (subsurface region) has two maxima (peaks) straddling symmetrically a minimum. Interpretation of these results in terms of ray optics, Oseen's extinction theorem, and the Cerenkov effect are given.

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).

Cross-correlation of point series using a new method

NASA Technical Reports Server (NTRS)

Strothers, Richard B.

1994-01-01

Traditional methods of cross-correlation of two time series do not apply to point time series. Here, a new method, devised specifically for point series, utilizes a correlation measure that is based in the rms difference (or, alternatively, the median absolute difference) between nearest neightbors in overlapped segments of the two series. Error estimates for the observed locations of the points, as well as a systematic shift of one series with respect to the other to accommodate a constant, but unknown, lead or lag, are easily incorporated into the analysis using Monte Carlo techniques. A methodological restriction adopted here is that one series be treated as a template series against which the other, called the target series, is cross-correlated. To estimate a significance level for the correlation measure, the adopted alternative (null) hypothesis is that the target series arises from a homogeneous Poisson process. The new method is applied to cross-correlating the times of the greatest geomagnetic storms with the times of maximum in the undecennial solar activity cycle.

Workplace Exercise for Control of Occupational Neck/Shoulder Disorders: A Review of Prospective Studies

PubMed Central

Lowe, Brian D; Dick, Robert B

2014-01-01

A review was conducted of prospective studies (1997–2014) examining the efficacy of exercise as a workplace intervention to control neck/shoulder pain, symptoms, and disability. The review identified 38 relevant studies – 20 were classified with positive effects, 13 with null effects, and 5 as inconclusive. Of the positive studies, 12 were consistent with Level I evidence, 3 with Level II evidence, and 5 with Level IV evidence. Specific resistance training (SRT) exercise appeared to be associated with more positive studies (eight Level I studies) than other exercise modalities such as general resistance training, general physical exercise, stretching, and movement awareness exercises. Studies of longer trial duration tended toward more null findings and lower program compliance. Evidence for a primary preventive effect of workplace exercise is minimal. The findings of this review suggest that workplace exercise can be effective as tertiary prevention and therapeutic relief of neck/shoulder symptoms, at least over the shorter term. PMID:25780338

Changing world extreme temperature statistics

NASA Astrophysics Data System (ADS)

Finkel, J. M.; Katz, J. I.

2018-04-01

We use the Global Historical Climatology Network--daily database to calculate a nonparametric statistic that describes the rate at which all-time daily high and low temperature records have been set in nine geographic regions (continents or major portions of continents) during periods mostly from the mid-20th Century to the present. This statistic was defined in our earlier work on temperature records in the 48 contiguous United States. In contrast to this earlier work, we find that in every region except North America all-time high records were set at a rate significantly (at least $3\\sigma$) higher than in the null hypothesis of a stationary climate. Except in Antarctica, all-time low records were set at a rate significantly lower than in the null hypothesis. In Europe, North Africa and North Asia the rate of setting new all-time highs increased suddenly in the 1990's, suggesting a change in regional climate regime; in most other regions there was a steadier increase.

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.

Robustness of survival estimates for radio-marked animals

USGS Publications Warehouse

Bunck, C.M.; Chen, C.-L.

1992-01-01

Telemetry techniques are often used to study the survival of birds and mammals; particularly whcn mark-recapture approaches are unsuitable. Both parametric and nonparametric methods to estimate survival have becn developed or modified from other applications. An implicit assumption in these approaches is that the probability of re-locating an animal with a functioning transmitter is one. A Monte Carlo study was conducted to determine the bias and variance of the Kaplan-Meier estimator and an estimator based also on the assumption of constant hazard and to eva!uate the performance of the two-sample tests associated with each. Modifications of each estimator which allow a re-Iocation probability of less than one are described and evaluated. Generallv the unmodified estimators were biased but had lower variance. At low sample sizes all estimators performed poorly. Under the null hypothesis, the distribution of all test statistics reasonably approximated the null distribution when survival was low but not when it was high. The power of the two-sample tests were similar.

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.

On the Electron Diffusion Region in Asymmetric Reconnection with a Guide Magnetic Field

NASA Technical Reports Server (NTRS)

Hesse, Michael; Liu, Yi-Hsin; Chen, Li-Jen; Bessho, Naoki; Kuznetsova, Masha; Birn, Joachim; Burch, James L.

2016-01-01

Particle-in-cell simulations in a 2.5-D geometry and analytical theory are employed to study the electron diffusion region in asymmetric reconnection with a guide magnetic field. The analysis presented here demonstrates that similar to the case without guide field, in-plane flow stagnation and null of the in-plane magnetic field are well separated. In addition, it is shown that the electric field at the local magnetic X point is again dominated by inertial effects, whereas it remains dominated by nongyrotropic pressure effects at the in-plane flow stagnation point. A comparison between local electron Larmor radii and the magnetic gradient scale lengths predicts that distribution should become nongyrotropic in a region enveloping both field reversal and flow stagnation points. This prediction is verified by an analysis of modeled electron distributions, which show clear evidence of mixing in the critical region.

Upper and lower mantle anisotropy inferred from comprehensive SKS and SKKS splitting measurements from India

NASA Astrophysics Data System (ADS)

Roy, Sunil K.; Ravi Kumar, M.; Srinagesh, D.

2014-04-01

In this study, we investigate the upper mantle anisotropy beneath India using high quality SKS and SKKS waveforms from 382 teleseismic earthquakes recorded at 119 broadband seismic stations. In addition, we present evidence for anisotropy in the D″ layer beneath southeast Asia using SKS and SKKS splitting discrepancies on the same seismogram. During this exercise, we obtain 200 new splitting measurements from 35 stations recently deployed in the Indo-Gangetic plains (IGP), central India and northeast India. While the delay times between the fast and slow axes of anisotropy (δt) range from 0.3 to 1.7 s, the fast polarization azimuths (Φ) at a majority of stations in the IGP and central India coincide with the absolute plate motion of India implying shear at the base of the lithosphere as the dominant mechanism for forging anisotropy. However, stations in NE India reveal fast polarization azimuths mainly in the ENE-WSW direction suggestive of lithospheric strain induced by the ongoing Indo-Eurasian collision. Our analysis for D″ anisotropy yielded a total of 100 SKS-SKKS pairs, which can be categorized into those exhibiting (I) null measurements for one phase and significant splitting for the other phase, (II) null measurement for both the phases, (III) significant splitting for both the phases. A pair is considered to be anomalous if the splitting difference between SKS and SKKS is ⩾0.5 s and the individual split time is ⩾0.5 s. Using this criterion, we obtain 12 measurements under category III and 9 under category I that show a null measurement for SKS and large splitting for the SKKS phase. Further, we quantify the strength of the lower mantle anisotropy by correcting the SKKS measurement for the upper mantle anisotropy obtained by the SKS phase on the same seismogram. The SKS delay times are found to be consistently less than SKKS times, suggesting that the SKS phases do not capture the lower mantle anisotropy in comparison to their SKKS counterparts. Seven coherent measurements thus obtained reveal measurable D″ anisotropy, with fast polarization azimuths oriented mainly in the ENE-WSW direction. These results suggest presence of a large region of deformation in the lowermost mantle beneath southeast Asia. A possible model for anisotropy in these regions could be the presence of slab material that pounded upon the core mantle boundary (CMB) and is experiencing large shear deformation, resulting in lattice preferred orientation (LPO) of the lower mantle (Van der Hilst and Kárason, 1999; Long, 2009). The other possibility is the phase transformation from MgSiO3 perovskite to a more stable post-perovskite phase under favorable conditions, which results in LPO of the lower mantle.

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.

On computation of p-values in parametric linkage analysis.

PubMed

Kurbasic, Azra; Hössjer, Ola

2004-01-01

Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi2(0) + 1/2 chi2(1)) distribution under the null hypothesis of no linkage when only one point (one marker) on the chromosome is studied. In this paper, we show, both by simulations and theoretical arguments, that the null hypothesis distribution of Zmax has no simple form when more than one marker is used (multipoint analysis). In fact, the distribution of Zmax depends on the number of families, their structure, the assumed genetic model, marker denseness, and marker informativity. This means that a constant critical limit of Zmax leads to tests associated with different significance levels. Because of the above-mentioned problems, from the statistical point of view the maximal lod score should be supplemented by a p-value when results are reported. Copyright (c) 2004 S. Karger AG, Basel.

A nonparametric significance test for sampled networks.

PubMed

Elliott, Andrew; Leicht, Elizabeth; Whitmore, Alan; Reinert, Gesine; Reed-Tsochas, Felix

2018-01-01

Our work is motivated by an interest in constructing a protein-protein interaction network that captures key features associated with Parkinson's disease. While there is an abundance of subnetwork construction methods available, it is often far from obvious which subnetwork is the most suitable starting point for further investigation. We provide a method to assess whether a subnetwork constructed from a seed list (a list of nodes known to be important in the area of interest) differs significantly from a randomly generated subnetwork. The proposed method uses a Monte Carlo approach. As different seed lists can give rise to the same subnetwork, we control for redundancy by constructing a minimal seed list as the starting point for the significance test. The null model is based on random seed lists of the same length as a minimum seed list that generates the subnetwork; in this random seed list the nodes have (approximately) the same degree distribution as the nodes in the minimum seed list. We use this null model to select subnetworks which deviate significantly from random on an appropriate set of statistics and might capture useful information for a real world protein-protein interaction network. The software used in this paper are available for download at https://sites.google.com/site/elliottande/. The software is written in Python and uses the NetworkX library. ande.elliott@gmail.com or felix.reed-tsochas@sbs.ox.ac.uk. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

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).

A nonparametric significance test for sampled networks

PubMed Central

Leicht, Elizabeth; Whitmore, Alan; Reinert, Gesine; Reed-Tsochas, Felix

2018-01-01

Abstract Motivation Our work is motivated by an interest in constructing a protein–protein interaction network that captures key features associated with Parkinson’s disease. While there is an abundance of subnetwork construction methods available, it is often far from obvious which subnetwork is the most suitable starting point for further investigation. Results We provide a method to assess whether a subnetwork constructed from a seed list (a list of nodes known to be important in the area of interest) differs significantly from a randomly generated subnetwork. The proposed method uses a Monte Carlo approach. As different seed lists can give rise to the same subnetwork, we control for redundancy by constructing a minimal seed list as the starting point for the significance test. The null model is based on random seed lists of the same length as a minimum seed list that generates the subnetwork; in this random seed list the nodes have (approximately) the same degree distribution as the nodes in the minimum seed list. We use this null model to select subnetworks which deviate significantly from random on an appropriate set of statistics and might capture useful information for a real world protein–protein interaction network. Availability and implementation The software used in this paper are available for download at https://sites.google.com/site/elliottande/. The software is written in Python and uses the NetworkX library. Contact ande.elliott@gmail.com or felix.reed-tsochas@sbs.ox.ac.uk Supplementary information Supplementary data are available at Bioinformatics online. PMID:29036452

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.

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

PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer.

PubMed

Hsu, Jessie Hao-Ru; Hubbell-Engler, Benjamin; Adelmant, Guillaume; Huang, Jialiang; Joyce, Cailin E; Vazquez, Francisca; Weir, Barbara A; Montgomery, Philip; Tsherniak, Aviad; Giacomelli, Andrew O; Perry, Jennifer A; Trowbridge, Jennifer; Fujiwara, Yuko; Cowley, Glenn S; Xie, Huafeng; Kim, Woojin; Novina, Carl D; Hahn, William C; Marto, Jarrod A; Orkin, Stuart H

2017-09-01

Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613-25. ©2017 AACR . ©2017 American Association for Cancer Research.

Observing Exoplanets with High-dispersion Coronagraphy. II. Demonstration of an Active Single-mode Fiber Injection Unit

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

Mawet, D.; Ruane, G.; Xuan, W.

2017-04-01

High-dispersion coronagraphy (HDC) optimally combines high-contrast imaging techniques such as adaptive optics/wavefront control plus coronagraphy to high spectral resolution spectroscopy. HDC is a critical pathway toward fully characterizing exoplanet atmospheres across a broad range of masses from giant gaseous planets down to Earth-like planets. In addition to determining the molecular composition of exoplanet atmospheres, HDC also enables Doppler mapping of atmosphere inhomogeneities (temperature, clouds, wind), as well as precise measurements of exoplanet rotational velocities. Here, we demonstrate an innovative concept for injecting the directly imaged planet light into a single-mode fiber, linking a high-contrast adaptively corrected coronagraph to a high-resolutionmore » spectrograph (diffraction-limited or not). Our laboratory demonstration includes three key milestones: close-to-theoretical injection efficiency, accurate pointing and tracking, and on-fiber coherent modulation and speckle nulling of spurious starlight signal coupling into the fiber. Using the extreme modal selectivity of single-mode fibers, we also demonstrated speckle suppression gains that outperform conventional image-based speckle nulling by at least two orders of magnitude.« less

Observing Exoplanets with High-dispersion Coronagraphy. II. Demonstration of an Active Single-mode Fiber Injection Unit

NASA Astrophysics Data System (ADS)

Mawet, D.; Ruane, G.; Xuan, W.; Echeverri, D.; Klimovich, N.; Randolph, M.; Fucik, J.; Wallace, J. K.; Wang, J.; Vasisht, G.; Dekany, R.; Mennesson, B.; Choquet, E.; Delorme, J.-R.; Serabyn, E.

2017-04-01

High-dispersion coronagraphy (HDC) optimally combines high-contrast imaging techniques such as adaptive optics/wavefront control plus coronagraphy to high spectral resolution spectroscopy. HDC is a critical pathway toward fully characterizing exoplanet atmospheres across a broad range of masses from giant gaseous planets down to Earth-like planets. In addition to determining the molecular composition of exoplanet atmospheres, HDC also enables Doppler mapping of atmosphere inhomogeneities (temperature, clouds, wind), as well as precise measurements of exoplanet rotational velocities. Here, we demonstrate an innovative concept for injecting the directly imaged planet light into a single-mode fiber, linking a high-contrast adaptively corrected coronagraph to a high-resolution spectrograph (diffraction-limited or not). Our laboratory demonstration includes three key milestones: close-to-theoretical injection efficiency, accurate pointing and tracking, and on-fiber coherent modulation and speckle nulling of spurious starlight signal coupling into the fiber. Using the extreme modal selectivity of single-mode fibers, we also demonstrated speckle suppression gains that outperform conventional image-based speckle nulling by at least two orders of magnitude.

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.

A pseudo-equilibrium thermodynamic model of information processing in nonlinear brain dynamics.

PubMed

Freeman, Walter J

2008-01-01

Computational models of brain dynamics fall short of performance in speed and robustness of pattern recognition in detecting minute but highly significant pattern fragments. A novel model employs the properties of thermodynamic systems operating far from equilibrium, which is analyzed by linearization near adaptive operating points using root locus techniques. Such systems construct order by dissipating energy. Reinforcement learning of conditioned stimuli creates a landscape of attractors and their basins in each sensory cortex by forming nerve cell assemblies in cortical connectivity. Retrieval of a selected category of stored knowledge is by a phase transition that is induced by a conditioned stimulus, and that leads to pattern self-organization. Near self-regulated criticality the cortical background activity displays aperiodic null spikes at which analytic amplitude nears zero, and which constitute a form of Rayleigh noise. Phase transitions in recognition and recall are initiated at null spikes in the presence of an input signal, owing to the high signal-to-noise ratio that facilitates capture of cortex by an attractor, even by very weak activity that is typically evoked by a conditioned stimulus.

Studies of short-range tungsten migration in DIII-D divertor

NASA Astrophysics Data System (ADS)

Rudakov, D. L.; Stangeby, P. C.; Elder, J. D.; Ding, R.; Abrams, T.; Unterberg, E. A.; Briesemeister, A.; Donovan, D.; McLean, A. G.; Guo, H. Y.; Thomas, D. M.; Hinson, E.; Wampler, W. R.; Watkins, J. G.

2016-10-01

Two toroidal rings of 5 cm wide W-coated TZM inserts were installed in the lower divertor of DIII-D. Migration of W on the graphite tile surfaces 1-6 cm radially outwards from the outermost ring was studied in a series of 23 reproducible lower single null L-mode discharges with the Outer Strike Point (OSP) placed on the ring. The discharges used 3.2 MW of NBI heating power; plasma density and electron temperature at the OSP were about 1x1020m-3 and 30 eV. W gross erosion rates were measured via monitoring 400.9 nm WI line and applying S/XB coefficient. W deposition was measured on a graphite DiMES sample used as a divertor collector probe. The sample featured two 1 mm wide radial inserts; one was exposed for the whole experiment, the other was exchanged every 4-8 plasma discharges. Measurements of the areal density of W on the inserts by post-mortem RBS analysis show that W deposition is largest in the area of net carbon deposition, possibly due to W re-erosion suppression by C deposits. Measured W coverage in the area of net C erosion is comparable to ERO modeling predictions. Supported by US DOE under DE-FG02-07ER54917, DE-AC04-94AL85000, DE-AC05-00OR22725, DE-AC52-07NA27344, DE-FC02-04ER54698.

Effects of resistivity and rotation on the linear plasma response to non-axisymmetric magnetic perturbations on DIII-D

DOE PAGES

Haskey, Shaun R.; Lanctot, Matthew J.; Liu, Y. Q.; ...

2015-01-05

Parameter scans show the strong dependence of the plasma response on the poloidal structure of the applied field highlighting the importance of being able to control this parameter using non-axisymmetric coil sets. An extensive examination of the linear single fluid plasma response to n = 3 magnetic perturbations in L-mode DIII-D lower single null plasmas is presented. The effects of plasma resistivity, toroidal rotation and applied field structure are calculated using the linear single fluid MHD code, MARS-F. Measures which separate the response into a pitch-resonant and resonant field amplification (RFA) component are used to demonstrate the extent to whichmore » resonant screening and RFA occurs. The ability to control the ratio of pitch-resonant fields to RFA by varying the phasing between upper and lower resonant magnetic perturbations coils sets is shown. The predicted magnetic probe outputs and displacement at the x-point are also calculated for comparison with experiments. Additionally, modelling of the linear plasma response using experimental toroidal rotation profiles and Spitzer like resistivity profiles are compared with results which provide experimental evidence of a direct link between the decay of the resonant screening response and the formation of a 3D boundary. As a result, good agreement is found during the initial application of the MP, however, later in the shot a sudden drop in the poloidal magnetic probe output occurs which is not captured in the linear single fluid modelling.« 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.

A review of radiative detachment studies in tokamak advanced magnetic divertor configurations

DOE PAGES

Soukhanovskii, V. A.

2017-04-28

The present vision for a plasma–material interface in the tokamak is an axisymmetric poloidal magnetic X-point divertor. Four tasks are accomplished by the standard poloidal X-point divertor: plasma power exhaust; particle control (D/T and He pumping); reduction of impurity production (source); and impurity screening by the divertor scrape-off layer. A low-temperature, low heat flux divertor operating regime called radiative detachment is viewed as the main option that addresses these tasks for present and future tokamaks. Advanced magnetic divertor configuration has the capability to modify divertor parallel and cross-field transport, radiative and dissipative losses, and detachment front stability. Advanced magnetic divertormore » configurations are divided into four categories based on their salient qualitative features: (1) multiple standard X-point divertors; (2) divertors with higher order nulls; (3) divertors with multiple X-points; and (4) long poloidal leg divertors (and also with multiple X-points). As a result, this paper reviews experiments and modeling in the area of radiative detachment in the advanced magnetic divertor configurations.« less

A review of radiative detachment studies in tokamak advanced magnetic divertor configurations

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

Soukhanovskii, V. A.

The present vision for a plasma–material interface in the tokamak is an axisymmetric poloidal magnetic X-point divertor. Four tasks are accomplished by the standard poloidal X-point divertor: plasma power exhaust; particle control (D/T and He pumping); reduction of impurity production (source); and impurity screening by the divertor scrape-off layer. A low-temperature, low heat flux divertor operating regime called radiative detachment is viewed as the main option that addresses these tasks for present and future tokamaks. Advanced magnetic divertor configuration has the capability to modify divertor parallel and cross-field transport, radiative and dissipative losses, and detachment front stability. Advanced magnetic divertormore » configurations are divided into four categories based on their salient qualitative features: (1) multiple standard X-point divertors; (2) divertors with higher order nulls; (3) divertors with multiple X-points; and (4) long poloidal leg divertors (and also with multiple X-points). As a result, this paper reviews experiments and modeling in the area of radiative detachment in the advanced magnetic divertor configurations.« less

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.

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101.

PubMed

Li, Jihong; Freedman, John C; Evans, Daniel R; McClane, Bruce A

2017-03-01

Clostridium perfringens type D strains cause enterotoxemia and enteritis in livestock via epsilon toxin production. In type D strain CN3718, CodY was previously shown to increase the level of epsilon toxin production and repress sporulation. C. perfringens type A strains producing C. perfringens enterotoxin (CPE) cause human food poisoning and antibiotic-associated diarrhea. Sporulation is critical for C. perfringens type A food poisoning since spores contribute to transmission and resistance in the harsh food environment and sporulation is essential for CPE production. Therefore, the current study asked whether CodY also regulates sporulation and CPE production in SM101, a derivative of C. perfringens type A food-poisoning strain NCTC8798. An isogenic codY -null mutant of SM101 showed decreased levels of spore formation, along with lower levels of CPE production. A complemented strain recovered wild-type levels of both sporulation and CPE production. When this result was coupled with the earlier results obtained with CN3718, it became apparent that CodY regulation of sporulation varies among different C. perfringens strains. Results from quantitative reverse transcriptase PCR analysis clearly demonstrated that, during sporulation, codY transcript levels remained high in SM101 but rapidly declined in CN3718. In addition, abrB gene expression patterns varied significantly between codY -null mutants of SM101 and CN3718. Compared to the levels in their wild-type parents, the level of abrB gene expression decreased in the CN3718 codY -null mutant strain but significantly increased in the SM101 codY -null mutant strain, demonstrating CodY-dependent regulation differences in abrB expression between these two strains. This difference appears to be important since overexpression of the abrB gene in SM101 reduced the levels of sporulation and enterotoxin production, supporting the involvement of AbrB repression in regulating C. perfringens sporulation. Copyright © 2017 American Society for Microbiology.

CodY Promotes Sporulation and Enterotoxin Production by Clostridium perfringens Type A Strain SM101

PubMed Central

Li, Jihong; Freedman, John C.; Evans, Daniel R.

2017-01-01

ABSTRACT Clostridium perfringens type D strains cause enterotoxemia and enteritis in livestock via epsilon toxin production. In type D strain CN3718, CodY was previously shown to increase the level of epsilon toxin production and repress sporulation. C. perfringens type A strains producing C. perfringens enterotoxin (CPE) cause human food poisoning and antibiotic-associated diarrhea. Sporulation is critical for C. perfringens type A food poisoning since spores contribute to transmission and resistance in the harsh food environment and sporulation is essential for CPE production. Therefore, the current study asked whether CodY also regulates sporulation and CPE production in SM101, a derivative of C. perfringens type A food-poisoning strain NCTC8798. An isogenic codY-null mutant of SM101 showed decreased levels of spore formation, along with lower levels of CPE production. A complemented strain recovered wild-type levels of both sporulation and CPE production. When this result was coupled with the earlier results obtained with CN3718, it became apparent that CodY regulation of sporulation varies among different C. perfringens strains. Results from quantitative reverse transcriptase PCR analysis clearly demonstrated that, during sporulation, codY transcript levels remained high in SM101 but rapidly declined in CN3718. In addition, abrB gene expression patterns varied significantly between codY-null mutants of SM101 and CN3718. Compared to the levels in their wild-type parents, the level of abrB gene expression decreased in the CN3718 codY-null mutant strain but significantly increased in the SM101 codY-null mutant strain, demonstrating CodY-dependent regulation differences in abrB expression between these two strains. This difference appears to be important since overexpression of the abrB gene in SM101 reduced the levels of sporulation and enterotoxin production, supporting the involvement of AbrB repression in regulating C. perfringens sporulation. PMID:28052992

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2015-11-01

Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2-59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

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

Mota, Linda C.; Barfield, Christina; Hernandez, Juan P.

2011-05-01

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

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

PubMed Central

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

2011-01-01

Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investigating the role of PXR in protecting individuals from NP. Wild-type (WT), PXR-null, and humanized PXR (hPXR) mice were treated with NP at 0, 50 or 75 mg/kg/day for one week, and cytochrome P450 (CYP) induction, liver histopathology, and serum NP concentrations were examined. WT mice treated with NP showed induction of Cyp2b, and male-specific induction of Cyp2c and Cyp3a. CYPs were not induced in PXR-null mice, demonstrating that PXR is necessary for NP-mediated CYP induction. CAR-mediated CYP induction was not observed in the PXR-null mice despite previous data demonstrating NP is also a CAR activator. hPXR mice only showed moderate Cyp induction, suggesting that hPXR is not as sensitive to NP as mPXR in vivo. NP-mediated Cyp3a induction from three human hepatocyte donors was not significant, confirming that hPXR is not very sensitive to NP-mediated CYP induction. Lastly, mice with PXR (mPXR and hPXR) showed lower NP serum concentrations than PXR-null mice treated with NP suggesting that PXR plays a role in decreasing liver toxicity by basally regulating Phase I-III detoxification enzymes that promote the metabolism and elimination of NP. In summary, PXR is required for NP-mediated CYP-induction, and mPXR mediates greater CYP induction than hPXR in vivo, and the presence of PXR, especially mPXR, is associated with altered histopathology and increased clearance of NP. PMID:21376070

THE α-GLYCEROPHOSPHATE CYCLE IN DROSOPHILA MELANOGASTER

PubMed Central

O'Brien, Stephen J.; Shimada, Yoshio

1974-01-01

"Null" mutations previously isolated at the αGpdh-1 locus of Drosophila melanogaster, because of disruption of the energy-producing α-glycerophosphate cycle, severely restrict the flight ability and relative viability of affected individuals. Two "null" alleles, αGpdh-1 BO-1-4, and αGpdh-1 BO-1-5, when made hemizygous with a deficiency of the αGpdh-1 locus, Df(2L)GdhA, were rendered homozygous by recombination with and selective elimination of the Df(2L)GdhA chromosome. After over 25 generations, a homozygous αGpdh-1 BO-1-4 stock regained the ability to fly despite the continued absence of measurable αGPDH activity. Inter se heterozygotes of three noncomplementing αGpdh-1 "null" alleles and the "adapted" αGpdh-1 BO-1-4 homozygotes were examined for metabolic enzymatic activities related to the energy-producing and pyridine nucleotide-regulating functions of the α-glycerophosphate cycle in Drosophila. The enzyme functions tested included glyceraldehyde-3-phosphate dehydrogenase, cytoplasmic and soluble malate dehydrogenase, lactate dehydrogenase, mitochondrial NADH oxidation, oxidative phosphorylation, and respiratory control with the substrates α-glycerophosphate, succinate, and pyruvate. These activities in any of the mutant genotypes in early adult life were indistinguishable from those in the wild type. There was, however, a premature deterioration and atrophy of the ultrastructural integrity of flight muscle sarcosomes observed by electron microscopy in the "null" mutants. These observations were correlated with a decrease in state 3 mitochondrial oxidation with α-glycerophosphate, succinate, and pyruvate, as well as with loss of respiratory control in adults as early as 2 wk after eclosion. Such observations, which normally are seen in aged dipterans, were accompanied by premature mortality of the mutant heterozygotes. The adapted αGpdh-1 BO-1-4 was identical with wild type in each of the aging characters with the single exception of lowered rates of mitochondrial oxidative phosphorylation. PMID:4154945

Type III Solar Radio Burst Source Region Splitting due to a Quasi-separatrix Layer

NASA Astrophysics Data System (ADS)

McCauley, Patrick I.; Cairns, Iver H.; Morgan, John; Gibson, Sarah E.; Harding, James C.; Lonsdale, Colin; Oberoi, Divya

2017-12-01

We present low-frequency (80–240 MHz) radio imaging of type III solar radio bursts observed by the Murchison Widefield Array on 2015 September 21. The source region for each burst splits from one dominant component at higher frequencies into two increasingly separated components at lower frequencies. For channels below ∼132 MHz, the two components repetitively diverge at high speeds (0.1c–0.4c) along directions tangent to the limb, with each episode lasting just ∼2 s. We argue that both effects result from the strong magnetic field connectivity gradient that the burst-driving electron beams move into. Persistence mapping of extreme-ultraviolet jets observed by the Solar Dynamics Observatory reveals quasi-separatrix layers (QSLs) associated with coronal null points, including separatrix dome, spine, and curtain structures. Electrons are accelerated at the flare site toward an open QSL, where the beams follow diverging field lines to produce the source splitting, with larger separations at larger heights (lower frequencies). The splitting motion within individual frequency bands is interpreted as a projected time-of-flight effect, whereby electrons traveling along the outer field lines take slightly longer to excite emission at adjacent positions. Given this interpretation, we estimate an average beam speed of 0.2c. We also qualitatively describe the quiescent corona, noting in particular that a disk-center coronal hole transitions from being dark at higher frequencies to bright at lower frequencies, turning over around 120 MHz. These observations are compared to synthetic images based on the MHD algorithm outside a sphere (MAS) model, which we use to flux-calibrate the burst data.

Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.

PubMed

Carlsten, Chris; Blomberg, Anders; Pui, Mandy; Sandstrom, Thomas; Wong, Sze Wing; Alexis, Neil; Hirota, Jeremy

2016-01-01

Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. 18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust. NCT01792232. 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/

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

Arabidopsis plants harbouring a mutation in AtSUC2, encoding the predominant sucrose/proton symporter necessary for efficient phloem transport, are able to complete their life cycle and produce viable seed

PubMed Central

Srivastava, Avinash C.; Dasgupta, Kasturi; Ajieren, Eric; Costilla, Gabriella; McGarry, Roisin C.; Ayre, Brian G.

2009-01-01

Background and Aims AtSUC2 encodes a sucrose/proton symporter that localizes throughout the collection and transport phloem and is necessary for efficient transport of sucrose from source to sink tissues in Arabidopsis thaliana. Plants harbouring homozygous AtSUC2 null alleles accumulate sugar, starch, and anthocyanin in mature leaves, have severely delayed development and stunted growth and, in previous studies, failed to complete their life cycle by producing viable seed. Methods An AtSUC2 allele with a T-DNA insertion in the second intron was analysed. Full-length transcript from this allele is not produced, and a truncated protein translated from sequences upstream of the insertion site did not catalyse sucrose uptake into yeast, supporting the contention that this is a null allele. Mutant plants were grown in a growth chamber with a diurnal light/dark cycle, and growth patterns recorded. Key Results This allele (SALK_038124, designated AtSUC2-4) has the hallmarks of previously described null alleles but, despite compromised carbon partitioning and growth, produces viable seeds. The onset of flowering was chronologically delayed but occurred at the same point in the plastochron index as wild type. Conclusions AtSUC2 is important for phloem loading and is therefore fundamental to phloem transport and plant productivity, but plants can complete their life cycle and produce viable seed in its absence. Arabidopsis appears to have mechanisms for mobilizing reduced carbon from the phloem into developing seeds independent of AtSUC2. PMID:19789176

Variant-specific quantification of factor H in plasma reveals null alleles associated with atypical hemolytic uremic syndrome

PubMed Central

Hakobyan, Svetlana; Tortajada, Agustín; Harris, Claire L.; de Córdoba, Santiago Rodríguez; Morgan, B. Paul

2011-01-01

Atypical hemolytic uremic syndrome (aHUS) associates with complement alternative pathway defects in over 50% of cases. Mutations in factor H (fH) are most common, usually point mutations affecting complement surface regulation and sometimes null mutations in heterozygosity. The latter are difficult to identify; although consistently low plasma fH concentration is suggestive, definitive proof has required the demonstration that the mutant sequence does not express in vitro. Here, novel reagents and assays that distinguish and individually quantify the common fH-Y402H polymorphic variants were used to identify alleles of the CFH gene resulting in low or no (‘null’) expression of full-length fH, but normal or increased expression of the alternative splice product FHL-1, also detected in these assays. Their use in an aHUS cohort identified three Y402H heterozygotes with low or absent fH-H402 but normal or increased FHL-1 levels. Novel mutations in heterozygosis explained the null phenotype in two cases, confirmed by family studies in one. In the third case, family studies showed that a known mutation was present on the Y allele; the cause of the reduced expression of H allele was not found, although data suggested altered fH/FHL-1 splicing. In each family, inheritance of “low expression” or “null” alleles for fH strongly associated with aHUS. These assays provide a rapid means to identify fH expression defects in aHUS without resorting to gene sequencing or expression analysis. PMID:20703214

2010 August 1–2 Sympathetic Eruptions. II. Magnetic Topology of the MHD Background Field

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

Titov, Viacheslav S.; Mikić, Zoran; Török, Tibor

Using a potential field source-surface (PFSS) model, we recently analyzed the global topology of the background coronal magnetic field for a sequence of coronal mass ejections (CMEs) that occurred on 2010 August 1–2. Here we repeat this analysis for the background field reproduced by a magnetohydrodynamic (MHD) model that incorporates plasma thermodynamics. As for the PFSS model, we find that all three CME source regions contain a coronal hole (CH) that is separated from neighboring CHs by topologically very similar pseudo-streamer structures. However, the two models yield very different results for the size, shape, and flux of the CHs. Wemore » find that the helmet-streamer cusp line, which corresponds to a source-surface null line in the PFSS model, is structurally unstable and does not form in the MHD model. Our analysis indicates that, generally, in MHD configurations, this line instead consists of a multiple-null separator passing along the edge of disconnected-flux regions. Some of these regions are transient and may be the origin of the so-called streamer blobs. We show that the core topological structure of such blobs is a three-dimensional “plasmoid” consisting of two conjoined flux ropes of opposite handedness, which connect at a spiral null point of the magnetic field. Our analysis reveals that such plasmoids also appear in pseudo-streamers on much smaller scales. These new insights into the coronal magnetic topology provide some intriguing implications for solar energetic particle events and for the properties of the slow solar wind.« less

Formation of the Sun-aligned arc region and the void (polar slot) under the null-separator structure

NASA Astrophysics Data System (ADS)

Tanaka, T.; Obara, T.; Watanabe, M.; Fujita, S.; Ebihara, Y.; Kataoka, R.

2017-04-01

From the global magnetosphere-ionosphere coupling simulation, we examined the formation of the Sun-aligned arc region and the void (polar slot) under the northward interplanetary magnetic field (IMF) with negative By condition. In the magnetospheric null-separator structure, the separatrices generated from two null points and two separators divide the entire space into four types of magnetic region, i.e., the IMF, the northern open magnetic field, the southern open magnetic field, and the closed magnetic field. In the ionosphere, the Sun-aligned arc region and the void are reproduced in the distributions of simulated plasma pressure and field-aligned current. The outermost closed magnetic field lines on the boundary (separatrix) between the northern open magnetic field and the closed magnetic field are projected to the northern ionosphere at the boundary between the Sun-aligned arc region and the void, both on the morning and evening sides. The magnetic field lines at the plasma sheet inner edge are projected to the equatorward boundary of the oval. Therefore, the Sun-aligned arc region is on the closed magnetic field lines of the plasma sheet. In the plasma sheet, an inflated structure (bulge) is generated at the junction of the tilted plasma sheet in the far-to-middle tail and nontilted plasma sheet in the ring current region. In the Northern Hemisphere, the bulge is on the evening side wrapped by the outermost closed magnetic field lines that are connected to the northern evening ionosphere. This inflated structure (bulge) is associated with shear flows that cause the Sun-aligned arc.

Arabidopsis plants harbouring a mutation in AtSUC2, encoding the predominant sucrose/proton symporter necessary for efficient phloem transport, are able to complete their life cycle and produce viable seed.

PubMed

Srivastava, Avinash C; Dasgupta, Kasturi; Ajieren, Eric; Costilla, Gabriella; McGarry, Roisin C; Ayre, Brian G

2009-11-01

AtSUC2 encodes a sucrose/proton symporter that localizes throughout the collection and transport phloem and is necessary for efficient transport of sucrose from source to sink tissues in Arabidopsis thaliana. Plants harbouring homozygous AtSUC2 null alleles accumulate sugar, starch, and anthocyanin in mature leaves, have severely delayed development and stunted growth and, in previous studies, failed to complete their life cycle by producing viable seed. An AtSUC2 allele with a T-DNA insertion in the second intron was analysed. Full-length transcript from this allele is not produced, and a truncated protein translated from sequences upstream of the insertion site did not catalyse sucrose uptake into yeast, supporting the contention that this is a null allele. Mutant plants were grown in a growth chamber with a diurnal light/dark cycle, and growth patterns recorded. This allele (SALK_038124, designated AtSUC2-4) has the hallmarks of previously described null alleles but, despite compromised carbon partitioning and growth, produces viable seeds. The onset of flowering was chronologically delayed but occurred at the same point in the plastochron index as wild type. AtSUC2 is important for phloem loading and is therefore fundamental to phloem transport and plant productivity, but plants can complete their life cycle and produce viable seed in its absence. Arabidopsis appears to have mechanisms for mobilizing reduced carbon from the phloem into developing seeds independent of AtSUC2.

Nonparametric relevance-shifted multiple testing procedures for the analysis of high-dimensional multivariate data with small sample sizes.

PubMed

Frömke, Cornelia; Hothorn, Ludwig A; Kropf, Siegfried

2008-01-27

In many research areas it is necessary to find differences between treatment groups with several variables. For example, studies of microarray data seek to find a significant difference in location parameters from zero or one for ratios thereof for each variable. However, in some studies a significant deviation of the difference in locations from zero (or 1 in terms of the ratio) is biologically meaningless. A relevant difference or ratio is sought in such cases. This article addresses the use of relevance-shifted tests on ratios for a multivariate parallel two-sample group design. Two empirical procedures are proposed which embed the relevance-shifted test on ratios. As both procedures test a hypothesis for each variable, the resulting multiple testing problem has to be considered. Hence, the procedures include a multiplicity correction. Both procedures are extensions of available procedures for point null hypotheses achieving exact control of the familywise error rate. Whereas the shift of the null hypothesis alone would give straight-forward solutions, the problems that are the reason for the empirical considerations discussed here arise by the fact that the shift is considered in both directions and the whole parameter space in between these two limits has to be accepted as null hypothesis. The first algorithm to be discussed uses a permutation algorithm, and is appropriate for designs with a moderately large number of observations. However, many experiments have limited sample sizes. Then the second procedure might be more appropriate, where multiplicity is corrected according to a concept of data-driven order of hypotheses.

2010 August 1-2 Sympathetic Eruptions. II. Magnetic Topology of the MHD Background Field

NASA Astrophysics Data System (ADS)

Titov, Viacheslav S.; Mikić, Zoran; Török, Tibor; Linker, Jon A.; Panasenco, Olga

2017-08-01

Using a potential field source-surface (PFSS) model, we recently analyzed the global topology of the background coronal magnetic field for a sequence of coronal mass ejections (CMEs) that occurred on 2010 August 1-2. Here we repeat this analysis for the background field reproduced by a magnetohydrodynamic (MHD) model that incorporates plasma thermodynamics. As for the PFSS model, we find that all three CME source regions contain a coronal hole (CH) that is separated from neighboring CHs by topologically very similar pseudo-streamer structures. However, the two models yield very different results for the size, shape, and flux of the CHs. We find that the helmet-streamer cusp line, which corresponds to a source-surface null line in the PFSS model, is structurally unstable and does not form in the MHD model. Our analysis indicates that, generally, in MHD configurations, this line instead consists of a multiple-null separator passing along the edge of disconnected-flux regions. Some of these regions are transient and may be the origin of the so-called streamer blobs. We show that the core topological structure of such blobs is a three-dimensional “plasmoid” consisting of two conjoined flux ropes of opposite handedness, which connect at a spiral null point of the magnetic field. Our analysis reveals that such plasmoids also appear in pseudo-streamers on much smaller scales. These new insights into the coronal magnetic topology provide some intriguing implications for solar energetic particle events and for the properties of the slow solar wind.

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.

Aldose reductase mediates retinal microglia activation

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

Chang, Kun-Che; Shieh, Biehuoy; Petrash, J. Mark, E-mail: mark.petrash@ucdenver.edu

Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1{sup GFP} mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migrationmore » in vivo. When tested on an AR{sup WT} background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.« less

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.

The study of heat flux for disruption on experimental advanced superconducting tokamak

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

Yang, Zhendong, E-mail: dongyz@ipp.ac.cn, E-mail: jafang@dhu.edu.cn; Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031; Fang, Jianan, E-mail: dongyz@ipp.ac.cn, E-mail: jafang@dhu.edu.cn

Disruption of the plasma is one of the most dangerous instabilities in tokamak. During the disruption, most of the plasma thermal energy is lost, which causes damages to the plasma facing components. Infrared (IR) camera is an effective tool to detect the temperature distribution on the first wall, and the energy deposited on the first wall can be calculated from the surface temperature profile measured by the IR camera. This paper concentrates on the characteristics of heat flux distribution onto the first wall under different disruptions, including the minor disruption and the vertical displacement events (VDE) disruption. Several minor disruptionsmore » have been observed before the major disruption under the high plasma density in experimental advanced superconducting tokamak. During the minor disruption, the heat fluxes are mainly deposited on the upper/lower divertors. The magnetic configuration prior to the minor disruption is a lower single null with the radial distance between the two separatrices in the outer midplane dR{sub sep} = −2 cm, while it changes to upper single null (dR{sub sep} = 1.4 cm) during the minor disruption. As for the VDE disruption, the spatial distribution of heat flux exhibits strong toroidal and radial nonuniformity, and the maximum heat flux received on the dome plate can be up to 11 MW/m{sup 2}.« less

γ-glutamyl transpeptidase 1 specifically suppresses green-light avoidance via GABAA receptors in Drosophila.

PubMed

Liu, Jiangqu; Gong, Zhefeng; Liu, Li

2014-08-01

Drosophila larvae innately show light avoidance behavior. Compared with robust blue-light avoidance, larvae exhibit relatively weaker green-light responses. In our previous screening for genes involved in larval light avoidance, compared with control w(1118) larvae, larvae with γ-glutamyl transpeptidase 1 (Ggt-1) knockdown or Ggt-1 mutation were found to exhibit higher percentage of green-light avoidance which was mediated by Rhodopsin6 (Rh6) photoreceptors. However, their responses to blue light did not change significantly. By adjusting the expression level of Ggt-1 in different tissues, we found that Ggt-1 in malpighian tubules was both necessary and sufficient for green-light avoidance. Our results showed that glutamate levels were lower in Ggt-1 null mutants compared with controls. Feeding Ggt-1 null mutants glutamate can normalize green-light avoidance, indicating that high glutamate concentrations suppressed larval green-light avoidance. However, rather than directly, glutamate affected green-light avoidance indirectly through GABA, the level of which was also lower in Ggt-1 mutants compared with controls. Mutants in glutamate decarboxylase 1, which encodes GABA synthase, and knockdown lines of the GABAA receptor, both exhibit elevated levels of green-light avoidance. Thus, our results elucidate the neurobiological mechanisms mediating green-light avoidance, which was inhibited in wild-type larvae. © 2014 International Society for Neurochemistry.

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

P53 Suppression of Homologous Recombination and Tumorigenesis

DTIC Science & Technology

2011-01-01

huge strides have been made in the numbers of mice breed and relevant cells collected for the purposes of experiments outlined in the aims below. The PI... breeding colony of R172P, R172H, Wild type and p53 null mice in order to have sufficient numbers of animals to perform the in vivo pun assay. Mouse...Strains and Breeding Cohorts Mice heterozygous for the point mutations p53R172P and p53R172H both on a C57BL/6 genetic background were kindly

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

Kerner, Ryan; Mann, R.B.

We investigate quantum tunnelling methods for calculating black hole temperature, specifically the null-geodesic method of Parikh and Wilczek and the Hamilton-Jacobi Ansatz method of Angheben et al. We consider application of these methods to a broad class of spacetimes with event horizons, including Rindler and nonstatic spacetimes such as Kerr-Newman and Taub-NUT. We obtain a general form for the temperature of Taub-NUT-AdS black holes that is commensurate with other methods. We examine the limitations of these methods for extremal black holes, taking the extremal Reissner-Nordstrom spacetime as a case in point.

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

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

Interconnections between various analytic approaches applicable to third-order nonlinear differential equations

PubMed Central

Mohanasubha, R.; Chandrasekar, V. K.; Senthilvelan, M.; Lakshmanan, M.

2015-01-01

We unearth the interconnection between various analytical methods which are widely used in the current literature to identify integrable nonlinear dynamical systems described by third-order nonlinear ODEs. We establish an important interconnection between the extended Prelle–Singer procedure and λ-symmetries approach applicable to third-order ODEs to bring out the various linkages associated with these different techniques. By establishing this interconnection we demonstrate that given any one of the quantities as a starting point in the family consisting of Jacobi last multipliers, Darboux polynomials, Lie point symmetries, adjoint-symmetries, λ-symmetries, integrating factors and null forms one can derive the rest of the quantities in this family in a straightforward and unambiguous manner. We also illustrate our findings with three specific examples. PMID:27547076

Interconnections between various analytic approaches applicable to third-order nonlinear differential equations.

PubMed

Mohanasubha, R; Chandrasekar, V K; Senthilvelan, M; Lakshmanan, M

2015-04-08

We unearth the interconnection between various analytical methods which are widely used in the current literature to identify integrable nonlinear dynamical systems described by third-order nonlinear ODEs. We establish an important interconnection between the extended Prelle-Singer procedure and λ-symmetries approach applicable to third-order ODEs to bring out the various linkages associated with these different techniques. By establishing this interconnection we demonstrate that given any one of the quantities as a starting point in the family consisting of Jacobi last multipliers, Darboux polynomials, Lie point symmetries, adjoint-symmetries, λ-symmetries, integrating factors and null forms one can derive the rest of the quantities in this family in a straightforward and unambiguous manner. We also illustrate our findings with three specific examples.

Bounds on OPE coefficients from interference effects in the conformal collider

NASA Astrophysics Data System (ADS)

Córdova, Clay; Maldacena, Juan; Turiaci, Gustavo J.

2017-11-01

We apply the average null energy condition to obtain upper bounds on the three-point function coefficients of stress tensors and a scalar operator, < TTOi>, in general CFTs. We also constrain the gravitational anomaly of U(1) currents in four-dimensional CFTs, which are encoded in three-point functions of the form 〈 T T J 〉. In theories with a large N AdS dual we translate these bounds into constraints on the coefficient of a higher derivative bulk term of the form ∫ϕ W 2. We speculate that these bounds also apply in de-Sitter. In this case our results constrain inflationary observables, such as the amplitude for chiral gravity waves that originate from higher derivative terms in the Lagrangian of the form ϕ W W ∗.

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

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 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 ftsH gene of Bacillus subtilis is involved in major cellular processes such as sporulation, stress adaptation and secretion.

PubMed

Deuerling, E; Mogk, A; Richter, C; Purucker, M; Schumann, W

1997-03-01

The ftsH gene of Bacillus subtilis has been identified as a general stress gene which is transiently induced after thermal or osmotic upshift. The FtsH protein exhibits 70.1% homology to FtsH of Escherichia coli which constitutes an essential ATP- and Zn(2+)-dependent protease anchored in the cytoplasmic membrane via two N-terminal transmembrane domains. This paper describes the isolation and functional characterization of an ftsH null mutant which was obtained by integration of a cat-cassette near the 5' end of ftsH, thereby preventing the synthesis of FtsH protein. In contrast to the situation in E. coli, ftsH is dispensable in B. subtilis but results in a pleiotropic phenotype. While the mutant cells grew mostly as large filaments under physiological conditions, they turned out to be extremely sensitive to heat and salt stress. Although ftsH is necessary for adaptation to heat, it is not involved in the regulation of the heat-shock response. The induction profiles of representative genes of the CIRCE and sigma-B regulon and class III heat-shock genes ion and clpC were identical in the wild type and the ftsH null mutant. Furthermore, the ftsH knockout strain was unable to sporulate, and this failure was probably due to the absence of Spo0A protein which is essential for entry into the sporulation programme. In addition, secretion of bulk exoproteins was severely impaired in the ftsH null mutant after entry into stationary phase. The alpha-amylase and subtilisin activity in the supernatant was specifically tested. Whereas the activity of alpha-amylase increased after entry into stationary phase in both the wild type and the ftsH mutant strain, that of subtilisin encoded by aprE was prevented at the level of transcription in the mutant. Most of these results can be explained by the failure to synthesize appropriate amounts of Spo0A protein in the ftsH null mutant and point to ftsH as a developmental checkpoint.

Lymphocyte changes in beta-thalassaemia major.

PubMed Central

Musumeci, S; Schiliro, G; Romeo, M A; Sciotto, A; Rosalba, A; Pizzarelli, G

1979-01-01

Lymphocyte subpopulations were studied in 20 hypertransfused patients with beta-thalassaemia major, some of whom had been splenectomised. B-lymphocytes were normal but T-lymphocytes were decreased in all patients. The T-cell count was lower in the splenectomised patients than in the nonsplenectomised ones. In the former, the active rosette-forming lymphocytes were also diminished, but the difference was not significant. In all patients the percentage of null cells was greater and the activity of K-cells increased compared with controls. PMID:316991

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

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

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.

Effects of Heterogeniety on Spatial Pattern Analysis of Wild Pistachio Trees in Zagros Woodlands, Iran

NASA Astrophysics Data System (ADS)

Erfanifard, Y.; Rezayan, F.

2014-10-01

Vegetation heterogeneity biases second-order summary statistics, e.g., Ripley's K-function, applied for spatial pattern analysis in ecology. Second-order investigation based on Ripley's K-function and related statistics (i.e., L- and pair correlation function g) is widely used in ecology to develop hypothesis on underlying processes by characterizing spatial patterns of vegetation. The aim of this study was to demonstrate effects of underlying heterogeneity of wild pistachio (Pistacia atlantica Desf.) trees on the second-order summary statistics of point pattern analysis in a part of Zagros woodlands, Iran. The spatial distribution of 431 wild pistachio trees was accurately mapped in a 40 ha stand in the Wild Pistachio & Almond Research Site, Fars province, Iran. Three commonly used second-order summary statistics (i.e., K-, L-, and g-functions) were applied to analyse their spatial pattern. The two-sample Kolmogorov-Smirnov goodness-of-fit test showed that the observed pattern significantly followed an inhomogeneous Poisson process null model in the study region. The results also showed that heterogeneous pattern of wild pistachio trees biased the homogeneous form of K-, L-, and g-functions, demonstrating a stronger aggregation of the trees at the scales of 0-50 m than actually existed and an aggregation at scales of 150-200 m, while regularly distributed. Consequently, we showed that heterogeneity of point patterns may bias the results of homogeneous second-order summary statistics and we also suggested applying inhomogeneous summary statistics with related null models for spatial pattern analysis of heterogeneous vegetations.

Imaging gray matter with concomitant null point imaging from the phase sensitive inversion recovery sequence.

PubMed

Mougin, Olivier; Abdel-Fahim, Rasha; Dineen, Robert; Pitiot, Alain; Evangelou, Nikos; Gowland, Penny

2016-11-01

To present an improved three-dimensional (3D) interleaved phase sensitive inversion recovery (PSIR) sequence including a concomitantly acquired new contrast, null point imaging (NPI), to help detect and classify abnormalities in cortical gray matter. The 3D gradient echo PSIR images were acquired at 0.6 mm isotropic resolution on 11 multiple sclerosis (MS) patients and 9 controls subjects using a 7 Tesla (T) MRI scanner, and 2 MS patients at 3T. Cortical abnormalities were delineated on the NPI/PSIR data and later classified according to position in the cortex. The NPI helped detect cortical lesions within the cortical ribbon with increased, positive contrast compared with the PSIR. It also provided improved intrinsic delineation of the ribbon, increasing confidence in classifying the lesions' locations. The proposed PSIR facilitates the classification of cortical lesions by providing two T 1 -weighted 3D datasets with isotropic resolution, including the NPI showing cortical lesions with clear delineation of the gray/white matter boundary and minimal partial volume effects. Magn Reson Med 76:1512-1516, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Medical service provider networks.

PubMed

Mougeot, Michel; Naegelen, Florence

2018-05-17

In many countries, health insurers or health plans choose to contract either with any willing providers or with preferred providers. We compare these mechanisms when two medical services are imperfect substitutes in demand and are supplied by two different firms. In both cases, the reimbursement is higher when patients select the in-network provider(s). We show that these mechanisms yield lower prices, lower providers' and insurer's profits, and lower expense than in the uniform-reimbursement case. Whatever the degree of product differentiation, a not-for-profit insurer should prefer selective contracting and select a reimbursement such that the out-of-pocket expense is null. Although all providers join the network under any-willing-provider contracting in the absence of third-party payment, an asymmetric equilibrium may exist when this billing arrangement is implemented. Copyright © 2018 John Wiley & Sons, Ltd.

Direct Contra Naïve-Indirect Comparison of Clinical Failure Rates between High-Viscosity GIC and Conventional Amalgam Restorations: An Empirical Study

PubMed Central

Mickenautsch, Steffen; Yengopal, Veerasamy

2013-01-01

Background Naïve-indirect comparisons are comparisons between competing clinical interventions’ evidence from separate (uncontrolled) trials. Direct comparisons are comparisons within randomised control trials (RCTs). The objective of this empirical study is to test the null-hypothesis that trends and performance differences inferred from naïve-indirect comparisons and from direct comparisons/RCTs regarding the failure rates of amalgam and direct high-viscosity glass-ionomer cement (HVGIC) restorations in permanent posterior teeth have similar direction and magnitude. Methods A total of 896 citations were identified through systematic literature search. From these, ten and two uncontrolled clinical longitudinal studies for HVGIC and amalgam, respectively, were included for naïve-indirect comparison and could be matched with three out twenty RCTs. Summary effects sizes were computed as Odds ratios (OR; 95% Confidence intervals) and compared with those from RCTs. Trend directions were inferred from 95% Confidence interval overlaps and direction of point estimates; magnitudes of performance differences were inferred from the median point estimates (OR) with 25% and 75% percentile range, for both types of comparison. Mann-Whitney U test was applied to test for statistically significant differences between point estimates of both comparison types. Results Trends and performance differences inferred from naïve-indirect comparison based on evidence from uncontrolled clinical longitudinal studies and from direct comparisons based on RCT evidence are not the same. The distributions of the point estimates differed significantly for both comparison types (Mann–Whitney U  =  25, nindirect  =  26; ndirect  =  8; p  =  0.0013, two-tailed). Conclusion The null-hypothesis was rejected. Trends and performance differences inferred from either comparison between HVGIC and amalgam restorations failure rates in permanent posterior teeth are not the same. It is recommended that clinical practice guidance regarding HVGICs should rest on direct comparisons via RCTs and not on naïve-indirect comparisons based on uncontrolled longitudinal studies in order to avoid inflation of effect estimates. PMID:24205220

Direct contra naïve-indirect comparison of clinical failure rates between high-viscosity GIC and conventional amalgam restorations: an empirical study.

PubMed

Mickenautsch, Steffen; Yengopal, Veerasamy

2013-01-01

Naïve-indirect comparisons are comparisons between competing clinical interventions' evidence from separate (uncontrolled) trials. Direct comparisons are comparisons within randomised control trials (RCTs). The objective of this empirical study is to test the null-hypothesis that trends and performance differences inferred from naïve-indirect comparisons and from direct comparisons/RCTs regarding the failure rates of amalgam and direct high-viscosity glass-ionomer cement (HVGIC) restorations in permanent posterior teeth have similar direction and magnitude. A total of 896 citations were identified through systematic literature search. From these, ten and two uncontrolled clinical longitudinal studies for HVGIC and amalgam, respectively, were included for naïve-indirect comparison and could be matched with three out twenty RCTs. Summary effects sizes were computed as Odds ratios (OR; 95% Confidence intervals) and compared with those from RCTs. Trend directions were inferred from 95% Confidence interval overlaps and direction of point estimates; magnitudes of performance differences were inferred from the median point estimates (OR) with 25% and 75% percentile range, for both types of comparison. Mann-Whitney U test was applied to test for statistically significant differences between point estimates of both comparison types. Trends and performance differences inferred from naïve-indirect comparison based on evidence from uncontrolled clinical longitudinal studies and from direct comparisons based on RCT evidence are not the same. The distributions of the point estimates differed significantly for both comparison types (Mann-Whitney U  =  25, n(indirect)  =  26; n(direct)  =  8; p  =  0.0013, two-tailed). The null-hypothesis was rejected. Trends and performance differences inferred from either comparison between HVGIC and amalgam restorations failure rates in permanent posterior teeth are not the same. It is recommended that clinical practice guidance regarding HVGICs should rest on direct comparisons via RCTs and not on naïve-indirect comparisons based on uncontrolled longitudinal studies in order to avoid inflation of effect estimates.

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.

High-order optical vortex position detection using a Shack-Hartmann wavefront sensor.

PubMed

Luo, Jia; Huang, Hongxin; Matsui, Yoshinori; Toyoda, Haruyoshi; Inoue, Takashi; Bai, Jian

2015-04-06

Optical vortex (OV) beams have null-intensity singular points, and the intensities in the region surrounding the singular point are quite low. This low intensity region influences the position detection accuracy of phase singular point, especially for high-order OV beam. In this paper, we propose a new method for solving this problem, called the phase-slope-combining correlation matching method. A Shack-Hartmann wavefront sensor (SH-WFS) is used to measure phase slope vectors at lenslet positions of the SH-WFS. Several phase slope vectors are combined into one to reduce the influence of low-intensity regions around the singular point, and the combined phase slope vectors are used to determine the OV position with the aid of correlation matching with a pre-calculated database. Experimental results showed that the proposed method works with high accuracy, even when detecting an OV beam with a topological charge larger than six. The estimated precision was about 0.15 in units of lenslet size when detecting an OV beam with a topological charge of up to 20.

Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

PubMed

Nicolet-Barousse, Laurence; Blanchard, Anne; Roux, Christian; Pietri, Laurence; Bloch-Faure, May; Kolta, Sami; Chappard, Christine; Geoffroy, Valérie; Morieux, Caroline; Jeunemaitre, Xavier; Shull, Gary E; Meneton, Pierre; Paillard, Michel; Houillier, Pascal; De Vernejoul, Marie-Christine

2005-05-01

Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion. Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD. To understand the underlying mechanisms, Ca and bone metabolism were studied in two models of genetic inactivation of the thiazide-sensitive NaCl cotransporter (NCC): patients with Gitelman syndrome (GS) and Ncc knockout (Ncc(-/-)) mice. Ca metabolism was analyzed in GS patients and Ncc(-/-) mice under conditions of low dietary Ca. BMD was measured by DXA in patients and mice, and bone histomorphometry was analyzed in mice. GS patients had low plasma Mg. They exhibited reduced UVCa, but similar serum Ca and GFR as control subjects, suggesting increased renal Ca reabsorption. Blood PTH was lower despite lower serum ionized Ca, and Mg repletion almost corrected both relative hypoparathyroidism and low UVCa. BMD was significantly increased in GS patients at both lumbar (+7%) and femoral (+16%) sites, and osteocalcin was reduced. In Ncc(-/-) mice, serum Ca and GFR were unchanged, but UVCa was reduced and PTH was elevated; Mg repletion largely corrected both abnormalities. Trabecular and cortical BMD were higher than in Ncc(+/+) mice (+4% and +5%, respectively), and despite elevated PTH, were associated with higher cortical thickness and lower endosteal osteoclastic surface. Higher BMD is observed in GS patients and Ncc(-/-) mice. Relative hypoparathyroidism (human) and bone resistance to PTH (mice), mainly caused by Mg depletion, can explain the low bone remodeling and normal/low serum Ca despite increased renal Ca reabsorption.

Laron Dwarfism and Non-Insulin-Dependent Diabetes Mellitus in the Hnf-1α Knockout Mouse

PubMed Central

Lee, Ying-Hue; Sauer, Brian; Gonzalez, Frank J.

1998-01-01

Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1α) were produced by use of the Cre-loxP recombination system. HNF-1α-null mice are viable but sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non-insulin-dependent diabetes mellitus (NIDDM). In contrast to an earlier HNF-1α-null mouse line that had been produced by use of standard gene disruption methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P. Bach, C. Babinet, and M. Yaniv, Cell 84:575–585, 1996), these mice exhibited no increased mortality and only minimal renal dysfunction during the first 6 months of development. Both dwarfism and NIDDM are most likely due to the loss of expression of insulin-like growth factor I (IGF-I) and lower levels of insulin, resulting in stunted growth and elevated serum glucose levels, respectively. These results confirm the functional significance of the HNF-1α regulatory elements that had previously been shown to reside in the promoter regions of both the IGF-I and the insulin genes. PMID:9566924

Mule determines the apoptotic response to HDAC inhibitors by targeted ubiquitination and destruction of HDAC2

PubMed Central

Zhang, Jing; Kan, Shu; Huang, Brian; Hao, Zhenyue; Mak, Tak W.; Zhong, Qing

2011-01-01

Histone deacetylases (HDACs) are major epigenetic modulators involved in a broad spectrum of human diseases including cancers. Administration of HDAC inhibitors (HDACis) leads to growth inhibition, differentiation, and apoptosis of cancer cells. Understanding the regulatory mechanism of HDACs is imperative to harness the therapeutic potentials of HDACis. Here we show that HDACi- and DNA damage-induced apoptosis are severely compromised in mouse embryonic fibroblasts lacking a HECT domain ubiquitin ligase, Mule (Mcl-1 ubiquitin ligase E3). Mule specifically targets HDAC2 for ubiquitination and degradation. Accumulation of HDAC2 in Mule-deficient cells leads to compromised p53 acetylation as well as crippled p53 transcriptional activation, accumulation, and apoptotic response upon DNA damage and Nutlin-3 treatments. These defects in Mule-null cells can be partially reversed by HDACis and fully rescued by lowering the elevated HDAC2 in Mule-null cells to the normal levels as in wild-type cells. Taken together, our results reveal a critical regulatory mechanism of HDAC2 by Mule and suggest this pathway determines the cellular response to HDACis and DNA damage. PMID:22016339

An ellipsometric approach towards the description of inhomogeneous polymer-based Langmuir layers

PubMed Central

Rottke, Falko O; Schulz, Burkhard; Richau, Klaus; Kratz, Karl

2016-01-01

Summary The applicability of nulling-based ellipsometric mapping as a complementary method next to Brewster angle microscopy (BAM) and imaging ellipsometry (IE) is presented for the characterization of ultrathin films at the air–water interface. First, the methodology is demonstrated for a vertically nonmoving Langmuir layer of star-shaped, 4-arm poly(ω-pentadecalactone) (PPDL-D4). Using nulling-based ellipsometric mapping, PPDL-D4-based inhomogeneously structured morphologies with a vertical dimension in the lower nm range could be mapped. In addition to the identification of these structures, the differentiation between a monolayer and bare water was possible. Second, the potential and limitations of this method were verified by applying it to more versatile Langmuir layers of telechelic poly[(rac-lactide)-co-glycolide]-diol (PLGA). All ellipsometric maps were converted into thickness maps by introduction of the refractive index that was derived from independent ellipsometric experiments, and the result was additionally evaluated in terms of the root mean square roughness, R q. Thereby, a three-dimensional view into the layers was enabled and morphological inhomogeneity could be quantified. PMID:27826490

Unconscious perception: a model-based approach to method and evidence.

PubMed

Snodgrass, Michael; Bernat, Edward; Shevrin, Howard

2004-07-01

Unconscious perceptual effects remain controversial because it is hard to rule out alternative conscious perception explanations for them. We present a novel methodological framework, stressing the centrality of specifying the single-process conscious perception model (i.e., the null hypothesis). Various considerations, including those of SDT (Macmillan & Creelman, 1991), suggest that conscious perception functions hierarchically, in such a way that higher level effects (e.g., semantic priming) should not be possible without lower level discrimination (i.e., detection and identification). Relatedly, alternative conscious perception accounts (as well as the exhaustiveness, null sensitivity, and exclusiveness problems-Reingold & Merikle, 1988, 1990) predict positive relationships between direct and indirect measures. Contrariwise, our review suggests that negative and/or nonmonotonic relationships are found, providing strong evidence for unconscious perception and further suggesting that conscious and unconscious perceptual influences are functionally exclusive (cf. Jones, 1987), in such a way that the former typically override the latter when both are present. Consequently, unconscious perceptual effects manifest reliably only when conscious perception is completely absent, which occurs at the objective detection (but not identification) threshold.

Activation of Dun1 in response to nuclear DNA instability accounts for the increase in mitochondrial point mutations in Rad27/FEN1 deficient S. cerevisiae.

PubMed

Kaniak-Golik, Aneta; Kuberska, Renata; Dzierzbicki, Piotr; Sledziewska-Gojska, Ewa

2017-01-01

Rad27/FEN1 nuclease that plays important roles in the maintenance of DNA stability in the nucleus has recently been shown to reside in mitochondria. Accordingly, it has been established that Rad27 deficiency causes increased mutagenesis, but decreased microsatellite instability and homologous recombination in mitochondria. Our current analysis of mutations leading to erythromycin resistance indicates that only some of them arise in mitochondrial DNA and that the GC→AT transition is a hallmark of the mitochondrial mutagenesis in rad27 null background. We also show that the mitochondrial mutator phenotype resulting from Rad27 deficiency entirely depends on the DNA damage checkpoint kinase Dun1. DUN1 inactivation suppresses the mitochondrial mutator phenotype caused by Rad27 deficiency and this suppression is eliminated at least in part by subsequent deletion of SML1 encoding a repressor of ribonucleotide reductase. We conclude that Rad27 deficiency causes a mitochondrial mutator phenotype via activation of DNA damage checkpoint kinase Dun1 and that a Dun1-mediated increase of dNTP pools contributes to this phenomenon. These results point to the nuclear DNA instability as the source of mitochondrial mutagenesis. Consistently, we show that mitochondrial mutations occurring more frequently in yeast devoid of Rrm3, a DNA helicase involved in rDNA replication, are also dependent on Dun1. In addition, we have established that overproduction of Exo1, which suppresses DNA damage sensitivity and replication stress in nuclei of Rad27 deficient cells, but does not enter mitochondria, suppresses the mitochondrial mutagenesis. Exo1 overproduction restores also a great part of allelic recombination and microsatellite instability in mitochondria of Rad27 deficient cells. In contrast, the overproduction of Exo1 does not influence mitochondrial direct-repeat mediated deletions in rad27 null background, pointing to this homologous recombination pathway as the direct target of Rad27 activity in mitochondria.

Activation of Dun1 in response to nuclear DNA instability accounts for the increase in mitochondrial point mutations in Rad27/FEN1 deficient S. cerevisiae

PubMed Central

Dzierzbicki, Piotr

2017-01-01

Rad27/FEN1 nuclease that plays important roles in the maintenance of DNA stability in the nucleus has recently been shown to reside in mitochondria. Accordingly, it has been established that Rad27 deficiency causes increased mutagenesis, but decreased microsatellite instability and homologous recombination in mitochondria. Our current analysis of mutations leading to erythromycin resistance indicates that only some of them arise in mitochondrial DNA and that the GC→AT transition is a hallmark of the mitochondrial mutagenesis in rad27 null background. We also show that the mitochondrial mutator phenotype resulting from Rad27 deficiency entirely depends on the DNA damage checkpoint kinase Dun1. DUN1 inactivation suppresses the mitochondrial mutator phenotype caused by Rad27 deficiency and this suppression is eliminated at least in part by subsequent deletion of SML1 encoding a repressor of ribonucleotide reductase. We conclude that Rad27 deficiency causes a mitochondrial mutator phenotype via activation of DNA damage checkpoint kinase Dun1 and that a Dun1-mediated increase of dNTP pools contributes to this phenomenon. These results point to the nuclear DNA instability as the source of mitochondrial mutagenesis. Consistently, we show that mitochondrial mutations occurring more frequently in yeast devoid of Rrm3, a DNA helicase involved in rDNA replication, are also dependent on Dun1. In addition, we have established that overproduction of Exo1, which suppresses DNA damage sensitivity and replication stress in nuclei of Rad27 deficient cells, but does not enter mitochondria, suppresses the mitochondrial mutagenesis. Exo1 overproduction restores also a great part of allelic recombination and microsatellite instability in mitochondria of Rad27 deficient cells. In contrast, the overproduction of Exo1 does not influence mitochondrial direct-repeat mediated deletions in rad27 null background, pointing to this homologous recombination pathway as the direct target of Rad27 activity in mitochondria. PMID:28678842

Pofut1 point-mutations that disrupt O-fucosyltransferase activity destabilize the protein and abolish Notch1 signaling during mouse somitogenesis

PubMed Central

Suzuki, Emiko; Saga, Yumiko

2017-01-01

The segmental pattern of the vertebrate body is established via the periodic formation of somites from the presomitic mesoderm (PSM). This periodical process is controlled by the cyclic and synchronized activation of Notch signaling in the PSM. Protein O-fucosyltransferase1 (Pofut1), which transfers O-fucose to the EGF domains of the Notch1 receptor, is indispensable for Notch signaling activation. The Drosophila homologue Ofut1 was reported to control Notch localization via two different mechanisms, working as a chaperone for Notch or as a regulator of Notch endocytosis. However, these were found to be independent of O-fucosyltransferase activity because the phenotypes were rescued by Ofut1 mutants lacking O-fucosyltransferase activity. Pofut1 may also be involved in the Notch receptor localization in mice. However, the contribution of enzymatic activity of Pofut1 to the Notch receptor dynamics remains to be elucidated. In order to clarify the importance of the O-fucosyltransferase activity of Pofut1 for Notch signaling activation and the protein localization in the PSM, we established mice carrying point mutations at the 245th a.a. or 370-372th a.a., highly conserved amino-acid sequences whose mutations disrupt the O-fucosyltransferase activity of both Drosophila Ofut1 and mammalian Pofut1, with the CRISPR/Cas9 mediated genome-engineering technique. Both mutants displayed the same severely perturbed somite formation and Notch1 subcellular localization defects as the Pofut1 null mutants. In the mutants, Pofut1 protein, but not RNA, became undetectable by E9.5. Furthermore, both wild-type and mutant Pofut1 proteins were degraded through lysosome dependent machinery. Pofut1 protein loss in the point mutant embryos caused the same phenotypes as those observed in Pofut1 null embryos. PMID:29095923

Magnetic Topology of the Global MHD Configuration on 2010 August 1-2

NASA Astrophysics Data System (ADS)

Titov, V. S.; Mikic, Z.; Torok, T.; Linker, J.; Panasenco, O.

2014-12-01

It appears that the global magnetic topology of the solar corona predetermines to a large extent the magnetic flux transfer during solar eruptions. We have recently analyzed the global topology for a source-surface model of the background magnetic field at the time of the 2010 August 1-2 sympathetic CMEs (Titov et al. 2012). Now we extend this analysis to a more accurate thermodynamic MHD model of the solar corona. As for the source-surface model, we find a similar triplet of pseudo-streamers in the source regions of the eruptions. The new study confirms that all these pseudo-streamers contain separatrix curtains that fan out from a basic magnetic null point, individual for each of the pseudo-streamers. In combination with the associated separatrix domes, these separatrix curtains fully isolate adjacent coronal holes of the like polarity from each other. However, the size and shape of the coronal holes, as well as their open magnetic fluxes and the fluxes in the lobes of the separatrix domes, are very different for the two models. The definition of the open separator field lines, where the (interchange) reconnection between open and closed magnetic flux takes place, is also modified, since the structurally unstable source-surface null lines do not exist anymore in the MHD model. In spite of all these differences, we reassert our earlier hypothesis that magnetic reconnection at these nulls and the associated separators likely plays a key role in coupling the successive eruptions observed by SDO and STEREO. The results obtained provide further validation of our recent simplified MHD model of sympathetic eruptions (Török et al. 2011). Research supported by NASA's Heliophysics Theory and LWS Programs, and NSF/SHINE and NSF/FESD.

Protein Kinase A Regulatory Subunit Isoforms Regulate Growth and Differentiation in Mucor circinelloides: Essential Role of PKAR4

PubMed Central

Ocampo, J.; McCormack, B.; Navarro, E.; Moreno, S.; Garre, V.

2012-01-01

The protein kinase A (PKA) signaling pathway plays a role in regulating growth and differentiation in the dimorphic fungus Mucor circinelloides. PKA holoenzyme is comprised of two catalytic (C) and two regulatory (R) subunits. In M. circinelloides, four genes encode the PKAR1, PKAR2, PKAR3, and PKAR4 isoforms of R subunits. We have constructed null mutants and demonstrate that each isoform has a different role in growth and differentiation. The most striking finding is that pkaR4 is an essential gene, because only heterokaryons were obtained in knockout experiments. Heterokaryons with low levels of wild-type nuclei showed an impediment in the emission of the germ tube, suggesting a pivotal role of this gene in germ tube emergence. The remaining null strains showed different alterations in germ tube emergence, sporulation, and volume of the mother cell. The pkaR2 null mutant showed an accelerated germ tube emission and was the only mutant that germinated under anaerobic conditions when glycine was used as a nitrogen source, suggesting that pkaR2 participates in germ tube emergence by repressing it. From the measurement of the mRNA and protein levels of each isoform in the wild-type and knockout strains, it can be concluded that the expression of each subunit has its own mechanism of differential regulation. The PKAR1 and PKAR2 isoforms are posttranslationally modified by ubiquitylation, suggesting another regulation point in the specificity of the signal transduction. The results indicate that each R isoform has a different role in M. circinelloides physiology, controlling the dimorphism and contributing to the specificity of cyclic AMP (cAMP)-PKA pathway. PMID:22635921

Light rays and the tidal gravitational pendulum

NASA Astrophysics Data System (ADS)

Farley, A. N. St J.

2018-05-01

Null geodesic deviation in classical general relativity is expressed in terms of a scalar function, defined as the invariant magnitude of the connecting vector between neighbouring light rays in a null geodesic congruence projected onto a two-dimensional screen space orthogonal to the rays, where λ is an affine parameter along the rays. We demonstrate that η satisfies a harmonic oscillator-like equation with a λ-dependent frequency, which comprises terms accounting for local matter affecting the congruence and tidal gravitational effects from distant matter or gravitational waves passing through the congruence, represented by the amplitude, of a complex Weyl driving term. Oscillating solutions for η imply the presence of conjugate or focal points along the rays. A polarisation angle, is introduced comprising the orientation of the connecting vector on the screen space and the phase, of the Weyl driving term. Interpreting β as the polarisation of a gravitational wave encountering the light rays, we consider linearly polarised waves in the first instance. A highly non-linear, second-order ordinary differential equation, (the tidal pendulum equation), is then derived, so-called due to its analogy with the equation describing a non-linear, variable-length pendulum oscillating under gravity. The variable pendulum length is represented by the connecting vector magnitude, whilst the acceleration due to gravity in the familiar pendulum formulation is effectively replaced by . A tidal torque interpretation is also developed, where the torque is expressed as a coupling between the moment of inertia of the pendulum and the tidal gravitational field. Precessional effects are briefly discussed. A solution to the tidal pendulum equation in terms of familiar gravitational lensing variables is presented. The potential emergence of chaos in general relativity is discussed in the context of circularly, elliptically or randomly polarised gravitational waves encountering the null congruence.

New Class of Precision Antimicrobials Redefines Role of Clostridium difficile S-layer in Virulence and Viability

PubMed Central

Kirk, Joseph A.; Gebhart, Dana; Buckley, Anthony M.; Lok, Stephen; Scholl, Dean; Douce, Gillian R.; Govoni, Gregory R.; Fagan, Robert P.

2017-01-01

Avidocin-CDs are a new class of precision bactericidal agents that do not damage resident gut microbiota and are unlikely to promote the spread of antibiotic resistance. The precision killing properties result from the fusion of bacteriophage receptor binding proteins (RBPs) to a lethal contractile scaffold from an R-type bacteriocin. We recently described the prototypic Avidocin-CD, Av-CD291.2, that specifically kills C. difficile ribotype 027 strains and prevents colonization of mice. We have since selected two rare Av-CD291.2 resistant mutants of strain R20291 (RT027; S-layer cassette type-4, SCLT-4). These mutants have distinct point mutations in the slpA gene that result in an S-layer null phenotype. Reversion of the mutations to wild-type restored normal SLCT-4 S-layer formation and Av-CD291.2 sensitivity; however, complementation with other SCLT alleles did not restore Av-CD291.2 sensitivity despite restoring S-layer formation. Using newly identified phage RBPs, we constructed a panel of new Avidocin-CDs that kill C. difficile isolates in an SLCT-dependent manner, confirming the S-layer as the receptor in every case. In addition to bacteriophage adsorption, characterization of the S-layer null mutant also uncovered important roles for SlpA in sporulation, resistance to lysozyme and LL-37, and toxin production. Surprisingly, the S-layer-null mutant was found to persist in the hamster gut despite its completely attenuated virulence. Avidocin-CDs have significant therapeutic potential for the treatment and prevention of C. difficile Infection (CDI) given their exquisite specificity for the pathogen. Furthermore, the emergence of resistance forces mutants to trade virulence for continued viability and, therefore, greatly reduce their potential clinical impact. PMID:28878013

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.

FBXW7 mutations typically found in human cancers are distinct from null alleles and disrupt lung development

PubMed Central

Davis, Hayley; Lewis, Annabelle; Spencer-Dene, Bradley; Tateossian, Hilda; Stamp, Gordon; Behrens, Axel; Tomlinson, Ian

2011-01-01

FBXW7 is the substrate recognition component of a SCF-type E3 ubiquitin ligase. It has multiple targets such as Notch1, c-Jun, and cyclin E that function in critical developmental and signalling pathways. Mutations in FBXW7 are often found in many types of cancer. In most cases, these mutations do not inactivate the protein, but are mono-allelic missense changes at specific arginine resides involved in substrate binding. We have hypothesized that FBXW7 mutations are selected in cancers for reasons other than haploinsufficiency or full loss-of-function. Given that the existing mutant Fbxw7 mice carry null alleles, we created a mouse model carrying one of the commonly occurring point mutations (Fbxw7) in the WD40 substrate recognition domain of Fbxw7. Mice heterozygous for this mutation apparently developed normally in utero, died perinatally due to a defect in lung development, and in some cases showed cleft palate and eyelid fusion defects. By comparison, Fbxw7+/− mice were viable and developed normally. Fbxw7−/− animals died of vascular abnormalities at E10.5. We screened known FBXW7 targets for changes in the lungs of the Fbxw7R482Q/+ mice and found Tgif1 and Klf5 to be up-regulated. Fbxw7 alleles are not functionally equivalent to heterozygous or homozygous null alleles, and we propose that they are selected in tumourigenesis because they cause a selective or partial loss of FBXW7 function. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:21503901

Optical testing of the LSST combined primary/tertiary mirror

NASA Astrophysics Data System (ADS)

Tuell, Michael T.; Martin, Hubert M.; Burge, James H.; Gressler, William J.; Zhao, Chunyu

2010-07-01

The Large Synoptic Survey Telescope (LSST) utilizes a three-mirror design in which the primary (M1) and tertiary (M3) mirrors are two concentric aspheric surfaces on one monolithic substrate. The substrate material is Ohara E6 borosilicate glass, in a honeycomb sandwich configuration, currently in production at The University of Arizona's Steward Observatory Mirror Lab. In addition to the normal requirements for smooth surfaces of the appropriate prescriptions, the alignment of the two surfaces must be accurately measured and controlled in the production lab. Both the pointing and centration of the two optical axes are important parameters, in addition to the axial spacing of the two vertices. This paper describes the basic metrology systems for each surface, with particular attention to the alignment of the two surfaces. These surfaces are aspheric enough to require null correctors for each wavefront. Both M1 and M3 are concave surfaces with both non-zero conic constants and higher-order terms (6th order for M1 and both 6th and 8th orders for M3). M1 is hyperboloidal and can utilize a standard Offner null corrector. M3 is an oblate ellipsoid, so has positive spherical aberration. We have chosen to place a phase-etched computer-generated hologram (CGH) between the mirror surface and the center-of-curvature (CoC), whereas the M1 null lens is beyond the CoC. One relatively new metrology tool is the laser tracker, which is relied upon to measure the alignment and spacings. A separate laser tracker system will be used to measure both surfaces during loose abrasive grinding and initial polishing.

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

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

Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice

PubMed Central

Xu, Fen; Burk, David; Gao, Zhanguo; Yin, Jun; Zhang, Xia

2012-01-01

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue. PMID:22315447

Association study between GSTT1 and GSTM1 polymorphisms and risk of preeclampsia in Chinese population.

PubMed

Guan, Linbo; Fan, Ping; Liu, Xinghui; Liu, Rui; Chen, Yihong; Ye, Liyan; Chen, Jinxin; Zhu, Yue; Liu, Yu; Bai, Huai

2016-09-01

Preeclampsia is a pregnancy-specific disorder associated with oxidative stress. The glutathione S-transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1) have previously been reported. The aim of this study was to investigate the association of GST gene polymorphisms with the risk of preeclampsia in Chinese subjects. The case-control population consists of 525 subjects. The genotyping of the GSTT1 and GSTM1 polymorphisms was carried out on genomic DNA using the multiplex polymerase chain reaction (PCR). We calculated odds ratios (ORs), adjusted for the confounding variables, to estimate the association between gene polymorphisms and preeclampsia. The GSTT1 null genotype was found to be protective from the development of preeclampsia (odds ratios 0.645, 95% confidence interval 0.421-0.989; P=0.044). Further analysis showed that a combination of deletion genotypes of the GSTT1 and GSTM1 genes conferred an even lower risk of preeclampsia (OR=0.470, 95%CI=0.255-0.866; P=0.015). There is no relationship between the GSTT1 and GSTM1 gene polymorphisms and blood pressure levels in pregnant women with and without preeclampsia. Our data suggest that a GSTT1 null polymorphism might be associated with decreased risk for preeclampsia in the Chinese population, and that this risk decreases with the combination of both GSTT1 and GSTM1 null polymorphisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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…

Eisenhart lifts and symmetries of time-dependent systems

NASA Astrophysics Data System (ADS)

Cariglia, M.; Duval, C.; Gibbons, G. W.; Horváthy, P. A.

2016-10-01

Certain dissipative systems, such as Caldirola and Kannai's damped simple harmonic oscillator, may be modelled by time-dependent Lagrangian and hence time dependent Hamiltonian systems with n degrees of freedom. In this paper we treat these systems, their projective and conformal symmetries as well as their quantisation from the point of view of the Eisenhart lift to a Bargmann spacetime in n + 2 dimensions, equipped with its covariantly constant null Killing vector field. Reparametrisation of the time variable corresponds to conformal rescalings of the Bargmann metric. We show how the Arnold map lifts to Bargmann spacetime. We contrast the greater generality of the Caldirola-Kannai approach with that of Arnold and Bateman. At the level of quantum mechanics, we are able to show how the relevant Schrödinger equation emerges naturally using the techniques of quantum field theory in curved spacetimes, since a covariantly constant null Killing vector field gives rise to well defined one particle Hilbert space. Time-dependent Lagrangians arise naturally also in cosmology and give rise to the phenomenon of Hubble friction. We provide an account of this for Friedmann-Lemaître and Bianchi cosmologies and how it fits in with our previous discussion in the non-relativistic limit.

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.

3D Visualization of Earthquake Focal Mechanisms Using ArcScene

USGS Publications Warehouse

Labay, Keith A.; Haeussler, Peter J.

2007-01-01

In addition to the default settings, there are several other options in 3DFM that can be adjusted. The appearance of the symbols can be changed by (1) creating rings around the fault planes that are colored based on magnitude, (2) showing only the fault planes instead of a sphere, (3) drawing a flat disc that identifies the primary nodal plane, (4) or by displaying the null, pressure, and tension axes. The size of the symbols can be changed by adjusting their diameter, scaling them based on the magnitude of the earthquake, or scaling them by the estimated size of the rupture patch based on earthquake magnitude. It is also possible to filter the data using any combination of the strike, dip, rake, magnitude, depth, null axis plunge, pressure axis plunge, tension axis plunge, or fault type values of the points. For a large dataset, these filters can be used to create different subsets of symbols. Symbols created by 3DFM are stored in graphics layers that appear in the ArcScene® table of contents. Multiple graphics layers can be created and saved to preserve the output from different symbol options.

Cystamine restores GSTA3 levels in Vanin-1 null mice.

PubMed

Di Leandro, Luana; Maras, Bruno; Schininà, M Eugenia; Dupré, Silvestro; Koutris, Ilias; Martin, Florent M; Naquet, Philippe; Galland, Franck; Pitari, Giuseppina

2008-03-15

Free cysteamine levels in mouse tissues have been strictly correlated to the presence of membrane-bound pantetheinase activity encoded by Vanin-1. Vanin-1 is involved in many biological processes in mouse, from thymus homing to sexual development. Vanin-1 -/- mice are fertile and grow and develop normally; they better control inflammation and most of the knockout effects were rescued by cystamine treatment. Gene structure analysis showed the presence of an oxidative stimuli-responsive ARE-like sequence in the promoter. In this paper we investigate antioxidant-detoxifying enzymatic activities at the tissue level, comparing Vanin-1 -/- and wild-type mice. In Vanin-1 null animals we pointed out a decrease in the Se-independent glutathione peroxidase activity. The decrease in enzymatic activity appeared to be correlated to an impairment of GST isoenzyme levels. In particular a significant drop in GSTA3 together with a minor decrement in GSTM1 and an increase in GSTP1 levels was detected in Vanin-1 -/- livers. Cystamine administration to Vanin-1 -/- mice restored specifically GSTA3 levels and the corresponding enzymatic activity without influencing protein expression. A possible role of cystamine on protein stability/folding can be postulated.

Favorable effects of turbulent plasma mixing on the performance of innovative tokamak divertors

NASA Astrophysics Data System (ADS)

Ryutov, D. D.; Cohen, R. H.; Rognlien, T. D.; Umansky, M. V.

2013-10-01

The problem of reducing the heat load on plasma-facing components is one of the most demanding issues for MFE devices. The general approach to the solution of this problem is the use of a specially configured poloidal magnetic field, so called magnetic divertors. In recent years, novel divertors possessing the 2-nd and 3-rd order nulls of the poloidal field (PF) have been proposed. They are called a ``snowflake'' (SF) and a ``cloverleaf'' (CL) divertor, respectively, due to characteristic shape of the magnetic separatrix. Among several beneficial features of such divertors is an effect of strong turbulent plasma mixing that is intrinsic to the zone of weak PF near the null-point. The turbulence spreads the heat flux between multiple divertor exhaust channels and increases the heat flux width within each channel. Among physical processes affecting the onset of convection the curvature-driven mode of axisymmetric rolls is most prominent. The effect is quite significant for the SF and is even stronger for the CL divertor. Projections to future ITER-scale facilities are discussed. Work performed for U.S. DoE by LLNL under Contract DE-AC52-07NA27344.

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.

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.

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.

Stationary QH-mode plasmas with high and wide pedestal at low rotation on DIII-D

DOE PAGES

Chen, Xi; Burrell, K. H.; Osborne, T. H.; ...

2016-09-30

A stationary, quiescent H-mode (QH-mode) regime with a wide pedestal and improved confinement at low rotation has been discovered on DIII-D with reactor relevant edge parameters and no ELMs. As the injected neutral beam torque is ramped down and the edge ExB rotation shear reduces, the transition from standard QH to the wide pedestal QH-mode occurs. And at the transition, the coherent edge harmonic oscillations (EHO) that usually regulate the standard QH edge cease and broadband edge MHD modes appear along with a rapid increase in the pedestal pressure height (by ≤60%) and width (by ≤50%). We posit that themore » enhanced edge turbulence-driven transport, enabled by the lower edge ExB flow shear due to lower torque reduces the pedestal gradient and, combined with the high edge instability limit provided by the balanced double-null plasma shape, permits the development of a broader and thus higher pedestal that is turbulence-transport-limited. Even with the significantly enhanced pedestal pressure, the edge operating point is below the peeling ballooning mode stability boundary and thus without ELMs. Improved transport in the outer core region (0.8≤ρ≤0.9) owing to increased ExB flow shear in that region and the enhanced pedestal boost the overall confinement by up to 45%. Our findings advance the physics basis for developing stationary ELM-free high-confinement operation at low rotation for future burning plasma where similar collisionality and rotation levels are expected.« less

Are strict vegetarians protected against prostate cancer?

PubMed

Tantamango-Bartley, Yessenia; Knutsen, Synnove F; Knutsen, Raymond; Jacobsen, Bjarne K; Fan, Jing; Beeson, W Lawrence; Sabate, Joan; Hadley, David; Jaceldo-Siegl, Karen; Penniecook, Jason; Herring, Patti; Butler, Terry; Bennett, Hanni; Fraser, Gary

2016-01-01

According to the American Cancer Society, prostate cancer accounts for ∼27% of all incident cancer cases among men and is the second most common (noncutaneous) cancer among men. The relation between diet and prostate cancer is still unclear. Because people do not consume individual foods but rather foods in combination, the assessment of dietary patterns may offer valuable information when determining associations between diet and prostate cancer risk. This study aimed to examine the association between dietary patterns (nonvegetarian, lacto-ovo-vegetarian, pesco-vegetarian, vegan, and semi-vegetarian) and prostate cancer incidence among 26,346 male participants of the Adventist Health Study-2. In this prospective cohort study, cancer cases were identified by matching to cancer registries. Cox proportional hazards regression analysis was performed to estimate HRs by using age as the time variable. In total, 1079 incident prostate cancer cases were identified. Around 8% of the study population reported adherence to the vegan diet. Vegan diets showed a statistically significant protective association with prostate cancer risk (HR: 0.65; 95% CI: 0.49, 0.85). After stratifying by race, the statistically significant association with a vegan diet remained only for the whites (HR: 0.63; 95% CI: 0.46, 0.86), but the multivariate HR for black vegans showed a similar but nonsignificant point estimate (HR: 0.69; 95% CI: 0.41, 1.18). Vegan diets may confer a lower risk of prostate cancer. This lower estimated risk is seen in both white and black vegan subjects, although in the latter, the CI is wider and includes the null. © 2016 American Society for Nutrition.

Are strict vegetarians protected against prostate cancer?1

PubMed Central

Knutsen, Synnove F; Knutsen, Raymond; Jacobsen, Bjarne K; Fan, Jing; Beeson, W Lawrence; Sabate, Joan; Hadley, David; Jaceldo-Siegl, Karen; Penniecook, Jason; Herring, Patti; Butler, Terry; Bennett, Hanni; Fraser, Gary

2016-01-01

Background: According to the American Cancer Society, prostate cancer accounts for ∼27% of all incident cancer cases among men and is the second most common (noncutaneous) cancer among men. The relation between diet and prostate cancer is still unclear. Because people do not consume individual foods but rather foods in combination, the assessment of dietary patterns may offer valuable information when determining associations between diet and prostate cancer risk. Objective: This study aimed to examine the association between dietary patterns (nonvegetarian, lacto-ovo-vegetarian, pesco-vegetarian, vegan, and semi-vegetarian) and prostate cancer incidence among 26,346 male participants of the Adventist Health Study-2. Design: In this prospective cohort study, cancer cases were identified by matching to cancer registries. Cox proportional hazards regression analysis was performed to estimate HRs by using age as the time variable. Results: In total, 1079 incident prostate cancer cases were identified. Around 8% of the study population reported adherence to the vegan diet. Vegan diets showed a statistically significant protective association with prostate cancer risk (HR: 0.65; 95% CI: 0.49, 0.85). After stratifying by race, the statistically significant association with a vegan diet remained only for the whites (HR: 0.63; 95% CI: 0.46, 0.86), but the multivariate HR for black vegans showed a similar but nonsignificant point estimate (HR: 0.69; 95% CI: 0.41, 1.18). Conclusion: Vegan diets may confer a lower risk of prostate cancer. This lower estimated risk is seen in both white and black vegan subjects, although in the latter, the CI is wider and includes the null. PMID:26561618

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.

Magnetic Reconnection in Strongly Magnetized Regions of the Low Solar Chromosphere

NASA Astrophysics Data System (ADS)

Ni, Lei; Lukin, Vyacheslav S.; Murphy, Nicholas A.; Lin, Jun

2018-01-01

Magnetic reconnection in strongly magnetized regions around the temperature minimum region of the low solar atmosphere is studied by employing MHD-based simulations of a partially ionized plasma within a reactive 2.5D multi-fluid model. It is shown that in the absence of magnetic nulls in a low β plasma, the ionized and neutral fluid flows are well-coupled throughout the reconnection region. However, non-equilibrium ionization–recombination dynamics play a critical role in determining the structure of the reconnection region, leading to much lower temperature increases and a faster magnetic reconnection rate as compared to simulations that assume plasma to be in ionization–recombination equilibrium. The rate of ionization of the neutral component of the plasma is always faster than recombination within the current sheet region even when the initial plasma β is as high as {β }0=1.46. When the reconnecting magnetic field is in excess of a kilogauss and the plasma β is lower than 0.0145, the initially weakly ionized plasmas can become fully ionized within the reconnection region and the current sheet can be strongly heated to above 2.5× {10}4 K, even as most of the collisionally dissipated magnetic energy is radiated away. The Hall effect increases the reconnection rate slightly, but in the absence of magnetic nulls it does not result in significant asymmetries or change the characteristics of the reconnection current sheet down to meter scales.

Determination of the two methyl group orientations at vapor/acetone interface with polarization null angle method in SFG vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Hua; Gan, Wei; Wu, Bao-hua; Wu, Dan; Zhang, Zhen; Wang, Hong-fei

2005-06-01

We report a direct measurement of the orientation of the two CH 3 groups of acetone molecule at the vapor/acetone interface. The interfacial acetone molecule is found well-ordered, with one methyl group points away around 14.4° ± 1.9° and another into the bulk liquid around 102.8° ± 1.9° from the interface normal, and thus the C dbnd O group points into the bulk around 135.8° ± 1.9°. These results directly confirmed the highly ordered and even crystal like interfacial structure of the vapor/acetone interface from previous MD simulation. The general formulation and accurate determination of the orientational parameter D can be used to treat interfaces with complex molecular orientations.

"Snowflake" divertor configuration in NSTX

NASA Astrophysics Data System (ADS)

Soukhanovskii, V. A.; Ahn, J.-W.; Bell, R. E.; Gates, D. A.; Gerhardt, S.; Kaita, R.; Kolemen, E.; Kugel, H. W.; Leblanc, B. P.; Maingi, R.; Maqueda, R.; McLean, A.; Menard, J. E.; Mueller, D. M.; Paul, S. F.; Raman, R.; Roquemore, A. L.; Ryutov, D. D.; Scott, H. A.

2011-08-01

Steady-state handling of divertor heat flux is a critical issue for present and future conventional and spherical tokamaks with compact high power density divertors. A novel "snowflake" divertor (SFD) configuration that takes advantage of magnetic properties of a second-order poloidal null has been predicted to have a larger plasma-wetted area and a larger divertor volume, in comparison with a standard first-order poloidal X-point divertor configuration. The SFD was obtained in 0.8 MA, 4-6 MW NBI-heated H-mode discharges in NSTX using two divertor magnetic coils. The SFD led to a partial detachment of the outer strike point even in low-collisionality scrape-off layer plasma obtained with lithium coatings in NSTX. Significant divertor peak heat flux reduction and impurity screening have been achieved simultaneously with good core confinement and MHD properties.

Dynamical analysis of continuous higher-order hopfield networks for combinatorial optimization.

PubMed

Atencia, Miguel; Joya, Gonzalo; Sandoval, Francisco

2005-08-01

In this letter, the ability of higher-order Hopfield networks to solve combinatorial optimization problems is assessed by means of a rigorous analysis of their properties. The stability of the continuous network is almost completely clarified: (1) hyperbolic interior equilibria, which are unfeasible, are unstable; (2) the state cannot escape from the unitary hypercube; and (3) a Lyapunov function exists. Numerical methods used to implement the continuous equation on a computer should be designed with the aim of preserving these favorable properties. The case of nonhyperbolic fixed points, which occur when the Hessian of the target function is the null matrix, requires further study. We prove that these nonhyperbolic interior fixed points are unstable in networks with three neurons and order two. The conjecture that interior equilibria are unstable in the general case is left open.

Naked shell singularities on the brane

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

Seahra, Sanjeev S.

By utilizing nonstandard slicings of 5-dimensional Schwarzschild and Schwarzschild-AdS manifolds based on isotropic coordinates, we generate static and spherically-symmetric braneworld spacetimes containing shell-like naked null singularities. For planar slicings, we find that the brane-matter sourcing the solution is a perfect fluid with an exotic equation of state and a pressure singularity where the brane crosses the bulk horizon. From a relativistic point of view, such a singularity is required to maintain matter infinitesimally above the surface of a black hole. From the point of view of the AdS/CFT conjecture, the singular horizon can be seen as one possible quantum correctionmore » to a classical black hole geometry. Various generalizations of planar slicings are also considered for a Ricci-flat bulk, and we find that singular horizons and exotic matter distributions are common features.« less

Preliminary design of a prototype particulate stack sampler. [For stack gas temperature under 300/sup 0/C

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

Elder, J.C.; Littlefield, L.G.; Tillery, M.I.

1978-06-01

A preliminary design of a prototype particulate stack sampler (PPSS) has been prepared, and development of several components is under way. The objective of this Environmental Protection Agency (EPA)-sponsored program is to develop and demonstrate a prototype sampler with capabilities similar to EPA Method 5 apparatus but without some of the more troublesome aspects. Features of the new design include higher sampling flow; display (on demand) of all variables and periodic calculation of percent isokinetic, sample volume, and stack velocity; automatic control of probe and filter heaters; stainless steel surfaces in contact with the sample stream; single-point particle size separationmore » in the probe nozzle; null-probe capability in the nozzle; and lower weight in the components of the sampling train. Design considerations will limit use of the PPSS to stack gas temperatures under approximately 300/sup 0/C, which will exclude sampling some high-temperature stacks such as incinerators. Although need for filter weighing has not been eliminated in the new design, introduction of a variable-slit virtual impactor nozzle may eliminate the need for mass analysis of particles washed from the probe. Component development has shown some promise for continuous humidity measurement by an in-line wet-bulb, dry-bulb psychrometer.« less

A plasma generator utilizing the high intensity ASTROMAG magnets

NASA Technical Reports Server (NTRS)

Sullivan, James D.; Post, R. S.; Lane, B. G.; Tarrh, J. M.

1986-01-01

The magnet configuration for the proposed particle astrophysics magnet facility (ASTROMAG) on the space station includes a cusp magnetic field with an intensity of a few tesla. With these large magnets (or others) located in the outer ionosphere, many quite interesting and unique plasma physics experiments become possible. First there are studies utilizing the magnet alone to examine the supersonic, sub-Alfvenic interaction with the ambient medium; the scale length for the magnet perturbation is approx. 20 m. The magnetic field geometry when combined with the Earth's and their relative motion will give rise to a host of plasma phenomena: ring nulls, x-points, ion-acoustic and lower-hybrid shocks, electron heating (possible shuttle glow without a surface) launching of Alfvenwaves, etc. Second, active experiments are possible for a controlled study of fundamental plasma phenomena. A controlled variable species plasma can be made by using an RF ion source; use of two soft iron rings placed about the line cusp would give an adequate resonance zone (ECH or ICH) and a confining volume suitable for gas efficiency. The emanating plasma can be used to study free expansion of plasma along and across field lines (polar wind), plasma flows around the space platform, turbulent mixing in the wake region, long wavelength spectrum of convecting modes, plasma-dust interactions, etc.

Effect of solar flares flux on the propagation and modal composition of VLF signal in the lower ionosphere

NASA Astrophysics Data System (ADS)

Bouderba, Yasmina; Nait Amor, Samir; Tribeche, Mouloud

2015-04-01

The VLF radio waves propagating in the Earth-Ionosphere waveguide are sensitive to the ionospheric disturbances due to X rays solar flux. In order to understand the VLF signal response to the solar flares, the LWPC code is used to simulate the signal perturbation parameters (amplitude and phase) at fixed solar zenith angle. In this work, we used the NRK-Algiers signal data and the study was done for different flares classes. The results show that the perturbed parameters increase with the increasing solar flares flux. This increases is due to the growth of the electron density resulting from the changes of the Wait's parameters. However, the behavior of the perturbation parameters as function of distance shows different forms of signal perturbations. It was also observed that the null points move towards the transmitter location when the flare flux increases which is related to the modal composition of the propagating signal. Effectively, for a given mode, the plot of the attenuation coefficient as function of the flare flux shows a decreases when the flux increases which is more significant for high modes. Thus, the solar flares effect is to amplify the VLF signal by reducing the attenuation coefficient.

Characterization of the Stabilized Test Bench of Nulling Interferometry PERSÉE

NASA Astrophysics Data System (ADS)

Lozi, Julien; Ollivier, M.; Cassaing, F.; Le Duigou, J.; CNES; Onera/Dota/HRA; IAS; LESIA; OCA; TAS

2013-01-01

There are two problems with the observation of exoplanets: the contrast between the planet and the star and their very low separation. One technique solving these problems is nulling interferometry: two pupils are recombined to make a destructive interference on the star, and their base is adjusted to create a constructive interference on the planet. However, to ensure a sufficient extinction of the star, the optical path difference between the beams must be around the nanometer, and the pointing must be better than one hundredth of Airy disk, despite the external disturbances.To validate the critical points of such a space mission, a laboratory demonstrator, PERSÉE, was defined by a consortium led by the french space agency CNES, including IAS, LESIA, ONERA, OCA and Thales Alenia Space and integrated in Paris Observatory. This bench simulates the entire space mission (interferometer and nanometric cophasing system). Its goal is to deliver and maintain an extinction of 10^-4 stable at better than 10^-5 over a few hours in the presence of typical injected disturbances.My thesis work consisted in integrating the bench in successive stages and to develop calibration procedures. This helped me to characterize the critical elements separately before grouping them. After having implemented the control loops of the cophasing system, their precise analysis helped me to reduce down to 0.3 nm rms the residual OPD, and 0.4 % of the Airy disk the residual tip/tilt, despite disturbances of tens of nanometers, consisting of several tens of vibrational frequencies between 1 and 100 Hz. This has been achieved by the implementation of a linear quadratic Gaussian controller, parameterized by the preliminary measurement of the disturbance to minimize. Thanks to these excellent results, I obtained on the band [1.65 - 2.45] µm a record null rate of 8.8x10^-6 stabilized at 9x10^-7 over a few hours, a decade better than the original specifications. An extrapolation of these results to the case of a space mission shows that the expected performance is achievable if the available flux is sufficiently important. With telescopes of 40 cm and a control frequency around 100 Hz, stars brighter than magnitude 9 should be observable.

Activity of SHIP, Which Prevents Expression of Interleukin 1β, Is Reduced in Patients With Crohn's Disease.

PubMed

Ngoh, Eyler N; Weisser, Shelley B; Lo, Young; Kozicky, Lisa K; Jen, Roger; Brugger, Hayley K; Menzies, Susan C; McLarren, Keith W; Nackiewicz, Dominika; van Rooijen, Nico; Jacobson, Kevan; Ehses, Jan A; Turvey, Stuart E; Sly, Laura M

2016-02-01

Crohn's disease (CD) is associated with a dysregulated immune response to commensal micro-organisms in the intestine. Mice deficient in inositol polyphosphate 5'-phosphatase D (INPP5D, also known as SHIP) develop intestinal inflammation resembling that of patients with CD. SHIP is a negative regulator of PI3Kp110α activity. We investigated mechanisms of intestinal inflammation in Inpp5d(-/-) mice (SHIP-null mice), and SHIP levels and activity in intestinal tissues of subjects with CD. We collected intestines from SHIP-null mice, as well as Inpp5d(+/+) mice (controls), and measured levels of cytokines of the interleukin 1 (IL1) family (IL1α, IL1β, IL1ra, and IL6) by enzyme-linked immunosorbent assay. Macrophages were isolated from lamina propria cells of mice, IL1β production was measured, and mechanisms of increased IL1β production were investigated. Macrophages were incubated with pan-phosphatidylinositol 3-kinase inhibitors or PI3Kp110α-specific inhibitors. Some mice were given an antagonist of the IL1 receptor; macrophages were depleted from ilea of mice using clodronate-containing liposomes. We obtained ileal biopsies from sites of inflammation and peripheral blood mononuclear cells (PBMCs) from treatment-naïve subjects with CD or without CD (controls), and measured SHIP levels and activity. PBMCs were incubated with lipopolysaccharide and adenosine triphosphate, and levels of IL1β production were measured. Inflamed intestinal tissues and intestinal macrophages from SHIP-null mice produced higher levels of IL1B and IL18 than intestinal tissues from control mice. We found PI3Kp110α to be required for macrophage transcription of Il1b. Macrophage depletion or injection of an IL1 receptor antagonist reduced ileal inflammation in SHIP-null mice. Inflamed ileal tissues and PBMCs from patients with CD had lower levels of SHIP protein than controls (P < .0001 and P < .0002, respectively). There was an inverse correlation between levels of SHIP activity in PBMCs and induction of IL1β production by lipopolysaccharide and adenosine triphosphate (R(2) = .88). Macrophages from SHIP-deficient mice have increased PI3Kp110α-mediated transcription of Il1b, which contributes to spontaneous ileal inflammation. SHIP levels and activity are lower in intestinal tissues and peripheral blood samples from patients with CD than controls. There is an inverse correlation between SHIP activity and induction of IL1β production by lipopolysaccharide and adenosine triphosphate in PBMCs. Strategies to reduce IL1B might be developed to treat patients with CD found to have low SHIP activity. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

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...