Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat.

PubMed

Konik-Rose, Christine; Thistleton, Jenny; Chanvrier, Helene; Tan, Ihwa; Halley, Peter; Gidley, Michael; Kosar-Hashemi, Behjat; Wang, Hong; Larroque, Oscar; Ikea, Joseph; McMaugh, Steve; Regina, Ahmed; Rahman, Sadequr; Morell, Matthew; Li, Zhongyi

2007-11-01

Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat.

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

PubMed

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

2016-03-01

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

Examining speed versus selection in connectivity models using elk migration as an example

USGS Publications Warehouse

Brennan, Angela; Hanks, Ephraim M.; Merkle, Jerod A.; Cole, Eric K.; Dewey, Sarah R.; Courtemanch, Alyson B.; Cross, Paul C.

2018-01-01

ContextLandscape resistance is vital to connectivity modeling and frequently derived from resource selection functions (RSFs). RSFs estimate relative probability of use and tend to focus on understanding habitat preferences during slow, routine animal movements (e.g., foraging). Dispersal and migration, however, can produce rarer, faster movements, in which case models of movement speed rather than resource selection may be more realistic for identifying habitats that facilitate connectivity.ObjectiveTo compare two connectivity modeling approaches applied to resistance estimated from models of movement rate and resource selection.MethodsUsing movement data from migrating elk, we evaluated continuous time Markov chain (CTMC) and movement-based RSF models (i.e., step selection functions [SSFs]). We applied circuit theory and shortest random path (SRP) algorithms to CTMC, SSF and null (i.e., flat) resistance surfaces to predict corridors between elk seasonal ranges. We evaluated prediction accuracy by comparing model predictions to empirical elk movements.ResultsAll connectivity models predicted elk movements well, but models applied to CTMC resistance were more accurate than models applied to SSF and null resistance. Circuit theory models were more accurate on average than SRP models.ConclusionsCTMC can be more realistic than SSFs for estimating resistance for fast movements, though SSFs may demonstrate some predictive ability when animals also move slowly through corridors (e.g., stopover use during migration). High null model accuracy suggests seasonal range data may also be critical for predicting direct migration routes. For animals that migrate or disperse across large landscapes, we recommend incorporating CTMC into the connectivity modeling toolkit.

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.

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.

Thermally driven spin-Seebeck transport in chiral dsDNA-based molecular devices

NASA Astrophysics Data System (ADS)

Nian, L. L.; Zhang, Rong; Tang, F. R.; Tang, Jun; Bai, Long

2018-03-01

By employing the nonequilibrium Green's function technique, we study the thermal-induced spin-Seebeck transport through a chiral double-stranded DNA (dsDNA) connected to a normal-metal and a ferromagnetic lead. How the main parameters of the dsDNA-based system influence the spin-Seebeck transport is analyzed at length, and the thermally created charge (spin-related) current displays the rectification effect and the negative differential thermal conductance feature. More importantly, the spin current exhibits the rectification behavior of the spin-Seebeck effect; even the perfect spin-Seebeck effect can be obtained with the null charge current. Thus, the chiral dsDNA-based system can act as a spin(charge)-Seebeck diode, spin(charge)-Seebeck switch, and spin(charge)-Seebeck transistor. Our results provide new ways to design spin caloritronic devices based on dsDNA or other organic molecules.

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.

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

PubMed Central

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

2014-01-01

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

Examining speed versus selection in connectivity models using elk migration as an example

USGS Publications Warehouse

Brennan, Angela; Hanks, EM; Merkle, JA; Cole, EK; Dewey, SR; Courtemanch, AB; Cross, Paul C.

2018-01-01

Context: Landscape resistance is vital to connectivity modeling and frequently derived from resource selection functions (RSFs). RSFs estimate relative probability of use and tend to focus on understanding habitat preferences during slow, routine animal movements (e.g., foraging). Dispersal and migration, however, can produce rarer, faster movements, in which case models of movement speed rather than resource selection may be more realistic for identifying habitats that facilitate connectivity. Objective: To compare two connectivity modeling approaches applied to resistance estimated from models of movement rate and resource selection. Methods: Using movement data from migrating elk, we evaluated continuous time Markov chain (CTMC) and movement-based RSF models (i.e., step selection functions [SSFs]). We applied circuit theory and shortest random path (SRP) algorithms to CTMC, SSF and null (i.e., flat) resistance surfaces to predict corridors between elk seasonal ranges. We evaluated prediction accuracy by comparing model predictions to empirical elk movements. Results: All models predicted elk movements well, but models applied to CTMC resistance were more accurate than models applied to SSF and null resistance. Circuit theory models were more accurate on average than SRP algorithms. Conclusions: CTMC can be more realistic than SSFs for estimating resistance for fast movements, though SSFs may demonstrate some predictive ability when animals also move slowly through corridors (e.g., stopover use during migration). High null model accuracy suggests seasonal range data may also be critical for predicting direct migration routes. For animals that migrate or disperse across large landscapes, we recommend incorporating CTMC into the connectivity modeling toolkit.

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

NASA Astrophysics Data System (ADS)

Crank, Willie; Ali, Halima; Punjabi, Alkesh

2009-11-01

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

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

PubMed

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

2017-02-20

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

What Produce Energetic Flares with X-Shaped Ribbons on the Outskirts of Solar Active Region?

NASA Astrophysics Data System (ADS)

Liu, Rui; Chen, Jun; Wang, Yuming; Kailiu

2016-10-01

Typical solar flares display two quasi-parallel, bright ribbons on the chromosphere. In between is the polarity inversion line separating concentrated magnetic fluxes of opposite polarities in active regions (ARs). Intriguingly a series of flares exhibiting X-shaped ribbons occur at the similar location on the outskirts of NOAA AR 11967, where magnetic fluxes are scattered, yet three of them are alarmingly energetic. The X shape is similar in UV/EUV with hard X-ray emission projected in the center, which cannot be accommodated in the standard flare model. Mapping out magnetic connectivities in potential fields, we found that the X morphology is dictated by the intersection of two quasi-separatrix layers, i.e., a hyperbolic flux tube (HFT), within which a separator connecting a double null is embedded. This topology is not purely local but regulated by fluxes and flows over the whole AR. The nonlinear force-free field model suggests the formation of a current layer at the HFT, where the current dissipation can be mapped to the X-shaped ribbons via field-aligned heat conduction. These results highlight the critical role of structural skeletons in 3D magnetic reconnection.

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.

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

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

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

2007-06-15

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

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

PubMed

Qiu, Mali; Wu, Xu; Qu, Xiaobing

2016-09-01

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

The snowflake divertor

NASA Astrophysics Data System (ADS)

Ryutov, D. D.; Soukhanovskii, V. A.

2015-11-01

The snowflake magnetic configuration is characterized by the presence of two closely spaced poloidal field nulls that create a characteristic hexagonal (reminiscent of a snowflake) separatrix structure. The magnetic field properties and the plasma behaviour in the snowflake are determined by the simultaneous action of both nulls, this generating a lot of interesting physics, as well as providing a chance for improving divertor performance. Among potential beneficial effects of this geometry are: increased volume of a low poloidal field around the null, increased connection length, and the heat flux sharing between multiple divertor channels. The authors summarise experimental results obtained with the snowflake configuration on several tokamaks. Wherever possible, relation to the existing theoretical models is described.

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

PubMed

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

2012-01-01

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

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

PubMed Central

Daude, Nathalie; Westaway, David

2012-01-01

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

A Geometric Framework for the Kinematics of Crystals With Defects

DTIC Science & Technology

2006-02-01

which parallel transport preserves dot products of vectors, i.e. r G G ¼ 0. It is called the Levi - Civita connection [57] or the Riemannian connection...yielding a null covariant derivative of the metric tensor is called a metric connection. The Levi – Civita connection of (8) is metric. Note that in...tensor formed by inserting the Levi – Civita con- nection (8) into (10). A geometric space B0 with metric G having R G ¼ 0 is called flat. One may show

Motion perception during variable-radius swing motion in darkness.

PubMed

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

2009-10-01

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

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

PubMed

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

2018-01-01

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

Improving the Nulling Beamformer Using Subspace Suppression.

PubMed

Rana, Kunjan D; Hämäläinen, Matti S; Vaina, Lucia M

2018-01-01

Magnetoencephalography (MEG) captures the magnetic fields generated by neuronal current sources with sensors outside the head. In MEG analysis these current sources are estimated from the measured data to identify the locations and time courses of neural activity. Since there is no unique solution to this so-called inverse problem, multiple source estimation techniques have been developed. The nulling beamformer (NB), a modified form of the linearly constrained minimum variance (LCMV) beamformer, is specifically used in the process of inferring interregional interactions and is designed to eliminate shared signal contributions, or cross-talk, between regions of interest (ROIs) that would otherwise interfere with the connectivity analyses. The nulling beamformer applies the truncated singular value decomposition (TSVD) to remove small signal contributions from a ROI to the sensor signals. However, ROIs with strong crosstalk will have high separating power in the weaker components, which may be removed by the TSVD operation. To address this issue we propose a new method, the nulling beamformer with subspace suppression (NBSS). This method, controlled by a tuning parameter, reweights the singular values of the gain matrix mapping from source to sensor space such that components with high overlap are reduced. By doing so, we are able to measure signals between nearby source locations with limited cross-talk interference, allowing for reliable cortical connectivity analysis between them. In two simulations, we demonstrated that NBSS reduces cross-talk while retaining ROIs' signal power, and has higher separating power than both the minimum norm estimate (MNE) and the nulling beamformer without subspace suppression. We also showed that NBSS successfully localized the auditory M100 event-related field in primary auditory cortex, measured from a subject undergoing an auditory localizer task, and suppressed cross-talk in a nearby region in the superior temporal sulcus.

Minimum spanning tree analysis of the human connectome

PubMed Central

Sommer, Iris E.; Bohlken, Marc M.; Tewarie, Prejaas; Draaisma, Laurijn; Zalesky, Andrew; Di Biase, Maria; Brown, Jesse A.; Douw, Linda; Otte, Willem M.; Mandl, René C.W.; Stam, Cornelis J.

2018-01-01

Abstract One of the challenges of brain network analysis is to directly compare network organization between subjects, irrespective of the number or strength of connections. In this study, we used minimum spanning tree (MST; a unique, acyclic subnetwork with a fixed number of connections) analysis to characterize the human brain network to create an empirical reference network. Such a reference network could be used as a null model of connections that form the backbone structure of the human brain. We analyzed the MST in three diffusion‐weighted imaging datasets of healthy adults. The MST of the group mean connectivity matrix was used as the empirical null‐model. The MST of individual subjects matched this reference MST for a mean 58%–88% of connections, depending on the analysis pipeline. Hub nodes in the MST matched with previously reported locations of hub regions, including the so‐called rich club nodes (a subset of high‐degree, highly interconnected nodes). Although most brain network studies have focused primarily on cortical connections, cortical–subcortical connections were consistently present in the MST across subjects. Brain network efficiency was higher when these connections were included in the analysis, suggesting that these tracts may be utilized as the major neural communication routes. Finally, we confirmed that MST characteristics index the effects of brain aging. We conclude that the MST provides an elegant and straightforward approach to analyze structural brain networks, and to test network topological features of individual subjects in comparison to empirical null models. PMID:29468769

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

PubMed

van de Vrugt, Henri J; Koomen, Mireille; Bakker, Sietske; Berns, Mariska A D; Cheng, Ngan Ching; van der Valk, Martin A; de Vries, Yne; Rooimans, Martin A; Oostra, Anneke B; Hoatlin, Maureen E; Te Riele, Hein; Joenje, Hans; Arwert, Fré

2011-12-10

Fanconi anemia (FA) is a heritable disease characterized by bone marrow failure, congenital abnormalities, and cancer predisposition. The 15 identified FA genes operate in a molecular pathway to preserve genomic integrity. Within this pathway the FA core complex operates as an ubiquitin ligase that activates the complex of FANCD2 and FANCI to coordinate DNA repair. The FA core complex is formed by at least 12 proteins. However, only the FANCL subunit displays ubiquitin ligase activity. FANCA and FANCG are members of the FA core complex for which no other functions have been described than to participate in protein interactions. In this study we generated mice with combined null alleles for Fanca and Fancg to identify extended functions for these genes by characterizing the double mutant mice and cells. Double mutant a(-/-)/g(-/-) mice were born at near Mendelian frequencies without apparent developmental abnormalities. Histological analysis of a(-/-)/g(-/-) mice revealed a Leydig cell hyperplasia and frequent vacuolization of Sertoli cells in testes, while ovaries were depleted from developing follicles and displayed an interstitial cell hyperplasia. These gonadal aberrations were associated with a compromised fertility of a(-/-)/g(-/-) males and females. During the first year of life a(-/-)/g(-/-) did not develop malignancies or bone marrow failure. At the cellular level a(-/-)/g(-/-), Fanca(-/-), and Fancg(-/-) cells proved equally compromised in DNA crosslink and homology-directed repair. Overall the phenotype of a(-/-)/g(-/-) double knockout mice and cells appeared highly similar to the phenotype of Fanca or Fancg single knockouts. The lack of an augmented phenotype suggest that null mutations in Fanca or Fancg are fully epistatic, making additional important functions outside of the FA core complex highly unlikely. 2011 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-07-01

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

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

PubMed

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

2018-04-01

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

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.

Connective tissue growth factor is required for skeletal development and postnatal skeletal homeostasis in male mice.

PubMed

Canalis, Ernesto; Zanotti, Stefano; Beamer, Wesley G; Economides, Aris N; Smerdel-Ramoya, Anna

2010-08-01

Connective tissue growth factor (CTGF), a member of the cysteine-rich 61 (Cyr 61), CTGF, nephroblastoma overexpressed (NOV) (CCN) family of proteins, is synthesized by osteoblasts, and its overexpression inhibits osteoblastogenesis and causes osteopenia. The global inactivation of Ctgf leads to defective endochondral bone formation and perinatal lethality; therefore, the consequences of Ctgf inactivation on the postnatal skeleton are not known. To study the function of CTGF, we generated Ctgf(+/LacZ) heterozygous null mice and tissue-specific null Ctgf mice by mating Ctgf conditional mice, where Ctgf is flanked by lox sequences with mice expressing the Cre recombinase under the control of the paired-related homeobox gene 1 (Prx1) enhancer (Prx1-Cre) or the osteocalcin promoter (Oc-Cre). Ctgf(+/LacZ) heterozygous mice exhibited transient osteopenia at 1 month of age secondary to decreased trabecular number. A similar osteopenic phenotype was observed in 1-month-old Ctgf conditional null male mice generated with Prx1-Cre, suggesting that the decreased trabecular number was secondary to impaired endochondral bone formation. In contrast, when the conditional deletion of Ctgf was achieved by Oc-Cre, an osteopenic phenotype was observed only in 6-month-old male mice. Osteoblast and osteoclast number, bone formation, and eroded surface were not affected in Ctgf heterozygous or conditional null mice. In conclusion, CTGF is necessary for normal skeletal development but to a lesser extent for postnatal skeletal homeostasis.

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations

PubMed Central

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-01-01

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. PMID:24975579

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

PubMed Central

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

2000-01-01

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

Initial development of the DIII–D snowflake divertor control

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Can one ever prove that neutrinos are Dirac particles?

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

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.

Topology and Singularities in Cosmological Spacetimes Obeying the Null Energy Condition

NASA Astrophysics Data System (ADS)

Galloway, Gregory J.; Ling, Eric

2018-06-01

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

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

Busbey, A.B.

A number of methods and products, both hardware and software, to allow data exchange between Apple Macintosh computers and MS-DOS based systems. These included serial null modem connections, MS-DOS hardware and/or software emulation, MS-DOS disk-reading hardware and networking.

Hypothalamic-pituitary cytokine network.

PubMed

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

2004-01-01

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

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

PubMed

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

2009-09-01

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

The Green Bank Northern Celestial Cap Pulsar Survey. II. The Discovery and Timing of 10 Pulsars

NASA Astrophysics Data System (ADS)

Kawash, A. M.; McLaughlin, M. A.; Kaplan, D. L.; DeCesar, M. E.; Levin, L.; Lorimer, D. R.; Lynch, R. S.; Stovall, K.; Swiggum, J. K.; Fonseca, E.; Archibald, A. M.; Banaszak, S.; Biwer, C. M.; Boyles, J.; Cui, B.; Dartez, L. P.; Day, D.; Ernst, S.; Ford, A. J.; Flanigan, J.; Heatherly, S. A.; Hessels, J. W. T.; Hinojosa, J.; Jenet, F. A.; Karako-Argaman, C.; Kaspi, V. M.; Kondratiev, V. I.; Leake, S.; Lunsford, G.; Martinez, J. G.; Mata, A.; Matheny, T. D.; Mcewen, A. E.; Mingyar, M. G.; Orsini, A. L.; Ransom, S. M.; Roberts, M. S. E.; Rohr, M. D.; Siemens, X.; Spiewak, R.; Stairs, I. H.; van Leeuwen, J.; Walker, A. N.; Wells, B. L.

2018-04-01

We present timing solutions for 10 pulsars discovered in 350 MHz searches with the Green Bank Telescope. Nine of these were discovered in the Green Bank Northern Celestial Cap survey and one was discovered by students in the Pulsar Search Collaboratory program during an analysis of drift-scan data. Following the discovery and confirmation with the Green Bank Telescope, timing has yielded phase-connected solutions with high-precision measurements of rotational and astrometric parameters. Eight of the pulsars are slow and isolated, including PSR J0930‑2301, a pulsar with a nulling fraction lower limit of ∼30% and a nulling timescale of seconds to minutes. This pulsar also shows evidence of mode changing. The remaining two pulsars have undergone recycling, accreting material from binary companions, resulting in higher spin frequencies. PSR J0557‑2948 is an isolated, 44 ms pulsar that has been partially recycled and is likely a former member of a binary system that was disrupted by a second supernova. The paucity of such so-called “disrupted binary pulsars” (DRPs) compared to double neutron star (DNS) binaries can be used to test current evolutionary scenarios, especially the kicks imparted on the neutron stars in the second supernova. There is some evidence that DRPs have larger space velocities, which could explain their small numbers. PSR J1806+2819 is a 15 ms pulsar in a 44-day orbit with a low-mass white dwarf companion. We did not detect the companion in archival optical data, indicating that it must be older than 1200 Myr.

Optomechanical design of near-null subaperture test system based on counter-rotating CGH plates

NASA Astrophysics Data System (ADS)

Li, Yepeng; Chen, Shanyong; Song, Bing; Li, Shengyi

2014-09-01

In off-axis subapertures of most convex aspheres, astigmatism and coma dominate the aberrations with approximately quadratic and linear increase as the off-axis distance increases. A pair of counter-rotating computer generated hologram (CGH) plates is proposed to generate variable amount of Zernike terms Z4 and Z6, correcting most of the astigmatism and coma for subapertures located at different positions on surfaces of various aspheric shapes. The residual subaperture aberrations are then reduced within the vertical range of measurement of the interferometer, which enables near-null test of aspheres flexibly. The alignment tolerances for the near-null optics are given with optomechanical analysis. Accordingly a novel design for mounting and aligning the CGH plates is proposed which employs three concentric rigid rings. The CGH plate is mounted in the inner ring which is supported by two couples of ball-end screws in connection with the middle ring. The CGH plate along with the inner ring is hence able to be translated in X-axis and tipped by adjusting the screws. Similarly the middle ring is able to be translated in Y-axis and tilted by another two couples of screws orthogonally arranged and connected to the outer ring. This design is featured by the large center-through hole, compact size and capability of four degrees-of-freedom alignment (lateral shift and tip-tilt). It reduces the height measured in the direction of optical axis as much as possible, which is particularly advantageous for near-null test of convex aspheres. The CGH mounts are then mounted on a pair of center-through tables realizing counter-rotation. Alignment of the interferometer, the CGHs, the tables and the test surface is also discussed with a reasonable layout of the whole test system. The interferometer and the near-null optics are translated by a three-axis stage while the test mirror is rotated and tilted by two rotary tables. Experimental results are finally given to show the near-null subaperture test capability of the system for a convex even asphere.

Heating of the corona by magnetic singularities

NASA Technical Reports Server (NTRS)

Antiochos, Spiro K.

1990-01-01

Theoretical models of current-sheet formation and magnetic heating in the solar corona are examined analytically. The role of photospheric connectivity in determining the topology of the coronal magnetic field and its equilibrium properties is explored; nonequilibrium models of current-sheet formation (assuming an initially well connected field) are described; and particular attention is given to models with discontinuous connectivity, where magnetic singularities arise from smooth footpoint motions. It is shown that current sheets arise from connectivities in which the photospheric flux structure is complex, with three or more polarity regions and a magnetic null point within the corona.

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.

PubMed

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-09-01

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. © 2014 Anatomical Society.

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

PubMed Central

2018-01-01

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

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.

Ultimate Limit State Assessment of Timber Bolt Connection Subjected to Double Unequal Shears

NASA Astrophysics Data System (ADS)

Musilek, Josef; Plachy, Jan

2017-10-01

Nowadays the problems occur when a structure engineer need to assess the ultimate limit state of timber bolt connection which is subjected to double unequal shears. This assessment of ultimate limit state shows the reliability of these connections. In assessing the reliability of this connection in ultimate limit state is a problem, because the formulas and equations that are currently available in design standards and available literature, describing only connections loaded symmetrically - this mean that they describe the timber bolt connection subjected to double equal shears. This fact causes problems because structural engineers have no available support, according to which they could assess reliability of the connection in terms of the ultimate limit state. They must therefore often report following an asymmetrically loaded connections carry about using formulas, which are primarily designed for checking connections loaded symmetrically. This leads logically to the fact that it is not respected by the actual behaviour of the connection in the ultimate limit state. Formulas derived in this paper provide the possibility to assess the ultimate limit state for such connection. The formulas derived in this article allow to carry out a reliability assessment of the ultimate limit state of timber bolt connection subjected to double shear. The using of the formulas derived in this paper leads to better description of the behaviour of this type of connection and also to the more economic design. An example of using these derived formulas is shown. There is shown in this example, how to assess the reliability of timber bolt connection subjected to double unequal shears in terms of ultimate limit states.

Initial development of the DIII–D snowflake divertor control

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

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

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

Initial development of the DIII–D snowflake divertor control

DOE PAGES

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

2018-04-11

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

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

PubMed Central

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

2002-01-01

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

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

PubMed Central

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

2009-01-01

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

Doubling down on naturalness with a supersymmetric twin Higgs

NASA Astrophysics Data System (ADS)

Craig, Nathaniel; Howe, Kiel

2014-03-01

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

29 CFR Appendix H to Subpart R of... - Double Connections: Illustration of a Clipped End Connection and a Staggered Connection: Non...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Connection and a Staggered Connection: Non-Mandatory Guidelines for Complying With § 1926.756(c)(1) H Appendix H to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY... CONSTRUCTION Steel Erection Pt. 1926, Subpt. R, App. H Appendix H to Subpart R of Part 1926—Double Connections...

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

PubMed

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

2007-10-01

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

29 CFR Appendix H to Subpart R of... - Double Connections: Illustration of a Clipped End Connection and a Staggered Connection: Non...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Appendix H to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY... CONSTRUCTION Steel Erection Pt. 1926, Subpt. R, App. H Appendix H to Subpart R of Part 1926—Double Connections...

29 CFR Appendix H to Subpart R of... - Double Connections: Illustration of a Clipped End Connection and a Staggered Connection: Non...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Appendix H to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY... CONSTRUCTION Steel Erection Pt. 1926, Subpt. R, App. H Appendix H to Subpart R of Part 1926—Double Connections...

29 CFR Appendix H to Subpart R of... - Double Connections: Illustration of a Clipped End Connection and a Staggered Connection: Non...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Appendix H to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY... CONSTRUCTION Steel Erection Pt. 1926, Subpt. R, App. H Appendix H to Subpart R of Part 1926—Double Connections...

29 CFR Appendix H to Subpart R of... - Double Connections: Illustration of a Clipped End Connection and a Staggered Connection: Non...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Appendix H to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY... CONSTRUCTION Steel Erection Pt. 1926, Subpt. R, App. H Appendix H to Subpart R of Part 1926—Double Connections...

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

PubMed

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

1999-09-01

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

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.

Myopathic changes in murine skeletal muscle lacking synemin

PubMed Central

García-Pelagio, Karla P.; Muriel, Joaquin; O'Neill, Andrea; Desmond, Patrick F.; Lovering, Richard M.; Lund, Linda; Bond, Meredith

2015-01-01

Diseases of striated muscle linked to intermediate filament (IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle. PMID:25567810

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

PubMed

Pan, Luyuan; Broadie, Kendal S

2007-11-07

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

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

PubMed

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

2001-06-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

Tipper, Donald J.; Harley, Carol A

2002-01-01

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

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

PubMed Central

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

2008-01-01

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

Neurogenin 1 Null Mutant Ears Develop Fewer, Morphologically Normal Hair Cells in Smaller Sensory Epithelia Devoid of Innervation

PubMed Central

Ma, Qiufu; Anderson, David J.

2000-01-01

The proneuronal gene neurogenin 1 (ngn1) is essential for development of the inner-ear sensory neurons that are completely absent in ngn1 null mutants. Neither afferent, efferent, nor autonomic nerve fibers were detected in the ears of ngn1 null mutants. We suggest that efferent and autonomic fibers are lost secondarily to the absence of afferents. In this article we show that ngn1 null mutants develop smaller sensory epithelia with morphologically normal hair cells. In particular, the saccule is reduced dramatically and forms only a small recess with few hair cells along a duct connecting the utricle with the cochlea. Hair cells of newborn ngn1 null mutants show no structural abnormalities, suggesting that embryonic development of hair cells is independent of innervation. However, the less regular pattern of dispersal within sensory epithelia may be caused by some effects of afferents or to the stunted growth of the sensory epithelia. Tracing of facial and stato-acoustic nerves in control and ngn1 null mutants showed that only the distal, epibranchial, placode-derived sensory neurons of the geniculate ganglion exist in mutants. Tracing further showed that these geniculate ganglion neurons project exclusively to the solitary tract. In addition to the normal complement of facial branchial and visceral motoneurons, ngn1 null mutants have some trigeminal motoneurons and contralateral inner-ear efferents projecting, at least temporarily, through the facial nerve. These data suggest that some neurons in the brainstem (e.g., inner-ear efferents, trigeminal motoneurons) require afferents to grow along and redirect to ectopic cranial nerve roots in the absence of their corresponding sensory roots. PMID:11545141

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.

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

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

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

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

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.

Energy levels of double triangular graphene quantum dots

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

Liang, F. X.; Jiang, Z. T., E-mail: ztjiang616@hotmail.com; Zhang, H. Y.

2014-09-28

We investigate theoretically the energy levels of the coupled double triangular graphene quantum dots (GQDs) based on the tight-binding Hamiltonian model. The double GQDs including the ZZ-type, ZA-type, and AA-type GQDs with the two GQDs having the zigzag or armchair boundaries can be coupled together via different interdot connections, such as the direct coupling, the chains of benzene rings, and those of carbon atoms. It is shown that the energy spectrum of the coupled double GQDs is the amalgamation of those spectra of the corresponding two isolated GQDs with the modification triggered by the interdot connections. The interdot connection ismore » inclined to lift up the degeneracies of the energy levels in different degree, and as the connection changes from the direct coupling to the long chains, the removal of energy degeneracies is suppressed in ZZ-type and AA-type double GQDs, which indicates that the two coupled GQDs are inclined to become decoupled. Then we consider the influences on the spectra of the coupled double GQDs induced by the electric fields applied on the GQDs or the connection, which manifests as the global spectrum redistribution or the local energy level shift. Finally, we study the symmetrical and asymmetrical energy spectra of the double GQDs caused by the substrates supporting the two GQDs, clearly demonstrating how the substrates affect the double GQDs' spectrum. This research elucidates the energy spectra of the coupled double GQDs, as well as the mechanics of manipulating them by the electric field and the substrates, which would be a significant reference for designing GQD-based devices.« less

Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity

PubMed Central

Kyriakides, Themis R.; Leach, Kathleen J.; Hoffman, Allan S.; Ratner, Buddy D.; Bornstein, Paul

1999-01-01

Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex phenotype characterized chiefly by abnormalities in fibroblasts, connective tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibroblasts in vitro also was evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their attachment was further compromised on ox-PDMS. After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice. However, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In addition, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extracellular matrix component, TSP2, can influence the nature of the FBR, in particular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of the tissue surrounding an implanted device is desired. PMID:10200282

Precision Tests of a Quantum Hall Effect Device DC Equivalent Circuit Using Double-Series and Triple-Series Connections

PubMed Central

Jeffery, A.; Elmquist, R. E.; Cage, M. E.

1995-01-01

Precision tests verify the dc equivalent circuit used by Ricketts and Kemeny to describe a quantum Hall effect device in terms of electrical circuit elements. The tests employ the use of cryogenic current comparators and the double-series and triple-series connection techniques of Delahaye. Verification of the dc equivalent circuit in double-series and triple-series connections is a necessary step in developing the ac quantum Hall effect as an intrinsic standard of resistance. PMID:29151768

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

High Performance Double-null Plasma Operation Under Radiating Divertor Conditions

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

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

PubMed Central

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

1999-01-01

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

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

PubMed

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

2002-07-19

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

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.

Radical screen transversal lightlike submanifolds of indefinite Kaehler manifolds admitting a quarter-symmetric non-metric connection

NASA Astrophysics Data System (ADS)

Gupta, Garima; Kumar, Rakesh; Nagaich, Rakesh Kumar

We study radical screen transversal (ST)-lightlike submanifolds of an indefinite Kaehler manifold admitting a quarter-symmetric non-metric connection and obtain a necessary and sufficient condition for the screen distribution of a radical ST-lightlike submanifold to be integrable. We also study totally umbilical radical ST-lightlike submanifolds and obtain some characterization theorems for a radical ST-lightlike submanifold to be a lightlike product manifold. Finally, we establish some results regarding the vanishes of null sectional curvature.

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2013-01-01

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

Experimental study on the strength of double shear timber connection using bamboo dowel fastener

NASA Astrophysics Data System (ADS)

Anshari, Buan; Sugiartha, Wayan; Mahmud, Fathmah; Rofaida, Aryani; Pathurrahman

2017-11-01

Utilization of timber and bamboo as building materials was very promising for now and future. As renewable resources they have high mechanical properties, lightweight, environmentally friendly and economic. Utilization of bamboo as connector was rarely published. Therefore, this study focused on utilization of non-metal material as connector in timber structure especially for beam and column. This research was conducted in the laboratory to examine the strength of double shear timber connection by using glued in rods (bamboo dowel) as connector with variation of adhesive thickness. As control specimen was used bamboo dowel Ø14 mm without adhesive in double shear connection. The results showed that the strength of double shear timber connection by using glued in rods (bamboo dowel) as connector could increased by 41% to resist axial force higher than the control one.

Geomorphic controls on elevational gradients of species richness.

PubMed

Bertuzzo, Enrico; Carrara, Francesco; Mari, Lorenzo; Altermatt, Florian; Rodriguez-Iturbe, Ignacio; Rinaldo, Andrea

2016-02-16

Elevational gradients of biodiversity have been widely investigated, and yet a clear interpretation of the biotic and abiotic factors that determine how species richness varies with elevation is still elusive. In mountainous landscapes, habitats at different elevations are characterized by different areal extent and connectivity properties, key drivers of biodiversity, as predicted by metacommunity theory. However, most previous studies directly correlated species richness to elevational gradients of potential drivers, thus neglecting the interplay between such gradients and the environmental matrix. Here, we investigate the role of geomorphology in shaping patterns of species richness. We develop a spatially explicit zero-sum metacommunity model where species have an elevation-dependent fitness and otherwise neutral traits. Results show that ecological dynamics over complex terrains lead to the null expectation of a hump-shaped elevational gradient of species richness, a pattern widely observed empirically. Local species richness is found to be related to the landscape elevational connectivity, as quantified by a newly proposed metric that applies tools of complex network theory to measure the closeness of a site to others with similar habitat. Our theoretical results suggest clear geomorphic controls on elevational gradients of species richness and support the use of the landscape elevational connectivity as a null model for the analysis of the distribution of biodiversity.

Geomorphic controls on elevational gradients of species richness

PubMed Central

Bertuzzo, Enrico; Carrara, Francesco; Mari, Lorenzo; Altermatt, Florian; Rodriguez-Iturbe, Ignacio; Rinaldo, Andrea

2016-01-01

Elevational gradients of biodiversity have been widely investigated, and yet a clear interpretation of the biotic and abiotic factors that determine how species richness varies with elevation is still elusive. In mountainous landscapes, habitats at different elevations are characterized by different areal extent and connectivity properties, key drivers of biodiversity, as predicted by metacommunity theory. However, most previous studies directly correlated species richness to elevational gradients of potential drivers, thus neglecting the interplay between such gradients and the environmental matrix. Here, we investigate the role of geomorphology in shaping patterns of species richness. We develop a spatially explicit zero-sum metacommunity model where species have an elevation-dependent fitness and otherwise neutral traits. Results show that ecological dynamics over complex terrains lead to the null expectation of a hump-shaped elevational gradient of species richness, a pattern widely observed empirically. Local species richness is found to be related to the landscape elevational connectivity, as quantified by a newly proposed metric that applies tools of complex network theory to measure the closeness of a site to others with similar habitat. Our theoretical results suggest clear geomorphic controls on elevational gradients of species richness and support the use of the landscape elevational connectivity as a null model for the analysis of the distribution of biodiversity. PMID:26831107

Do Causal and Concessive Connectives Guide Emotional Expectancies in Comprehension? A Double-Task Paradigm Using Emotional Icons

ERIC Educational Resources Information Center

Morera, Yurena; León, José A.; Escudero, Inmaculada; de Vega, Manuel

2017-01-01

Continuity and discontinuity are sometimes marked in discourse by means of connectives. This study tested for the first time whether causal and concessive connectives induce expectations of emotional continuity and discontinuity, respectively. Using a novel double-task paradigm, participants first listened to an antecedent clause with a causal or…

Implementation of the 3D edge plasma code EMC3-EIRENE on NSTX

DOE PAGES

Lore, J. D.; Canik, J. M.; Feng, Y.; ...

2012-05-09

The 3D edge transport code EMC3-EIRENE has been applied for the first time to the NSTX spherical tokamak. A new disconnected double null grid has been developed to allow the simulation of plasma where the radial separation of the inner and outer separatrix is less than characteristic widths (e.g. heat flux width) at the midplane. Modelling results are presented for both an axisymmetric case and a case where 3D magnetic field is applied in an n = 3 configuration. In the vacuum approximation, the perturbed field consists of a wide region of destroyed flux surfaces and helical lobes which aremore » a mixture of long and short connection length field lines formed by the separatrix manifolds. This structure is reflected in coupled 3D plasma fluid (EMC3) and kinetic neutral particle (EIRENE) simulations. The helical lobes extending inside of the unperturbed separatrix are filled in by hot plasma from the core. The intersection of the lobes with the divertor results in a striated flux footprint pattern on the target plates. As a result, profiles of divertor heat and particle fluxes are compared with experimental data, and possible sources of discrepancy are discussed.« less

Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability

PubMed Central

Greenbury, Sam F.; Schaper, Steffen; Ahnert, Sebastian E.; Louis, Ard A.

2016-01-01

Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps—a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure—to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so increase evolvability. PMID:26937652

Two-Wire to Four-Wire Audio Converter

NASA Technical Reports Server (NTRS)

Talley, G. L., Jr; Seale, B. L.

1983-01-01

Simple circuit provides interface between normally incompatible voicecommunication lines. Circuit maintains 40 dB of isolation between input and output halves of four-wire line permitting two-wire line to be connected. Balancing potentiometer, Rg, adjusts gain of IC2 to null feed through from input to output. Adjustment is done on workbench just after assembly.

Double metric, generalized metric, and α' -deformed double field theory

NASA Astrophysics Data System (ADS)

Hohm, Olaf; Zwiebach, Barton

2016-03-01

We relate the unconstrained "double metric" of the "α' -geometry" formulation of double field theory to the constrained generalized metric encoding the spacetime metric and b -field. This is achieved by integrating out auxiliary field components of the double metric in an iterative procedure that induces an infinite number of higher-derivative corrections. As an application, we prove that, to first order in α' and to all orders in fields, the deformed gauge transformations are Green-Schwarz-deformed diffeomorphisms. We also prove that to first order in α' the spacetime action encodes precisely the Green-Schwarz deformation with Chern-Simons forms based on the torsionless gravitational connection. This seems to be in tension with suggestions in the literature that T-duality requires a torsionful connection, but we explain that these assertions are ambiguous since actions that use different connections are related by field redefinitions.

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

USDA-ARS?s Scientific Manuscript database

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

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

PubMed Central

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

2011-01-01

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

Adaptive mesh refinement for characteristic grids

NASA Astrophysics Data System (ADS)

Thornburg, Jonathan

2011-05-01

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

Behavior of Double-Web Angles Beam to column connections

NASA Astrophysics Data System (ADS)

Fakih, K. Al; Chin, S. C.; Doh, S. I.

2018-04-01

This paper contains the study performed on the behavior of double-web angles by using finite element analysis computer package known as “Abaqus”. The aim of this present study was simulating the behavior of double-web angles (DWA) steel connections. The purpose of this article is to provide the basis for the fastest and most economical design and analysis and to ensure the required steel connection strength. This study, started used review method of behavior of steel beam-to-column bolted connections. Two models of different cross-section were examined under the effect of concentrated load and different boundary conditions. In all the studied case, material nonlinearity was accounted. A sample study on DWA connections was carried out using both material and geometric nonlinearities. This object will be of great value to anyone who wants to better understand the behavior of the steel beam to column connection. The results of the study have a field of reference for future research for members of the development of the steel connection approach with simulation model design.

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.

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.

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

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.

Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

DTIC Science & Technology

2015-09-01

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

Supersymmetric Galileons

DOE PAGES

Khoury, Justin; Lehners, Jean -Luc; Ovrut, Burt A.

2011-08-15

Galileon theories are of considerable interest since they allow for stable violations of the null energy condition. Since such violations could have occurred during a high-energy regime in the history of our universe, we are motivated to study supersymmetric extensions of these theories. This is carried out in this paper, where we construct generic classes of N = 1 supersymmetric Galileon Lagrangians. They are shown to admit non-equivalent stress-energy tensors and, hence, vacua manifesting differing conditions for violating the null energy condition. The temporal and spatial fluctuations of all component fields of the supermultiplet are analyzed and shown to bemore » stable on a large number of such backgrounds. In the process, we uncover a surprising connection between conformal Galileon and ghost condensate theories, allowing for a deeper understanding of both types of theories.« less

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.

Functional Dependence for Calculation of Additional Real-Power Losses in a Double-Wound Supply Transformer Caused by Unbalanced Active Inductive Load in a Star Connection with an Insulated Neutral

ERIC Educational Resources Information Center

Kostinskiy, Sergey S.; Troitskiy, Anatoly I.

2016-01-01

This article deals with the problem of calculating the additional real-power losses in double-wound supply transformers with voltage class 6 (10)/0,4 kV, caused by unbalanced active inductive load connected in a star connection with an insulated neutral. When solving the problem, authors used the theory of electric circuits, method of balanced…

Abnormal connection of the inferior vena cava to the left atrium with double outlet right ventricle and heterotaxia: a case report.

PubMed

Günal, N; Bilgiç, A; Lenk, M K; Yurdakul, Y; Sarigül, A; Ispir, S

1996-03-01

A 4-year-old boy with abnormal connection of the inferior vena cava to the left atrium and double outlet right ventricle and right atrial isomerism is presented. The anomalies were detected by echocardiography and angiography, and later verified through surgical intervention.

The New Concept of Univentricular Heart

PubMed Central

Frescura, Carla; Thiene, Gaetano

2014-01-01

The concept of univentricular heart moved from hearts with only one ventricle connected with atria [double inlet ventricle or absent atrioventricular (AV) connection] to hearts not amenable to biventricular repair, namely hearts with two ventricles unable to sustain separately pulmonary and systemic circulations in sequence. In the latter definition, even hearts with one hypoplastic ventricle are considered “functional” univentricular hearts. They include pulmonary/aortic atresia or severe stenosis with hypoplastic ventricle, and rare conditions like huge intramural cardiac tumors and Ebstein anomaly with extreme atrialization of right ventricular cavity. In this setting, the surgical repair is univentricular with “Fontan” operation, bypassing the ventricular mass. In other words, functionally univentricular heart is a condition in which, after surgery, only one ventricle sustain systemic circulation. Univentricular hearts (double inlet or absent AV connection) almost invariably show two ventricular chambers, one main and one accessory, which lacks an inlet portion. The latter is located posteriorly when morphologically left and anteriorly when morphologically right. As far as double inlet left ventricle, this is usually associated with discordant ventriculo-arterial (VA) connection (transposition of the great arteries) and all the blood flow to the aorta, which takes origin from the hypoplastic anterior right ventricle, is ventricular septal defect (bulbo-ventricular foramen) dependent. If restrictive, an aortic arch obstruction may be present. Double inlet left ventricle may be rarely associated with VA concordance (Holmes heart). As far as double inlet right ventricle with posterior hypoplastic left ventricular cavity, ventriculo-arterial connection is usually of double outlet type; thus the term double inlet–outlet right ventricle may be coined. Absent right or left AV connection may develop in the setting of both d- or l-loop, whatever the situs. In this condition, the contra-lateral patent AV valve may be either mitral or tricuspid in terms of morphology and the underlying ventricle (main chamber) either morphologically left or right. Establishing the loop, whatever right or left (also called right or left ventricular topology), is a fundamental step in the segmental-sequential analysis of congenital heart disease. PMID:25072035

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

Methylation of Gibberellins by Arabidopsis GAMT1 and GAMT2[W

PubMed Central

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

2007-01-01

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

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

PubMed

Bale, Laurie K; Conover, Cheryl A

2005-08-01

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

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

DOE PAGES

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

2015-06-26

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

Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.

PubMed

de Salas-Quiroga, Adán; Díaz-Alonso, Javier; García-Rincón, Daniel; Remmers, Floortje; Vega, David; Gómez-Cañas, María; Lutz, Beat; Guzmán, Manuel; Galve-Roperh, Ismael

2015-11-03

The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

Rigor and academic achievement: Career academies versus traditional class structure

NASA Astrophysics Data System (ADS)

Kyees, Linda L.

The purpose of this study was to determine if students who attended high school Career Academy classes, as part of Career and Technical Education, showed greater academic achievement than students who attended traditional high school classes. While all participants attended schools in the same school district, and were seeking the same goal of graduation with a standard diploma, the Career Academy students had the benefit of all classes being directed by a team of teachers who helped them connect their learning to their desired career through collaborative learning projects and assignments. The traditional high school classes taught each subject independent of other subjects and did not have specific connections to desired career goals of the students. The study used a causal-comparative research design and the participants included 1,142 students from 11th and 12th grades who attended 9 high schools in a diversely populated area of central Florida with 571 enrolled in the Career Academies and 571 enrolled in traditional classes. The 10th-grade FCAT scores served as the dependent variable. All students attended similar classes with similar content, making the primary variable the difference in academic gains between students participating in the Career Academy design and the traditional design classes. Using the Man-Whitney U Test resulted in the Career Academy group achieving the higher scores overall. This resulted in rejection of the first null-hypothesis. Further examination determined that the 10th-grade FCAT scores were greater for the average students group, which comprised the largest portion of the participant group, also resulted in rejection of the second null-hypothesis. The gifted and at-risk student group scores resulted in failure to reject the third and fourth null-hypotheses.

Formation of a three-dimensional plasma boundary after decay of the plasma response to resonant magnetic perturbation fields

NASA Astrophysics Data System (ADS)

Schmitz, O.; Evans, T. E.; Fenstermacher, M. E.; Lanctot, M. J.; Lasnier, C. L.; Mordijck, S.; Moyer, R. A.; Reimerdes, H.; the DIII-D Team

2014-01-01

First time experimental evidence is presented for a direct link between the decay of a n = 3 plasma response and the formation of a three-dimensional (3D) plasma boundary. We inspect a lower single-null L-mode plasma which first reacts at sufficiently high rotation with an ideal resonant screening response to an external toroidal mode number n = 3 resonant magnetic perturbation field. Decay of this response due to reduced bulk plasma rotation changes the plasma state considerably. Signatures such as density pump out and a spin up of the edge rotation—which are usually connected to formation of a stochastic boundary—are detected. Coincident, striation of the divertor single ionized carbon emission and a 3D emission structure in double ionized carbon at the separatrix is seen. The striated C II pattern follows in this stage the perturbed magnetic footprint modelled without a plasma response (vacuum approach). This provides for the first time substantial experimental evidence, that a 3D plasma boundary with direct impact on the divertor particle flux pattern is formed as soon as the internal plasma response decays. The resulting divertor structure follows the vacuum modelled magnetic field topology. However, the inward extension of the perturbed boundary layer can still not directly be determined from these measurements.

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

PubMed

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

2011-12-01

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

Calculating observables in inhomogeneous cosmologies. Part I: general framework

NASA Astrophysics Data System (ADS)

Hellaby, Charles; Walters, Anthony

2018-02-01

We lay out a general framework for calculating the variation of a set of cosmological observables, down the past null cone of an arbitrarily placed observer, in a given arbitrary inhomogeneous metric. The observables include redshift, proper motions, area distance and redshift-space density. Of particular interest are observables that are zero in the spherically symmetric case, such as proper motions. The algorithm is based on the null geodesic equation and the geodesic deviation equation, and it is tailored to creating a practical numerical implementation. The algorithm provides a method for tracking which light rays connect moving objects to the observer at successive times. Our algorithm is applied to the particular case of the Szekeres metric. A numerical implementation has been created and some results will be presented in a subsequent paper. Future work will explore the range of possibilities.

Teleparallel equivalent of Lovelock gravity

NASA Astrophysics Data System (ADS)

González, P. A.; Vásquez, Yerko

2015-12-01

There is a growing interest in modified gravity theories based on torsion, as these theories exhibit interesting cosmological implications. In this work inspired by the teleparallel formulation of general relativity, we present its extension to Lovelock gravity known as the most natural extension of general relativity in higher-dimensional space-times. First, we review the teleparallel equivalent of general relativity and Gauss-Bonnet gravity, and then we construct the teleparallel equivalent of Lovelock gravity. In order to achieve this goal, we use the vielbein and the connection without imposing the Weitzenböck connection. Then, we extract the teleparallel formulation of the theory by setting the curvature to null.

Double-outlet right ventricle: Pathology and angiocardiography.

PubMed

Freedom, Robert M.; Yoo, Shi-Joon

2000-01-01

Double-outlet right ventricle is but one form of abnormal ventriculoarterial connection. The definition that more than half of each great artery originates above the morphologically right ventricle is arbitrary. As pointed out by Lecompte, those features that should be defined in hearts with the ventriculoarterial connection of double-outlet right ventricle (and indeed other forms of abnormal ventriculoarterial connection) include the nature of the infundibular septum, ventriculoinfundibular fold, trabeculoseptomargin-alis, attachments of infundibular septum to anterior or posterior limb of trabeculoseptomargin-alis, the size and position of the ventricular septal defect, the spatial relation of great artery(s) to the ventricular septal defect, the spatial relationship between the great, and the distance between the tricuspid and pulmonary valves and the semilunar valves. Copyright 2000 by W.B. Saunders Company

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

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.

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

PubMed

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

2013-01-01

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

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

PubMed Central

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

1999-01-01

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

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

PubMed Central

Nicastro, Holly L.; Dunn, Barbara K.

2013-01-01

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

Reciprocity in spatial evolutionary public goods game on double-layered network

NASA Astrophysics Data System (ADS)

Kim, Jinho; Yook, Soon-Hyung; Kim, Yup

2016-08-01

Spatial evolutionary games have mainly been studied on a single, isolated network. However, in real world systems, many interaction topologies are not isolated but many different types of networks are inter-connected to each other. In this study, we investigate the spatial evolutionary public goods game (SEPGG) on double-layered random networks (DRN). Based on the mean-field type arguments and numerical simulations, we find that SEPGG on DRN shows very rich interesting phenomena, especially, depending on the size of each layer, intra-connectivity, and inter-connected couplings, the network reciprocity of SEPGG on DRN can be drastically enhanced through the inter-connected coupling. Furthermore, SEPGG on DRN can provide a more general framework which includes the evolutionary dynamics on multiplex networks and inter-connected networks at the same time.

Reciprocity in spatial evolutionary public goods game on double-layered network

PubMed Central

Kim, Jinho; Yook, Soon-Hyung; Kim, Yup

2016-01-01

Spatial evolutionary games have mainly been studied on a single, isolated network. However, in real world systems, many interaction topologies are not isolated but many different types of networks are inter-connected to each other. In this study, we investigate the spatial evolutionary public goods game (SEPGG) on double-layered random networks (DRN). Based on the mean-field type arguments and numerical simulations, we find that SEPGG on DRN shows very rich interesting phenomena, especially, depending on the size of each layer, intra-connectivity, and inter-connected couplings, the network reciprocity of SEPGG on DRN can be drastically enhanced through the inter-connected coupling. Furthermore, SEPGG on DRN can provide a more general framework which includes the evolutionary dynamics on multiplex networks and inter-connected networks at the same time. PMID:27503801

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

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

NASA Astrophysics Data System (ADS)

Farhat, Hamidullah; Punjabi, Alkesh; Ali, Halima

2006-10-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2016-07-01

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

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

PubMed

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

2017-07-27

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

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.

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

PubMed

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

2015-10-01

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

Designing of Timber Bolt Connection Subjected To Double Unequal Shears

NASA Astrophysics Data System (ADS)

Musilek, Josef; Plachy, Jan

2017-10-01

The paper deals with load-carrying capacity of bolted connections subjected to unequal double shear with thin plates as outer members and inner timber member. This type of connection is usually widespread and in building support structures made of wood is commonly used. This may occur for example in skeletal structures which contain structural elements based on wood, but also for smaller wooden buildings. Specifically, this type of connection can be found in ceiling structures in the joint joists and beams. If one joist greater margin than the second, bringing the load on the side of the joists of a larger span greater loads than on the side with a smaller span joist. Structure engineer, who is designing such a connection, must use for the design of the connection design procedures and formulas from which he or she calculates the design resistance in order to carry out further assessment of the reliability of the connection in the ultimate limit state. The load-carrying capacity of this connections type can be calculated at present according to Johansen’s equations, which are also contained in present European standard for the design timber structures -Eurocode 5. These Johansen’s equations assume that the loads which act on the outer plates are equal. For this reason, the structure engineer is often forced to use formulas intended for the timber bolt connection subjected to double equal shear and he or she must find ways how to use them although the formulas are not suitable. This paper deals with the case, when the loads acting on the outer plates are unequal.

False Position, Double False Position and Cramer's Rule

ERIC Educational Resources Information Center

Boman, Eugene

2009-01-01

We state and prove the methods of False Position (Regula Falsa) and Double False Position (Regula Duorum Falsorum). The history of both is traced from ancient Egypt and China through the work of Fibonacci, ending with a connection between Double False Position and Cramer's Rule.

Clinical Comparison of Full and Partial Double Pedicle Flaps with Connective Tissue Grafts for Treatment of Gingival Recession

PubMed Central

Ranjbari, Ardeshir; Gholami, Gholam Ali; Amid, Reza; Kadkhodazadeh, Mahdi; Youssefi, Navid; Mehdizadeh, Amir Reza; Aghaloo, Maryam

2016-01-01

Statement of the Problem Gingival recession has been considered as the most challenging issue in the field of periodontal plastic surgery. Purpose The purpose of this study was to evaluate the clinical efficacy of root coverage procedures by using partial thickness double pedicle graft and compare it with full thickness double pedicle graft. Materials and Method Eight patients, aged 15 to 58 years including 6 females and 2 males with 20 paired (mirror image) defects with class I and II gingival recession were randomly assigned into two groups. Clinical parameters such as recession depth, recession width, clinical attachment level, probing depth, and width of keratinized tissue were measured at the baseline and 6 months post-surgery. A mucosal double papillary flap was elevated and the respective root was thoroughly planed. The connective tissue graft was harvested from the palate, and then adapted over the root. The pedicle flap was secured over the connective tissue graft and sutured. The surgical technique was similar in the control group except for the prepared double pedicle graft which was full thickness. Results The mean root coverage was 88.14% (2.83 mm) in the test group and 85.7% (2.75 mm) in the control group. No statistical differences were found in the mean reduction of vertical recession, width of recession, or probing depth between the test and control groups. In both procedures, the width of keratinized tissue increased after three months and the difference between the two groups was not statistically significant in this respect. Conclusion Connective tissue with partial and full thickness double pedicle grafts can be successfully used for treatment of marginal gingival recession. PMID:27602394

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.

PubMed

Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa

2010-12-28

Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival

PubMed Central

Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa

2010-01-01

Cilia function as cell sensors in many organs, and their disorders are referred to as “ciliopathies.” Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors. PMID:21148103

Steel shear strength of anchors with stand-off base plates.

DOT National Transportation Integrated Search

2013-09-01

Sign and signal structures are often connected to concrete foundations through a stand-off annular base plate with a double-nut anchor bolt connection, which leaves exposed anchor bolt lengths below leveling nuts used in these connections. Cantilever...

Astrocytes refine cortical connectivity at dendritic spines

PubMed Central

Risher, W Christopher; Patel, Sagar; Kim, Il Hwan; Uezu, Akiyoshi; Bhagat, Srishti; Wilton, Daniel K; Pilaz, Louis-Jan; Singh Alvarado, Jonnathan; Calhan, Osman Y; Silver, Debra L; Stevens, Beth; Calakos, Nicole; Soderling, Scott H; Eroglu, Cagla

2014-01-01

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines. DOI: http://dx.doi.org/10.7554/eLife.04047.001 PMID:25517933

Passive Localization of Underwater Acoustic Beacons

DTIC Science & Technology

1993-09-01

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

Sound transmission of cavity walls due to structure borne transmission via point and line connections.

PubMed

Davy, John L

2012-08-01

The author has published equations for predicting the air borne sound transmission of double leaf cavity walls due to the structure borne sound transmission across the air cavity via (possibly resilient) line connections, but has never published the full derivation of these equations. The author also derived equations for the case when the connections are rigid point connections but has never used them or published them or their derivations. This paper will present the full derivation of the author's theory of the air borne sound transmission of double leaf cavity walls due to the structure borne sound transmission across the air cavity via point or line connections which are modeled as four pole networks. The theoretical results will be compared with experimental results on wooden stud cavity walls from the National Research Council of Canada because the screw spacing is given for these results. This enables connections via studs and screws to be modeled as point connections and avoids the need to make any assumptions about the compliance of the equivalent point or line connections.

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

PubMed

Mayhew, Terry M; Lucocq, John M

2011-03-01

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

Scaling of Average Weighted Receiving Time on Double-Weighted Koch Networks

NASA Astrophysics Data System (ADS)

Dai, Meifeng; Ye, Dandan; Hou, Jie; Li, Xingyi

2015-03-01

In this paper, we introduce a model of the double-weighted Koch networks based on actual road networks depending on the two weight factors w,r ∈ (0, 1]. The double weights represent the capacity-flowing weight and the cost-traveling weight, respectively. Denote by wFij the capacity-flowing weight connecting the nodes i and j, and denote by wCij the cost-traveling weight connecting the nodes i and j. Let wFij be related to the weight factor w, and let wCij be related to the weight factor r. This paper assumes that the walker, at each step, starting from its current node, moves to any of its neighbors with probability proportional to the capacity-flowing weight of edge linking them. The weighted time for two adjacency nodes is the cost-traveling weight connecting the two nodes. We define the average weighted receiving time (AWRT) on the double-weighted Koch networks. The obtained result displays that in the large network, the AWRT grows as power-law function of the network order with the exponent, represented by θ(w,r) = ½ log2(1 + 3wr). We show that the AWRT exhibits a sublinear or linear dependence on network order. Thus, the double-weighted Koch networks are more efficient than classic Koch networks in receiving information.

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

PubMed

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

2017-06-01

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

Exploring growth-defence trade-offs in Arabidopsis: phytochrome B inactivation requires JAZ10 to suppress plant immunity but not to trigger shade-avoidance responses.

PubMed

Cerrudo, Ignacio; Caliri-Ortiz, M Emilia; Keller, Mercedes M; Degano, M Eugenia; Demkura, Patricia V; Ballaré, Carlos L

2017-05-01

Under conditions that involve a high risk of competition for light among neighbouring plants, shade-intolerant species often display increased shoot elongation and greater susceptibility to pathogens and herbivores. The functional links between morphological and defence responses to crowding are not well understood. In Arabidopsis, the protein JAZ10 is thought to play a key role connecting the inactivation of the photoreceptor phytochrome B (phyB), which takes place under competition for light, with the repression of jasmonate-mediated plant defences. Here, we show that a null mutation of the JAZ10 gene in Arabidopsis did not affect plant growth nor did it suppress the shade-avoidance responses elicited by phyB inactivation. However, the jaz10 mutation restored many of the defence traits that are missing in the phyB mutant, including the ability to express robust responses to jasmonate and to accumulate indolic glucosinolates. Furthermore, the jaz10phyB double mutant showed a significantly increased resistance to the pathogenic fungus Botrytis cinerea compared with the phyB parental line. Our results demonstrate that, by inactivating JAZ10, it is possible to partially uncouple shade avoidance from defence suppression in Arabidopsis. These findings may provide clues to improve plant resistance to pathogens in crops that are planted at high density. © 2016 John Wiley & Sons Ltd.

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

PubMed Central

Siller, Saul S.; Broadie, Kendal

2011-01-01

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

Fatigue Failure of External Hexagon Connections on Cemented Implant-Supported Crowns.

PubMed

Malta Barbosa, João; Navarro da Rocha, Daniel; Hirata, Ronaldo; Freitas, Gileade; Bonfante, Estevam A; Coelho, Paulo G

2018-01-17

To evaluate the probability of survival and failure modes of different external hexagon connection systems restored with anterior cement-retained single-unit crowns. The postulated null hypothesis was that there would be no differences under accelerated life testing. Fifty-four external hexagon dental implants (∼4 mm diameter) were used for single cement-retained crown replacement and divided into 3 groups: (3i) Full OSSEOTITE, Biomet 3i (n = 18); (OL) OEX P4, Osseolife Implants (n = 18); and (IL) Unihex, Intra-Lock International (n = 18). Abutments were torqued to the implants, and maxillary central incisor crowns were cemented and subjected to step-stress-accelerated life testing in water. Use-level probability Weibull curves and probability of survival for a mission of 100,000 cycles at 200 N (95% 2-sided confidence intervals) were calculated. Stereo and scanning electron microscopes were used for failure inspection. The beta values for 3i, OL, and IL (1.60, 1.69, and 1.23, respectively) indicated that fatigue accelerated the failure of the 3 groups. Reliability for the 3i and OL (41% and 68%, respectively) was not different between each other, but both were significantly lower than IL group (98%). Abutment screw fracture was the failure mode consistently observed in all groups. Because the reliability was significantly different between the 3 groups, our postulated null hypothesis was rejected.

The Double in Quest to Save the Protagonist

ERIC Educational Resources Information Center

Maleska, Kalina

2015-01-01

This essay explores the theme of the double in Umberto Eco's "The Island of the Day Before," Joseph Conrad's "The Secret Sharer" and Zivko Chingo's "The Big Water." While traditionally the double is connected with the evil alter-ego of the protagonist, what brings these three works together (by an Italian, English and…

Double muscling in cattle due to mutations in the myostatin gene

PubMed Central

McPherron, Alexandra C.; Lee, Se-Jin

1997-01-01

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

[Double fertilization in flowering plants: 1898-2008].

PubMed

Kordium, E L

2008-01-01

A short review of the results of investigations in the field of plant embryology in vivo and in vitro which are directly connected with the discovery of double fertilization in flowering plants by S.G. Navashin is presented. These results have been obtained by using the methods of electron and fluorescence microscopy, cytophotometry, cultures of isolated ovules, sperms, eggs, and embryo sac central cells. The question on an origin of the female gametophyte of flowering plants, double fertilization, and endosperm are discussed. It is emphasized that the progress in this field is connected mostly with the study of molecular processes which control the development and functioning of a female gametophyte and sporophyte at the early stages of ontogenesis.

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

PubMed

Holsclaw, Julie Korda; Sekelsky, Jeff

2017-05-01

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

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

PubMed

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

2018-04-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-01

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

Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic beta-cells.

PubMed

Hatanaka, Masayuki; Tanabe, Katsuya; Yanai, Akie; Ohta, Yasuharu; Kondo, Manabu; Akiyama, Masaru; Shinoda, Koh; Oka, Yoshitomo; Tanizawa, Yukio

2011-04-01

Wolfram syndrome is an autosomal recessive disorder characterized by juvenile-onset insulin-dependent diabetes mellitus and optic atrophy. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER) resident transmembrane protein. The Wfs1-null mouse exhibits progressive insulin deficiency causing diabetes. Previous work suggested that the function of the WFS1 protein is connected to unfolded protein response and to intracellular Ca(2+) homeostasis. However, its precise molecular function in pancreatic β-cells remains elusive. In our present study, immunofluorescent and electron-microscopic analyses revealed that WFS1 localizes not only to ER but also to secretory granules in pancreatic β-cells. Intragranular acidification was assessed by measuring intracellular fluorescence intensity raised by the acidotrophic agent, 3-[2,4-dinitroanilino]-3'-amino-N-methyldipropyramine. Compared with wild-type β-cells, there was a 32% reduction in the intensity in WFS1-deficient β-cells, indicating the impairment of granular acidification. This phenotype may, at least partly, account for the evidence that Wfs1-null islets have impaired proinsulin processing, resulting in an increased circulating proinsulin level. Morphometric analysis using electron microscopy evidenced that the density of secretory granules attached to the plasma membrane was significantly reduced in Wfs1-null β-cells relative to that in wild-type β-cells. This may be relevant to the recent finding that granular acidification is required for the priming of secretory granules preceding exocytosis and may partly explain the fact that glucose-induced insulin secretion is profoundly impaired in young prediabetic Wfs1-null mice. These results thus provide new insights into the molecular mechanisms of β-cell dysfunction in patients with Wolfram syndrome.

Autism-Relevant Social Abnormalities and Cognitive Deficits in Engrailed-2 Knockout Mice

PubMed Central

Brielmaier, Jennifer; Matteson, Paul G.; Silverman, Jill L.; Senerth, Julia M.; Kelly, Samantha; Genestine, Matthieu; Millonig, James H.

2012-01-01

ENGRAILED 2 (En2), a homeobox transcription factor, functions as a patterning gene in the early development and connectivity of rodent hindbrain and cerebellum, and regulates neurogenesis and development of monoaminergic pathways. To further understand the neurobiological functions of En2, we conducted neuroanatomical expression profiling of En2 wildtype mice. RTQPCR assays demonstrated that En2 is expressed in adult brain structures including the somatosensory cortex, hippocampus, striatum, thalamus, hypothalamus and brainstem. Human genetic studies indicate that EN2 is associated with autism. To determine the consequences of En2 mutations on mouse behaviors, including outcomes potentially relevant to autism, we conducted comprehensive phenotyping of social, communication, repetitive, and cognitive behaviors. En2 null mutants exhibited robust deficits in reciprocal social interactions as juveniles and adults, and absence of sociability in adults, replicated in two independent cohorts. Fear conditioning and water maze learning were impaired in En2 null mutants. High immobility in the forced swim test, reduced prepulse inhibition, mild motor coordination impairments and reduced grip strength were detected in En2 null mutants. No genotype differences were found on measures of ultrasonic vocalizations in social contexts, and no stereotyped or repetitive behaviors were observed. Developmental milestones, general health, olfactory abilities, exploratory locomotor activity, anxiety-like behaviors and pain responses did not differ across genotypes, indicating that the behavioral abnormalities detected in En2 null mutants were not attributable to physical or procedural confounds. Our findings provide new insight into the role of En2 in complex behaviors and suggest that disturbances in En2 signaling may contribute to neuropsychiatric disorders marked by social and cognitive deficits, including autism spectrum disorders. PMID:22829897

Redox crisis underlies conditional light–dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA

PubMed Central

Diamond, Spencer; Rubin, Benjamin E.; Shultzaberger, Ryan K.; Chen, You; Barber, Chase D.; Golden, Susan S.

2017-01-01

Cyanobacteria evolved a robust circadian clock, which has a profound influence on fitness and metabolism under daily light–dark (LD) cycles. In the model cyanobacterium Synechococcus elongatus PCC 7942, a functional clock is not required for diurnal growth, but mutants defective for the response regulator that mediates transcriptional rhythms in the wild-type, regulator of phycobilisome association A (RpaA), cannot be cultured under LD conditions. We found that rpaA-null mutants are inviable after several hours in the dark and compared the metabolomes of wild-type and rpaA-null strains to identify the source of lethality. Here, we show that the wild-type metabolome is very stable throughout the night, and this stability is lost in the absence of RpaA. Additionally, an rpaA mutant accumulates excessive reactive oxygen species (ROS) during the day and is unable to clear it during the night. The rpaA-null metabolome indicates that these cells are reductant-starved in the dark, likely because enzymes of the primary nighttime NADPH-producing pathway are direct targets of RpaA. Because NADPH is required for processes that detoxify ROS, conditional LD lethality likely results from inability of the mutant to activate reductant-requiring pathways that detoxify ROS when photosynthesis is not active. We identified second-site mutations and growth conditions that suppress LD lethality in the mutant background that support these conclusions. These results provide a mechanistic explanation as to why rpaA-null mutants die in the dark, further connect the clock to metabolism under diurnal growth, and indicate that RpaA likely has important unidentified functions during the day. PMID:28074036

The ultraviolet variations of iota Cas

NASA Technical Reports Server (NTRS)

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

1976-01-01

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

The research of full automatic oil filtering control technology of high voltage insulating oil

NASA Astrophysics Data System (ADS)

Gong, Gangjun; Zhang, Tong; Yan, Guozeng; Zhang, Han; Chen, Zhimin; Su, Chang

2017-09-01

In this paper, the design scheme of automatic oil filter control system for transformer oil in UHV substation is summarized. The scheme specifically includes the typical double tank filter connection control method of the transformer oil of the UHV substation, which distinguishes the single port and the double port connection structure of the oil tank. Finally, the design scheme of the temperature sensor and respirator is given in detail, and the detailed evaluation and application scenarios are given for reference.

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.

Replicability of time-varying connectivity patterns in large resting state fMRI samples.

PubMed

Abrol, Anees; Damaraju, Eswar; Miller, Robyn L; Stephen, Julia M; Claus, Eric D; Mayer, Andrew R; Calhoun, Vince D

2017-12-01

The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain's inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Replicability of time-varying connectivity patterns in large resting state fMRI samples

PubMed Central

Abrol, Anees; Damaraju, Eswar; Miller, Robyn L.; Stephen, Julia M.; Claus, Eric D.; Mayer, Andrew R.; Calhoun, Vince D.

2018-01-01

The past few years have seen an emergence of approaches that leverage temporal changes in whole-brain patterns of functional connectivity (the chronnectome). In this chronnectome study, we investigate the replicability of the human brain’s inter-regional coupling dynamics during rest by evaluating two different dynamic functional network connectivity (dFNC) analysis frameworks using 7 500 functional magnetic resonance imaging (fMRI) datasets. To quantify the extent to which the emergent functional connectivity (FC) patterns are reproducible, we characterize the temporal dynamics by deriving several summary measures across multiple large, independent age-matched samples. Reproducibility was demonstrated through the existence of basic connectivity patterns (FC states) amidst an ensemble of inter-regional connections. Furthermore, application of the methods to conservatively configured (statistically stationary, linear and Gaussian) surrogate datasets revealed that some of the studied state summary measures were indeed statistically significant and also suggested that this class of null model did not explain the fMRI data fully. This extensive testing of reproducibility of similarity statistics also suggests that the estimated FC states are robust against variation in data quality, analysis, grouping, and decomposition methods. We conclude that future investigations probing the functional and neurophysiological relevance of time-varying connectivity assume critical importance. PMID:28916181

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

PubMed Central

2015-01-01

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

Double strand breaks may be a missing link between entropy and aging.

PubMed

Lenart, Peter; Bienertová-Vašků, Julie

2016-07-01

It has been previously suggested that an increase in entropy production leads to aging. However, the mechanisms linking increased entropy production in living mass to aging are currently unclear. Even though entropy cannot be easily associated with any specific molecular damage, the increase of entropy in structural mass may be connected with heat stress, which is known to generate double strand breaks. Double strand breaks, which are in turn known to play an important role in process of aging, are thus connected to both aging and an increase of entropy. In view of these associations, we propose a new model where the increase of entropy leads to the formation of double strand breaks, resulting in an aging phenotype. This not only offers a new perspective on aging research and facilitates experimental validation, but could also serve as a useful explanatory tool. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2002-02-01

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

Flatspace chiral supergravity

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

Maintaining Limited-Range Connectivity Among Second-Order Agents

DTIC Science & Technology

2016-07-07

we consider ad-hoc networks of robotic agents with double integrator dynamics. For such networks, the connectivity maintenance problems are: (i) do...hoc networks of mobile autonomous agents. This loose ter- minology refers to groups of robotic agents with limited mobility and communica- tion...connectivity can be preserved. 3.1. Networks of robotic agents with second-order dynamics and the connectivity maintenance problem. We begin by

Quantifying three dimensional reconnection in fragmented current layers

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

Wyper, P. F., E-mail: peter.f.wyper@nasa.gov; Hesse, M., E-mail: michael.hesse-1@nasa.gov

There is growing evidence that when magnetic reconnection occurs in high Lundquist number plasmas such as in the Solar Corona or the Earth's Magnetosphere it does so within a fragmented, rather than a smooth current layer. Within the extent of these fragmented current regions, the associated magnetic flux transfer and energy release occur simultaneously in many different places. This investigation focusses on how best to quantify the rate at which reconnection occurs in such layers. An analytical theory is developed which describes the manner in which new connections form within fragmented current layers in the absence of magnetic nulls. Itmore » is shown that the collective rate at which new connections form can be characterized by two measures; a total rate which measures the true rate at which new connections are formed and a net rate which measures the net change of connection associated with the largest value of the integral of E{sub ||} through all of the non-ideal regions. Two simple analytical models are presented which demonstrate how each should be applied and what they quantify.« less

Bias stress instability of double-gate a-IGZO TFTs on polyimide substrate

NASA Astrophysics Data System (ADS)

Cho, Won-Ju; Ahn, Min-Ju

2017-09-01

In this study, flexible double-gate thin-film transistor (TFT)-based amorphous indium-galliumzinc- oxide (a-IGZO) was fabricated on a polyimide substrate. Double-gate operation with connected front and back gates was compared with a single-gate operation. As a result, the double-gate a- IGZO TFT exhibited enhanced electrical characteristics as well as improved long-term reliability. Under positive- and negative-bias temperature stress, the threshold voltage shift of the double-gate operation was much smaller than that of the single-gate operation.

Functional Neuroanatomical Evidence for the Double-Deficit Hypothesis of Developmental Dyslexia

PubMed Central

Norton, Elizabeth S.; Black, Jessica M.; Stanley, Leanne M.; Tanaka, Hiroko; Gabrieli, John D. E.; Sawyer, Carolyn; Hoeft, Fumiko

2015-01-01

The double-deficit hypothesis of dyslexia posits that both rapid naming and phonological impairments can cause reading difficulties, and that individuals who have both of these deficits show greater reading impairments compared to those with a single deficit. Despite extensive behavioral research, the brain basis of poor reading with a double-deficit has never been investigated. The goal of the study was to evaluate the double-deficit hypothesis using functional MRI. Activation patterns during a printed word rhyme judgment task in 90 children with a wide range of reading abilities showed dissociation between brain regions that were sensitive to phonological awareness (left inferior frontal and inferior parietal regions) and rapid naming (right cerebellar lobule VI). More specifically, the double-deficit group showed less activation in the fronto-parietal reading network compared to children with only a deficit in phonological awareness, who in turn showed less activation than the typically-reading group. On the other hand, the double-deficit group showed less cerebellar activation compared to children with only a rapid naming deficit, who in turn showed less activation than the typically-reading children. Functional connectivity analyses revealed that bilateral prefrontal regions were key for linking brain regions associated with phonological awareness and rapid naming, with the double-deficit group being the most aberrant in their connectivity. Our study provides the first functional neuroanatomical evidence for the double-deficit hypothesis of developmental dyslexia. PMID:24953957

Computational architecture of the yeast regulatory network

NASA Astrophysics Data System (ADS)

Maslov, Sergei; Sneppen, Kim

2005-12-01

The topology of regulatory networks contains clues to their overall design principles and evolutionary history. We find that while in- and out-degrees of a given protein in the regulatory network are not correlated with each other, there exists a strong negative correlation between the out-degree of a regulatory protein and in-degrees of its targets. Such correlation positions large regulatory modules on the periphery of the network and makes them rather well separated from each other. We also address the question of relative importance of different classes of proteins quantified by the lethality of null-mutants lacking one of them as well as by the level of their evolutionary conservation. It was found that in the yeast regulatory network highly connected proteins are in fact less important than their low-connected counterparts.

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

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

PubMed

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

2015-09-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-07-01

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

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

PubMed

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

2017-05-01

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

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

PubMed

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

2002-12-01

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

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

PubMed

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

2013-04-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

1997-01-01

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

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

PubMed Central

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

2016-01-01

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

A Novel Study Connecting Ultra-High Energy Cosmic Rays, Neutrinos, and Gamma-Rays

NASA Astrophysics Data System (ADS)

Coenders, Stefan; Resconi, Elisa; Padovani, Paolo; Giommi, Paolo; Caccianiga, Lorenzo

We present a novel study connecting ultra-high energy cosmic rays, neutrinos, and gamma-rays with the objective to identify common counterparts of the three astrophysical messengers. In the test presented here, we first identify potential hadronic sources by filtering gamma-ray emitters that are in spatial coincidence with IceCube neutrinos. Subsequently, these objects are correlated against ultra-high energy cosmic rays detected by the Pierre Auger Observatory and the Telescope Array, scanning in gamma-ray flux and angular separation between sources and cosmic rays. A maximal excess of 80 cosmic rays (41.9 expected) is observed for the second catalog of hard Fermi-LAT objects of blazars of the high synchrotron peak type. This corresponds to a deviation from the null-hypothesis of 2.94σ . No excess is observed for objects not in spatial connection with neutrinos. The gamma-ray sources that make up the excess are blazars of the high synchrotron peak type.

Multilayer networks reveal the spatial structure of seed-dispersal interactions across the Great Rift landscapes.

PubMed

Timóteo, Sérgio; Correia, Marta; Rodríguez-Echeverría, Susana; Freitas, Helena; Heleno, Ruben

2018-01-10

Species interaction networks are traditionally explored as discrete entities with well-defined spatial borders, an oversimplification likely impairing their applicability. Using a multilayer network approach, explicitly accounting for inter-habitat connectivity, we investigate the spatial structure of seed-dispersal networks across the Gorongosa National Park, Mozambique. We show that the overall seed-dispersal network is composed by spatially explicit communities of dispersers spanning across habitats, functionally linking the landscape mosaic. Inter-habitat connectivity determines spatial structure, which cannot be accurately described with standard monolayer approaches either splitting or merging habitats. Multilayer modularity cannot be predicted by null models randomizing either interactions within each habitat or those linking habitats; however, as habitat connectivity increases, random processes become more important for overall structure. The importance of dispersers for the overall network structure is captured by multilayer versatility but not by standard metrics. Highly versatile species disperse many plant species across multiple habitats, being critical to landscape functional cohesion.

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

PubMed Central

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

2016-01-01

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

The Asymmetric Continental Shelf Wave in Response to the Synoptic Wind Burst in a Semienclosed Double-Shelf Basin

NASA Astrophysics Data System (ADS)

Qu, Lixin; Lin, Xiaopei; Hetland, Robert D.; Guo, Jingsong

2018-01-01

The primary goal of this study is to investigate the asymmetric structure of continental shelf wave in a semienclosed double-shelf basin, such as the Yellow Sea. Supported by in situ observations and realistic numerical simulations, it is found that in the Yellow Sea, the shelf wave response to the synoptic wind forcing does not match the mathematically symmetric solution of classic double-shelf wave theory, but rather exhibits a westward shift. To study the formation mechanism of this asymmetric structure, an idealized model was used and two sets of experiments were conducted. The results confirm that the asymmetric structure is due to the existence of a topographic waveguide connecting both shelves. For a semienclosed basin, such as the Yellow Sea, a connection at the end of the basin eliminates the potential vorticity barrier between the two shelves and hence plays a role as a connecting waveguide for shelf waves. This waveguide enables the shelf wave to propagate from one shelf to the other shelf and produces the asymmetric response in sea level and upwind flow evolutions.

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

PubMed

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

2017-03-01

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

Live Imaging of Type I Collagen Assembly Dynamics in Osteoblasts Stably Expressing GFP and mCherry-Tagged Collagen Constructs.

PubMed

Lu, Yongbo; Kamel-El Sayed, Suzan A; Wang, Kun; Tiede-Lewis, LeAnn M; Grillo, Michael A; Veno, Patricia A; Dusevich, Vladimir; Phillips, Charlotte L; Bonewald, Lynda F; Dallas, Sarah L

2018-06-01

Type I collagen is the most abundant extracellular matrix protein in bone and other connective tissues and plays key roles in normal and pathological bone formation as well as in connective tissue disorders and fibrosis. Although much is known about the collagen biosynthetic pathway and its regulatory steps, the mechanisms by which it is assembled extracellularly are less clear. We have generated GFPtpz and mCherry-tagged collagen fusion constructs for live imaging of type I collagen assembly by replacing the α2(I)-procollagen N-terminal propeptide with GFPtpz or mCherry. These novel imaging probes were stably transfected into MLO-A5 osteoblast-like cells and fibronectin-null mouse embryonic fibroblasts (FN-null-MEFs) and used for imaging type I collagen assembly dynamics and its dependence on fibronectin. Both fusion proteins co-precipitated with α1(I)-collagen and remained intracellular without ascorbate but were assembled into α1(I) collagen-containing extracellular fibrils in the presence of ascorbate. Immunogold-EM confirmed their ultrastuctural localization in banded collagen fibrils. Live cell imaging in stably transfected MLO-A5 cells revealed the highly dynamic nature of collagen assembly and showed that during assembly the fibril networks are continually stretched and contracted due to the underlying cell motion. We also observed that cell-generated forces can physically reshape the collagen fibrils. Using co-cultures of mCherry- and GFPtpz-collagen expressing cells, we show that multiple cells contribute collagen to form collagen fiber bundles. Immuno-EM further showed that individual collagen fibrils can receive contributions of collagen from more than one cell. Live cell imaging in FN-null-MEFs expressing GFPtpz-collagen showed that collagen assembly was both dependent upon and dynamically integrated with fibronectin assembly. These GFP-collagen fusion constructs provide a powerful tool for imaging collagen in living cells and have revealed novel and fundamental insights into the dynamic mechanisms for the extracellular assembly of collagen. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

Thermal performance of a customized multilayer insulation (MLI)

NASA Technical Reports Server (NTRS)

Leonhard, K. E.

1976-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2008-06-01

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

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

DOE PAGES

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

2016-12-24

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

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

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

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

2015-12-13

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

Magnetopause Transects

NASA Technical Reports Server (NTRS)

Sonnerup, B. U. O; Guo, M.

1996-01-01

A novel method is described for reconstruction of two-dimensional current-layer structures from measurements taken by a single spacecraft traversing the layer. In its present form, the method is applicable only to 2D magnetohydrostatic structures that are passively convected past the observing spacecraft. It is tested on a magnetopause crossing of the tangential-discontinuity type by the spacecraft AMPTE/IRM. The magnetic structures recovered include a magnetic island located between two X-type nulls as well as a magnetic 'worm hole' through which a bundle of weak magnetic flux appears to connect the magnetosphere and the magnetosheath.

Magnetopause transects

NASA Astrophysics Data System (ADS)

Sonnerup, B. U. Ö.; Guo, M.

A novel method is described for reconstruction of two-dimensional current-layer structures from measurements taken by a single spacecraft traversing the layer. In its present form, the method is applicable only to 2D magneto-hydrostatic structures that are passively convected past the observing spacecraft. It is tested on a magnetopause crossing of the tangential-discontinuity type by the spacecraft AMPTE/IRM. The magnetic structures recovered include a magnetic island located between two X-type nulls as well as a magnetic ‘worm hole’ through which a bundle of weak magnetic flux appears to connect the magnetosphere and the magnetosheath.

Double-dissociation between the mechanism leading to impulsivity and inattention in Attention Deficit Hyperactivity Disorder: A resting-state functional connectivity study.

PubMed

Sanefuji, Masafumi; Craig, Michael; Parlatini, Valeria; Mehta, Mitul A; Murphy, Declan G; Catani, Marco; Cerliani, Leonardo; Thiebaut de Schotten, Michel

2017-01-01

Two core symptoms characterize Attention Deficit Hyperactivity Disorder (ADHD) subtypes: inattentiveness and hyperactivity-impulsivity. While previous brain imaging research investigated ADHD as if it was a homogenous condition, its two core symptoms may originate from different brain mechanisms. We, therefore, hypothesized that the functional connectivity of cortico-striatal and attentional networks would be different between ADHD subtypes. We studied 165 children (mean age 10.93 years; age range, 7-17 year old) diagnosed as having ADHD based on their revised Conner's rating scale score and 170 typical developing individuals (mean age 11.46 years; age range, 7-17 year old) using resting state functional fMRI. Groups were matched for age, IQ and head motion during the MRI acquisition. We fractionated the ADHD group into predominantly inattentive, hyperactive-impulsive and combined subtypes based on their revised Conner's rating scale score. We then analyzed differences in resting state functional connectivity of the cortico-striatal and attentional networks between these subtypes. We found a double dissociation of functional connectivity in the cortico-striatal and ventral attentional networks, reflecting the subtypes of the ADHD participants. Particularly, the hyperactive-impulsive subtype was associated with increased connectivity in cortico-striatal network, whereas the inattentive subtype was associated with increased connectivity in the right ventral attention network. Our study demonstrated for the first time a right lateralized, double dissociation between specific networks associated with hyperactivity-impulsivity and inattentiveness in ADHD children, providing a biological basis for exploring symptom dimensions and revealing potential targets for more personalized treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

General Theory of the Double Fed Synchronous Machine. Ph.D. Thesis - Swiss Technological Univ., 1950

NASA Technical Reports Server (NTRS)

El-Magrabi, M. G.

1982-01-01

Motor and generator operation of a double-fed synchronous machine were studied and physically and mathematically treated. Experiments with different connections, voltages, etc. were carried out. It was concluded that a certain degree of asymmetry is necessary for the best utilization of the machine.

Steel shear strength of anchors with stand-off base plates : [technical summary].

DOT National Transportation Integrated Search

2013-09-01

Sign and signal structures are often connected : to concrete foundations through an annular base : plate set on anchor bolts. The plate is leveled : with nuts beneath it and secured with nuts : above it a double-nut connection. In many : in...

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.

A review of thermoregulation and physiological performance in reptiles: what is the role of phenotypic flexibility?

PubMed

Seebacher, Frank

2005-10-01

Biological functions are dependent on the temperature of the organism. Animals may respond to fluctuation in the thermal environment by regulating their body temperature and by modifying physiological and biochemical rates. Phenotypic flexibility (reversible phenotypic plasticity, acclimation, or acclimatisation in rate functions occurs in all major taxonomic groups and may be considered as an ancestral condition. Within the Reptilia, representatives from all major groups show phenotypic flexibility in response to long-term or chronic changes in the thermal environment. Acclimation or acclimatisation in reptiles are most commonly assessed by measuring whole animal responses such as oxygen consumption, but whole animal responses are comprised of variation in individual traits such as enzyme activities, hormone expression, and cardiovascular functions. The challenge now lies in connecting the changes in the components to the functioning of the whole animal and its fitness. Experimental designs in research on reptilian thermal physiology should incorporate the capacity for reversible phenotypic plasticity as a null-hypothesis, because the significance of differential body temperature-performance relationships (thermal reaction norms) between individuals, populations, or species cannot be assessed without testing that null-hypothesis.

Total cavo-pulmonary connection without foreign material for asplenic heart associated with partial anomalous pulmonary venous connection.

PubMed

Agematsu, Kouta; Naito, Yuji; Aoki, Mitsuru; Fujiwara, Tadashi

2008-04-01

The presented case was a 3-year-old boy diagnosed with asplenia (SLL), double outlet right ventricle, pulmonary stenosis, atrioventricular septal defect, hypoplastic left ventricle and partial anomalous pulmonary venous connection to the superior vena cava. Partial anomalous pulmonary venous connection was repaired by translocation of pulmonary artery to avoid pulmonary venous obstruction when Glenn anastomosis was performed. Total cavo-pulmonary connection was established by re-routing the inferior vena cava to pulmonary artery using the atrial septal remnant and the left atrium free wall flap.

Resolving anatomical and functional structure in human brain organization: identifying mesoscale organization in weighted network representations.

PubMed

Lohse, Christian; Bassett, Danielle S; Lim, Kelvin O; Carlson, Jean M

2014-10-01

Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease.

Landscape genetics of a pollinator longhorn beetle [Typocerus v. velutinus (Olivier)] on a continuous habitat surface.

PubMed

Abdel Moniem, H E M; Schemerhorn, B J; DeWoody, J A; Holland, J D

2016-10-01

Landscape connectivity, the degree to which the landscape structure facilitates or impedes organismal movement and gene flow, is increasingly important to conservationists and land managers. Metrics for describing the undulating shape of continuous habitat surfaces can expand the usefulness of continuous gradient surfaces that describe habitat and predict the flow of organisms and genes. We adopted a landscape gradient model of habitat and used surface metrics of connectivity to model the genetic continuity between populations of the banded longhorn beetle [Typocerus v. velutinus (Olivier)] collected at 17 sites across a fragmentation gradient in Indiana, USA. We tested the hypothesis that greater habitat connectivity facilitates gene flow between beetle populations against a null model of isolation by distance (IBD). We used next-generation sequencing to develop 10 polymorphic microsatellite loci and genotype the individual beetles to assess the population genetic structure. Isolation by distance did not explain the population genetic structure. The surface metrics model of habitat connectivity explained the variance in genetic dissimilarities 30 times better than the IBD model. We conclude that surface metrology of habitat maps is a powerful extension of landscape genetics in heterogeneous landscapes. © 2016 John Wiley & Sons Ltd.

Habitat connectivity and in-stream vegetation control temporal variability of benthic invertebrate communities.

PubMed

Huttunen, K-L; Mykrä, H; Oksanen, J; Astorga, A; Paavola, R; Muotka, T

2017-05-03

One of the key challenges to understanding patterns of β diversity is to disentangle deterministic patterns from stochastic ones. Stochastic processes may mask the influence of deterministic factors on community dynamics, hindering identification of the mechanisms causing variation in community composition. We studied temporal β diversity (among-year dissimilarity) of macroinvertebrate communities in near-pristine boreal streams across 14 years. To assess whether the observed β diversity deviates from that expected by chance, and to identify processes (deterministic vs. stochastic) through which different explanatory factors affect community variability, we used a null model approach. We observed that at the majority of sites temporal β diversity was low indicating high community stability. When stochastic variation was unaccounted for, connectivity was the only variable explaining temporal β diversity, with weakly connected sites exhibiting higher community variability through time. After accounting for stochastic effects, connectivity lost importance, suggesting that it was related to temporal β diversity via random colonization processes. Instead, β diversity was best explained by in-stream vegetation, community variability decreasing with increasing bryophyte cover. These results highlight the potential of stochastic factors to dampen the influence of deterministic processes, affecting our ability to understand and predict changes in biological communities through time.

On the absence of radio haloes in clusters with double relics

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

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

PubMed

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

2012-05-01

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

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

PubMed

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

2009-01-20

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

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

PubMed

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

2002-06-01

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

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

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

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

2012-01-01

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

System and Method for Null-Lens Wavefront Sensing

NASA Technical Reports Server (NTRS)

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

2015-01-01

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

Adaptive jammer nulling in EHF communications satellites

NASA Astrophysics Data System (ADS)

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

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

Broken chiral symmetry on a null plane

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

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

2013-10-15

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

Three-dimensionally arrayed and mutually connected 1.2-nm nanopores for high-performance electric double layer capacitor.

PubMed

Itoi, Hiroyuki; Nishihara, Hirotomo; Kogure, Taichi; Kyotani, Takashi

2011-02-09

Zeolite-templated carbon is a promising candidate as an electrode material for constructing an electric double layer capacitor with both high-power and high-energy densities, due to its three-dimensionally arrayed and mutually connected 1.2-nm nanopores. This carbon exhibits both very high gravimetric (140-190 F g(-1)) and volumetric (75-83 F cm(-3)) capacitances in an organic electrolyte solution. Moreover, such a high capacitance can be well retained even at a very high current up to 20 A g(-1). This extraordinary high performance is attributed to the unique pore structure.

Performance characteristics of a nanoscale double-gate reconfigurable array

NASA Astrophysics Data System (ADS)

Beckett, Paul

2008-12-01

The double gate transistor is a promising device applicable to deep sub-micron design due to its inherent resistance to short-channel effects and superior subthreshold performance. Using both TCAD and SPICE circuit simulation, it is shown that the characteristics of fully depleted dual-gate thin-body Schottky barrier silicon transistors will not only uncouple the conflicting requirements of high performance and low standby power in digital logic, but will also allow the development of a locally-connected reconfigurable computing mesh. The magnitude of the threshold shift effect will scale with device dimensions and will remain compatible with oxide reliability constraints. A field-programmable architecture based on the double gate transistor is described in which the operating point of the circuit is biased via one gate while the other gate is used to form the logic array, such that complex heterogeneous computing functions may be developed from this homogeneous, mesh-connected organization.

Generating a Double-Scroll Attractor by Connecting a Pair of Mutual Mirror-Image Attractors via Planar Switching Control

NASA Astrophysics Data System (ADS)

Sun, Changchun; Chen, Zhongtang; Xu, Qicheng

2017-12-01

An original three-dimensional (3D) smooth continuous chaotic system and its mirror-image system with eight common parameters are constructed and a pair of symmetric chaotic attractors can be generated simultaneously. Basic dynamical behaviors of two 3D chaotic systems are investigated respectively. A double-scroll chaotic attractor by connecting the pair of mutual mirror-image attractors is generated via a novel planar switching control approach. Chaos can also be controlled to a fixed point, a periodic orbit and a divergent orbit respectively by switching between two chaotic systems. Finally, an equivalent 3D chaotic system by combining two 3D chaotic systems with a switching law is designed by utilizing a sign function. Two circuit diagrams for realizing the double-scroll attractor are depicted by employing an improved module-based design approach.

29 CFR 1926.951 - Tools and protective equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... falling objects, electric shock, or burns. (b) Personal climbing equipment. (1) Body belts with straps or...) Be equipped with three-wire cord having the ground wire permanently connected to the tool frame and... “Double Insulated”; or (iii) Be connected to the power supply by means of an isolating transformer, or...

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

PubMed

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

2005-07-01

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

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.

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.

New self-magnetically insulated connection of multilevel accelerators to a common load

DOE PAGES

VanDevender, J. Pace; Langston, William L.; Pasik, Michael F.; ...

2015-03-04

A new way to connect pulsed-power modules to a common load is presented. Unlike previous connectors, the clam shell magnetically insulated transmission line (CSMITL) has magnetic nulls only at large radius where the cathode electric field is kept below the threshold for emission, has only a simply connected magnetic topology to avoid plasma motion along magnetic field lines into highly stressed gaps, and has electron injectors that ensure efficient electron flow even in the limiting case of self-limited MITLs. Multilevel magnetically insulated transmission lines with a posthole convolute are the standard solution but associated losses limit the performance of state-of-the-artmore » accelerators. Mitigating these losses is critical for the next generation of pulsed-power accelerators. A CSMITL has been successfully implemented on the Saturn accelerator. A reference design for the Z accelerator is derived and presented. The design conservatively meets the design requirements and shows excellent transport efficiency in three simulations of increasing complexity: circuit simulations, electromagnetic fields only with Emphasis, fields plus electron and ion emission with Quicksilver.« less

Electrophysiological characteristics of the Marshall bundle in humans

PubMed Central

Han, Seongwook; Joung, Boyoung; Scanavacca, Mauricio; Sosa, Eduardo; Chen, Peng-Sheng; Hwang, Chun

2010-01-01

BACKGROUND Marshall bundles (MBs) are the muscle bundles within the ligament of Marshall. OBJECTIVE This trial sought to the electrophysiological characteristics of the MB and the anatomical connections between MB and left atrium (LA) in patients with persistent atrial fibrillation (AF). METHODS We enrolled 72 patients (male:female 59:13, age 59.9 ± 9.4 years) who underwent MB mapping and ablation for AF. MB mapping was done via an endocardial or epicardial approach during sinus rhythm and AF. RESULTS Recordings were successful in 64 of 72 patients (89%). A single connection was noted in 11 of 64 patients between the MB and the coronary sinus (CS) muscle sleeves. The MB recordings showed distinct MB potentials with a proximal-to-distal activation pattern during sinus rhythm. During AF, organized passive activations and dissociated slow MB ectopic activities were commonly observed in this type of connection. Double connections to both CS and LA around left pulmonary veins were noted in 23 of 64 patients (36%). After the ablation of the distal connection, MB recording showed typical double potentials as in single connection. Multiple connections were noted in 30 of 64 patients (47%). During sinus rhythm, the earliest activation was in the middle of the MB. The activation patterns were irregular and variable in each patient. During AF, rapid and fractionated complex activations were noted in all patients of this group. CONCLUSION We documented 3 different types of MB–LA connections. Rapid and fractionated activations were most commonly observed in the MB that had multiple LA connections. PMID:20188860

Miniaturization design and implementation of magnetic field coupled RFID antenna

NASA Astrophysics Data System (ADS)

Hu, Tiling

2013-03-01

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

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

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

Chen, Pisin; Yeom, Dong-han

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

Is it really naked? On cosmic censorship in string theory

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

Frolov, Andrei V.

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

Looking for a bulk point

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

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

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

Looking for a bulk point

DOE PAGES

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

2017-01-03

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

Fiction, History and Pedagogy: A Double-Edged Sword

ERIC Educational Resources Information Center

Clark, Penney; Sears, Alan

2017-01-01

There are many areas of overlap between history and fiction. Teachers of history have long recognized this connection and used a range of fictional accounts in their teaching. In this article, we argue that fiction is a double-edged sword that must be handled carefully. On the one hand, it presents compelling characters and accounts that provide…

[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.

The Connection between Employee Basic Skills & Productivity. Workforce & Workplace Literacy Series.

ERIC Educational Resources Information Center

BCEL Brief, 1993

1993-01-01

The experience of a number of specific local workplace programs indicates a definite connection between the provision of employee basic skills programs and increased worker productivity. One Tennessee company, for example, reports a 95 percent drop in costs resulting from worker mistakes and a doubling of worker productivity since the company…

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

ALAM,TODD M.

Monte Carlo simulations of phosphate tetrahedron connectivity distributions in alkali and alkaline earth phosphate glasses are reported. By utilizing a discrete bond model, the distribution of next-nearest neighbor connectivities between phosphate polyhedron for random, alternating and clustering bonding scenarios was evaluated as a function of the relative bond energy difference. The simulated distributions are compared to experimentally observed connectivities reported for solid-state two-dimensional exchange and double-quantum NMR experiments of phosphate glasses. These Monte Carlo simulations demonstrate that the polyhedron connectivity is best described by a random distribution in lithium phosphate and calcium phosphate glasses.

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2009-01-01

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

Structure-Function Network Mapping and Its Assessment via Persistent Homology

PubMed Central

2017-01-01

Understanding the relationship between brain structure and function is a fundamental problem in network neuroscience. This work deals with the general method of structure-function mapping at the whole-brain level. We formulate the problem as a topological mapping of structure-function connectivity via matrix function, and find a stable solution by exploiting a regularization procedure to cope with large matrices. We introduce a novel measure of network similarity based on persistent homology for assessing the quality of the network mapping, which enables a detailed comparison of network topological changes across all possible thresholds, rather than just at a single, arbitrary threshold that may not be optimal. We demonstrate that our approach can uncover the direct and indirect structural paths for predicting functional connectivity, and our network similarity measure outperforms other currently available methods. We systematically validate our approach with (1) a comparison of regularized vs. non-regularized procedures, (2) a null model of the degree-preserving random rewired structural matrix, (3) different network types (binary vs. weighted matrices), and (4) different brain parcellation schemes (low vs. high resolutions). Finally, we evaluate the scalability of our method with relatively large matrices (2514x2514) of structural and functional connectivity obtained from 12 healthy human subjects measured non-invasively while at rest. Our results reveal a nonlinear structure-function relationship, suggesting that the resting-state functional connectivity depends on direct structural connections, as well as relatively parsimonious indirect connections via polysynaptic pathways. PMID:28046127

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

The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity

PubMed Central

Gibson, William S; Cho, Shinho; Abulseoud, Osama A; Gorny, Krzysztof R; Felmlee, Joel P; Welker, Kirk M; Klassen, Bryan T; Min, Hoon-Ki; Lee, Kendall H

2017-01-01

Abstract Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect. PMID:27001680

Constructing networks from a dynamical system perspective for multivariate nonlinear time series.

PubMed

Nakamura, Tomomichi; Tanizawa, Toshihiro; Small, Michael

2016-03-01

We describe a method for constructing networks for multivariate nonlinear time series. We approach the interaction between the various scalar time series from a deterministic dynamical system perspective and provide a generic and algorithmic test for whether the interaction between two measured time series is statistically significant. The method can be applied even when the data exhibit no obvious qualitative similarity: a situation in which the naive method utilizing the cross correlation function directly cannot correctly identify connectivity. To establish the connectivity between nodes we apply the previously proposed small-shuffle surrogate (SSS) method, which can investigate whether there are correlation structures in short-term variabilities (irregular fluctuations) between two data sets from the viewpoint of deterministic dynamical systems. The procedure to construct networks based on this idea is composed of three steps: (i) each time series is considered as a basic node of a network, (ii) the SSS method is applied to verify the connectivity between each pair of time series taken from the whole multivariate time series, and (iii) the pair of nodes is connected with an undirected edge when the null hypothesis cannot be rejected. The network constructed by the proposed method indicates the intrinsic (essential) connectivity of the elements included in the system or the underlying (assumed) system. The method is demonstrated for numerical data sets generated by known systems and applied to several experimental time series.

MAGNETIC NULL POINTS IN KINETIC SIMULATIONS OF SPACE PLASMAS

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

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

2016-03-01

We present a systematic attempt to study magnetic null points and the associated magnetic energy conversion in kinetic particle-in-cell simulations of various plasma configurations. We address three-dimensional simulations performed with the semi-implicit kinetic electromagnetic code iPic3D in different setups: variations of a Harris current sheet, dipolar and quadrupolar magnetospheres interacting with the solar wind, and a relaxing turbulent configuration with multiple null points. Spiral nulls are more likely created in space plasmas: in all our simulations except lunar magnetic anomaly (LMA) and quadrupolar mini-magnetosphere the number of spiral nulls prevails over the number of radial nulls by a factor of 3–9.more » We show that often magnetic nulls do not indicate the regions of intensive energy dissipation. Energy dissipation events caused by topological bifurcations at radial nulls are rather rare and short-lived. The so-called X-lines formed by the radial nulls in the Harris current sheet and LMA simulations are rather stable and do not exhibit any energy dissipation. Energy dissipation is more powerful in the vicinity of spiral nulls enclosed by magnetic flux ropes with strong currents at their axes (their cross sections resemble 2D magnetic islands). These null lines reminiscent of Z-pinches efficiently dissipate magnetic energy due to secondary instabilities such as the two-stream or kinking instability, accompanied by changes in magnetic topology. Current enhancements accompanied by spiral nulls may signal magnetic energy conversion sites in the observational data.« less

Downhole tool

DOEpatents

Hall, David R.; Muradov, Andrei; Pixton, David S.; Dahlgren, Scott Steven; Briscoe, Michael A.

2007-03-20

A double shouldered downhole tool connection comprises box and pin connections having mating threads intermediate mating primary and secondary shoulders. The connection further comprises a secondary shoulder component retained in the box connection intermediate a floating component and the primary shoulders. The secondary shoulder component and the pin connection cooperate to transfer a portion of makeup load to the box connection. The downhole tool may be selected from the group consisting of drill pipe, drill collars, production pipe, and reamers. The floating component may be selected from the group consisting of electronics modules, generators, gyroscopes, power sources, and stators. The secondary shoulder component may comprises an interface to the box connection selected from the group consisting of radial grooves, axial grooves, tapered grooves, radial protrusions, axial protrusions, tapered protrusions, shoulders, and threads.

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.

Double soft graviton theorems and Bondi-Metzner-Sachs symmetries

NASA Astrophysics Data System (ADS)

Anupam, A. H.; Kundu, Arpan; Ray, Krishnendu

2018-05-01

It is now well understood that Ward identities associated with the (extended) BMS algebra are equivalent to single soft graviton theorems. In this work, we show that if we consider nested Ward identities constructed out of two BMS charges, a class of double soft factorization theorems can be recovered. By making connections with earlier works in the literature, we argue that at the subleading order, these double soft graviton theorems are the so-called consecutive double soft graviton theorems. We also show how these nested Ward identities can be understood as Ward identities associated with BMS symmetries in scattering states defined around (non-Fock) vacua parametrized by supertranslations or superrotations.

Steady-state and dynamic characteristics of a 20-kHz spacecraft power system - Control of harmonic resonance

NASA Technical Reports Server (NTRS)

Wasynczuk, O.; Krause, P. C.; Biess, J. J.; Kapustka, R.

1990-01-01

A detailed computer simulation was used to illustrate the steady-state and dynamic operating characteristics of a 20-kHz resonant spacecraft power system. The simulated system consists of a parallel-connected set of DC-inductor resonant inverters (drivers), a 440-V cable, a node transformer, a 220-V cable, and a transformer-rectifier-filter (TRF) AC-to-DC receiver load. Also included in the system are a 1-kW 0.8-pf RL load and a double-LC filter connected at the receiving end of the 20-kHz AC system. The detailed computer simulation was used to illustrate the normal steady-state operating characteristics and the dynamic system performance following, for example, TRF startup. It is shown that without any filtering the given system exhibits harmonic resonances due to an interaction between the switching of the source and/or load converters and the AC system. However, the double-LC filter at the receiving-end of the AC system and harmonic traps connected in series with each of the drivers significantly reduce the harmonic distortion of the 20-kHz bus voltage. Significant additional improvement in the waveform quality can be achieved by including a double-LC filter with each driver.

Feasibility Study of Residential Grid-Connected Solar Photovoltaic Systems in the State of Indiana

NASA Astrophysics Data System (ADS)

Al-Odeh, Mahmoud

This study aims to measure the financial viability of installing and using a residential grid-connected PV system in the State of Indiana while predicting its performance in eighteen geographical locations within the state over the system's expected lifetime. The null hypothesis of the study is that installing a PV system for a single family residence in the State of Indiana will not pay for itself within 25 years. Using a systematic approach consisting of six steps, data regarding the use of renewable energy in the State of Indiana was collected from the website of the US Department of Energy to perform feasibility analysis of the installation and use of a standard-sized residential PV system. The researcher was not able to reject the null hypothesis that installing a PV system for a single family residence in the State of Indiana will not pay for itself within 25 years. This study found that the standard PV system does not produce a positive project balance and does not pay for itself within 25 years (the life time of the system) assuming the average cost of a system. The government incentive programs are not enough to offset the cost of installing the system against the cost of the electricity that would not be purchased from the utility company. It can be concluded that the cost of solar PV is higher than the market valuation of the power it produces; thus, solar PV did not compete on the cost basis with the traditional competitive energy sources. Reducing the capital cost will make the standard PV system economically viable in Indiana. The study found that the capital cost for the system should be reduced by 15% - 56%.

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

PubMed

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

2017-06-23

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

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

PubMed

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

2013-12-01

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

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

PubMed Central

Novozhilova, Natalia M.; Turco, Salvatore J.

2017-01-01

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

Temporal motifs reveal homophily, gender-specific patterns, and group talk in call sequences.

PubMed

Kovanen, Lauri; Kaski, Kimmo; Kertész, János; Saramäki, Jari

2013-11-05

Recent studies on electronic communication records have shown that human communication has complex temporal structure. We study how communication patterns that involve multiple individuals are affected by attributes such as sex and age. To this end, we represent the communication records as a colored temporal network where node color is used to represent individuals' attributes, and identify patterns known as temporal motifs. We then construct a null model for the occurrence of temporal motifs that takes into account the interaction frequencies and connectivity between nodes of different colors. This null model allows us to detect significant patterns in call sequences that cannot be observed in a static network that uses interaction frequencies as link weights. We find sex-related differences in communication patterns in a large dataset of mobile phone records and show the existence of temporal homophily, the tendency of similar individuals to participate in communication patterns beyond what would be expected on the basis of their average interaction frequencies. We also show that temporal patterns differ between dense and sparse neighborhoods in the network. Because also this result is independent of interaction frequencies, it can be seen as an extension of Granovetter's hypothesis to temporal networks.

Temporal motifs reveal homophily, gender-specific patterns, and group talk in call sequences

PubMed Central

Kovanen, Lauri; Kaski, Kimmo; Kertész, János; Saramäki, Jari

2013-01-01

Recent studies on electronic communication records have shown that human communication has complex temporal structure. We study how communication patterns that involve multiple individuals are affected by attributes such as sex and age. To this end, we represent the communication records as a colored temporal network where node color is used to represent individuals’ attributes, and identify patterns known as temporal motifs. We then construct a null model for the occurrence of temporal motifs that takes into account the interaction frequencies and connectivity between nodes of different colors. This null model allows us to detect significant patterns in call sequences that cannot be observed in a static network that uses interaction frequencies as link weights. We find sex-related differences in communication patterns in a large dataset of mobile phone records and show the existence of temporal homophily, the tendency of similar individuals to participate in communication patterns beyond what would be expected on the basis of their average interaction frequencies. We also show that temporal patterns differ between dense and sparse neighborhoods in the network. Because also this result is independent of interaction frequencies, it can be seen as an extension of Granovetter’s hypothesis to temporal networks. PMID:24145424

Organic double layer element driven by triboelectric nanogenerator: Study of carrier behavior by non-contact optical method

NASA Astrophysics Data System (ADS)

Chen, Xiangyu; Taguchi, Dai; Manaka, Takaaki; Iwamoto, Mitsumasa

2016-02-01

By using optical electric-field-induced second-harmonic generation (EFISHG) technique, we studied carrier behavior caused by contact electrification (CE) in an organic double-layer element. This double-layer sample was half suspended in the open air, where one electrode (anode or cathode) was connected with a Cu foil for electrification while the other electrode was floated. Results showed two distinct carrier behaviors, depending on the (anode or cathode) connections to the Cu foil, and these carrier behaviors were analyzed based on the Maxwell-Wagner model. The double-layer sample works as a simple solar cell device. The photovoltaic effect and CE process have been proved to be two paralleled effects without strong interaction with each other, while photoconductivity changing in the sample can enhance the relaxation of CE induced charges. By probing the carrier behavior in this half-suspended device, the EFISHG technique has been demonstrated to be an effective non-contact method for clarifying the CE effect on related energy harvesting devices and electronics devices. Meanwhile, the related physical analysis in this letter is also useful for elucidating the fundamental characteristic of hybrid energy system based on solar cell and triboelectric nanogenerator.

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

PubMed Central

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

2002-01-01

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

Adaptive Nulling for the Terrestrial Planet Finder Interferometer

NASA Technical Reports Server (NTRS)

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

2006-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

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.

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

A general methodology for population analysis

NASA Astrophysics Data System (ADS)

Lazov, Petar; Lazov, Igor

2014-12-01

For a given population with N - current and M - maximum number of entities, modeled by a Birth-Death Process (BDP) with size M+1, we introduce utilization parameter ρ, ratio of the primary birth and death rates in that BDP, which, physically, determines (equilibrium) macrostates of the population, and information parameter ν, which has an interpretation as population information stiffness. The BDP, modeling the population, is in the state n, n=0,1,…,M, if N=n. In presence of these two key metrics, applying continuity law, equilibrium balance equations concerning the probability distribution pn, n=0,1,…,M, of the quantity N, pn=Prob{N=n}, in equilibrium, and conservation law, and relying on the fundamental concepts population information and population entropy, we develop a general methodology for population analysis; thereto, by definition, population entropy is uncertainty, related to the population. In this approach, what is its essential contribution, the population information consists of three basic parts: elastic (Hooke's) or absorption/emission part, synchronization or inelastic part and null part; the first two parts, which determine uniquely the null part (the null part connects them), are the two basic components of the Information Spectrum of the population. Population entropy, as mean value of population information, follows this division of the information. A given population can function in information elastic, antielastic and inelastic regime. In an information linear population, the synchronization part of the information and entropy is absent. The population size, M+1, is the third key metric in this methodology. Namely, right supposing a population with infinite size, the most of the key quantities and results for populations with finite size, emerged in this methodology, vanish.

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

PubMed

Doll, Caleb A; Broadie, Kendal

2016-05-01

Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early-use critical period. Copyright © 2016 Elsevier Inc. All rights reserved.

Atmospheric reaction systems as null-models to identify structural traces of evolution in metabolism.

PubMed

Holme, Petter; Huss, Mikael; Lee, Sang Hoon

2011-05-06

The metabolism is the motor behind the biological complexity of an organism. One problem of characterizing its large-scale structure is that it is hard to know what to compare it to. All chemical reaction systems are shaped by the same physics that gives molecules their stability and affinity to react. These fundamental factors cannot be captured by standard null-models based on randomization. The unique property of organismal metabolism is that it is controlled, to some extent, by an enzymatic machinery that is subject to evolution. In this paper, we explore the possibility that reaction systems of planetary atmospheres can serve as a null-model against which we can define metabolic structure and trace the influence of evolution. We find that the two types of data can be distinguished by their respective degree distributions. This is especially clear when looking at the degree distribution of the reaction network (of reaction connected to each other if they involve the same molecular species). For the Earth's atmospheric network and the human metabolic network, we look into more detail for an underlying explanation of this deviation. However, we cannot pinpoint a single cause of the difference, rather there are several concurrent factors. By examining quantities relating to the modular-functional organization of the metabolism, we confirm that metabolic networks have a more complex modular organization than the atmospheric networks, but not much more. We interpret the more variegated modular arrangement of metabolism as a trace of evolved functionality. On the other hand, it is quite remarkable how similar the structures of these two types of networks are, which emphasizes that the constraints from the chemical properties of the molecules has a larger influence in shaping the reaction system than does natural selection.

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 Solution Space for a System of Null-State Partial Differential Equations: Part 4

NASA Astrophysics Data System (ADS)

Flores, Steven M.; Kleban, Peter

2015-01-01

This article is the last of four that completely and rigorously characterize a solution space for a homogeneous system of 2 N + 3 linear partial differential equations in 2 N variables that arises in conformal field theory (CFT) and multiple Schramm-Löwner evolution (SLE). The system comprises 2 N null-state equations and three conformal Ward identities that govern CFT correlation functions of 2 N one-leg boundary operators. In the first two articles (Flores and Kleban in Commun Math Phys, 2012; Flores and Kleban, in Commun Math Phys, 2014), we use methods of analysis and linear algebra to prove that dim , with C N the Nth Catalan number. Using these results in the third article (Flores and Kleban, in Commun Math Phys, 2013), we prove that dim and is spanned by (real-valued) solutions constructed with the Coulomb gas (contour integral) formalism of CFT. In this article, we use these results to prove some facts concerning the solution space . First, we show that each of its elements equals a sum of at most two distinct Frobenius series in powers of the difference between two adjacent points (unless is odd, in which case a logarithmic term may appear). This establishes an important element in the operator product expansion for one-leg boundary operators, assumed in CFT. We also identify particular elements of , which we call connectivity weights, and exploit their special properties to conjecture a formula for the probability that the curves of a multiple-SLE process join in a particular connectivity. This leads to new formulas for crossing probabilities of critical lattice models inside polygons with a free/fixed side-alternating boundary condition, which we derive in Flores et al. (Partition functions and crossing probabilities for critical systems inside polygons, in preparation). Finally, we propose a reason for why the exceptional speeds [certain values that appeared in the analysis of the Coulomb gas solutions in Flores and Kleban (Commun Math Phys, 2013)] and the minimal models of CFT are connected.

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.

Epidemic dynamics and endemic states in complex networks

NASA Astrophysics Data System (ADS)

Pastor-Satorras, Romualdo; Vespignani, Alessandro

2001-06-01

We study by analytical methods and large scale simulations a dynamical model for the spreading of epidemics in complex networks. In networks with exponentially bounded connectivity we recover the usual epidemic behavior with a threshold defining a critical point below that the infection prevalence is null. On the contrary, on a wide range of scale-free networks we observe the absence of an epidemic threshold and its associated critical behavior. This implies that scale-free networks are prone to the spreading and the persistence of infections whatever spreading rate the epidemic agents might possess. These results can help understanding computer virus epidemics and other spreading phenomena on communication and social networks.

The ``cinquefoil" resistive/Hall measurement geometry

NASA Astrophysics Data System (ADS)

Koon, Daniel W.

2000-03-01

This talk begins by analyzing the charge transport weighting functions -- the sensitivity of resistive and Hall measurements to local macroscopic inhomogeneities -- of bridge-shaped transport specimens. As expected, such measurements sample only that region of the specimen between the central voltage electrodes, in the limit of narrow current channels connected by even narrower arms to the voltage electrodes. The bridge geometry has a few advantages over the van der Pauw cloverleaf geometry -- including ease in zeroing out the null-field Hall voltage -- but also some disadvantages. The talk concludes with an analysis of a hybrid geometry, the “cinquefoil” or five-leafed clover, which combines the best features of both.

Interplay of symmetries and other integrability quantifiers in finite-dimensional integrable nonlinear dynamical systems

PubMed Central

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

2016-01-01

In this work, we establish a connection between the extended Prelle–Singer procedure and other widely used analytical methods to identify integrable systems in the case of nth-order nonlinear ordinary differential equations (ODEs). By synthesizing these methods, we bring out the interlink between Lie point symmetries, contact symmetries, λ-symmetries, adjoint symmetries, null forms, Darboux polynomials, integrating factors, the Jacobi last multiplier and generalized λ-symmetries corresponding to the nth-order ODEs. We also prove these interlinks with suitable examples. By exploiting these interconnections, the characteristic quantities associated with different methods can be deduced without solving the associated determining equations. PMID:27436964

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

NASA Technical Reports Server (NTRS)

Arend, David J.; Saunders, John D.

2009-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2010-10-01

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

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

PubMed Central

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

2016-01-01

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

Novel MRI methodology to detect human whole-brain connectivity changes after ingestion of fructose or glucose

NASA Astrophysics Data System (ADS)

Tsao, Sinchai; Wilkins, Bryce; Page, Kathleen A.; Singh, Manbir

2012-03-01

A novel MRI protocol has been developed to investigate the differential effects of glucose or fructose consumption on whole-brain functional brain connectivity. A previous study has reported a decrease in the fMRI blood oxygen level dependent (BOLD) signal of the hypothalamus following glucose ingestion, but due to technical limitations, was restricted to a single slice covering the hypothalamus, and thus unable to detect whole-brain connectivity. In another previous study, a protocol was devised to acquire whole-brain fMRI data following food intake, but only after restricting image acquisition to an MR sampling or repetition time (TR) of 20s, making the protocol unsuitable to detect functional connectivity above 0.025Hz. We have successfully implemented a continuous 36-min, 40 contiguous slices, whole-brain BOLD acquisition protocol on a 3T scanner with TR=4.5s to ensure detection of up to 0.1Hz frequencies for whole-brain functional connectivity analysis. Human data were acquired first with ingestion of water only, followed by a glucose or fructose drink within the scanner, without interrupting the scanning. Whole-brain connectivity was analyzed using standard correlation methodology in the 0.01-0.1 Hz range. The correlation coefficient differences between fructose and glucose ingestion among targeted regions were converted to t-scores using the water-only correlation coefficients as a null condition. Results show a dramatic increase in the hypothalamic connectivity to the hippocampus, amygdala, insula, caudate and the nucleus accumben for fructose over glucose. As these regions are known to be key components of the feeding and reward brain circuits, these results suggest a preference for fructose ingestion.

Toroidally symmetric plasma vortex at tokamak divertor null point

DOE PAGES

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

2016-03-09

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

Off-Axis Nulling Transfer Function Measurement: A First Assessment

NASA Technical Reports Server (NTRS)

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

Ultrastructural organization of connective tissue microfibrils in the posterior chamber of the eye in vivo and in vitro.

PubMed

Inoue, S

1995-02-01

The ultrastructural organization of connective tissue microfibrils was studied in the mouse eye and also by means of in vitro experiments for reconstituting microfibrils. In the posterior chamber of the eye of the C57BL/6J mouse, 3 nm-wide ribbon-like double-tracked structures were present and were periodically associated on either side with 3.5 nm-wide particulate structures identified as pentosomes, the subunits of amyloid P component (AP). At certain sites, such composite structures were observed in various stages of helical winding, and in these helices, pentosomes were preferentially localized internally. In helices in the final stages of winding, the resulting rods appeared increasingly similar to those of microfibrils. In experiments in vitro, incubation of chondroitin sulfate proteoglycan (CSPG) in TRIS buffer, pH 7.4, at 35 degrees C for 1 h produced random aggregates of 3 nm-wide double-tracked structures similar to those observed in the eye. Co-incubation of CSPG and AP resulted in the formation of rod-like structures arranged parallel to one another in approximately 50 nm-thick sheet-like layers. These rods were ultrastructurally similar to microfibrils and were made up of helically wound, 3 nm-wide double-tracked structures containing pentosomes within their core. The results of in vivo as well as in vitro experiments suggest the possibility that the connective tissue microfibril is composed of helically wound, CSPG-containing, 3 nm-wide double-tracked structures periodically associated with pentosomes which, as the helix becomes progressively tighter, fit with one another at the core of the helix to form successive 8.5 nm-wide disks of AP segments.

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

PubMed Central

Mittal, Nimisha; Muthuswami, Rohini

2017-01-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2010-11-15

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

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

PubMed

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

2016-10-01

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

Nonlinear Modeling of Radial Stellar Pulsations

NASA Astrophysics Data System (ADS)

Smolec, R.

2009-09-01

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

Loss of Vitamin D Receptor Produces Polyuria by Increasing Thirst

PubMed Central

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

2008-01-01

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

Loss of vitamin D receptor produces polyuria by increasing thirst.

PubMed

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

2008-12-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

Tennese, Alysa A; Wevrick, Rachel

2011-03-01

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

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

PubMed

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

2015-05-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed Central

Keighren, Margaret A.; Flockhart, Jean H.

2016-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2016-01-01

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

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

PubMed

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

2013-10-01

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

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

PubMed Central

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

2008-01-01

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

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

PubMed

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

2008-04-01

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

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

PubMed

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

2016-10-01

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

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

PubMed

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

2002-10-10

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

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

USGS Publications Warehouse

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

2012-01-01

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

Disruption avoidance and fast ramp-down techniques for the DIII-D experimental scenarios

NASA Astrophysics Data System (ADS)

Barr, Jayson; Eidietis, N. W.; Humphreys, D. A.; Sammuli, B.; Luce, T.

2017-10-01

Plasma current ramp-down in ITER will continue in H-mode from 15 MA to 10 MA, and will keep a diverted shape until termination. This is in contrast to the limited ramp-down scenarios typically used in DIII-D operations. Additionally, fast emergency ramp-down scenarios for ITER and future reactors are a priority for disruption avoidance. New experiments in DIII-D use the ramp-down phase of a variety of experiments including in the ITER baseline scenario to survey and identify optimized ramp-down scenarios for both scheduled terminations and terminations triggered by off-normal event detection. Systematic scans in current ramp-rate (1-5 MA/s), neutral beam power (including βN feedback) and ramp-down shaping (limited versus continued diverted) have identified fast ramp-down scenarios for Lower Single Null (LSN) and Double Null (DN) plasmas. Scenario-specific methods and their rates of successful termination will be presented and compared relative to a historical data-set of ramp-down programming in the limiter configuration. Locked modes are found to be the most significant challenge to disruption avoidance in diverted ramp-downs. Results for LSN diverted discharges that begin the rampdown with large locked-modes will also be presented. If available, results of similar experiments on EAST will be presented. Work supported by US DOE under DE-FC02-04ER54698 and DE-SC0010685.

Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex Regulating Collagen Lysyl Hydroxylation

PubMed Central

Weis, MaryAnn; Rai, Jyoti; Hudson, David M.; Dimori, Milena; Zimmerman, Sarah M.; Hogue, William R.; Swain, Frances L.; Burdine, Marie S.; Mackintosh, Samuel G.; Tackett, Alan J.; Suva, Larry J.; Eyre, David R.

2016-01-01

Collagen is a major component of the extracellular matrix and its integrity is essential for connective tissue and organ function. The importance of proteins involved in intracellular collagen post-translational modification, folding and transport was recently highlighted from studies on recessive forms of osteogenesis imperfecta (OI). Here we describe the critical role of SC65 (Synaptonemal Complex 65, P3H4), a leprecan-family member, as part of an endoplasmic reticulum (ER) complex with prolyl 3-hydroxylase 3. This complex affects the activity of lysyl-hydroxylase 1 potentially through interactions with the enzyme and/or cyclophilin B. Loss of Sc65 in the mouse results in instability of this complex, altered collagen lysine hydroxylation and cross-linking leading to connective tissue defects that include low bone mass and skin fragility. This is the first indication of a prolyl-hydroxylase complex in the ER controlling lysyl-hydroxylase activity during collagen synthesis. PMID:27119146

The role of weak selection and high mutation rates in nearly neutral evolution.

PubMed

Lawson, Daniel John; Jensen, Henrik Jeldtoft

2009-04-21

Neutral dynamics occur in evolution if all types are 'effectively equal' in their reproductive success, where the definition of 'effectively equal' depends on the population size and the details of mutations. Empirically observed neutral genetic evolution in extremely large clonal populations can only be explained under current models if selection is completely absent. Such models typically consider the case where population dynamics occurs on a different timescale to evolution. However, this assumption is invalid when mutations are not rare in a whole population. We show that this has important consequences for the occurrence of neutral evolution in clonal populations. In highly connected type spaces, neutral dynamics can occur for all population sizes despite significant selective differences, via the forming of effectively neutral networks connecting rare neutral types. Biological implications include an explanation for the high diversity of rare types that survive in large clonal populations, and a theoretical justification for the use of neutral null models.

Propagation of spiking regularity and double coherence resonance in feedforward networks.

PubMed

Men, Cong; Wang, Jiang; Qin, Ying-Mei; Deng, Bin; Tsang, Kai-Ming; Chan, Wai-Lok

2012-03-01

We investigate the propagation of spiking regularity in noisy feedforward networks (FFNs) based on FitzHugh-Nagumo neuron model systematically. It is found that noise could modulate the transmission of firing rate and spiking regularity. Noise-induced synchronization and synfire-enhanced coherence resonance are also observed when signals propagate in noisy multilayer networks. It is interesting that double coherence resonance (DCR) with the combination of synaptic input correlation and noise intensity is finally attained after the processing layer by layer in FFNs. Furthermore, inhibitory connections also play essential roles in shaping DCR phenomena. Several properties of the neuronal network such as noise intensity, correlation of synaptic inputs, and inhibitory connections can serve as control parameters in modulating both rate coding and the order of temporal coding.

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.

The concept of double inlet-double outlet right ventricle: a distinct congenital heart disease.

PubMed

Spadotto, Veronica; Frescura, Carla; Ho, Siew Yen; Thiene, Gaetano

The aim of this study was to estimate the incidence and to analyze the anatomy of double inlet-double outlet right ventricle complex and its associated cardiac anomalies in our autopsy series. Among the 1640 hearts with congenital heart disease of our Anatomical Collection, we reviewed the specimens with double inlet-double outlet right ventricle, according to the sequential-segmental analysis, identifying associated cardiac anomalies and examining lung histology to assess the presence of pulmonary vascular disease. We identified 14 hearts with double inlet-double outlet right ventricle (0.85%). Right atrial isomerism was observed in 10 hearts, situs solitus in 3 and left atrial isomerism in one. Regarding the mode of atrioventricular connection, all hearts but one had a common atrioventricular valve. Systemic or pulmonary venous abnormalities were noted in all patients with atrial isomerism. In nine patients a valvular or subvalvular pulmonary stenosis was present. Among the functionally "univentricular hearts", double inlet- double outlet right ventricle represents a peculiar entity, mostly in association with right atrial isomerism. Multiple cardiac anomalies are associated and may complicate surgical repair. Copyright © 2016 Elsevier Inc. All rights reserved.

Chinook salmon use of spawning patches: relative roles of habitat quality, size, and connectivity.

PubMed

Isaak, Daniel J; Thurow, Russell F; Rieman, Bruce E; Dunham, Jason B

2007-03-01

Declines in many native fish populations have led to reassessments of management goals and shifted priorities from consumptive uses to species preservation. As management has shifted, relevant environmental characteristics have evolved from traditional metrics that described local habitat quality to characterizations of habitat size and connectivity. Despite the implications this shift has for how habitats may be prioritized for conservation, it has been rare to assess the relative importance of these habitat components. We used an information-theoretic approach to select the best models from sets of logistic regressions that linked habitat quality, size, and connectivity to the occurrence of chinook salmon (Oncorhynchus tshawytscha) nests. Spawning distributions were censused annually from 1995 to 2004, and data were complemented with field measurements that described habitat quality in 43 suitable spawning patches across a stream network that drained 1150 km2 in central Idaho. Results indicated that the most plausible models were dominated by measures of habitat size and connectivity, whereas habitat quality was of minor importance. Connectivity was the strongest predictor of nest occurrence, but connectivity interacted with habitat size, which became relatively more important when populations were reduced. Comparison of observed nest distributions to null model predictions confirmed that the habitat size association was driven by a biological mechanism when populations were small, but this association may have been an area-related sampling artifact at higher abundances. The implications for habitat management are that the size and connectivity of existing habitat networks should be maintained whenever possible. In situations where habitat restoration is occurring, expansion of existing areas or creation of new habitats in key areas that increase connectivity may be beneficial. Information about habitat size and connectivity also could be used to strategically prioritize areas for improvement of local habitat quality, with areas not meeting minimum thresholds being deemed inappropriate for pursuit of restoration activities.

Chinook salmon use of spawning patches: Relative roles of habitat quality, size, and connectivity

USGS Publications Warehouse

Isaak, D.J.; Thurow, R.F.; Rieman, B.E.; Dunham, J.B.

2007-01-01

Declines in many native fish populations have led to reassessments of management goals and shifted priorities from consumptive uses to species preservation. As management has shifted, relevant environmental characteristics have evolved from traditional metrics that described local habitat quality to characterizations of habitat size and connectivity. Despite the implications this shift has for how habitats may be prioritized for conservation, it has been rare to assess the relative importance of these habitat components. We used an information-theoretic approach to select the best models from sets of logistic regressions that linked habitat quality, size, and connectivity to the occurrence of chinook salmon (Oncorhynchus tshawytscha) nests. Spawning distributions were censused annually from 1995 to 2004, and data were complemented with field measurements that described habitat quality in 43 suitable spawning patches across a stream network that drained 1150 km 2 in central Idaho. Results indicated that the most plausible models were dominated by measures of habitat size and connectivity, whereas habitat quality was of minor importance. Connectivity was the strongest predictor of nest occurrence, but connectivity interacted with habitat size, which became relatively more important when populations were reduced. Comparison of observed nest distributions to null model predictions confirmed that the habitat size association was driven by a biological mechanism when populations were small, but this association may have been an area-related sampling artifact at higher abundances. The implications for habitat management are that the size and connectivity of existing habitat networks should be maintained whenever possible. In situations where habitat restoration is occurring, expansion of existing areas or creation of new habitats in key areas that increase connectivity may be beneficial. Information about habitat size and connectivity also could be used to strategically prioritize areas for improvement of local habitat quality, with areas not meeting minimum thresholds being deemed inappropriate for pursuit of restoration activities. ?? 2007 by the Ecological Society of America.

Structure solution of network materials by solid-state NMR without knowledge of the crystallographic space group.

PubMed

Brouwer, Darren H

2013-01-01

An algorithm is presented for solving the structures of silicate network materials such as zeolites or layered silicates from solid-state (29)Si double-quantum NMR data for situations in which the crystallographic space group is not known. The algorithm is explained and illustrated in detail using a hypothetical two-dimensional network structure as a working example. The algorithm involves an atom-by-atom structure building process in which candidate partial structures are evaluated according to their agreement with Si-O-Si connectivity information, symmetry restraints, and fits to (29)Si double quantum NMR curves followed by minimization of a cost function that incorporates connectivity, symmetry, and quality of fit to the double quantum curves. The two-dimensional network material is successfully reconstructed from hypothetical NMR data that can be reasonably expected to be obtained for real samples. This advance in "NMR crystallography" is expected to be important for structure determination of partially ordered silicate materials for which diffraction provides very limited structural information. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2006-01-01

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

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

NASA Astrophysics Data System (ADS)

Burke-Spolaor, S.

2011-06-01

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

Qualification of a Null Lens Using Image-Based Phase Retrieval

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

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

PubMed Central

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

2014-01-01

Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. PMID:24200853

Null conformal Killing-Yano tensors and Birkhoff theorem

NASA Astrophysics Data System (ADS)

Ferrando, Joan Josep; Sáez, Juan Antonio

2016-04-01

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

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

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

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

PubMed

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

2016-02-01

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

Impaired clock output by altered connectivity in the circadian network.

PubMed

Fernández, María de la Paz; Chu, Jessie; Villella, Adriana; Atkinson, Nigel; Kay, Steve A; Ceriani, María Fernanda

2007-03-27

Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.

Simplicial lattices in classical and quantum gravity: Mathematical structure and application

NASA Astrophysics Data System (ADS)

Lafave, Norman Joseph

1989-03-01

Geometrodynamics can be understood more clearly in the language of geometry than in the language of differential equations. This is the primary motivation for the development of calculational schemes based on Regge Calculus as an alternative to those schemes based on Ricci Calculus. The mathematics of simplicial lattices were developed to the same level of sophistication as the mathematics of pseudo--Riemannian geometry for continuum manifolds. This involves the definition of the simplicial analogues of several concepts from differential topology and differential geometry-the concept of a point, tangent spaces, forms, tensors, parallel transport, covariant derivatives, connections, and curvature. These simplicial analogues are used to define the Einstein tensor and the extrinsic curvature on a simplicial geometry. This mathematical formalism was applied to the solution of several outstanding problems in the development of a Regge Calculus based computational scheme for general geometrodynamic problems. This scheme is based on a 3 + 1 splitting of spacetime within the Regge Calculus prescription known as Null-Strut Calculus (NSC). NSC describes the foliation of spacetime into spacelike hypersurfaces built of tetrahedra. These hypersurfaces are coupled by light rays (null struts) to past and future momentum-like structures, geometrically dual to the tetrahedral lattice of the hypersurface. Avenues of investigation for NSC in quantum gravity are described.

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

Double outlet right ventricle

MedlinePlus

... disease that is present from birth (congenital) . The aorta connects to the right ventricle (RV, the chamber ... carries oxygen-poor blood to the lungs) and aorta (which carries oxygen-rich blood from the heart ...

Double-pointed 30-gauge needle for keratocentesis.

PubMed

Angi, M R; Endara, N I

1985-12-01

A new, efficient instrument for performing keratocentesis for aqueous humour aspiration and anterior chamber microinfusion is described. It consists of a double-pointed 30-gauge needle, a liquid container (a nonflexible vinyl tube plugged at one end with a rubber stopper) and a aspiration-infusion syringe connected to the container and needle by a flexible vinyl tube. The instrument's advantages are a safer technique, complete collection of the aqueous humour and better handling of the sample.

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

PubMed

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

2014-02-28

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

Science Results From The ARCADE Open-Aperture Cryogenic Balloon Payload

NASA Technical Reports Server (NTRS)

Kogut, Alan J.

2010-01-01

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

Macroscopic and microscopic evaluation of a new implant design supporting immediately loaded full arch rehabilitation

PubMed Central

Tetè, Stefano; Zizzari, Vincenzo; De Carlo, Alessandro; Sinjari, Bruna; Gherlone, Enrico

2012-01-01

Summary The purpose of this study is to evaluate macroscopic and microscopic appearance of a new implant design, with particular emphasis given to the type of prosthesis connection. Two dental implants of the same type (Torque Type®, WinSix®, BioSAFin. S.r.l. - Ancona, Italy), with sandblasted and acid etched surfaces (Micro Rough Surface®), but differing from each other for the prosthesis connection system, were examined by scanning electron microscope (SEM) analysis at different magnifications: TTI implant, with a hexagonal internal connection, and TTX implant, with a hexagonal external connection. SEM analysis showed that the Torque Type® implant is characterized by a truncated cone shape with tapered tips. The implant body showed a double loop thread and double pitch with blunt tips. For both types of connection, the implant neck was 0.7 mm in height with a 3% taper. This implant design may be able to guarantee osteotomic properties at the time of insertion in a surgical site suitably prepared, a facilitated screwing, thanks to the thread pitch and to the broad and deep draining grooves, thereby ensuring a good primary stability. The different connection design appears defined and precise, in order to ensure a good interface between the fixture and the prosthetic components. Therefore, this design appears to be particularly suitable in cases where a good primary stability is necessary and a precise coupling between endosseous and prosthetic components, as it allows an easy insertion of the fixture even in conditions of reduced bone availability, and in cases of immediately loaded full-arch rehabilitations. PMID:23087785

Macroscopic and microscopic evaluation of a new implant design supporting immediately loaded full arch rehabilitation.

PubMed

Tetè, Stefano; Zizzari, Vincenzo; De Carlo, Alessandro; Sinjari, Bruna; Gherlone, Enrico

2012-04-01

The purpose of this study is to evaluate macroscopic and microscopic appearance of a new implant design, with particular emphasis given to the type of prosthesis connection. Two dental implants of the same type (Torque Type(®), WinSix(®), BioSAFin. S.r.l. - Ancona, Italy), with sandblasted and acid etched surfaces (Micro Rough Surface(®)), but differing from each other for the prosthesis connection system, were examined by scanning electron microscope (SEM) analysis at different magnifications: TTI implant, with a hexagonal internal connection, and TTX implant, with a hexagonal external connection. SEM analysis showed that the Torque Type(®) implant is characterized by a truncated cone shape with tapered tips. The implant body showed a double loop thread and double pitch with blunt tips. For both types of connection, the implant neck was 0.7 mm in height with a 3% taper. This implant design may be able to guarantee osteotomic properties at the time of insertion in a surgical site suitably prepared, a facilitated screwing, thanks to the thread pitch and to the broad and deep draining grooves, thereby ensuring a good primary stability. The different connection design appears defined and precise, in order to ensure a good interface between the fixture and the prosthetic components. Therefore, this design appears to be particularly suitable in cases where a good primary stability is necessary and a precise coupling between endosseous and prosthetic components, as it allows an easy insertion of the fixture even in conditions of reduced bone availability, and in cases of immediately loaded full-arch rehabilitations.

Effects of Network Structure, Competition and Memory Time on Social Spreading Phenomena

NASA Astrophysics Data System (ADS)

Gleeson, James P.; O'Sullivan, Kevin P.; Baños, Raquel A.; Moreno, Yamir

2016-04-01

Online social media has greatly affected the way in which we communicate with each other. However, little is known about what fundamental mechanisms drive dynamical information flow in online social systems. Here, we introduce a generative model for online sharing behavior that is analytically tractable and that can reproduce several characteristics of empirical micro-blogging data on hashtag usage, such as (time-dependent) heavy-tailed distributions of meme popularity. The presented framework constitutes a null model for social spreading phenomena that, in contrast to purely empirical studies or simulation-based models, clearly distinguishes the roles of two distinct factors affecting meme popularity: the memory time of users and the connectivity structure of the social network.

Asymptotic behavior for systems of nonlinear wave equations with multiple propagation speeds in three space dimensions

NASA Astrophysics Data System (ADS)

Katayama, Soichiro

We consider the Cauchy problem for systems of nonlinear wave equations with multiple propagation speeds in three space dimensions. Under the null condition for such systems, the global existence of small amplitude solutions is known. In this paper, we will show that the global solution is asymptotically free in the energy sense, by obtaining the asymptotic pointwise behavior of the derivatives of the solution. Nonetheless we can also show that the pointwise behavior of the solution itself may be quite different from that of the free solution. In connection with the above results, a theorem is also developed to characterize asymptotically free solutions for wave equations in arbitrary space dimensions.

Holographic repulsion and confinement in gauge theory

NASA Astrophysics Data System (ADS)

Husain, Viqar; Kothawala, Dawood

2013-02-01

We show that for asymptotically anti-de Sitter (AdS) backgrounds with negative energy, such as the AdS soliton and regulated negative-mass AdS-Schwarzshild metrics, the Wilson loop expectation value in the AdS/CFT conjecture exhibits a Coulomb to confinement transition. We also show that the quark-antiquark (q \\bar{q}) potential can be interpreted as affine time along null geodesics on the minimal string worldsheet and that its intrinsic curvature provides a signature of transition to confinement phase. Our results suggest a generic (holographic) relationship between confinement in gauge theory and repulsive gravity, which in turn is connected with singularity avoidance in quantum gravity. Communicated by P R L V Moniz

Probing transcription-specific outputs of β-catenin in vivo

PubMed Central

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

2011-01-01

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

Magnetoacoustic Waves in a Stratified Atmosphere with a Magnetic Null Point

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

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

2017-03-01

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

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

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

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

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

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

PubMed

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

2018-01-01

Ecological stressors (i.e., environmental factors outside their normal range of variation) can mediate each other through their interactions, leading to unexpected combined effects on communities. Determining whether the net effect of stressors is ecologically surprising requires comparing their cumulative impact to a null model that represents the linear combination of their individual effects (i.e., an additive expectation). However, we show that standard additive and multiplicative null models that base their predictions on the effects of single stressors on community properties (e.g., species richness or biomass) do not provide this linear expectation, leading to incorrect interpretations of antagonistic and synergistic responses by communities. We present an alternative, the compositional null model, which instead bases its predictions on the effects of stressors on individual species, and then aggregates them to the community level. Simulations demonstrate the improved ability of the compositional null model to accurately provide a linear expectation of the net effect of stressors. We simulate the response of communities to paired stressors that affect species in a purely additive fashion and compare the relative abilities of the compositional null model and two standard community property null models (additive and multiplicative) to predict these linear changes in species richness and community biomass across different combinations (both positive, negative, or opposite) and intensities of stressors. The compositional model predicts the linear effects of multiple stressors under almost all scenarios, allowing for proper classification of net effects, whereas the standard null models do not. Our findings suggest that current estimates of the prevalence of ecological surprises on communities based on community property null models are unreliable, and should be improved by integrating the responses of individual species to the community level as does our compositional null model. © 2017 John Wiley & Sons Ltd.

High frequency generation in the corona: Resonant cavities

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Towards a double field theory on para-Hermitian manifolds

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

Vaisman, Izu

In a previous paper, we have shown that the geometry of double field theory has a natural interpretation on flat para-Kähler manifolds. In this paper, we show that the same geometric constructions can be made on any para-Hermitian manifold. The field is interpreted as a compatible (pseudo-)Riemannian metric. The tangent bundle of the manifold has a natural, metric-compatible bracket that extends the C-bracket of double field theory. In the para-Kähler case, this bracket is equal to the sum of the Courant brackets of the two Lagrangian foliations of the manifold. Then, we define a canonical connection and an action ofmore » the field that correspond to similar objects of double field theory. Another section is devoted to the Marsden-Weinstein reduction in double field theory on para-Hermitian manifolds. Finally, we give examples of fields on some well-known para-Hermitian manifolds.« less

STM/STS Study of the Sb (111) Surface

NASA Astrophysics Data System (ADS)

Chekmazov, S. V.; Bozhko, S. I.; Smirnov, A. A.; Ionov, A. M.; Kapustin, A. A.

An Sb crystal is a Peierls insulator. Formation of double layers in the Sb structure is due to the shift of atomic planes (111) next but one along the C3 axis. Atomic layers inside the double layer are connected by covalent bonds. The interaction between double layers is determined mainly by Van der Waals forces. The cleave of an Sb single crystal used to be via break of Van der Waals bonds. However, using scanning tunneling microscopy (STM) and spectroscopy (STS) we demonstrated that apart from islands equal in thickness to the double layer, steps of one atomic layer in height also exist on the cleaved Sb (111) surface. Formation of "unpaired" (111) planes on the surface leads to a local break of conditions of Peierls transition. STS experiment reveals higher local density of states (LDOS) measured for "unpaired" (111) planes in comparison with those for the double layer.

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.

Statistical and hydrodynamic properties of double-ring polymers with a fixed linking number between twin rings.

PubMed

Uehara, Erica; Deguchi, Tetsuo

2014-01-28

For a double-ring polymer in solution we evaluate the mean-square radius of gyration and the diffusion coefficient through simulation of off-lattice self-avoiding double polygons consisting of cylindrical segments with radius rex of unit length. Here, a self-avoiding double polygon consists of twin self-avoiding polygons which are connected by a cylindrical segment. We show numerically that several statistical and dynamical properties of double-ring polymers in solution depend on the linking number of the constituent twin ring polymers. The ratio of the mean-square radius of gyration of self-avoiding double polygons with zero linking number to that of no topological constraint is larger than 1, in particular, when the radius of cylindrical segments rex is small. However, the ratio is almost constant with respect to the number of vertices, N, and does not depend on N. The large-N behavior of topological swelling is thus quite different from the case of knotted random polygons.

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

Olshevsky, Vyacheslav; Lapenta, Giovanni; Divin, Andrey

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

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

PubMed

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

2017-08-01

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

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

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

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

Current progress on TPFI nulling architectures at Jet Propulsion Laboratory

NASA Technical Reports Server (NTRS)

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

2005-01-01

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

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

PubMed

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

2017-06-01

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

Load Carrying Capacity of Metal Dowel Type Connections of Timber Structures

NASA Astrophysics Data System (ADS)

Gocál, Jozef

2014-12-01

This paper deals with the load-carrying capacity calculation of laterally loaded metal dowel type connections according to Eurocode 5. It is based on analytically derived, relatively complicated mathematical relationships, and thus it can be quite laborious for practical use. The aim is to propose a possible simplification of the calculation. Due to quite a great variability of fasteners' types and the connection arrangements, the attention is paid to the most commonly used nailed connections. There was performed quite an extensive parametric study focused on the calculation of load-carrying capacity of the simple shear and double shear plane nail connections, joining two or three timber parts of softwood or hardwood. Based on the study results, in conclusion there are presented simplifying recommendations for practical design.

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.

Mixing at double-Tee junctions with unequal pipe sizes in ...

EPA Pesticide Factsheets

Pipe flow mixing with various solute concentrations and flow rates at pipe junctions is investigated. The degree of mixing affects the spread of contaminants in a water distribution system. Many studies have been conducted on the mixing at the cross junctions. Yet a few have focused on double-Tee junctions of unequal pipe sizes. To investigate the solute mixing at double-Tee junctions with unequal pipe sizes, a series of experiments were conducted in a turbulent regime (Re=12500–50000) with different Reynolds number ratios and connecting pipe lengths. It is shown that dimensionless outlet concentrations depended on mixing mechanism at the impinging interface of junctions. Junction with a larger pipe size ratio is associated with more complete mixing. The inlet Reynolds number ratio affects mixing more strongly than the outlet Reynolds number ratio. Furthermore, the dimensionless connecting pipe length in a double-Tee played an important and complicated role in the flow mixing. Based on these results, two-dimensional isopleth maps were developed for the calculation of normalized north outlet concentration. This journal article is to communicate the research results on pipe juncture mixing, a widespread and important phenomena in distribution system water quality analysis. The research outcome improves EPANET modeling capability for safe water supplies. In addition, the research is one of the outputs from the EPA-MOST bilateral cooperative research Project #1

Average weighted receiving time on the non-homogeneous double-weighted fractal networks

NASA Astrophysics Data System (ADS)

Ye, Dandan; Dai, Meifeng; Sun, Yu; Su, Weiyi

2017-05-01

In this paper, based on actual road networks, a model of the non-homogeneous double-weighted fractal networks is introduced depending on the number of copies s and two kinds of weight factors wi ,ri(i = 1 , 2 , … , s) . The double-weights represent the capacity-flowing weights and the cost-traveling weights, respectively. Denote by wijF the capacity-flowing weight connecting the nodes i and j, and denote by wijC the cost-traveling weight connecting the nodes i and j. Let wijF be related to the weight factors w1 ,w2 , … ,ws, and let wijC be related to the weight factors r1 ,r2 , … ,rs. Assuming that the walker, at each step, starting from its current node, moves to any of its neighbors with probability proportional to the capacity-flowing weight of edge linking them. The weighted time for two adjacency nodes is the cost-traveling weight connecting the two nodes. The average weighted receiving time (AWRT) is defined on the non-homogeneous double-weighted fractal networks. AWRT depends on the relationships of the number of copies s and two kinds of weight factors wi ,ri(i = 1 , 2 , … , s) . The obtained remarkable results display that in the large network, the AWRT grows as a power-law function of the network size Ng with the exponent, represented by θ =logs(w1r1 +w2r2 + ⋯ +wsrs) < 1 when w1r1 +w2r2 + ⋯ +wsrs ≠ 1, which means that the smaller the value of w1r1 +w2r2 + ⋯ +wsrs is, the more efficient the process of receiving information is. Especially when w1r1 +w2r2 + ⋯ +wsrs = 1, AWRT grows with increasing order Ng as logNg or (logNg) 2 . In the classic fractal networks, the average receiving time (ART) grows with linearly with the network size Ng. Thus, the non-homogeneous double-weighted fractal networks are more efficient than classic fractal networks in term of receiving information.

Specifications for Managed Strings, Second Edition

DTIC Science & Technology

2010-05-01

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

An omnibus test for the global null hypothesis.

PubMed

Futschik, Andreas; Taus, Thomas; Zehetmayer, Sonja

2018-01-01

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

Continuous development of current sheets near and away from magnetic nulls

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

Kumar, Sanjay; Bhattacharyya, R.

2016-04-15

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

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

PubMed

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

2009-02-10

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

The Importance of Proving the Null

PubMed Central

Gallistel, C. R.

2010-01-01

Null hypotheses are simple, precise, and theoretically important. Conventional statistical analysis cannot support them; Bayesian analysis can. The challenge in a Bayesian analysis is to formulate a suitably vague alternative, because the vaguer the alternative is (the more it spreads out the unit mass of prior probability), the more the null is favored. A general solution is a sensitivity analysis: Compute the odds for or against the null as a function of the limit(s) on the vagueness of the alternative. If the odds on the null approach 1 from above as the hypothesized maximum size of the possible effect approaches 0, then the data favor the null over any vaguer alternative to it. The simple computations and the intuitive graphic representation of the analysis are illustrated by the analysis of diverse examples from the current literature. They pose 3 common experimental questions: (a) Are 2 means the same? (b) Is performance at chance? (c) Are factors additive? PMID:19348549

Light cone structure near null infinity of the Kerr metric

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

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

2007-02-15

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

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

PubMed

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

1999-08-01

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

MS Grunsfeld during cable IFM

NASA Image and Video Library

1997-02-24

STS081-360-003 (12-22 Jan. 1997) --- Astronaut John M. Grunsfeld performs an inflight maintenance (IFM) task to re-activate power cables connected to experiments in the Spacehab Double Module (DM), onboard the Space Shuttle Atlantis.

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

DOE PAGES

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

2016-03-11

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

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

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

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

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

Automatic control and detector for three-terminal resistance measurement

DOEpatents

Fasching, George E.

1976-10-26

A device is provided for automatic control and detection in a three-terminal resistance measuring instrument. The invention is useful for the rapid measurement of the resistivity of various bulk material with a three-terminal electrode system. The device maintains the current through the sample at a fixed level while measuring the voltage across the sample to detect the sample resistance. The three-electrode system contacts the bulk material and the current through the sample is held constant by means of a control circuit connected to a first of the three electrodes and works in conjunction with a feedback controlled amplifier to null the voltage between the first electrode and a second electrode connected to the controlled amplifier output. An A.C. oscillator provides a source of sinusoidal reference voltage of the frequency at which the measurement is to be executed. Synchronous reference pulses for synchronous detectors in the control circuit and an output detector circuit are provided by a synchronous pulse generator. The output of the controlled amplifier circuit is sampled by an output detector circuit to develop at an output terminal thereof a D.C. voltage which is proportional to the sample resistance R. The sample resistance is that segment of the sample between the area of the first electrode and the third electrode, which is connected to ground potential.

Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-{beta} responsiveness

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

Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua

2008-03-10

Background: The matricellular protein connective tissue growth factor (CCN2) has been implicated in pathological fibrosis, but its physiologic role remains elusive. In vitro, transforming growth factor-{beta} (TGF-{beta}) induces CCN2 expression in mesenchymal cells. Because CCN2 can enhance profibrotic responses elicited by TGF-{beta}, it has been proposed that CCN2 functions as an essential downstream signaling mediator for TGF-{beta}. To explore this notion, we characterized TGF-{beta}-induced activation of fibroblasts from CCN2-null (CCN2{sup -/-}) mouse embryos. Methods: The regulation of CCN2 expression was examined in vivo in a model of fibrosis induced by bleomycin. Cellular TGF-{beta} signal transduction and regulation of collagen genemore » expression were examined in CCN2{sup -/-} MEFs by immunohistochemistry, Northern, Western and RT-PCR analysis, immunocytochemistry and transient transfection assays. Results: Bleomycin-induced skin fibrosis in the mouse was associated with substantial CCN2 up-regulation in lesional fibroblasts. Whereas in vitro proliferation rate of CCN2{sup -/-} MEFs was markedly reduced compared to wild type MEFs, TGF-{beta}-induced activation of the Smad pathways, including Smad2 phosphorylation, Smad2/3 and Smad4 nuclear accumulation and Smad-dependent transcriptional responses, were unaffected by loss of CCN2. The stimulation of COL1A2 and fibronectin mRNA expression and promoter activity, and of corresponding protein levels, showed comparable time and dose-response in wild type and CCN2{sup -/-} MEFs, whereas stimulation of alpha smooth muscle actin and myofibroblast transdifferentiation showed subtle impairment in MEFs lacking CCN2. Conclusion: Whereas endogenous CCN2 plays a role in regulation of proliferation and TGF-{beta}-induced myofibroblast transdifferentiation, it appears to be dispensable for Smad-dependent stimulation of collagen and extracellular matrix synthesis in murine embryonic fibroblasts.« less

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

PubMed

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

2015-03-01

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

The origin of nulls mode changes and timing noise in pulsars

NASA Astrophysics Data System (ADS)

Jones, P. B.

A solvable polar cap model obtained previously has normal states which may be associated with radio emission and null states. The solutions cannot be time-independent; the neutron star surface temperature T and mean surface nuclear charge Z are both functions of time. The normal and null states, and the transitions between them, form closed cycles in the T-Z plane. Normal-null transitions can occur inside a fraction of the area on the neutron star surface intersected by open magnetic flux lines. The fraction increases with pulsar period and becomes unity when the pulsar nears extinction. Frequency noise, mode changes, and pulse nulls have a common explanation in the transitions.

The origin of nulls, mode changes and timing noise in pulsars

NASA Astrophysics Data System (ADS)

Jones, P. B.

1982-09-01

A solvable polar cap model obtained previously has normal states which may be associated with radio emission, and null states. The solutions cannot be time-independent; the neutron star surface temperature T and mean surface nuclear charge Z are both functions of time. The normal and null states and the transitions between them, form closed cycles in the T-Z plane. Normal-null transitions can occur inside a fraction of the area of the neutron star surface intersected by open magnetic flux lines. The fraction increases with pulsar period and becomes unity when the pulsar nears extinction. Frequency noise, mode changes and pulse nulls have a common explanation in the transitions.

Peripheral Frequency of CD4+ CD28− Cells in Acute Ischemic Stroke

PubMed Central

Tuttolomondo, Antonino; Pecoraro, Rosaria; Casuccio, Alessandra; Di Raimondo, Domenico; Buttà, Carmelo; Clemente, Giuseppe; Corte, Vittoriano della; Guggino, Giuliana; Arnao, Valentina; Maida, Carlo; Simonetta, Irene; Maugeri, Rosario; Squatrito, Rosario; Pinto, Antonio

2015-01-01

Abstract CD4+ CD28− T cells also called CD28 null cells have been reported as increased in the clinical setting of acute coronary syndrome. Only 2 studies previously analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic stroke but, to our knowledge, peripheral frequency of CD28 null cells in each TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that CD4+ cells and, in particular, the CD28 null cell subset could show a different degree of peripheral percentage in subjects with acute ischemic stroke in relation to clinical subtype and severity of ischemic stroke. The aim of our study was to analyze peripheral frequency of CD28 null cells in subjects with acute ischemic stroke in relation to TOAST diagnostic subtype, and to evaluate their relationship with scores of clinical severity of acute ischemic stroke, and their predictive role in the diagnosis of acute ischemic stroke and diagnostic subtype We enrolled 98 consecutive subjects admitted to our recruitment wards with a diagnosis of ischemic stroke. As controls we enrolled 66 hospitalized patients without a diagnosis of acute ischemic stroke. Peripheral frequency of CD4+ and CD28 null cells has been evaluated with a FACS Calibur flow cytometer. Subjects with acute ischemic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to control subjects without acute ischemic stroke. Subjects with cardioembolic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to subjects with other TOAST subtypes. We observed a significant relationship between CD28 null cells peripheral percentage and Scandinavian Stroke Scale and NIHSS scores. ROC curve analysis showed that CD28 null cell percentage may be useful to differentiate between stroke subtypes. These findings seem suggest a possible role for a T-cell component also in acute ischemic stroke clinical setting showing a different peripheral frequency of CD28 null cells in relation of each TOAST subtype of stroke. PMID:25997053

Measurement Via Optical Near-Nulling and Subaperture Stitching

NASA Technical Reports Server (NTRS)

Forbes, Greg; De Vries, Gary; Murphy, Paul; Brophy, Chris

2012-01-01

A subaperture stitching interferometer system provides near-nulling of a subaperture wavefront reflected from an object of interest over a portion of a surface of the object. A variable optical element located in the radiation path adjustably provides near-nulling to facilitate stitching of subaperture interferograms, creating an interferogram representative of the entire surface of interest. This enables testing of aspheric surfaces without null optics customized for each surface prescription. The surface shapes of objects such as lenses and other precision components are often measured with interferometry. However, interferometers have a limited capture range, and thus the test wavefront cannot be too different from the reference or the interference cannot be analyzed. Furthermore, the performance of the interferometer is usually best when the test and reference wavefronts are nearly identical (referred to as a null condition). Thus, it is necessary when performing such measurements to correct for known variations in shape to ensure that unintended variations are within the capture range of the interferometer and accurately measured. This invention is a system for nearnulling within a subaperture stitching interferometer, although in principle, the concept can be employed by wavefront measuring gauges other than interferometers. The system employs a light source for providing coherent radiation of a subaperture extent. An object of interest is placed to modify the radiation (e.g., to reflect or pass the radiation), and a variable optical element is located to interact with, and nearly null, the affected radiation. A detector or imaging device is situated to obtain interference patterns in the modified radiation. Multiple subaperture interferograms are taken and are stitched, or joined, to provide an interferogram representative of the entire surface of the object of interest. The primary aspect of the invention is the use of adjustable corrective optics in the context of subaperture stitching near-nulling interferometry, wherein a complex surface is analyzed via multiple, separate, overlapping interferograms. For complex surfaces, the problem of managing the identification and placement of corrective optics becomes even more pronounced, to the extent that in most cases the null corrector optics are specific to the particular asphere prescription and no others (i.e. another asphere requires completely different null correction optics). In principle, the near-nulling technique does not require subaperture stitching at all. Building a near-null system that is practically useful relies on two key features: simplicity and universality. If the system is too complex, it will be difficult to calibrate and model its manufacturing errors, rendering it useless as a precision metrology tool and/or prohibitively expensive. If the system is not applicable to a wide range of test parts, then it does not provide significant value over conventional null-correction technology. Subaperture stitching enables simpler and more universal near-null systems to be effective, because a fraction of a surface is necessarily less complex than the whole surface (excepting the extreme case of a fractal surface description). The technique of near-nulling can significantly enhance aspheric subaperture stitching capability by allowing the interferometer to capture a wider range of aspheres. More over, subaperture stitching is essential to a truly effective near-nulling system, since looking at a fraction of the surface keeps the wavefront complexity within the capability of a relatively simple nearnull apparatus. Furthermore, by reducing the subaperture size, the complexity of the measured wavefront can be reduced until it is within the capability of the near-null design.

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

PubMed Central

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

2016-01-01

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/−), 31.4% had GSTT1 (−/+) alleles, and 6.4% had null genotypes (−/−) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/−, 30.5% were −/+, and 8.4% were −/−. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes. PMID:27294127

Genetic characterization of p27(kip1) and stathmin in controlling cell proliferation in vivo.

PubMed

Berton, Stefania; Pellizzari, Ilenia; Fabris, Linda; D'Andrea, Sara; Segatto, Ilenia; Canzonieri, Vincenzo; Marconi, Daniela; Schiappacassi, Monica; Benevol, Sara; Gattei, Valter; Colombatti, Alfonso; Belletti, Barbara; Baldassarre, Gustavo

2014-01-01

The CDK inhibitor p27(kip1) is a critical regulator of cell cycle progression, but the mechanisms by which p27(kip1) controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27(kip1) binding partner. To get more insights into the in vivo significance of this interaction, we generated p27(kip1) and stathmin double knock-out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27(kip1) null mice linked to the hyper-proliferative behavior, such as the increased body and organ weight, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27(kip1) null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profiling of mouse thymuses confirmed the phenotypes observed in vivo, showing that DKO clustered with WT more than with p27 knock-out tissue. Taken together, our results demonstrate that stathmin cooperates with p27(kip1) to control the early phase of G1 to S phase transition and that this function may be of particular relevance in the context of tumor progression.

Drosophila Growth and Development in the Absence of dMyc and dMnt

PubMed Central

Pierce, Sarah B.; Yost, Cynthia; Anderson, Sarah A. R.; Flynn, Erin M.; Delrow, Jeffrey; Eisenman, Robert N.

2008-01-01

Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in dm results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMyc leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the dm null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt. PMID:18241851

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

PubMed Central

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

2006-01-01

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

Foxa1 and Foxa2 are required for formation of the intervertebral discs.

PubMed

Maier, Jennifer A; Lo, YinTing; Harfe, Brian D

2013-01-01

The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2)), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-);Foxa2(c/c);ShhcreER(T2) double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.

Foxa1 and Foxa2 Are Required for Formation of the Intervertebral Discs

PubMed Central

Maier, Jennifer A.; Lo, YinTing; Harfe, Brian D.

2013-01-01

The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreERT2), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1−/−;Foxa2c/c;ShhcreERT2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord. PMID:23383217

pKAMA-ITACHI Vectors for Highly Efficient CRISPR/Cas9-Mediated Gene Knockout in Arabidopsis thaliana

PubMed Central

2017-01-01

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) system is widely used as a tool for genome engineering in various organisms. A complex consisting of Cas9 and single guide RNA (sgRNA) induces a DNA double-strand break in a sequence-specific manner, resulting in knockout. Some binary vectors for CRISPR/Cas9 in plants have been reported, but there is a problem with low efficiency. Here, we present a newly developed, highly efficient CRISPR/Cas9 vector for Arabidopsis thaliana, pKAMA-ITACHI Red (pKIR), harboring the RIBOSOMAL PROTEIN S5 A (RPS5A) promoter to drive Cas9. The RPS5A promoter maintains high constitutive expression at all developmental stages starting from the egg cell and including meristematic cells. Even in the T1 generation, pKIR induced null phenotypes in some genes: PHYTOENE DESATURASE 3 (PDS3), AGAMOUS (AG) and DUO POLLEN 1 (DUO1). Mutations induced by pKIR were carried in the germ cell line of the T1 generation. Surprisingly, in some lines, 100% of the T2 plants had the adh1 (ALCOHOL DEHYDROGENASE 1) null phenotype, indicating that pKIR strongly induced heritable mutations. Cas9-free T2 mutant plants were obtained by removing T2 seeds expressing a fluorescent marker in pKIR. Our results suggest that the pKIR system is a powerful molecular tool for genome engineering in Arabidopsis. PMID:27856772

Important Functional Roles of Basigin in Thymocyte Development and T cell Activation

PubMed Central

Yao, Hui; Teng, Yan; Sun, Qian; Xu, Jing; Chen, Ya-Tong; Hou, Ning; Cheng, Xuan; Yang, Xiao; Chen, Zhi-Nan

2014-01-01

Basigin is a highly glycosylated transmembrane protein that is expressed in a broad range of tissues and is involved in a number of physiological and pathological processes. However, the in vivo role of basigin remains unknown. To better understand the physiological and pathological functions of basigin in vivo, we generated a conditional null allele by introducing two loxP sites flanking exons 2 and 7 of the basigin gene (Bsg). Bsgfl/fl mice were born at the expected Mendelian ratio and showed a similar growth rate compared with wildtype mice. After crossing these mice with Lck-Cre transgenic mice, basigin expression was specifically inactivated in T cells in the resulting Lck-Cre; Bsgfl/fl mice. Although the birth and growth rate of Lck-Cre; Bsgfl/fl mice were similar to control mice, thymus development was partially arrested in Lck-Cre; Bsgfl/fl mice, specifically at the CD4+CD8+ double-positive (DP) and CD4 single-positive (CD4+CD8-, CD4SP) stages. In addition, CD4+ T cell activation was enhanced upon Concanavalin A (Con A) or anti-CD3/anti-CD28 stimulation but not upon PMA/Ionomycin stimulation in the absence of basigin. Overall, this study provided the first in vivo evidence for the function of basigin in thymus development. Moreover, the successful generation of the conditional null basigin allele provides a useful tool for the study of distinct physiological or pathological functions of basigin in different tissues at different development stages. PMID:24391450

Genetic characterization of p27kip1 and stathmin in controlling cell proliferation in vivo

PubMed Central

Berton, Stefania; Pellizzari, Ilenia; Fabris, Linda; D'Andrea, Sara; Segatto, Ilenia; Canzonieri, Vincenzo; Marconi, Daniela; Schiappacassi, Monica; Benevol, Sara; Gattei, Valter; Colombatti, Alfonso; Belletti, Barbara; Baldassarre, Gustavo

2014-01-01

The CDK inhibitor p27kip1 is a critical regulator of cell cycle progression, but the mechanisms by which p27kip1 controls cell proliferation in vivo are still not fully elucidated. We recently demonstrated that the microtubule destabilizing protein stathmin is a relevant p27kip1 binding partner. To get more insights into the in vivo significance of this interaction, we generated p27kip1 and stathmin double knock-out (DKO) mice. Interestingly, thorough characterization of DKO mice demonstrated that most of the phenotypes of p27kip1 null mice linked to the hyper-proliferative behavior, such as the increased body and organ weight, the outgrowth of the retina basal layer and the development of pituitary adenomas, were reverted by co-ablation of stathmin. In vivo analyses showed a reduced proliferation rate in DKO compared to p27kip1 null mice, linked, at molecular level, to decreased kinase activity of CDK4/6, rather than of CDK1 and CDK2. Gene expression profiling of mouse thymuses confirmed the phenotypes observed in vivo, showing that DKO clustered with WT more than with p27 knock-out tissue. Taken together, our results demonstrate that stathmin cooperates with p27kip1 to control the early phase of G1 to S phase transition and that this function may be of particular relevance in the context of tumor progression. PMID:25486569

A Defect in DNA Ligase4 Enhances the Frequency of TALEN-Mediated Targeted Mutagenesis in Rice1[OPEN

PubMed Central

Cermak, Tomas; Sugimoto, Kazuhiko; Saika, Hiroaki; Mori, Akiko; Osakabe, Keishi; Hamada, Masao; Katayose, Yuichi; Voytas, Daniel F.

2016-01-01

We have established methods for site-directed mutagenesis via transcription activator-like effector nucleases (TALENs) in the endogenous rice (Oryza sativa) waxy gene and demonstrated stable inheritance of TALEN-induced somatic mutations to the progeny. To analyze the role of classical nonhomologous end joining (cNHEJ) and alternative nonhomologous end joining (altNHEJ) pathways in TALEN-induced mutagenesis in plant cells, we investigated whether a lack of DNA Ligase4 (Lig4) affects the kinetics of TALEN-induced double-strand break repair in rice cells. Deep-sequencing analysis revealed that the frequency of all types of mutations, namely deletion, insertion, combination of insertion with deletion, and substitution, in lig4 null mutant calli was higher than that in a lig4 heterozygous mutant or the wild type. In addition, the ratio of large deletions (greater than 10 bp) and deletions repaired by microhomology-mediated end joining (MMEJ) to total deletion mutations in lig4 null mutant calli was higher than that in the lig4 heterozygous mutant or wild type. Furthermore, almost all insertions (2 bp or greater) were shown to be processed via copy and paste of one or more regions around the TALENs cleavage site and rejoined via MMEJ regardless of genetic background. Taken together, our findings indicate that the dysfunction of cNHEJ leads to a shift in the repair pathway from cNHEJ to altNHEJ or synthesis-dependent strand annealing. PMID:26668331

Trigger Factor can antagonize both SecB and DnaK/DnaJ chaperone functions in Escherichia coli

PubMed Central

Ullers, Ronald S.; Ang, Debbie; Schwager, Françoise; Georgopoulos, Costa; Genevaux, Pierre

2007-01-01

Polypeptides emerging from the ribosome are assisted by a pool of molecular chaperones and targeting factors, which enable them to efficiently partition as cytoplasmic, integral membrane, or exported proteins. In Escherichia coli, the chaperones SecB, Trigger Factor (TF), and DnaK are key players in this process. Here, we report that, as with dnaK or dnaJ mutants, a secB null strain exhibits a strong cold-sensitive (Cs) phenotype. Through suppressor analyses, we found that inactivating mutations in the tig gene encoding TF fully relieve both the Cs phenotype and protein aggregation observed in the absence of SecB. This antagonistic effect of TF depends on its ribosome-binding and chaperone activities but unrelated to its peptidyl-prolyl cis/trans isomerase (PPIase) activity. Furthermore, in contrast to the previously known synergistic action of TF and DnaK/DnaJ above 30°C, a tig null mutation partially suppresses the Cs phenotype exhibited by a compromised DnaK/DnaJ chaperone machine. The antagonistic role of TF is further exemplified by the fact that the secB dnaJ double mutant is viable only in the absence of TF. Finally, we show that, in the absence of TF, more SecA and ribosomes are associated with the inner membrane, suggesting that the presence of TF directly or indirectly interferes with the process of cotranslational protein targeting to the Sec translocon. PMID:17360615

Dynamics of networks of excitatory and inhibitory neurons in response to time-dependent inputs.

PubMed

Ledoux, Erwan; Brunel, Nicolas

2011-01-01

We investigate the dynamics of recurrent networks of excitatory (E) and inhibitory (I) neurons in the presence of time-dependent inputs. The dynamics is characterized by the network dynamical transfer function, i.e., how the population firing rate is modulated by sinusoidal inputs at arbitrary frequencies. Two types of networks are studied and compared: (i) a Wilson-Cowan type firing rate model; and (ii) a fully connected network of leaky integrate-and-fire (LIF) neurons, in a strong noise regime. We first characterize the region of stability of the "asynchronous state" (a state in which population activity is constant in time when external inputs are constant) in the space of parameters characterizing the connectivity of the network. We then systematically characterize the qualitative behaviors of the dynamical transfer function, as a function of the connectivity. We find that the transfer function can be either low-pass, or with a single or double resonance, depending on the connection strengths and synaptic time constants. Resonances appear when the system is close to Hopf bifurcations, that can be induced by two separate mechanisms: the I-I connectivity and the E-I connectivity. Double resonances can appear when excitatory delays are larger than inhibitory delays, due to the fact that two distinct instabilities exist with a finite gap between the corresponding frequencies. In networks of LIF neurons, changes in external inputs and external noise are shown to be able to change qualitatively the network transfer function. Firing rate models are shown to exhibit the same diversity of transfer functions as the LIF network, provided delays are present. They can also exhibit input-dependent changes of the transfer function, provided a suitable static non-linearity is incorporated.

Birational geometry of Fano double spaces of index two

NASA Astrophysics Data System (ADS)

Pukhlikov, Aleksandr V.

2010-10-01

We study birational geometry of Fano varieties realized as double covers \\sigma\\colon V\\to{\\ P}^M, M\\ge5, branched over generic smooth hypersurfaces W=W_{2(M-1)} of degree 2(M-1). We prove that the only structures of a rationally connected fibre space on V are pencil-subsystems of the free linear system \\vert{-\\frac12K_V}\\vert. The groups of birational and biregular self-maps of V coincide: \\operatorname{Bir}V=\\operatorname{Aut}V.

The use of acoustically tuned resonators to improve the sound transmission loss of double panel partitions

NASA Astrophysics Data System (ADS)

Mason, J. M.; Fahy, F. J.

1986-10-01

The effectiveness of tuned Helmholtz resonators connected to the partition cavity in double-leaf partitions utilized in situations requiring low weight structures with high transmission loss is investigated as a method of improving sound transmission loss. This is demonstrated by a simple theoretical model and then experimentally verified. Results show that substantial improvements may be obtained at and around the mass-air-mass frequency for a total resonator volume 15 percent of the cavity volume.

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.

Morgantown People Mover Phase II : Impact Assessment

DOT National Transportation Integrated Search

1984-02-01

This report describes an assessment of the Morgantown People Mover (MPM) system, which is an automated guideway transit system extending over 5,300 meters (3.3 miles) of double lane guideway, connecting West Virginia University's downtown campus with...

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

PubMed Central

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

2016-01-01

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

Nematode distributions as spatial null models for macroinvertebrate species richness across environmental gradients: A case from mountain lakes.

PubMed

de Mendoza, Guillermo; Traunspurger, Walter; Palomo, Alejandro; Catalan, Jordi

2017-05-01

Nematode species are widely tolerant of environmental conditions and disperse passively. Therefore, the species richness distribution in this group might largely depend on the topological distribution of the habitats and main aerial and aquatic dispersal pathways connecting them. If so, the nematode species richness distributions may serve as null models for evaluating that of other groups more affected by environmental gradients. We investigated this hypothesis in lakes across an altitudinal gradient in the Pyrenees. We compared the altitudinal distribution, environmental tolerance, and species richness, of nematodes with that of three other invertebrate groups collected during the same sampling: oligochaetes, chironomids, and nonchironomid insects. We tested the altitudinal bias in distributions with t -tests and the significance of narrow-ranging altitudinal distributions with randomizations. We compared results between groups with Fisher's exact tests. We then explored the influence of environmental factors on species assemblages in all groups with redundancy analysis (RDA), using 28 environmental variables. And, finally, we analyzed species richness patterns across altitude with simple linear and quadratic regressions. Nematode species were rarely biased from random distributions (5% of species) in contrast with other groups (35%, 47%, and 50%, respectively). The altitudinal bias most often shifted toward low altitudes (85% of biased species). Nematodes showed a lower portion of narrow-ranging species than any other group, and differed significantly from nonchironomid insects (10% and 43%, respectively). Environmental variables barely explained nematode assemblages (RDA adjusted R 2  = 0.02), in contrast with other groups (0.13, 0.19 and 0.24). Despite these substantial differences in the response to environmental factors, species richness across altitude was unimodal, peaking at mid elevations, in all groups. This similarity indicates that the spatial distribution of lakes across altitude is a primary driver of invertebrate richness. Provided that nematodes are ubiquitous, their distribution offers potential null models to investigate species richness across environmental gradients in other ecosystem types and biogeographic regions.

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

PubMed

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

2016-04-29

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

Residential self-selection bias in the estimation of built environment effects on physical activity between adolescence and young adulthood.

PubMed

Boone-Heinonen, Janne; Guilkey, David K; Evenson, Kelly R; Gordon-Larsen, Penny

2010-10-04

Built environment research is dominated by cross-sectional designs, which are particularly vulnerable to residential self-selection bias resulting from health-related attitudes, neighborhood preferences, or other unmeasured characteristics related to both neighborhood choice and health-related outcomes. We used cohort data from the National Longitudinal Study of Adolescent Health (United States; Wave I, 1994-95; Wave III, 2001-02; n = 12,701) and a time-varying geographic information system. Longitudinal relationships between moderate to vigorous physical activity (MVPA) bouts and built and socioeconomic environment measures (landcover diversity, pay and public physical activity facilities per 10,000 population, street connectivity, median household income, and crime rate) from adolescence to young adulthood were estimated using random effects models (biased by unmeasured confounders) and fixed effects models (within-person estimator, which adjusts for unmeasured confounders that are stable over time). Random effects models yielded null associations except for negative crime-MVPA associations [coefficient (95% CI): -0.056 (-0.083, -0.029) in males, -0.061 (-0.090, -0.033) in females]. After controlling for measured and time invariant unmeasured characteristics using within-person estimators, MVPA was higher with greater physical activity pay facilities in males [coefficient (95% CI): 0.024 (0.006, 0.042)], and lower with higher crime rates in males [coefficient (95% CI): -0.107 (-0.140, -0.075)] and females [coefficient (95% CI): -0.046 (-0.083, -0.009)]. Other associations were null or in the counter-intuitive direction. Comparison of within-person estimates to estimates unadjusted for unmeasured characteristics suggest that residential self-selection can bias associations toward the null, as opposed to its typical characterization as a positive confounder. Differential environment-MVPA associations by residential relocation suggest that studies examining changes following residential relocation may be vulnerable to selection bias. The authors discuss complexities of adjusting for residential self-selection and residential relocation, particularly during the adolescent to young adult transition.

Comparing species interaction networks along environmental gradients.

PubMed

Pellissier, Loïc; Albouy, Camille; Bascompte, Jordi; Farwig, Nina; Graham, Catherine; Loreau, Michel; Maglianesi, Maria Alejandra; Melián, Carlos J; Pitteloud, Camille; Roslin, Tomas; Rohr, Rudolf; Saavedra, Serguei; Thuiller, Wilfried; Woodward, Guy; Zimmermann, Niklaus E; Gravel, Dominique

2018-05-01

Knowledge of species composition and their interactions, in the form of interaction networks, is required to understand processes shaping their distribution over time and space. As such, comparing ecological networks along environmental gradients represents a promising new research avenue to understand the organization of life. Variation in the position and intensity of links within networks along environmental gradients may be driven by turnover in species composition, by variation in species abundances and by abiotic influences on species interactions. While investigating changes in species composition has a long tradition, so far only a limited number of studies have examined changes in species interactions between networks, often with differing approaches. Here, we review studies investigating variation in network structures along environmental gradients, highlighting how methodological decisions about standardization can influence their conclusions. Due to their complexity, variation among ecological networks is frequently studied using properties that summarize the distribution or topology of interactions such as number of links, connectance, or modularity. These properties can either be compared directly or using a procedure of standardization. While measures of network structure can be directly related to changes along environmental gradients, standardization is frequently used to facilitate interpretation of variation in network properties by controlling for some co-variables, or via null models. Null models allow comparing the deviation of empirical networks from random expectations and are expected to provide a more mechanistic understanding of the factors shaping ecological networks when they are coupled with functional traits. As an illustration, we compare approaches to quantify the role of trait matching in driving the structure of plant-hummingbird mutualistic networks, i.e. a direct comparison, standardized by null models and hypothesis-based metaweb. Overall, our analysis warns against a comparison of studies that rely on distinct forms of standardization, as they are likely to highlight different signals. Fostering a better understanding of the analytical tools available and the signal they detect will help produce deeper insights into how and why ecological networks vary along environmental gradients. © 2017 Cambridge Philosophical Society.

Winding Schemes for Wide Constant Power Range of Double Stator Transverse Flux Machine

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

Husain, Tausif; Hassan, Iftekhar; Sozer, Yilmaz

2015-05-01

Different ring winding schemes for double sided transverse flux machines are investigated in this paper for wide speed operation. The windings under investigation are based on two inverters used in parallel. At higher power applications this arrangement improves the drive efficiency. The new winding structure through manipulation of the end connection splits individual sets into two and connects the partitioned turns from individual stator sets in series. This configuration offers the flexibility of torque profiling and a greater flux weakening region. At low speeds and low torque only one winding set is capable of providing the required torque thus providingmore » greater fault tolerance. At higher speeds one set is dedicated to torque production and the other for flux control. The proposed method improves the machine efficiency and allows better flux weakening which is desirable for traction applications.« less

Double synchronized switch harvesting (DSSH): a new energy harvesting scheme for efficient energy extraction.

PubMed

Lallart, Mickaël; Garbuio, Lauric; Petit, Lionel; Richard, Claude; Guyomar, Daniel

2008-10-01

This paper presents a new technique for optimized energy harvesting using piezoelectric microgenerators called double synchronized switch harvesting (DSSH). This technique consists of a nonlinear treatment of the output voltage of the piezoelectric element. It also integrates an intermediate switching stage that ensures an optimal harvested power whatever the load connected to the microgenerator. Theoretical developments are presented considering either constant vibration magnitude, constant driving force, or independent extraction. Then experimental measurements are carried out to validate the theoretical predictions. This technique exhibits a constant output power for a wide range of load connected to the microgenerator. In addition, the extracted power obtained using such a technique allows a gain up to 500% in terms of maximal power output compared with the standard energy harvesting method. It is also shown that such a technique allows a fine-tuning of the trade-off between vibration damping and energy harvesting.

A global interaction network maps a wiring diagram of cellular function

PubMed Central

Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

2017-01-01

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

Terrestrial Planet Finder Interferometer Technology Status and Plans

NASA Technical Reports Server (NTRS)

Lawson, Perter R.; Ahmed, A.; Gappinger, R. O.; Ksendzov, A.; Lay, O. P.; Martin, S. R.; Peters, R. D.; Scharf, D. P.; Wallace, J. K.; Ware, B.

2006-01-01

A viewgraph presentation on the technology status and plans for Terrestrial Planet Finder Interferometer is shown. The topics include: 1) The Navigator Program; 2) TPF-I Project Overview; 3) Project Organization; 4) Technology Plan for TPF-I; 5) TPF-I Testbeds; 6) Nulling Error Budget; 7) Nulling Testbeds; 8) Nulling Requirements; 9) Achromatic Nulling Testbed; 10) Single Mode Spatial Filter Technology; 11) Adaptive Nuller Testbed; 12) TPF-I: Planet Detection Testbed (PDT); 13) Planet Detection Testbed Phase Modulation Experiment; and 14) Formation Control Testbed.

Surfactant-Associated Protein A Provides Critical Immunoprotection in Neonatal Mice▿

PubMed Central

George, Caroline L. S.; Goss, Kelli L.; Meyerholz, David K.; Lamb, Fred S.; Snyder, Jeanne M.

2008-01-01

The collectins surfactant-associated protein A (SP-A) and SP-D are components of innate immunity that are present before birth. Both proteins bind pathogens and assist in clearing infection. The significance of SP-A and SP-D as components of the neonatal immune system has not been investigated. To determine the role of SP-A and SP-D in neonatal immunity, wild-type, SP-A null, and SP-D null mice were bred in a bacterium-laden environment (corn dust bedding) or in a semisterile environment (cellulose fiber bedding). When reared in the corn dust bedding, SP-A null pups had significant mortality (P < 0.001) compared to both wild-type and SP-D null pups exposed to the same environment. The mortality of the SP-A null pups was associated with significant gastrointestinal tract pathology but little lung pathology. Moribund SP-A null newborn mice exhibited Bacillus sp. and Enterococcus sp. peritonitis. When the mother or newborn produced SP-A, newborn survival was significantly improved (P < 0.05) compared to the results when there was a complete absence of SP-A in both the mother and the pup. Significant sources of SP-A likely to protect a newborn include the neonatal lung and gastrointestinal tract but not the lactating mammary tissue of the mother. Furthermore, exogenous SP-A delivered by mouth to newborn SP-A null pups with SP-A null mothers improved newborn survival in the corn dust environment. Therefore, a lack of SP-D did not affect newborn survival, while SP-A produced by either the mother or the pup or oral exogenous SP-A significantly reduced newborn mortality associated with environmentally induced infection in SP-A null newborns. PMID:17967856

P value and the theory of hypothesis testing: an explanation for new researchers.

PubMed

Biau, David Jean; Jolles, Brigitte M; Porcher, Raphaël

2010-03-01

In the 1920s, Ronald Fisher developed the theory behind the p value and Jerzy Neyman and Egon Pearson developed the theory of hypothesis testing. These distinct theories have provided researchers important quantitative tools to confirm or refute their hypotheses. The p value is the probability to obtain an effect equal to or more extreme than the one observed presuming the null hypothesis of no effect is true; it gives researchers a measure of the strength of evidence against the null hypothesis. As commonly used, investigators will select a threshold p value below which they will reject the null hypothesis. The theory of hypothesis testing allows researchers to reject a null hypothesis in favor of an alternative hypothesis of some effect. As commonly used, investigators choose Type I error (rejecting the null hypothesis when it is true) and Type II error (accepting the null hypothesis when it is false) levels and determine some critical region. If the test statistic falls into that critical region, the null hypothesis is rejected in favor of the alternative hypothesis. Despite similarities between the two, the p value and the theory of hypothesis testing are different theories that often are misunderstood and confused, leading researchers to improper conclusions. Perhaps the most common misconception is to consider the p value as the probability that the null hypothesis is true rather than the probability of obtaining the difference observed, or one that is more extreme, considering the null is true. Another concern is the risk that an important proportion of statistically significant results are falsely significant. Researchers should have a minimum understanding of these two theories so that they are better able to plan, conduct, interpret, and report scientific experiments.

Sf29 Gene of Spodoptera frugiperda Multiple Nucleopolyhedrovirus Is a Viral Factor That Determines the Number of Virions in Occlusion Bodies▿

PubMed Central

Simón, Oihane; Williams, Trevor; Asensio, Aaron C.; Ros, Sarhay; Gaya, Andrea; Caballero, Primitivo; Possee, Robert D.

2008-01-01

The genome of Spodoptera frugiperda multiple nucleopolyhedrovirus (NPV) was inserted into a bacmid (Sfbac) and used to produce a mutant lacking open reading frame 29 (Sf29null). Sf29null bacmid DNA was able to generate an infection in S. frugiperda. Approximately six times less DNA was present in occlusion bodies (OBs) produced by the Sf29null bacmid in comparison to viruses containing this gene. This reduction in DNA content was consistent with fewer virus particles being packaged within Sf29null bacmid OBs, as determined by fractionation of dissolved polyhedra and comparison of occlusion-derived virus (ODV) infectivity in cell culture. DNA from Sfbac, Sf29null, or Sf29null-repair, in which the gene deletion had been repaired, were equally infectious when used to transfect S. frugiperda. All three viruses produced similar numbers of OBs, although those from Sf29null were 10-fold less infectious than viruses with the gene. Insects infected with Sf29null bacmid died ∼24 h later than positive controls, consistent with the reduced virus particle content of Sf29null OBs. Transcripts from Sf29 were detected in infected insects 12 h prior to those from the polyhedrin gene. Homologs to Sf29 were present in other group II NPVs, and similar sequences were present in entomopoxviruses. Analysis of the Sf29 predicted protein sequence revealed signal peptide and transmembrane domains, but the presence of 12 potential N-glycosylation sites suggest that it is not an ODV envelope protein. Other motifs, including zinc-binding and threonine-rich regions, suggest degradation and adhesion functions. We conclude that Sf29 is a viral factor that determines the number of ODVs occluded in each OB. PMID:18550678

Constitutive Androgen Receptor-Null Mice Are Sensitive to the Toxic Effects of Parathion: Association with Reduced Cytochrome P450-Mediated Parathion MetabolismS⃞

PubMed Central

Mota, Linda C.; Hernandez, Juan P.

2010-01-01

Constitutive androgen receptor (CAR) is activated by several chemicals and in turn regulates multiple detoxification genes. Our research demonstrates that parathion is one of the most potent, environmentally relevant CAR activators with an EC50 of 1.43 μM. Therefore, animal studies were conducted to determine whether CAR was activated by parathion in vivo. Surprisingly, CAR-null mice, but not wild-type (WT) mice, showed significant parathion-induced toxicity. However, parathion did not induce Cyp2b expression, suggesting that parathion is not a CAR activator in vivo, presumably because of its short half-life. CAR expression is also associated with the expression of several drug-metabolizing cytochromes P450 (P450). CAR-null mice demonstrate lower expression of Cyp2b9, Cyp2b10, Cyp2c29, and Cyp3a11 primarily, but not exclusively in males. Therefore, we incubated microsomes from untreated WT and CAR-null mice with parathion in the presence of esterase inhibitors to determine whether CAR-null mice show perturbed P450-mediated parathion metabolism compared with that in WT mice. The metabolism of parathion to paraoxon and p-nitrophenol (PNP) was reduced in CAR-null mice with male CAR-null mice showing reduced production of both paraoxon and PNP, and female CAR-null mice showing reduced production of only PNP. Overall, the data indicate that CAR-null mice metabolize parathion slower than WT mice. These results provide a potential mechanism for increased sensitivity of individuals with lower CAR activity such as newborns to parathion and potentially other chemicals due to decreased metabolic capacity. PMID:20573718

Hot gas engine heater head

DOEpatents

Berntell, John O.

1983-01-01

A heater head for a multi-cylinder double acting hot gas engine in which each cylinder is surrounded by an annular regenerator unit, and in which the tops of each cylinder and its surrounding regenerator are interconnected by a multiplicity of heater tubes. A manifold for the heater tubes has a centrally disposed duct connected to the top of the cylinder and surrounded by a wider duct connecting the other ends of the heater tubes with the regenerator unit.

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

PubMed

Manfroi, Silvia; Scarcello, Antonio; Pagliaro, Pasqualepaolo

2015-10-01

Molecular genetic studies on Duffy blood group antigens have identified mutations underlying rare FY*Null and FY*X alleles. FY*Null has a high frequency in Blacks, especially from sub-Saharan Africa, while its frequency is not defined in Caucasians. FY*X allele, associated with Fy(a-b+w) phenotype, has a frequency of 2-3.5% in Caucasian people while it is absent in Blacks. During the project of extensive blood group genotyping in patients affected by hemoglobinopathies, we identified FY*X/FY*Null and FY*A/FY*Null genotypes in a Caucasian thalassemic family from Sardinia. We speculate on the frequency of FY*X and FY*Null alleles in Caucasian and Black people; further, we focused on the association of FY*X allele with weak Fyb antigen expression on red blood cells and its identification performing high sensitivity serological typing methods or genotyping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Position sensor for a fuel injection element in an internal combustion engine

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

Fulkerson, D.E.; Geske, M.L.

1987-08-18

This patent describes an electronic circuit for dynamically sensing and processing signals representative of changes in a magnet field, the circuit comprising: means for sensing a change in a magnetic field external to the circuit and providing an output representative of the change; circuit means electronically coupled with the output of the sensing means for providing an output indicating the presence of the magnetic field change; and a nulling circuit coupled with the output of the sensing means and across the indicating circuit means for nulling the electronic circuit responsive to the sensing means output, to thereby avoid ambient magneticmore » fields temperature and process variations, and wherein the nulling circuit comprises a capacitor coupled to the output of the nulling circuit, means for charging and discharging the capacitor responsive to any imbalance in the input to the nulling circuit, and circuit means coupling the capacitor with the output of the sensing means for nulling any imbalance during the charging or discharging of the capacitor.« less

Naked singularity resolution in cylindrical collapse

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

Kurita, Yasunari; Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto, 606-8502; Nakao, Ken-ichi

In this paper, we study the gravitational collapse of null dust in cylindrically symmetric spacetime. The naked singularity necessarily forms at the symmetry axis. We consider the situation in which null dust is emitted again from the naked singularity formed by the collapsed null dust and investigate the backreaction by this emission for the naked singularity. We show a very peculiar but physically important case in which the same amount of null dust as that of the collapsed one is emitted from the naked singularity as soon as the ingoing null dust hits the symmetry axis and forms the nakedmore » singularity. In this case, although this naked singularity satisfies the strong curvature condition by Krolak (limiting focusing condition), geodesics which hit the singularity can be extended uniquely across the singularity. Therefore, we may say that the collapsing null dust passes through the singularity formed by itself and then leaves for infinity. Finally, the singularity completely disappears and the flat spacetime remains.« less

Evaluation of null-point detection methods on simulation data

NASA Astrophysics Data System (ADS)

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

2014-05-01

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

The importance of proving the null.

PubMed

Gallistel, C R

2009-04-01

Null hypotheses are simple, precise, and theoretically important. Conventional statistical analysis cannot support them; Bayesian analysis can. The challenge in a Bayesian analysis is to formulate a suitably vague alternative, because the vaguer the alternative is (the more it spreads out the unit mass of prior probability), the more the null is favored. A general solution is a sensitivity analysis: Compute the odds for or against the null as a function of the limit(s) on the vagueness of the alternative. If the odds on the null approach 1 from above as the hypothesized maximum size of the possible effect approaches 0, then the data favor the null over any vaguer alternative to it. The simple computations and the intuitive graphic representation of the analysis are illustrated by the analysis of diverse examples from the current literature. They pose 3 common experimental questions: (a) Are 2 means the same? (b) Is performance at chance? (c) Are factors additive? (c) 2009 APA, all rights reserved

Independently variable phase and stroke control for a double acting Stirling engine

DOEpatents

Berchowitz, David M.

1983-01-01

A phase and stroke control apparatus for the pistons of a Stirling engine includes a ring on the end of each piston rod in which a pair of eccentrics is arranged in series, torque transmitting relationship. The outer eccentric is rotatably mounted in the ring and is rotated by the orbiting ring; the inner eccentric is mounted on an output shaft. The two eccentrics are mounted for rotation together within the ring during normal operation. A device is provided for rotating one eccentric with respect to another to change the effective eccentricity of the pair of eccentrics. A separately controlled phase adjustment is provided to null the phase change introduced by the change in the orientation of the outer eccentric, and also to enable the phase of the pistons to be changed independently of the stroke change.

Direct Search for Dark Matter with DarkSide

NASA Astrophysics Data System (ADS)

Agnes, P.; Alexander, T.; Alton, A.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Brigatti, A.; Brodsky, J.; Budano, F.; Cadonati, L.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; Cocco, A. G.; Crippa, L.; D'Angelo, D.; D'Incecco, M.; Davini, S.; De Deo, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Goretti, A.; Grandi, L.; Gromov, M.; Guan, M. Y.; Guardincerri, Y.; Hackett, B.; Herner, K.; Hungerford, E. V.; Ianni, Al; Ianni, An; Jollet, C.; Keeter, K.; Kendziora, C.; Kidner, S.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kurlej, A.; Li, P. X.; Loer, B.; Lombardi, P.; Love, C.; Ludhova, L.; Luitz, S.; Ma, Y. Q.; Machulin, I.; Mandarano, A.; Mari, S.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meroni, E.; Meyers, P. D.; Milincic, R.; Montanari, D.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B.; Muratova, V.; Musico, P.; Nelson, A.; Odrowski, S.; Okounkova, M.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Papp, L.; Parmeggiano, S.; Parsells, R.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; Pugachev, D.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Renshaw, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Segreto, E.; Semenov, D.; Shields, E.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Unzhakov, E.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A.; Westerdale, S.; Wojcik, M.; Wright, A.; Xiang, X.; Xu, J.; Yang, C. G.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhu, C.; Zuzel, G.

2015-11-01

The DarkSide experiment is designed for the direct detection of Dark Matter with a double phase liquid Argon TPC operating underground at Laboratori Nazionali del Gran Sasso. The TPC is placed inside a 30 tons liquid organic scintillator sphere, acting as a neutron veto, which is in turn installed inside a 1 kt water Cherenkov detector. The current detector is running since November 2013 with a 50 kg atmospheric Argon fill and we report here the first null results of a Dark Matter search for a (1422 ± 67) kg.d exposure. This result correspond to a 90% CL upper limit on the WIMP-nucleon cross section of 6.1 × 10-44 cm2 (for a WIMP mass of 100 GeV/c2) and it's currently the most sensitive limit obtained with an Argon target.

Hierarchy of Certain Types of DNA Splicing Systems

NASA Astrophysics Data System (ADS)

Yusof, Yuhani; Sarmin, Nor Haniza; Goode, T. Elizabeth; Mahmud, Mazri; Heng, Fong Wan

A Head splicing system (H-system)consists of a finite set of strings (words) written over a finite alphabet, along with a finite set of rules that acts on the strings by iterated cutting and pasting to create a splicing language. Any interpretation that is aligned with Tom Head's original idea is one in which the strings represent double-stranded deoxyribonucleic acid (dsDNA) and the rules represent the cutting and pasting action of restriction enzymes and ligase, respectively. A new way of writing the rule sets is adopted so as to make the biological interpretation transparent. This approach is used in a formal language- theoretic analysis of the hierarchy of certain classes of splicing systems, namely simple, semi-simple and semi-null splicing systems. The relations between such systems and their associated languages are given as theorems, corollaries and counterexamples.

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach.

PubMed

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-18

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach

NASA Astrophysics Data System (ADS)

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-01

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

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

Super-BMS3 algebras from {N}=2 flat supergravities

NASA Astrophysics Data System (ADS)

Lodato, Ivano; Merbis, Wout

2016-11-01

We consider two possible flat space limits of three dimensional {N}=(1, 1) AdS supergravity. They differ by how the supercharges are scaled with the AdS radius ℓ: the first limit (democratic) leads to the usual super-Poincaré theory, while a novel `twisted' theory of supergravity stems from the second (despotic) limit. We then propose boundary conditions such that the asymptotic symmetry algebras at null infinity correspond to supersymmetric extensions of the BMS algebras previously derived in connection to non- and ultra-relativistic limits of the {N}=(1, 1) Virasoro algebra in two dimensions. Finally, we study the supersymmetric energy bounds and find the explicit form of the asymptotic and global Killing spinors of supersymmetric solutions in both flat space supergravity theories.

Dystroglycan and muscular dystrophies related to the dystrophin-glycoprotein complex.

PubMed

Sciandra, Francesca; Bozzi, Manuela; Bianchi, Marzia; Pavoni, Ernesto; Giardina, Bruno; Brancaccio, Andrea

2003-01-01

Dystroglycan (DG) is an adhesion molecule composed of two subunits, alpha and beta, that are produced by the post-translational cleavage of a single precursor molecule. DG is a pivotal component of the dystrophin-glycoprotein complex (DGC), which connects the extracellular matrix to the cytoskeleton in skeletal muscle and many other tissues. Some muscular dystrophies are caused by mutations of DGC components, such as dystrophin, sarcoglycan or laminin-2, or also of DGC-associated molecules, such as caveolin-3. DG-null mice died during early embriogenesis and no neuromuscular diseases directly associated to genetic abnormalities of DG were identified so far. However, DG plays a crucial role for muscle integrity since its targeting at the sarcolemma is often perturbed in DGC-related neuromuscular disorders.

The contribution of scalars to N = 4 SYM amplitudes II: Young tableaux, asymptotic factorisation and strong coupling

NASA Astrophysics Data System (ADS)

Bonini, Alfredo; Fioravanti, Davide; Piscaglia, Simone; Rossi, Marco

2018-06-01

We disentangle the contribution of scalars to the OPE series of null hexagonal Wilson loops/MHV gluon scattering amplitudes in multicolour N = 4 SYM. In specific, we develop a systematic computation of the SU (4) matrix part of the Wilson loop by means of Young tableaux (with several examples). Then, we use a peculiar factorisation property (when a group of rapidities becomes large) to deduce an explicit polar form. Furthermore, we emphasise the advantages of expanding the logarithm of the Wilson loop in terms of 'connected functions' as we apply this procedure to find an explicit strong coupling expansion (definitively proving that the leading order can prevail on the classical AdS5 string contribution).

Space confinement and rotation stress induced self-organization of double-helix nanostructure: a nanotube twist with a moving catalyst head.

PubMed

Zhao, Meng-Qiang; Zhang, Qiang; Tian, Gui-Li; Huang, Jia-Qi; Wei, Fei

2012-05-22

Inorganic materials with double-helix structure have attracted intensive attention due to not only their elegant morphology but also their amazing morphology-related potential applications. The investigation on the formation mechanism of the inorganic double-helix nanostructure is the first step for the fundamental studies of their materials or physical properties. Herein, we demonstrated the space confinement and rotation stress induced self-organization mechanism of the carbon nanotube (CNT)-array double helices under scanning electron microscopy by directly observing their formation process from individual layered double hydroxide flakes, which is a kind of hydrotalcite-like material composed of positively charged layers and charge-balancing interlayer anions. Space confinement is considered to be the most important extrinsic factor for the formation of CNT-array double helices. Synchronous growth of the CNT arrays oppositely from LDH flakes with space confinement on both sides at the same time is essential for the growth of CNT-array double helices. Coiling of the as-grown CNT arrays into double helices will proceed by self-organization, tending to the most stable morphology in order to release their internal rotation stress. Based on the demonstrated mechanism, effective routes were carried out to improve the selectivity for CNT-array double helices. The work provides a promising method for the fabrication of double-helix nanostructures with their two helices connected at the end by self-assembly.

Gustatory papillae and taste bud development and maintenance in the absence of TrkB ligands BDNF and NT-4.

PubMed

Ito, Akira; Nosrat, Christopher A

2009-09-01

Taste buds and the peripheral nerves innervating them are two important components of the peripheral gustatory system. They require appropriate connections for the taste system to function. Neurotrophic factors play crucial roles in the innervation of peripheral sensory organs and tissues. Both brain-derived neurotrophic factor (BDNF) null-mutated and neurotrophin-4 (NT-4) null-mutated mice exhibit peripheral gustatory deficits. BDNF and NT-4 bind to a common high affinity tyrosine kinase receptor, TrkB (NTRK-2), and a common p75 neurotrophin receptor (NGFR). We are currently using a transgenic mouse model to study peripheral taste system development and innervation in the absence of both TrkB ligands. We show that taste cell progenitors express taste cell markers during early stages of taste bud development in both BDNF(-/-)xNT-4(-/-) and wild-type mice. At early embryonic stages, taste bud progenitors express Troma-1, Shh, and Sox2 in all mice. At later stages, lack of innervation becomes a prominent feature in BDNF(-/-)xNT-4(-/-) mice leading to a decreasing number of fungiform papillae and morphologically degenerating taste cells. A total loss of vallate taste cells also occurs in postnatal transgenic mice. Our data indicate an initial independence but a later permissive and essential role for innervation in taste bud development and maintenance.

Why double-stranded RNA resists condensation

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

Tolokh, Igor S.; Pabit, Suzette; Katz, Andrea M.

2014-09-15

The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to attraction between the negatively charged helices and eventually to condensation. Surprisingly, this effect is suppressed in double-stranded RNA, which carries the same charge as the DNA, but assumes a different double helical form. However, additional characterization of short (25 base-pairs) nucleic acid (NA) duplex structures by circular dichroism shows that measured differences in condensation are not solely determined by duplex helical geometry. Here we combine experiment, theory, and atomistic simulations to propose a mechanism that connects the observed variations in condensation of short NA duplexesmore » with the spatial variation of cobalt hexammine (CoHex) binding at the NA duplex surface. The atomistic picture that emerged showed that CoHex distributions around the NA reveals two major NA-CoHex binding modes -- internal and external -- distinguished by the proximity of bound CoHex to the helical axis. Decreasing trends in experimentally observed condensation propensity of the four studied NA duplexes (from B-like form of homopolymeric DNA, to mixed sequence DNA, to DNA:RNA hybrid, to A-like RNA) are explained by the progressive decrease of a single quantity: the fraction of CoHex ions in the external binding mode. Thus, while NA condensation depends on a complex interplay between various structural and sequence features, our coupled experimental and theoretical results suggest a new model in which a single parameter connects the NA condensation propensity with geometry and sequence dependence of CoHex binding.« less

Pronouns in Catalan: Information, Discourse and Strategy

ERIC Educational Resources Information Center

Mayol, Laia

2009-01-01

This thesis investigates the variation between null and overt pronouns in subject position in Catalan, a null subject language. I argue that null and overt subject pronouns are two resources that speakers efficiently deploy to signal their intended interpretation regarding antecedent choice or semantic meaning, and that communicative agents…

The Importance of Proving the Null

ERIC Educational Resources Information Center

Gallistel, C. R.

2009-01-01

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

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

EPA Science Inventory

Background: Simulation studies have previously demonstrated that time-series analyses using smoothing splines correctly model null health-air pollution associations. Methods: We repeatedly simulated season, meteorology and air quality for the metropolitan area of Atlanta from cyc...

Complex Fuzzy Set-Valued Complex Fuzzy Measures and Their Properties

PubMed Central

Ma, Shengquan; Li, Shenggang

2014-01-01

Let F*(K) be the set of all fuzzy complex numbers. In this paper some classical and measure-theoretical notions are extended to the case of complex fuzzy sets. They are fuzzy complex number-valued distance on F*(K), fuzzy complex number-valued measure on F*(K), and some related notions, such as null-additivity, pseudo-null-additivity, null-subtraction, pseudo-null-subtraction, autocontionuous from above, autocontionuous from below, and autocontinuity of the defined fuzzy complex number-valued measures. Properties of fuzzy complex number-valued measures are studied in detail. PMID:25093202

Comparison null imaging ellipsometry using polarization rotator

NASA Astrophysics Data System (ADS)

Park, Sungmo; Kim, Eunsung; Kim, Jiwon; An, Ilsin

2018-05-01

In this study, two-reflection imaging ellipsometry is carried out to compare the changes in polarization states between two samples. By using a polarization rotator, the parallel and perpendicular components of polarization are easily switched between the two samples being compared. This leads to an intensity image consisting of null and off-null points depending on the difference in optical characteristics between the two samples. This technique does not require any movement of optical elements for nulling and can be used to detect defects or surface contamination for quality control of samples.

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

NASA Astrophysics Data System (ADS)

Konoplya, R. A.; Stuchlík, Z.

2017-08-01

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

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

NASA Astrophysics Data System (ADS)

Zhang, Zhiwei; Wang, Zhenyu

2017-10-01

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

The relationship of the local food environment with obesity: A systematic review of methods, study quality, and results.

PubMed

Cobb, Laura K; Appel, Lawrence J; Franco, Manuel; Jones-Smith, Jessica C; Nur, Alana; Anderson, Cheryl A M

2015-07-01

To examine the relationship between local food environments and obesity and assess the quality of studies reviewed. Systematic keyword searches identified studies from US and Canada that assessed the relationship of obesity to local food environments. We applied a quality metric based on design, exposure and outcome measurement, and analysis. We identified 71 studies representing 65 cohorts. Overall, study quality was low; 60 studies were cross-sectional. Associations between food outlet availability and obesity were predominantly null. Among non-null associations, we saw a trend toward inverse associations between supermarket availability and obesity (22 negative, 4 positive, 67 null) and direct associations between fast food and obesity (29 positive, 6 negative, 71 null) in adults. We saw direct associations between fast food availability and obesity in lower income children (12 positive, 7 null). Indices including multiple food outlets were most consistently associated with obesity in adults (18 expected, 1 not expected, 17 null). Limiting to higher quality studies did not affect results. Despite the large number of studies, we found limited evidence for associations between local food environments and obesity. The predominantly null associations should be interpreted cautiously due to the low quality of available studies. © 2015 The Obesity Society.

The Lande-Kirkpatrick mechanism is the null model of evolution by intersexual selection: implications for meaning, honesty, and design in intersexual signals.

PubMed

Prum, Richard O

2010-11-01

The Fisher-inspired, arbitrary intersexual selection models of Lande (1981) and Kirkpatrick (1982), including both stable and unstable equilibrium conditions, provide the appropriate null model for the evolution of traits and preferences by intersexual selection. Like the Hardy–Weinberg equilibrium, the Lande–Kirkpatrick (LK) mechanism arises as an intrinsic consequence of genetic variation in trait and preference in the absence of other evolutionary forces. The LK mechanism is equivalent to other intersexual selection mechanisms in the absence of additional selection on preference and with additional trait-viability and preference-viability correlations equal to zero. The LK null model predicts the evolution of arbitrary display traits that are neither honest nor dishonest, indicate nothing other than mating availability, and lack any meaning or design other than their potential to correspond to mating preferences. The current standard for demonstrating an arbitrary trait is impossible to meet because it requires proof of the null hypothesis. The LK null model makes distinct predictions about the evolvability of traits and preferences. Examples of recent intersexual selection research document the confirmationist pitfalls of lacking a null model. Incorporation of the LK null into intersexual selection will contribute to serious examination of the extent to which natural selection on preferences shapes signals.

Viewing condition dependence of the gaze-evoked nystagmus in Arnold Chiari type 1 malformation.

PubMed

Ghasia, Fatema F; Gulati, Deepak; Westbrook, Edward L; Shaikh, Aasef G

2014-04-15

Saccadic eye movements rapidly shift gaze to the target of interest. Once the eyes reach a given target, the brainstem ocular motor integrator utilizes feedback from various sources to assure steady gaze. One of such sources is cerebellum whose lesion can impair neural integration leading to gaze-evoked nystagmus. The gaze evoked nystagmus is characterized by drifts moving the eyes away from the target and a null position where the drifts are absent. The extent of impairment in the neural integration for two opposite eccentricities might determine the location of the null position. Eye in the orbit position might also determine the location of the null. We report this phenomenon in a patient with Arnold Chiari type 1 malformation who had intermittent esotropia and horizontal gaze-evoked nystagmus with a shift in the null position. During binocular viewing, the null was shifted to the right. During monocular viewing, when the eye under cover drifted nasally (secondary to the esotropia), the null of the gaze-evoked nystagmus reorganized toward the center. We speculate that the output of the neural integrator is altered from the bilateral conflicting eye in the orbit position secondary to the strabismus. This could possibly explain the reorganization of the location of the null position. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India.

PubMed

Mastana, Sarabjit S; Kaur, Antarpreet; Hale, Rachel; Lindley, Martin R

2013-12-01

Glutathione S-transferases (GSTs) belong to a group of multigene and multifunctional detoxification enzymes, which defend cells against a wide variety of toxic insults and oxidative stress. Oxidative stress leads to cellular dysfunction which contributes to the pathophysiology of diseases such as cancer, atherosclerosis, and diabetes mellitus. It is important to assess whether the glutathione S-Transferase (GSTT1, GSTM1 and GSTP1) genotypes are associated with type 2 diabetes mellitus as deletion polymorphisms have an impaired capability to counteract the oxidative stress which is a feature of diabetes. GSTT1, GSTM1 and GSTP1 gene polymorphisms were analysed in 321 patients and 309 healthy controls from an endogamous population from north India. An association analysis was carried out at two levels (a) individual genes and (b) their double and triple combinations. The proportion of GSTT1 and GSTM1 null genotypes was higher in diabetics compared to controls (GSTT1 30.8 vs. 21.0 %; GSTM1 49.5 vs. 27.2 %). The frequency of the null genotype at both loci was higher in diabetics (19.6 vs. 7.8 %) leading to an odds ratio of 2.90 (CI 1.76-4.78, P < 0.0001). At GSTP1locus, patients had a higher frequency of the V/V genotype (15.6 vs. 7.5 %) and significant susceptible odds ratio (2.56, CI 1.47-4.48, P < 0.001). A combination of null genotypes at GSTT1 and GSTM1 loci and V/V genotype of GSTP1 locus showed highest odds ratio (9.64, CI 1.53-60.63, P < 0.01). Overall this study highlights that GST genes may play an important role in the pathogenesis of type 2 diabetes. The risk is higher in individuals carrying more than one susceptible genotype at these loci. The potential role of GST polymorphisms as markers of susceptibility to type 2 diabetes needs further investigations in a larger number of patients and populations.

Predictive uncertainty analysis of a saltwater intrusion model using null-space Monte Carlo

USGS Publications Warehouse

Herckenrath, Daan; Langevin, Christian D.; Doherty, John

2011-01-01

Because of the extensive computational burden and perhaps a lack of awareness of existing methods, rigorous uncertainty analyses are rarely conducted for variable-density flow and transport models. For this reason, a recently developed null-space Monte Carlo (NSMC) method for quantifying prediction uncertainty was tested for a synthetic saltwater intrusion model patterned after the Henry problem. Saltwater intrusion caused by a reduction in fresh groundwater discharge was simulated for 1000 randomly generated hydraulic conductivity distributions, representing a mildly heterogeneous aquifer. From these 1000 simulations, the hydraulic conductivity distribution giving rise to the most extreme case of saltwater intrusion was selected and was assumed to represent the "true" system. Head and salinity values from this true model were then extracted and used as observations for subsequent model calibration. Random noise was added to the observations to approximate realistic field conditions. The NSMC method was used to calculate 1000 calibration-constrained parameter fields. If the dimensionality of the solution space was set appropriately, the estimated uncertainty range from the NSMC analysis encompassed the truth. Several variants of the method were implemented to investigate their effect on the efficiency of the NSMC method. Reducing the dimensionality of the null-space for the processing of the random parameter sets did not result in any significant gains in efficiency and compromised the ability of the NSMC method to encompass the true prediction value. The addition of intrapilot point heterogeneity to the NSMC process was also tested. According to a variogram comparison, this provided the same scale of heterogeneity that was used to generate the truth. However, incorporation of intrapilot point variability did not make a noticeable difference to the uncertainty of the prediction. With this higher level of heterogeneity, however, the computational burden of generating calibration-constrained parameter fields approximately doubled. Predictive uncertainty variance computed through the NSMC method was compared with that computed through linear analysis. The results were in good agreement, with the NSMC method estimate showing a slightly smaller range of prediction uncertainty than was calculated by the linear method. Copyright 2011 by the American Geophysical Union.

Vibro-acoustic modelling of aircraft double-walls with structural links using Statistical Energy Analysis

NASA Astrophysics Data System (ADS)

Campolina, Bruno L.

The prediction of aircraft interior noise involves the vibroacoustic modelling of the fuselage with noise control treatments. This structure is composed of a stiffened metallic or composite panel, lined with a thermal and acoustic insulation layer (glass wool), and structurally connected via vibration isolators to a commercial lining panel (trim). The goal of this work aims at tailoring the noise control treatments taking design constraints such as weight and space optimization into account. For this purpose, a representative aircraft double-wall is modelled using the Statistical Energy Analysis (SEA) method. Laboratory excitations such as diffuse acoustic field and point force are addressed and trends are derived for applications under in-flight conditions, considering turbulent boundary layer excitation. The effect of the porous layer compression is firstly addressed. In aeronautical applications, compression can result from the installation of equipment and cables. It is studied analytically and experimentally, using a single panel and a fibrous uniformly compressed over 100% of its surface. When compression increases, a degradation of the transmission loss up to 5 dB for a 50% compression of the porous thickness is observed mainly in the mid-frequency range (around 800 Hz). However, for realistic cases, the effect should be reduced since the compression rate is lower and compression occurs locally. Then the transmission through structural connections between panels is addressed using a four-pole approach that links the force-velocity pair at each side of the connection. The modelling integrates experimental dynamic stiffness of isolators, derived using an adapted test rig. The structural transmission is then experimentally validated and included in the double-wall SEA model as an equivalent coupling loss factor (CLF) between panels. The tested structures being flat, only axial transmission is addressed. Finally, the dominant sound transmission paths are identified in the 100 Hz to 10 kHz frequency range for double-walls under diffuse acoustic field and under point-force excitations. Non-resonant transmission is higher at low frequencies (frequencies lower than 1 kHz) while the structure-borne and the airborne paths dominate at mid- and high-frequencies, around 1 kHz and higher, respectively. An experimental validation on double-walls shows that the model is able to predict changes in the overall transmission caused by different structural couplings (rigid coupling, coupling via isolators and structurally uncoupled). Noise reduction means adapted to each transmission path, such as absorption, dissipation and structural decoupling, may be then derived. Keywords: Statistical energy analysis, Vibration isolator, Double-wall, Transfer path analysis, Transmission Loss.

Jet Inlet Efficiency

DTIC Science & Technology

2013-08-08

Lay down plastic sheeting that is double the size of the mold covered in fabric in order to fully envelope the mold. o Line half of the sheet (in...the mold and connect to clay tape to create an air tight sealed bag with a hose leading to the outside pump. o Once the seal is created, turn on the...connected pump to remove all air from the bag that has been created.  Ensure that as air is removed, the bag fits the form of the desired mold as

"Null-E" magnetic bearings

NASA Astrophysics Data System (ADS)

Filatov, Alexei Vladimirovich

2002-09-01

Using electromagnetic forces to suspend rotating objects (rotors) without mechanical contact is often an appealing technical solution. Magnetic suspensions are typically required to have adequate load capacity and stiffness, and low rotational loss. Other desired features include low price, high reliability and manufacturability. With recent advances in permanent-magnet materials, the required forces can often be obtained by simply using the interaction between permanent magnets. While a magnetic bearing based entirely on permanent magnets could be expected to be inexpensive, reliable and easy to manufacture, a fundamental physical principle known as Earnshaw's theorem maintains that this type of suspension cannot be statically stable. Therefore, some other physical mechanisms must be included. One such mechanism employs the interaction between a conductor and a nonuniform magnetic field in relative motion. Its advantages include simplicity, reliability, wide range of operating temperature and system autonomy (no external wiring and power supplies are required). The disadvantages of the earlier embodiments were high rotational loss, low stiffness and load capacity. This dissertation proposes a novel type of magnetic bearing stabilized by the field-conductor interaction. One of the advantages of this bearing is that no electric field, E, develops in the conductor during the rotor rotation when the system is in no-load equilibrium. Because of this we refer to it as the Null-E Bearing. Null-E Bearings have potential for lower rotational loss and higher load capacity and stiffness than other bearings utilizing the field-conductor interaction. Their performance is highly insensitive to manufacturing inaccuracies. The Null-E Bearing in its basic form can be augmented with supplementary electronics to improve its performance. Depending on the degree of the electronics involvement, a variety of magnetic bearings can be developed ranging from a completely passive to an active magnetic bearing of a novel type. This dissertation contains theoretical analysis of the Null-E Bearing operation, including derivation of the stability conditions and estimation of some of the rotational losses. The validity of the theoretical conclusions has been demonstrated by building and testing a prototype in which non-contact suspension of a 3.2-kg rotor is achieved at spin speeds above 18 Hz.

Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease.

PubMed

Dai, Mei; Liou, Benjamin; Swope, Brittany; Wang, Xiaohong; Zhang, Wujuan; Inskeep, Venette; Grabowski, Gregory A; Sun, Ying; Pan, Dao

2016-01-01

To study the neuronal deficits in neuronopathic Gaucher Disease (nGD), the chronological behavioral profiles and the age of onset of brain abnormalities were characterized in a chronic nGD mouse model (9V/null). Progressive accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) in the brain of 9V/null mice were observed at as early as 6 and 3 months of age for GC and GS, respectively. Abnormal accumulation of α-synuclein was present in the 9V/null brain as detected by immunofluorescence and Western blot analysis. In a repeated open-field test, the 9V/null mice (9 months and older) displayed significantly less environmental habituation and spent more time exploring the open-field than age-matched WT group, indicating the onset of short-term spatial memory deficits. In the marble burying test, the 9V/null group had a shorter latency to initiate burying activity at 3 months of age, whereas the latency increased significantly at ≥12 months of age; 9V/null females buried significantly more marbles to completion than the WT group, suggesting an abnormal response to the instinctive behavior and an abnormal activity in non-associative anxiety-like behavior. In the conditional fear test, only the 9V/null males exhibited a significant decrease in response to contextual fear, but both genders showed less response to auditory-cued fear compared to age- and gender-matched WT at 12 months of age. These results indicate hippocampus-related emotional memory defects. Abnormal gait emerged in 9V/null mice with wider front-paw and hind-paw widths, as well as longer stride in a gender-dependent manner with different ages of onset. Significantly higher liver- and spleen-to-body weight ratios were detected in 9V/null mice with different ages of onsets. These data provide temporal evaluation of neurobehavioral dysfunctions and brain pathology in 9V/null mice that can be used for experimental designs to evaluate novel therapies for nGD.

Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease

PubMed Central

Dai, Mei; Liou, Benjamin; Swope, Brittany; Wang, Xiaohong; Zhang, Wujuan; Inskeep, Venette; Grabowski, Gregory A.; Sun, Ying; Pan, Dao

2016-01-01

To study the neuronal deficits in neuronopathic Gaucher Disease (nGD), the chronological behavioral profiles and the age of onset of brain abnormalities were characterized in a chronic nGD mouse model (9V/null). Progressive accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) in the brain of 9V/null mice were observed at as early as 6 and 3 months of age for GC and GS, respectively. Abnormal accumulation of α-synuclein was present in the 9V/null brain as detected by immunofluorescence and Western blot analysis. In a repeated open-field test, the 9V/null mice (9 months and older) displayed significantly less environmental habituation and spent more time exploring the open-field than age-matched WT group, indicating the onset of short-term spatial memory deficits. In the marble burying test, the 9V/null group had a shorter latency to initiate burying activity at 3 months of age, whereas the latency increased significantly at ≥12 months of age; 9V/null females buried significantly more marbles to completion than the WT group, suggesting an abnormal response to the instinctive behavior and an abnormal activity in non-associative anxiety-like behavior. In the conditional fear test, only the 9V/null males exhibited a significant decrease in response to contextual fear, but both genders showed less response to auditory-cued fear compared to age- and gender-matched WT at 12 months of age. These results indicate hippocampus-related emotional memory defects. Abnormal gait emerged in 9V/null mice with wider front-paw and hind-paw widths, as well as longer stride in a gender-dependent manner with different ages of onset. Significantly higher liver- and spleen-to-body weight ratios were detected in 9V/null mice with different ages of onsets. These data provide temporal evaluation of neurobehavioral dysfunctions and brain pathology in 9V/null mice that can be used for experimental designs to evaluate novel therapies for nGD. PMID:27598339

Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

PubMed

ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

2018-06-20

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

Influence of Choice of Null Network on Small-World Parameters of Structural Correlation Networks

PubMed Central

Hosseini, S. M. Hadi; Kesler, Shelli R.

2013-01-01

In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures. PMID:23840672

Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse

PubMed Central

Braun, Anne; Zhang, Songwen; Miettinen, Helena E.; Ebrahim, Shamsah; Holm, Teresa M.; Vasile, Eliza; Post, Mark J.; Yoerger, Danita M.; Picard, Michael H.; Krieger, Joshua L.; Andrews, Nancy C.; Simons, Michael; Krieger, Monty

2003-01-01

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5–6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between ≈3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease. PMID:12771386

Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers

PubMed Central

Fukada, So-ichiro; Yamaguchi, Masahiko; Kokubo, Hiroki; Ogawa, Ryo; Uezumi, Akiyoshi; Yoneda, Tomohiro; Matev, Miroslav M.; Motohashi, Norio; Ito, Takahito; Zolkiewska, Anna; Johnson, Randy L.; Saga, Yumiko; Miyagoe-Suzuki, Yuko; Tsujikawa, Kazutake; Takeda, Shin’ichi; Yamamoto, Hiroshi

2011-01-01

Satellite cells, which are skeletal muscle stem cells, divide to provide new myonuclei to growing muscle fibers during postnatal development, and then are maintained in an undifferentiated quiescent state in adult skeletal muscle. This state is considered to be essential for the maintenance of satellite cells, but their molecular regulation is unknown. We show that Hesr1 (Hey1) and Hesr3 (Heyl) (which are known Notch target genes) are expressed simultaneously in skeletal muscle only in satellite cells. In Hesr1 and Hesr3 single-knockout mice, no obvious abnormalities of satellite cells or muscle regenerative potentials are observed. However, the generation of undifferentiated quiescent satellite cells is impaired during postnatal development in Hesr1/3 double-knockout mice. As a result, myogenic (MyoD and myogenin) and proliferative (Ki67) proteins are expressed in adult satellite cells. Consistent with the in vivo results, Hesr1/3-null myoblasts generate very few Pax7+ MyoD– undifferentiated cells in vitro. Furthermore, the satellite cell number gradually decreases in Hesr1/3 double-knockout mice even after it has stabilized in control mice, and an age-dependent regeneration defect is observed. In vivo results suggest that premature differentiation, but not cell death, is the reason for the reduced number of satellite cells in Hesr1/3 double-knockout mice. These results indicate that Hesr1 and Hesr3 are essential for the generation of adult satellite cells and for the maintenance of skeletal muscle homeostasis. PMID:21989910

DNA recombination-initiation plays a role in the extremely biased inheritance of yeast [rho-] mitochondrial DNA that contains the replication origin ori5.

PubMed

Ling, Feng; Hori, Akiko; Shibata, Takehiko

2007-02-01

Hypersuppressiveness, as observed in Saccharomyces cerevisiae, is an extremely biased inheritance of a small mitochondrial DNA (mtDNA) fragment that contains a replication origin (HS [rho(-)] mtDNA). Our previous studies showed that concatemers (linear head-to-tail multimers) are obligatory intermediates for mtDNA partitioning and are primarily formed by rolling-circle replication mediated by Mhr1, a protein required for homologous mtDNA recombination. In this study, we found that Mhr1 is required for the hypersuppressiveness of HS [ori5] [rho(-)] mtDNA harboring ori5, one of the replication origins of normal ([rho(+)]) mtDNA. In addition, we detected an Ntg1-stimulated double-strand break at the ori5 locus. Purified Ntg1, a base excision repair enzyme, introduced a double-stranded break by itself into HS [ori5] [rho(-)] mtDNA at ori5 isolated from yeast cells. Both hypersuppressiveness and concatemer formation of HS [ori5] [rho(-)] mtDNA are simultaneously suppressed by the ntg1 null mutation. These results support a model in which, like homologous recombination, rolling-circle HS [ori5] [rho(-)] mtDNA replication is initiated by double-stranded breakage in ori5, followed by Mhr1-mediated homologous pairing of the processed nascent DNA ends with circular mtDNA. The hypersuppressiveness of HS [ori5] [rho(-)] mtDNA depends on a replication advantage furnished by the higher density of ori5 sequences and on a segregation advantage furnished by the higher genome copy number on transmitted concatemers.

Arabidopsis Chloroplast Mini-Ribonuclease III Participates in rRNA Maturation and Intron Recycling

PubMed Central

Hotto, Amber M.; Castandet, Benoît; Gilet, Laetitia; Higdon, Andrea; Condon, Ciarán; Stern, David B.

2015-01-01

RNase III proteins recognize double-stranded RNA structures and catalyze endoribonucleolytic cleavages that often regulate gene expression. Here, we characterize the functions of RNC3 and RNC4, two Arabidopsis thaliana chloroplast Mini-RNase III-like enzymes sharing 75% amino acid sequence identity. Whereas rnc3 and rnc4 null mutants have no visible phenotype, rnc3/rnc4 (rnc3/4) double mutants are slightly smaller and chlorotic compared with the wild type. In Bacillus subtilis, the RNase Mini-III is integral to 23S rRNA maturation. In Arabidopsis, we observed imprecise maturation of 23S rRNA in the rnc3/4 double mutant, suggesting that exoribonucleases generated staggered ends in the absence of specific Mini-III-catalyzed cleavages. A similar phenotype was found at the 3′ end of the 16S rRNA, and the primary 4.5S rRNA transcript contained 3′ extensions, suggesting that Mini-III catalyzes several processing events of the polycistronic rRNA precursor. The rnc3/4 mutant showed overaccumulation of a noncoding RNA complementary to the 4.5S-5S rRNA intergenic region, and its presence correlated with that of the extended 4.5S rRNA precursor. Finally, we found rnc3/4-specific intron degradation intermediates that are probable substrates for Mini-III and show that B. subtilis Mini-III is also involved in intron regulation. Overall, this study extends our knowledge of the key role of Mini-III in intron and noncoding RNA regulation and provides important insight into plastid rRNA maturation. PMID:25724636

Probing transcription-specific outputs of β-catenin in vivo.

PubMed

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

2011-12-15

β-Catenin, apart from playing a cell-adhesive role, is a key nuclear effector of Wnt signaling. Based on activity assays in Drosophila, we generated mouse strains where the endogenous β-catenin protein is replaced by mutant forms, which retain the cell adhesion function but lack either or both of the N- and the C-terminal transcriptional outputs. The C-terminal activity is essential for mesoderm formation and proper gastrulation, whereas N-terminal outputs are required later during embryonic development. By combining the double-mutant β-catenin with a conditional null allele and a Wnt1-Cre driver, we probed the role of Wnt/β-catenin signaling in dorsal neural tube development. While loss of β-catenin protein in the neural tube results in severe cell adhesion defects, the morphology of cells and tissues expressing the double-mutant form is normal. Surprisingly, Wnt/β-catenin signaling activity only moderately regulates cell proliferation, but is crucial for maintaining neural progenitor identity and for neuronal differentiation in the dorsal spinal cord. Our model animals thus allow dissecting signaling and structural functions of β-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. © 2011 by Cold Spring Harbor Laboratory Press

Differential Requirements for c-Myc in Chronic Hematopoietic Hyperplasia and Acute Hematopoietic Malignancies in Pten-null Mice

PubMed Central

Zhang, Jun; Xiao, Yechen; Guo, Yinshi; Breslin, Peter; Zhang, Shubin; Wei, Wei; Zhang, Zhou; Zhang, Jiwang

2011-01-01

Myeloproliferative disorders (MPDs), lymphoproliferative disorders (LPDs), acute T-lymphocytic or myeloid leukemia and T-lymphocytic lymphoma were developed in inducible Pten-knockout (Pten−/−) mice. The appearance of these multiple diseases in one animal model provides an opportunity to study the pathogenesis of multiple diseases simultaneously. To study whether Myc function is required for the development of these hematopoietic disorders in Pten−/− mice, we generated inducible Pten/Myc double-knockout mice (Pten−/−/Myc−/−). By comparing the hematopoietic phenotypes of these double-knockout mice with those of Pten−/− mice, we found that both sets of animals developed MPDs and LPDs. However, none of the compound-mutant mice developed acute leukemia or lymphoma. Interestingly, in contrast to the MPDs which developed in Pten−/− mice which are dominated by granulocytes, megakaryocytes predominate in the MPDs of Pten−/−/Myc−/− mice. Our study suggests that the deregulation of PI3K/Akt signaling in Pten−/− hematopoietic cells protects these cells from apoptotic cell death, resulting in chronic proliferative disorders. But due to the differential requirement for Myc in granulocyte as compared to megakaryocyte proliferation, Myc deletion converts Pten−/− MPDs from granulocyte-dominated to megakaryocyte-dominated conditions. Myc is absolutely required for the development of acute hematopoietic malignancies. PMID:21926961

RAP80, ubiquitin and SUMO in the DNA damage response.

PubMed

Lombardi, Patrick M; Matunis, Michael J; Wolberger, Cynthia

2017-08-01

A decade has passed since the first reported connection between RAP80 and BRCA1 in DNA double-strand break repair. Despite the initial identification of RAP80 as a factor localizing BRCA1 to DNA double-strand breaks and potentially promoting homologous recombination, there is increasing evidence that RAP80 instead suppresses homologous recombination to fine-tune the balance of competing DNA repair processes during the S/G 2 phase of the cell cycle. RAP80 opposes homologous recombination by inhibiting DNA end-resection and sequestering BRCA1 into the BRCA1-A complex. Ubiquitin and SUMO modifications of chromatin at DNA double-strand breaks recruit RAP80, which contains distinct sequence motifs that recognize ubiquitin and SUMO. Here, we review RAP80's role in repressing homologous recombination at DNA double-strand breaks and how this role is facilitated by its ability to bind ubiquitin and SUMO modifications.

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.

Divertor with a third-order null of the poloidal field

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

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

2013-09-15

A concept and preliminary feasibility analysis of a divertor with the third-order poloidal field null is presented. The third-order null is the point where not only the field itself but also its first and second spatial derivatives are zero. In this case, the separatrix near the null-point has eight branches, and the number of strike-points increases from 2 (as in the standard divertor) to six. It is shown that this magnetic configuration can be created by a proper adjustment of the currents in a set of three divertor coils. If the currents are somewhat different from the required values, themore » configuration becomes that of three closely spaced first-order nulls. Analytic approach, suitable for a quick orientation in the problem, is used. Potential advantages and disadvantages of this configuration are briefly discussed.« less

Investigation on efficiency declines due to spectral overlap between LDAs pump and laser medium in high power double face pumped slab laser

NASA Astrophysics Data System (ADS)

Lang, Ye; Chen, Yanzhong; Liao, Lifen; Guo, Guangyan; He, Jianguo; Fan, Zhongwei

2018-03-01

In high power diode lasers, the input cooling water temperature would affect both output power and output spectrum. In double face pumped slab laser, the spectrum of two laser diode arrays (LDAs) must be optimized for efficiency reason. The spectrum mismatch of two LDAs would result in energy storing decline. In this work, thermal induced efficiency decline due to spectral overlap between high power LDAs and laser medium was investigated. A numerical model was developed to describe the energy storing variation with changing LDAs cooling water temperature and configuration (series/parallel connected). A confirmatory experiment was conducted using a double face pumped slab module. The experiment results show good agreements with simulations.

Both genetic deletion and pharmacological blockade of lysophosphatidic acid LPA1 receptor results in increased alcohol consumption.

PubMed

Castilla-Ortega, Estela; Pavón, Francisco Javier; Sánchez-Marín, Laura; Estivill-Torrús, Guillermo; Pedraza, Carmen; Blanco, Eduardo; Suárez, Juan; Santín, Luis; Rodríguez de Fonseca, Fernando; Serrano, Antonia

2016-04-01

Lysophosphatidic acid species (LPA) are lipid bioactive signaling molecules that have been recently implicated in the modulation of emotional and motivational behaviors. The present study investigates the consequences of either genetic deletion or pharmacological blockade of lysophosphatidic acid receptor-1 (LPA1) in alcohol consumption. The experiments were performed in alcohol-drinking animals by using LPA1-null mice and administering the LPA1 receptor antagonist Ki16425 in both mice and rats. In the two-bottle free choice paradigm, the LPA1-null mice preferred the alcohol more than their wild-type counterparts. Whereas the male LPA1-null mice displayed this higher preference at all doses tested, the female LPA1-null mice only consumed more alcohol at 6% concentration. The male LPA1-null mice were then further characterized, showing a notably increased ethanol drinking after a deprivation period and a reduced sleep time after acute ethanol administration. In addition, LPA1-null mice were more anxious than the wild-type mice in the elevated plus maze test. For the pharmacological experiments, the acute administration of the antagonist Ki16425 consistently increased ethanol consumption in both wild-type mice and rats; while it did not modulate alcohol drinking in the LPA1-null mice and lacked intrinsic rewarding properties and locomotor effects in a conditioned place preference paradigm. In addition, LPA1-null mice exhibited a marked reduction on the expression of glutamate-transmission-related genes in the prefrontal cortex similar to those described in alcohol-exposed rodents. Results suggest a relevant role for the LPA/LPA1 signaling system in alcoholism. In addition, the LPA1-null mice emerge as a new model for genetic vulnerability to excessive alcohol drinking. The pharmacological manipulation of LPA1 receptor arises as a new target for the study and treatment of alcoholism. Copyright © 2015 Elsevier Ltd. All rights reserved.

On Nulling, Drifting, and Their Interactions in PSRs J1741-0840 and J1840-0840

NASA Astrophysics Data System (ADS)

Gajjar, V.; Yuan, J. P.; Yuen, R.; Wen, Z. G.; Liu, Z. Y.; Wang, N.

2017-12-01

We report detailed investigation of nulling and drifting behavior of two pulsars PSRs J1741-0840 and J1840-0840 observed from the Giant Meterwave Radio Telescope at 625 MHz. PSR J1741-0840 was found to show a nulling fraction (NF) of around 30% ± 5% while PSR J1840-0840 was shown to have an NF of around 50% ± 6%. We measured drifting behavior from different profile components in PSR J1840-0840 for the first time with the leading component showing drifting with 13.5 ± 0.7 periods while the weak trailing component showed drifting of around 18 ± 1 periods. Large nulling hampers accuracy of these quantities derived using standard Fourier techniques. A more accurate comparison was drawn from driftband slopes, measured after sub-pulse modeling. These measurements revealed interesting sporadic and irregular drifting behavior in both pulsars. We conclude that the previously reported different drifting periodicities in the trailing component of PSR J1741-0840 is likely due to the spread in these driftband slopes. We also find that both components of PSR J1840-0840 show similar driftband slopes within the uncertainties. Unique nulling-drifting interaction is identified in PSR J1840-0840 where, on most occasions, the pulsar tends to start nulling after what appears to be the end of a driftband. Similarly, when the pulsar switches back to an emission phase, on most occasions it starts at the beginning of a new driftband in both components. Such behaviors have not been detected in any other pulsars to our knowledge. We also found that PSR J1741-0840 seems to have no memory of its previous burst phase while PSR J1840-0840 clearly exhibits memory of its previous state even after longer nulls for both components. We discuss possible explanations for these intriguing nulling-drifting interactions seen in both pulsars based on various pulsar nulling models.

Apolipoprotein AI Deficiency Inhibits Serum Opacity Factor Activity against Plasma High Density Lipoprotein via a Stabilization Mechanism

PubMed Central

Rosales, Corina; Patel, Niket; Gillard, Baiba K.; Yelamanchili, Dedipya; Yang, Yaliu; Courtney, Harry S.; Santos, Raul D.; Gotto, Antonio M.; Pownall, Henry J.

2016-01-01

The reaction of Streptococcal serum opacity factor (SOF) against plasma high-density lipoproteins (HDL) produces a large cholesteryl ester-rich microemulsion (CERM), a smaller neo HDL that is apolipoprotein (apo) AI-poor, and lipid-free apo AI. SOF is active vs. both human and mouse plasma HDL. In vivo injection of SOF into mice reduces plasma cholesterol ~40% in 3 hours while forming the same products observed in vitro, but at different ratios. Previous studies supported the hypothesis that labile apo AI is required for the SOF reaction vs. HDL. Here we further tested that hypothesis by studies of SOF against HDL from apo AI-null mice. When injected into apo AI-null mice, SOF reduced plasma cholesterol ~35% in three hours. The reaction of SOF vs. apo AI-null HDL in vitro produced a CERM and neo HDL, but no lipid-free apo. Moreover, according to the rate of CERM formation, the extent and rate of the SOF reaction vs. apo AI-null mouse HDL was less than that against wild-type (WT) mouse HDL. Chaotropic perturbation studies using guanidine hydrochloride showed that apo AI-null HDL was more stable than WT HDL. Human apo AI added to apo AI-null HDL was quantitatively incorporated, giving reconstituted HDL. Both SOF and guanidine hydrochloride displaced apo AI from the reconstituted HDL. These results support the conclusion that apo AI-null HDL is more stable than WT HDL because it lacks apo AI, a labile protein that is readily displaced by physico-chemical and biochemical perturbations. Thus, apo AI-null HDL is less SOF-reactive than WT HDL. The properties of apo AI-null HDL can be partially restored to those of WT HDL by the spontaneous incorporation of human apo AI. It remains to be determined what other HDL functions are affected by apo AI deletion. PMID:25790332

Adaptive Nulling for Interferometric Detection of Planets

NASA Technical Reports Server (NTRS)

Lay, Oliver P.; Peters, Robert D.

2010-01-01

An adaptive-nulling method has been proposed to augment the nulling-optical- interferometry method of detection of Earth-like planets around distant stars. The method is intended to reduce the cost of building and aligning the highly precise optical components and assemblies needed for nulling. Typically, at the mid-infrared wavelengths used for detecting planets orbiting distant stars, a star is millions of times brighter than an Earth-sized planet. In order to directly detect the light from the planet, it is necessary to remove most of the light coming from the star. Nulling interferometry is one way to suppress the light from the star without appreciably suppressing the light from the planet. In nulling interferometry in its simplest form, one uses two nominally identical telescopes aimed in the same direction and separated laterally by a suitable distance. The light collected by the two telescopes is processed through optical trains and combined on a detector. The optical trains are designed such that the electric fields produced by an on-axis source (the star) are in anti-phase at the detector while the electric fields from the planet, which is slightly off-axis, combine in phase, so that the contrast ratio between the star and the planet is greatly decreased. If the electric fields from the star are exactly equal in amplitude and opposite in phase, then the star is effectively nulled out. Nulling is effective only if it is complete in the sense that it occurs simultaneously in both polarization states and at all wavelengths of interest. The need to ensure complete nulling translates to extremely tight demands upon the design and fabrication of the complex optical trains: The two telescopes must be highly symmetric, the reflectivities of the many mirrors in the telescopes and other optics must be carefully tailored, the optical coatings must be extremely uniform, sources of contamination must be minimized, optical surfaces must be nearly ideal, and alignments must be extremely precise. Satisfaction of all of these requirements entails substantial cost.

Cruciferous Vegetables Have Variable Effects on Biomarkers of Systemic Inflammation in a Randomized Controlled Trial in Healthy Young Adults12

PubMed Central

Navarro, Sandi L.; Schwarz, Yvonne; Song, Xiaoling; Wang, Ching-Yun; Chen, Chu; Trudo, Sabrina P.; Kristal, Alan R.; Kratz, Mario; Eaton, David L.; Lampe, Johanna W.

2014-01-01

Background: Isothiocyanates in cruciferous vegetables modulate signaling pathways critical to carcinogenesis, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of inflammation. Glutathione S-transferase (GST) M1 and GSTT1 metabolize isothiocyanates; genetic variants may result in differences in biologic response. Objective: The objective of this study was to test whether consumption of cruciferous or cruciferous plus apiaceous vegetables altered serum concentrations of interleukin (IL)-6, IL-8, C-reactive protein (CRP), tumor necrosis factor (TNF) α, and soluble TNF receptor (sTNFR) I and II, and whether this response was GSTM1/GSTT1 genotype dependent. Methods: In a randomized crossover trial, healthy men (n = 32) and women (n = 31) aged 20–40 y consumed 4 14-d controlled diets: basal (vegetable-free), single-dose cruciferous (1xC) [7 g vegetables/kg body weight (BW)], double-dose cruciferous (2xC) (14 g/kg BW), and cruciferous plus apiaceous (carrot family) (1xC+A) vegetables (7 and 4 g/kg BW, respectively), with a 21-d washout period between each intervention. Urinary isothiocyanate excretion was also evaluated as a marker of systemic isothiocyanate exposure. Fasting morning blood and urine samples were collected on days 0 and 14 and analyzed. Results: IL-6 concentrations were significantly lower on day 14 of the 2xC and 1xC+A diets than with the basal diet [−19% (95% CI: −30%, −0.1%) and −20% (95% CI: −31%, -0.7%), respectively]. IL-8 concentrations were higher after the 1xC+A diet (+16%; 95% CI: 4.2%, 35.2%) than after the basal diet. There were no effects of diet on CRP, TNF-α, or sTNFRI or II. There were significant differences between GSTM1-null/GSTT1+ individuals for several biomarkers in response to 1xC+A compared with basal diets (CRP: −37.8%; 95% CI: −58.0%, −7.4%; IL-6: −48.6%; 95% CI: −49.6%, −12.0%; IL-8: 16.3%; 95% CI: 6.7%, 57.7%) and with the 2xC diet compared with the basal diet (IL-8: −33.2%; 95% CI: −43.0%, −1.4%; sTNFRI: −7.5%; 95% CI: −12.7%, −2.3%). There were no significant reductions in biomarker concentrations in response to diet among GSTM1+/GSTT1+ or GSTM1-null/GSTT1-null individuals. Twenty-four-hour urinary isothiocyanate excretion was not associated with any of the inflammation markers overall; however, IL-6 was inversely associated with total isothiocyanate excretion in GSTM1-null/GSTT1-null individuals (β = −0.12; 95% CI: −0.19, −0.05). Conclusions: In this young, healthy population, consumption of cruciferous and apiaceous vegetables reduced circulating IL-6; however, results for other biomarkers of inflammation were not consistent. PMID:25165394

Effects of ion concentration on thermally-chargeable double-layer supercapacitors

NASA Astrophysics Data System (ADS)

Lim, Hyuck; Lu, Weiyi; Chen, Xi; Qiao, Yu

2013-11-01

The concept of thermally-chargeable supercapacitor was discussed and validated experimentally. As two double-layer supercapacitor-type devices were placed at different temperatures and connected, due to the thermal dependence of surface charge structures, the electrode potentials became different, and thermal energy could be harvested and stored as electric energy. The important effect of ion concentration was investigated. The results were quite different from the prediction of conventional surface theory, which should be attributed to the unique behaviors of the ions confined in the nanoporous electrodes.

Effects of ion concentration on thermally-chargeable double-layer supercapacitors.

PubMed

Lim, Hyuck; Lu, Weiyi; Chen, Xi; Qiao, Yu

2013-11-22

The concept of thermally-chargeable supercapacitor was discussed and validated experimentally. As two double-layer supercapacitor-type devices were placed at different temperatures and connected, due to the thermal dependence of surface charge structures, the electrode potentials became different, and thermal energy could be harvested and stored as electric energy. The important effect of ion concentration was investigated. The results were quite different from the prediction of conventional surface theory, which should be attributed to the unique behaviors of the ions confined in the nanoporous electrodes.

Regional and Large-Scale Climate Influences on Tree-Ring Reconstructed Null Zone Position in San Francisco Bay

NASA Astrophysics Data System (ADS)

Stahle, D.; Griffin, D.; Cleaveland, M.; Fye, F.; Meko, D.; Cayan, D.; Dettinger, M.; Redmond, K.

2007-05-01

A new network of 36 moisture sensitive tree-ring chronologies has been developed in and near the drainage basins of the Sacramento and San Joaquin Rivers. The network is based entirely on blue oak (Quercus douglasii), which is a California endemic found from the lower forest border up into the mixed conifer zone in the Coast Ranges, Sierra Nevada, and Cascades. These blue oak tree-ring chronologies are highly correlated with winter-spring precipitation totals, Sacramento and San Joaquin streamflow, and with seasonal variations in salinity and null zone position in San Francisco Bay. Null zone is the non-tidal bottom water location where density-driven salinity and river-driven freshwater currents balance (zero flow). It is the area of highest turbidity, water residence time, sediment accumulation, and net primary productivity in the estuary. Null zone position is measured by the distance from the Golden Gate of the 2 per mil bottom water isohaline and is primarily controlled by discharge from the Sacramento and San Joaquin Rivers (and ultimately by winter-spring precipitation). The location of the null zone is an estuarine habitat indicator, a policy variable used for ecosystem management, and can have a major impact on biological resources in the San Francisco estuary. Precipitation-sensitive blue oak chronologies can be used to estimate null zone position based on the strong biogeophysical interaction among terrestrial, aquatic, and estuarine ecosystems, orchestrated by precipitation. The null zone reconstruction is 626-years long and provides a unique long term perspective on the interannual to decadal variability of this important estuarine habitat indicator. Consecutive two-year droughts (or longer) allow the null zone to shrink into the confined upper reaches of Suisun Bay, causing a dramatic reduction in phytoplankton production and favoring colonization of the estuary by marine biota. The reconstruction indicates an approximate 10 year recurrence interval between these consecutive two-year droughts and null zone maxima. Composite analyses of the Palmer drought index over North America indicate that the drought and wetness regimes associated with maxima and minima in reconstructed null zone position are largely restricted to the California sector. Composite analyses of the 20th century global sea surface temperature (SST) field indicate that wet years over central California with good oak growth, high flows, and a seaward position for the null zone (minima) are associated with warm El Nino conditions and a "Pineapple Express" SST pattern. The composite SST pattern is not as strong during dry years with poor growth, low flows, and a landward position of the null zone (maxima), but the composite warm SST anomaly in the eastern North Pacific during maxima would be consistent with a persistent ridge and drought over western North America.

Identification of Noninvasive Biomarkers for Alcohol-Induced Liver Disease Using Urinary Metabolomics and the Ppara-null Mouse

PubMed Central

Manna, Soumen K.; Patterson, Andrew D.; Yang, Qian; Krausz, Kristopher W.; Li, Henghong; Idle, Jeffrey R.; Fornace, Albert J.; Gonzalez, Frank J.

2010-01-01

Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively non-specific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study the metabolic changes associated with alcohol-induced liver disease were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-β-D-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model. PMID:20540569

pyNSMC: A Python Module for Null-Space Monte Carlo Uncertainty Analysis

NASA Astrophysics Data System (ADS)

White, J.; Brakefield, L. K.

2015-12-01

The null-space monte carlo technique is a non-linear uncertainty analyses technique that is well-suited to high-dimensional inverse problems. While the technique is powerful, the existing workflow for completing null-space monte carlo is cumbersome, requiring the use of multiple commandline utilities, several sets of intermediate files and even a text editor. pyNSMC is an open-source python module that automates the workflow of null-space monte carlo uncertainty analyses. The module is fully compatible with the PEST and PEST++ software suites and leverages existing functionality of pyEMU, a python framework for linear-based uncertainty analyses. pyNSMC greatly simplifies the existing workflow for null-space monte carlo by taking advantage of object oriented design facilities in python. The core of pyNSMC is the ensemble class, which draws and stores realized random vectors and also provides functionality for exporting and visualizing results. By relieving users of the tedium associated with file handling and command line utility execution, pyNSMC instead focuses the user on the important steps and assumptions of null-space monte carlo analysis. Furthermore, pyNSMC facilitates learning through flow charts and results visualization, which are available at many points in the algorithm. The ease-of-use of the pyNSMC workflow is compared to the existing workflow for null-space monte carlo for a synthetic groundwater model with hundreds of estimable parameters.

Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population.

PubMed

Abbas, Shania; Raza, Syed Tasleem; Chandra, Anu; Rizvi, Saliha; Ahmed, Faisal; Eba, Ale; Mahdi, Farzana

2015-01-01

Hypertension has a multi-factorial background based on genetic and environmental interactive factors. ACE, FABP2 and GST genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. The present study was carried out to investigate the association of ACE (rs4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism with essential HTN cases and controls. This study includes 138 essential hypertension (HTN) patients and 116 age-, sex- and ethnicity-matched control subjects. GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphisms were evaluated by multiplex PCR, ACE (rs4646994) gene polymorphisms by PCR and FABP2 (rs1799883) gene polymorphisms by PCR-RFLP method. Significant differences were obtained in the frequencies of ACE DD, II genotype (p = 0.006, 0.003), GSTT1 null, GSTM1 positive genotype (p = 0.048, 0.010) and FABP2 Ala54/Ala54 genotype (p = 0.049) between essential HTN cases and controls. It is concluded that ACE (rs 4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism are associated with HTN. Further investigation with a larger sample size may be required to validate this study.

FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly

PubMed Central

Jurak Begonja, Antonija; Hoffmeister, Karin M.; Hartwig, John H.

2011-01-01

Filamin A (FlnA) is a large cytoplasmic protein that crosslinks actin filaments and anchors membrane receptors and signaling intermediates. FlnAloxP PF4-Cre mice that lack FlnA in the megakaryocyte (MK) lineage have a severe macrothrombocytopenia because of accelerated platelet clearance. Macrophage ablation by injection of clodronate-encapsulated liposomes increases blood platelet counts in FlnAloxP PF4-Cre mice and reveals the desintegration of FlnA-null platelets into microvesicles, a process that occurs spontaneously during storage. FlnAloxP PF4-Cre bone marrows and spleens have a 2.5- to 5-fold increase in MK numbers, indicating increased thrombopoiesis in vivo. Analysis of platelet production in vitro reveals that FlnA-null MKs prematurely convert their cytoplasm into large CD61+ platelet-sized particles, reminiscent of the large platelets observed in vivo. FlnA stabilizes the platelet von Willebrand factor receptor, as surface expression of von Willebrand factor receptor components is normal on FlnA-null MKs but decreased on FlnA-null platelets. Further, FlnA-null platelets contain multiple GPIbα degradation products and have increased expression of the ADAM17 and MMP9 metalloproteinases. Together, the findings indicate that FlnA-null MKs prematurely release large and fragile platelets that are removed rapidly from the circulation by macrophages. PMID:21652675

Screen-printed back-to-back electroanalytical sensors.

PubMed

Metters, Jonathan P; Randviir, Edward P; Banks, Craig E

2014-11-07

We introduce the concept of screen-printed back-to-back electroanalytical sensors where in this facile and generic approach, screen-printed electrodes are printed back-to-back with a common electrical connection to the two working electrodes with the counter and reference electrodes for each connected in the same manner as a normal "traditional" screen-printed sensor would be. This approach utilises the usually redundant back of the screen-printed sensor, converting this "dead-space" into a further electrochemical sensor which results in improvements in the analytical performance. In the use of the back-to-back design, the electrode area is consequently doubled with improvements in the analytical performance observed with the analytical sensitivity (gradient of a plot of peak height/analytical signal against concentration) doubling and the corresponding limit-of-detection being reduced. We also demonstrate that through intelligent electrode design, a quadruple in the observed analytical sensitivity can also be realised when double microband electrodes are used in the back-to-back configuration as long as they are placed sufficiently apart such that no diffusional interaction occurs. Such work is generic in nature and can be facilely applied to a plethora of screen-printed (and related) sensors utilising the commonly overlooked redundant back of the electrode providing facile improvements in the electroanalytical performance.

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…

Never forget a name: white matter connectivity predicts person memory

PubMed Central

Metoki, Athanasia; Alm, Kylie H.; Wang, Yin; Ngo, Chi T.; Olson, Ingrid R.

2018-01-01

Through learning and practice, we can acquire numerous skills, ranging from the simple (whistling) to the complex (memorizing operettas in a foreign language). It has been proposed that complex learning requires a network of brain regions that interact with one another via white matter pathways. One candidate white matter pathway, the uncinate fasciculus (UF), has exhibited mixed results for this hypothesis: some studies have shown UF involvement across a range of memory tasks, while other studies report null results. Here, we tested the hypothesis that the UF supports associative memory processes and that this tract can be parcellated into subtracts that support specific types of memory. Healthy young adults performed behavioral tasks (two face-name learning tasks, one word pair memory task) and underwent a diffusion-weighted imaging scan. Our results revealed that variation in UF microstructure was significantly associated with individual differences in performance on both face-name tasks, as well as the word association memory task. A UF sub-tract, functionally defined by its connectivity between face-selective regions in the anterior temporal lobe and orbitofrontal cortex, selectively predicted face-name learning. In contrast, connectivity between the fusiform face patch and both anterior face patches had no predictive validity. These findings suggest that there is a robust and replicable relationship between the UF and associative learning and memory. Moreover, this large white matter pathway can be subdivided to reveal discrete functional profiles. PMID:28646241

Multi-electrode double layer capacitor having single electrolyte seal and aluminum-impregnated carbon cloth electrodes

DOEpatents

Farahmandi, C. J.; Dispennette, J. M.; Blank, E.; Kolb, A. C.

1999-05-25

A single cell, multi-electrode high performance double layer capacitor includes first and second flat stacks of electrodes adapted to be housed in a closeable two-part capacitor case which includes only a single electrolyte seal. Each electrode stack has a plurality of electrodes connected in parallel, with the electrodes of one stack being interleaved with the electrodes of the other stack to form an interleaved stack, and with the electrodes of each stack being electrically connected to respective capacitor terminals. A porous separator sleeve is inserted over the electrodes of one stack before interleaving to prevent electrical shorts between the electrodes. The electrodes are made by folding a compressible, low resistance, aluminum-impregnated carbon cloth, made from activated carbon fibers, around a current collector foil, with a tab of the foils of each electrode of each stack being connected in parallel and connected to the respective capacitor terminal. The height of the interleaved stack is somewhat greater than the inside height of the closed capacitor case, thereby requiring compression of the interleaved electrode stack when placed inside of the case, and thereby maintaining the interleaved electrode stack under modest constant pressure. The closed capacitor case is filled with an electrolytic solution and sealed. A preferred electrolytic solution is made by dissolving an appropriate salt into acetonitrile (CH[sub 3]CN). In one embodiment, the two parts of the capacitor case are conductive and function as the capacitor terminals. 32 figs.

Method of making a multi-electrode double layer capacitor having single electrolyte seal and aluminum-impregnated carbon cloth electrodes

DOEpatents

Farahmandi, C. Joseph; Dispennette, John M.; Blank, Edward; Kolb, Alan C.

2002-09-17

A single cell, multi-electrode high performance double layer capacitor includes first and second flat stacks of electrodes adapted to be housed in a closeable two-part capacitor case which includes only a single electrolyte seal. Each electrode stack has a plurality of electrodes connected in parallel, with the electrodes of one stack being interleaved with the electrodes of the other stack to form an interleaved stack, and with the electrodes of each stack being electrically connected to respective capacitor terminals. A porous separator is positioned against the electrodes of one stack before interleaving to prevent electrical shorts between the electrodes. The electrodes are made by folding a compressible, low resistance, aluminum-impregnated carbon cloth, made from activated carbon fibers, around a current collector foil, with a tab of the foils of each electrode of each stack being connected in parallel and connected to the respective capacitor terminal. The height of the interleaved stack is somewhat greater than the inside height of the closed capacitor case, thereby requiring compression of the interleaved electrode stack when placed inside of the case, and thereby maintaining the interleaved electrode stack under modest constant pressure. The closed capacitor case is filled with an electrolytic solution and sealed. A preferred electrolytic solution is made by dissolving an appropriate salt into acetonitrile (CH.sub.3 CN). In one embodiment, the two parts of the capacitor case are conductive and function as the capacitor terminals.

Multi-electrode double layer capacitor having single electrolyte seal and aluminum-impregnated carbon cloth electrodes

DOEpatents

Farahmandi, C Joseph [San Diego, CA; Dispennette, John M [Oceanside, CA; Blank, Edward [San Diego, CA; Kolb, Alan C [Rancho Santa Fe, CA

1999-05-25

A single cell, multi-electrode high performance double layer capacitor includes first and second flat stacks of electrodes adapted to be housed in a closeable two-part capacitor case which includes only a single electrolyte seal. Each electrode stack has a plurality of electrodes connected in parallel, with the electrodes of one stack being interleaved with the electrodes of the other stack to form an interleaved stack, and with the electrodes of each stack being electrically connected to respective capacitor terminals. A porous separator sleeve is inserted over the electrodes of one stack before interleaving to prevent electrical shorts between the electrodes. The electrodes are made by folding a compressible, low resistance, aluminum-impregnated carbon cloth, made from activated carbon fibers, around a current collector foil, with a tab of the foils of each electrode of each stack being connected in parallel and connected to the respective capacitor terminal. The height of the interleaved stack is somewhat greater than the inside height of the closed capacitor case, thereby requiring compression of the interleaved electrode stack when placed inside of the case, and thereby maintaining the interleaved electrode stack under modest constant pressure. The closed capacitor case is filled with an electrolytic solution and sealed. A preferred electrolytic solution is made by dissolving an appropriate salt into acetonitrile (CH.sub.3 CN). In one embodiment, the two parts of the capacitor case are conductive and function as the capacitor terminals.

Multi-electrode double layer capacitor having single electrolyte seal and aluminum-impregnated carbon cloth electrodes

DOEpatents

Farahmandi, C. Joseph; Dispennette, John M.; Blank, Edward; Kolb, Alan C.

1999-01-19

A single cell, multi-electrode high performance double layer capacitor includes first and second flat stacks of electrodes adapted to be housed in a closeable two-part capacitor case which includes only a single electrolyte seal. Each electrode stack has a plurality of electrodes connected in parallel, with the electrodes of one stack being interleaved with the electrodes of the other stack to form an interleaved stack, and with the electrodes of each stack being electrically connected to respective capacitor terminals. A porous separator sleeve is inserted over the electrodes of one stack before interleaving to prevent electrical shorts between the electrodes. The electrodes are made by folding a compressible, low resistance, aluminum-impregnated carbon cloth, made from activated carbon fibers, around a current collector foil, with a tab of the foils of each electrode of each stack being connected in parallel and connected to the respective capacitor terminal. The height of the interleaved stack is somewhat greater than the inside height of the closed capacitor case, thereby requiring compression of the interleaved electrode stack when placed inside of the case, and thereby maintaining the interleaved electrode stack under modest constant pressure. The closed capacitor case is filled with an electrolytic solution and sealed. A preferred electrolytic solution is made by dissolving an appropriate salt into acetonitrile (CH.sub.3 CN). In one embodiment, the two parts of the capacitor case are conductive and function as the capacitor terminals.

Multi-electrode double layer capacitor having single electrolyte seal and aluminum-impregnated carbon cloth electrodes

DOEpatents

Farahmandi, C.J.; Dispennette, J.M.; Blank, E.; Kolb, A.C.

1999-01-19

A single cell, multi-electrode high performance double layer capacitor includes first and second flat stacks of electrodes adapted to be housed in a closeable two-part capacitor case which includes only a single electrolyte seal. Each electrode stack has a plurality of electrodes connected in parallel, with the electrodes of one stack being interleaved with the electrodes of the other stack to form an interleaved stack, and with the electrodes of each stack being electrically connected to respective capacitor terminals. A porous separator sleeve is inserted over the electrodes of one stack before interleaving to prevent electrical shorts between the electrodes. The electrodes are made by folding a compressible, low resistance, aluminum-impregnated carbon cloth, made from activated carbon fibers, around a current collector foil, with a tab of the foils of each electrode of each stack being connected in parallel and connected to the respective capacitor terminal. The height of the interleaved stack is somewhat greater than the inside height of the closed capacitor case, thereby requiring compression of the interleaved electrode stack when placed inside of the case, and thereby maintaining the interleaved electrode stack under modest constant pressure. The closed capacitor case is filled with an electrolytic solution and sealed. A preferred electrolytic solution is made by dissolving an appropriate salt into acetonitrile (CH{sub 3}CN). In one embodiment, the two parts of the capacitor case are conductive and function as the capacitor terminals. 32 figs.

An advanced NMR protocol for the structural characterization of aluminophosphate glasses.

PubMed

van Wüllen, Leo; Tricot, Grégory; Wegner, Sebastian

2007-10-01

In this work a combination of complementary advanced solid-state nuclear magnetic resonance (NMR) strategies is employed to analyse the network organization in aluminophosphate glasses to an unprecedented level of detailed insight. The combined results from MAS, MQMAS and (31)P-{(27)Al}-CP-heteronuclear correlation spectroscopy (HETCOR) NMR experiments allow for a detailed speciation of the different phosphate and aluminate species present in the glass. The interconnection of these local building units to an extended three-dimensional network is explored employing heteronuclear dipolar and scalar NMR approaches to quantify P-O-Al connectivity by (31)P{(27)Al}-heteronuclear multiple quantum coherence (HMQC), -rotational echo adiabatic passage double resonance (REAPDOR) and -HETCOR NMR as well as (27)Al{(31)P}-rotational echo double resonance (REDOR) NMR experiments, complemented by (31)P-2D-J-RESolved MAS NMR experiments to probe P-O-P connectivity utilizing the through bond scalar J-coupling. The combination of the results from the various NMR approaches enables us to not only quantify the phosphate units present in the glass but also to identify their respective structural environments within the three-dimensional network on a medium length scale employing a modified Q notation, Q(n)(m),(AlO)(x), where n denotes the number of connected tetrahedral phosphate, m gives the number of aluminate species connected to a central phosphate unit and x specifies the nature of the bonded aluminate species (i.e. 4, 5 or 6 coordinate aluminium).

Method of making a multi-electrode double layer capacitor having single electrolyte seal and aluminum-impregnated carbon cloth electrodes

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

Farahmandi, C. Joseph; Dispennette, John M.; Blank, Edward

A method of making a double layer capacitior includes first and second flat stacks of electrodes adapted to be housed in a closeable two-part capacitor case which includes only a single electrolyte seal. Each electrode stack has a plurality of electrodes connected in parallel, with the electrodes of one stack being interleaved with the electrodes of the other stack to form an interleaved stack, and with the electrodes of each stack being electrically connected to respective capacitor terminals. A porous separator is positioned against the electrodes of one stack before interleaving to prevent electrical shorts between the electrodes. The electrodesmore » are made by folding a compressible, low resistance, aluminum-impregnated carbon cloth, made from activated carbon fibers, around a current collector foil, with a tab of the foils of each electrode of each stack being connected in parallel and connected to the respective capacitor terminal. The height of the interleaved stack is somewhat greater than the inside height of the closed capacitor case, thereby requiring compression of the interleaved electrode stack when placed inside of the case, and thereby maintaining the interleaved electrode stack under modest constant pressure. The closed capacitor case is filled with an electrolytic solution and sealed. A preferred electrolytic solution is made by dissolving an appropriate salt into acetonitrile (CH.sub.3 CN). In one embodiment, the two arts of the capacitor case are conductive and function as the capacitor terminals.« less

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

PubMed

Singh, Navneet; Chakrabarty, Subhas

2013-11-15

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

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

PubMed

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

2010-12-01

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

Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

PubMed Central

Milner, Derek J.; Mavroidis, Manolis; Weisleder, Noah; Capetanaki, Yassemi

2000-01-01

Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K m) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant role in mitochondrial positioning and respiratory function in cardiac and skeletal muscle. PMID:10995435

The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.

PubMed

Barberi, Theresa J; Dunkle, Alexis; He, You-Wen; Racioppi, Luigi; Means, Anthony R

2012-01-01

Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that potently activate naïve T cells, thereby bridging innate and adaptive immune responses. When challenged with LPS, Pin1-null mice failed to accumulate spleen conventional dendritic cells (cDC). Analysis of steady-state spleen DC populations revealed that Pin1-null mice had fewer CD8+ cDC. This defect was recapitulated by culturing Pin1-null bone marrow with the DC-instructive cytokine Flt3 Ligand. Additionally, injection of Flt3 Ligand for 9 days failed to induce robust expansion of CD8+ cDC in Pin1-null mice. Upon infection with Listeria monocytogenes, Pin1-null mice were defective in stimulating proliferation of adoptively transferred WT CD8+ T cells, suggesting that decreases in Pin1 null CD8+ cDC may affect T cell responses to infection in vivo. Finally, upon analyzing expression of proteins involved in DC development, elevated expression of PU.1 was detected in Pin1-null cells, which resulted from an increase in PU.1 protein half-life. We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity.

Hepatic effects of a methionine-choline-deficient diet in hepatocyte RXRalpha-null mice.

PubMed

Gyamfi, Maxwell Afari; Tanaka, Yuji; He, Lin; Klaassen, Curtis D; Wan, Yu-Jui Yvonne

2009-01-15

Retinoid X receptor-alpha (RXRalpha) is an obligate partner for several nuclear hormone receptors that regulate important physiological processes in the liver. In this study the impact of hepatocyte RXRalpha deficiency on methionine and choline deficient (MCD) diet-induced steatosis, oxidative stress, inflammation, and hepatic transporters gene expression were examined. The mRNA of sterol regulatory element-binding protein (SREBP)-regulated genes, important for lipid synthesis, were not altered in wild type (WT) mice, but were increased 2.0- to 5.4-fold in hepatocyte RXRalpha-null (H-RXRalpha-null) mice fed a MCD diet for 14 days. Furthermore, hepatic mRNAs and proteins essential for fatty acid beta-oxidation were not altered in WT mice, but were decreased in the MCD diet-fed H-RXRalpha-null mice, resulting in increased hepatic free fatty acid levels. Cyp2e1 enzyme activity and lipid peroxide levels were induced only in MCD-fed WT mice. In contrast, hepatic mRNA levels of pro-inflammatory factors were increased only in H-RXRalpha-null mice fed the MCD diet. Hepatic uptake transporters Oatp1a1 and Oatp1b2 mRNA levels were decreased in WT mice fed the MCD diet, whereas the efflux transporter Mrp4 was increased. However, in the H-RXRalpha-null mice, the MCD diet only moderately decreased Oatp1a1 and induced both Oatp1a4 and Mrp4 gene expression. Whereas the MCD diet increased serum bile acid levels and alkaline phosphatase activity in both WT and H-RXRalpha-null mice, serum ALT levels were induced (2.9-fold) only in the H-RXRalpha-null mice. In conclusion, these data suggest a critical role for RXRalpha in hepatic fatty acid homeostasis and protection against MCD-induced hepatocyte injury.

Altered Anterior Segment Biometric Parameters in Mice Deficient in SPARC.

PubMed

Ho, Henrietta; Htoon, Hla M; Yam, Gary Hin-Fai; Toh, Li Zhen; Lwin, Nyein Chan; Chu, Stephanie; Lee, Ying Shi; Wong, Tina T; Seet, Li-Fong

2017-01-01

Secreted protein acidic and rich in cysteine (SPARC) and Hevin are structurally related matricellular proteins involved in extracellular matrix assembly. In this study, we compared the anterior chamber biometric parameters and iris collagen properties in SPARC-, Hevin- and SPARC-/Hevin-null with wild-type (WT) mice. The right eyes of 53 WT, 35 SPARC-, 56 Hevin-, and 63 SPARC-/Hevin-null mice were imaged using the RTVue-100 Fourier-domain optical coherence tomography system. The parameters measured were anterior chamber depth (ACD), trabecular-iris space area (TISA), angle opening distance (AOD), and pupil diameter. Biometric data were analyzed using analysis of covariance and adjusted for age, sex, and pupil diameter. Expression of Col1a1, Col8a1, and Col8a2 transcripts in the irises was measured by quantitative polymerase chain reaction. Collagen fibril thickness was evaluated by transmission electron microscopy. Mice that were SPARC- and SPARC-/Hevin-null had 1.28- and 1.25-fold deeper ACD, 1.45- and 1.53-fold larger TISA, as well as 1.42- and 1.51-fold wider AOD than WT, respectively. These measurements were not significantly different between SPARC- and SPARC-/Hevin-null mice. The SPARC-null iris expressed lower Col1a1, but higher Col8a1 and Col8a2 transcripts compared with WT. Collagen fibrils in the SPARC- and SPARC-/Hevin-null irises were 1.5- and 1.7-fold thinner than WT, respectively. The Hevin-null iris did not differ from WT in these collagen properties. SPARC-null mice have deeper anterior chamber as well as wider drainage angles compared with WT. Therefore, SPARC plays a key role in influencing the spatial organization of the anterior segment, potentially via modulation of collagen properties, while Hevin is not likely to be involved.

Characterization of CpSte11, a MAPKKK gene of Cryphonectria parasitica, and initial evidence of its involvement in the pheromone response pathway.

PubMed

Park, Jin-Ah; Kim, Jung-Mi; Park, Seung-Moon; Kim, Dae-Hyuk

2012-04-01

The gene CpSte11 of Cryphonectria parasitica, which encodes a yeast Ste11 homologue, was cloned and characterized. Gene replacement analysis revealed a high frequency of CpSte11 null mutants. When compared with the wild-type parent strain, CpSte11 null mutants showed no difference in terms of growth rate or pigmentation. However, CpSte11 null mutants showed a marked decrease in both the number and size of stromal pustules on chestnut twigs. The virulence test showed that, in comparison with those of the wild-type and virus-infected hypovirulent strains, CpSte11 null mutants produced necrotic areas of intermediate size. Disruption of the CpSte11 gene also resulted in defects in female fertility. Down-regulation of transcripts for the mating pheromone precursor gene, Mf2/2, and mating response transcription factors, such as cpst12 and pro1, was observed in CpSte11 null mutants. The down-regulation of Mf2/2, cpst12 and pro1 was also observed in the mutant phenotype of Cpmk2, a mating response Fus3-like mitogen-activated protein kinase (MAPK) gene, but not in the mutant of Cpmk1, a high-osmolarity glycerol Hog1-like MAPK gene. These results indicate that the cloned CpSte11 gene is functionally involved in the mating response pathway and acts through downstream targets, including Cpmk2, cpst12, pro1 and Mf2/2. However, the characteristics of the CpSte11 null mutant were fully phenocopied only in the cpst12 null mutant, but not in other studied null mutants of components of the putative mating response pathway. © 2011 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2011 BSPP AND BLACKWELL PUBLISHING LTD.

Treatment of gingival recession defects with xenogenic collagen matrix: a histologic report.

PubMed

Camelo, Marcelo; Nevins, Myron; Nevins, Marc L; Schupbach, Peter; Kim, David M

2012-04-01

The connective tissue graft (CTG) in conjunction with a coronally advanced flap is still regarded as the gold standard treatment for gingival recession defects. Increased surgical morbidity as well as limited tissue availability continues to spur interest in alternatives to the CTG. The current case report examines a porcine-derived, double-layer collagen matrix as an alternative to the CTG in managing Miller Class I and II recession defects. A long junctional epithelial attachment as well as connective tissue adhesion were noted when collagen matrix was used in conjunction with a coronally advanced flap in recession treatment protocols. The results suggest that it is possible to obtain root coverage without harvesting connective tissue.

Population connectivity of the plating coral Agaricia lamarcki from southwest Puerto Rico

NASA Astrophysics Data System (ADS)

Hammerman, Nicholas M.; Rivera-Vicens, Ramon E.; Galaska, Matthew P.; Weil, Ernesto; Appledoorn, Richard S.; Alfaro, Monica; Schizas, Nikolaos V.

2018-03-01

Identifying genetic connectivity and discrete population boundaries is an important objective for management of declining Caribbean reef-building corals. A double digest restriction-associated DNA sequencing protocol was utilized to generate 321 single nucleotide polymorphisms to estimate patterns of horizontal and vertical gene flow in the brooding Caribbean plate coral, Agaricia lamarcki. Individual colonies ( n = 59) were sampled from eight locations throughout southwestern Puerto Rico from six shallow ( 10-20 m) and two mesophotic habitats ( 30-40 m). Descriptive summary statistics (fixation index, F ST), analysis of molecular variance, and analysis through landscape and ecological associations and discriminant analysis of principal components estimated high population connectivity with subtle subpopulation structure among all sampling localities.

Hyperactive error responses and altered connectivity in ventromedial and frontoinsular cortices in obsessive-compulsive disorder.

PubMed

Stern, Emily R; Welsh, Robert C; Fitzgerald, Kate D; Gehring, William J; Lister, Jamey J; Himle, Joseph A; Abelson, James L; Taylor, Stephan F

2011-03-15

Patients with obsessive-compulsive disorder (OCD) show abnormal functioning in ventral frontal brain regions involved in emotional/motivational processes, including anterior insula/frontal operculum (aI/fO) and ventromedial frontal cortex (VMPFC). While OCD has been associated with an increased neural response to errors, the influence of motivational factors on this effect remains poorly understood. To investigate the contribution of motivational factors to error processing in OCD and to examine functional connectivity between regions involved in the error response, functional magnetic resonance imaging data were measured in 39 OCD patients (20 unmedicated, 19 medicated) and 38 control subjects (20 unmedicated, 18 medicated) during an error-eliciting interference task where motivational context was varied using monetary incentives (null, loss, and gain). Across all errors, OCD patients showed reduced deactivation of VMPFC and greater activation in left aI/FO compared with control subjects. For errors specifically resulting in a loss, patients further hyperactivated VMPFC, as well as right aI/FO. Independent of activity associated with task events, OCD patients showed greater functional connectivity between VMPFC and regions of bilateral aI/FO and right thalamus. Obsessive-compulsive disorder patients show greater activation in neural regions associated with emotion and valuation when making errors, which could be related to altered intrinsic functional connectivity between brain networks. These results highlight the importance of emotional/motivational responses to mistakes in OCD and point to the need for further study of network interactions in the disorder. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Subpulse drifting, nulling, and mode changing in PSR J1822-2256

NASA Astrophysics Data System (ADS)

Basu, Rahul; Mitra, Dipanjan

2018-05-01

We report a detailed observational study of the single pulses from the pulsar J1822-2256. The pulsar shows the presence of subpulse drifting, nulling as well as multiple emission modes. During these observations the pulsar existed primarily in two modes; mode A with prominent drift bands and mode B which was more disorderly without any clear subpulse drifting. A third mode C was also seen for a short duration with a different drifting periodicity compared to mode A. The nulls were present throughout the observations but were more frequent during the disorderly B mode. The nulling also exhibited periodicity with a clear peak in the fluctuation spectra. Before the transition from mode A to nulling the pulsar switched to a third drifting state with periodicity different from both mode A and C. The diversity seen in the single pulse behaviour from the pulsar J1822-2256 provides an unique window into the emission physics.

Association of PTSD symptoms with asthma attacks among hurricane Katrina survivors.

PubMed

Arcaya, Mariana C; Lowe, Sarah R; Rhodes, Jean E; Waters, Mary C; Subramanian, S V

2014-12-01

The relationship between posttraumatic stress disorder (PTSD) and asthma in the wake of natural disasters is poorly understood. Using pre- and postdisaster data (N = 405) from the Resilience in Survivors of Katrina (RISK) project, we examined associations between PTSD symptoms, measured by the Impact of Event Scale-Revised (IES-R), and self-reported postdisaster asthma attacks. A 1-point increase in the IES-R avoidance score, which corresponded to one standard deviation change in this sample, was associated with double the odds of reporting an asthma attack or episode since the hurricane, 95% CI Revise spacing among characters: [1.22, 4.16]. Association with hyperarousal and intrusion symptoms was null. Further research using objective measures of asthma morbidity is needed; nevertheless, these findings may help inform postdisaster health services delivery and predisaster mitigation planning. Copyright © 2014 International Society for Traumatic Stress Studies.

The effect of safety factor profile on transport in steady-state, high-performance scenarios

DOE PAGES

Holcomb, C. T.; Ferron, J. R.; Luce, T. C.; ...

2012-03-09

In this study, an analysis of the dependence of transport on the safety factor profile in high-performance, steady-state scenario discharges is presented. This is based on experimental scans of q 95 and q min taken with fixed β N, toroidal field, double-null plasma shape, divertor pumping, and electron cyclotron current drive input. The temperature and thermal diffusivity profiles were found to vary considerably with the q-profile, and these variations were significantly different for electrons and ions. With fixed q 95, both temperature profiles increase and broaden as q min is increased and the magnetic shear becomes low or negative inmore » the inner half radius, but these temperature profile changes are stronger for the electrons. Power balance calculations show the peak in the ion thermal diffusivity (χ i) at ρ – 0.6 – 0.8 increases with q 95 or q min.« less