Expression levels of DNA replication and repair genes predict regional somatic repeat instability in the brain but are not altered by polyglutamine disease protein expression or age.

PubMed

Mason, Amanda G; Tomé, Stephanie; Simard, Jodie P; Libby, Randell T; Bammler, Theodor K; Beyer, Richard P; Morton, A Jennifer; Pearson, Christopher E; La Spada, Albert R

2014-03-15

Expansion of CAG/CTG trinucleotide repeats causes numerous inherited neurological disorders, including Huntington's disease (HD), several spinocerebellar ataxias and myotonic dystrophy type 1. Expanded repeats are genetically unstable with a propensity to further expand when transmitted from parents to offspring. For many alleles with expanded repeats, extensive somatic mosaicism has been documented. For CAG repeat diseases, dramatic instability has been documented in the striatum, with larger expansions noted with advancing age. In contrast, only modest instability occurs in the cerebellum. Using microarray expression analysis, we sought to identify the genetic basis of these regional instability differences by comparing gene expression in the striatum and cerebellum of aged wild-type C57BL/6J mice. We identified eight candidate genes enriched in cerebellum, and validated four--Pcna, Rpa1, Msh6 and Fen1--along with a highly associated interactor, Lig1. We also explored whether expression levels of mismatch repair (MMR) proteins are altered in a line of HD transgenic mice, R6/2, that is known to show pronounced regional repeat instability. Compared with wild-type littermates, MMR expression levels were not significantly altered in R6/2 mice regardless of age. Interestingly, expression levels of these candidates were significantly increased in the cerebellum of control and HD human samples in comparison to striatum. Together, our data suggest that elevated expression levels of DNA replication and repair proteins in cerebellum may act as a safeguard against repeat instability, and may account for the dramatically reduced somatic instability present in this brain region, compared with the marked instability observed in the striatum.

Detection of significant variation in acoustic output of an electromagnetic lithotriptor.

PubMed

Pishchalnikov, Yuri A; McAteer, James A; Vonderhaar, R Jason; Pishchalnikova, Irina V; Williams, James C; Evan, Andrew P

2006-11-01

We describe the observation of significant instability in the output of an electromagnetic lithotriptor. This instability had a form that was not detected by routine assessment, but rather was observed only by collecting many consecutive shock waves in nonstop regimen. A Dornier DoLi-50 lithotriptor used exclusively for basic research was tested and approved by the regional technician. This assessment included hydrophone measures at select power levels with the collection of about 25 shock waves per setting. Subsequent laboratory characterization used a fiberoptic hydrophone and storage oscilloscope for data acquisition. Waveforms were collected nonstop for hundreds of pulses. Output was typically stable for greater than 1,000 shock waves but substantial fluctuations in acoustic pressures were also observed. For example, output at power level 3 (mean peak positive acoustic pressure +/- SD normally 44 +/- 2 MPa) increased dramatically to greater than 50 MPa or decreased significantly to approximately 30 MPa for hundreds of shock waves. The cause of instability was eventually traced to a faulty lithotriptor power supply. Instability in lithotriptor acoustic output can occur and it may not be detected by routine assessment. Collecting waveforms in a nonstop regimen dramatically increases sampling size, improving the detection of instability. Had the instability that we observed occurred during patient treatment, the energy delivered may well have exceeded the planned dose. Since the potential for adverse effects in lithotripsy increases as the dose is increased, it would be valuable to develop ways to better monitor the acoustic output of lithotriptors.

DNA Secondary Structure at Chromosomal Fragile Sites in Human Disease

PubMed Central

Thys, Ryan G; Lehman, Christine E; Pierce, Levi C. T; Wang, Yuh-Hwa

2015-01-01

DNA has the ability to form a variety of secondary structures that can interfere with normal cellular processes, and many of these structures have been associated with neurological diseases and cancer. Secondary structure-forming sequences are often found at chromosomal fragile sites, which are hotspots for sister chromatid exchange, chromosomal translocations, and deletions. Structures formed at fragile sites can lead to instability by disrupting normal cellular processes such as DNA replication and transcription. The instability caused by disruption of replication and transcription can lead to DNA breakage, resulting in gene rearrangements and deletions that cause disease. In this review, we discuss the role of DNA secondary structure at fragile sites in human disease. PMID:25937814

The influence of wall resonances on the levitation of objects in a single-axis acoustic processing chamber

NASA Technical Reports Server (NTRS)

Ross, B. B.

1980-01-01

Instabilities were observed in high temperature, single axis acoustic processing chambers. At certain temperatures, strong wall resonances were generated within the processing chamber itself and these transverse resonances were thought sufficient to disrupt the levitation well. These wall resonances are apparently not strong enough to cause instabilities in the levitation well.

Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted Nuclear Lamina.

PubMed

Gonzalo, Susana; Kreienkamp, Ray

2016-01-01

The organization of the genome within the nuclear space is viewed as an additional level of regulation of genome function, as well as a means to ensure genome integrity. Structural proteins associated with the nuclear envelope, in particular lamins (A- and B-type) and lamin-associated proteins, play an important role in genome organization. Interestingly, there is a whole body of evidence that links disruptions of the nuclear lamina with DNA repair defects and genomic instability. Here, we describe a few standard techniques that have been successfully utilized to identify mechanisms behind DNA repair defects and genomic instability in cells with an altered nuclear lamina. In particular, we describe protocols to monitor changes in the expression of DNA repair factors (Western blot) and their recruitment to sites of DNA damage (immunofluorescence); kinetics of DNA double-strand break repair after ionizing radiation (neutral comet assays); frequency of chromosomal aberrations (FISH, fluorescence in situ hybridization); and alterations in telomere homeostasis (Quantitative-FISH). These techniques have allowed us to shed some light onto molecular mechanisms by which alterations in A-type lamins induce genomic instability, which could contribute to the pathophysiology of aging and aging-related diseases.

The role of zonal flows in disc gravito-turbulence

NASA Astrophysics Data System (ADS)

Vanon, R.

2018-07-01

The work presented here focuses on the role of zonal flows in the self-sustenance of gravito-turbulence in accretion discs. The numerical analysis is conducted using a bespoke pseudo-spectral code in fully compressible, non-linear conditions. The disc in question, which is modelled using the shearing sheet approximation, is assumed to be self-gravitating, viscous, and thermally diffusive; a constant cooling time-scale is also considered. Zonal flows are found to emerge at the onset of gravito-turbulence and they remain closely linked to the turbulent state. A cycle of zonal flow formation and destruction is established, mediated by a slow mode instability (which allows zonal flows to grow) and a non-axisymmetric instability (which disrupts the zonal flow), which is found to repeat numerous times. It is in fact the disruptive action of the non-axisymmetric instability to form new leading and trailing shearing waves, allowing energy to be extracted from the background flow and ensuring the self-sustenance of the gravito-turbulent regime.

The role of zonal flows in disc gravito-turbulence

NASA Astrophysics Data System (ADS)

Vanon, R.

2018-04-01

The work presented here focuses on the role of zonal flows in the self-sustenance of gravito-turbulence in accretion discs. The numerical analysis is conducted using a bespoke pseudo-spectral code in fully compressible, non-linear conditions. The disc in question, which is modelled using the shearing sheet approximation, is assumed to be self-gravitating, viscous, and thermally diffusive; a constant cooling timescale is also considered. Zonal flows are found to emerge at the onset of gravito-turbulence and they remain closely linked to the turbulent state. A cycle of zonal flow formation and destruction is established, mediated by a slow mode instability (which allows zonal flows to grow) and a non-axisymmetric instability (which disrupts the zonal flow), which is found to repeat numerous times. It is in fact the disruptive action of the non-axisymmetric instability to form new leading and trailing shearing waves, allowing energy to be extracted from the background flow and ensuring the self-sustenance of the gravito-turbulent regime.

Analysis of the 20th November 2003 Extreme Geomagnetic Storm using CTIPe Model and GNSS Data

NASA Astrophysics Data System (ADS)

Fernandez-Gomez, I.; Borries, C.; Codrescu, M.

2016-12-01

The ionospheric instabilities produced by solar activity generate disturbances in ionospheric density (ionospheric storms) with important terrestrial consequences such as disrupting communications and positioning. During the 20th November 2003 extreme geomagnetic storm, significant perturbations were produced in the ionosphere - thermosphere system. In this work, we replicate how this system responded to the onset of this particular storm, using the Coupled Thermosphere Ionosphere Plasmasphere electrodynamics physics based model. CTIPe simulates the changes in the neutral winds, temperature, composition and electron densities. Although modelling the ionosphere under this conditions is a challenging task due to energy flow uncertainties, the model reproduces some of the storm features necessary to interpret the physical mechanisms behind the Total Electron Content (TEC) increase and the dramatic changes in composition during this event.Corresponding effects are observed in the TEC simulations from other physics based models and from observations derived from Global Navigation Satellite System (GNSS) and ground-based measurements.The study illustrates the necessity of using both, measurements and models, to have a complete understanding of the processes that are most likely responsible for the observed effects.

BRCA1 interaction of centrosomal protein Nlp is required for successful mitotic progression.

PubMed

Jin, Shunqian; Gao, Hua; Mazzacurati, Lucia; Wang, Yang; Fan, Wenhong; Chen, Qiang; Yu, Wei; Wang, Mingrong; Zhu, Xueliang; Zhang, Chuanmao; Zhan, Qimin

2009-08-21

Breast cancer susceptibility gene BRCA1 is implicated in the control of mitotic progression, although the underlying mechanism(s) remains to be further defined. Deficiency of BRCA1 function leads to disrupted mitotic machinery and genomic instability. Here, we show that BRCA1 physically interacts and colocalizes with Nlp, an important molecule involved in centrosome maturation and spindle formation. Interestingly, Nlp centrosomal localization and its protein stability are regulated by normal cellular BRCA1 function because cells containing BRCA1 mutations or silenced for endogenous BRCA1 exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation. Its is likely that the BRCA1 regulation of Nlp stability involves Plk1 suppression. Inhibition of endogenous Nlp via the small interfering RNA approach results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy, which mimic the phenotypes of disrupted BRCA1. Thus, BRCA1 interaction of Nlp might be required for the successful mitotic progression, and abnormalities of Nlp lead to genomic instability.

BRCA1 Interaction of Centrosomal Protein Nlp Is Required for Successful Mitotic Progression*♦

PubMed Central

Jin, Shunqian; Gao, Hua; Mazzacurati, Lucia; Wang, Yang; Fan, Wenhong; Chen, Qiang; Yu, Wei; Wang, Mingrong; Zhu, Xueliang; Zhang, Chuanmao; Zhan, Qimin

2009-01-01

Breast cancer susceptibility gene BRCA1 is implicated in the control of mitotic progression, although the underlying mechanism(s) remains to be further defined. Deficiency of BRCA1 function leads to disrupted mitotic machinery and genomic instability. Here, we show that BRCA1 physically interacts and colocalizes with Nlp, an important molecule involved in centrosome maturation and spindle formation. Interestingly, Nlp centrosomal localization and its protein stability are regulated by normal cellular BRCA1 function because cells containing BRCA1 mutations or silenced for endogenous BRCA1 exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation. Its is likely that the BRCA1 regulation of Nlp stability involves Plk1 suppression. Inhibition of endogenous Nlp via the small interfering RNA approach results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy, which mimic the phenotypes of disrupted BRCA1. Thus, BRCA1 interaction of Nlp might be required for the successful mitotic progression, and abnormalities of Nlp lead to genomic instability. PMID:19509300

Clinical Evaluation and Physical Exam Findings in Patients with Anterior Shoulder Instability.

PubMed

Lizzio, Vincent A; Meta, Fabien; Fidai, Mohsin; Makhni, Eric C

2017-12-01

The goal of this paper is to provide an overview in evaluating the patient with suspected or known anteroinferior glenohumeral instability. There is a high rate of recurrent subluxations or dislocations in young patients with history of anterior shoulder dislocation, and recurrent instability will increase likelihood of further damage to the glenohumeral joint. Proper identification and treatment of anterior shoulder instability can dramatically reduce the rate of recurrent dislocation and prevent subsequent complications. Overall, the anterior release or surprise test demonstrates the best sensitivity and specificity for clinically diagnosing anterior shoulder instability, although other tests also have favorable sensitivities, specificities, positive likelihood ratios, negative likelihood ratios, and inter-rater reliabilities. Anterior shoulder instability is a relatively common injury in the young and athletic population. The combination of history and performing apprehension, relocation, release or surprise, anterior load, and anterior drawer exam maneuvers will optimize sensitivity and specificity for accurately diagnosing anterior shoulder instability in clinical practice.

Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis

PubMed Central

Opendak, Maya; Offit, Lily; Monari, Patrick; Schoenfeld, Timothy J.; Sonti, Anup N.; Cameron, Heather A.

2016-01-01

Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP–thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus. SIGNIFICANCE STATEMENT To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP–thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior. PMID:27358459

SHEET PLASMA DEVICE

DOEpatents

Henderson, O.A.

1962-07-17

An ion-electron plasma heating apparatus of the pinch tube class was developed wherein a plasma is formed by an intense arc discharge through a gas and is radially constricted by the magnetic field of the discharge. To avoid kink and interchange instabilities which can disrupt a conventional arc shortiy after it is formed, the apparatus is a pinch tube with a flat configuration for forming a sheet of plasma between two conductive plates disposed parallel and adjacent to the plasma sheet. Kink instabilities are suppressed by image currents induced in the conductive plates while the interchange instabilities are neutrally stable because of the flat plasma configuration wherein such instabilities may occur but do not dynamically increase in amplitude. (AEC)

Feedback-Assisted Extension of the Tokamak Operating Space to Low Safety Factor

NASA Astrophysics Data System (ADS)

Hanson, J. M.

2013-10-01

Recent DIII-D experiments have demonstrated stable operation at very low edge safety factor, q95 <~ 2 through the use of magnetic feedback to control the n = 1 resistive wall mode (RWM) instability. The performance of tokamak fusion devices may benefit from increased plasma current, and thus, decreased q. However, disruptive stability limits are commonly encountered in experiments at qedge ~ 2 (limited plasmas) and q95 ~ 2 (diverted plasmas), limiting exploration of low q regimes. In the recent DIII-D experiments, the impact and control of key disruptive instabilities was studied. Locked n = 1 modes with exponential growth times on the order of the wall eddy current decay timescale τw preceded disruptions at q95 = 2 . The instabilities have a poloidal structure that is consistent with VALEN simulations of the RWM mode structure at q95 = 2 . Applying proportional gain magnetic feedback control of the n = 1 mode resulted in stabilized operation with q95 reaching 1.9, and an extension of the discharge lifetime for > 100τw . Loss of feedback control was accompanied by power supply saturation, followed by a rapidly growing n = 1 mode and disruption. Comparisons of the feedback dynamics with VALEN simulations will be presented. The DIII-D results complement and will be discussed alongside recent RFX-MOD demonstrations of RWM control using magnetic feedback in limited tokamak discharges with qedge < 2. These results call attention to the utility of magnetic feedback in significantly extending the tokamak operational space and potentially opening a new route to economical fusion power production. Supported by the US Department of Energy under DE-FG02-04ER54761 and DE-FC02-04ER54698.

Experimental Evidence for Magnetorotational Instability in a Taylor-Couette Flow under the Influence of a Helical Magnetic Field

NASA Astrophysics Data System (ADS)

Stefani, Frank; Gundrum, Thomas; Gerbeth, Gunter; Rüdiger, Günther; Schultz, Manfred; Szklarski, Jacek; Hollerbach, Rainer

2006-11-01

A recent Letter [R. Hollerbach and G. Rüdiger, Phys. Rev. Lett. 95, 124501 (2005)PRLTAO0031-900710.1103/PhysRevLett.95.124501] has shown that the threshold for the onset of the magnetorotational instability in a Taylor-Couette flow is dramatically reduced if both axial and azimuthal magnetic fields are imposed. In agreement with this prediction, we present results of a Taylor-Couette experiment with the liquid metal alloy GaInSn, showing evidence for the existence of the magnetorotational instability at Reynolds numbers of order 1000 and Hartmann numbers of order 10.

Competing Turing and Faraday Instabilities in Longitudinally Modulated Passive Resonators.

PubMed

Copie, François; Conforti, Matteo; Kudlinski, Alexandre; Mussot, Arnaud; Trillo, Stefano

2016-04-08

We experimentally investigate the interplay of Turing (modulational) and Faraday (parametric) instabilities in a bistable passive nonlinear resonator. The Faraday branch is induced via parametric resonance owing to a periodic modulation of the resonator dispersion. We show that the bistable switching dynamics is dramatically affected by the competition between the two instability mechanisms, which dictates two completely novel scenarios. At low detunings from resonance, switching occurs between the stable stationary lower branch and the Faraday-unstable upper branch, whereas at high detunings we observe the crossover between the Turing and Faraday periodic structures. The results are well explained in terms of the universal Lugiato-Lefever model.

Spontaneous symmetry breaking by double lithium adsorption in polyacenes

NASA Astrophysics Data System (ADS)

Ortiz, Yenni. P.; Seligman, Thomas H.

2010-12-01

We show that adsorption of one lithium atom to polyacenes, i.e. chains of linearly fused benzene rings, will cause such chains to be slightly deformed. If we adsorb a second identical atom on the opposite side of the same ring, this deformation is dramatically enhanced despite the fact that a symmetric configuration seems possible. We argue, that this may be due to an instability of the Jahn-Teller type possibly indeed to a Peierls instability.

Spontaneous symmetry breaking by double lithium adsorption in polyacenes

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

Ortiz, Yenni. P.; Seligman, Thomas H.; Centro Internacional de Ciencias, Cuernavaca, Morelos

2010-12-23

We show that adsorption of one lithium atom to polyacenes, i.e. chains of linearly fused benzene rings, will cause such chains to be slightly deformed. If we adsorb a second identical atom on the opposite side of the same ring, this deformation is dramatically enhanced despite the fact that a symmetric configuration seems possible. We argue, that this may be due to an instability of the Jahn-Teller type possibly indeed to a Peierls instability.

Linear MHD stability analysis of post-disruption plasmas in ITER

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

Aleynikova, K., E-mail: ksenia.aleynikova@gmail.com; Huijsmans, G. T. A.; Aleynikov, P.

2016-05-15

Most of the plasma current can be replaced by a runaway electron (RE) current during plasma disruptions in ITER. In this case the post-disruption plasma current profile is likely to be more peaked than the pre-disruption profile. The MHD activity of such plasma will affect the runaway electron generation and confinement and the dynamics of the plasma position evolution (Vertical Displacement Event), limiting the timeframe for runaway electrons and disruption mitigation. In the present paper, we evaluate the influence of the possible RE seed current parameters on the onset of the MHD instabilities. By varying the RE seed current profile,more » we search for subsequent plasma evolutions with the highest and the lowest MHD activity. This information can be applied to a development of desirable ITER disruption scenario.« less

Validation of an Adaptive Combustion Instability Control Method for Gas-Turbine Engines

NASA Technical Reports Server (NTRS)

Kopasakis, George; DeLaat, John C.; Chang, Clarence T.

2004-01-01

This paper describes ongoing testing of an adaptive control method to suppress high frequency thermo-acoustic instabilities like those found in lean-burning, low emission combustors that are being developed for future aircraft gas turbine engines. The method called Adaptive Sliding Phasor Averaged Control, was previously tested in an experimental rig designed to simulate a combustor with an instability of about 530 Hz. Results published earlier, and briefly presented here, demonstrated that this method was effective in suppressing the instability. Because this test rig did not exhibit a well pronounced instability, a question remained regarding the effectiveness of the control methodology when applied to a more coherent instability. To answer this question, a modified combustor rig was assembled at the NASA Glenn Research Center in Cleveland, Ohio. The modified rig exhibited a more coherent, higher amplitude instability, but at a lower frequency of about 315 Hz. Test results show that this control method successfully reduced the instability pressure of the lower frequency test rig. In addition, due to a certain phenomena discovered and reported earlier, the so called Intra-Harmonic Coupling, a dramatic suppression of the instability was achieved by focusing control on the second harmonic of the instability. These results and their implications are discussed, as well as a hypothesis describing the mechanism of intra-harmonic coupling.

Mechanics of instability-related delimination growth

NASA Technical Reports Server (NTRS)

Whitcomb, John D.

1988-01-01

Local buckling of a delaminated group of plies can lead to higher interlaminar stresses and delamination growth. The mechanics of instability-related delamination growth (IRDG) had been described previously for the through-width delamination. This paper describes the mechanics of IRDG for the embedded delamination subjected to either uniaxial or axisymmetric loads. The mechanics of IRDG are used to explain the dramatic differences in strain-energy release rates observed for the through-width, the axisymmetrically loaded embedded delamination, and the uniaxially loaded embedded delamination.

Multimode Regimes in Quantum Cascade Lasers: From Coherent Instabilities to Spatial Hole Burning

DTIC Science & Technology

2009-02-10

from which absorption can take place; and although not very significant, there is always bulk n2 of the material. 1 A. E. Siegman , Lasers ...2007 4. TI11.E AND SUBTITI..E 5a. CONTRACT NUMBER Multimode regimes in quantum cascade lasers : from coherent W91INF-04-I-0253 instabilities to spatial...quantum cascade lasers (QCLs). In narrow devices it is found that above a second threshold the laser spectrwn dramatically broadens showing multimode

Electromagnetic Modeling of the Passive Stabilization Loop at EAST

NASA Astrophysics Data System (ADS)

Ji, Xiang; Song, Yuntao; Wu, Songtao; Wang, Zhibin; Shen, Guang; Liu, Xufeng; Cao, Lei; Zhou, Zibo; Peng, Xuebing; Wang, Chenghao

2012-09-01

A passive stabilization loop (PSL) has been designed and manufactured in order to enhance the control of vertical instability and accommodate the new stage for high-performance plasma at EAST. Eddy currents are induced by vertical displacement events (VDEs) and disruption, which can produce a magnetic field to control the vertical instability of the plasma in a short timescale. A finite element model is created and meshed using ANSYS software. Based on the simulation of plasma VDEs and disruption, the distribution and decay curve of the eddy currents on the PSL are obtained. The largest eddy current is 200 kA and the stress is 68 MPa at the outer current bridge, which is the weakest point of the PSL because of the eddy currents and the magnetic fields. The analysis results provide the supporting data for the structural design.

Cerebrospinal fluid enhancement on fluid attenuated inversion recovery images after carotid artery stenting with neuroprotective balloon occlusions: hemodynamic instability and blood-brain barrier disruption.

PubMed

Ogami, Ryo; Nakahara, Toshinori; Hamasaki, Osamu; Araki, Hayato; Kurisu, Kaoru

2011-10-01

A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors were examined. CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.

Particle drift model for Z-pinch-driven magneto-Rayleigh-Taylor instability

NASA Astrophysics Data System (ADS)

Dan, Jia Kun; Xu, Qiang; Wang, Kun Lun; Ren, Xiao Dong; Huang, Xian Bin

2016-09-01

A theoretical model of Z-pinch driven magneto-Rayleigh-Taylor instability is proposed based on the particle drift point of view, which can explain the helical instability structure observed in premagnetized imploding liner experiments. It is demonstrated that all possible drift motions, including polarization drift, gradient drift, and curvature drift, which can lead to charge separations, each will attribute to an effective gravity acceleration. Theoretical predictions given by this model are dramatically different from those given by previous theories which have been readily recovered in the theory presented here as a limiting case. The theory shows qualitative agreement with available experimental data of the pitch angle and provides certain predictions to be verified.

Dynamics of an n = 1 explosive instability and its role in high-β disruptions

NASA Astrophysics Data System (ADS)

Aydemir, A. Y.; Park, B. H.; In, Y. K.

2018-01-01

Some low-n kink-ballooning modes not far from marginal stability are shown to exhibit a bifurcation between two very distinct nonlinear paths that depends sensitively on the background transport levels and linear perturbation amplitudes. The particular instability studied in this work is an n=1 mode dominated by an m/n=2/1 component. It is driven by a large pressure gradient in weak magnetic shear and can appear in various high- \

Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA.

PubMed

Lopez, Christopher R; Singh, Shivani; Hambarde, Shashank; Griffin, Wezley C; Gao, Jun; Chib, Shubeena; Yu, Yang; Ira, Grzegorz; Raney, Kevin D; Kim, Nayun

2017-06-02

G-quadruplex or G4 DNA is a non-B secondary DNA structure consisting of a stacked array of guanine-quartets that can disrupt critical cellular functions such as replication and transcription. When sequences that can adopt Non-B structures including G4 DNA are located within actively transcribed genes, the reshaping of DNA topology necessary for transcription process stimulates secondary structure-formation thereby amplifying the potential for genome instability. Using a reporter assay designed to study G4-induced recombination in the context of an actively transcribed locus in Saccharomyces cerevisiae, we tested whether co-transcriptional activator Sub1, recently identified as a G4-binding factor, contributes to genome maintenance at G4-forming sequences. Our data indicate that, upon Sub1-disruption, genome instability linked to co-transcriptionally formed G4 DNA in Top1-deficient cells is significantly augmented and that its highly conserved DNA binding domain or the human homolog PC4 is sufficient to suppress G4-associated genome instability. We also show that Sub1 interacts specifically with co-transcriptionally formed G4 DNA in vivo and that yeast cells become highly sensitivity to G4-stabilizing chemical ligands by the loss of Sub1. Finally, we demonstrate the physical and genetic interaction of Sub1 with the G4-resolving helicase Pif1, suggesting a possible mechanism by which Sub1 suppresses instability at G4 DNA. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Tracking Climate Change through the Spatiotemporal Dynamics of the Teletherms, the Statistically Hottest and Coldest Days of the Year

DOE PAGES

Dodds, Peter Sheridan; Mitchell, Lewis; Reagan, Andrew J.; ...

2016-05-11

Instabilities and long term shifts in seasons, whether induced by natural drivers or human activities, pose great disruptive threats to ecological, agricultural, and social systems. Here, we propose, measure, and explore two fundamental markers of location-sensitive seasonal variations: the Summer and Winter Teletherms—the on-average annual dates of the hottest and coldest days of the year. We analyze daily temperature extremes recorded at 1218 stations across the contiguous United States from 1853–2012, and observe large regional variation with the Summer Teletherm falling up to 90 days after the Summer Solstice, and 50 days for the Winter Teletherm after the Winter Solstice.more » We show that Teletherm temporal dynamics are substantive with clear and in some cases dramatic shifts reflective of system bifurcations. We also compare recorded daily temperature extremes with output from two regional climate models finding considerable though relatively unbiased error. In conclusion, our work demonstrates that Teletherms are an intuitive, powerful, and statistically sound measure of local climate change, and that they pose detailed, stringent challenges for future theoretical and computational models.« less

PTEN in the maintenance of genome integrity: From DNA replication to chromosome segregation.

PubMed

Hou, Sheng-Qi; Ouyang, Meng; Brandmaier, Andrew; Hao, Hongbo; Shen, Wen H

2017-10-01

Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. © 2017 WILEY Periodicals, Inc.

A decades-long fast-rise-exponential-decay flare in low-luminosity AGN NGC 7213

NASA Astrophysics Data System (ADS)

Yan, Zhen; Xie, Fu-Guo

2018-03-01

We analysed the four-decades-long X-ray light curve of the low-luminosity active galactic nucleus (LLAGN) NGC 7213 and discovered a fast-rise-exponential-decay (FRED) pattern, i.e. the X-ray luminosity increased by a factor of ≈4 within 200 d, and then decreased exponentially with an e-folding time ≈8116 d (≈22.2 yr). For the theoretical understanding of the observations, we examined three variability models proposed in the literature: the thermal-viscous disc instability model, the radiation pressure instability model, and the TDE model. We find that a delayed tidal disruption of a main-sequence star is most favourable; either the thermal-viscous disc instability model or radiation pressure instability model fails to explain some key properties observed, thus we argue them unlikely.

Nonlinear spatial evolution of inviscid instabilities on hypersonic boundary layers

NASA Technical Reports Server (NTRS)

Wundrow, David W.

1996-01-01

The spatial development of an initially linear vorticity-mode instability on a compressible flat-plate boundary layer is considered. The analysis is done in the framework of the hypersonic limit where the free-stream Mach number M approaches infinity. Nonlinearity is shown to become important locally, in a thin critical layer, when sigma, the deviation of the phase speed from unity, becomes o(M(exp -8/7)) and the magnitude of the pressure fluctuations becomes 0(sigma(exp 5/2)M(exp 2)). The unsteady flow outside the critical layer takes the form of a linear instability wave but with its amplitude completely determined by the nonlinear flow within the critical layer. The coupled set of equations which govern the critical-layer dynamics reflect a balance between spatial-evolution, (linear and nonlinear) convection and nonlinear vorticity-generation terms. The numerical solution to these equations shows that nonlinear effects produce a dramatic reduction in the instability-wave amplitude.

Cerebrospinal Fluid Enhancement on Fluid Attenuated Inversion Recovery Images After Carotid Artery Stenting with Neuroprotective Balloon Occlusions: Hemodynamic Instability and Blood-Brain Barrier Disruption

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

Ogami, Ryo, E-mail: ogami.r@mazda.co.jp; Nakahara, Toshinori; Hamasaki, Osamu

2011-10-15

Purpose: A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Methods: Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors weremore » examined. Results: CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Conclusions: Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.« less

Radiographic signs of static carpal instability with distal end radius fractures: is current treatment adequate?

PubMed

Bunker, D L J; Pappas, G; Moradi, P; Dowd, M B

2012-01-01

Patients presenting with distal end radius fractures may have concomitant carpal instability due to disruption of the scapholunate ligament. This study examined the incidence of static radiographic signs of carpal instability in patients with distal radial fractures before and after fracture treatment. We performed a retrospective radiographic study of 141 patients presenting to Central Middlesex Hospital, London between January 2002-May 2004 with distal end radius fractures. We used abnormal scapholunate angle as the primary indicator of possible carpal dissociation. Abnormal scapholunate angles were noted in 39% of patients at presentation and 35% of patients after treatment with no statistically significant intra-patient variability. Persistent static radiographic signs of carpal instability are high in this subset of patients. The long-term morbidity of persistent wrist instability may be avoided by early radiological diagnosis with clinical correlation to identify carpal ligament injuries and initiate treatment that addresses both the bony and ligamentous components of the injury.

Passive runaway electron suppression in tokamak disruptions

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

Smith, H. M.; Helander, P.; Boozer, A. H.

2013-07-15

Runaway electrons created in disruptions pose a serious problem for tokamaks with large current. It would be desirable to have a runaway electron suppression method which is passive, i.e., a method that does not rely on an uncertain disruption prediction system. One option is to let the large electric field inherent in the disruption drive helical currents in the wall. This would create ergodic regions in the plasma and increase the runaway losses. Whether these regions appear at a suitable time and place to affect the formation of the runaway beam depends on disruption parameters, such as electron temperature andmore » density. We find that it is difficult to ergodize the central plasma before a beam of runaway current has formed. However, the ergodic outer region will make the Ohmic current profile contract, which can lead to instabilities that yield large runaway electron losses.« less

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

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

Tokamak plasma current disruption infrared control system

DOEpatents

Kugel, H.W.; Ulrickson, M.

1984-04-16

This invention is directed to the diagnosis and detection of gross or macroinstabilities in a magnetically-confined fusion plasma device. Detection is performed in real time, and is prompt such that correction of the instability can be initiated in a timely fashion.

Ankle instability.

PubMed

Ferran, Nicholas A; Oliva, Francesco; Maffulli, Nicola

2009-06-01

Acute ankle sprains are common, and if inadequately treated may result in chronic instability. Lateral ankle injuries are most common, with deltoid injuries rare and associated with ankle fractures/dislocation. Medial ankle instability is rare. Functional management of acute lateral ankle sprains is the treatment of choice, with acute ligament repair reserved for athletes. Chronic lateral ankle instability is initially managed conservatively, however, failure of rehabilitation is an indication for surgical management. Nonanatomic tenodesis reconstructions have poor long-term results, sacrifice peroneal tendons, and disrupt normal ankle and hindfoot biomechanics. Anatomic repair of the anterior talofibular and calcaneofibular ligaments is recommended when the quality of the ruptured ligaments permits. Anatomic reconstruction with autograft or allograft should be performed when ligaments are attenuated. The role of arthroscopic reconstruction is evolving. Ankle arthroscopy should be performed at the time of repair or reconstruction and should address any other intra-articular causes of pain.

Glenohumeral instability: evaluation with MR arthrography.

PubMed

Beltran, J; Rosenberg, Z S; Chandnani, V P; Cuomo, F; Beltran, S; Rokito, A

1997-01-01

Magnetic resonance arthrography is superior to other imaging techniques in evaluation of the glenohumeral joint. Normal variants that can be diagnostic pitfalls include the anterosuperior sublabral foramen, the Buford complex, and hyaline cartilage under the labrum. Anteroinferior dislocation is the most frequent cause of anterior glenohumeral instability and produces a constellation of lesions (anteroinferior labral tear, classic and osseous Bankart lesions, Hill-Sachs lesion). Variants of anteroinferior labral tears include anterior labroligamentous periosteal sleeve avulsion and glenoid labral articular disruption. Anterior glenohumeral instability can also involve tears of the anterior or anterosuperior labrum or the glenohumeral ligaments. Posterior glenohumeral instability can involve a posterior labral tear, posterior capsular stripping or laxity; fracture, erosion, or sclerosis and ectopic ossification of the posterior glenoid fossa; reverse Hill-Sachs lesion; McLaughlin fracture; or posterosuperior glenoid impingement. Superior labral anterior and posterior lesions involve the superior labrum with varying degrees of biceps tendon involvement.

Runaway Geneeration In Disruptions Of Plasmas In TFTR

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

Fredrickson, E. D.; Bell, M. G.; Taylor, G.

2014-03-31

Many disruptions in the Tokamak Fusion Test Reactor (TFTR) [D. Meade and the TFTR Group, in Proceedings of the International Conference on Plasma Physics and Controlled Nuclear Fusion, Washington, DC, 1990 (International Atomic Energy Agency, Vienna, 1991), Vol. 1, pp. 9-24] produced populations of runaway electrons which carried a significant fraction of the original plasma current. In this paper, we describe experiments where, following a disruption of a low-beta, reversed shear plasma, currents of up to 1 MA carried mainly by runaway electrons were controlled and then ramped down to near zero using the ohmic transformer. In the longer lastingmore » runaway plasmas, Parail-Pogutse instabilities were observed.« less

Dark matter substructure in numerical simulations: a tale of discreteness noise, runaway instabilities, and artificial disruption

NASA Astrophysics Data System (ADS)

van den Bosch, Frank C.; Ogiya, Go

2018-04-01

To gain understanding of the complicated, non-linear, and numerical processes associated with the tidal evolution of dark matter subhaloes in numerical simulation, we perform a large suite of idealized simulations that follow individual N-body subhaloes in a fixed, analytical host halo potential. By varying both physical and numerical parameters, we investigate under what conditions the subhaloes undergo disruption. We confirm the conclusions from our more analytical assessment in van den Bosch et al. that most disruption is numerical in origin; as long as a subhalo is resolved with sufficient mass and force resolution, a bound remnant survives. This implies that state-of-the-art cosmological simulations still suffer from significant overmerging. We demonstrate that this is mainly due to inadequate force softening, which causes excessive mass loss and artificial tidal disruption. In addition, we show that subhaloes in N-body simulations are susceptible to a runaway instability triggered by the amplification of discreteness noise in the presence of a tidal field. These two processes conspire to put serious limitations on the reliability of dark matter substructure in state-of-the-art cosmological simulations. We present two criteria that can be used to assess whether individual subhaloes in cosmological simulations are reliable or not, and advocate that subhaloes that satisfy either of these two criteria be discarded from further analysis. We discuss the potential implications of this work for several areas in astrophysics.

The external kink mode in diverted tokamaks

DOE PAGES

Turnbull, Alan D.; Hanson, Jeremy M.; Turco, Francesca; ...

2016-06-16

Here, an explanation is provided for the disruptive instability in diverted tokamaks when the safety factor at the 95% poloidal flux surface, q 95, is driven below 2.0. The instability is a resistive kink counterpart to the current-driven ideal mode that traditionally explained the corresponding disruption in limited cross-sections when q edge, the safety factor at the outermost closed flux surface, lies just below a rational value. Experimentally, external kink modes are observed in limiter configurations as the current in a tokamak is ramped up and q edge decreases through successive rational surfaces. For q edge < 2, the instabilitymore » is always encountered and is highly disruptive. However, diverted plasmas, in which q edge is formally infinite in the magnetohydrodynamic (MHD) model, have presented a longstanding difficulty since the theory would predict stability, yet, the disruptive limit occurs in practice when q 95, reaches 2. It is shown from numerical calculations that a resistive kink mode is linearly destabilized by the rapidly increasing resistivity at the plasma edge when q 95 < 2, but q edge >> 2. The resistive kink behaves much like the ideal kink with predominantly kink or interchange parity and no real sign of a tearing component. However, the growth rates scale with a fractional power of the resistivity near the q = 2 surface. The results have a direct bearing on the conventional edge cutoff procedures used in most ideal MHD codes, as well as implications for ITER and for future reactor options.« less

HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability.

PubMed

Zhao, Jun-Wei; Fang, Fang; Guo, Yi; Zhu, Tai-Lin; Yu, Yun-Yun; Kong, Fan-Fei; Han, Ling-Fei; Chen, Dong-Sheng; Li, Fang

2016-11-25

The integration of human papilloma virus (HPV) into host genome is one of the critical steps that lead to the progression of precancerous lesion into cancer. However, the mechanisms and consequences of such integration events are poorly understood. This study aims to explore those questions by studying high risk HPV16 integration in women with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (SCC). Specifically, HPV integration status of 13 HPV16-infected patients were investigated by ligation-mediated PCR (DIPS-PCR) followed by DNA sequencing. In total, 8 HPV16 integration sites were identified inside or around genes associated with cancer development. In particular, the well-studied tumor suppressor genes SCAI was found to be integrated by HPV16, which would likely disrupt its expression and therefore facilitate the migration of tumor. On top of that, we observed several cases of chromosome translocation events coincide with HPV integration, which suggests the existence of chromosome instability. Additionally, short overlapping sequences were observed between viral derived and host derived fragments in viral-cellular junctions, indicating that integration was mediated by micro homology-mediated DNA repair pathway. Overall, our study suggests a model in which HPV16 might contribute to oncogenesis not only by disrupting tumor suppressor genes, but also by inducing chromosome instability.

The disruptive orthopaedic surgeon: implications for patient safety and malpractice liability.

PubMed

Patel, Pranay; Robinson, Brooke S; Novicoff, Wendy M; Dunnington, Gary L; Brenner, Michael J; Saleh, Khaled J

2011-11-02

Disruptive physician behavior imperils patient safety, erodes the morale of other health care providers, and dramatically increases the risk of malpractice litigation. Increasing patient volume, decreasing physician reimbursement, malpractice litigation, elevated stress, and growing job dissatisfaction have been implicated in disruptive behavior, which has emerged as one of the major challenges in health care. Because the aging patient population relies increasingly on orthopaedic services to maintain quality of life, improving professionalism and eradicating disruptive behavior are urgent concerns in orthopaedic surgery. Although many steps have been taken by The Joint Commission to improve patient care and define disruptive behavior, there is further room for improvement by physicians. Barriers to eliminating disruptive behavior by orthopaedic surgeons include fear of retaliation, lack of awareness among the surgeon's peers, and financial factors. Surgeons have a duty to address patterns of negative peer behavior for the benefit of patient care. This manuscript addresses the causes and consequences of disruptive physician behavior as well as management strategies, especially in orthopaedic surgery.

Statistical simulation of the magnetorotational dynamo.

PubMed

Squire, J; Bhattacharjee, A

2015-02-27

Turbulence and dynamo induced by the magnetorotational instability (MRI) are analyzed using quasilinear statistical simulation methods. It is found that homogenous turbulence is unstable to a large-scale dynamo instability, which saturates to an inhomogenous equilibrium with a strong dependence on the magnetic Prandtl number (Pm). Despite its enormously reduced nonlinearity, the dependence of the angular momentum transport on Pm in the quasilinear model is qualitatively similar to that of nonlinear MRI turbulence. This demonstrates the importance of the large-scale dynamo and suggests how dramatically simplified models may be used to gain insight into the astrophysically relevant regimes of very low or high Pm.

Changing Families, Changing Workplaces

ERIC Educational Resources Information Center

Bianchi, Suzanne M.

2011-01-01

American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income…

Name Changes in Medically Important Fungi and Their Implications for Clinical Practice

PubMed Central

de Hoog, G. Sybren; Chaturvedi, Vishnu; Denning, David W.; Dyer, Paul S.; Frisvad, Jens Christian; Geiser, David; Gräser, Yvonne; Guarro, Josep; Haase, Gerhard; Kwon-Chung, Kyung-Joo; Meyer, Wieland; Pitt, John I.; Samson, Robert A.; Tintelnot, Kathrin; Vitale, Roxana G.; Walsh, Thomas J.

2014-01-01

Recent changes in the Fungal Code of Nomenclature and developments in molecular phylogeny are about to lead to dramatic changes in the naming of medically important molds and yeasts. In this article, we present a widely supported and simple proposal to prevent unnecessary nomenclatural instability. PMID:25297326

Bequeathing Family Continuity.

ERIC Educational Resources Information Center

Spanier, Graham B.

1989-01-01

Notes that many children who experience abuse, family disruption, or poverty reach adulthood with a strong commitment to family life. Questions whether changes in American families are indicators of pathology, deterioration, and instability; and asks how dysfunctional families transmit commitment to the concept of family to succeeding generations.…

Risk management consideration in the bioeconomy

Treesearch

Camilla Abbati de Assis; Ronalds Gonzalez; Stephen Kelley; Hasan Jameel; Ted Bilek; Jesse Daystar; Robert Handfield; Jay Golden; Jeff Prestemon; Damien Singh

2017-01-01

In investing in a new venture, companies aim to increase their competitiveness and generate value in scenarios where volatile markets, geopolitical instabilities, and disruptive technologies create uncertainty and risk. The biobased industry poses additional challenges as it competes in a mature, highly efficient market, dominated by...

Beam-beam interaction study of medium energy eRHIC

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

Hao,Y.; Litvinenko, V. N.; Ptitsyn, V.

Medium Energy eRHIC (MeRHIC), the first stage design of eRHIC, includes a multi-pass ERL that provides 4GeV high quality electron beam to collide with the ion beam of RHIC. It delivers a minimum luminosity of 10{sup 32} cm{sup -2}s{sup -1}. Beam-beam effects present one of major factors limiting the luminosity of colliders. In this paper, both beam-beam effects on the electron beam and the proton beam in MeRHIC are investigated. The beam-beam interaction can induce a head-tail type instability of the proton beam referred to as the kink instability. Thus, beam stability conditions should be established to avoid proton beammore » loss. Also, the electron beam transverse disruption by collisions has to be evaluated to ensure that the beam quality is good enough for the energy recovery pass. The relation of proton beam stability, electron disruption and consequential luminosity are carried out after thorough discussion.« less

Simulations of Low-q Disruptions in the Compact Toroidal Hybrid Experiment

NASA Astrophysics Data System (ADS)

Howell, E. C.; Hanson, J. D.; Ennis, D. A.; Hartwell, G. J.; Maurer, D. A.

2017-10-01

Resistive MHD simulations of low-q disruptions in the Compact Toroidal Hybrid Device (CTH) are performed using the NIMROD code. CTH is a current-carrying stellarator used to study the effects of 3D shaping on MHD stability. Experimentally, it is observed that the application of 3D vacuum fields allows CTH to operate with edge safety factor less than 2.0. However, these low-q discharges often disrupt after peak current if the applied 3D fields are too weak. Nonlinear simulations are initialized using model VMEC equilibria representative of low-q discharges with weak vacuum transform. Initially a series of symmetry preserving island chains are excited at the q=6/5, 7/5, 8/5, and 9/5 rational surfaces. These island chains act as transport barriers preventing stochastic magnetic fields in the edge from penetrating into the core. As the simulation progresses, predominately m/n=3/2 and 4/3 instabilities are destabilized. As these instabilities grow to large amplitude they destroy the symmetry preserving islands leading to large regions of stochastic fields. A current spike and loss of core thermal confinement occurs when the innermost island chain (6/5) is destroyed. Work Supported by US-DOE Grant #DE-FG02-03ER54692.

Effect of von Karman Vortex Shedding on Regular and Open-slit V-gutter Stabilized Turbulent Premixed Flames

DTIC Science & Technology

2012-04-01

Both flame lengths shrink and large scale disruptions occur downstream with vortex shedding carrying reaction zones. Flames in both flameholders...9) the flame structure changes dramatically for both regular and open-slit V-gutter. Both flame lengths shrink and large scale disruptions occur...reduces the flame length . However, qualitatively the open-slit V-gutter appears to be more sensitive than the regular V-gutter. Both flames remain

Thermoelectrokinetic instability in micro/nanoscales

NASA Astrophysics Data System (ADS)

Ganchenko, Georgy; Ganchenko, Natalia

2016-11-01

A novel sophisticated type of electro-hydrodynamic instability in an electrolyte solution near ion-selective surfaces in an external electric field is discovered theoretically. The key mechanism of the instability is caused by Joule heating but dramatically differs from the well-known Raleigh-Benard convection. The investigation is based on the Nernst-Planck-Poisson-Navier-Stokes system along with the energy equation and corresponding BCs. The 1D quiescent steady state in microscales can be unstable with respect to either short-wave Rubinstein-Zaltzman or long-wave thermoelectokinenetic instability. The last one prevails in long microchannels and good enough thermal insulation of the system. In addition to the linear stability analysis a direct numerical simulation of the full 3D nonlinear system is fulfilled using a parallel computing. In the final coherent structures salt concentration, temperature and electric current are localized in narrow long fingers normal to the ion-selective surface while space charge forms crown-like micro-patterns. The investigation results can be useful in desalination problem.

Sleep architecture in insomniacs with severe benzodiazepine abuse.

PubMed

Manconi, Mauro; Ferri, Raffaele; Miano, Silvia; Maestri, Michelangelo; Bottasini, Valentina; Zucconi, Marco; Ferini-Strambi, Luigi

2017-06-01

Benzodiazepines (BZDs) are the most commonly prescribed compounds in insomnia. A long-term of BZDs use may cause dependence and abuse. The aim of this study was to evaluate sleep architecture and microstructure (in terms of cyclic alternating pattern - CAP - analysis and of sleep EEG power spectral analysis) in a group of long-term users of high doses of BZDs for their primary chronic insomnia. Twenty patients consecutively admitted at the Sleep Centre for drug discontinuation and 13 matched healthy controls underwent a full nocturnal video-polysomnographic recording, after one adaptation night. Significant differences were found in time in bed, REM sleep latency and sleep stage 1% which were increased in patients compared to controls, while CAP rate was dramatically decreased. During NREM sleep, patients showed a clear decrease in the relative power of delta band. Our data demonstrate that in adults with chronic insomnia, long-term use of high doses of BZDs induces a severe disruption of sleep microstructure, while sleep architecture seems to be much less affected. The long term use of high doses of BZDs for chronic insomnia induces a marked depression of slow wave activity and of its physiological instability. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Simulation, Theory, and Observations of the Spectrum of the Rayleigh-Taylor Instability due to Laser Imprint of Planar Targets

NASA Astrophysics Data System (ADS)

Keskinen, M. J.; Karasik, Max; Bates, J. W.; Schmitt, A. J.

2006-10-01

A limitation on the efficiency of high gain direct drive inertial confinement fusion is the extent of pellet disruption caused by the Rayleigh-Taylor (RT) instability. The RT instability can be seeded by pellet surface irregularities and/or laser imprint nonuniformities. It is important to characterize the evolution of the RT instability, e.g., the k-spectrum of areal mass. In this paper we study the time-dependent evolution of the spectrum of the Rayleigh-Taylor instability due to laser imprint in planar targets. This is achieved using the NRL FAST hydrodynamic simulation code together with analytical models. It is found that the optically smoothed laser imprint-driven RT spectrum develops into an inverse power law in k-space after several linear growth times. FAST simulation code results are compared with recent NRL Nike KrF laser experimental data. An analytical model, which is a function of Froude and Atwood numbers, is derived for the RT spectrum and favorably compared with both FAST simulation and Nike observations.

Instability in Parent-Child Coresidence and Adolescent Development in Urban South Africa.

PubMed

Marteleto, Letícia J; Cavanagh, Shannon; Prickett, Kate; Clark, Shelley

2016-03-01

There is widespread recognition of the importance of family stability for child development. South Africa presents an interesting context in which to study the consequences of family instability because of the traditionally fluid nature of household composition due to labor migration, child fostering, and non-marital fertility. More recently, the HIV pandemic has added another source of instability. Within South Africa, however, patterns of instability differ markedly across racial groups. We use the Cape Area Panel Study (CAPS) data to examine the implications of changes in parent-child coresidence for educational and sexual development of young South Africans. We show that changes in maternal and paternal coresidence have implications for the timing of sexual initiation for both black and coloured adolescents. Maternal and paternal transitions also lead to poorer educational outcomes for coloured adolescents, but parental disruptions are not significantly related to educational outcomes for blacks. These findings suggest that the implications of coresidential instability vary by race, reflecting racial differences with respect to cultural, social, and economic conditions. © 2016 The Population Council, Inc.

Simulations of Instabilities in Tidal Tails

NASA Astrophysics Data System (ADS)

Comparetta, Justin N.; Quillen, A. C.

2010-05-01

We use graphics cards to run a hybrid test particle/N-body simulation to integrate 4 million massless particle trajectories within fully self-consistent N-body simulations of 128,000 - 256,000 particles. The number of massless particles allows us to resolve fine structure in the spatial distribution and phase space of a dwarf galaxy that is disrupted in the tidal field of a Milky Way type galaxy. The tidal tails exhibit clumping or a smoke-like appearance. By running simulations with different satellite particle mass, number of massive vs massless particles and with and without a galaxy disk, we have determined that the instabilities are not due to numerical noise or shocking as the satellite passes through the disk of the Galaxy. The instability is possibly a result of self-gravity which indicates it may be due to Jeans instabilities. Simulations involving different halo particle mass may suggest limitations on dark matter halo substructure. We find that the instabilities are visible in velocity space as well as real space and thus could be identified from velocity surveys as well as number counts.

Fanconi anemia and the cell cycle: new perspectives on aneuploidy

PubMed Central

2014-01-01

Fanconi anemia (FA) is a complex heterogenic disorder of genomic instability, bone marrow failure, cancer predisposition, and congenital malformations. The FA signaling network orchestrates the DNA damage recognition and repair in interphase as well as proper execution of mitosis. Loss of FA signaling causes chromosome instability by weakening the spindle assembly checkpoint, disrupting centrosome maintenance, disturbing resolution of ultrafine anaphase bridges, and dysregulating cytokinesis. Thus, the FA genes function as guardians of genome stability throughout the cell cycle. This review discusses recent advances in diagnosis and clinical management of Fanconi anemia and presents the new insights into the origins of genomic instability in FA. These new discoveries may facilitate the development of rational therapeutic strategies for FA and for FA-deficient malignancies in the general population. PMID:24765528

Destabilization of glacial climate by the radiative impact of Atlantic Meridional Overturning Circulation disruptions

NASA Astrophysics Data System (ADS)

Galbraith, Eric D.; Merlis, Timothy M.; Palter, Jaime B.

2016-08-01

During each of the dramatic global warmings that ended the Pleistocene ice ages, the Atlantic Meridional Overturning Circulation (AMOC) was disrupted. It is not clear whether this was a contributing cause or simply an effect of deglaciation. Here we show that in an ensemble of simulations with a global climate model, AMOC disruption causes a consistent and sustained positive radiative imbalance of 0.4 W m-2. The imbalance is accommodated by heat accumulation in the ocean interior, representing an overall planetary warming, subsequently released by deep convection in the North Atlantic when the AMOC resumes. The results suggest a means by which AMOC disruptions could have helped to tip the planet out of stable glaciated states. However, the fact that AMOC disruptions occurred during prior Heinrich Stadials without causing deglaciation shows that other factors, such as ice sheet dynamics, or controls on CO2, were also key for deglaciation.

Modeling, measuring, and mitigating instability growth in liner implosions on Z

NASA Astrophysics Data System (ADS)

Peterson, Kyle

2015-11-01

Electro-thermal instabilities result from non-uniform heating due to temperature dependence in the conductivity of a material. In this talk, we will discuss the role of electro-thermal instabilities on the dynamics of magnetically accelerated implosion systems. We present simulations that show electro-thermal instabilities form immediately after the surface material of a conductor melts and can act as a significant seed to subsequent magneto-Rayleigh-Taylor (MRT) instability growth. We discuss measurement results from experiments performed on Sandia National Laboratories Z accelerator to investigate signatures of electro-thermal instability growth on well-characterized initially solid aluminum or beryllium rods driven with a 20 MA, 100 ns risetime current pulse. These measurements show good agreement with electro-thermal instability simulations and exhibit larger instability growth than can be explained by MRT theory alone. Recent experiments have confirmed simulation predictions of dramatically reduced instability growth in solid metallic rods when thick dielectric coatings are used to mitigate density perturbations arising from the electro-thermal instability. These results provide further evidence that the inherent surface roughness of the target is not the dominant seed for the MRT instability, in contrast with most inertial confinement fusion approaches. These results suggest a new technique for substantially reducing the integral MRT growth in magnetically driven implosions. Indeed, recent results on the Z facility with 100 km/s Al and Be liner implosions show substantially reduced growth. These new results include axially magnetized, CH-coated beryllium liner radiographs in which the inner liner surface is observed to be remarkably straight and uniform at a radius of about 120 microns (convergence ratio ~20). Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy under contract DE-AC04-94AL85000.

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

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

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

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

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.

Costal cartilage fractures and disruptions in a rugby football player.

PubMed

Lopez, Victor; Ma, Richard; Li, Xinning; Steele, John; Allen, Answorth A

2013-05-01

Costal cartilage fracture of the rib cage, or costochondral, is a rare sporting injury. For contact athletes, the instability of the rib cage may lead to potential serious complications, similar to rib fractures or thorax disruption. Most authors recommend initial conservative treatment with surgery reserved for only recalcitrant cases. We report a case of an amateur American male rugby football player who sustained a costal cartilage fracture and disruption involving the anterior left fifth and sixth rib costal cartilages. The case highlights the difficulty in establishing the diagnosis based on clinical examination and standard radiographs alone. Computed tomography was used to assist in diagnosing this destabilizing injury to the rib cage. Costal cartilage fractures and disruptions in athletes are rarely reported in the literature and can have serious implications for the athlete's ability to return to play if the rib cage is destabilized.

THE INSTABILITY OF ESTROGENIC CHEMICALS DURING LABORATORY STATIC EXPOSURE CONDITIONS WITH MALE FATHEAD MINNOWS

EPA Science Inventory

Endocrine disrupting chemicals (EDCs) such as Para-nonylphenol (NP), estradiol (E2), estrone (E1), estriol (E3) and ethynylestradiol (EE2) are shown to be ubiquitous in surface waters, sediments and sludge. These EDCs are known to induce vitellogenin gene (Vg) expression in male...

Nigeria Country Analysis Brief

EIA Publications

2016-01-01

Nigeria is currently the largest oil producer in Africa and was the world's fourth-largest exporter of LNG in 2015. Nigeria's oil production is hampered by instability and supply disruptions, while its natural gas sector is restricted by the lack of infrastructure to commercialize natural gas that is currently flared (burned off).

A current disruption mechanism in the neutral sheet for triggering substorm expansions

NASA Technical Reports Server (NTRS)

Lui, A. T. Y.; Mankofsky, A.; Chang, C.-L.; Papadopoulos, K.; Wu, C. S.

1989-01-01

Two main areas were addressed in support of an effort to understand mechanism responsible for the broadband electrostatic noise (BEN) observed in the magnetotail. The first area concerns the generation of BEN in the boundary layer region of the magnetotail whereas the second area concerns the occassional presence of BEN in the neutral sheet region. For the generation of BEN in the boundary layer region, a hybrid simulation code was developed to perform reliable longtime, quiet, highly resolved simulations of field aligned electron and ion beam flow. The result of the simulation shows that broadband emissions cannot be generated by beam-plasma instability if realistic values of the ion beam parameters are used. The waves generated from beam-plasma instability are highly discrete and are of high frequencies. For the plasma sheet boundary layer condition, the wave frequencies are in the kHz range, which is incompatible with the observation that the peak power in BEN occur in the 10's of Hz range. It was found that the BEN characteristics are more consistent with lower hybrid drift instability. For the occasional presence of BEN in the neutral sheet region, a linear analysis of the kinetic cross-field streaming instability appropriate to the neutral sheet condition just prior to onset of substorm expansion was performed. By solving numerically the dispersion relation, it was found that the instability has a growth time comparable to the onset time scale of substorm onset. The excited waves have a mixed polarization in the lower hybrid frequency range. The imposed drift driving the instability corresponds to unmagnetized ions undergoing current sheet acceleration in the presence of a cross-tail electric field. The required electric field strength is in the 10 mV/m range which is well within the observed electric field values detected in the neutral sheet during substorms. This finding can potentially account for the disruption of cross-tail current and its diversion to the ionosphere to form the substorm current wedge. Furthermore, a number of features associated with substorm expansion onset can be understood based on this substorm onset scenario.

REHABILITATION FOLLOWING MEDIAL PATELLOFEMORAL LIGAMENT RECONSTRUCTION FOR PATELLAR INSTABILITY

PubMed Central

Prohaska, Daniel

2017-01-01

Patellar instability is a common problem seen by physical therapists, athletic trainers and orthopedic surgeons. Although following an acute dislocation, conservative rehabilitation is usually the first line of defense; refractory cases exist that may require surgical intervention. Substantial progress has been made in the understanding of the medial patellofemoral ligament (MPFL) and its role as the primary stabilizer to lateral patellar displacement. Medial patellofemoral ligament disruption is now considered to be the essential lesion following acute patellar dislocation due to significantly high numbers of ruptures following this injury. Evidence is now mounting that demonstrates the benefits of early reconstruction with a variety of techniques. Recently rehabilitation has become more robust and progressive due to our better understanding of soft tissue reconstruction and repair techniques. The purpose of this manuscript is to describe the etiology of patellar instability, the anatomy and biomechanics and examination of patellofemoral instability, and to describe surgical intervention and rehabilitation following MPFL rupture. Level of Evidence 5 PMID:28593102

Arthroscopic and magnetic resonance image appearance and reconstruction of the anterior talofibular ligament in cases of apparent functional ankle instability.

PubMed

Takao, Masato; Innami, Ken; Matsushita, Takashi; Uchio, Yuji; Ochi, Mitsuo

2008-08-01

Many patients report feeling functional ankle instability, despite having no clinically demonstrable lateral instability. Some patients who experience functional instability of the ankle have substantial abnormalities of the anterior talofibular ligament despite having apparently normal lateral laxity in clinical examination. Case series; Level of evidence, 4. Fourteen patients who had functional ankle instability after sprain, despite having no clinically demonstrable lateral instability, were included in this study. All subjects underwent standard stress radiography, magnetic resonance imaging, and ankle arthroscopy. These patients were treated with anatomical reconstruction of the anterior talofibular ligament. Arthroscopic assessment revealed 3 cases with no ligamentous structure with scar tissue, 9 cases with partial ligament tears and scar tissue on the disrupted anterior talofibular ligament fiber, and 2 cases of abnormal course of the ligament at the fibular or talar attachment. Magnetic resonance imaging revealed the following: 5 cases of discontinuity of the anterior talofibular ligament, 2 cases of narrowing of the anterior talofibular ligament, 4 cases of high-intensity lesion in the anterior talofibular ligament, and 3 normal cases. The mean American Orthopaedic Foot and Ankle Society Ankle Hindfoot scale score was 66.2 +/- 3.2 points at preoperation and 92.3 +/- 4.4 points 2 years after surgery. All patients in this study with functional ankle instability, despite their having no demonstrable abnormal lateral laxity, had morphologic ligamentous abnormality on arthroscopic assessment.

Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome.

PubMed

McIntyre, Rebecca E; Lakshminarasimhan Chavali, Pavithra; Ismail, Ozama; Carragher, Damian M; Sanchez-Andrade, Gabriela; Forment, Josep V; Fu, Beiyuan; Del Castillo Velasco-Herrera, Martin; Edwards, Andrew; van der Weyden, Louise; Yang, Fengtang; Ramirez-Solis, Ramiro; Estabel, Jeanne; Gallagher, Ferdia A; Logan, Darren W; Arends, Mark J; Tsang, Stephen H; Mahajan, Vinit B; Scudamore, Cheryl L; White, Jacqueline K; Jackson, Stephen P; Gergely, Fanni; Adams, David J

2012-01-01

Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpj(tm/tm)) that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpj(tm/tm) embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpj(tm/tm) embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome.

Disruption of Mouse Cenpj, a Regulator of Centriole Biogenesis, Phenocopies Seckel Syndrome

PubMed Central

McIntyre, Rebecca E.; Lakshminarasimhan Chavali, Pavithra; Forment, Josep V.; Fu, Beiyuan; Del Castillo Velasco-Herrera, Martin; Edwards, Andrew; van der Weyden, Louise; Yang, Fengtang; Ramirez-Solis, Ramiro; Estabel, Jeanne; Gallagher, Ferdia A.; Logan, Darren W.; Arends, Mark J.; Tsang, Stephen H.; Mahajan, Vinit B.; Scudamore, Cheryl L.; White, Jacqueline K.; Jackson, Stephen P.; Gergely, Fanni; Adams, David J.

2012-01-01

Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpjtm/tm) that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpjtm/tm embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpjtm/tm embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome. PMID:23166506

Simulations of vertical disruptions with VDE code: Hiro and Evans currents

NASA Astrophysics Data System (ADS)

Li, Xujing; Di Hu Team; Leonid Zakharov Team; Galkin Team

2014-10-01

The recently created numerical code VDE for simulations of vertical instability in tokamaks is presented. The numerical scheme uses the Tokamak MHD model, where the plasma inertia is replaced by the friction force, and an adaptive grid numerical scheme. The code reproduces well the surface currents generated at the plasma boundary by the instability. Five regimes of the vertical instability are presented: (1) Vertical instability in a given plasma shaping field without a wall; (2) The same with a wall and magnetic flux ΔΨ|plX< ΔΨ|Xwall(where X corresponds to the X-point of a separatrix); (3) The same with a wall and magnetic flux ΔΨ|plX> ΔΨ|Xwall; (4) Vertical instability without a wall with a tile surface at the plasma path; (5) The same in the presence of a wall and a tile surface. The generation of negative Hiro currents along the tile surface, predicted earlier by the theory and measured on EAST in 2012, is well-reproduced by simulations. In addition, the instability generates the force-free Evans currents at the free plasma surface. The new pattern of reconnection of the plasma with the vacuum magnetic field is discovered. This work is supported by US DoE Contract No. DE-AC02-09-CH11466.

Instability growth for magnetized liner inertial fusion seeded by electro-thermal, electro-choric, and material strength effects

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

Pecover, J. D.; Chittenden, J. P.

A critical limitation of magnetically imploded systems such as magnetized liner inertial fusion (MagLIF) [Slutz et al., Phys. Plasmas 17, 056303 (2010)] is the magneto-Rayleigh-Taylor (MRT) instability which primarily disrupts the outer surface of the liner. MagLIF-relevant experiments have showed large amplitude multi-mode MRT instability growth growing from surface roughness [McBride et al., Phys. Rev. Lett. 109, 135004 (2012)], which is only reproduced by 3D simulations using our MHD code Gorgon when an artificially azimuthally correlated initialisation is added. We have shown that the missing azimuthal correlation could be provided by a combination of the electro-thermal instability (ETI) and anmore » “electro-choric” instability (ECI); describing, respectively, the tendency of current to correlate azimuthally early in time due to temperature dependent Ohmic heating; and an amplification of the ETI driven by density dependent resistivity around vapourisation. We developed and implemented a material strength model in Gorgon to improve simulation of the solid phase of liner implosions which, when applied to simulations exhibiting the ETI and ECI, gave a significant increase in wavelength and amplitude. Full circumference simulations of the MRT instability provided a significant improvement on previous randomly initialised results and approached agreement with experiment.« less

The Case for Neo-Keynesianism: In Defence of the Welfare State

ERIC Educational Resources Information Center

Van Heertum, Richard

2013-01-01

Neoliberalism is the dominant economic paradigm in the globe today. It has led to stagnant wages, high unemployment, increased income inequality and a decline in quality of life for the average citizen in the industrialised world over the past 30?years. It has also fomented a dramatic increase in economic instability, culminating in the 2007…

The social consequences of teenage parenthood.

PubMed

Furstenberg, F F

1976-01-01

The adolescent mothers consistently experienced great difficulty in realizing their life plans, when compared with their classmates who did not become pregnant premaritally in their early teens. Marital instability, school disruption, economic problems, and difficulty in family size regulation and child-rearing were some of the complications brought on by their premature, unscheduled childbearing.

Functional Analytic Psychotherapy (FAP) for Cluster B Personality Disorders: Creating Meaning, Mattering, and Skills

ERIC Educational Resources Information Center

Pankey, Julieann

2012-01-01

There are ten identified personality disorders, broken into three clusters: A, B, and C. Individuals with a cluster B diagnosis may demonstrate marked displays of emotional instability, erratic and disruptive patterns around interpersonal relationships, a myopic and restricted range of affect, a pronounced lack of empathy and insight, barriers…

Children’s experiences of family disruption in Sweden: Differentials by parent education over three decades

PubMed Central

Kennedy, Sheela; Thomson, Elizabeth

2010-01-01

This paper examines the living arrangements of Swedish children from 1970 through 1999 using the Level of Living Survey. Sweden, with low levels of economic inequality and a generous welfare state, provides an important context for studying socioeconomic differentials in family structure. We find that, although differences by parent education in non-marital childbearing are substantial and persistent, cohabiting childbearing is common even among highly educated Swedish parents. Educational differences in family instability were small during the 1970s, but increased over time as a result of rising union disruption among less-educated parents (secondary graduates or less). Children in more advantaged families experienced substantially less change in family structure and instability over the study period. Although cohabiting parents were more likely to separate than parents married at the child’s birth, differences were greater for the less-educated. Data limitations precluded investigating these differences across time. We conclude that educational differences in children’s living arrangements in Sweden have grown, but remain small in international comparisons. PMID:21113397

Induction of Chromosome Instability by Activation of Yes-Associated Protein and Forkhead Box M1 in Liver Cancer.

PubMed

Weiler, Sofia M E; Pinna, Federico; Wolf, Thomas; Lutz, Teresa; Geldiyev, Aman; Sticht, Carsten; Knaub, Maria; Thomann, Stefan; Bissinger, Michaela; Wan, Shan; Rössler, Stephanie; Becker, Diana; Gretz, Norbert; Lang, Hauke; Bergmann, Frank; Ustiyan, Vladimir; Kalin, Tatiana V; Singer, Stephan; Lee, Ju-Seog; Marquardt, Jens U; Schirmacher, Peter; Kalinichenko, Vladimir V; Breuhahn, Kai

2017-06-01

Many different types of cancer cells have chromosome instability. The hippo pathway leads to phosphorylation of the transcriptional activator yes-associated protein 1 (YAP1, YAP), which regulates proliferation and has been associated with the development of liver cancer. We investigated the effects of hippo signaling via YAP on chromosome stability and hepatocarcinogenesis in humans and mice. We analyzed transcriptome data from 242 patients with hepatocellular carcinoma (HCC) to search for gene signatures associated with chromosomal instability (CIN); we investigated associations with overall survival time and cancer recurrence using Kaplan-Meier curves. We analyzed changes in expression of these signature genes, at mRNA and protein levels, after small interfering RNA-mediated silencing of YAP in Sk-Hep1, SNU182, HepG2, or pancreatic cancer cells, as well as incubation with thiostrepton (an inhibitor of forkhead box M1 [FOXM1]) or verteporfin (inhibitor of the interaction between YAP and TEA domain transcription factor 4 [TEAD4]). We performed co-immunoprecipitation and chromatin immunoprecipitation experiments. We collected liver tissues from mice that express a constitutively active form of YAP (YAP S127A ) and analyzed gene expression signatures and histomorphologic parameters associated with chromosomal instability. Mice were given injections of thiostrepton and livers were collected and analyzed by immunoblotting, immunohistochemistry, histology, and real-time polymerase chain reaction. We performed immunohistochemical analyses on tissue microarrays of 105 HCCs and 7 nontumor liver tissues. Gene expression patterns associated with chromosome instability, called CIN25 and CIN70, were detected in HCCs from patients with shorter survival time or early cancer recurrence. TEAD4 and YAP were required for CIN25 and CIN70 signature expression via induction and binding of FOXM1. Disrupting the interaction between YAP and TEAD4 with verteporfin, or inhibiting FOXM1 with thiostrepton, reduced the chromosome instability gene expression patterns. Hyperplastic livers and tumors from YAP S127A mice had increased CIN25 and CIN70 gene expression patterns, aneuploidy, and defects in mitosis. Injection of YAP S127A mice with thiostrepton reduced liver overgrowth and signs of chromosomal instability. In human HCC tissues, high levels of nuclear YAP correlated with increased chromosome instability gene expression patterns and aneuploidy. By analyzing cell lines, genetically modified mice, and HCC tissues, we found that YAP cooperates with FOXM1 to contribute to chromosome instability. Agents that disrupt this pathway might be developed as treatments for liver cancer. Transcriptome data are available in the Gene Expression Omnibus public database (accession numbers: GSE32597 and GSE73396). Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Reconfinement and loss of stability in jets from active galactic nuclei

NASA Astrophysics Data System (ADS)

Gourgouliatos, Konstantinos N.; Komissarov, Serguei S.

2018-02-01

Jets powered by active galactic nuclei appear impressively stable compared with their terrestrial and laboratory counterparts—they can be traced from their origin to distances exceeding their injection radius by up to a billion times1,2. However, some less energetic jets get disrupted and lose their coherence on the scale of their host galaxy1,3. Quite remarkably, on the same scale, these jets are expected to become confined by the thermal pressure of the intra-galactic gas2. Motivated by these observations, we have started a systematic study of active galactic nuclei jets undergoing reconfinement via computer simulations. Here, we show that in the case of unmagnetized relativistic jets, the reconfinement is accompanied by the development of an instability and transition to a turbulent state. During their initial growth, the perturbations have a highly organized streamwise-oriented structure, indicating that it is not the Kelvin-Helmholtz instability, the instability which has been the main focus of the jet stability studies so far4,5. Instead, it is closely related to the centrifugal instability6. This instability is likely to be behind the division of active galactic nuclei jets into two morphological types in the Fanaroff-Riley classification7.

Explosion of comet Shoemaker-Levy 9 on entry into the Jovian atmosphere

NASA Technical Reports Server (NTRS)

Mac Low, Mordecai-Mark; Zahnle, Kevin

1994-01-01

We use the astrophysical hydrocode ZEUS to compute high-resolution models of the disruption and deceleration of cometary fragments striking Jupiter. We find that simple analytic and semianalytic models work well for kilometer-size impactors. We show that previous numerical models that placed the explosion much deeper in the atmosphere failed to fully resolve important gasdynamical instabilities. These instabilities tear the comet apart, greatly increase its effective cross section, and bring it to an abrupt halt. A 1 km diameter fragment loses over 90% of its kinetic energy within a single scale height at an atmospheric pressure of order 10 bars. For all practical purposes, it explodes.

Can Disks Produce Companions by Gravitational Fragmentation?

NASA Astrophysics Data System (ADS)

Durisen, Richard H.

The nonlinear outcome of gravitational instabilities in disks depends critically on the thermal physics of the gas. Under conditions where thermal energy is lost efficiently, disks disrupt into dense arms, arclets, and clumps. However, the evidence about whether clumps can ever become permanent bound objects is currently inconclusive. Under conditions where cooling is less efficient or where a balance between heating and cooling is achieved, the amplitudes reached by gravitational instabilities are relatively modest. The result is disk heating and transport of mass and angular momentum rather than condensation of bound companions. Future numerical simulations need to resolve the disk vertical structure and include more realistic equations of state and energy transport.

Mitigation of Hot Electrons from Laser-Plasma Instabilities in Laser-Generated X-Ray Sources

NASA Astrophysics Data System (ADS)

Fein, Jeffrey R.

This thesis describes experiments to understand and mitigate energetic or "hot" electrons from laser-plasma instabilities (LPIs) in an effort to improve radiographic techniques using laser-generated x-ray sources. Initial experiments on the OMEGA-60 laser show evidence of an underlying background generated by x-rays with energies over 10 keV on radiographs using backlit pinhole radiography, whose source is consistent with hard x-rays from LPI-generated hot electrons. Mitigating this background can dramatically reduce uncertainties in measured object densities from radiographs and may be achieved by eliminating the target components in which LPIs are most likely to grow. Experiments were performed on the OMEGA-EP laser to study hot electron production from laser-plasma instabilities in high-Z plasmas relevant to laser-generated x-ray sources. Measurements of hard x-rays show a dramatic reduction in hot-electron energy going from low-Z CH to high-Z Au targets, in a manner that is consistent with steepening electron density profiles that were also measured. The profile-steepening, we infer, increased thresholds of LPIs and contributed to the reduced hot-electron production at higher Z. Possible mechanisms for generating hot electrons include the two-plasmon decay and stimulated Raman scattering instabilities driven by multiple laser beams. Radiation hydrodynamic simulations using the CRASH code predict that both of these instabilities were above threshold with linear threshold parameters that decreased with increasing Z due to steepening length-scales, as well as enhanced laser absorption and increased collisional and Landau damping of electron plasma waves. Another set of experiments were performed on the OMEGA-60 laser to test whether hard x-ray background could be mitigated in backlit pinhole imagers by controlling laser-plasma instabilities. Based on the results above, we hypothesized that LPIs and hot electrons that lead to hard x-ray background would be reduced by increasing the atomic number of the irradiated components in the pinhole imagers. Using higher-Z materials we demonstrate significant reduction in x-rays between 30-70 keV and 70% increase in the signal-to-background ratio. Based on this, a proposed backlighter and detector setup predicts a signal-to-background ratio of up to 4.5:1.

I. Plants

Treesearch

Dean Pearson; Steve Sutherland; Jack Butler; Jane Smith; Carolyn Sieg

2011-01-01

Exotic plants dramatically impact natural communities and disrupt ecosystem services (Mack and others 2000). Although the bulk of current impacts are caused by relatively few exotic species, many additional exotics that are currently established at low levels are increasing in density and distribution and present substantial imminent threats. Additionally, new exotic...

Inertioelastic Flow Instability at a Stagnation Point

NASA Astrophysics Data System (ADS)

Burshtein, Noa; Zografos, Konstantinos; Shen, Amy Q.; Poole, Robert J.; Haward, Simon J.

2017-10-01

A number of important industrial applications exploit the ability of small quantities of high molecular weight polymer to suppress instabilities that arise in the equivalent flow of Newtonian fluids, a particular example being turbulent drag reduction. However, it can be extremely difficult to probe exactly how the polymer acts to, e.g., modify the streamwise near-wall eddies in a fully turbulent flow. Using a novel cross-slot flow configuration, we exploit a flow instability in order to create and study a single steady-state streamwise vortex. By quantitative experiment, we show how the addition of small quantities (parts per million) of a flexible polymer to a Newtonian solvent dramatically affects both the onset conditions for this instability and the subsequent growth of the axial vorticity. Complementary numerical simulations with a finitely extensible nonlinear elastic dumbbell model show that these modifications are due to the growth of polymeric stress within specific regions of the flow domain. Our data fill a significant gap in the literature between the previously reported purely inertial and purely elastic flow regimes and provide a link between the two by showing how the instability mode is transformed as the fluid elasticity is varied. Our results and novel methods are relevant to understanding the mechanisms underlying industrial uses of weakly elastic fluids and also to understanding inertioelastic instabilities in more confined flows through channels with intersections and stagnation points.

Endocrine Disrupting Chemicals and Disease Susceptibility

PubMed Central

Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

2011-01-01

Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

Endocrine disrupting chemicals and disease susceptibility.

PubMed

Schug, Thaddeus T; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J

2011-11-01

Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products--including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. Published by Elsevier Ltd.

Burning the Candle at Both Ends: Extramarital Sex as a Precursor of Marital Disruption.

PubMed

Demaris, Alfred

2013-11-01

This study examines several aspects of the association between engaging in extramarital sex and the disruption of one's marriage. In particular: is there a differential effect on disruption depending on the gender of the perpetrator? Is the effect of infidelity primarily due to its negative impact on marital quality and one's resistance to divorce? Are there characteristics of marriages that condition the effect of infidelity? Panel data on 1621 respondents followed from 1980 - 2000 in the Marital Instability Over the Life Course survey were utilized to answer these questions. Interval-censored Cox regression analysis revealed several noteworthy findings. Reports of problems due to extramarital involvement were strongly related to marital disruption, even holding constant the quality of the marriage. Although men were about three times more likely to be the cheating spouse, there was no difference in the effect of an affair on the marriage according to gender of the cheater. Approximately 40% of the effect of extramarital sex on disruption is accounted for by the mediating factors. Two moderators of infidelity's positive effect on disruption were found: the effect was substantially stronger for very religious couples, but weaker when the wife was in the labor force.

Comparison of runaway electron generation parameters in small, medium-sized and large tokamaks—A survey of experiments in COMPASS, TCV, ASDEX-Upgrade and JET

NASA Astrophysics Data System (ADS)

Plyusnin, V. V.; Reux, C.; Kiptily, V. G.; Pautasso, G.; Decker, J.; Papp, G.; Kallenbach, A.; Weinzettl, V.; Mlynar, J.; Coda, S.; Riccardo, V.; Lomas, P.; Jachmich, S.; Shevelev, A. E.; Alper, B.; Khilkevitch, E.; Martin, Y.; Dux, R.; Fuchs, C.; Duval, B.; Brix, M.; Tardini, G.; Maraschek, M.; Treutterer, W.; Giannone, L.; Mlynek, A.; Ficker, O.; Martin, P.; Gerasimov, S.; Potzel, S.; Paprok, R.; McCarthy, P. J.; Imrisek, M.; Boboc, A.; Lackner, K.; Fernandes, A.; Havlicek, J.; Giacomelli, L.; Vlainic, M.; Nocente, M.; Kruezi, U.; COMPASS Team; TCV Team; ASDEX-Upgrade Team; EUROFusion MST1 Team; contributors, JET

2018-01-01

This paper presents a survey of the experiments on runaway electrons (RE) carried out recently in frames of EUROFusion Consortium in different tokamaks: COMPASS, ASDEX-Upgrade, TCV and JET. Massive gas injection (MGI) has been used in different scenarios for RE generation in small and medium-sized tokamaks to elaborate the most efficient and reliable ones for future RE experiments. New data on RE generated at disruptions in COMPASS and ASDEX-Upgrade was collected and added to the JET database. Different accessible parameters of disruptions, such as current quench rate, conversion rate of plasma current into runaways, etc have been analysed for each tokamak and compared to JET data. It was shown, that tokamaks with larger geometrical sizes provide the wider limits for spatial and temporal variation of plasma parameters during disruptions, thus extending the parameter space for RE generation. The second part of experiments was dedicated to study of RE generation in stationary discharges in COMPASS, TCV and JET. Injection of Ne/Ar have been used to mock-up the JET MGI runaway suppression experiments. Secondary RE avalanching was identified and quantified for the first time in the TCV tokamak in RE generating discharges after massive Ne injection. Simulations of the primary RE generation and secondary avalanching dynamics in stationary discharges has demonstrated that RE current fraction created via avalanching could achieve up to 70-75% of the total plasma current in TCV. Relaxations which are reminiscent the phenomena associated to the kinetic instability driven by RE have been detected in RE discharges in TCV. Macroscopic parameters of RE dominating discharges in TCV before and after onset of the instability fit well to the empirical instability criterion, which was established in the early tokamaks and examined by results of recent numerical simulations.

AN MHD AVALANCHE IN A MULTI-THREADED CORONAL LOOP

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

Hood, A. W.; Cargill, P. J.; Tam, K. V.

For the first time, we demonstrate how an MHD avalanche might occur in a multithreaded coronal loop. Considering 23 non-potential magnetic threads within a loop, we use 3D MHD simulations to show that only one thread needs to be unstable in order to start an avalanche even when the others are below marginal stability. This has significant implications for coronal heating in that it provides for energy dissipation with a trigger mechanism. The instability of the unstable thread follows the evolution determined in many earlier investigations. However, once one stable thread is disrupted, it coalesces with a neighboring thread andmore » this process disrupts other nearby threads. Coalescence with these disrupted threads then occurs leading to the disruption of yet more threads as the avalanche develops. Magnetic energy is released in discrete bursts as the surrounding stable threads are disrupted. The volume integrated heating, as a function of time, shows short spikes suggesting that the temporal form of the heating is more like that of nanoflares than of constant heating.« less

Harmonic growth of spherical Rayleigh-Taylor instability in weakly nonlinear regime

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

Liu, Wanhai; LHD, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190; Chen, Yulian

Harmonic growth in classical Rayleigh-Taylor instability (RTI) on a spherical interface is analytically investigated using the method of the parameter expansion up to the third order. Our results show that the amplitudes of the first four harmonics will recover those in planar RTI as the interface radius tends to infinity compared against the initial perturbation wavelength. The initial radius dramatically influences the harmonic development. The appearance of the second-order feedback to the initial unperturbed interface (i.e., the zeroth harmonic) makes the interface move towards the spherical center. For these four harmonics, the smaller the initial radius is, the faster theymore » grow.« less

Dynamic excitations in membranes induced by optical tweezers.

PubMed Central

Bar-Ziv, R; Moses, E; Nelson, P

1998-01-01

We present the phenomenology of transformations in lipid bilayers that are excited by laser tweezers. A variety of dynamic instabilities and shape transformations are observed, including the pearling instability, expulsion of vesicles, and more exotic ones, such as the formation of passages. Our physical picture of the laser-membrane interaction is based on the generation of tension in the bilayer and loss of surface area. Although tension is the origin of the pearling instability, it does not suffice to explain expulsion of vesicles, where we observe opening of giant pores and creeping motion of bilayers. We present a quantitative theoretical framework to understand most of the observed phenomenology. The main hypothesis is that lipid is pulled into the optical trap by the familiar dielectric effect, is disrupted, and finally is repackaged into an optically unresolvable suspension of colloidal particles. This suspension, in turn, can produce osmotic pressure and depletion forces, driving the observed transformations. PMID:9649388

Itinerant density wave instabilities at classical and quantum critical points

DOE PAGES

Feng, Yejun; van Wezel, Jasper; Wang, Jiyang; ...

2015-07-27

Charge ordering in metals is a fundamental instability of the electron sea, occurring in a host of materials and often linked to other collective ground states such as superconductivity. What is difficult to parse, however, is whether the charge order originates among the itinerant electrons or whether it arises from the ionic lattice. Here in this study we employ high-resolution X-ray diffraction, combined with high-pressure and low-temperature techniques and theoretical modelling, to trace the evolution of the ordering wavevector Q in charge and spin density wave systems at the approach to both thermal and quantum phase transitions. The non-monotonic behaviourmore » of Q with pressure and the limiting sinusoidal form of the density wave point to the dominant role of the itinerant instability in the vicinity of the critical points, with little influence from the lattice. Fluctuations rather than disorder seem to disrupt coherence.« less

Magnetic field line reconnection experiments. V - Current disruptions and double layers

NASA Technical Reports Server (NTRS)

Stenzel, R. L.; Gekelman, W.; Wild, N.

1983-01-01

An investigation is conducted of the stability of a large laboratory plasma current sheet, which has been generated in the process of magnetic field line reconnection, with respect to local current increases. Magnetic flux variations in regions remote from the current sheet generate an inductive voltage in the current loop that drops off inside the plasma in the form of a potential double layer, leading to particle acceleration with velocities much larger than those expected from the steady state electric fields in the plasma. A model for the mechanism of the current disruptions is formulated in which the potential structure leads to ion expulsion, creating a localized density drop. The associated current drop in an inductive circuit drives the potential structure, providing feedback for the disruptive instability. Similarities to, and differences from, magnetospheric substorm phenomena are noted.

A current disruption mechanism in the neutral sheet - A possible trigger for substorm expansions

NASA Technical Reports Server (NTRS)

Lui, A. T. Y.; Mankofsky, A.; Chang, C.-L.; Papadopoulos, K.; Wu, C. S.

1990-01-01

A linear analysis is performed to investigate the kinetic cross-field streaming instability in the earth's magnetotail neutral sheet region. Numerical solution of the dispersion equation shows that the instability can occur under conditions expected for the neutral sheet just prior to the onset of substorm expansion. The excited waves are obliquely propagating whistlers with a mixed polarization in the lower hybrid frequency range. The ensuing turbulence of this instability can lead to a local reduction of the cross-tail current causing it to continue through the ionosphere to form a substorm current wedge. A substorm expansion onset scenario is proposed based on this instability in which the relative drift between ions and electrons is primarily due to unmagnetized ions undergoing current sheet acceleration in the presence of a cross-tail electric field. The required electric field strength is within the range of electric field values detected in the neutral sheet region during substorm intervals. The skew in local time of substorm onset location and the three conditions under which substorm onset is observed can be understood on the basis of the proposed scenario.

Geographies of Social Exclusion: Education Access in the Philippines

ERIC Educational Resources Information Center

Symaco, Lorraine Pe

2013-01-01

Despite the massive education sector of the country, the Philippines--being located in the Pacific Ring of Fire and the typhoon belt--is home to a number of natural instabilities that frequently disrupt the school calendar. Conflict areas in selected parts of the island of Mindanao and the remote geographic features of the country also pose…

Lymphatic Leak Complicating Central Venous Catheter Insertion

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

Barnacle, Alex M., E-mail: alexbarnacle@yahoo.co.uk; Kleidon, Tricia M.

2005-12-15

Many of the risks associated with central venous access are well recognized. We report a case of inadvertent lymphatic disruption during the insertion of a tunneled central venous catheter in a patient with raised left and right atrial pressures and severe pulmonary hypertension, which led to significant hemodynamic instability. To our knowledge, this rare complication is previously unreported.

Reactive Attachment Disorder: Implications for School Readiness and School Functioning

ERIC Educational Resources Information Center

Schwartz, Eric; Davis, Andrew S.

2006-01-01

School readiness and functioning in children diagnosed with Reactive Attachment Disorder (RAD) are important issues due to the dramatic impact RAD has on multiple areas of development. The negative impact of impaired or disrupted early relationships, characterized by extreme neglect, abuse, parental mental illness, domestic violence, and repeated…

Navigating Disruptive Innovation in Undergraduate Business Education

ERIC Educational Resources Information Center

Behara, Ravi S.; Davis, Mark M.

2015-01-01

The undergraduate business education landscape is dramatically changing and will continue to do so for the foreseeable future. Many of the changes are being driven by increasing costs, advances in technology, rapid globalization, and an increasingly diverse workforce and customer base, and are occurring simultaneously in both the business world…

Children of Divorce: Facilitating Well-Being.

ERIC Educational Resources Information Center

Hutchinson, Roger L.; Spangler, Sharon L.

Both the increased frequency of divorce and the resultant increase in single-parent households have experienced dramatic increases since World War II. In many instances, divorce is a major disruptive experience that imposes primary impact upon all family members. Characteristically, various levels of adjustment are required of family members amid…

Are pulsars spun up or down by SASI spiral modes?

NASA Astrophysics Data System (ADS)

Kazeroni, Rémi; Guilet, Jérôme; Foglizzo, Thierry

2017-10-01

Pulsars may either be spun up or down by hydrodynamic instabilities during the supernova explosion of massive stars. Besides rapidly rotating cases related to bipolar explosions, stellar rotation may affect the explosion of massive stars in the more common situations where the centrifugal force is minor. Using 2D simulations of a simplified set-up in cylindrical geometry, we examine the impact of rotation on the standing accretion shock instability (SASI) and the corotation instability, also known as low-T/|W|. The influence of rotation on the saturation amplitude of these instabilities depends on the specific angular momentum in the accretion flow and the ratio of the shock to the neutron star radii. The spiral mode of SASI becomes more vigorous with faster rotation only if this ratio is large enough. A corotation instability develops at large rotation rates and impacts the dynamics more dramatically, leading to a strong one-armed spiral wave. Non-axisymmetric instabilities are able to redistribute angular momentum radially and affect the pulsar spin at birth. A systematic study of the relationship between the core rotation period of the progenitor and the initial pulsar spin is performed. Stellar rotation rates for which pulsars are spun up or down by SASI are estimated. Rapidly spinning progenitors are modestly spun down by spiral modes, less than ˜30 per cent, when a corotation instability develops. Given the observational constraints on pulsar spin periods at birth, this suggests that rapid rotation might not play a significant hydrodynamic role in most core-collapse supernovae.

Papaloizou-Pringle instability suppression by the magnetorotational instability in relativistic accretion discs

NASA Astrophysics Data System (ADS)

Bugli, M.; Guilet, J.; Müller, E.; Del Zanna, L.; Bucciantini, N.; Montero, P. J.

2018-03-01

Geometrically thick tori with constant specific angular momentum have been widely used in the last decades to construct numerical models of accretion flows on to black holes. Such discs are prone to a global non-axisymmetric hydrodynamic instability, known as Papaloizou-Pringle instability (PPI), which can redistribute angular momentum and also lead to an emission of gravitational waves. It is, however, not clear yet how the development of the PPI is affected by the presence of a magnetic field and by the concurrent development of the magnetorotational instability (MRI). We present a numerical analysis using three-dimensional GRMHD simulations of the interplay between the PPI and the MRI considering, for the first time, an analytical magnetized equilibrium solution as initial condition. In the purely hydrodynamic case, the PPI selects as expected the large-scale m = 1 azimuthal mode as the fastest growing and non-linearly dominant mode. However, when the torus is threaded by a weak toroidal magnetic field, the development of the MRI leads to the suppression of large-scale modes and redistributes power across smaller scales. If the system starts with a significantly excited m = 1 mode, the PPI can be dominant in a transient phase, before being ultimately quenched by the MRI. Such dynamics may well be important in compact star mergers and tidal disruption events.

Possible Rapid Gas Giant Planet Formation in the Solar Nebula and Other Protoplanetary Disks.

PubMed

Boss

2000-06-20

Gas giant planets have been detected in orbit around an increasing number of nearby stars. Two theories have been advanced for the formation of such planets: core accretion and disk instability. Core accretion, the generally accepted mechanism, requires several million years or more to form a gas giant planet in a protoplanetary disk like the solar nebula. Disk instability, on the other hand, can form a gas giant protoplanet in a few hundred years. However, disk instability has previously been thought to be important only in relatively massive disks. New three-dimensional, "locally isothermal," hydrodynamical models without velocity damping show that a disk instability can form Jupiter-mass clumps, even in a disk with a mass (0.091 M middle dot in circle within 20 AU) low enough to be in the range inferred for the solar nebula. The clumps form with initially eccentric orbits, and their survival will depend on their ability to contract to higher densities before they can be tidally disrupted at successive periastrons. Because the disk mass in these models is comparable to that apparently required for the core accretion mechanism to operate, the models imply that disk instability could obviate the core accretion mechanism in the solar nebula and elsewhere.

Merging Black Holes

NASA Technical Reports Server (NTRS)

Centrella, Joan

2012-01-01

The final merger of two black holes is expected to be the strongest source of gravitational waves for both ground-based detectors such as LIGO and VIRGO, as well as future. space-based detectors. Since the merger takes place in the regime of strong dynamical gravity, computing the resulting gravitational waveforms requires solving the full Einstein equations of general relativity on a computer. For many years, numerical codes designed to simulate black hole mergers were plagued by a host of instabilities. However, recent breakthroughs have conquered these instabilities and opened up this field dramatically. This talk will focus on.the resulting 'gold rush' of new results that is revealing the dynamics and waveforms of binary black hole mergers, and their applications in gravitational wave detection, testing general relativity, and astrophysics

Merging Black Holes

NASA Technical Reports Server (NTRS)

Centrella, Joan

2010-01-01

The final merger of two black holes is expected to be the strongest source of gravitational waves for both ground-based detectors such as LIGO and VIRGO, as well as the space-based LISA. Since the merger takes place in the regime of strong dynamical gravity, computing the resulting gravitational waveforms requires solving the full Einstein equations of general relativity on a computer. For many years, numerical codes designed to simulate black hole mergers were plagued by a host of instabilities. However, recent breakthroughs have conquered these instabilities and opened up this field dramatically. This talk will focus on the resulting gold rush of new results that are revealing the dynamics and waveforms of binary black hole mergers, and their applications in gravitational wove detection, testing general relativity, and astrophysics.

Merging Black Holes

NASA Technical Reports Server (NTRS)

Centrella, Joan

2010-01-01

The final merger of two black holes is expected to be the strongest source of gravitational waves for both ground-based detectors such as LIGO and VIRGO, as well as the space-based LISA. Since the merger takes place in the regime of strong dynamical gravity, computing the resulting gravitational waveforms requires solving the full Einstein equations of general relativity on a computer. For many years, numerical codes designed to simulate black hole mergers were plagued by a host of instabilities. However, recent breakthroughs have conquered these instabilities and opened up this field dramatically. This talk will focus on the resulting gold rush of new results that are revealing the dynamics and waveforms of binary black hole mergers, and their applications in gravitational wave detection, testing general relativity, and astrophysics.

Evolution of inviscid Kelvin-Helmholtz instability from a piecewise linear shear layer

NASA Astrophysics Data System (ADS)

Guha, Anirban; Rahmani, Mona; Lawrence, Gregory

2012-11-01

Here we study the evolution of 2D, inviscid Kelvin-Helmholtz instability (KH) ensuing from a piecewise linear shear layer. Although KH pertaining to smooth shear layers (eg. Hyperbolic tangent profile) has been thorough investigated in the past, very little is known about KH resulting from sharp shear layers. Pozrikidis and Higdon (1985) have shown that piecewise shear layer evolves into elliptical vortex patches. This non-linear state is dramatically different from the well known spiral-billow structure of KH. In fact, there is a little acknowledgement that elliptical vortex patches can represent non-linear KH. In this work, we show how such patches evolve through the interaction of vorticity waves. Our work is based on two types of computational methods (i) Contour Dynamics: a boundary-element method which tracks the evolution of the contour of a vortex patch using Lagrangian marker points, and (ii) Direct Numerical Simulation (DNS): an Eulerian pseudo-spectral method heavily used in studying hydrodynamic instability and turbulence.

Burning the Candle at Both Ends: Extramarital Sex as a Precursor of Marital Disruption

PubMed Central

DeMaris, Alfred

2012-01-01

This study examines several aspects of the association between engaging in extramarital sex and the disruption of one’s marriage. In particular: is there a differential effect on disruption depending on the gender of the perpetrator? Is the effect of infidelity primarily due to its negative impact on marital quality and one’s resistance to divorce? Are there characteristics of marriages that condition the effect of infidelity? Panel data on 1621 respondents followed from 1980 – 2000 in the Marital Instability Over the Life Course survey were utilized to answer these questions. Interval-censored Cox regression analysis revealed several noteworthy findings. Reports of problems due to extramarital involvement were strongly related to marital disruption, even holding constant the quality of the marriage. Although men were about three times more likely to be the cheating spouse, there was no difference in the effect of an affair on the marriage according to gender of the cheater. Approximately 40% of the effect of extramarital sex on disruption is accounted for by the mediating factors. Two moderators of infidelity’s positive effect on disruption were found: the effect was substantially stronger for very religious couples, but weaker when the wife was in the labor force. PMID:24634559

Simulation study of disruption characteristics in KSTAR

NASA Astrophysics Data System (ADS)

Lee, Jongkyu; Kim, J. Y.; Kessel, C. E.; Poli, F.

2012-10-01

A detailed simulation study of disruption in KSTAR had been performed using the Tokamak Simulation Code(TSC) [1] during the initial design phase of KSTAR [2]. Recently, however, a partial modification in the structure of passive plate was made in relation to reduce eddy current and increase the efficiency of control of vertical position. A substantial change can then occur in disruption characteristics and plasma behavior during disruption due to changes in passive plate structure. Because of this, growth rate of vertical instability is expected to be increased and eddy current and its associated electomagnetic force are expected to be reduced. To check this in more detail, a new simulation study is here given with modified passive plate structure of KSTAR. In particular, modeling of vertical disruption that is vertical displacement event (VDE) was carried out. We calculated vertical growth rate for a drift phase of plasma and electromagnetic force acting on PFC structures and compared the results between in a new model and an old model. [4pt] [1] S.C. Jardin, N. Pomphrey and J. Delucia, J. Comp. Phys. 66, 481 (1986).[0pt] [2] J.Y. Kim, S.Y. Cho and KSTAR Team, Disruption load analysis on KSTAR PFC structures, J. Accel. Plasma Res. 5, 149 (2000).

Can Good Principals Keep Teachers in Disadvantaged Schools? Linking Principal Effectiveness to Teacher Satisfaction and Turnover in Hard-to-Staff Environments

ERIC Educational Resources Information Center

Grissom, Jason A.

2011-01-01

Background: High rates of teacher turnover likely mean greater school instability, disruption of curricular cohesiveness, and a continual need to hire inexperienced teachers, who typically are less effective, as replacements for teachers who leave. Unfortunately, research consistently finds that teachers who work in schools with large numbers of…

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

Bourham, Mohamed A.; Gilligan, John G.

Safety considerations in large future fusion reactors like ITER are important before licensing the reactor. Several scenarios are considered hazardous, which include safety of plasma-facing components during hard disruptions, high heat fluxes and thermal stresses during normal operation, accidental energy release, and aerosol formation and transport. Disruption events, in large tokamaks like ITER, are expected to produce local heat fluxes on plasma-facing components, which may exceed 100 GW/m{sup 2} over a period of about 0.1 ms. As a result, the surface temperature dramatically increases, which results in surface melting and vaporization, and produces thermal stresses and surface erosion. Plasma-facing componentsmore » safety issues extends to cover a wide range of possible scenarios, including disruption severity and the impact of plasma-facing components on disruption parameters, accidental energy release and short/long term LOCA's, and formation of airborne particles by convective current transport during a LOVA (water/air ingress disruption) accident scenario. Study, and evaluation of, disruption-induced aerosol generation and mobilization is essential to characterize database on particulate formation and distribution for large future fusion tokamak reactor like ITER. In order to provide database relevant to ITER, the SIRENS electrothermal plasma facility at NCSU has been modified to closely simulate heat fluxes expected in ITER.« less

Cortical–Subcortical Interactions in Hypersomnia Disorders: Mechanisms Underlying Cognitive and Behavioral Aspects of the Sleep–Wake Cycle

PubMed Central

Larson-Prior, Linda J.; Ju, Yo-El; Galvin, James E.

2014-01-01

Subcortical circuits mediating sleep–wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders (HDs) such as narcolepsy and Kleine–Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep–wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, HDs are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where electroencephalogram demonstrates abnormal function in cortical regions associated with cognitive fluctuations (CFs). Moreover, functional connectivity MRI shows instability of cortical networks in individuals with CFs. We propose that the inability to stabilize neural state due to disruptions in the sleep–wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders. PMID:25309500

The radiation asymmetry in MGI rapid shutdown on J-TEXT tokamak

NASA Astrophysics Data System (ADS)

Tong, Ruihai; Chen, Zhongyong; Huang, Duwei; Cheng, Zhifeng; Zhang, Xiaolong; Zhuang, Ge; J-TEXT Team

2017-10-01

Disruptions, the sudden termination of tokamak fusion plasmas by instabilities, have the potential to cause severe material wall damage to large tokamaks like ITER. The mitigation of disruption damage is an essential part of any fusion reactor system. Massive gas injection (MGI) rapid shutdown is a technique in which large amounts of noble gas are injected into the plasma in order to safely radiate the plasma energy evenly over the entire plasma-facing first wall. However, the radiated energy during the thermal quench (TQ) in massive gas injection (MGI) induced disruptions is found toroidal asymmetric, and the degrees of asymmetry correlate with the gas penetration and MGI induced magnetohydrodynamics (MHD) activities. A toroidal and poloidal array of ultraviolet photodiodes (AXUV) has been developed to investigate the radiation asymmetry on J-TEXT tokamak. Together with the upgraded mirnov probe arrays, the relation between MGI triggered MHD activities with radiation asymmetry is studied.

Characteristics of Low-q(a) Disruptions in the Compact Toroidal Hybrid

NASA Astrophysics Data System (ADS)

Pandya, M. D.; Archmiller, M. C.; Ennis, D. A.; Hartwell, G. J.; Maurer, D. A.

2014-10-01

Tokamak disruptions are dramatic events that lead to a sudden loss of plasma confinement. Disruptions that occur at low edge safety-factor, q (a) , limit the operation of tokamaks to q (a) >= 2 . The Compact Toroidal Hybrid (CTH) is a torsatron-tokamak hybrid with a helical field coil and vertical field coils to establish a stellartor equilibrium, while an ohmic coil induces plasma current. A feature of the CTH device is the ability to adjust the vacuum rotational transform, tvac (t =1/q ), by varying the ratio of current in the helical and toroidal field coils. The value of edge tvac can be varied from about 0.02 to 0.3 (qvac (a) ~ 50 to 3.3). Plasma discharges in CTH are routinely observed to operate with q (a) < 2 , and in some cases as low as q (a) ~ 1 . 1 . In CTH, low-q(a) disruptions are observed with a dominant m/n=3/2 precursor. The disruptivity of plasma discharges is over 80% when tvac (a) < 0 . 04 (qvac (a) < 25) and as tvac (a) is increased further, the disruptivity of the plasma discharges decreases. The disruptions are completely suppressed for tvac (a) > 0 . 07 (qvac (a) ~ 14) . This work is supported by US Department of Energy Grant No. DE-FG02-00ER54610.

Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

PubMed Central

De Coster, Sam; van Larebeke, Nicolas

2012-01-01

The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand. PMID:22991565

Disrupting Aviation: An Exploratory Study of the Opportunities and Risks of Tablet Computers in Commercial Flight Operations

ERIC Educational Resources Information Center

Boyne, Matthew

2013-01-01

Commercial flight operational safety has dramatically improved in the last 30 years because of enhanced crew coordination, communication, leadership and team development. Technology insertion into cockpit operations, however, has been shown to create crew distractions, resulting in flight safety risks, limited use given policy limitations and…

Disrupting the Master Narrative: Global Politics, Historical Memory, and the Implications for Naturalization Education

ERIC Educational Resources Information Center

Gordon, Daryl M.

2010-01-01

Dramatic increases in immigration pose challenges for democratic citizenship education to involve national members with different historical memories and current experiences of national belonging. The article draws on ethnographic research with Laotian refugees, who were the target of U.S. violence during the Vietnam War and later became…

The Impact of the Divorce Process on the Family.

ERIC Educational Resources Information Center

Rudolph, Linda B.

One of the most dramatic changes in the American culture in recent years is the emergence of a family unit experiencing stages of disruption and reorganization as a common pattern. The stereotypical middle-class, suburban family continues to exist, but other variations of families exist also, family units for which past guidelines and assumptions…

The Effects on Monopsony on Strategy and Leadership in Ontario Colleges. Professional File. Number 28

ERIC Educational Resources Information Center

Cooke, Michael

2008-01-01

The period 1995 to 2005 was one of significant turbulence for Ontario colleges, marked by increasing globalization, immigration, disruptions in the labour market, new technologies and dramatic reductions in government operating grants. This study examines how colleges and their leaders responded to those strategic challenges in their official…

Percutaneous cannulated screw fixation of sacral fractures and sacroiliac joint disruptions with CT-controlled guidewires performed by interventionalists: single center experience in treating posterior pelvic instability.

PubMed

Fischer, Sebastian; Vogl, Thomas J; Marzi, Ingo; Zangos, Stephan; Wichmann, Julian L; Scholtz, Jan-Erik; Mack, Martin G; Schmidt, Sven; Eichler, Katrin

2015-02-01

The purpose of our study was to evaluate minimally invasive sacroiliac screw fixation for treatment of posterior pelvic instability with the help of CT controlled guidewires, assess its accuracy, safety and effectiveness, and discuss potential pitfalls. 100 guidewires and hollow titan screws were inserted in 38 patients (49.6±19.5 years) suffering from 35 sacral fractures and/or 16 sacroiliac joint disruptions due to 33 (poly-)traumatic, 2 osteoporotic and 1 post-infectious conditions. The guidewire and screw positions were analyzed in multiplanar reconstructions. The mean minimal distance between guidewire and adjacent neural foramina was 4.5±2.01mm, with a distinctly higher precision in S1 than S2. Eight guidewires showed cortical contacts, resulting in a total of 2% mismatched screws with subsequent wall violation. The fracture gaps were reduced from 3.6±0.53mm to 1.2±0.54mm. During follow-up 3 cases of minor iatrogenic sacral impaction (<5mm) due to the bolting and 2 cases of screw loosening were observed. Interventional time was 84.0min with a mean of 2.63 screws per patient whilst acquiring a mean of 93.7 interventional CT-images (DLP 336.7mGycm). The treatment of posterior pelvic instability with a guidewire-based screw insertion technique under CT-imaging results in a very high accuracy and efficacy with a low complication rate. Careful attention should be drawn to radiation levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bcr/Abl interferes with the Fanconi anemia/BRCA pathway: implications in the chromosomal instability of chronic myeloid leukemia cells.

PubMed

Valeri, Antonio; Alonso-Ferrero, Maria Eugenia; Río, Paula; Pujol, María Roser; Casado, José A; Pérez, Laura; Jacome, Ariana; Agirre, Xabier; Calasanz, Maria José; Hanenberg, Helmut; Surrallés, Jordi; Prosper, Felipe; Albella, Beatriz; Bueren, Juan A

2010-12-28

Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. Although it is well known that CML cells are genetically unstable, the mechanisms accounting for this genomic instability are still poorly understood. Because the Fanconi anemia (FA) pathway is believed to control several mechanisms of DNA repair, we investigated whether this pathway was disrupted in CML cells. Our data show that CML cells have a defective capacity to generate FANCD2 nuclear foci, either in dividing cells or after DNA damage. Similarly, human cord blood CD34(+) cells transduced with BCR/ABL retroviral vectors showed impaired FANCD2 foci formation, whereas FANCD2 monoubiquitination in these cells was unaffected. Soon after the transduction of CD34(+) cells with BCR/ABL retroviral vectors a high proportion of cells with supernumerary centrosomes was observed. Similarly, BCR/ABL induced a high proportion of chromosomal abnormalities, while mediated a cell survival advantage after exposure to DNA cross-linking agents. Significantly, both the impaired formation of FANCD2 nuclear foci, and also the predisposition of BCR/ABL cells to develop centrosomal and chromosomal aberrations were reverted by the ectopic expression of BRCA1. Taken together, our data show for the first time a disruption of the FA/BRCA pathway in BCR/ABL cells, suggesting that this defective pathway should play an important role in the genomic instability of CML by the co-occurrence of centrosomal amplification and DNA repair deficiencies.

Fast Molecular Cloud Destruction Requires Fast Cloud Formation

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

Mac Low, Mordecai-Mark; Burkert, Andreas; Ibáñez-Mejía, Juan C., E-mail: mordecai@amnh.org, E-mail: burkert@usm.lmu.de, E-mail: ibanez@ph1.uni-koeln.de

A large fraction of the gas in the Galaxy is cold, dense, and molecular. If all this gas collapsed under the influence of gravity and formed stars in a local free-fall time, the star formation rate in the Galaxy would exceed that observed by more than an order of magnitude. Other star-forming galaxies behave similarly. Yet, observations and simulations both suggest that the molecular gas is indeed gravitationally collapsing, albeit hierarchically. Prompt stellar feedback offers a potential solution to the low observed star formation rate if it quickly disrupts star-forming clouds during gravitational collapse. However, this requires that molecular cloudsmore » must be short-lived objects, raising the question of how so much gas can be observed in the molecular phase. This can occur only if molecular clouds form as quickly as they are destroyed, maintaining a global equilibrium fraction of dense gas. We therefore examine cloud formation timescales. We first demonstrate that supernova and superbubble sweeping cannot produce dense gas at the rate required to match the cloud destruction rate. On the other hand, Toomre gravitational instability can reach the required production rate. We thus argue that, although dense, star-forming gas may last only around a single global free-fall time; the dense gas in star-forming galaxies can globally exist in a state of dynamic equilibrium between formation by gravitational instability and disruption by stellar feedback. At redshift z ≳ 2, the Toomre instability timescale decreases, resulting in a prediction of higher molecular gas fractions at early times, in agreement with the observations.« less

Sudden onset odontoid fracture caused by cervical instability in hypotonic cerebral palsy.

PubMed

Shiohama, Tadashi; Fujii, Katsunori; Kitazawa, Katsuhiko; Takahashi, Akiko; Maemoto, Tatsuo; Honda, Akihito

2013-11-01

Fractures of the upper cervical spine rarely occur but carry a high rate of mortality and neurological disabilities in children. Although odontoid fractures are commonly caused by high-impact injuries, cerebral palsy children with cervical instability have a risk of developing spinal fractures even from mild trauma. We herein present the first case of an odontoid fracture in a 4-year-old boy with cerebral palsy. He exhibited prominent cervical instability due to hypotonic cerebral palsy from infancy. He suddenly developed acute respiratory failure, which subsequently required mechanical ventilation. Neuroimaging clearly revealed a type-III odontoid fracture accompanied by anterior displacement with compression of the cervical spinal cord. Bone mineral density was prominently decreased probably due to his long-term bedridden status and poor nutritional condition. We subsequently performed posterior internal fixation surgically using an onlay bone graft, resulting in a dramatic improvement in his respiratory failure. To our knowledge, this is the first report of an odontoid fracture caused by cervical instability in hypotonic cerebral palsy. Since cervical instability and decreased bone mineral density are frequently associated with cerebral palsy, odontoid fractures should be cautiously examined in cases of sudden onset respiratory failure and aggravated weakness, especially in hypotonic cerebral palsy patients. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Trisomy 21 and facial developmental instability.

PubMed

Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T

2013-05-01

The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. Copyright © 2013 Wiley Periodicals, Inc.

Pms2 Suppresses Large Expansions of the (GAA·TTC)n Sequence in Neuronal Tissues

PubMed Central

Bourn, Rebecka L.; De Biase, Irene; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Al-Mahdawi, Sahar; Pook, Mark A.; Bidichandani, Sanjay I.

2012-01-01

Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR) pathway are required for instability of the expanded (CAG·CTG)n sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC)n sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC)n sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC)n sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia) but not in non-neuronal tissues (heart and kidney), without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC)n sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway. PMID:23071719

Pms2 suppresses large expansions of the (GAA·TTC)n sequence in neuronal tissues.

PubMed

Bourn, Rebecka L; De Biase, Irene; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Al-Mahdawi, Sahar; Pook, Mark A; Bidichandani, Sanjay I

2012-01-01

Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR) pathway are required for instability of the expanded (CAG·CTG)(n) sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC)(n) sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC)(n) sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC)(n) sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia) but not in non-neuronal tissues (heart and kidney), without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC)(n) sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway.

The Mediating Role of Parenting in the Associations between Household Chaos and Children’s Representations of Family Dysfunction

PubMed Central

Zvara, B.J.; Mills-Koonce, W.R.; Garrett-Peters, P.; Wagner, N.J.; Vernon-Feagans, L.; Cox, M.

2014-01-01

Children’s drawings are thought to reflect their mental representations of self and their interpersonal relations within families. Household chaos is believed to disrupt key proximal processes related to optimal development. The present study examines the mediating role of parenting behaviors in the relations between two measures of household chaos, instability and disorganization, and how they may be evidenced in children’s representations of family dysfunction as derived from their drawings. The sample (N= 962) is from a longitudinal study of rural poverty exploring the ways in which child, family, and contextual factors shape development over time. Findings reveal that, after controlling for numerous factors including child and primary caregiver covariates, there were significant indirect effects from cumulative family disorganization, but not cumulative family instability, on children’s representation of family dysfunction through parenting behaviors. Results suggest that the proximal effects of daily disorganization outweigh the effects of periodic instability overtime. PMID:25329862

Colliding winds from early-type stars in binary systems

NASA Technical Reports Server (NTRS)

Stevens, Ian R.; Blondin, John M.; Pollock, A. M. T.

1992-01-01

The dynamics of the wind and shock structure formed by the wind collision in early-type binary systems is examined by means of a 2D hydrodynamics code, which self-consistently accounts for radiative cooling, and represents a significant improvement over previous attempts to model these systems. The X-ray luminosity and spectra of the shock-heated region, accounting for wind attenuation and the influence of different abundances on the resultant level and spectra of X-ray emission are calculated. A variety of dynamical instabilities that are found to dominate the intershock region is examined. These instabilities are found to be particularly important when postshock material is able to cool. These instabilities disrupt the postshock flow and add a time variability of order 10 percent to the X-ray luminosity. The X-ray spectrum of these systems is found to vary with the nuclear abundances of winds. These theoretical models are used to study several massive binary systems, in particular V444 Cyg and HD 193793.

Aniakchak sockeye salmon investigations

USGS Publications Warehouse

Hamon, Troy R.; Pavey, Scott A.; Miller, Joe L.; Nielsen, Jennifer L.

2005-01-01

Aniakchak National Monument and Preserve provides unusual and dramatic landscapes shaped by numerous volcanic eruptions, a massive flood, enormous landslides, and ongoing geological change. The focal point of the monument is Aniakchak Caldera, a restless volcano that embodies the instability of the Alaska Peninsula. This geological instability creates a dynamic and challenging environment for the biological occupants of Aniakchak and unparalleled opportunities for scientists to measure the adaptability of organisms and ecosystems to change. The sockeye salmon (Oncorhynchus nerka) is one member of the Aniakchak ecosystem that has managed to adapt to geologic upheaval and is now thriving in the park. Aside from just surviving in the harsh environment, these salmon are also noteworthy for providing essential marinederived nutrients to plants and animals and as a source of food for historic and present day people in the region.

Isolated Disruption of the Right Coronary Artery Following a Steam Pop during Cavotricuspid Linear Ablation with a Contact Force Catheter.

PubMed

Brunelli, Michele; Frommhold, Markus; Back, Dieter; Mierzwa, Marco; Lauer, Bernard; Geller, J Christoph

2016-07-01

A 70-year-old woman with persistent atrial fibrillation underwent pulmonary vein isolation and linear ablation with a contact sensor catheter. During cavotricuspid isthmus ablation, a steam pop resulted in cardiac tamponade, and the patient developed severe hypotension despite successful pericardial puncture and minimal residual pericardial effusion. Right coronary artery angiography revealed extravasal contrast medium accumulation posterior of the Crux Cordis. Emergent cardiac surgery confirmed isolated disruption of the artery in the absence of additional heart perforation. Although contact sensor catheters may reduce complications, steam pops can still occur and result in dramatic complications. © 2016 Wiley Periodicals, Inc.

Role of Ankle Arthroscopy in Management of Acute Ankle Fracture.

PubMed

Chan, Kwok Bill; Lui, Tun Hing

2016-11-01

To report the operative findings of ankle arthroscopy during open reduction and internal fixation of acute ankle fractures. This was a retrospective review of 254 consecutive patients with acute ankle fractures who were treated with open reduction and internal fixation of the fractures, and ankle arthroscopy was performed at the same time. The accuracy of fracture reduction, the presence of syndesmosis disruption and its reduction, and the presence of ligamentous injuries and osteochondral lesions were documented. Second-look ankle arthroscopy was performed during syndesmosis screw removal 6 weeks after the key operation. There were 6 patients with Weber A, 177 patients with Weber B, 51 patients with Weber C, and 20 patients with isolated medial malleolar fractures. Syndesmosis disruption was present in 0% of patients with Weber A fracture, 52% of patients with Weber B fracture, 92% of patients with Weber C fracture, and 20% of the patients with isolated medial malleolar fracture. Three patients with Weber B and one patient with Weber C fracture have occult syndesmosis instability after screw removal. Osteochondral lesion was present in no patient with Weber A fracture, 26% of the Weber B cases, 24% of the Weber C cases, and 20% of isolated medial malleolar fracture cases. The association between the presence of deep deltoid ligament tear and syndesmosis disruption (warranting syndesmosis screw fixation) in Weber B cases was statistically significant but not in Weber C cases. There was no statistically significant association between the presence of posterior malleolar fracture and syndesmosis instability that warrant screw fixation. Ankle arthroscopy is a useful adjuvant tool to understand the severity and complexity of acute ankle fracture. Direct arthroscopic visualization ensures detection and evaluation of intra-articular fractures, syndesmosis disruption, and associated osteochondral lesions and ligamentous injuries. Level IV, case series. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Instability following total knee arthroplasty.

PubMed

Rodriguez-Merchan, E Carlos

2011-10-01

Background Knee prosthesis instability (KPI) is a frequent cause of failure of total knee arthroplasty. Moreover, the degree of constraint required to achieve immediate and long-term stability in total knee arthroplasty (TKA) is frequently debated. Questions This review aims to define the problem, analyze risk factors, and review strategies for prevention and treatment of KPI. Methods A PubMed (MEDLINE) search of the years 2000 to 2010 was performed using two key words: TKA and instability. One hundred and sixty-five initial articles were identified. The most important (17) articles as judged by the author were selected for this review. The main criteria for selection were that the articles addressed and provided solutions to the diagnosis and treatment of KPI. Results Patient-related risk factors predisposing to post-operative instability include deformity requiring a large surgical correction and aggressive ligament release, general or regional neuromuscular pathology, and hip or foot deformities. KPI can be prevented in most cases with appropriate selection of implants and good surgical technique. When ligament instability is anticipated post-operatively, the need for implants with a greater degree of constraint should be anticipated. In patients without significant varus or valgus malalignment and without significant flexion contracture, the posterior cruciate ligament (PCL) can be retained. However, the PCL should be sacrificed when deformity exists particularly in patients with rheumatoid arthritis, previous patellectomy, previous high tibial osteotomy or distal femoral osteotomy, and posttraumatic osteoarthritis with disruption of the PCL. In most cases, KPI requires revision surgery. Successful outcomes can only be obtained if the cause of KPI is identified and addressed. Conclusions Instability following TKA is a common cause of the need for revision. Typically, knees with deformity, rheumatoid arthritis, previous patellectomy or high tibial osteotomy, and posttraumatic arthritis carry higher risks of post-operative instability and are indications for more constrained TKA designs. Instability following TKA usually requires revision surgery which must address the cause of the instability for success.

Protostellar Disk Instabilities and the Formation of Substellar Companions

NASA Astrophysics Data System (ADS)

Pickett, Brian K.; Durisen, Richard H.; Cassen, Patrick; Mejia, Annie C.

2000-09-01

Recent numerical simulations of self-gravitating protostellar disks have suggested that gravitational instabilities can lead to the production of substellar companions. In these simulations, the disk is typically assumed to be locally isothermal; i.e., the initial, axisymmetric temperature in the disk remains everywhere unchanged. Such an idealized condition implies extremely efficient cooling for outwardly moving parcels of gas. While we have seen disk disruption in our own locally isothermal simulations of a small, massive protostellar disk, no long-lived companions formed as a result of the instabilities. Instead, thermal and tidal effects and the complex interactions of the disk material prevented permanent condensations from forming, despite the vigorous growth of spiral instabilities. In order to compare our results more directly with those of other authors, we here present three-dimensional evolutions of an older, larger, but less massive protostellar disk. We show that potentially long-lived condensations form only for the extreme of local isothermality, and then only when severe restrictions are placed on the natural tendency of the protostellar disk to expand in response to gravitational instabilities. A more realistic adiabatic evolution leads to vertical and radial expansion of the disk but no clump formation. We conclude that isothermal disk calculations cannot demonstrate companion formation by disk fragmentation but only suggest it at best. It will be necessary in future numerical work on this problem to treat the disk thermodynamics more realistically.

Emerging State Policy in Online Special Education

ERIC Educational Resources Information Center

Basham, James D.; Carter, Richard A., Jr.; Rice, Mary Frances; Ortiz, Kelsey

2016-01-01

There has been a dramatic increase and acceptance of online learning in the last decade. In its various forms, online learning has begun to disrupt the status quo of K-12 education and, in turn, special education. The growing prevalence of K-12 online learning provides a grounded opportunity to reflect on traditions and redesign policies, systems,…

Watered by Tempests: Hurricanes in the Cultural Fabric of the United Houma Nation

ERIC Educational Resources Information Center

D'Oney, J. Daniel

2008-01-01

Hurricanes Katrina and Rita affected hundreds of thousands in southern Louisiana. To say that they touched people of every stripe and color dramatically is a gross understatement. Aside from the loss of life and property damage, families were uprooted, traditions disrupted, and one of the largest migrations in American history forced on a state…

Arthroscopic Findings in Anterior Shoulder Instability

PubMed Central

Hantes, Michael; Raoulis, Vasilios

2017-01-01

Background: In the last years, basic research and arthroscopic surgery, have improved our understanding of shoulder anatomy and pathology. It is a fact that arthroscopic treatment of shoulder instability has evolved considerably over the past decades. The aim of this paper is to present the variety of pathologies that should be identified and treated during shoulder arthroscopy when dealing with anterior shoulder instability cases. Methods: A review of the current literature regarding arthroscopic shoulder anatomy, anatomic variants, and arthroscopic findings in anterior shoulder instability, is presented. In addition, correlation of arthroscopic findings with physical examination and advanced imaging (CT and MRI) in order to improve our understanding in anterior shoulder instability pathology is discussed. Results: Shoulder instability represents a broad spectrum of disease and a thorough understanding of the pathoanatomy is the key for a successful treatment of the unstable shoulder. Patients can have a variety of pathologies concomitant with a traditional Bankart lesion, such as injuries of the glenoid (bony Bankart), injuries of the glenoid labrum, superiorly (SLAP) or anteroinferiorly (e.g. anterior labroligamentous periosteal sleeve avulsion, and Perthes), capsular lesions (humeral avulsion of the glenohumeral ligament), and accompanying osseous-cartilage lesions (Hill-Sachs, glenolabral articular disruption). Shoulder arthroscopy allows for a detailed visualization and a dynamic examination of all anatomic structures, identification of pathologic findings, and treatment of all concomitant lesions. Conclusion: Surgeons must be well prepared and understanding the normal anatomy of the glenohumeral joint, including its anatomic variants to seek for the possible pathologic lesions in anterior shoulder instability during shoulder arthroscopy. Patient selection criteria, improved surgical techniques, and implants available have contributed to the enhancement of clinical and functional outcomes to the point that arthroscopic treatment is considered nowadays the standard of care. PMID:28400880

Methyltransferases mediate cell memory of a genotoxic insult.

PubMed

Rugo, R E; Mutamba, J T; Mohan, K N; Yee, T; Chaillet, J R; Greenberger, J S; Engelward, B P

2011-02-10

Characterization of the direct effects of DNA-damaging agents shows how DNA lesions lead to specific mutations. Yet, serum from Hiroshima survivors, Chernobyl liquidators and radiotherapy patients can induce a clastogenic effect on naive cells, showing indirect induction of genomic instability that persists years after exposure. Such indirect effects are not restricted to ionizing radiation, as chemical genotoxins also induce heritable and transmissible genomic instability phenotypes. Although such indirect induction of genomic instability is well described, the underlying mechanism has remained enigmatic. Here, we show that mouse embryonic stem cells exposed to γ-radiation bear the effects of the insult for weeks. Specifically, conditioned media from the progeny of exposed cells can induce DNA damage and homologous recombination in naive cells. Notably, cells exposed to conditioned media also elicit a genome-destabilizing effect on their neighbouring cells, thus demonstrating transmission of genomic instability. Moreover, we show that the underlying basis for the memory of an insult is completely dependent on two of the major DNA cytosine methyltransferases, Dnmt1 and Dnmt3a. Targeted disruption of these genes in exposed cells completely eliminates transmission of genomic instability. Furthermore, transient inactivation of Dnmt1, using a tet-suppressible allele, clears the memory of the insult, thus protecting neighbouring cells from indirect induction of genomic instability. We have thus demonstrated that a single exposure can lead to long-term, genome-destabilizing effects that spread from cell to cell, and we provide a specific molecular mechanism for these persistent bystander effects. Collectively, our results impact the current understanding of risks from toxin exposures and suggest modes of intervention for suppressing genomic instability in people exposed to carcinogenic genotoxins.

Angular Momentum Transport in Thin Magnetically Arrested Disks

NASA Astrophysics Data System (ADS)

Marshall, Megan D.; Avara, Mark J.; McKinney, Jonathan C.

2018-05-01

In accretion disks with large-scale ordered magnetic fields, the magnetorotational instability (MRI) is marginally suppressed, so other processes may drive angular momentum transport leading to accretion. Accretion could then be driven by large-scale magnetic fields via magnetic braking, and large-scale magnetic flux can build-up onto the black hole and within the disk leading to a magnetically-arrested disk (MAD). Such a MAD state is unstable to the magnetic Rayleigh-Taylor (RT) instability, which itself leads to vigorous turbulence and the emergence of low-density highly-magnetized bubbles. This instability was studied in a thin (ratio of half-height H to radius R, H/R ≈ 0.1) MAD simulation, where it has a more dramatic effect on the dynamics of the disk than for thicker disks. Large amounts of flux are pushed off the black hole into the disk, leading to temporary decreases in stress, then this flux is reprocessed as the stress increases again. Throughout this process, we find that the dominant component of the stress is due to turbulent magnetic fields, despite the suppression of the axisymmetric MRI and the dominant presence of large-scale magnetic fields. This suggests that the magnetic RT instability plays a significant role in driving angular momentum transport in MADs.

Fate of very low-mass secondaries in accreting binaries and the 1.5-ms pulsar

NASA Technical Reports Server (NTRS)

Ruderman, M. A.; Shaham, J.

1983-01-01

It is shown analytically that the canonical stability postulate for low-mass binaries can be inaccurate when the secondary component mass is less than 0.02 solar mass. The adjustable evolutionary parameter h is demonstrated to have a value (in terms of the mass flow effects) of 2/3, less than which catastrophic instability and tidal disruption of the secondary might occur. The disrupted secondary would be reduced to a remnant significantly smaller in mass than the earth, and not be observable visually. Additionally, close passage by another star could accelerate or initiate the process. The model is applicable to the pulsar binary PSR1937+214, and is noted not to conflict with spin-up theories.

Resilience of natural gas networks during conflicts, crises and disruptions.

PubMed

Carvalho, Rui; Buzna, Lubos; Bono, Flavio; Masera, Marcelo; Arrowsmith, David K; Helbing, Dirk

2014-01-01

Human conflict, geopolitical crises, terrorist attacks, and natural disasters can turn large parts of energy distribution networks offline. Europe's current gas supply network is largely dependent on deliveries from Russia and North Africa, creating vulnerabilities to social and political instabilities. During crises, less delivery may mean greater congestion, as the pipeline network is used in ways it has not been designed for. Given the importance of the security of natural gas supply, we develop a model to handle network congestion on various geographical scales. We offer a resilient response strategy to energy shortages and quantify its effectiveness for a variety of relevant scenarios. In essence, Europe's gas supply can be made robust even to major supply disruptions, if a fair distribution strategy is applied.

Pattern formation, social forces, and diffusion instability in games with success-driven motion

NASA Astrophysics Data System (ADS)

Helbing, Dirk

2009-02-01

A local agglomeration of cooperators can support the survival or spreading of cooperation, even when cooperation is predicted to die out according to the replicator equation, which is often used in evolutionary game theory to study the spreading and disappearance of strategies. In this paper, it is shown that success-driven motion can trigger such local agglomeration and may, therefore, be used to supplement other mechanisms supporting cooperation, like reputation or punishment. Success-driven motion is formulated here as a function of the game-theoretical payoffs. It can change the outcome and dynamics of spatial games dramatically, in particular as it causes attractive or repulsive interaction forces. These forces act when the spatial distributions of strategies are inhomogeneous. However, even when starting with homogeneous initial conditions, small perturbations can trigger large inhomogeneities by a pattern-formation instability, when certain conditions are fulfilled. Here, these instability conditions are studied for the prisoner’s dilemma and the snowdrift game. Furthermore, it is demonstrated that asymmetrical diffusion can drive social, economic, and biological systems into the unstable regime, if these would be stable without diffusion.

A cross-field current instability for substorm expansions

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

Lui, A.T.Y.; Chang, C.L.; Mankofsky, A.

1991-07-01

The authors investigate a cross-field current instability (CFCI) as a candidate for current disruption during substorm expansions. The numerical solution of the linear dispersion equation indicates that (1) the proposed instability can occur at the inner edge or the midsection of the neutral sheet just prior to the substorm expansion onset although the former environment is found more favorable at the same drift speed scaled to the ion thermal speed, (2) the computed growth time is comparable to the substorm onset time, and (3) the excited waves have a mixed polarization with frequencies near the ion gyrofrequency at the innermore » edge and near the lower hybrid frequency in the midtail region. On the basis of this analysis, they propose a substorm development scenario in which plasma sheet thinning during the substorm growth phase leads to an enhancement in the relative drift between ions and electrons. This results in the neutral sheet being susceptible to the CHCI and initiates the diversion of the cross-tail current through the ionosphere. Whether or not a substorm current wedge is ultimately formed is regulated by the ionospheric condition. A large number of substorm features can be readily understood with the proposed scheme. These include (1) precursory activities (pseudobreakups) prior to substorm onset, (2) substorm initiation region to be spatially localized, (3) three different solar wind conditions for substorm occurence, (4) skew towards evening local times for substorm onset locations, (5) different acceleration characteristics between ions and electrons, (6) tailward spreading of current disruption region after substorm onset, and (7) local time expansion of substorm current wedge with possible discrete westward jump for the evening expansion.« less

Evening cortisol is associated with intra-individual instability in daytime napping in nursing home residents with dementia: an allostatic load perspective.

PubMed

Woods, Diana Lynn; Yefimova, Maria

2012-10-01

Circadian rhythm disruption, reflected in alterations in sleep-wake activity and daytime napping behavior, is consistently reported in nursing home (NH) residents with dementia. This disruption may be reflected in day-to-day instability. The concept of allostatic load (AL), a measure of cumulative biological burden over a lifetime, may be a helpful model for understanding cortisol diurnal rhythm and daytime napping activity in this population. The purpose of this study was to examine the association between intra-individual daytime napping episodes and basal cortisol diurnal rhythm in NH residents with dementia in the context of AL. U sing a within-individual longitudinal design (N = 51), the authors observed and recorded daytime napping activity every 20 min for 10 hr per day across 4 consecutive days. The authors obtained saliva samples 4 times each day (upon participants' waking and within 1 hr, 6 hr, and 12 hr of participants' wake time) for cortisol analysis. The authors categorized participants as high changers (HCs; day-to-day instability in napping activity) or low changers (LCs; day-to-day stability). There were no significant differences in resident characteristics between groups. There was a significant difference between HCs and LCs in napping episodes (F = 4.86, p = .03), with an interaction effect of evening cortisol on napping episodes in the HC group (F = 10.161, p = .001). NH residents with unstable day-to-day napping episodes are more responsive to alterations in evening cortisol, an index of a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. They may also be more amenable to environmental intervention, an avenue for further research.

Postural stability in the elderly during sensory perturbations and dual tasking: the influence of refractive blur.

PubMed

Anand, Vijay; Buckley, John G; Scally, Andy; Elliott, David B

2003-07-01

To determine the influence of refractive blur on postural stability during somatosensory and vestibular system perturbation and dual tasking. Fifteen healthy, elderly subjects (mean age, 71 +/- 5 years), who had no history of falls and had normal vision, were recruited. Postural stability during standing was assessed using a force platform, and was determined as the root mean square (RMS) of the center of pressure (COP) signal in the anterior-posterior (A-P) and medial-lateral directions collected over a 30-second period. Data were collected under normal standing conditions and with somatosensory and vestibular system perturbations. Measurements were repeated with an additional physical and/or cognitive task. Postural stability was measured under conditions of binocular refractive blur of 0, 1, 2, 4, and 8 D and with eyes closed. The data were analyzed with a population-averaged linear model. The greatest increases in postural instability were due to disruptions of the somatosensory and vestibular systems. Increasing refractive blur caused increasing postural instability, and its effect was greater when the input from the other sensory systems was disrupted. Performing an additional cognitive and physical task increased A-P RMS COP further. All these detrimental effects on postural stability were cumulative. The findings highlight the multifactorial nature of postural stability and indicate why the elderly, many of whom have poor vision and musculoskeletal and central nervous system degeneration, are at greater risk of falling. The findings also highlight that standing instability in both normal and perturbed conditions was significantly increased with refractive blur. Correcting visual impairment caused by uncorrected refractive error could be a useful intervention strategy to help prevent falls and fall-related injuries in the elderly.

Unstable argininosuccinate lyase in variant forms of the urea cycle disorder argininosuccinic aciduria.

PubMed

Hu, Liyan; Pandey, Amit V; Balmer, Cécile; Eggimann, Sandra; Rüfenacht, Véronique; Nuoffer, Jean-Marc; Häberle, Johannes

2015-09-01

Loss of function of the urea cycle enzyme argininosuccinate lyase (ASL) is caused by mutations in the ASL gene leading to ASL deficiency (ASLD). ASLD has a broad clinical spectrum ranging from life-threatening severe neonatal to asymptomatic forms. Different levels of residual ASL activity probably contribute to the phenotypic variability but reliable expression systems allowing clinically useful conclusions are not yet available. In order to define the molecular characteristics underlying the phenotypic variability, we investigated all ASL mutations that were hitherto identified in patients with late onset or mild clinical and biochemical courses by ASL expression in human embryonic kidney 293 T cells. We found residual activities >3% of ASL wild type (WT) in nine of 11 ASL mutations. Six ASL mutations (p.Arg95Cys, p.Ile100Thr, p.Val178Met, p.Glu189Gly, p.Val335Leu, and p.Arg379Cys) with residual activities ≥16% of ASL WT showed no significant or less than twofold reduced Km values, but displayed thermal instability. Computational structural analysis supported the biochemical findings by revealing multiple effects including protein instability, disruption of ionic interactions and hydrogen bonds between residues in the monomeric form of the protein, and disruption of contacts between adjacent monomeric units in the ASL tetramer. These findings suggest that the clinical and biochemical course in variant forms of ASLD is associated with relevant residual levels of ASL activity as well as instability of mutant ASL proteins. Since about 30% of known ASLD genotypes are affected by mutations studied here, ASLD should be considered as a candidate for chaperone treatment to improve mutant protein stability.

3D Stagnation instabilities in MagLIF loads on the Z Generator

NASA Astrophysics Data System (ADS)

Jennings, Christopher

2017-10-01

Experiments with Magnetized Liner Inertial Fusion (MagLIF) loads have successfully demonstrated the premise of magnetized fusion. While these experiments are increasingly well diagnosed, many of the measurements (particularly during stagnation) are time integrated, limited in spatial resolution or require additional assumptions to interpret in the context of a structured, rapidly evolving system. As such, there is some ambiguity over what may be limiting performance. Poor laser coupling in preheating the fuel prior to implosion has been suggested as a mechanism. Mix of high Z contaminants that cool the fuel is also a significant concern. In addition, time integrated crystal imaging has shown significant structure in the final fuel assembly indicating potential disruption from instabilities. Understanding the balance between these degradation mechanisms is vital to progress with MagLif. We compare several sets of experimental data with synthetically generated data from systematically varied 3D resistive-MHD simulations to gain insight into the relative contributions of different degradation mechanisms. We demonstrate how some measurements strongly indicate disruption from liner material penetrating into the fuel at stagnation, and discuss the implications this has for how MagLif targets work and scale to larger drive currents. We then explore the extent to which different combinations of instability development, current delivery, high-Z mix into the fuel and initial laser deposition can be differentiated in our existing measurements. Better determining the dominant degradation mechanisms can directly influence the direction we take to improve performance, or our confidence in scaling these targets to higher currents. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc. for the U.S. DoE's NNSA under contract DE-NA0003525.

Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue

DTIC Science & Technology

2015-06-01

complex disrupts cell-cycle checkpoints, induces chromosomal instability, and contributes to aneuploidy (18). In addi- tion, PSMA is negatively regulated by...promoting complex and induces chromosomal insta- bility. Mol Cancer Ther 2008;7:2142–51. 19. Serda RE, Bisoffi M, Thompson TA, Ji M, Omdahl JL...incidence among men with low antioxidant nutritional intake.23,24 However, there are con- flicting data regarding the association between rs4880 and

Multi-Wavelength Imaging of Solar Plasma - High-Beta Disruption Model of Solar Flares -

NASA Astrophysics Data System (ADS)

Shibasaki, Kiyoto

Solar atmosphere is filled with plasma and magnetic field. Activities in the atmosphere are due to plasma instabilities in the magnetic field. To understand the physical mechanisms of activities / instabilities, it is necessary to know the physical conditions of magnetized plasma, such as temperature, density, magnetic field, and their spatial structures and temporal developments. Multi-wavelength imaging is essential for this purpose. Imaging observations of the Sun at microwave, X-ray, EUV and optical ranges are routinely going on. Due to free exchange of original data among solar physics and related field communities, we can easily combine images covering wide range of spectrum. Even under such circumstances, we still do not understand the cause of activities in the solar atmosphere well. The current standard model of solar activities is based on magnetic reconnection: release of stored magnetic energy by reconnection is the cause of solar activities on the Sun such as solar flares. However, recent X-ray, EUV and microwave observations with high spatial and temporal resolution show that dense plasma is involved in activities from the beginning. Based on these observations, I propose a high-beta model of solar activities, which is very similar to high-beta disruptions in magnetically confined fusion experiments.

Interacting tilt and kink instabilities in repelling current channels

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

Keppens, R.; Porth, O.; Xia, C., E-mail: rony.keppens@wis.kuleuven.be

2014-11-01

We present a numerical study in resistive magnetohydrodynamics (MHD) where the initial equilibrium configuration contains adjacent, oppositely directed, parallel current channels. Since oppositely directed current channels repel, the equilibrium is liable to an ideal magnetohydrodynamic tilt instability. This tilt evolution, previously studied in planar settings, involves two magnetic islands or flux ropes, which on Alfvénic timescales undergo a combined rotation and separation. This in turn leads to the creation of (near) singular current layers, posing severe challenges to numerical approaches. Using our open-source grid-adaptive MPI-AMRVAC software, we revisit the planar evolution case in compressible MHD, as well as its extensionmore » to two-and-a-half-dimensional (2.5D) and full three-dimensional (3D) scenarios. As long as the third dimension can be ignored, pure tilt evolutions result that are hardly affected by out of plane magnetic field components. In all 2.5D runs, our simulations do show secondary tearing type disruptions throughout the near singular current sheets in the far nonlinear saturation regime. In full 3D runs, both current channels can be liable to additional ideal kink deformations. We discuss the effects of having both tilt and kink instabilities acting simultaneously in the violent, reconnection-dominated evolution. In 3D, both the tilt and the kink instabilities can be stabilized by tension forces. As a concrete space plasma application, we argue that interacting tilt-kink instabilities in repelling current channels provide a novel route to initiate solar coronal mass ejections, distinctly different from the currently favored pure kink or torus instability routes.« less

Sleep and circadian rhythms

NASA Technical Reports Server (NTRS)

Monk, Timothy H.

1991-01-01

Three interacting processes are involved in the preservation of circadian rhythms: (1) endogenous rhythm generation mechanisms, (2) entrainment mechanisms to keep these rhythms 'on track', and (3) exogenous masking processes stemming from changes in environment and bahavior. These processes, particularly the latter two, can be dramatically affected in individuals of advanced age and in space travelers, with a consequent disruption in sleep and daytime functioning. This paper presents results of a phase-shift experiment investigating the age-related effects of the exogeneous component of circadian rhythms in various physiological and psychological functions by comparing these functions in middle aged and old subjects. Dramatic differences were found between the two age groups in measures of sleep, mood, activation, and performance efficiency.

AFM of the ultrastructural and mechanical properties of lipid-raft-disrupted and/or cold-treated endothelial cells.

PubMed

Wu, Li; Huang, Jie; Yu, Xiaoxue; Zhou, Xiaoqing; Gan, Chaoye; Li, Ming; Chen, Yong

2014-02-01

The nonionic detergent extraction at 4 °C and the cholesterol-depletion-induced lipid raft disruption are the two widely used experimental strategies for lipid raft research. However, the effects of raft disruption and/or cold treatment on the ultrastructural and mechanical properties of cells are still unclear. Here, we evaluated the effects of raft disruption and/or cold (4 °C) treatment on these properties of living human umbilical vein endothelial cells (HUVECs). At first, the cholesterol-depletion-induced raft disruption was visualized by confocal microscopy and atomic force microscopy (AFM) in combination with fluorescent quantum dots. Next, the cold-induced cell contraction and the formation of end-branched filopodia were observed by confocal microscopy and AFM. Then, the cell-surface ultrastructures were imaged by AFM, and the data showed that raft disruption and cold treatment induced opposite effects on cell-surface roughness (a significant decrease and a significant increase, respectively). Moreover, the cell-surface mechanical properties (stiffness and adhesion force) of raft-disrupted- and/or cold-treated HUVECs were measured by the force measurement function of AFM. We found that raft disruption and cold treatment induced parallel effects on cell stiffness (increase) or adhesion force (decrease) and that the combination of the two treatments caused dramatically strengthened effects. Finally, raft disruption was found to significantly impair cell migration as previously reported, whereas temporary cold treatment only caused a slight but nonsignificant decrease in cell migration performed at physiological temperature. Although the mechanisms for causing these results might be complicated and more in-depth studies will be needed, our data may provide important information for better understanding the effects of raft disruption or cold treatment on cells and the two strategies for lipid raft research.

Toward Ubiquitous BCIs

NASA Astrophysics Data System (ADS)

Allison, Brendan Z.

The preceding chapters in this book described modern BCI systems. This concluding chapter instead discusses future directions. While there are some specific predictions, I mainly analyze key factors and trends relating to practical mainstream BCI development. While I note some disruptive technologies that could dramatically change BCIs, this chapter focuses mainly on realistic, incremental progress and how progress could affect user groups and ethical issues.

A factor involved in efficient breakdown of supersonic streamwise vortices

NASA Astrophysics Data System (ADS)

Hiejima, Toshihiko

2015-03-01

Spatially developing processes in supersonic streamwise vortices were numerically simulated at Mach number 5.0. The vortex evolution largely depended on the azimuthal vorticity thickness of the vortices, which governs the negative helicity profile. Large vorticity thickness greatly enhanced the centrifugal instability, with consequent development of perturbations with competing wavenumbers outside the vortex core. During the transition process, supersonic streamwise vortices could generate large-scale spiral structures and a number of hairpin like vortices. Remarkably, the transition caused a dramatic increase in the total fluctuation energy of hypersonic flows, because the negative helicity profile destabilizes the flows due to helicity instability. Unstable growth might also relate to the correlation length between the axial and azimuthal vorticities of the streamwise vortices. The knowledge gained in this study is important for realizing effective fuel-oxidizer mixing in supersonic combustion engines.

Reduced ion bootstrap current drive on NTM instability

NASA Astrophysics Data System (ADS)

Qu, Hongpeng; Wang, Feng; Wang, Aike; Peng, Xiaodong; Li, Jiquan

2018-05-01

The loss of bootstrap current inside magnetic island plays a dominant role in driving the neoclassical tearing mode (NTM) instability in tokamak plasmas. In this work, we investigate the finite-banana-width (FBW) effect on the profile of ion bootstrap current in the island vicinity via an analytical approach. The results show that even if the pressure gradient vanishes inside the island, the ion bootstrap current can partly survive due to the FBW effect. The efficiency of the FBW effect is higher when the island width becomes smaller. Nevertheless, even when the island width is comparable to the ion FBW, the unperturbed ion bootstrap current inside the island cannot be largely recovered by the FBW effect, and thus the current loss still exists. This suggests that FBW effect alone cannot dramatically reduce the ion bootstrap current drive on NTMs.

From the 2-dimensional unstable polyelectrolyte multilayer to the 3-dimensional stable dry polyelectrolyte capsules.

PubMed

Li, Xiaodong; Zhang, Jianxiang; Hu, Qiaoling; Li, Xiaohui

2011-11-01

Polystyrene-poly(acrylic acid)/poly(allylamine hydrochloride) polyelectrolyte multilayer was found to be instable and apt to reconstruct in the pure water. By depositing polystyrene-poly(acrylic acid)/poly(allylamine hydrochloride) multilayer on the polystyrene-poly(acrylic acid) hybrid CaCO(3) templates, novel polyelectrolyte capsules could be prepared after the removal of the templates. The resultant capsules could keep their three-dimensional (3D) spherical shape after being dried at room temperature, dramatically different from the conventional polyelectrolyte capsules based on nonhybrid templates by layer-by-layer procedure. The instable polyelectrolyte multilayer, hybrid templates, and assembly cycles were demonstrated to be three indispensable factors responsible for the formation of this type of 3D stable capsules. The formation mechanism was also discussed in this study. Copyright © 2011 Elsevier Inc. All rights reserved.

Disruption of the air-sea interface and formation of two-phase transitional layer in hurricane conditions

NASA Astrophysics Data System (ADS)

Soloviev, A.; Matt, S.; Fujimura, A.

2012-04-01

The change of the air-sea interaction regime in hurricane conditions is linked to the mechanism of direct disruption of the air-sea interface by pressure fluctuations working against surface tension forces (Soloviev and Lukas, 2010). The direct disruption of the air-sea interface due to the Kelvin-Helmholtz (KH) instability and formation of a two-phase transitional layer have been simulated with a computational fluid dynamics model. The volume of fluid multiphase model included surface tension at the water-air interface. The model was initialized with either a flat interface or short wavelets. Wind stress was applied at the upper boundary of the air layer, ranging from zero stress to hurricane force stress in different experiments. Under hurricane force wind, the numerical model demonstrated disruption of the air-water interface and the formation of spume and the two-phase transition layer. In the presence of a transition layer, the air-water interface is no longer explicitly identifiable. As a consequence, the analysis of dimensions suggests a linear dependence for velocity and logarithm of density on depth (which is consistent with the regime of marginal stability in the transition layer). The numerical simulations confirmed the presence of linear segments in the corresponding profiles within the transition layer. This permitted a parameterization of the equivalent drag coefficient due to the presence of the two-phase transition layer at the air-sea interface. This two-phase layer parameterization represented the lower limit imposed on the drag coefficient under hurricane conditions. The numerical simulations helped to reduce the uncertainty in the critical Richardson number applicable to the air-sea interface and in the values of two dimensionless constants; this reduced the uncertainty in the parameterization of the lower limit on the drag coefficient. The available laboratory data (Donelan et al., 2004) are bounded by the two-phase layer parameterization from below and the wave resistance parameterization from above. The available field data (Powell et al., 2003; Black et al., 2007) fall between these two parameterizations, for wind speeds of up to 50 m/s. A few points from the dropsonde data from Powell et al. (2003), obtained at very high wind speeds, are below the theoretical lower limit on the drag coefficient. We also conducted a numerical experiment with imposed short wavelets. Streamwise coherent structures were observed on the water surface, which were especially prominent on the top of wave crests. These intermittent streamwise structures on the top of wavelets, with periodicity in the transverse direction, presumably were a result of the Tollmien-Schlichting (TS) instability. Similar processes take place at the atomization of liquid fuels in cryogenic and diesel engines (Yecko et al., 2002). According to McNaughton and Brunet (2002), the nonlinear stage of the TS instability results in streamwise streaks followed by fluid ejections. This mechanism can contribute to the generation of spume in the form of streaks. Foam streaks are an observable feature on photographic images of the ocean surface under hurricane conditions. The mechanism of the TS instability can also contribute to dispersion of oil spills and other pollutants in hurricane conditions.

Impact of the "Symmetric Instability of the Computational Kind" at mesoscale- and submesoscale-permitting resolutions

NASA Astrophysics Data System (ADS)

Ducousso, Nicolas; Le Sommer, J.; Molines, J.-M.; Bell, M.

2017-12-01

The energy- and enstrophy-conserving momentum advection scheme (EEN) used over the last 10 years in NEMO is subject to a spurious numerical instability. This instability, referred to as the Symmetric Instability of the Computational Kind (SICK), arises from a discrete imbalance between the two components of the vector-invariant form of momentum advection. The properties and the method for removing this instability have been documented by Hollingsworth et al. (1983), but the extent to which the SICK may interfere with processes of interest at mesoscale- and submesoscale-permitting resolutions is still unkown. In this paper, the impact of the SICK in realistic ocean model simulations is assessed by comparing model integrations with different versions of the EEN momentum advection scheme. Investigations are undertaken with a global mesoscale-permitting resolution (1/4 °) configuration and with a regional North Atlantic Ocean submesoscale-permitting resolution (1/60 °) configuration. At both resolutions, the instability is found to alter primarily the most energetic current systems, such as equatorial jets, western boundary currents and coherent vortices. The impact of the SICK is found to increase with model resolution with a noticeable impact at mesoscale-permitting resolution and a dramatic impact at submesoscale-permitting resolution. The SICK is shown to distort the normal functioning of current systems, by redirecting the slow energy transfer between balanced motions to a spurious energy transfer to internal inertia-gravity waves and to dissipation. Our results indicate that the SICK is likely to have significantly corrupted NEMO solutions (when run with the EEN scheme) at mesocale-permitting and finer resolutions over the last 10 years.

Foot placement control and gait instability among people with stroke

PubMed Central

Dean, Jesse C.; Kautz, Steven A.

2016-01-01

Gait instability is a common problem following stroke, as evidenced by increases in fall risk and fear of falling. However, the mechanism underlying gait instability is currently unclear. We recently found that young, healthy humans use a consistent gait stabilization strategy of actively controlling their mediolateral foot placement based on the concurrent mechanical state of the stance limb. In the present work, we tested whether people with stroke (n = 16) and age-matched controls (n = 19) used this neuromechanical strategy. Specifically, we used multiple linear regressions to test whether (1) swing phase gluteus medius (GM) activity was influenced by the simultaneous state of the stance limb and (2) mediolateral foot placement location was influenced by swing phase GM activity and the mechanical state of the swing limb at the start of the step. We found that both age-matched controls and people with stroke classified as having a low fall risk (Dynamic Gait Index [DGI] score >19) essentially used the stabilization strategy previously described in young controls. In contrast, this strategy was disrupted for people with stroke classified as higher fall risk (DGI

Parent figure transitions and delinquency and drug use among early adolescent children of substance abusers.

PubMed

Keller, Thomas E; Catalano, Richard F; Haggerty, Kevin P; Fleming, Charles B

2002-01-01

Children of substance abusing parents have an elevated risk for experiencing disruptions in household composition and for engaging in problem behaviors. This study investigated whether multiple parent figure transitions predicted the likelihood of delinquency and drug use among a sample of early adolescents with parents receiving methadone treatment for opiate addiction. Controlling for baseline delinquency, child characteristics, family conflict, parental depression, and parent criminal history, a greater number of parenting disruptions during the longitudinal study period was associated with a higher probability of delinquent behavior. Gender moderated the effect of parent figure transitions in a parallel analysis for drug use. After accounting for baseline drug use and potentially confounding factors, only adolescent females had a higher likelihood of drug use as the number of family disruptions increased. In contrast, age was strongly associated with drug use for males. A subgroup of youths who experienced tremendous family instability and had no single consistent parent figure during the study period were at extreme risk for delinquent behavior. The findings are interpreted in terms of cumulative stress resulting from multiple parenting disruptions over time and differential influences on the expression of problem behaviors depending on gender.

Plasmoid Instability in Forming Current Sheets

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

Comisso, L.; Lingam, M.; Huang, Y. -M.

The plasmoid instability has revolutionized our understanding of magnetic reconnection in astrophysical environments. By preventing the formation of highly elongated reconnection layers, it is crucial in enabling the rapid energy conversion rates that are characteristic of many astrophysical phenomena. Most previous studies have focused on Sweet–Parker current sheets, which are unattainable in typical astrophysical systems. Here we derive a general set of scaling laws for the plasmoid instability in resistive and visco-resistive current sheets that evolve over time. Our method relies on a principle of least time that enables us to determine the properties of the reconnecting current sheet (aspect ratio and elapsed time) and the plasmoid instability (growth rate, wavenumber, inner layer width) at the end of the linear phase. After this phase the reconnecting current sheet is disrupted and fast reconnection can occur. The scaling laws of the plasmoid instability are not simple power laws, and they depend on the Lundquist number (S), the magnetic Prandtl number (P m), the noise of the system (more » $${\\psi }_{0}$$), the characteristic rate of current sheet evolution ($$1/\\tau $$), and the thinning process. We also demonstrate that previous scalings are inapplicable to the vast majority of astrophysical systems. Furthermore, we explore the implications of the new scaling relations in astrophysical systems such as the solar corona and the interstellar medium. In both of these systems, we show that our scaling laws yield values for the growth rate, wavenumber, and aspect ratio that are much smaller than the Sweet–Parker–based scalings.« less

Plasmoid Instability in Forming Current Sheets

DOE PAGES

Comisso, L.; Lingam, M.; Huang, Y. -M.; ...

2017-11-28

The plasmoid instability has revolutionized our understanding of magnetic reconnection in astrophysical environments. By preventing the formation of highly elongated reconnection layers, it is crucial in enabling the rapid energy conversion rates that are characteristic of many astrophysical phenomena. Most previous studies have focused on Sweet–Parker current sheets, which are unattainable in typical astrophysical systems. Here we derive a general set of scaling laws for the plasmoid instability in resistive and visco-resistive current sheets that evolve over time. Our method relies on a principle of least time that enables us to determine the properties of the reconnecting current sheet (aspect ratio and elapsed time) and the plasmoid instability (growth rate, wavenumber, inner layer width) at the end of the linear phase. After this phase the reconnecting current sheet is disrupted and fast reconnection can occur. The scaling laws of the plasmoid instability are not simple power laws, and they depend on the Lundquist number (S), the magnetic Prandtl number (P m), the noise of the system (more » $${\\psi }_{0}$$), the characteristic rate of current sheet evolution ($$1/\\tau $$), and the thinning process. We also demonstrate that previous scalings are inapplicable to the vast majority of astrophysical systems. Furthermore, we explore the implications of the new scaling relations in astrophysical systems such as the solar corona and the interstellar medium. In both of these systems, we show that our scaling laws yield values for the growth rate, wavenumber, and aspect ratio that are much smaller than the Sweet–Parker–based scalings.« less

Trisomy 21 and Facial Developmental Instability

PubMed Central

Starbuck, John M.; Cole, Theodore M.; Reeves, Roger H.; Richtsmeier, Joan T.

2013-01-01

The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the “amplified developmental instability” hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: 1) DS individuals (n=55); 2) biological siblings of DS individuals (n=55); 3) and 4) two samples of typically developing individuals (n=55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. PMID:23505010

[Kelvin-Helmholtz instability in protostellar jets

NASA Technical Reports Server (NTRS)

Stone, James; Hardee, Philip

1996-01-01

NASA grant NAG 5 2866, funded by the Astrophysics Theory Program, enabled the study the Kelvin-Helmholtz instability in protostellar jets. In collaboration with co-investigator Philip Hardee, the PI derived the analytic dispersion relation for the instability in including a cooling term in the energy equation which was modeled as one of two different power laws. Numerical solutions to this dispersion relation over a wide range of perturbation frequencies, and for a variety of parameter values characterizing the jet (such as Mach number, and density ratio) were found It was found that the growth rates and wavelengths associated with unstable roots of the dispersion relation in cooling jets are significantly different than those associated with adiabatic jets, which have been studied previously. In collaboration with graduate student Jianjun Xu (funded as a research associate under this grant), hydrodynamical simulations were used to follow the growth of the instability into the nonlinear regime. It was found that asymmetric surface waves lead to large amplitude, sinusoidal distortions of the jet, and ultimately to disruption Asymmetric body waves, on the other hand, result in the formation of shocks in the jet beam in the nonlinear regime. In cooling jets, these shocks lead to the formation of dense knots and filaments of gas within the jet. For sufficiently high perturbation frequencies, however, the jet cannot respond and it remains symmetric. Applying these results to observed systems, such as the Herbig-Haro jets HH34, HH111 and HH47 which have been observed with the Hubble Space Telescope, we predicted that some of the asymmetric structures observed in these systems could be attributed to the K-H modes, but that perturbations on timescales associated with the inner disk (about 1 year) would be too rapid to cause disruption. Moreover, it was discovered that weak shock 'spurs' in the ambient gas produced by ripples in the jet surface due to nonlinear, modes of surface and/or body waves could accelerate the ambient gas to low velocity. This latter effect represents a new mechanism by which supersonic jets can accelerate low velocity outflows.

Postural stability changes in the elderly with cataract simulation and refractive blur.

PubMed

Anand, Vijay; Buckley, John G; Scally, Andy; Elliott, David B

2003-11-01

To determine the influence of cataractous and refractive blur on postural stability and limb-load asymmetry (LLA) and to establish how postural stability changes with the spatial frequency and contrast of the visual stimulus. Thirteen elderly subjects (mean age, 70.76 +/- 4.14 [SD] years) with no history of falls and normal vision were recruited. Postural stability was determined as the root mean square [RMS] of the center of pressure (COP) signal in the anterior-posterior (A-P) and medial-lateral directions and LLA was determined as the ratio of the average body weight placed on the more-loaded limb to the less-loaded limb, recorded during a 30-second period. Data were collected under normal standing conditions and with somatosensory system input disrupted. Measurements were repeated with four visual targets with high (8 cyc/deg) or low (2 cyc/deg) spatial frequency and high (Weber contrast, approximately 95%) or low (Weber contrast, approximately 25%) contrast. Postural stability was measured under conditions of binocular refractive blur of 0, 1, 2, 4, and 8 D and with cataract simulation. The data were analyzed in a population-averaged linear model. The cataract simulation caused significant increases in postural instability equivalent to that caused by 8-D blur conditions, and its effect was greater when the input from the somatosensory system was disrupted. High spatial frequency targets increased postural instability. Refractive blur, cataract simulation, or eye closure had no effect on LLA. Findings indicate that cataractous and refractive blur increase postural instability, and show why the elderly, many of whom have poor vision along with musculoskeletal and central nervous system degeneration, are at greater risk of falling. Findings also highlight that changes in contrast sensitivity rather than resolution changes are responsible for increasing postural instability. Providing low spatial frequency information in certain environments may be useful in maintaining postural stability. Correcting visual impairment caused by uncorrected refractive error and cataracts could be a useful intervention strategy to help prevent falls and fall-related injuries in the elderly.

A Study of the Unstable Modes in High Mach Number Gaseous Jets and Shear Layers

NASA Astrophysics Data System (ADS)

Bassett, Gene Marcel

1993-01-01

Instabilities affecting the propagation of supersonic gaseous jets have been studied using high resolution computer simulations with the Piecewise-Parabolic-Method (PPM). These results are discussed in relation to jets from galactic nuclei. These studies involve a detailed treatment of a single section of a very long jet, approximating the dynamics by using periodic boundary conditions. Shear layer simulations have explored the effects of shear layers on the growth of nonlinear instabilities. Convergence of the numerical approximations has been tested by comparing jet simulations with different grid resolutions. The effects of initial conditions and geometry on the dominant disruptive instabilities have also been explored. Simulations of shear layers with a variety of thicknesses, Mach numbers and densities perturbed by incident sound waves imply that the time for the excited kink modes to grow large in amplitude and disrupt the shear layer is taug = (546 +/- 24) (M/4)^{1.7 } (Apert/0.02) ^{-0.4} delta/c, where M is the jet Mach number, delta is the half-width of the shear layer, and A_ {pert} is the perturbation amplitude. For simulations of periodic jets, the initial velocity perturbations set up zig-zag shock patterns inside the jet. In each case a single zig-zag shock pattern (an odd mode) or a double zig-zag shock pattern (an even mode) grows to dominate the flow. The dominant kink instability responsible for these shock patterns moves approximately at the linear resonance velocity, nu_ {mode} = cextnu_ {relative}/(cjet + c_ {ext}). For high resolution simulations (those with 150 or more computational zones across the jet width), the even mode dominates if the even penetration is higher in amplitude initially than the odd perturbation. For low resolution simulations, the odd mode dominates even for a stronger even mode perturbation. In high resolution simulations the jet boundary rolls up and large amounts of external gas are entrained into the jet. In low resolution simulations this entrainment process is impeded by numerical viscosity. The three-dimensional jet simulations behave similarly to two-dimensional jet runs with the same grid resolutions.

TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability

PubMed Central

Germann, Susanne M.; Schramke, Vera; Pedersen, Rune Troelsgaard; Gallina, Irene; Eckert-Boulet, Nadine; Oestergaard, Vibe H.

2014-01-01

DNA anaphase bridges are a potential source of genome instability that may lead to chromosome breakage or nondisjunction during mitosis. Two classes of anaphase bridges can be distinguished: DAPI-positive chromatin bridges and DAPI-negative ultrafine DNA bridges (UFBs). Here, we establish budding yeast Saccharomyces cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism. Together with the single-stranded DNA binding protein RPA, TopBP1/Dpb11 binds to UFBs, and depletion of TopBP1/Dpb11 led to an accumulation of chromatin bridges. Importantly, the NoCut checkpoint that delays progression from anaphase to abscission in yeast was activated by both UFBs and chromatin bridges independently of Dpb11, and disruption of the NoCut checkpoint in Dpb11-depleted cells led to genome instability. In conclusion, we propose that TopBP1/Dpb11 prevents accumulation of anaphase bridges via stimulation of the Mec1/ATR kinase and suppression of homologous recombination. PMID:24379413

TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability.

PubMed

Germann, Susanne M; Schramke, Vera; Pedersen, Rune Troelsgaard; Gallina, Irene; Eckert-Boulet, Nadine; Oestergaard, Vibe H; Lisby, Michael

2014-01-06

DNA anaphase bridges are a potential source of genome instability that may lead to chromosome breakage or nondisjunction during mitosis. Two classes of anaphase bridges can be distinguished: DAPI-positive chromatin bridges and DAPI-negative ultrafine DNA bridges (UFBs). Here, we establish budding yeast Saccharomyces cerevisiae and the avian DT40 cell line as model systems for studying DNA anaphase bridges and show that TopBP1/Dpb11 plays an evolutionarily conserved role in their metabolism. Together with the single-stranded DNA binding protein RPA, TopBP1/Dpb11 binds to UFBs, and depletion of TopBP1/Dpb11 led to an accumulation of chromatin bridges. Importantly, the NoCut checkpoint that delays progression from anaphase to abscission in yeast was activated by both UFBs and chromatin bridges independently of Dpb11, and disruption of the NoCut checkpoint in Dpb11-depleted cells led to genome instability. In conclusion, we propose that TopBP1/Dpb11 prevents accumulation of anaphase bridges via stimulation of the Mec1/ATR kinase and suppression of homologous recombination.

Can Parenting Intervention Prevent Cascading Effects From Placement Instability to Insecure Attachment to Externalizing Problems in Maltreated Toddlers?

PubMed

Pasalich, Dave S; Fleming, Charles B; Oxford, Monica L; Zheng, Yao; Spieker, Susan J

2016-08-01

Multiple placement changes disrupt continuity in caregiving and undermine well-being in children in child welfare. This study conducted secondary data analysis of a randomized controlled trial to examine whether a relationship-based intervention, Promoting First Relationships(©) (PFR), reduced risk for a maladaptive cascade from placement instability to less secure attachment to elevated externalizing problems. Participants included caregivers (birth or foster/kin) of toddlers (10-24 months) recently transitioned to their care because of child welfare placement decisions. Although main effects of PFR on security and externalizing problems were not previously observed, this study's results revealed that PFR attenuated the association between multiple placement changes (baseline) and less security (postintervention) and that the indirect effect of placement instability on greater externalizing problems (6-month follow-up) via less security was evident only in toddlers in the comparison condition. These findings shed light on how a history of multiple caregiver changes may influence toddlers' risk for poor adjustment in subsequent placements, and the promise of supporting caregivers through a parenting intervention to prevent such risk. © The Author(s) 2016.

Can parenting intervention prevent cascading effects from placement instability to insecure attachment to externalizing problems in maltreated toddlers?

PubMed Central

Pasalich, Dave S.; Fleming, Charles B.; Oxford, Monica L.; Zheng, Yao; Spieker, Susan J.

2016-01-01

Multiple placement changes disrupt continuity in caregiving and undermine well-being in children in child welfare. This study conducted secondary data analysis of a randomized controlled trial to examine whether a relationship-based intervention, Promoting First Relationships© (PFR), reduced risk for a maladaptive cascade from placement instability to less secure attachment to elevated externalizing problems. Participants included caregivers (birth or foster/kin) of toddlers (10–24 months) recently transitioned to their care because of child welfare placement decisions. Although main effects of PFR on security and externalizing problems were not previously observed, this study’s results revealed that PFR attenuated the association between multiple placement changes (baseline) and less security (postintervention), and that the indirect effect of placement instability on greater externalizing problems (6-month follow-up) via less security was evident only in toddlers in the comparison condition. These findings shed light on how a history of multiple caregiver changes may influence toddlers’ risk for poor adjustment in subsequent placements, and the promise of supporting caregivers through a parenting intervention to prevent such risk. PMID:27381935

Nonlinear physics of electrical wave propagation in the heart: a review

NASA Astrophysics Data System (ADS)

Alonso, Sergio; Bär, Markus; Echebarria, Blas

2016-09-01

The beating of the heart is a synchronized contraction of muscle cells (myocytes) that is triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media with applications to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact for cardiac arrhythmias.

Disruption of Spectrin-Like Cytoskeleton in Differentiating Keratinocytes by PKCδ Activation Is Associated with Phosphorylated Adducin

PubMed Central

Zhao, Kong-Nan; Masci, Paul P.; Lavin, Martin F.

2011-01-01

Spectrin is a central component of the cytoskeletal protein network in a variety of erythroid and non-erythroid cells. In keratinocytes, this protein has been shown to be pericytoplasmic and plasma membrane associated, but its characteristics and function have not been established in these cells. Here we demonstrate that spectrin increases dramatically in amount and is assembled into the cytoskeleton during differentiation in mouse and human keratinocytes. The spectrin-like cytoskeleton was predominantly organized in the granular and cornified layers of the epidermis and disrupted by actin filament inhibitors, but not by anti-mitotic drugs. When the cytoskeleton was disrupted PKCδ was activated by phosphorylation on Thr505. Specific inhibition of PKCδ(Thr505) activation with rottlerin prevented disruption of the spectrin-like cytoskeleton and the associated morphological changes that accompany differentiation. Rottlerin also inhibited specific phosphorylation of the PKCδ substrate adducin, a cytoskeletal protein. Furthermore, knock-down of endogenous adducin affected not only expression of adducin, but also spectrin and PKCδ, and severely disrupted organization of the spectrin-like cytoskeleton and cytoskeletal distribution of both adducin and PKCδ. These results demonstrate that organization of a spectrin-like cytoskeleton is associated with keratinocytes differentiation, and disruption of this cytoskeleton is mediated by either PKCδ(Thr505) phosphorylation associated with phosphorylated adducin or due to reduction of endogenous adducin, which normally connects and stabilizes the spectrin-actin complex. PMID:22163289

Disruption of Saturn's quasi-periodic equatorial oscillation by the great northern storm

NASA Astrophysics Data System (ADS)

Fletcher, Leigh N.; Guerlet, Sandrine; Orton, Glenn S.; Cosentino, Richard G.; Fouchet, Thierry; Irwin, Patrick G. J.; Li, Liming; Flasar, F. Michael; Gorius, Nicolas; Morales-Juberías, Raúl

2017-11-01

The equatorial middle atmospheres of the Earth1, Jupiter2 and Saturn3,4 all exhibit a remarkably similar phenomenon—a vertical, cyclic pattern of alternating temperatures and zonal (east-west) wind regimes that propagate slowly downwards with a well-defined multi-year period. Earth's quasi-biennial oscillation (QBO) (observed in the lower stratospheric winds with an average period of 28 months) is one of the most regular, repeatable cycles exhibited by our climate system1,5,6, and yet recent work has shown that this regularity can be disrupted by events occurring far away from the equatorial region, an example of a phenomenon known as atmospheric teleconnection7,8. Here, we reveal that Saturn's equatorial quasi-periodic oscillation (QPO) (with an 15-year period3,9) can also be dramatically perturbed. An intense springtime storm erupted at Saturn's northern mid-latitudes in December 201010-12, spawning a gigantic hot vortex in the stratosphere at 40° N that persisted for three years13. Far from the storm, the Cassini temperature measurements showed a dramatic 10 K cooling in the 0.5-5 mbar range across the entire equatorial region, disrupting the regular QPO pattern and significantly altering the middle-atmospheric wind structure, suggesting an injection of westward momentum into the equatorial wind system from waves generated by the northern storm. Hence, as on Earth, meteorological activity at mid-latitudes can have a profound effect on the regular atmospheric cycles in Saturn's tropics, demonstrating that waves can provide horizontal teleconnections between the phenomena shaping the middle atmospheres of giant planets.

Resilience of Natural Gas Networks during Conflicts, Crises and Disruptions

PubMed Central

Carvalho, Rui; Buzna, Lubos; Bono, Flavio; Masera, Marcelo; Arrowsmith, David K.; Helbing, Dirk

2014-01-01

Human conflict, geopolitical crises, terrorist attacks, and natural disasters can turn large parts of energy distribution networks offline. Europe's current gas supply network is largely dependent on deliveries from Russia and North Africa, creating vulnerabilities to social and political instabilities. During crises, less delivery may mean greater congestion, as the pipeline network is used in ways it has not been designed for. Given the importance of the security of natural gas supply, we develop a model to handle network congestion on various geographical scales. We offer a resilient response strategy to energy shortages and quantify its effectiveness for a variety of relevant scenarios. In essence, Europe's gas supply can be made robust even to major supply disruptions, if a fair distribution strategy is applied. PMID:24621655

Prototypical model for tensional wrinkling in thin sheets

PubMed Central

Davidovitch, Benny; Schroll, Robert D.; Vella, Dominic; Adda-Bedia, Mokhtar; Cerda, Enrique A.

2011-01-01

The buckling and wrinkling of thin films has recently seen a surge of interest among physicists, biologists, mathematicians, and engineers. This activity has been triggered by the growing interest in developing technologies at ever-decreasing scales and the resulting necessity to control the mechanics of tiny structures, as well as by the realization that morphogenetic processes, such as the tissue-shaping instabilities occurring in animal epithelia or plant leaves, often emerge from mechanical instabilities of cell sheets. Although the most basic buckling instability of uniaxially compressed plates was understood by Euler more than two centuries ago, recent experiments on nanometrically thin (ultrathin) films have shown significant deviations from predictions of standard buckling theory. Motivated by this puzzle, we introduce here a theoretical model that allows for a systematic analysis of wrinkling in sheets far from their instability threshold. We focus on the simplest extension of Euler buckling that exhibits wrinkles of finite length—a sheet under axisymmetric tensile loads. The first study of this geometry, which is attributed to Lamé, allows us to construct a phase diagram that demonstrates the dramatic variation of wrinkling patterns from near-threshold to far-from-threshold conditions. Theoretical arguments and comparison to experiments show that the thinner the sheet is, the smaller is the compressive load above which the far-from-threshold regime emerges. This observation emphasizes the relevance of our analysis for nanomechanics applications. PMID:22042841

Operation in low edge safety factor regime and passive disruption avoidance due to stellarator rotational transform in the Compact Toroidal Hybrid

NASA Astrophysics Data System (ADS)

Pandya, M. D.; Ennis, D. A.; Hartwell, G. J.; Maurer, D. A.

2015-11-01

Low edge safety factor operation at a value less than two (q (a) = 1 /ttot (a) < 2) is routine on the Compact Toroidal Hybrid device. Presently, the operational space of this current carrying stellarator extends down to q (a) = 1 . 2 without significant n = 1 kink mode activity after the initial plasma current rise of the discharge. The disruption dynamics of these low q (a) plasmas depend upon the fraction of rotational transform produced by external stellarator coils to that generated by the plasma current. We observe that when about 10% of the total rotational transform is supplied by the stellarator coils, low q (a) disruptions are passively suppressed and avoided even though q (a) < 2 . When the plasma does disrupt, the instability precursors measured and implicated as the cause are internal tearing modes with poloidal, m, and toroidal, n, mode numbers of m / n = 3 / 2 and 4 / 3 observed by external magnetic sensors, and m / n = 1 / 1 activity observed by core soft x-ray emissivity measurements. Even though q (a) passes through and becomes much less than two, external n = 1 kink mode activity does not appear to play a significant role in the observed disruption phenomenology. This work is supported by US Department of Energy Grant No. DE-FG02-00ER54610.

Low edge safety factor operation and passive disruption avoidance in current carrying plasmas by the addition of stellarator rotational transform

NASA Astrophysics Data System (ADS)

Pandya, M. D.; ArchMiller, M. C.; Cianciosa, M. R.; Ennis, D. A.; Hanson, J. D.; Hartwell, G. J.; Hebert, J. D.; Herfindal, J. L.; Knowlton, S. F.; Ma, X.; Massidda, S.; Maurer, D. A.; Roberds, N. A.; Traverso, P. J.

2015-11-01

Low edge safety factor operation at a value less than two ( q (a )=1 /ι̷tot(a )<2 ) is routine on the Compact Toroidal Hybrid device with the addition of sufficient external rotational transform. Presently, the operational space of this current carrying stellarator extends down to q (a )=1.2 without significant n = 1 kink mode activity after the initial plasma current rise phase of the discharge. The disruption dynamics of these low edge safety factor plasmas depend upon the fraction of helical field rotational transform from external stellarator coils to that generated by the plasma current. We observe that with approximately 10% of the total rotational transform supplied by the stellarator coils, low edge q disruptions are passively suppressed and avoided even though q(a) < 2. When the plasma does disrupt, the instability precursors measured and implicated as the cause are internal tearing modes with poloidal, m, and toroidal, n, helical mode numbers of m /n =3 /2 and 4/3 observed on external magnetic sensors and m /n =1 /1 activity observed on core soft x-ray emissivity measurements. Even though the edge safety factor passes through and becomes much less than q(a) < 2, external n = 1 kink mode activity does not appear to play a significant role in the disruption phenomenology observed.

Stripped interstellar gas in cluster cooling flows

NASA Technical Reports Server (NTRS)

Soker, Noam; Bregman, Joel N.; Sarazin, Craig L.

1991-01-01

It is suggested that nonlinear perturbations which lead to thermal instabilities in cooling flows might start as blobs of interstellar gas which are stipped out of cluster galaxies. Assuming that most of the gas produced by stellar mass loss in cluster galaxies is stripped from the galaxies, the total rate of such stripping is roughly 100 solar masses/yr, which is similar to the rates of cooling in cluster cooling flows. It is possible that a substantial portion of the cooling gas originates as blobs of interstellar gas stripped from galaxies. The magnetic fields within and outside of the low-entropy perturbations may help to maintain their identities by suppressing both thermal conduction and Kelvin-Helmholtz instabilities. These density fluctuations may disrupt the propagation of radio jets through the intracluster gas, which may be one mechanism for producing wideangle-tail radio galaxies.

How high energy fluxes may affect Rayleigh–Taylor instability growth in young supernova remnants

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

Kuranz, Carolyn C.; Park, Hye -Sook; Huntington, Channing M.

Here, energy-transport effects can alter the structure that develops as a supernova evolves into a supernova remnant. The Rayleigh–Taylor instability is thought to produce structure at the interface between the stellar ejecta and the circumstellar matter, based on simple models and hydrodynamic simulations. Here we report experimental results from the National Ignition Facility to explore how large energy fluxes, which are present in supernovae, affect this structure. We observed a reduction in Rayleigh–Taylor growth. In analyzing the comparison with supernova SN1993J, a Type II supernova, we found that the energy fluxes produced by heat conduction appear to be larger thanmore » the radiative energy fluxes, and large enough to have dramatic consequences. No reported astrophysical simulations have included radiation and heat conduction self-consistently in modeling supernova remnants and these dynamics should be noted in the understanding of young supernova remnants.« less

How high energy fluxes may affect Rayleigh–Taylor instability growth in young supernova remnants

DOE PAGES

Kuranz, Carolyn C.; Park, Hye -Sook; Huntington, Channing M.; ...

2018-04-19

Here, energy-transport effects can alter the structure that develops as a supernova evolves into a supernova remnant. The Rayleigh–Taylor instability is thought to produce structure at the interface between the stellar ejecta and the circumstellar matter, based on simple models and hydrodynamic simulations. Here we report experimental results from the National Ignition Facility to explore how large energy fluxes, which are present in supernovae, affect this structure. We observed a reduction in Rayleigh–Taylor growth. In analyzing the comparison with supernova SN1993J, a Type II supernova, we found that the energy fluxes produced by heat conduction appear to be larger thanmore » the radiative energy fluxes, and large enough to have dramatic consequences. No reported astrophysical simulations have included radiation and heat conduction self-consistently in modeling supernova remnants and these dynamics should be noted in the understanding of young supernova remnants.« less

Over-limiting Current and Control of Dendritic Growth by Surface Conduction in Nanopores

PubMed Central

Han, Ji-Hyung; Khoo, Edwin; Bai, Peng; Bazant, Martin Z.

2014-01-01

Understanding over-limiting current (faster than diffusion) is a long-standing challenge in electrochemistry with applications in desalination and energy storage. Known mechanisms involve either chemical or hydrodynamic instabilities in unconfined electrolytes. Here, it is shown that over-limiting current can be sustained by surface conduction in nanopores, without any such instabilities, and used to control dendritic growth during electrodeposition. Copper electrodeposits are grown in anodized aluminum oxide membranes with polyelectrolyte coatings to modify the surface charge. At low currents, uniform electroplating occurs, unaffected by surface modification due to thin electric double layers, but the morphology changes dramatically above the limiting current. With negative surface charge, growth is enhanced along the nanopore surfaces, forming surface dendrites and nanotubes behind a deionization shock. With positive surface charge, dendrites avoid the surfaces and are either guided along the nanopore centers or blocked from penetrating the membrane. PMID:25394685

Buckling instability in amorphous carbon films

NASA Astrophysics Data System (ADS)

Zhu, X. D.; Narumi, K.; Naramoto, H.

2007-06-01

In this paper, we report the buckling instability in amorphous carbon films on mirror-polished sapphire (0001) wafers deposited by ion beam assisted deposition at various growth temperatures. For the films deposited at 150 °C, many interesting stress relief patterns are found, which include networks, blisters, sinusoidal patterns with π-shape, and highly ordered sinusoidal waves on a large scale. Starting at irregular buckling in the centre, the latter propagate towards the outer buckling region. The maximum length of these ordered patterns reaches 396 µm with a height of ~500 nm and a wavelength of ~8.2 µm. However, the length decreases dramatically to 70 µm as the deposition temperature is increased to 550 °C. The delamination of the film appears instead of sinusoidal waves with a further increase of the deposition temperature. This experimental observation is correlated with the theoretic work of Crosby (1999 Phys. Rev. E 59 R2542).

Recent developments on SU UMa stars - theory vs. observation

NASA Astrophysics Data System (ADS)

Cannizzo, John K.

2015-01-01

Kepler light curves of short period dwarf novae have resparked interest in the nature of superoutbursts and led to the question: Is the thermal-tidal instability needed, or can the plain vanilla version of the accretion disk limit cycle do the job all by itself? A detailed time-resolved study of an eclipsing SU UMa system during superoutburst onset should settle the question - if there is a dramatic contraction of the disk at superoutburst onset, Osaki's thermal-tidal model would be preferred; if not, the plain disk instability model would be sufficient. I will present recent results that support the contention by Osaki & Kato that the time varying negative superhump frequencies can be taken as a surrogate for the outer disk radius variations. Finally, it may be necessaryto look beyond the short period dwarf novae to gain perspective on the nature of embedded precursors in long outbursts.

The Goertler vortex instability mechanism in three-dimensional boundary layers

NASA Technical Reports Server (NTRS)

Hall, P.

1984-01-01

The two dimensional boundary layer on a concave wall is centrifugally unstable with respect to vortices aligned with the basic flow for sufficiently high values of the Goertler number. However, in most situations of practical interest the basic flow is three dimensional and previous theoretical investigations do not apply. The linear stability of the flow over an infinitely long swept wall of variable curvature is considered. If there is no pressure gradient in the boundary layer the instability problem can always be related to an equivalent two dimensional calculation. However, in general, this is not the case and even for small values of the crossflow velocity field dramatic differences between the two and three dimensional problems emerge. When the size of the crossflow is further increased, the vortices in the neutral location have their axes locally perpendicular to the vortex lines of the basic flow.

Spin noise amplification and giant noise in optical microcavity

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

Ryzhov, I. I.; Poltavtsev, S. V.; Kozlov, G. G.

2015-06-14

When studying the spin-noise-induced fluctuations of Kerr rotation in a quantum-well microcavity, we have found a dramatic increase of the noise signal (by more than two orders of magnitude) in the vicinity of anti-crossing of the polariton branches. The effect is explained by nonlinear optical instability of the microcavity giving rise to the light-power-controlled amplification of the polarization noise signal. In the framework of the developed model of built-in amplifier, we also interpret the nontrivial spectral and intensity-related properties of the observed noise signal below the region of anti-crossing of polariton branches. The discovered effect of optically controllable amplification ofmore » broadband polarization signals in microcavities in the regime of optical instability may be of interest for detecting weak oscillations of optical anisotropy in fundamental research and for other applications in optical information processing.« less

Aurora B Interaction of Centrosomal Nlp Regulates Cytokinesis*

PubMed Central

Yan, Jie; Jin, Shunqian; Li, Jia; Zhan, Qimin

2010-01-01

Cytokinesis is a fundamental cellular process, which ensures equal abscission and fosters diploid progenies. Aberrant cytokinesis may result in genomic instability and cell transformation. However, the underlying regulatory machinery of cytokinesis is largely undefined. Here, we demonstrate that Nlp (Ninein-like protein), a recently identified BRCA1-associated centrosomal protein that is required for centrosomes maturation at interphase and spindle formation in mitosis, also contributes to the accomplishment of cytokinesis. Through immunofluorescent analysis, Nlp is found to localize at midbody during cytokinesis. Depletion of endogenous Nlp triggers aborted division and subsequently leads to multinucleated phenotypes. Nlp can be recruited by Aurora B to the midbody apparatus via their physical association at the late stage of mitosis. Disruption of their interaction induces aborted cytokinesis. Importantly, Nlp is characterized as a novel substrate of Aurora B and can be phosphorylated by Aurora B. The specific phosphorylation sites are mapped at Ser-185, Ser-448, and Ser-585. The phosphorylation at Ser-448 and Ser-585 is likely required for Nlp association with Aurora B and localization at midbody. Meanwhile, the phosphorylation at Ser-185 is vital to Nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability. Collectively, these observations demonstrate that regulation of Nlp by Aurora B is critical for the completion of cytokinesis, providing novel insights into understanding the machinery of cell cycle progression. PMID:20864540

Aurora B interaction of centrosomal Nlp regulates cytokinesis.

PubMed

Yan, Jie; Jin, Shunqian; Li, Jia; Zhan, Qimin

2010-12-17

Cytokinesis is a fundamental cellular process, which ensures equal abscission and fosters diploid progenies. Aberrant cytokinesis may result in genomic instability and cell transformation. However, the underlying regulatory machinery of cytokinesis is largely undefined. Here, we demonstrate that Nlp (Ninein-like protein), a recently identified BRCA1-associated centrosomal protein that is required for centrosomes maturation at interphase and spindle formation in mitosis, also contributes to the accomplishment of cytokinesis. Through immunofluorescent analysis, Nlp is found to localize at midbody during cytokinesis. Depletion of endogenous Nlp triggers aborted division and subsequently leads to multinucleated phenotypes. Nlp can be recruited by Aurora B to the midbody apparatus via their physical association at the late stage of mitosis. Disruption of their interaction induces aborted cytokinesis. Importantly, Nlp is characterized as a novel substrate of Aurora B and can be phosphorylated by Aurora B. The specific phosphorylation sites are mapped at Ser-185, Ser-448, and Ser-585. The phosphorylation at Ser-448 and Ser-585 is likely required for Nlp association with Aurora B and localization at midbody. Meanwhile, the phosphorylation at Ser-185 is vital to Nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability. Collectively, these observations demonstrate that regulation of Nlp by Aurora B is critical for the completion of cytokinesis, providing novel insights into understanding the machinery of cell cycle progression.

Perceived message sensation value and psychological reactance: a test of the dominant thought disruption hypothesis.

PubMed

Quick, Brian L

2013-01-01

The present study tests to see whether perceived message sensation value reduces psychological reactance within the context of anti-marijuana ads for television. After controlling for sensation seeking, biological sex, and marijuana use, the results indicate that message novelty is negatively associated with a freedom threat, whereas dramatic impact and emotional arousal were not associated with the antecedent to reactance. Results support the use of novel messages in future ads while at the same time offer an explanation to the challenges involved in creating effective anti-marijuana ads. Overall, the results provide partial support for the dominant thought disruption hypothesis and are discussed with an emphasis on the theoretical and practical implications for health communication researchers and practitioners.

MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.

PubMed

Tomé, Stéphanie; Manley, Kevin; Simard, Jodie P; Clark, Greg W; Slean, Meghan M; Swami, Meera; Shelbourne, Peggy F; Tillier, Elisabeth R M; Monckton, Darren G; Messer, Anne; Pearson, Christopher E

2013-01-01

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases.

MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice

PubMed Central

Simard, Jodie P.; Clark, Greg W.; Slean, Meghan M.; Swami, Meera; Shelbourne, Peggy F.; Tillier, Elisabeth R. M.; Monckton, Darren G.; Messer, Anne; Pearson, Christopher E.

2013-01-01

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases. PMID:23468640

Disruption of lysosome function promotes tumor growth and metastasis in Drosophila.

PubMed

Chi, Congwu; Zhu, Huanhu; Han, Min; Zhuang, Yuan; Wu, Xiaohui; Xu, Tian

2010-07-09

Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradation pathway components contribute to tumor development and progression. Loss-of-function mutations in the Class C vacuolar protein sorting (VPS) gene, deep orange (dor), dramatically promote tumor overgrowth and invasion of the Ras(V12) cells. Knocking down either of the two other components of the Class C VPS complex, carnation (car) and vps16A, also renders Ras(V12) cells capable for uncontrolled growth and metastatic behavior. Finally, chemical disruption of the lysosomal function by feeding animals with antimalarial drugs, chloroquine or monensin, leads to malignant tumor growth of the Ras(V12) cells. Taken together, our data provide evidence for a causative role of lysosome dysfunction in tumor growth and invasion and indicate that members of the Class C VPS complex behave as tumor suppressors.

Housing Mobility and Cognitive Development: Change in Verbal and Nonverbal Abilities

PubMed Central

Fowler, Patrick J.; McGrath, Lauren M.; Henry, David B.; Schoeny, Michael; Chavira, Dina; Taylor, Jeremy J.; Day, Orin

2015-01-01

This study investigates the influence of housing instability on verbal and nonverbal cognitive development among at-risk children and adolescents involved in the child welfare system. Frequent residential changes threaten child mental health, especially among low-income families. Little is known regarding disruptions to cognitive growth, specifically the impact on verbal and nonverbal abilities. The study tests whether developmental timing of housing mobility affects cognitive development beyond individual and family risks. A nationally representative study of families (n = 2,442) susceptible to housing and family instability tracked children and adolescents aged four to 14 years (M = 8.95 years) over 36 months following investigation by the child welfare system. Youth completed standardized cognitive assessments while caregivers reported on behavior problems and family risk at three time points. Latent growth models examined change in cognitive abilities over time. Housing mobility in the 12 months prior to baseline predicts lower verbal cognitive abilities that improve marginally. Similar effects emerge for all age groups; however, frequent moves in infancy diminish the influence of subsequent housing mobility on verbal tasks. Housing instability threatened cognitive development beyond child maltreatment, family changes, poverty, and other risks. Findings inform emerging research on environmental influences on neurocognitive development, as well as identify targets for early intervention. Systematic assessment of family housing problems, including through the child welfare system, provides opportunities for coordinated responses to prevent instability and cognitive threats. PMID:26184055

Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder.

PubMed

Zhu, Shanshan; Cordner, Zachary A; Xiong, Jiali; Chiu, Chi-Tso; Artola, Arabiye; Zuo, Yanning; Nelson, Andrew D; Kim, Tae-Yeon; Zaika, Natalya; Woolums, Brian M; Hess, Evan J; Wang, Xiaofang; Chuang, De-Maw; Pletnikov, Mikhail M; Jenkins, Paul M; Tamashiro, Kellie L; Ross, Christopher A

2017-09-26

Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition. Expression of c-fos was increased in cortical pyramidal neurons, consistent with increased neuronal activity due to disinhibition. The mice showed robust behavioral phenotypes reminiscent of aspects of human mania, ameliorated by antimania drugs lithium and valproate. Repeated social defeat stress resulted in repeated episodes of dramatic behavioral changes from hyperactivity to "depression-like" behavior, suggestive of some aspects of human bipolar disorder. Overall, we suggest that this Ank-G cKO mouse model recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. The model may be useful for studying disease pathophysiology and for developing experimental therapeutics.

Gunshot wounds to the spine in adolescents.

PubMed

Aryan, Henry E; Amar, Arun P; Ozgur, Burak M; Levy, Michael L

2005-10-01

The incidence of spinal instability after penetrating gunshot wounds to the spine in adolescents is unknown. We describe our experience over a 15-year period. Hospital records were reviewed retrospectively. After injury and emergency care, patients were transferred to a rehabilitation facility. Examinations were completed using the American Spinal Injury Association and Frankel scales on admission, discharge, and 6 and 12 months after injury. Severity of injury was described by: 1) degree of neurological damage, 2) degree of preserved neurological function, and 3) presence of instability. Sixty patients were identified with a mean age 15.6 years (+/- 2.7 yr). Twelve patients had cervical, 31 thoracic, and 17 lumbosacral injuries. No operative treatments were used in their care. Thirty-four patients had complete neurological deficits. Mean acute hospitalization was 21.1 days (+/- 22.8 d), and mean rehabilitation stay was 86.3 days (+/- 48.9 d), for a total hospitalization of 107.4 days (+/- 65.9 d). At 1 year, 19 patients were ambulatory and 53 were autonomous. Despite the presence of bony involvement in all, no evidence of spinal instability was noted on follow-up dynamic imaging. Even in two patients with apparent two-column disruption, no instability was noted. At 1-year follow-up, significant (nonfunctional) improvement was noted in the neurological examination (P < 0.0001). Improvements were most notable in those patients with cervical injuries, followed by thoracic and lumbar injuries. After penetrating gunshot wounds to the spine, patients at 1-year follow-up examinations have evidence of significant, but nonfunctional, improvement. No evidence of spinal instability was noted in this study, and no surgical intervention was required.

Toxins in Botanical Dietary Supplements: Blue Cohosh Components Disrupt Cellular Respiration and Mitochondrial Membrane Potential

PubMed Central

Datta, Sandipan; Mahdi, Fakhri; Ali, Zulfiqar; Jekabsons, Mika B.; Khan, Ikhlas A.; Nagle, Dale G.; Zhou, Yu-Dong

2014-01-01

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA “Black Box” warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3) exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage. PMID:24328138

Mood Fluctuation and Psychobiological Instability: The Same Core Functions Are Disrupted by Novel Psychoactive Substances and Established Recreational Drugs

PubMed Central

Parrott, Andrew C.

2018-01-01

Many novel psychoactive substances (NPS) have entered the recreational drug scene in recent years, yet the problems they cause are similar to those found with established drugs. This article will debate the psychobiological effects of these newer and more traditional substances. It will show how they disrupt the same core psychobiological functions, so damaging well-being in similar ways. Every psychoactive drug causes mood states to fluctuate. Users feel better on-drug, then feel worse off-drug. The strength of these mood fluctuations is closely related to their addiction potential. Cyclical changes can occur with many other core psychobiological functions, such as information processing and psychomotor speed. Hence the list of drug-related impairments can include: homeostatic imbalance, HPA axis disruption, increased stress, altered sleep patterns, neurohormonal changes, modified brain rhythms, neurocognitive impairments, and greater psychiatric vulnerability. Similar patterns of deficit are found with older drugs such as cocaine, nicotine and cannabis, and newer substances such as 3,4-methylenedioxymethamphetamine (MDMA), mephedrone and spice. All psychoactive drugs damage human well-being through similar basic neuropsychobiological mechanisms. PMID:29533974

Tokamak magneto-hydrodynamics and reference magnetic coordinates for simulations of plasma disruptions

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

Zakharov, Leonid E.; Li, Xujing

This paper formulates the Tokamak Magneto-Hydrodynamics (TMHD), initially outlined by X. Li and L. E. Zakharov [Plasma Science and Technology 17(2), 97–104 (2015)] for proper simulations of macroscopic plasma dynamics. The simplest set of magneto-hydrodynamics equations, sufficient for disruption modeling and extendable to more refined physics, is explained in detail. First, the TMHD introduces to 3-D simulations the Reference Magnetic Coordinates (RMC), which are aligned with the magnetic field in the best possible way. The numerical implementation of RMC is adaptive grids. Being consistent with the high anisotropy of the tokamak plasma, RMC allow simulations at realistic, very high plasmamore » electric conductivity. Second, the TMHD splits the equation of motion into an equilibrium equation and the plasma advancing equation. This resolves the 4 decade old problem of Courant limitations of the time step in existing, plasma inertia driven numerical codes. The splitting allows disruption simulations on a relatively slow time scale in comparison with the fast time of ideal MHD instabilities. A new, efficient numerical scheme is proposed for TMHD.« less

A Failure to Communicate

PubMed Central

Kronert, William A.; Melkani, Girish C.; Melkani, Anju; Bernstein, Sanford I.

2015-01-01

Our molecular modeling studies suggest a charge-dependent interaction between residues Glu-497 in the relay domain and Arg-712 in the converter domain of human β-cardiac myosin. To test the significance of this putative interaction, we generated transgenic Drosophila expressing indirect flight muscle myosin with charge reversal mutations in the relay (E496R) or converter (R713E). Each mutation yielded dramatic reductions in myosin Ca-ATPase activity (∼80%) as well as in basal (∼67%) and actin-activated (∼84%) Mg-ATPase activity. E496R myosin-induced in vitro actin-sliding velocity was reduced by 71% and R713E myosin permitted no actin motility. Indirect flight muscles of late pupae from each mutant displayed disrupted myofibril assembly, with adults having severely abnormal myofibrils and no flight ability. To understand the molecular basis of these defects, we constructed a putative compensatory mutant that expresses myosin with both E496R and R713E. Intriguingly, ATPase values were restored to ∼73% of wild-type and actin-sliding velocity increased to 40%. The double mutation suppresses myofibril assembly defects in pupal indirect flight muscles and dramatically reduces myofibril disruption in young adults. Although sarcomere organization is not sustained in older flies and flight ability is not restored in homozygotes, young heterozygotes fly well. Our results indicate that this charge-dependent interaction between the myosin relay and converter domains is essential to the mechanochemical cycle and sarcomere assembly. Furthermore, the same inter-domain interaction is disrupted when modeling human β-cardiac myosin heavy chain cardiomyopathy mutations E497D or R712L, implying that abolishing this salt bridge is one cause of the human disease. PMID:26446785

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

Bardóczi, L.; Rhodes, T. L.; Carter, T. A.

We report the first observation of localized modulation of turbulent density uctuations en (via Beam Emission Spectroscopy) by neoclassical tearing modes (NTMs) in the core of the DIII-D tokamak. NTMs are important as they often lead to severe degradation of plasma confinement and disruptions in high-confinement fusion experiments. Magnetic islands associated with NTMs significantly modify the profiles and turbulence drives. In this experiment n was found to be modulated by 14% across the island. Gyrokinetic simulations suggest that en could be dominantly driven by the ion temperature gradient (ITG) instability.

CEP152 is a genome maintenance protein disrupted in Seckel syndrome

PubMed Central

Kalay, Ersan; Yigit, Gökhan; Aslan, Yakup; Brown, Karen E; Pohl, Esther; Bicknell, Louise S; Kayserili, Hülya; Li, Yun; Tüysüz, Beyhan; Nürnberg, Gudrun; Kiess, Wieland; Koegl, Manfred; Baessmann, Ingelore; Buruk, Kurtulus; Toraman, Bayram; Kayipmaz, Saadettin; Kul, Sibel; Ikbal, Mevlit; Turner, Daniel J; Taylor, Martin S; Aerts, Jan; Scott, Carol; Milstein, Karen; Dollfus, Helene; Wieczorek, Dagmar; Brunner, Han G; Hurles, Matthew; Jackson, Andrew P; Rauch, Anita; Nürnberg, Peter; Karagüzel, Ahmet; Wollnik, Bernd

2012-01-01

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation. PMID:21131973

Convective cell generation by kinetic Alfven wave turbulence in the auroral ionosphere

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

Zhao, J. S.; Wu, D. J.; Yu, M. Y.

2012-06-15

Modulation of convective cells by kinetic Alfven wave (KAW) turbulence is investigated. The interaction is governed by a nonlinear dispersion relation for the convective cells. It is shown that KAW turbulence is disrupted by excitation of the large-scale convective motion through a resonant instability. Application of the results to the auroral ionosphere shows that cross-scale coupling of the KAW turbulence and convective cells plays an important role in the evolution of ionospheric plasma turbulence.

The dynamic instability in the hook/flagellum system that triggers bacterial flicks

NASA Astrophysics Data System (ADS)

Jabbarzadeh, Mehdi; Fu, Henry

2017-11-01

Dynamical bending, buckling, and polymorphic transformations of the flagellum are known to affect bacterial motility, but run-reverse-flick motility of monotrichous bacteria also involves the even more flexible hook, which connects the flagellum to the cell body. Here, we identify the dynamic buckling mechanism that produces flicks in Vibrio alginolyticus. Estimates of forces and torques on the hook from experimental observations suggest that flicks are triggered at stresses below the hook's static Euler buckling criterion. Using an accurate linearization of the Kirchoff rod model for the hook in a model of a swimming bacterium with rigid flagellum, we show that as hook stiffness decreases there is a transition from on-axis flagellar rotation with small hook deflections to flagellar precession with large deflections. When flagellum flexibility is incorporated, the precession is disrupted by significant flagellar bending - i.e., incipient flicks. The predicted onset of dynamic instabilities corresponds well with experimentally observed flick events.

Simulation of plasma double-layer structures

NASA Technical Reports Server (NTRS)

Borovsky, J. E.; Joyce, G.

1982-01-01

Electrostatic plasma double layers are numerically simulated by means of a magnetized 2 1/2 dimensional particle in cell method. The investigation of planar double layers indicates that these one dimensional potential structures are susceptible to periodic disruption by instabilities in the low potential plasmas. Only a slight increase in the double layer thickness with an increase in its obliqueness to the magnetic field is observed. Weak magnetization results in the double layer electric field alignment of accelerated particles and strong magnetization results in their magnetic field alignment. The numerical simulations of spatially periodic two dimensional double layers also exhibit cyclical instability. A morphological invariance in two dimensional double layers with respect to the degree of magnetization implies that the potential structures scale with Debye lengths rather than with gyroradii. Electron beam excited electrostatic electron cyclotron waves and (ion beam driven) solitary waves are present in the plasmas adjacent to the double layers.

The evolution of a localized nonlinear wave of the Kelvin-Helmholtz instability with gravity

NASA Astrophysics Data System (ADS)

Orazzo, Annagrazia; Hoepffner, Jérôme

2012-11-01

At the interface between two fluids of different density and in the presence of gravity, there are well known periodic surface waves which can propagate for long distances with little attenuation, as it is for instance the case at the surface of the sea. If wind is present, these waves progressively accumulate energy as they propagate and grow to large sizes—this is the Kelvin-Helmholtz instability. On the other hand, we show in this paper that for a given wind strength, there is potential for the growth of a localized nonlinear wave. This wave can reach a size such that the hydrostatic pressure drop from top to bottom equals the stagnation pressure of the wind. This process for the disruption of the flat interface is localized and nonlinear. We study the properties of this wave using numerical simulations of the Navier-Stokes equations.

Trophic network models explain instability of Early Triassic terrestrial communities

PubMed Central

Roopnarine, Peter D; Angielczyk, Kenneth D; Wang, Steve C; Hertog, Rachel

2007-01-01

Studies of the end-Permian mass extinction have emphasized potential abiotic causes and their direct biotic effects. Less attention has been devoted to secondary extinctions resulting from ecological crises and the effect of community structure on such extinctions. Here we use a trophic network model that combines topological and dynamic approaches to simulate disruptions of primary productivity in palaeocommunities. We apply the model to Permian and Triassic communities of the Karoo Basin, South Africa, and show that while Permian communities bear no evidence of being especially susceptible to extinction, Early Triassic communities appear to have been inherently less stable. Much of the instability results from the faster post-extinction diversification of amphibian guilds relative to amniotes. The resulting communities differed fundamentally in structure from their Permian predecessors. Additionally, our results imply that changing community structures over time may explain long-term trends like declining rates of Phanerozoic background extinction PMID:17609191

A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

PubMed Central

Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

2014-01-01

SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

A computational model of motor neuron degeneration.

PubMed

Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

2014-08-20

To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. Copyright © 2014 Elsevier Inc. All rights reserved.

Pattern Formation in Complex Fluids

NASA Astrophysics Data System (ADS)

Shelley, Michael

2000-03-01

Classical fluid instabilities -- such as the Saffman-Taylor instability in a Hele-Shaw cell -- are dramatically modified by using complex fluids. For example, polymeric liquids driven in a Hele-Shaw cell yield "dendritic" patterns with an apparent directional anisotropy. The dynamics of complex liquids can also lead to new instabilities and patterns, such as space-filling patterns formed by successive bucklings of growing "elastica" seen in the phase transition of a liquid crystalline material. Understanding such problems requires an interplay between physical modeling, mathematical analysis, and sophisticated nonlinear simulation. For the first problem, I will discuss a non-Newtonian version of Darcy's law for Hele-Shaw flow. This yields a free-boundary problem for the pattern formation, and requires the solution of a nonlinear elliptic equation in a time-dependent domain. This is pushing the development of adaptive grid methods that represent the geometry accurately and efficiently. Our simulations yield insight into how shear-thinning, as is evinced by polymeric liquids, can produce patterns reminiscent of experiment, with "dendritic fingers", side-branching, and reduced tip-splitting. In the second problem, a long filament in a smectic-A phase grows within an isotropic fluid. The splay deformation of the material gives this filament an elastic response. The macroscopic model describes the dynamics of a growing, elastic filament immersed in a Stokesian fluid. The model marries filament elasticity and tensile forces with a numerically tractable nonlocal slender-body theory. Analysis shows that growth of the filament, despite fluid drag, produces a buckling instability. When coupled to a nonlocal hydrodynamic self-interaction, our fully nonlinear simulations show that such instabilities iterate along the filament, and give "space-filling" patterns.

Onset of magnetic reconnection in a weakly collisional, high- β plasma

NASA Astrophysics Data System (ADS)

Alt, Andrew; Kunz, Matthew

2017-10-01

In a magnetized, weakly collisional plasma, the magnetic moment of the constituent particles is an adiabatic invariant. An increase of the magnetic-field strength in such a plasma thus leads to an increase in the thermal pressure perpendicular to the field lines. Above a β-dependent threshold, this pressure anisotropy drives the mirror instability, which produces strong distortions in the field lines and traps particles on ion-Larmor scales. The impact of this instability on magnetic reconnection is investigated using simple analytical and numerical models for the formation of a current sheet and the associated production of pressure anisotropy. The difficulty in maintaining an isotropic, Maxwellian particle distribution during the formation and subsequent thinning of a current sheet in a weakly collisional plasma, coupled with the low threshold for the mirror instability in a high- β plasma, imply that the topology of reconnecting magnetic fields can radically differ from the standard Harris-sheet profile often used in kinetic simulations of collisionless reconnection. Depending on the rate of current-sheet formation, this mirror-induced disruption may occur before standard tearing modes are able to develop. This work was supported by U.S. DOE contract DE-AC02-09CH11466.

Interactive HIV-1 Tat and morphine-induced synaptodendritic injury is triggered through focal disruptions in Na⁺ influx, mitochondrial instability, and Ca²⁺ overload.

PubMed

Fitting, Sylvia; Knapp, Pamela E; Zou, Shiping; Marks, William D; Bowers, M Scott; Akbarali, Hamid I; Hauser, Kurt F

2014-09-17

Synaptodendritic injury is thought to underlie HIV-associated neurocognitive disorders and contributes to exaggerated inflammation and cognitive impairment seen in opioid abusers with HIV-1. To examine events triggering combined transactivator of transcription (Tat)- and morphine-induced synaptodendritic injury systematically, striatal neuron imaging studies were conducted in vitro. These studies demonstrated nearly identical pathologic increases in dendritic varicosities as seen in Tat transgenic mice in vivo. Tat caused significant focal increases in intracellular sodium ([Na(+)]i) and calcium ([Ca(2+)]i) in dendrites that were accompanied by the emergence of dendritic varicosities. These effects were largely, but not entirely, attenuated by the NMDA and AMPA receptor antagonists MK-801 and CNQX, respectively. Concurrent morphine treatment accelerated Tat-induced focal varicosities, which were accompanied by localized increases in [Ca(2+)]i and exaggerated instability in mitochondrial inner membrane potential. Importantly, morphine's effects were prevented by the μ-opioid receptor antagonist CTAP and were not observed in neurons cultured from μ-opioid receptor knock-out mice. Combined Tat- and morphine-induced initial losses in ion homeostasis and increases in [Ca(2+)]i were attenuated by the ryanodine receptor inhibitor ryanodine, as well as pyruvate. In summary, Tat induced increases in [Na(+)]i, mitochondrial instability, excessive Ca(2+) influx through glutamatergic receptors, and swelling along dendrites. Morphine, acting via μ-opioid receptors, exacerbates these excitotoxic Tat effects at the same subcellular locations by mobilizing additional [Ca(2+)]i and by further disrupting [Ca(2+)]i homeostasis. We hypothesize that the spatiotemporal relationship of μ-opioid and aberrant AMPA/NMDA glutamate receptor signaling is critical in defining the location and degree to which opiates exacerbate the synaptodendritic injury commonly observed in neuroAIDS. Copyright © 2014 the authors 0270-6474/14/3412850-15$15.00/0.

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease.

PubMed

Dunn, Amy R; Stout, Kristen A; Ozawa, Minagi; Lohr, Kelly M; Hoffman, Carlie A; Bernstein, Alison I; Li, Yingjie; Wang, Minzheng; Sgobio, Carmelo; Sastry, Namratha; Cai, Huaibin; Caudle, W Michael; Miller, Gary W

2017-03-14

Members of the synaptic vesicle glycoprotein 2 (SV2) family of proteins are involved in synaptic function throughout the brain. The ubiquitously expressed SV2A has been widely implicated in epilepsy, although SV2C with its restricted basal ganglia distribution is poorly characterized. SV2C is emerging as a potentially relevant protein in Parkinson disease (PD), because it is a genetic modifier of sensitivity to l-DOPA and of nicotine neuroprotection in PD. Here we identify SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of PD. Genetic deletion of SV2C leads to reduced dopamine release in the dorsal striatum as measured by fast-scan cyclic voltammetry, reduced striatal dopamine content, disrupted α-synuclein expression, deficits in motor function, and alterations in neurochemical effects of nicotine. Furthermore, SV2C expression is dramatically altered in postmortem brain tissue from PD cases but not in Alzheimer disease, progressive supranuclear palsy, or multiple system atrophy. This disruption was paralleled in mice overexpressing mutated α-synuclein. These data establish SV2C as a mediator of dopamine neuron function and suggest that SV2C disruption is a unique feature of PD that likely contributes to dopaminergic dysfunction.

Modeling, Modal Properties, and Mesh Stiffness Variation Instabilities of Planetary Gears

NASA Technical Reports Server (NTRS)

Parker, Robert G.; Lin, Jian; Krantz, Timothy L. (Technical Monitor)

2001-01-01

Planetary gear noise and vibration are primary concerns in their applications in helicopters, automobiles, aircraft engines, heavy machinery and marine vehicles. Dynamic analysis is essential to the noise and vibration reduction. This work analytically investigates some critical issues and advances the understanding of planetary gear dynamics. A lumped-parameter model is built for the dynamic analysis of general planetary gears. The unique properties of the natural frequency spectra and vibration modes are rigorously characterized. These special structures apply for general planetary gears with cyclic symmetry and, in practically important case, systems with diametrically opposed planets. The special vibration properties are useful for subsequent research. Taking advantage of the derived modal properties, the natural frequency and vibration mode sensitivities to design parameters are investigated. The key parameters include mesh stiffnesses, support/bearing stiffnesses, component masses, moments of inertia, and operating speed. The eigen-sensitivities are expressed in simple, closed-form formulae associated with modal strain and kinetic energies. As disorders (e.g., mesh stiffness variation. manufacturing and assembling errors) disturb the cyclic symmetry of planetary gears, their effects on the free vibration properties are quantitatively examined. Well-defined veering rules are derived to identify dramatic changes of natural frequencies and vibration modes under parameter variations. The knowledge of free vibration properties, eigen-sensitivities, and veering rules provide important information to effectively tune the natural frequencies and optimize structural design to minimize noise and vibration. Parametric instabilities excited by mesh stiffness variations are analytically studied for multi-mesh gear systems. The discrepancies of previous studies on parametric instability of two-stage gear chains are clarified using perturbation and numerical methods. The operating conditions causing parametric instabilities are expressed in closed-form suitable for design guidance. Using the well-defined modal properties of planetary gears, the effects of mesh parameters on parametric instability are analytically identified. Simple formulae are obtained to suppress particular instabilities by adjusting contact ratios and mesh phasing.

Climate change and ecosystem disruption: the health impacts of the North American Rocky Mountain pine beetle infestation.

PubMed

Embrey, Sally; Remais, Justin V; Hess, Jeremy

2012-05-01

In the United States and Canada, pine forest ecosystems are being dramatically affected by an unprecedented pine beetle infestation attributed to climate change. Both decreased frequency of extremely cold days and warmer winter temperature averages have led to an enphytotic devastating millions of acres of pine forest. The associated ecosystem disruption has the potential to cause significant health impacts from a range of exposures, including increased runoff and water turbidity, forest fires, and loss of ecosystem services. We review direct and indirect health impacts and possible prevention strategies. The pine beetle infestation highlights the need for public health to adopt an ecological, systems-oriented view to anticipate the full range of potential health impacts from climate change and facilitate effective planned adaptation.

Climate Change and Ecosystem Disruption: The Health Impacts of the North American Rocky Mountain Pine Beetle Infestation

PubMed Central

Remais, Justin V.; Hess, Jeremy

2012-01-01

In the United States and Canada, pine forest ecosystems are being dramatically affected by an unprecedented pine beetle infestation attributed to climate change. Both decreased frequency of extremely cold days and warmer winter temperature averages have led to an enphytotic devastating millions of acres of pine forest. The associated ecosystem disruption has the potential to cause significant health impacts from a range of exposures, including increased runoff and water turbidity, forest fires, and loss of ecosystem services. We review direct and indirect health impacts and possible prevention strategies. The pine beetle infestation highlights the need for public health to adopt an ecological, systems-oriented view to anticipate the full range of potential health impacts from climate change and facilitate effective planned adaptation. PMID:22420788

MHD Effects of a Ferritic Wall on Tokamak Plasmas

NASA Astrophysics Data System (ADS)

Hughes, Paul E.

It has been recognized for some time that the very high fluence of fast (14.1MeV) neutrons produced by deuterium-tritium fusion will represent a major materials challenge for the development of next-generation fusion energy projects such as a fusion component test facility and demonstration fusion power reactor. The best-understood and most promising solutions presently available are a family of low-activation steels originally developed for use in fission reactors, but the ferromagnetic properties of these steels represent a danger to plasma confinement through enhancement of magnetohydrodynamic instabilities and increased susceptibility to error fields. At present, experimental research into the effects of ferromagnetic materials on MHD stability in toroidal geometry has been confined to demonstrating that it is still possible to operate an advanced tokamak in the presence of ferromagnetic components. In order to better quantify the effects of ferromagnetic materials on tokamak plasma stability, a new ferritic wall has been installated in the High Beta Tokamak---Extended Pulse (HBT-EP) device. The development, assembly, installation, and testing of this wall as a modular upgrade is described, and the effect of the wall on machine performance is characterized. Comparative studies of plasma dynamics with the ferritic wall close-fitting against similar plasmas with the ferritic wall retracted demonstrate substantial effects on plasma stability. Resonant magnetic perturbations (RMPs) are applied, demonstrating a 50% increase in n = 1 plasma response amplitude when the ferritic wall is near the plasma. Susceptibility of plasmas to disruption events increases by a factor of 2 or more with the ferritic wall inserted, as disruptions are observed earlier with greater frequency. Growth rates of external kink instabilities are observed to be twice as large in the presence of a close-fitting ferritic wall. Initial studies are made of the influence of mode rotation frequency on the ferritic effect, as well as observations of the effect of the ferritic wall on disruption halo currents.

Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

PubMed

Granic, Antoneta; Potter, Huntington

2013-01-01

Elevated low-density lipoprotein (LDL)-cholesterol is a risk factor for both Alzheimer's disease (AD) and Atherosclerosis (CVD), suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß) inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1) high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2) Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3) oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4) LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5) cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6) ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol consumption reduces the risk of developing atherosclerosis or AD. These results suggest a novel, cell cycle mechanism by which aberrant cholesterol homeostasis promotes neurodegeneration and atherosclerosis by disrupting chromosome segregation and potentially other aspects of microtubule physiology.

Mitotic Spindle Defects and Chromosome Mis-Segregation Induced by LDL/Cholesterol—Implications for Niemann-Pick C1, Alzheimer’s Disease, and Atherosclerosis

PubMed Central

Granic, Antoneta; Potter, Huntington

2013-01-01

Elevated low-density lipoprotein (LDL)-cholesterol is a risk factor for both Alzheimer’s disease (AD) and Atherosclerosis (CVD), suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy–in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß) inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1) high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis’ first prediction, 2) Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3) oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4) LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5) cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6) ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol’s aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol consumption reduces the risk of developing atherosclerosis or AD. These results suggest a novel, cell cycle mechanism by which aberrant cholesterol homeostasis promotes neurodegeneration and atherosclerosis by disrupting chromosome segregation and potentially other aspects of microtubule physiology. PMID:23593294

Toward a unified model of substorms

NASA Astrophysics Data System (ADS)

Machida, S.; Fukui, K.; Miyashita, Y.; Ieda, A.

2017-12-01

Numerous models of substorms have been proposed so far, and they are roughly divided into two categories, i.e., the outside-in category that is represented by the near-Earth neutral line (NENL) model and the inside-out category represented by the current disruption model or the ballooning instability model. Controversies have been raised for many years over the validity of those models. However, in recent years we have obtained important clues to solve this long-standing issue by analyzing THEMIS probe data for substorms and pseudo-substorms separately. [Fukui et al., 2017] The key is the plasma pressure in the equatorial region, and it was about 1.3 times higher in substorms, than the pseudo-substorm in the region between X -7 and -8 Re. However, no difference was found beyond X -10 Re. Therefore, the spatial gradient of the plasma pressure in the region of X -7.5 Re must be a necessary condition for the occurrence of substorm. Abrupt earthward flows originated from the catapult current sheet relaxation and subsequent magnetic reconnection at the NENL just prior to the onset is a common signature for both substorm and pseudo-substorm, which seems to be essentially a result of the tearing instability in the magnetotail. [Uchino and Machida, 2015] The subsequent earthward flows must initiate some instability, quite likely the ballooning instability around the flow braking region. Substorms do not occur only with the magnetic reconnection. If there is enough plasma pressure gradient, the system can develop into a substorm. Otherwise, it will end up with a pseudo-substorm. We emphasize that both NENL model and the ballooning instability model are partially correct but incomplete, and the true model of substorm can be constructed by synthesizing multiple models of substorm including at least these two models.

On the Mass and Luminosity Functions of Tidal Disruption Flares: Rate Suppression due to Black Hole Event Horizons

NASA Astrophysics Data System (ADS)

van Velzen, S.

2018-01-01

The tidal disruption of a star by a massive black hole is expected to yield a luminous flare of thermal emission. About two dozen of these stellar tidal disruption flares (TDFs) may have been detected in optical transient surveys. However, explaining the observed properties of these events within the tidal disruption paradigm is not yet possible. This theoretical ambiguity has led some authors to suggest that optical TDFs are due to a different process, such as a nuclear supernova or accretion disk instabilities. Here we present a test of a fundamental prediction of the tidal disruption event scenario: a suppression of the flare rate due to the direct capture of stars by the black hole. Using a recently compiled sample of candidate TDFs with black hole mass measurements, plus a careful treatment of selection effects in this flux-limited sample, we confirm that the dearth of observed TDFs from high-mass black holes is statistically significant. All the TDF impostor models we consider fail to explain the observed mass function; the only scenario that fits the data is a suppression of the rate due to direct captures. We find that this suppression can explain the low volumetric rate of the luminous TDF candidate ASASSN-15lh, thus supporting the hypothesis that this flare belongs to the TDF family. Our work is the first to present the optical TDF luminosity function. A steep power law is required to explain the observed rest-frame g-band luminosity, {dN}/{{dL}}g\\propto {L}g-2.5. The mean event rate of the flares in our sample is ≈ 1× {10}-4 galaxy‑1 yr‑1, consistent with the theoretically expected tidal disruption rate.

Clumps in the outer disk by disk instability: Why they are initially gas giants and the legacy of disruption

NASA Astrophysics Data System (ADS)

Boley, Aaron C.; Hayfield, Tristen; Mayer, Lucio; Durisen, Richard H.

2010-06-01

We explore the initial conditions for fragments in the extended regions (r≳50AU) of gravitationally unstable disks. We combine analytic estimates for the fragmentation of spiral arms with 3D SPH simulations to show that initial fragment masses are in the gas giant regime. These initial fragments will have substantial angular momentum, and should form disks with radii of a few AU. We show that clumps will survive for multiple orbits before they undergo a second, rapid collapse due to H 2 dissociation and that it is possible to destroy bound clumps by transporting them into the inner disk. The consequences of disrupted clumps for planet formation, dust processing, and disk evolution are discussed. We argue that it is possible to produce Earth-mass cores in the outer disk during the earliest phases of disk evolution.

Labral cuff refixation in the hip: rationale and operative technique for preserving the chondrolabral interface for labral repair: a case series

PubMed Central

Filan, David

2018-01-01

ABSTRACT Arthroscopic labral ‘takedown’ and refixation is utilized to permit adequate visualization and resection of the acetabular rim deformity, in patients with pincer or mixed femoroacetabular impingement. Deficiencies exist in present techniques, which include disruption of vital anatomical support and vascular structures to the labrum and chondrolabral junction, drill or anchor articular penetration risk, bunching, elevation and instability of the labrum. A new operative technique is described which preserves the important chondrolabral interface, accurately restoring the ‘flap seal’ of the acetabular labrum while minimizing vascular disruption and reducing the risk of drill and anchor penetration. A prospective series of 123 consecutive cases of pincer or mixed femoroacetabular impingement, treated with arthroscopic labral cuff refixation and preservation of the chondrolabral interface, is reported; operative technique and 2-year outcomes are presented. PMID:29423255

Structure and properties of composite films formed by cellulose nanocrystals and charged latex nanoparticles

NASA Astrophysics Data System (ADS)

Thérien-Aubin, Héloïse; Lukach, Ariella; Pitch, Natalie; Kumacheva, Eugenia

2015-04-01

We report the structural and optical properties of composite films formed from mixed suspensions of cellulose nanocrystals (CNCs) and fluorescent latex nanoparticles (NPs). We explored the effect of NP concentration, size, surface charge, glass transition temperature and film processing conditions on film structure and properties. The chiral nematic order, typical of CNC films, was preserved in films with up to 50 wt% of negatively-charged latex NPs. Composite films were characterized by macroscopically close-to-uniform fluorescence, birefringence, and circular dichroism properties. In contrast, addition of positively charged latex NPs led to gelation of CNC-latex suspensions and disruption of the chiral nematic order in the composite films. Large latex NPs disrupted the chiral nematic order to a larger extend than small NPs. Furthermore, the glass transition of latex NPs had a dramatic effect on the structure of CNC-latex films. Latex particles in the rubbery state were easily incorporated in the ordered CNC matrix and improved the structural integrity of its chiral nematic phase.We report the structural and optical properties of composite films formed from mixed suspensions of cellulose nanocrystals (CNCs) and fluorescent latex nanoparticles (NPs). We explored the effect of NP concentration, size, surface charge, glass transition temperature and film processing conditions on film structure and properties. The chiral nematic order, typical of CNC films, was preserved in films with up to 50 wt% of negatively-charged latex NPs. Composite films were characterized by macroscopically close-to-uniform fluorescence, birefringence, and circular dichroism properties. In contrast, addition of positively charged latex NPs led to gelation of CNC-latex suspensions and disruption of the chiral nematic order in the composite films. Large latex NPs disrupted the chiral nematic order to a larger extend than small NPs. Furthermore, the glass transition of latex NPs had a dramatic effect on the structure of CNC-latex films. Latex particles in the rubbery state were easily incorporated in the ordered CNC matrix and improved the structural integrity of its chiral nematic phase. Electronic supplementary information (ESI) available: Detailed latex synthesis. Additional characterization of the nanoparticles and films. See DOI: 10.1039/c5nr00660k

Convective Instability and Mass Transport of the Diffusion Layer in CO2 Sequestration

NASA Astrophysics Data System (ADS)

Backhaus, S.

2011-12-01

The long-term fate of supercritical (sc) CO2 in saline aquifers is critical to the security of carbon sequestration, an important option for eliminating or reducing the emissions of this most prevalent greenhouse gas. scCO2 is less dense than brine and floats to the top of the aquifer where it is trapped in a metastable state by a geologic feature such as a low permeability cap rock. Dissolution into the underlying brine creates a CO2-brine mixture that is denser than brine, eliminating buoyancy and removing the threat of CO2 escaping back to the atmosphere. If molecular diffusion were the only dissolution mechanism, the CO2 waste stream from a typical large coal-fired electrical power plant may take upward of 10,000 years to no longer pose a threat, however, a convective instability of the dense diffusion boundary layer between the scCO2 and the brine can dramatically increase the dissolution rates, shortening the lifetime of the scCO2 waste pool. We present results of 2D and 3D similitude-correct, laboratory-scale experiments using an analog fluid system. The experiments and flow visualization reveal the onset of the convective instability, the dynamics of the fluid flows during the convective processes, and the long-term mass transfer rates.

Mechanics modelling of fern cavitation catapult

NASA Astrophysics Data System (ADS)

Kang, Jingtian; Li, Kai; Tan, Huifeng; Wang, Changguo; Cai, Shengqiang

2017-12-01

Cavitation is often regarded as a failure mode in soft materials. An intriguing phenomenon has been recently discovered that fern sporangium can take advantage of drying-induced cavitation instability in annulus cells to disperse spores at an extraordinarily high acceleration. Briefly, the decrease of environmental humidity causes continuous bending of the sporangium and growth of cavities inside the annulus cells, with the elastic energy accumulated in sporangium walls. When the humidity is lower than a critical value, the cavities suddenly expand dramatically inside the cells, causing a quick release of the elastic energy stored in the annular structure. As a result, like a catapult, the sporangium snaps back and ejects the seeds at a high speed. Motivated by the observation, in this article, we study cavitation instability in a similar structure as the sporangium. To simplify the problem, in our model, the mechanics of cells in the sporangium are described by the polymer gel model, while the sporangium wall is modelled as a hyperelastic material. When the environmental humidity is lower than a critical value, through energetic analyses, we can predict the cavitation catapult phenomenon using the model. We hope that our study in this article can provide useful insights into the bio-inspired design of structures which can take advantage of cavitation instability in soft materials.

The local stability of the magnetized advection-dominated discs with the radial viscous force

NASA Astrophysics Data System (ADS)

Ghoreyshi, S. M.; Shadmehri, M.

2018-06-01

We study local stability of the advection-dominated optically thick (slim) and optically thin discs with purely toroidal magnetic field and the radial viscous force using a linear perturbation analysis. Our dispersion relation indicates that the presence of magnetic fields and radial viscous force cannot give rise to any new mode of the instability. We find, however, that growth rate of the thermal mode in the slim discs and that of the acoustic modes in the slim and optically thin discs are dramatically affected by the radial viscous force. This force tends to strongly decrease the growth rate of the outward-propagating acoustic mode (O-mode) in the short-wavelength limit, but it causes a slim disc to become thermally more unstable. This means that growth rate of the thermal mode increases in the presence of radial viscous force. This enhancement is more significant when the viscosity parameter is large. The growth rates of the thermal and acoustic modes depend on the magnetic field. Although the instability of O-mode for a stronger magnetic field case has a higher growth rate, the thermal mode of the slim discs can be suppressed when the magnetic field is strong. The inertial-acoustic instability of a magnetized disc may explain the quasi-periodic oscillations (QPOs) from the black holes.

Unstable Memories Create a High-Level Representation that Enables Learning Transfer.

PubMed

Mosha, Neechi; Robertson, Edwin M

2016-01-11

A memory is unstable, making it susceptible to interference and disruption, after its acquisition [1-4]. The function or possible benefit of a memory being unstable at its acquisition is not well understood. Potentially, instability may be critical for the communication between recently acquired memories, which would allow learning in one task to be transferred to the other subsequent task [1, 5]. Learning may be transferred between any memories that are unstable, even between different types of memory. Here, we test the link between a memory being unstable and the transfer of learning to a different type of memory task. We measured how learning in one task transferred to and thus improved learning in a subsequent task. There was transfer from a motor skill to a word list task and, vice versa, from a word list to a motor skill task. What was transferred was a high-level relationship between elements, rather than knowledge of the individual elements themselves. Memory instability was correlated with subsequent transfer, suggesting that transfer was related to the instability of the memory. Using different methods, we stabilized the initial memory, preventing it from being susceptible to interference, and found that these methods consistently prevented transfer to the subsequent memory task. This suggests that the transfer of learning across diverse tasks is due to a high-level representation that can only be formed when a memory is unstable. Our work has identified an important function of memory instability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Housing mobility and cognitive development: Change in verbal and nonverbal abilities.

PubMed

Fowler, Patrick J; McGrath, Lauren M; Henry, David B; Schoeny, Michael; Chavira, Dina; Taylor, Jeremy J; Day, Orin

2015-10-01

This study investigates the influence of housing instability on verbal and nonverbal cognitive development among at-risk children and adolescents involved in the child welfare system. Frequent residential changes threaten child mental health, especially among low-income families. Little is known regarding disruptions to cognitive growth, specifically the impact on verbal and nonverbal abilities. The study tests whether developmental timing of housing mobility affects cognitive development beyond individual and family risks. A nationally representative study of families (n=2,442) susceptible to housing and family instability tracked children and adolescents aged 4-14 years (M=8.95 years) over 36 months following investigation by the child welfare system. Youth completed standardized cognitive assessments while caregivers reported on behavior problems and family risk at three time points. Latent growth models examined change in cognitive abilities over time. Housing mobility in the 12 months prior to baseline predicts lower verbal cognitive abilities that improve marginally. Similar effects emerge for all age groups; however, frequent moves in infancy diminish the influence of subsequent housing mobility on verbal tasks. Housing instability threatened cognitive development beyond child maltreatment, family changes, poverty, and other risks. Findings inform emerging research on environmental influences on neurocognitive development, as well as identify targets for early intervention. Systematic assessment of family housing problems, including through the child welfare system, provides opportunities for coordinated responses to prevent instability and cognitive threats. Copyright © 2015 Elsevier Ltd. All rights reserved.

Family Structure, Maternal Dating, and Sexual Debut: Extending the Conceptualization of Instability.

PubMed

Zito, Rena Cornell; De Coster, Stacy

2016-05-01

Family structure influences the risk of early onset of sexual intercourse. This study proposes that the family structures associated with risk-single-mother, step-parent, and cohabiting-influence early sexual debut due to family instability, including shifts in family structure and maternal dating, which can undermine parental control and transmit messages about the acceptability of nonmarital sex. Previous research has not considered maternal dating as a component of family instability, assuming single mothers who date and those who do not date experience comparable levels of family disruption and transmit similar messages about the acceptability of nonmarital sex. Hypotheses are assessed using logistic regression models predicting the odds of early onset of sexual intercourse among 9959 respondents (53 % female, 47 % male) from the National Longitudinal Study of Adolescent to Adult Health. Respondents were ages 12-17 at the first wave of data collection and 18-26 at the third wave, when respondents reported the age at which they first had sexual intercourse. Results show that maternal dating is a source of family instability with repercussions for early sexual debut. Parental control and permissive attitudes towards teenage sex and pregnancy link at-risk family structures and maternal dating to early sexual initiation among females, though these variables do not fully explain family structure and maternal dating effects. Among males, the influence of maternal dating on early sexual debut is fully explained by the learning of permissive sexual attitudes.

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

PubMed Central

Hansen, R K; Bissell, M J

2010-01-01

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function. PMID:10903527

Changes in artistic style and behaviour in Parkinson's disease: dopamine and creativity.

PubMed

Kulisevsky, Jaime; Pagonabarraga, Javier; Martinez-Corral, Mercè

2009-05-01

We present a PD patient in whom dopamine agonists awoke a hidden creativity that led to a gradual increase in painting productivity evolving to a disruptive impulsive behaviour that shared many features with punding. A dramatic change in painting style related to a more emotional experience during the process of creation developed after treatment onset. This case suggests that changes in creativity in PD seem to be related to dopaminergic imbalance in the limbic system.

High flux femtosecond x-ray emission from the electron-hose instability in laser wakefield accelerators

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

Dong, C. F.; Zhao, T. Z.; Behm, K.

Here, bright and ultrashort duration x-ray pulses can be produced by through betatron oscillations of electrons during laser wakefield acceleration (LWFA). Our experimental measurements using the Hercules laser system demonstrate a dramatic increase in x-ray flux for interaction distances beyond the depletion/dephasing lengths, where the initial electron bunch injected into the first wake bucket catches up with the laser pulse front and the laser pulse depletes. A transition from an LWFA regime to a beam-driven plasma wakefield acceleration regime consequently occurs. The drive electron bunch is susceptible to the electron-hose instability and rapidly develops large amplitude oscillations in its tail,more » which leads to greatly enhanced x-ray radiation emission. We measure the x-ray flux as a function of acceleration length using a variable length gas cell. 3D particle-in-cell simulations using a Monte Carlo synchrotron x-ray emission algorithm elucidate the time-dependent variations in the radiation emission processes.« less

High flux femtosecond x-ray emission from the electron-hose instability in laser wakefield accelerators

NASA Astrophysics Data System (ADS)

Dong, C. F.; Zhao, T. Z.; Behm, K.; Cummings, P. G.; Nees, J.; Maksimchuk, A.; Yanovsky, V.; Krushelnick, K.; Thomas, A. G. R.

2018-04-01

Bright and ultrashort duration x-ray pulses can be produced by through betatron oscillations of electrons during laser wakefield acceleration (LWFA). Our experimental measurements using the Hercules laser system demonstrate a dramatic increase in x-ray flux for interaction distances beyond the depletion/dephasing lengths, where the initial electron bunch injected into the first wake bucket catches up with the laser pulse front and the laser pulse depletes. A transition from an LWFA regime to a beam-driven plasma wakefield acceleration regime consequently occurs. The drive electron bunch is susceptible to the electron-hose instability and rapidly develops large amplitude oscillations in its tail, which leads to greatly enhanced x-ray radiation emission. We measure the x-ray flux as a function of acceleration length using a variable length gas cell. 3D particle-in-cell simulations using a Monte Carlo synchrotron x-ray emission algorithm elucidate the time-dependent variations in the radiation emission processes.

Controlling Rayleigh-Taylor instabilities in solid liner implosions with rotating magnetic fields

NASA Astrophysics Data System (ADS)

Schmit, P. F.; McBride, R. D.; Robertson, G. K.; Velikovich, A. L.

2016-10-01

We report calculations demonstrating that a remarkable reduction in the growth of the magneto-Rayleigh-Taylor instability (MRTI) in initially solid, cylindrical metal shells can be achieved by applying a magnetic drive with a tilted, dynamic polarization, forming a solid-liner dynamic screw pinch (SLDSP). Using a self-consistent analytic framework, we demonstrate that MRTI growth factors of the most detrimental modes may be reduced by up to two orders of magnitude relative to conventional z-pinch implosions. One key application of this technique is to enable increasingly stable, higher performance liner implosions to achieve fusion. We weigh the potentially dramatic benefits of the SLDSP against the practical tradeoffs required to achieve the desired drive field history and identify promising target designs for future experimental and computational investigations. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. DoE's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Zim17/Tim15 links mitochondrial iron-sulfur cluster biosynthesis to nuclear genome stability.

PubMed

Díaz de la Loza, María Del Carmen; Gallardo, Mercedes; García-Rubio, María Luisa; Izquierdo, Alicia; Herrero, Enrique; Aguilera, Andrés; Wellinger, Ralf Erik

2011-08-01

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron-sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron-sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron-sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.

High flux femtosecond x-ray emission from the electron-hose instability in laser wakefield accelerators

DOE PAGES

Dong, C. F.; Zhao, T. Z.; Behm, K.; ...

2018-04-24

Here, bright and ultrashort duration x-ray pulses can be produced by through betatron oscillations of electrons during laser wakefield acceleration (LWFA). Our experimental measurements using the Hercules laser system demonstrate a dramatic increase in x-ray flux for interaction distances beyond the depletion/dephasing lengths, where the initial electron bunch injected into the first wake bucket catches up with the laser pulse front and the laser pulse depletes. A transition from an LWFA regime to a beam-driven plasma wakefield acceleration regime consequently occurs. The drive electron bunch is susceptible to the electron-hose instability and rapidly develops large amplitude oscillations in its tail,more » which leads to greatly enhanced x-ray radiation emission. We measure the x-ray flux as a function of acceleration length using a variable length gas cell. 3D particle-in-cell simulations using a Monte Carlo synchrotron x-ray emission algorithm elucidate the time-dependent variations in the radiation emission processes.« less

Microarray analysis identifies keratin loci as sensitive biomarkers for thyroid hormone disruption in the salamander Ambystoma mexicanum.

PubMed

Page, Robert B; Monaghan, James R; Samuels, Amy K; Smith, Jeramiah J; Beachy, Christopher K; Voss, S Randal

2007-02-01

Ambystomatid salamanders offer several advantages for endocrine disruption research, including genomic and bioinformatics resources, an accessible laboratory model (Ambystoma mexicanum), and natural lineages that are broadly distributed among North American habitats. We used microarray analysis to measure the relative abundance of transcripts isolated from A. mexicanum epidermis (skin) after exogenous application of thyroid hormone (TH). Only one gene had a >2-fold change in transcript abundance after 2 days of TH treatment. However, hundreds of genes showed significantly different transcript levels at days 12 and 28 in comparison to day 0. A list of 123 TH-responsive genes was identified using statistical, BLAST, and fold level criteria. Cluster analysis identified two groups of genes with similar transcription patterns: up-regulated versus down-regulated. Most notably, several keratins exhibited dramatic (1000 fold) increases or decreases in transcript abundance. Keratin gene expression changes coincided with morphological remodeling of epithelial tissues. This suggests that keratin loci can be developed as sensitive biomarkers to assay temporal disruptions of larval-to-adult gene expression programs. Our study has identified the first collection of loci that are regulated during TH-induced metamorphosis in a salamander, thus setting the stage for future investigations of TH disruption in the Mexican axolotl and other salamanders of the genus Ambystoma.

An autoantibody in narcolepsy disrupts colonic migrating motor complexes.

PubMed

Jackson, Michael W; Reed, Joanne H; Smith, Anthony J F; Gordon, Tom P

2008-12-03

Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The ex vivo whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.

The Magnetohydrodynamic Kelvin-Helmholtz Instability. III. The Role of Sheared Magnetic Field in Planar Flows

NASA Astrophysics Data System (ADS)

Jeong, Hyunju; Ryu, Dongsu; Jones, T. W.; Frank, Adam

2000-01-01

We have carried out simulations of the nonlinear evolution of the magnetohydrodynamic (MHD) Kelvin-Helmholtz (KH) instability for compressible fluids in 2.5 dimensions, extending our previous work by Frank et al. and Jones et al. In the present work we have simulated flows in the x-y plane in which a ``sheared'' magnetic field of uniform strength smoothly rotates across a thin velocity shear layer from the z-direction to the x-direction, aligned with the flow field. The sonic Mach number of the velocity transition is unity. Such flows containing a uniform field in the x-direction are linearly stable if the magnetic field strength is great enough that the Alfvénic Mach number MA=U0/cA<2. That limit does not apply directly to sheared magnetic fields, however, since the z-field component has almost no influence on the linear stability. Thus, if the magnetic shear layer is contained within the velocity shear layer, the KH instability may still grow, even when the field strength is quite large. So, here we consider a wide range of sheared field strengths covering Alfvénic Mach numbers, MA=142.9 to 2. We focus on dynamical evolution of fluid features, kinetic energy dissipation, and mixing of the fluid between the two layers, considering their dependence on magnetic field strength for this geometry. There are a number of differences from our earlier simulations with uniform magnetic fields in the x-y plane. For the latter, simpler case we found a clear sequence of behaviors with increasing field strength ranging from nearly hydrodynamic flows in which the instability evolves to an almost steady cat's eye vortex with enhanced dissipation, to flows in which the magnetic field disrupts the cat's eye once it forms, to, finally, flows that evolve very little before field-line stretching stabilizes the velocity shear layer. The introduction of magnetic shear can allow a cat's eye-like vortex to form, even when the field is stronger than the nominal linear instability limit given above. For strong fields that vortex is asymmetric with respect to the preliminary shear layer, however, so the subsequent dissipation is enhanced over the uniform field cases of comparable field strength. In fact, so long as the magnetic field achieves some level of dynamical importance during an eddy turnover time, the asymmetries introduced through the magnetic shear will increase flow complexity and, with that, dissipation and mixing. The degree of the fluid mixing between the two layers is strongly influenced by the magnetic field strength. Mixing of the fluid is most effective when the vortex is disrupted by magnetic tension during transient reconnection, through local chaotic behavior that follows.

Role of the Polarity Determinant Crumbs in Suppressing Mammalian Epithelial Tumor Progression

PubMed Central

Karp, Cristina M.; Tan, Ting Ting; Mathew, Robin; Nelson, Deidre; Mukherjee, Chandreyee; Degenhardt, Kurt; Karantza-Wadsworth, Vassiliki; White, Eileen

2009-01-01

Most tumors are epithelial-derived, and although disruption of polarity and aberrant cellular junction formation is a poor prognosticator in human cancer, the role of polarity determinants in oncogenesis is poorly understood. Using in vivo selection, we identified a mammalian orthologue of the Drosophila polarity regulator crumbs as a gene whose loss of expression promotes tumor progression. Immortal baby mouse kidney epithelial (iBMK) cells selected in vivo to acquire tumorigenicity displayed dramatic repression of crumbs3 (crb3) expression associated with disruption of tight junction formation, apicobasal polarity, and contact-inhibited growth. Restoration of crb3 expression restored junctions, polarity and contact inhibition, while suppressing migration and metastasis. These findings suggest a role for mammalian polarity determinants in suppressing tumorigenesis that may be analogous to the well-studied polarity tumor suppressor mechanisms in Drosophila. PMID:18519669

Additive Manufacturing and High-Performance Computing: a Disruptive Latent Technology

NASA Astrophysics Data System (ADS)

Goodwin, Bruce

2015-03-01

This presentation will discuss the relationship between recent advances in Additive Manufacturing (AM) technology, High-Performance Computing (HPC) simulation and design capabilities, and related advances in Uncertainty Quantification (UQ), and then examines their impacts upon national and international security. The presentation surveys how AM accelerates the fabrication process, while HPC combined with UQ provides a fast track for the engineering design cycle. The combination of AM and HPC/UQ almost eliminates the engineering design and prototype iterative cycle, thereby dramatically reducing cost of production and time-to-market. These methods thereby present significant benefits for US national interests, both civilian and military, in an age of austerity. Finally, considering cyber security issues and the advent of the ``cloud,'' these disruptive, currently latent technologies may well enable proliferation and so challenge both nuclear and non-nuclear aspects of international security.

Rupture of the gastrocnemius muscle in six foals.

PubMed

Jesty, Sophy A; Palmer, Jonathan E; Parente, Eric J; Schaer, Thomas P; Wilkins, Pamela A

2005-12-15

Rupture of the gastrocnemius muscle and subsequent disruption of the reciprocal mechanism of the hind limb was diagnosed in 6 foals examined at 7 hours to 3 weeks of age. In 2 foals, the musculoskeletal injury was detected as an ancillary finding to clinical signs of neurologic dysfunction ascribed to hypoxic ischemic insult during delivery, whereas in the other 4 foals, musculoskeletal injury, manifested as inability to rise or stand unsupported, was the chief complaint at admission. Five foals had a history of dystocia and assisted delivery. Common clinical signs were inability to rise, disruption of the reciprocal mechanism, swelling in the caudal aspect of the thigh, instability of the stifle joint, and stifle joint effusion. For mild gastrocnemius injury, exercise restriction via forced recumbency, with minimal or no bandaging, may be sufficient treatment. For more severe disruption of the muscle, limb stabilization via splinting and intensive nursing and monitoring are necessary. Four foals had important concurrent problems, including musculoskeletal deformations (joint contractures), hypoxic ischemic disease, and failure of passive transfer and associated problems (ie, sepsis, polyarthritis, and pneumonia). Moderate to severe gastrocnemius muscle injury is difficult to treat successfully, and the long-term prognosis for athletic function should be regarded as guarded.

iPTF Discovery of the Rapid “Turn-on” of a Luminous Quasar

DOE PAGES

Gezari, S.; Hung, T.; Cenko, S. B.; ...

2017-01-24

We present a radio-quiet quasar at z = 0.237 discovered "turning on" by the intermediate Palomar Transient Factory (iPTF). The transient, iPTF 16bco, was detected by iPTF in the nucleus of a galaxy with an archival Sloan Digital Sky Survey spectrum with weak narrow-line emission characteristic of a low-ionization nuclear emission-line region (LINER). Our follow-up spectra show the dramatic appearance of broad Balmer lines and a power-law continuum characteristic of a luminous ( L bol ≈ 10 45 erg s -1) type 1 quasar 12 yr later. Our photometric monitoring with PTF from 2009-2012 and serendipitous X-ray observations from themore » XMM-Newton Slew Survey in 2011 and 2015 constrain the change of state to have occurred less than 500 days before the iPTF detection. An enhanced broad Hα/[O iii] λ5007 line ratio in the type 1 state relative to other changing-look quasars also is suggestive of the most rapid change of state yet observed in a quasar. Here, we argue that the > 10 increase in Eddington ratio inferred from the brightening in UV and X-ray continuum flux is more likely due to an intrinsic change in the accretion rate of a preexisting accretion disk than an external mechanism such as variable obscuration, microlensing, or the tidal disruption of a star. However, further monitoring will be helpful in better constraining the mechanism driving this change of state. The rapid "turn-on" of the quasar is much shorter than the viscous infall timescale of an accretion disk and requires a disk instability that can develop around a ~ 10 8 M ⊙ black hole on timescales less than 1 yr.« less

Profound systemic inflammatory response syndrome following non-emergent intestinal surgery in children.

PubMed

Chawla, Bhani K; Teitelbaum, Daniel H

2013-09-01

Systemic inflammatory response syndrome (SIRS) is an uncommon but severe complication in surgical patients. While SIRS is well known, it is poorly described in the pediatric population. The goal of this study was to describe the incidence of profound SIRS following non-emergent intestinal surgery in children and to identify potential risk factors. A retrospective review was conducted for patients 0-19 years of age following intestinal surgery and/or lysis of adhesions from 01/01/1999-02/28/2012. Children were excluded for preoperative instability or frank bowel perforation. Patients were then placed in a post-operative SIRS or non-SIRS group as defined by the 2005 International Pediatric Sepsis Consensus Conference Guidelines (6. B. Goldstein, B. Giroir, A. Randolph, and Sepsis International Consensus Conference on Pediatric, 'International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics', Pediatr Crit Care Med, 6 (2005), 2-8.). SIRS was identified in 17 of the 381 patients. Logistic regression analysis was performed and showed heart disease, kidney disease, PN dependence, and intestinal obstruction to be predictive of post-operative SIRS. This study represents one of the first reports to identify a previously poorly described process of significant SIRS after intestinal surgery in children. Both systemic organ failure and intestinal dysfunction are strong risk factors for post-operative SIRS in children. Potentially, these pre-existing conditions may lead to disruption of normal intestinal flora or barrier function, which in turn may predispose these children to dramatic SIRS episodes after intestinal surgery. Understanding how these factors lead to SIRS will be critical to developing prevention strategies. © 2013 Elsevier Inc. All rights reserved.

Substorm theories: United they stand, divided they fall

NASA Technical Reports Server (NTRS)

Erickson, Gary M.

1995-01-01

Consensus on the timing and mapping of substorm features has permitted a synthesis of substorm models. Within the synthesis model the mechanism for onset of substorm expansion is still unknown. Possible mechanisms are: growth of an ion tearing mode, current disruption by a cross-field current instability, and magnetosphere-ionosphere coupling. While the synthesis model is consistent with overall substorm morphology, including near-Earth onset, none of the onset theories, taken individually, appear to account for substorm expansion onset. A grand synthesis with unification of the underlying onset theories appears necessary.

Side-force alleviation on slender, pointed forebodies at high angles of attack

NASA Technical Reports Server (NTRS)

Rao, D. M.

1978-01-01

A new device was proposed for alleviating high angle-of-attack side force on slender, pointed forebodies. A symmetrical pair of separation strips in the form of helical ridges are applied to the forebody to disrupt the primary lee-side vortices and thereby avoid the instability that produces vortex asymmetry. Preliminary wind tunnel tests at Mach 0.3 and Reynolds no. 5,250,000 on a variety of forebody configurations and on a wing-body combination at angles of attack up to 56 degrees, demonstrated the effectiveness of the device.

The flood event that affected Badajoz in November 1997

NASA Astrophysics Data System (ADS)

Lorente, P.; Hernández, E.; Queralt, S.; Ribera, P.

2008-04-01

The flooding episode of November 1997 in Badajoz was one of the most dramatic catastrophes in Spain: as a result, there were 21 fatalities and huge financial damages. The main purpose of this work is to assess the prevailing synoptic conditions as well as detailing the mesoscale effects by means of moisture sources and dynamic and thermodynamic instability analysis involved in the November 1997 Spanish severe weather episode. In order to achieve the above, this flood event is described in terms of moisture content evolution by means of individual particle simulation along 3-day back-trajectories. A Lagrangian model is applied in order to characterize the atmospheric particles involved in the focused case (localization, height and specific humidity) which give rise to sudden precipitation stream. Geopotential height and temperature fields were used to describe the synoptic situation. Thermodynamic indices, such as CAPE, SWEAT and KI, and dynamic parameters like potential vorticity anomaly at 330 K isentropic surface and Q vector divergence were also calculated in order to complete the analysis and to give a thorough weather frame taking into account the atmospheric instability. The results of this work suggest this flood event was due mainly to strong dynamic instability along with large amounts of moisture advected by a trough, while the thermodynamic instability played a secondary role. Finally, a new methodology based on a technique proposed by Tremblay (2005) has been developed in order to separate the precipitation into stratiform and convective components. It is evident that the event was associated with a predominant convective regime.

IRIS Si iv LINE PROFILES: AN INDICATION FOR THE PLASMOID INSTABILITY DURING SMALL-SCALE MAGNETIC RECONNECTION ON THE SUN

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

Innes, D. E.; Guo, L.-J.; Huang, Y.-M.

Our understanding of the process of fast reconnection has undergone a dramatic change in the last 10 years driven, in part, by the availability of high-resolution numerical simulations that have consistently demonstrated the break-up of current sheets into magnetic islands, with reconnection rates that become independent of Lundquist number, challenging the belief that fast magnetic reconnection in flares proceeds via the Petschek mechanism which invokes pairs of slow-mode shocks connected to a compact diffusion region. The reconnection sites are too small to be resolved with images, but these reconnection mechanisms, Petschek and the plasmoid instability, have reconnection sites with verymore » different density and velocity structures and so can be distinguished by high-resolution line-profile observations. Using IRIS spectroscopic observations we obtain a survey of typical line profiles produced by small-scale events thought to be reconnection sites on the Sun. Slit-jaw images are used to investigate the plasma heating and re-configuration at the sites. A sample of 15 events from 2 active regions is presented. The line profiles are complex with bright cores and broad wings extending to over 300 km s{sup −1}. The profiles can be reproduced with the multiple magnetic islands and acceleration sites that characterize the plasmoid instability but not by bi-directional jets that characterize the Petschek mechanism. This result suggests that if these small-scale events are reconnection sites, then fast reconnection proceeds via the plasmoid instability, rather than the Petschek mechanism during small-scale reconnection on the Sun.« less

The Electrostatic Instability for Realistic Pair Distributions in Blazar/EBL Cascades

NASA Astrophysics Data System (ADS)

Vafin, S.; Rafighi, I.; Pohl, M.; Niemiec, J.

2018-04-01

This work revisits the electrostatic instability for blazar-induced pair beams propagating through the intergalactic medium (IGM) using linear analysis and PIC simulations. We study the impact of the realistic distribution function of pairs resulting from the interaction of high-energy gamma-rays with the extragalactic background light. We present analytical and numerical calculations of the linear growth rate of the instability for the arbitrary orientation of wave vectors. Our results explicitly demonstrate that the finite angular spread of the beam dramatically affects the growth rate of the waves, leading to the fastest growth for wave vectors quasi-parallel to the beam direction and a growth rate at oblique directions that is only a factor of 2–4 smaller compared to the maximum. To study the nonlinear beam relaxation, we performed PIC simulations that take into account a realistic wide-energy distribution of beam particles. The parameters of the simulated beam-plasma system provide an adequate physical picture that can be extrapolated to realistic blazar-induced pairs. In our simulations, the beam looses only 1% of its energy, and we analytically estimate that the beam would lose its total energy over about 100 simulation times. An analytical scaling is then used to extrapolate the parameters of realistic blazar-induced pair beams. We find that they can dissipate their energy slightly faster by the electrostatic instability than through inverse-Compton scattering. The uncertainties arising from, e.g., details of the primary gamma-ray spectrum are too large to make firm statements for individual blazars, and an analysis based on their specific properties is required.

Simulating Gravitational Wave Emission from Massive Black Hole Binaries

NASA Technical Reports Server (NTRS)

Centrella, Joan

2008-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of very strong gravitational fields, we need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities, causing them to crash well before the black holes in the binary could complete even a single orbit. In the past few years, this situation has changed dramatically, with a series of amazing breakthroughs. This talk will focus on the recent advances that are revealing these waveforms. highlighting their astrophysical consequences and the dramatic new potential for discovery that arises when merging black holes will be observed using gravitational waves.

Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells

PubMed Central

Schiavone, Davide; Guilbaud, Guillaume; Murat, Pierre; Papadopoulou, Charikleia; Sarkies, Peter; Prioleau, Marie-Noëlle; Balasubramanian, Shankar; Sale, Julian E

2014-01-01

REV1-deficient chicken DT40 cells are compromised in replicating G quadruplex (G4)-forming DNA. This results in localised, stochastic loss of parental chromatin marks and changes in gene expression. We previously proposed that this epigenetic instability arises from G4-induced replication fork stalls disrupting the accurate propagation of chromatin structure through replication. Here, we test this model by showing that a single G4 motif is responsible for the epigenetic instability of the BU-1 locus in REV1-deficient cells, despite its location 3.5 kb from the transcription start site (TSS). The effect of the G4 is dependent on it residing on the leading strand template, but is independent of its in vitro thermal stability. Moving the motif to more than 4 kb from the TSS stabilises expression of the gene. However, loss of histone modifications (H3K4me3 and H3K9/14ac) around the transcription start site correlates with the position of the G4 motif, expression being lost only when the promoter is affected. This supports the idea that processive replication is required to maintain the histone modification pattern and full transcription of this model locus. PMID:25190518

DNA-damage response during mitosis induces whole-chromosome missegregation.

PubMed

Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

2014-11-01

Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

The role of magnetic fields in cluster cooling flows

NASA Technical Reports Server (NTRS)

Soker, Noam; Sarazin, Craig L.

1990-01-01

An investigation is made of the dynamical effects of the intracluster magnetic field, whose radial inflow and shear can produce a dramatic increase in the field's strength while rendering it more radial, with cooling flows. It is found that field reconnection is the most likely dominant-loss mechanism, so that buoyancy effects are probably not important. Attention is given to the effect of the magnetic field on thermal instabilities. The most important observable effect of the magnetic field in cooling flows will probably be very strong Faraday rotation of the polarization of radio sources within or behind the cooling flow.

The influence of gravity level during directional solidification of immiscible alloys

NASA Technical Reports Server (NTRS)

Andrews, J. B.; Schmale, A. L.; Sandlin, A. C.

1992-01-01

During directional solidification of immiscible (hypermonotectic) alloys it is theoretically possible to establish a stable macroscopically-planar solidification front, and thus avoid sedimentation. Unfortunately, convective instabilities often occur which interfere with the directional solidification process. In this paper, stability conditions are discussed and results presented from directional solidification studies carried out aboard NASA's KC-135 zero-g aircraft. Samples were directionally solidified while the effective gravity level was varied from approximately 0.01 g for 25 s to 1.8 g for 45 s. Dramatic variations in microstructure were observed with gravity level during solidification.

Influence of deposited nanoparticles on the spall strength of metals under the action of picosecond pulses of shock compression

NASA Astrophysics Data System (ADS)

Ebel, A. A.; Mayer, A. E.

2018-01-01

Molecular dynamic simulations of the generation and propagation of shock pulses of picosecond duration initiated by nanoscale impactors, and their interaction with the rear surface is carried out for aluminum and copper. It is shown that the presence of deposited nanoparticles on the rear surface increases the threshold value of the impact intensity leading to the rear spallation. The interaction of a shock wave with nanoparticles leads to severe plastic deformation in the surface layer of the metal including nanoparticles. A part of the compression pulse energy is expended on the plastic deformation, which suppresses the spall fracture. Spallation threshold substantially increases at large diameters of deposited nanoparticles, but instability develops on the rear surface of the target, which is accompanied by ejection of droplets. The instability disrupts the integrity of the rear surface, though the loss of integrity occurs through the ejection of mass, rather than a spallation.

Geomorphological features in the southern Canary Island Volcanic Province: The importance of volcanic processes and massive slope instabilities associated with seamounts

NASA Astrophysics Data System (ADS)

Palomino, Desirée; Vázquez, Juan-Tomás; Somoza, Luis; León, Ricardo; López-González, Nieves; Medialdea, Teresa; Fernández-Salas, Luis-Miguel; González, Francisco-Javier; Rengel, Juan Antonio

2016-02-01

The margin of the continental slope of the Volcanic Province of Canary Islands is characterised by seamounts, submarine hills and large landslides. The seabed morphology including detailed morphology of the seamounts and hills was analysed using multibeam bathymetry and backscatter data, and very high resolution seismic profiles. Some of the elevation data are reported here for the first time. The shape and distribution of characteristics features such as volcanic cones, ridges, slides scars, gullies and channels indicate evolutionary differences. Special attention was paid to recent geological processes that influenced the seamounts. We defined various morpho-sedimentary units, which are mainly due to massive slope instability that disrupt the pelagic sedimentary cover. We also studied other processes such as the role of deep bottom currents in determining sediment distribution. The sediments are interpreted as the result of a complex mixture of material derived from a) slope failures on seamounts and submarine hills; and b) slides and slumps on the continental slope.

Origins of Folding Instabilities on Polycrystalline Metal Surfaces

NASA Astrophysics Data System (ADS)

Beckmann, N.; Romero, P. A.; Linsler, D.; Dienwiebel, M.; Stolz, U.; Moseler, M.; Gumbsch, P.

2014-12-01

Wear and removal of material from polycrystalline metal surfaces is inherently connected to plastic flow. Here, plowing-induced unconstrained surface plastic flow on a nanocrystalline copper surface has been studied by massive molecular dynamics simulations and atomic force microscopy scratch experiments. In agreement with experimental findings, bulges in front of a model asperity develop into vortexlike fold patterns that mark the disruption of laminar flow. We identify dislocation-mediated plastic flow in grains with suitably oriented slip systems as the basic mechanism of bulging and fold formation. The observed folding can be fundamentally explained by the inhomogeneity of plasticity on polycrystalline surfaces which favors bulge formation on grains with suitably oriented slip system. This process is clearly distinct from Kelvin-Helmholtz instabilities in fluids, which have been previously suggested to resemble the formed surface fold patterns. The generated prow grows into a rough chip with stratified lamellae that are identified as the precursors of wear debris. Our findings demonstrate the importance of surface texture and grain structure engineering to achieve ultralow wear in metals.

Ankle syndesmotic injury.

PubMed

Zalavras, Charalampos; Thordarson, David

2007-06-01

Ankle syndesmotic injury does not necessarily lead to ankle instability; however, the coexistence of deltoid ligament injury critically destabilizes the ankle joint. Syndesmotic injury may occur in isolation or may be associated with ankle fracture. In the absence of fracture, physical examination findings suggestive of injury include ankle tenderness over the anterior aspect of the syndesmosis and a positive squeeze or external rotation test. Radiographic findings usually include increased tibiofibular clear space decreased tibiofibular overlap, and increased medial clear space. However, syndesmotic injury may not be apparent radiographically; thus, routine stress testing is necessary for detecting syndesmotic instability. The goals of management are to restore and maintain the normal tibiofibular relationship to allow for healing of the ligamentous structures of the syndesmosis. Fixation of the syndesmosis is indicated when evidence of a diastasis is present. This may be detected preoperatively, in the absence of fracture, or intraoperatively, after rigid fixation of the medial malleolus and fibula fractures. Failure to diagnose and stabilize syndesmotic disruption adversely affects outcome.

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

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

Hansen, R K; Bissell, M J

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellularmore » matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.« less

Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

NASA Technical Reports Server (NTRS)

Sun, E.; Gao, Y.; Chen, J.; Roberts, A. I.; Wang, X.; Chen, Z.; Shi, Y.

2004-01-01

Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

Quantification of Road Network Vulnerability and Traffic Impacts to Regional Landslide Hazards.

NASA Astrophysics Data System (ADS)

Postance, Benjamin; Hillier, John; Dixon, Neil; Dijkstra, Tom

2015-04-01

Slope instability represents a prevalent hazard to transport networks. In the UK regional road networks are frequently disrupted by multiple slope failures triggered during intense precipitation events; primarily due to a degree of regional homogeneity of slope materials, geomorphology and weather conditions. It is of interest to examine how different locations and combinations of slope failure impact road networks, particularly in the context of projected climate change and a 40% increase in UK road demand by 2040. In this study an extensive number (>50 000) of multiple failure event scenarios are simulated within a dynamic micro simulation to assess traffic impacts during peak flow (7 - 10 AM). Possible failure locations are selected within the county of Gloucestershire (3150 km2) using historic failure sites and British Geological Survey GeoSure data. Initial investigations employ a multiple linear regression analyses to consider the severity of traffic impacts, as measured by time, in respect of spatial and topographical network characteristics including connectivity, density and capacity in proximity to failure sites; the network distance between disruptions in multiple failure scenarios is used to consider the effects of spatial clustering. The UK Department of Transport road travel demand and UKCP09 weather projection data to 2080 provide a suitable basis for traffic simulations and probabilistic slope stability assessments. Future work will thus focus on the development of a catastrophe risk model to simulate traffic impacts under various narratives of future travel demand and slope instability under climatic change. The results of this investigation shall contribute to the understanding of road network vulnerabilities and traffic impacts from climate driven slope hazards.

Prescriber-pharmacist collaboration: re-engineering the partnership to optimize pain patient care.

PubMed

Ruble, James H

2013-12-01

The Walgreen Companies recently settled a Drug Enforcement Administration (DEA) administrative action and other investigations arising in connection with a controlled substance distribution facility in Florida and several of its retail pharmacies. These DEA enforcement actions upon a national chain pharmacy have resulted in a series of policies and professional practices that appear to functionally disrupt continuity of patient care. The policy issues transcend the professions and go to the core of our responsibilities to patients. It is unfortunate that regulations intended to prevent diversion also dramatically disrupt interprofessional relations. Based on public statements of professional organizations, unification on this issue seems possible. This presents an opportunity to revisit collaboration among prescribers and pharmacists in legislative and regulatory advocacy. A uniform definition of "legitimate medical purpose" is needed to maximize patient access to needed pharmacotherapy while remaining vigilant for diversion.

Learning and disrupting invariance in visual recognition with a temporal association rule

PubMed Central

Isik, Leyla; Leibo, Joel Z.; Poggio, Tomaso

2012-01-01

Learning by temporal association rules such as Foldiak's trace rule is an attractive hypothesis that explains the development of invariance in visual recognition. Consistent with these rules, several recent experiments have shown that invariance can be broken at both the psychophysical and single cell levels. We show (1) that temporal association learning provides appropriate invariance in models of object recognition inspired by the visual cortex, (2) that we can replicate the “invariance disruption” experiments using these models with a temporal association learning rule to develop and maintain invariance, and (3) that despite dramatic single cell effects, a population of cells is very robust to these disruptions. We argue that these models account for the stability of perceptual invariance despite the underlying plasticity of the system, the variability of the visual world and expected noise in the biological mechanisms. PMID:22754523

Disruptive Influences on Research in Academic Pathology Departments: Proposed Changes to the Common Rule Governing Informed Consent for Research Use of Biospecimens and to Rules Governing Return of Research Results.

PubMed

Sobel, Mark E; Dreyfus, Jennifer C

2017-01-01

Academic pathology departments will be dramatically affected by proposed United States federal government regulatory initiatives. Pathology research will be substantially altered if proposed changes to the Common Rule (Code of Federal Regulations: Protection of Human Subjects title 45 CFR 46) and regulations governing the return of individual research results are approved and finalized, even more so now that the Precision Medicine initiative has been launched. Together, these changes are disruptive influences on academic pathology research as we know it, straining limited resources and compromising advances in diagnostic and academic pathology. Academic research pathologists will be challenged over the coming years and must demonstrate leadership to ensure the continued availability of and the ethical use of research pathology specimens. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Tributyltin induces disruption of microfilament in HL7702 cells via MAPK-mediated hyperphosphorylation of VASP.

PubMed

Tu, Wei-Wei; Ji, Lin-Dan; Qian, Hai-Xia; Zhou, Mi; Zhao, Jin-Shun; Xu, Jin

2016-11-01

Tributyltin (TBT) has been widely used for various industrial purposes, and it has toxic effects on multiple organs and tissues. Previous studies have found that TBT could induce cytoskeletal disruption, especially of the actin filaments. However, the underlying mechanisms remain unclear. The aim of the present study was to determine whether TBT could induce microfilament disruption using HL7702 cells and then to assess for the total levels of various microfilament-associated proteins; finally, the involvement of the MAPK pathway was investigated. The results showed that after TBT treatment, F-actin began to depolymerize and lost its characteristic filamentous structure. The protein levels of Ezrin and Cofilin remained unchanged, the actin-related protein (ARP) 2/3 levels decreased slightly, and the vasodilator-stimulated phosphoprotein (VASP) decreased dramatically. However, the phosphorylation levels of VASP increased 2.5-fold, and the ratio of phosphorylated-VASP/unphosphorylated-VASP increased 31-fold. The mitogen-activated protein kinases (MAPKs) ERK and JNK were discovered to be activated. Inhibition of ERK and JNK not only largely diminished the TBT-induced hyperphosphorylation of VASP but also recovered the cellular morphology and rescued the cells from death. In summary, this study demonstrates that TBT-induced disruption of actin filaments is caused by the hyperphosphorylation of VASP through MAPK pathways. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1530-1538, 2016. © 2015 Wiley Periodicals, Inc.

Plantar-plate disruptions: "the severe turf-toe injury." three cases in contact athletes.

PubMed

Drakos, Mark C; Fiore, Russell; Murphy, Conor; DiGiovanni, Christopher W

2015-05-01

To present 3 cases of plantar-plate rupture and turf-toe injury in contact athletes at 1 university and to discuss appropriate diagnosis and treatment algorithms for each case. Turf toe is a common injury in athletes participating in outdoor cutting sports. However, it has been used as an umbrella term to describe many different injuries of the great toe. In some cases, the injury can be so severe that the plantar plate and sesamoid apparatus may be ruptured. These patients may be better managed with surgery than with traditional nonoperative interventions. Turf toe, plantar-plate disruption, sesamoid fracture. For stable injuries in which the plantar plate is not completely disrupted, nonoperative treatment with casting or a stiff-soled shoe, gradual weight bearing, and rehabilitation is the best practice. Unstable injuries require surgical intervention and plantar-plate repair. Turf toe and injury to the first metatarsophalangeal joint are relatively common injuries in athletes, but few researchers have detailed the operative and nonoperative treatments of plantar-plate disruption in these patients. We examine 3 cases that occurred over 4 seasons on a collegiate football team. Turf toe represents a wide array of pathologic conditions involving the first metatarsophalangeal joint. Stress and instability testing are key components to assess in determining whether surgical intervention is warranted to restore optimal function. Stiffer-soled shoes or shoes with steel-plate insertions may help to prevent these injuries and are useful tools for protection during the rehabilitation period.

The Dominance of Dynamic Barlike Instabilities in the Evolution of a Massive Stellar Core Collapse That ``Fizzles''

NASA Astrophysics Data System (ADS)

Imamura, James N.; Durisen, Richard H.

2001-03-01

Core collapse in a massive rotating star may halt at subnuclear density if the core contains angular momentum J>~1049 g cm2 s-1. An aborted collapse can lead to the formation of a rapidly rotating equilibrium object, which, because of its high electron fraction, Ye>0.4, and high entropy per baryon, Sb/k~1-2, is secularly and dynamically stable. The further evolution of such a ``fizzler'' is driven by deleptonization and cooling of the hot, dense material. These processes cause the fizzler both to contract toward neutron star densities and to spin up, driving it toward instability points of the barlike modes. Using linear stability analyses to study the latter case, we find that the stability properties of fizzlers are similar to those of Maclaurin spheroids and polytropes despite the nonpolytropic nature and extreme compressibility of the fizzler equation of state. For fizzlers with the specific angular momentum distribution of the Maclaurin spheroids, secular and dynamic barlike instabilities set in at T/|W|~0.14 and 0.27, respectively, where T is the rotational kinetic energy and W is the gravitational energy of the fizzler, the same limits as found for Maclaurin spheroids. For fizzlers in which angular momentum is more concentrated toward the equator, the secular stability limits drop dramatically. For the most extreme angular momentum distribution we consider, the secular stability limit for the barlike modes falls to T/|W|~0.038, compared with T/|W|~0.09-0.10 for the most extreme polytropic cases known previously (Imamura et al.). For fixed equation-of-state parameters, the secular and dynamic stability limits occur at roughly constant mass over the range of typical fizzler central densities. Deleptonization and cooling decrease the limiting masses on timescales shorter than the growth time for secular instability. Consequently, unless an evolving fizzler reaches neutron star densities first, it will always encounter dynamic barlike instabilities before secular instabilities have time to grow. Quasi-linear analysis shows that the angular momentum loss during the early nonlinear evolution of the dynamic barlike instability is dominated by Newtonian self-interaction gravitational torques rather than by the emission of gravitational wave (GW) radiation. GW emission may dominate after the initial dynamic evolutionary phase ends. Nonlinear hydrodynamics simulations with a proper equation of state will be required to determine the ultimate outcome of such evolutions and to refine predictions of GW production by barlike instabilities.

Scaling of the MHD perturbation amplitude required to trigger a disruption and predictions for ITER

NASA Astrophysics Data System (ADS)

de Vries, P. C.; Pautasso, G.; Nardon, E.; Cahyna, P.; Gerasimov, S.; Havlicek, J.; Hender, T. C.; Huijsmans, G. T. A.; Lehnen, M.; Maraschek, M.; Markovič, T.; Snipes, J. A.; the COMPASS Team; the ASDEX Upgrade Team; Contributors, JET

2016-02-01

The amplitude of locked instabilities, likely magnetic islands, seen as precursors to disruptions has been studied using data from the JET, ASDEX Upgrade and COMPASS tokamaks. It was found that the thermal quench, that often initiates the disruption, is triggered when the amplitude has reached a distinct level. This information can be used to determine thresholds for simple disruption prediction schemes. The measured amplitude in part depends on the distance of the perturbation to the measurement coils. Hence the threshold for the measured amplitude depends on the mode location (i.e. the rational q-surface) and thus indirectly on parameters such as the edge safety factor, q 95, and the internal inductance, li(3), that determine the shape of the q-profile. These dependencies can be used to set the disruption thresholds more precisely. For the ITER baseline scenario, with typically q 95  =  3.2, li(3)  =  0.9 and taking into account the position of the measurement coils on ITER, the maximum allowable measured locked mode amplitude normalized to engineering parameters was estimated to be a·B ML(r c)/I p  =  0.92 m mT/MA, or directly as a fraction edge poloidal magnetic field: B ML(r c)/B θ (a)  =  5 · 10-3. But these values decrease for operation at higher q 95 or lower li(3). The analysis found furthermore that the above empirical criterion to trigger a thermal quench is more consistent with a criterion derived with the concept of a critical island size, i.e. the thermal quench seemed to be triggered at a distinct island width.

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

PubMed Central

Yang, Qian; Zhang, Yafang; Liu, Xiuping; Wang, Nan; Song, Zhenyu; Wu, Kaili

2017-01-01

Models of benzalkonium chloride (BAC)-induced ocular disruption have been created and are widely used in various animals. This study aimed to compare the effects of BAC on the ocular surfaces of C57BL/6 and BALB/c mice. C57BL/6 and BALB/c mice were treated separately with BAC eye-drops at different concentrations. Eyes were evaluated by scoring epithelial disruption, corneal opacity and neovascularization in vivo, and by histological assays with hematoxylin/eosin (H/E) and periodic acid-Schiff stainings and by determining the expression of inflammatory factors in vitro on Days 7 and 14. The in vivo corneal epithelial disruption, corneal edema/opacity and neovascularization, which were in accordance with the results of the H/E staining and peaked at Day 7, were observed in a dose-dependent manner in the BAC-treated mice, with more severe signs in the C57BL/6 mice than the BALB/c mice. The loss of conjunctival goblet cells in the conjunctivas and the increasing expression of monocyte chemoattractant protein 1 (MCP-1), growth-regulated protein alpha (GROa) and macrophage inflammatory protein-1 alpha (MIP-1a) in the corneas were found in a dose-dependent manner in both strains of mice. Topical application of BAC can dramatically disrupt the ocular surfaces of C57BL/6 and BALB/c mice, and the disruptions were much more severe in the C57BL/6 mice that received high doses of BAC. PMID:28245636

Plasmon dispersion in strongly correlated superlattices

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

Lu, D.; Golden, K.I.; Kalman, G.

The dielectric response function of a strongly correlated superlattice is calculated in the quasilocalized charge (QLC) approximation. The resulting QLC static local-field correction, which contains both intralayer and interlayer pair-correlational effects, is identical to the correlational part of the third-frequency-moment sum-rule coefficient. This approximation treats the interlayer and intralayer couplings on an equal footing. The resulting dispersion relation is first analyzed to determine the effect of intralayer coupling on the out-of-phase acoustic-mode dispersion; in this approximation the interlayer coupling is suppressed and the mutual interaction of the layers is taken into account only through the average random-phase approximation (RPA) field.more » In the resulting mode dispersion, the onset of a finite-{ital k} ({ital k} being the in-plane wave number) reentrant low-frequency excitation developing (with decreasing {ital d}/{ital a}) into a dynamical instability is indicated ({ital a} being the in-plane Wigner-Seitz radius and {ital d} the distance between adjacent lattice planes). This dynamical instability parallels a static structural instability reported earlier both for a bilayer electron system and a superlattice and presumably indicates a structural change in the electron liquid. If one takes account of interlayer correlations beyond the RPA, the acoustic excitation spectrum is dramatically modified by the appearance of an energy gap which also has a stabilizing effect on the instability. We extend a previous energy gap study at {ital k}=0 [G. Kalman, Y. Ren, and K. I. Golden, Phys Rev. B {bold 50}, 2031 (1994)] to a calculation of the dispersion of the gapped acoustic excitation spectrum in the long-wavelength domain. {copyright} {ital 1996 The American Physical Society.}« less

Disease-associated repeat instability and mismatch repair.

PubMed

Schmidt, Monika H M; Pearson, Christopher E

2016-02-01

Expanded tandem repeat sequences in DNA are associated with at least 40 human genetic neurological, neurodegenerative, and neuromuscular diseases. Repeat expansion can occur during parent-to-offspring transmission, and arise at variable rates in specific tissues throughout the life of an affected individual. Since the ongoing somatic repeat expansions can affect disease age-of-onset, severity, and progression, targeting somatic expansion holds potential as a therapeutic target. Thus, understanding the factors that regulate this mutation is crucial. DNA repair, in particular mismatch repair (MMR), is the major driving force of disease-associated repeat expansions. In contrast to its anti-mutagenic roles, mammalian MMR curiously drives the expansion mutations of disease-associated (CAG)·(CTG) repeats. Recent advances have broadened our knowledge of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) repeats. Mutagenic slipped-DNA structures have been detected in patient tissues, and the size of the slip-out and their junction conformation can determine the involvement of MMR. Furthermore, the formation of other unusual DNA and R-loop structures is proposed to play a key role in MMR-mediated instability. A complex correlation is emerging between tissues showing varying amounts of repeat instability and MMR expression levels. Notably, naturally occurring polymorphic variants of DNA repair genes can have dramatic effects upon the levels of repeat instability, which may explain the variation in disease age-of-onset, progression and severity. An increasing grasp of these factors holds prognostic and therapeutic potential. Copyright © 2015 Elsevier B.V. All rights reserved.

The relationship between mammal faunas and climatic instability since the Last Glacial Maximum: A Nearctic vs. Western Palearctic comparison

NASA Astrophysics Data System (ADS)

Torres-Romero, Erik Joaquín; Varela, Sara; Fisher, Jason T.; Olalla-Tárraga, Miguel Á.

2017-07-01

Climate has played a key role in shaping the geographic patterns of biodiversity. The imprint of Quaternary climatic fluctuations is particularly evident on the geographic distribution of Holarctic faunas, which dramatically shifted their ranges following the alternation of glacial-interglacial cycles during the Pleistocene. Here, we evaluate the existence of differences between climatically stable and unstable regions - defined on the basis of climatic change velocity since the Last Glacial Maximum - in the geographic distribution of several biological attributes of extant terrestrial mammals of the Nearctic and Western Palearctic regions. Specifically, we use a macroecological approach to assess the dissimilarities in species richness, range size, body size, longevity and litter size of species that inhabit regions with contrasting histories of climatic stability. While several studies have documented how the distributional ranges of animals can be affected by long-term historic climatic fluctuations, there is less evidence on the species-specific traits that determine their responsiveness under such climatic instability. We find that climatically unstable areas have more widespread species and lower mammal richness than stable regions in both continents. We detected stronger signatures of historical climatic instability on the geographic distribution of body size in the Nearctic region, possibly reflecting lagged responses to recolonize deglaciated regions. However, the way that animals respond to climatic fluctuations varies widely among species and we were unable to find a relationship between climatic instability and other mammal life-history traits (longevity and litter size) in any of the two biogeographic regions. We, therefore, conclude that beyond some biological traits typical of macroecological analyses such as geographic range size and body size, it is difficult to infer the responsiveness of species distributions to climate change solely based on particular life-history traits.

Oncogenomic disruptions in arsenic-induced carcinogenesis

PubMed Central

Ng, Kevin W.; Stewart, Greg L.; Dummer, Trevor J.B.; Lam, Wan L.; Martinez, Victor D

2017-01-01

Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process. PMID:28179585

Ochratoxin a and mitotic disruption: mode of action analysis of renal tumor formation by ochratoxin A.

PubMed

Mally, Angela

2012-06-01

The mycotoxin and food contaminant ochratoxin A (OTA) is a potent renal carcinogen in rodents, but its mode of action (MoA) is still poorly defined. In 2006, the European Food Safety Authority concluded that there is a "lack of evidence for the existence of OTA-DNA adducts" and thus insufficient evidence to establish DNA reactivity as a MoA for tumor formation by OTA. In reviewing the available database on OTA toxicity, a MoA for renal carcinogenicity of OTA is developed that involves a combination of genetic instability and increased proliferative drive as consequences of OTA-mediated disruption of mitosis, whereby the organ- and site-specificity of tumor formation by OTA is determined by selective renal uptake of OTA into the proximal tubule epithelium. The proposed MoA is critically assessed with respect to concordance of dose-response of the suggested key events and tumor formation, their temporal association, consistency, and biological plausibility. Uncertainties, data gaps and needs for further research are highlighted.

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

Zakharov, Leonic E.; Li, Xujing

This paper formulates the Tokamak Magneto-Hydrodynamics (TMHD), initially outlined by X. Li and L.E. Zakharov [Plasma Science and Technology, accepted, ID:2013-257 (2013)] for proper simulations of macroscopic plasma dynamics. The simplest set of magneto-hydrodynamics equations, sufficient for disruption modeling and extendable to more refined physics, is explained in detail. First, the TMHD introduces to 3-D simulations the Reference Magnetic Coordinates (RMC), which are aligned with the magnetic field in the best possible way. The numerical implementation of RMC is adaptive grids. Being consistent with the high anisotropy of the tokamak plasma, RMC allow simulations at realistic, very high plasma electricmore » conductivity. Second, the TMHD splits the equation of motion into an equilibrium equation and the plasma advancing equation. This resolves the 4 decade old problem of Courant limitations of the time step in existing, plasma inertia driven numerical codes. The splitting allows disruption simulations on a relatively slow time scale in comparison with the fast time of ideal MHD instabilities. A new, efficient numerical scheme is proposed for TMHD.« less

Epidemiology of urban water distribution systems

NASA Astrophysics Data System (ADS)

Bardet, Jean-Pierre; Little, Richard

2014-08-01

Urban water distribution systems worldwide contain numerous old and fragile pipes that inevitably break, flood streets and damage property, and disrupt economic and social activities. Such breaks often present dramatically in temporal clusters as occurred in Los Angeles during 2009. These clustered pipe breaks share many characteristics with human mortality observed during extreme climatological events such as heat waves or air pollution. Drawing from research and empirical studies in human epidemiology, a framework is introduced to analyze the time variations of disruptive pipe breaks that can help water agencies better understand clustered pipe failures and institute measures to minimize the disruptions caused by them. It is posited that at any time, a cohort of the pipes comprising the water distribution system will be in a weakened state due to fatigue and corrosion. This frail cohort becomes vulnerable during normal operations and ultimately breaks due to rapid increase in crack lengths induced by abnormal stressors. The epidemiological harvesting model developed in this paper simulates an observed time series of monthly pipe breaks and has both explanatory and predictive power. It also demonstrates that models from nonengineering disciplines such as medicine can provide improved insights into the performance of infrastructure systems.

Enhanced membrane disruption and antibiotic action against pathogenic bacteria by designed histidine-rich peptides at acidic pH.

PubMed

Mason, A James; Gasnier, Claire; Kichler, Antoine; Prévost, Gilles; Aunis, Dominique; Metz-Boutigue, Marie-Hélène; Bechinger, Burkhard

2006-10-01

The histidine-rich amphipathic cationic peptide LAH4 has antibiotic and DNA delivery capabilities. Here, we explore the interaction of peptides from this family with model membranes as monitored by solid-state (2)H nuclear magnetic resonance and their antibiotic activities against a range of bacteria. At neutral pH, the membrane disruption is weak, but at acidic pH, the peptides strongly disturb the anionic lipid component of bacterial membranes and cause bacterial lysis. The peptides are effective antibiotics at both pH 7.2 and pH 5.5, although the antibacterial activity is strongly affected by the change in pH. At neutral pH, the LAH peptides were active against both methicillin-resistant and -sensitive Staphylococcus aureus strains but ineffective against Pseudomonas aeruginosa. In contrast, the LAH peptides were highly active against P. aeruginosa in an acidic environment, as is found in the epithelial-lining fluid of cystic fibrosis patients. Our results show that modest antibiotic activity of histidine-rich peptides can be dramatically enhanced by inducing membrane disruption, in this case by lowering the pH, and that histidine-rich peptides have potential as future antibiotic agents.

Modulation of Core Turbulent Density Fluctuations by Large-Scale Neoclassical Tearing Mode Islands in the DIII-D Tokamak

DOE PAGES

Bardóczi, L.; Rhodes, T. L.; Carter, T. A.; ...

2016-05-26

We report the first observation of localized modulation of turbulent density uctuations en (via Beam Emission Spectroscopy) by neoclassical tearing modes (NTMs) in the core of the DIII-D tokamak. NTMs are important as they often lead to severe degradation of plasma confinement and disruptions in high-confinement fusion experiments. Magnetic islands associated with NTMs significantly modify the profiles and turbulence drives. In this experiment n was found to be modulated by 14% across the island. Gyrokinetic simulations suggest that en could be dominantly driven by the ion temperature gradient (ITG) instability.

Achieving a long-lived high-beta plasma state by energetic beam injection

NASA Astrophysics Data System (ADS)

Guo, H. Y.; Binderbauer, M. W.; Tajima, T.; Milroy, R. D.; Steinhauer, L. C.; Yang, X.; Garate, E. G.; Gota, H.; Korepanov, S.; Necas, A.; Roche, T.; Smirnov, A.; Trask, E.

2015-04-01

Developing a stable plasma state with high-beta (ratio of plasma to magnetic pressures) is of critical importance for an economic magnetic fusion reactor. At the forefront of this endeavour is the field-reversed configuration. Here we demonstrate the kinetic stabilizing effect of fast ions on a disruptive magneto-hydrodynamic instability, known as a tilt mode, which poses a central obstacle to further field-reversed configuration development, by energetic beam injection. This technique, combined with the synergistic effect of active plasma boundary control, enables a fully stable ultra-high-beta (approaching 100%) plasma with a long lifetime.

Radio jet propagation and wide-angle tailed radio sources in merging galaxy cluster environments

NASA Technical Reports Server (NTRS)

Loken, Chris; Roettiger, Kurt; Burns, Jack O.; Norman, Michael

1995-01-01

The intracluster medium (ICM) within merging clusters of galaxies is likely to be in a violent or turbulent dynamical state which may have a significant effect on the evolution of cluster radio sources. We present results from a recent gas + N-body simulation of a cluster merger, suggesting that mergers can result in long-lived, supersonic bulk flows, as well as shocks, within a few hundred kiloparsecs of the core of the dominant cluster. These results have motivated our new two-dimensional and three-dimensional simulations of jet propagation in such environments. The first set of simulations models the ISM/ICM transition as a contact discontinuity with a strong velocity shear. A supersonic (M(sub j) = 6) jet crossing this discontinuity into an ICM with a transverse, supersonic wind bends continuously, becomes 'naked' on the upwind side, and forms a distended cocoon on the downwind side. In the case of a mildly supersonic jet (M(sub j) = 3), however, a shock is driven into the ISM and ISM material is pulled along with the jet into the ICM. Instabilities excited at the ISM/ICM interface result in the jet repeatedly pinching off and reestablishing itself in a series of 'disconnection events.' The second set of simulations deals with a jet encountering a shock in the merging cluster environment. A series of relatively high-resolution two-dimensional calculations is used to confirm earlier analysis predicting that the jet will not disrupt when the jet Mach number is greater than the shock Mach number. A jet which survives the encounter with the shock will decrease in radius and disrupt shortly thereafter as a result of the growth of Kelvin-Helmholtz instabilities. We also find, in disagreement with predictions, that the jet flaring angle decreases with increasing jet density. Finally, a three-dimensional simulation of a jet crossing an oblique shock gives rise to a morphology which resembles a wide-angle tailed radio source with the jet flaring at the shock and disrupting to form a long, turbulent tail which is dragged downstream by the preshock wind.

Scaled laboratory experiments explain the kink behaviour of the Crab Nebula jet

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

Li, C. K.; Tzeferacos, P.; Lamb, D.

X-ray images from the Chandra X-ray Observatory show that the South-East jet in the Crab nebula changes direction every few years. This remarkable phenomenon is also observed in jets associated with pulsar wind nebulae and other astrophysical objects, and therefore is a fundamental feature of astrophysical jet evolution that needs to be understood. Theoretical modeling and numerical simulations have suggested that this phenomenon may be a consequence of magnetic fields (B) and current-driven magnetohydrodynamic (MHD) instabilities taking place in the jet, but until now there has been no verification of this process in a controlled laboratory environment. Here we reportmore » the first such experiments, using scaled laboratory plasma jets generated by high-power lasers to model the Crab jet and monoenergetic-proton radiography to provide direct visualization and measurement of magnetic fields and their behavior. The toroidal magnetic field embedded in the supersonic jet triggered plasma instabilities and resulted in considerable deflections throughout the jet propagation, mimicking the kinks in the Crab jet. We also demonstrated that these kinks are stabilized by high jet velocity, consistent with the observation that instabilities alter the jet orientation but do not disrupt the overall jet structure. We successfully modeled these laboratory experiments with a validated three-dimensional (3D) numerical simulation, which in conjunction with the experiments provide compelling evidence that we have an accurate model of the most important physics of magnetic fields and MHD instabilities in the observed, kinked jet in the Crab nebula. The experiments initiate a novel approach in the laboratory for visualizing fields and instabilities associated with jets observed in various astrophysical objects, ranging from stellar to extragalactic systems. We expect that future work along this line will have important impact on the study and understanding of such fundamental astrophysical phenomena.« less

Scaled laboratory experiments explain the kink behaviour of the Crab Nebula jet

DOE PAGES

Li, C. K.; Tzeferacos, P.; Lamb, D.; ...

2016-10-07

X-ray images from the Chandra X-ray Observatory show that the South-East jet in the Crab nebula changes direction every few years. This remarkable phenomenon is also observed in jets associated with pulsar wind nebulae and other astrophysical objects, and therefore is a fundamental feature of astrophysical jet evolution that needs to be understood. Theoretical modeling and numerical simulations have suggested that this phenomenon may be a consequence of magnetic fields (B) and current-driven magnetohydrodynamic (MHD) instabilities taking place in the jet, but until now there has been no verification of this process in a controlled laboratory environment. Here we reportmore » the first such experiments, using scaled laboratory plasma jets generated by high-power lasers to model the Crab jet and monoenergetic-proton radiography to provide direct visualization and measurement of magnetic fields and their behavior. The toroidal magnetic field embedded in the supersonic jet triggered plasma instabilities and resulted in considerable deflections throughout the jet propagation, mimicking the kinks in the Crab jet. We also demonstrated that these kinks are stabilized by high jet velocity, consistent with the observation that instabilities alter the jet orientation but do not disrupt the overall jet structure. We successfully modeled these laboratory experiments with a validated three-dimensional (3D) numerical simulation, which in conjunction with the experiments provide compelling evidence that we have an accurate model of the most important physics of magnetic fields and MHD instabilities in the observed, kinked jet in the Crab nebula. The experiments initiate a novel approach in the laboratory for visualizing fields and instabilities associated with jets observed in various astrophysical objects, ranging from stellar to extragalactic systems. We expect that future work along this line will have important impact on the study and understanding of such fundamental astrophysical phenomena.« less

Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin.

PubMed

Baumann, Claudia; Wang, Xiaotian; Yang, Luhan; Viveiros, Maria M

2017-04-01

Mouse oocytes lack canonical centrosomes and instead contain unique acentriolar microtubule-organizing centers (aMTOCs). To test the function of these distinct aMTOCs in meiotic spindle formation, pericentrin (Pcnt), an essential centrosome/MTOC protein, was knocked down exclusively in oocytes by using a transgenic RNAi approach. Here, we provide evidence that disruption of aMTOC function in oocytes promotes spindle instability and severe meiotic errors that lead to pronounced female subfertility. Pcnt-depleted oocytes from transgenic (Tg) mice were ovulated at the metaphase-II stage, but show significant chromosome misalignment, aneuploidy and premature sister chromatid separation. These defects were associated with loss of key Pcnt-interacting proteins (γ-tubulin, Nedd1 and Cep215) from meiotic spindle poles, altered spindle structure and chromosome-microtubule attachment errors. Live-cell imaging revealed disruptions in the dynamics of spindle assembly and organization, together with chromosome attachment and congression defects. Notably, spindle formation was dependent on Ran GTPase activity in Pcnt-deficient oocytes. Our findings establish that meiotic division is highly error-prone in the absence of Pcnt and disrupted aMTOCs, similar to what reportedly occurs in human oocytes. Moreover, these data underscore crucial differences between MTOC-dependent and -independent meiotic spindle assembly. © 2017. Published by The Company of Biologists Ltd.

Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant α-Synuclein

PubMed Central

Ahsan, Nuzhat; Mishra, Satyendra; Jain, Manish Kumar; Surolia, Avadhesha; Gupta, Sarika

2015-01-01

Accumulating evidence suggests that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson’s disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against α-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of α-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of α-synuclein amyloidosis and toxicity in Parkinson’s disease and other synucleinopathies. PMID:25985292

17th Workshop on MHD Stability Control: addressing the disruption challenge for ITER

NASA Astrophysics Data System (ADS)

Buttery, Richard

2013-08-01

This annual workshop on magnetohydrodynamic stability control was held on 5-7 November 2012 at Columbia University in the city of New York, in the aftermath of a violent hydrodynamic instability event termed 'Hurricane Sandy'. Despite these challenging circumstances, Columbia University managed an excellent meeting, enabling the full participation of the community. This Workshop has been held since 1996 to help in the development of understanding and control of magnetohydrodynamic (MHD) instabilities for future fusion reactors. It covers a wide range of stability topics—from disruptions, to tearing modes, error fields, edge-localized modes (ELMs), resistive wall modes (RWMs) and ideal MHD—spanning many device types (tokamaks, stellarators and reversed field pinches) to identify commonalities in the physics and a means of control. The theme for 2012 was 'addressing the disruption challenge for ITER', and thus the first day had a heavy focus on both the avoidance and mitigation of disruptions in ITER. Key elements included understanding how to apply 3D fields to maintain stability, as well as managing the disruption process itself through mitigating loads in the thermal quench and handling so called 'runaway electrons'. This culminated in a panel discussion on the disruption mitigation strategy for ITER, which noted that heat load asymmetries during the thermal quench appear to be an artifact of MHD processes, and that runaway electron generation may be inevitable, suggesting research should focus on control and dissipation of the runaway beam. The workshop was combined this year with the annual US-Japan MHD Workshop, with a special section looking more deeply at 'Fundamentals of 3D Perturbed Equilibrium Control', with interesting sessions on 3D equilibrium reconstruction, RWM physics, novel control concepts such as non-magnetic sensing, adaptive control, q < 2 tokamak operation, and the effects of flow. The final day turned to tearing mode interactions, exploring the state of the art in 3D modeling, and innovative means of control through application of electromagnetic torques, use of electron cyclotron current drive and even the idea of electrostatic current drive. This concluded with a second panel discussion on the disruption avoidance strategy in ITER, which commented on the important role played by energetic particles in stability, ideas of active stability sensing and ways to progress 3D reconstruction. In this special section of Plasma Physics and Controlled Fusion , we present several of the invited and contributed papers from the 2012 workshop, which have been subject to the normal refereeing procedures of the journal. These give a sense of the exceptional quality of the presentations at this workshop, which may be found at: http://fusion.gat.com/conferences/mhd12/. The Program Committee deeply appreciates the participation and support our community continues to show in this workshop, which provides an unparalleled opportunity for in-depth discussion of MHD issues. We would also like to thank our hosts Columbia University, and in particular Professor Gerald Navratil, for outstanding support and facilities in the face of Hurricane Sandy's adversity. The meeting thanked outgoing Program Chair, Dr Richard Buttery from General Atomics, and welcomed next year's Program Chair, Professor David Maurer from Auburn University. The next meeting will be held in Santa Fe 18-20 November 2013.

Entrenched time delays versus accelerating opinion dynamics: are advanced democracies inherently unstable?

NASA Astrophysics Data System (ADS)

Gros, Claudius

2017-11-01

Modern societies face the challenge that the time scale of opinion formation is continuously accelerating in contrast to the time scale of political decision making. With the latter remaining of the order of the election cycle we examine here the case that the political state of a society is determined by the continuously evolving values of the electorate. Given this assumption we show that the time lags inherent in the election cycle will inevitable lead to political instabilities for advanced democracies characterized both by an accelerating pace of opinion dynamics and by high sensibilities (political correctness) to deviations from mainstream values. Our result is based on the observation that dynamical systems become generically unstable whenever time delays become comparable to the time it takes to adapt to the steady state. The time needed to recover from external shocks grows in addition dramatically close to the transition. Our estimates for the order of magnitude of the involved time scales indicate that socio-political instabilities may develop once the aggregate time scale for the evolution of the political values of the electorate falls below 7-15 months.

Laboring Underground: The Employment Patterns of Hispanic Immigrant Men in Durham, NC.

PubMed

Flippen, Chenoa A

2012-02-01

The dramatic increase in Hispanic immigration to the United States in recent decades has been coterminous with fundamental shifts in the labor market towards heightened flexibility, instability, and informality. As a result, the low-wage labor market is increasingly occupied by Hispanic immigrants, many of whom are undocumented. While numerous studies examine the implications for natives' employment prospects, our understanding of low-wage immigrants themselves remains underdeveloped. Drawing on original data collected in Durham, North Carolina, this article provides a more holistic account of immigrant Hispanic's labor market experiences, examining not only wages but also employment instability and benefit coverage. The analysis evaluates the role of human capital and immigration characteristics, including legal status, in shaping compensation outcomes, as well as the influence of other employment characteristics. Findings highlight the salience of nonstandard work arrangements such as subcontracting and informal employment to the labor market experiences of immigrant Hispanic men, and describe the constellation of risk factors that powerfully bound immigrant employment outcomes. Keywords: Hispanic; immigration; wages; low-wage labor market; employment relations.

Modeling of the Convection and Interaction of Ring Current, Plasmaspheric and Plasma Sheet Plasmas in the Inner Magnetosphere

NASA Technical Reports Server (NTRS)

Fok, Mei-Ching; Chen, Sheng-Hsien; Buzulukova, Natalia; Glocer, Alex

2010-01-01

Distinctive sources of ions reside in the plasmasphere, plasmasheet, and ring current regions at discrete energies constitute the major plasma populations in the inner/middle magnetosphere. They contribute to the electrodynamics of the ionosphere-magnetosphere system as important carriers of the global current system, in triggering; geomagnetic storm and substorms, as well as critical components of plasma instabilities such as reconnection and Kelvin-Helmholtz instability at the magnetospheric boundaries. Our preliminary analysis of in-situ measurements shoves the complexity of the plasmas pitch angle distributions at particularly the cold and warm plasmas, vary dramatically at different local times and radial distances from the Earth in response to changes in solar wind condition and Dst index. Using an MHD-ring current coupled code, we model the convection and interaction of cold, warm and energetic ions of plasmaspheric, plasmasheet, and ring current origins in the inner magnetosphere. We compare our simulation results with in-situ and remotely sensed measurements from recent instrumentation on Geotail, Cluster, THEMIS, and TWINS spacecraft.

Laboring Underground: The Employment Patterns of Hispanic Immigrant Men in Durham, NC

PubMed Central

Flippen, Chenoa A.

2012-01-01

The dramatic increase in Hispanic immigration to the United States in recent decades has been coterminous with fundamental shifts in the labor market towards heightened flexibility, instability, and informality. As a result, the low-wage labor market is increasingly occupied by Hispanic immigrants, many of whom are undocumented. While numerous studies examine the implications for natives’ employment prospects, our understanding of low-wage immigrants themselves remains underdeveloped. Drawing on original data collected in Durham, North Carolina, this article provides a more holistic account of immigrant Hispanic’s labor market experiences, examining not only wages but also employment instability and benefit coverage. The analysis evaluates the role of human capital and immigration characteristics, including legal status, in shaping compensation outcomes, as well as the influence of other employment characteristics. Findings highlight the salience of nonstandard work arrangements such as subcontracting and informal employment to the labor market experiences of immigrant Hispanic men, and describe the constellation of risk factors that powerfully bound immigrant employment outcomes. Keywords: Hispanic; immigration; wages; low-wage labor market; employment relations. PMID:22844159

Disruption of postural readaptation by inertial stimuli following space flight

NASA Technical Reports Server (NTRS)

Black, F. O.; Paloski, W. H.; Reschke, M. F.; Igarashi, M.; Guedry, F.; Anderson, D. J.

1999-01-01

Postural instability (relative to pre-flight) has been observed in all shuttle astronauts studied upon return from orbital missions. Postural stability was more closely examined in four shuttle astronaut subjects before and after an 8 day orbital mission. Results of the pre- and post-flight postural stability studies were compared with a larger (n = 34) study of astronauts returning from shuttle missions of similar duration. Results from both studies indicated that inadequate vestibular feedback was the most significant sensory deficit contributing to the postural instability observed post flight. For two of the four IML-1 astronauts, post-flight postural instability and rate of recovery toward their earth-normal performance matched the performance of the larger sample. However, post-flight postural control in one returning astronaut was substantially below mean performance. This individual, who was within normal limits with respect to postural control before the mission, indicated that recovery to pre-flight postural stability was also interrupted by a post-flight pitch plane rotation test. A similar, though less extreme departure from the mean recovery trajectory was present in another astronaut following the same post-flight rotation test. The pitch plane rotation stimuli included otolith stimuli in the form of both transient tangential and constant centripetal linear acceleration components. We inferred from these findings that adaptation on orbit and re-adaptation on earth involved a change in sensorimotor integration of vestibular signals most likely from the otolith organs.

Formation and evolution of magnetised filaments in wind-swept turbulent clumps

NASA Astrophysics Data System (ADS)

Banda-Barragan, Wladimir Eduardo; Federrath, Christoph; Crocker, Roland M.; Bicknell, Geoffrey Vincent; Parkin, Elliot Ross

2015-08-01

Using high-resolution three-dimensional simulations, we examine the formation and evolution of filamentary structures arising from magnetohydrodynamic interactions between supersonic winds and turbulent clumps in the interstellar medium. Previous numerical studies assumed homogenous density profiles, null velocity fields, and uniformly distributed magnetic fields as the initial conditions for interstellar clumps. Here, we have, for the first time, incorporated fractal clumps with log-normal density distributions, random velocity fields and turbulent magnetic fields (superimposed on top of a uniform background field). Disruptive processes, instigated by dynamical instabilities and akin to those observed in simulations with uniform media, lead to stripping of clump material and the subsequent formation of filamentary tails. The evolution of filaments in uniform and turbulent models is, however, radically different as evidenced by comparisons of global quantities in both scenarios. We show, for example, that turbulent clumps produce tails with higher velocity dispersions, increased gas mixing, greater kinetic energy, and lower plasma beta than their uniform counterparts. We attribute the observed differences to: 1) the turbulence-driven enhanced growth of dynamical instabilities (e.g. Kelvin-Helmholtz and Rayleigh-Taylor instabilities) at fluid interfaces, and 2) the localised amplification of magnetic fields caused by the stretching of field lines trapped in the numerous surface deformations of fractal clumps. We briefly discuss the implications of this work to the physics of the optical filaments observed in the starburst galaxy M82.

Phase stability limit of c-BN under hydrostatic and non-hydrostatic pressure conditions

NASA Astrophysics Data System (ADS)

Xiao, Jianwei; Du, Jinglian; Wen, Bin; Melnik, Roderick; Kawazoe, Yoshiyuki; Zhang, Xiangyi

2014-04-01

Phase stability limit of cubic boron nitride (c-BN) has been investigated by the crystal structure search technique. It indicated that this limit is ˜1000 GPa at hydrostatic pressure condition. Above this pressure, c-BN turns into a metastable phase with respect to rocksalt type boron nitride (rs-BN). However, rs-BN cannot be retained at 0 GPa owing to its instability at pressure below 250 GPa. For non-hydrostatic pressure conditions, the phase stability limit of c-BN is substantially lower than that under hydrostatic pressure conditions and it is also dramatically different for other pressure mode.

He-3-rich flares - A possible explanation

NASA Technical Reports Server (NTRS)

Fisk, L. A.

1978-01-01

A plasma mechanism is proposed to explain the dramatic enhancements in He-3 observed in He-3-rich flares. It is shown that a common current instability in the corona may heat ambient He-3(2+) over any other ion and thus may preferentially inject He-3 into the flare acceleration process. This mechanism operates when the abundance of He-4 and heavier elements is larger than normal in the coronal plasma. It may also preferentially heat and thus inject certain ions of iron. The mechanism thus provides a possible explanation for the observed correlation between He-3 and heavy enhancements in He-3-rich flares.

Phase stability limit of c-BN under hydrostatic and non-hydrostatic pressure conditions

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

Xiao, Jianwei; Du, Jinglian; Wen, Bin, E-mail: wenbin@ysu.edu.cn

2014-04-28

Phase stability limit of cubic boron nitride (c-BN) has been investigated by the crystal structure search technique. It indicated that this limit is ∼1000 GPa at hydrostatic pressure condition. Above this pressure, c-BN turns into a metastable phase with respect to rocksalt type boron nitride (rs-BN). However, rs-BN cannot be retained at 0 GPa owing to its instability at pressure below 250 GPa. For non-hydrostatic pressure conditions, the phase stability limit of c-BN is substantially lower than that under hydrostatic pressure conditions and it is also dramatically different for other pressure mode.

Centrifugal inertia effects in two-phase face seal films

NASA Technical Reports Server (NTRS)

Basu, P.; Hughes, W. F.; Beeler, R. M.

1987-01-01

A simplified, semianalytical model has been developed to analyze the effect of centrifugal inertia in two-phase face seals. The model is based on the assumption of isothermal flow through the seal, but at an elevated temperature, and takes into account heat transfer and boiling. Using this model, seal performance curves are obtained with water as the working fluid. It is shown that the centrifugal inertia of the fluid reduces the load-carrying capacity dramatically at high speeds and that operational instability exists under certain conditions. While an all-liquid seal may be starved at speeds higher than a 'critical' value, leakage always occurs under boiling conditions.

Stability and Control of Burning Tokamak Plasmas with Resistive Walls: Final Technical Report

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

Miller, George; Brennan, Dylan; Cole, Andrew

This project is focused on theoretical and computational development for quantitative prediction of the stability and control of the equilibrium state evolution in toroidal burning plasmas, including its interaction with the surrounding resistive wall. The stability of long pulse burning plasmas is highly sensitive to the physics of resonant layers in the plasma, sources of momentum and flow, kinetic effects of energetic particles, and boundary conditions at the wall, including feedback control and error fields. In ITER in particular, the low toroidal flow equilibrium state, sustained primarily by energetic alpha particles from fusion reactions, will require the consideration of allmore » of these key elements to predict quantitatively the stability and evolution. The principal investigators on this project have performed theoretical and computational analyses, guided by analytic modeling, to address this physics in realistic configurations. The overall goal has been to understand the key physics mechanisms that describe stable toroidal burning plasmas under active feedback control. Several relevant achievements have occurred during this project, leading to publications and invited conference presentations. In theoretical efforts, with the physics of the resonant layers, resistive wall, and toroidal momentum transport included, this study has extended from cylindrical resistive plasma - resistive wall models with feedback control to toroidal geometry with strong shaping to study mode coupling effects on the stability. These results have given insight into combined tearing and resistive wall mode behavior in simulations and experiment, while enabling a rapid exploration of plasma parameter space, to identify possible domains of interest for large plasma codes to investigate in more detail. Resonant field amplification and quasilinear torques in the presence of error fields and velocity shear have also been investigated. Here it was found, surprisingly, that the Maxwell torque on resonant layers in the plasma which exhibit finite real frequencies ωr in their response is significantly different from the conventional results based on tearing layers with pure real growth (or damping) rates. This observation suggests the possibility that the torque on the tearing layers can lock the plasma rotation to this finite phase velocity, which may lead to locking in which velocity shear is maintained. More broadly, the sources of all torques driving flows in magnetic confinement experiments is not fully understood, and this theoretical work may shed light on puzzling experimental results. It was also found that real frequencies occur over a wide range of plasma response regimes, and are indeed the norm and not the exception, often leading to profound effects on the locking torque. Also, the influence of trapped energetic ions orbiting over the resistive plasma mode structure, a critical effect in burning plasmas, was investigated through analytic modeling and analysis of simulations and experiment. This effort has shown that energetic ions can drive the development of disruptive instabilities, but also damp and stabilize the instabilities, depending on the details of the shear in the equilibrium magnetic field. This finding could be critical to maintaining stable operations in burning plasmas. In the most recent work, a series of simulations have been conducted to study the effect of differential flow and energetic ion effects on entry to the onset of a disruptive instability in the most realistic conditions possible, with preexisting nonlinearly saturated benign instabilities. Throughout this work, the linear and quasilinear theory of resonant layers with differential flow between them, their interaction with resistive wall and error fields, and energetic ions effects, have been used to understand realistic simulations of mode onset and the experimental discharges they represent. These studies will continue to answer remaining questions about the relation between theoretical results obtained in this project and observations of the onset and evolution of disruptive instabilities in experiment.« less

Clock gene Per2 as a controller of liver carcinogenesis

PubMed Central

Mteyrek, Ali; Filipski, Elisabeth; Guettier, Catherine; Okyar, Alper; Lévi, Francis

2016-01-01

Environmental disruption of molecular clocks promoted liver carcinogenesis and accelerated cancer progression in rodents. We investigated the specific role of clock gene Period 2 (Per2) for liver carcinogenesis and clock-controlled cellular proliferation, genomic instability and inflammation. We assessed liver histopathology, and determined molecular and physiology circadian patterns in mice on chronic diethylnitrosamine (DEN) exposure according to constitutive Per2 mutation. First, we found that Per2m/m liver displayed profound alterations in proliferation gene expression, including c-Myc derepression, phase-advanced Wee1, and arrhythmic Ccnb1 and K-ras mRNA expressions, as well as deregulated inflammation, through arrhythmic liver IL-6 protein concentration, in the absence of any DEN exposure. These changes could then make Per2m/m mice more prone to subsequently develop liver cancers on DEN. Indeed, primary liver cancers were nearly fourfold as frequent in Per2m/m mice as compared to wild-type (WT), 4 months after DEN exposure. The liver molecular clock was severely disrupted throughout the whole carcinogenesis process, including the initiation stage, i.e. within the initial 17 days on DEN. Per2m/m further exhibited increased c-Myc and Ccnb1 mean 24h expressions, lack of P53 response, and arrhythmic ATM, Wee1 and Ccnb1 expressions. DEN-induced tumor related inflammation was further promoted through increased protein concentrations of liver IL-6 and TNF-α as compared to WT during carcinogenesis initiation. Per2 mutation severely deregulated liver gene or protein expressions related to three cancer hallmarks, including uncontrolled proliferation, genomic instability, and tumor promoting inflammation, and accelerated liver carcinogenesis several-fold. Clock gene Per2 acted here as a liver tumor suppressor from initiation to progression. PMID:27494874

Overview of NSTX Upgrade initial results and modelling highlights

NASA Astrophysics Data System (ADS)

Menard, J. E.; Allain, J. P.; Battaglia, D. J.; Bedoya, F.; Bell, R. E.; Belova, E.; Berkery, J. W.; Boyer, M. D.; Crocker, N.; Diallo, A.; Ebrahimi, F.; Ferraro, N.; Fredrickson, E.; Frerichs, H.; Gerhardt, S.; Gorelenkov, N.; Guttenfelder, W.; Heidbrink, W.; Kaita, R.; Kaye, S. M.; Kriete, D. M.; Kubota, S.; LeBlanc, B. P.; Liu, D.; Lunsford, R.; Mueller, D.; Myers, C. E.; Ono, M.; Park, J.-K.; Podesta, M.; Raman, R.; Reinke, M.; Ren, Y.; Sabbagh, S. A.; Schmitz, O.; Scotti, F.; Sechrest, Y.; Skinner, C. H.; Smith, D. R.; Soukhanovskii, V.; Stoltzfus-Dueck, T.; Yuh, H.; Wang, Z.; Waters, I.; Ahn, J.-W.; Andre, R.; Barchfeld, R.; Beiersdorfer, P.; Bertelli, N.; Bhattacharjee, A.; Brennan, D.; Buttery, R.; Capece, A.; Canal, G.; Canik, J.; Chang, C. S.; Darrow, D.; Delgado-Aparicio, L.; Domier, C.; Ethier, S.; Evans, T.; Ferron, J.; Finkenthal, M.; Fonck, R.; Gan, K.; Gates, D.; Goumiri, I.; Gray, T.; Hosea, J.; Humphreys, D.; Jarboe, T.; Jardin, S.; Jaworski, M. A.; Koel, B.; Kolemen, E.; Ku, S.; La Haye, R. J.; Levinton, F.; Luhmann, N.; Maingi, R.; Maqueda, R.; McKee, G.; Meier, E.; Myra, J.; Perkins, R.; Poli, F.; Rhodes, T.; Riquezes, J.; Rowley, C.; Russell, D.; Schuster, E.; Stratton, B.; Stutman, D.; Taylor, G.; Tritz, K.; Wang, W.; Wirth, B.; Zweben, S. J.

2017-10-01

The National Spherical Torus Experiment (NSTX) has undergone a major upgrade, and the NSTX Upgrade (NSTX-U) Project was completed in the summer of 2015. NSTX-U first plasma was subsequently achieved, diagnostic and control systems have been commissioned, the H-mode accessed, magnetic error fields identified and mitigated, and the first physics research campaign carried out. During ten run weeks of operation, NSTX-U surpassed NSTX record pulse-durations and toroidal fields (TF), and high-performance ~1 MA H-mode plasmas comparable to the best of NSTX have been sustained near and slightly above the n  =  1 no-wall stability limit and with H-mode confinement multiplier H98y,2 above 1. Transport and turbulence studies in L-mode plasmas have identified the coexistence of at least two ion-gyro-scale turbulent micro-instabilities near the same radial location but propagating in opposite (i.e. ion and electron diamagnetic) directions. These modes have the characteristics of ion-temperature gradient and micro-tearing modes, respectively, and the role of these modes in contributing to thermal transport is under active investigation. The new second more tangential neutral beam injection was observed to significantly modify the stability of two types of Alfven eigenmodes. Improvements in offline disruption forecasting were made in the areas of identification of rotating MHD modes and other macroscopic instabilities using the disruption event characterization and forecasting code. Lastly, the materials analysis and particle probe was utilized on NSTX-U for the first time and enabled assessments of the correlation between boronized wall conditions and plasma performance. These and other highlights from the first run campaign of NSTX-U are described.

[Developmental instability of the organism as a result of pessimization of environment under anthropogenic transformation of natural landscapes].

PubMed

Shadrina, E G; Vol'pert, Ia L

2014-01-01

The value of fluctuating asymmetry is considered to be an indicator of the developmental instability of the organism. The consequences of activities of the mining industry plants, which are characterized by alienation and transformation of large areas of natural landscapes, are analyzed as an anthropogenic factor. The objects of study were small mammals (northern red-backed (Clethrionomys rutilus) and gray red-backed (Clethrionomys rufocanus) voles, tundra vole (Microtus oeconomus), Laxmann's (Sorex caecutiens) and tundra (S. tundrensis) shrews) and trees (Japanese white birch (Betula platyphylla), Betula divaricate, Betula exilis, Duschekiafruticosa, and common osier (Salix viminalis)). In total, 3500 skulls and approximately 30000 leaves collected in the taiga zone of Yakutia were studied. The index offluctuating asymmetry, as well as population parameters and composition of small mammal communities, were analyzed. The data on the value of the fluctuating asymmetry in the studied species in natural habitats are given. It is shown that, in natural conditions, this parameter can rise with deterioration in living conditions, particularly at the ecological periphery of the range. Anthropogenic transformation of natural landscapes creates an "anthropogenic periphery" and causes changes similar to the adaptive responses at the northern limit of the distribution of species. It was found that, through pollution and disruption of ecosystems, the mining industry affects all levels of organization of the living matter, but the population and cenotic parameters give an unambiguous response only at macroanthropogenic transformations. Increase in the level of fluctuating asymmetry is the most sensitive indicator of anthropogenic impact and it should also be taken into account that disruptions in the developmental stability of an organism reflect the destructive processes occurring in the population and community.

Overview of NSTX Upgrade Initial Results and Modelling Highlights

DOE Data Explorer

Menard, J.E. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000312923286); Allain, J.P.; Battaglia, D.J. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000188979740); Bedoya, F.; Bell, R.E. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:000000019544498X); Belova, E. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000215251027); Berkery, J.W. [Columbia University, New York, NY, United States of America; Boyer, M.D. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000268459155); Crocker, N.; Diallo, A. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:000000020706060X); Ebrahimi, F. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000331095367); Ferraro, N. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000263487827); Fredrickson, E. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Frerichs, H.; Gerhardt, S. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000225462194); Gorelenkov, N. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Guttenfelder, W. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:000000018181058X); Heidbrink, W.; Kaita, R. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000285159824); Kaye, S.M. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Kriete, D.M.; Kubota, S.; LeBlanc, B.P. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000314550129); Liu, D. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000191747078); Lunsford, R. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000335886801); Mueller, D. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000224563356); Myers, C.E.; Ono, M. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Park, J-K. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000324198667); Podesta, M. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000349750585); Raman, R. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000220273271); Reinke, M.; Ren, Y. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000198316035); Sabbagh, S.A.; Schmitz, O.; Scotti, F. [Lawrence Livermore National Laboratory, Livermore, CA, United States of America; Sechrest, Y.; Skinner, C.H. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Smith, D.R. [University of Wisconsin, Madison, WI, United States of America; Soukhanovskii, V.; Stoltzfus-Dueck, T. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000325876298); Yuh, H.; Wang, Z. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Waters, I.; Ahn, J-W.; Andre, R.; Barchfield, R.; Beiersdorfer, P.; Bertelli, N. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000293267585); Bhattacharjee, A. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000164110178); Boyle, D. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000180918169); Brennan, D.; Buttery, R.; Capece, A. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000341477174); Canal, G.; Canik, J.; Chang, C.S. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000233465731); Darrow, D. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Delgado-Aparicio, L. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000167394380); Domier, C.; Ethier, S. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Evans, T.; Ferron, J.; Finkenthal, M.; Fonck, R.; Gan, K.; Gates, D. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000156793124); Goumiri, I. [University of Wisconsin, Madison, WI, United States of America; Gray, T.; Hosea, J. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Humphreys, D.; Jarboe, T.; Jardin, S. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000163906908); Jaworski, M.A. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Koel, B.; Kolemen, E. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000342123247); Ku, S. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000299641208); LaHaye, R.J.; Levinton, F.; Luhmann Jr., N.; Maingi, R. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000312388121); Maqueda, R. [X Science LLC, Plainsboro, NJ, United States of America; McKee, G.; Meier, E.; Myra, J.; Perkins, R. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000272160201); Poli, F. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000339594371); Rhodes, T.; Riquezes, J.; Rowley, C. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000290995739); Russell, D.; Schuster, E.; Stratton, B. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Stutman, D.; Taylor, G. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000258487152); Tritz, K. [Johns Hopkins University, Baltimore, MD, United States of America; Wang, W. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Wirth, B.; Zweben, S.J. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States)] (ORCID:0000000217380586)

2017-01-01

The National Spherical Torus Experiment (NSTX) has undergone a major upgrade, and the NSTX Upgrade (NSTX-U) Project was completed in the summer of 2015. NSTX-U first plasma was subsequently achieved, diagnostic and control systems have been commissioned, H-Mode accessed, magnetic error fields identified and mitigated, and the first physics research campaign carried out. During 10 run weeks of operation, NSTX-U surpassed NSTX-record pulse-durations and toroidal fields, and high-performance ~1MA H-mode plasmas comparable to the best of NSTX have been sustained near and slightly above the n=1 no-wall stability limit and with H-mode confinement multiplier H98y2 above 1. Transport and turbulence studies in L-mode plasmas have identified the coexistence of at least two ion-gyro-scale turbulent micro-instabilities near the same radial location but propagating in opposite (i.e. ion and electron diamagnetic) directions. These modes have the characteristics of ion-temperature gradient and micro-tearing modes, respectively, and the role of these modes in contributing to thermal transport is under active investigation. The new second more tangential neutral beam injection was observed to significantly modify the stability of two types of Alfven Eigenmodes. Improvements in offline disruption forecasting were made in the areas of identification of rotating MHD modes and other macroscopic instabilities using the Disruption Event Characterization and Forecasting (DECAF) code. Lastly, the Materials Analysis and Particle Probe (MAPP) was utilized on NSTX-U for the first time and enabled assessments of the correlation between boronized wall conditions and plasma performance. These and other highlights from the first run campaign of NSTX-U are described.

Telomeres, Reproductive Aging, and Genomic Instability During Early Development.

PubMed

Keefe, David L

2016-12-01

Implantation rate decreases and miscarriage rate increases with advancing maternal age. The oocyte must be the locus of reproductive aging because donation of oocytes from younger to older women abrogates the effects of aging on fecundity. Nuclear transfer experiments in a mouse model of reproductive aging show that the reproductive aging phenotype segregates with the nucleus rather than the cytoplasm. A number of factors within the nucleus have been hypothesized to mediate reproductive aging, including disruption of cohesions, reduced chiasma, aneuploidy, disrupted meiotic spindles, and DNA damage caused by chronic exposure to reactive oxygen species. We have proposed telomere attrition as a parsimonious way to explain these diverse effects of aging on oocyte function. Telomeres are repetitive sequences of DNA and associated proteins, which form a loop (t loop) at chromosome ends. Telomeres prevent the blunt end of DNA from triggering a DNA damage response. Previously, we showed that experimental telomere shortening phenocopies reproductive aging in mice. Telomere shortening causes reduced synapsis and chiasma, chromosome fusions, embryo arrest and fragmentation, and abnormal meiotic spindles. Telomere length of polar bodies predicts the fragmentation of human embryos. Telomerase, the reverse transcriptase capable of reconstituting shortened telomeres, is only minimally active in oocytes and preimplantation embryos. Intriguingly, during the first cell cycles following activation, telomeres robustly elongate via a DNA double-strand break mechanism called alternative lengthening of telomeres (ALTs). Alternative lengthening of telomere takes place even in telomerase-null mice. This mechanism of telomere elongation previously had been found only in cancer cells lacking telomerase activity. We propose that ALT elongates telomeres across generations but does so at the cost of extensive genomic instability in preimplantation embryos. © The Author(s) 2016.

Overview of NSTX Upgrade initial results and modelling highlights

DOE PAGES

Menard, J. E.; Allain, J. P.; Battaglia, D. J.; ...

2017-06-20

The National Spherical Torus Experiment (NSTX) has undergone a major upgrade, and the NSTX Upgrade (NSTX-U) Project was completed in the summer of 2015. NSTX-U first plasma was subsequently achieved, diagnostic and control systems have been commissioned, the H-mode accessed, magnetic error fields identified and mitigated, and the first physics research campaign carried out. During ten run weeks of operation, NSTX-U surpassed NSTX record pulse-durations and toroidal fields (TF), and high-performance ~1 MA H-mode plasmas comparable to the best of NSTX have been sustained near and slightly above the n = 1 no-wall stability limit and with H-mode confinement multipliermore » H 98y,2 above 1. Transport and turbulence studies in L-mode plasmas have identified the coexistence of at least two ion-gyro-scale turbulent micro-instabilities near the same radial location but propagating in opposite (i.e. ion and electron diamagnetic) directions. These modes have the characteristics of ion-temperature gradient and micro-tearing modes, respectively, and the role of these modes in contributing to thermal transport is under active investigation. The new second more tangential neutral beam injection was observed to significantly modify the stability of two types of Alfven eigenmodes. Improvements in offline disruption forecasting were made in the areas of identification of rotating MHD modes and other macroscopic instabilities using the disruption event characterization and forecasting code. Finally, the materials analysis and particle probe was utilized on NSTX-U for the first time and enabled assessments of the correlation between boronized wall conditions and plasma performance. These and other highlights from the first run campaign of NSTX-U are described.« less

Synthetic Absorption Lines for a Clumpy Medium: A Spectral Signature for Cloud Acceleration in AGN?

NASA Technical Reports Server (NTRS)

Waters, Tim; Proga, Daniel; Dannen, Randall; Kallman, Timothy R.

2017-01-01

There is increasing evidence that the highly ionized multiphase components of AGN disc winds may be due to thermal instability. The ions responsible for forming the observed X-ray absorption lines may only exist in relatively cool clumps that can be identified with the so-called warm absorbers. Here we calculate synthetic absorption lines for such warm absorbers from first principles by combining 2D hydrodynamic solutions of a two-phase medium with a dense grid of photoionization models to determine the detailed ionization structure of the gas. Our calculations reveal that cloud disruption, which leads to a highly complicated velocity field (i.e. a clumpy flow), will only mildly affect line shapes and strengths when the warm gas becomes highly mixed but not depleted. Prior to complete disruption, clouds that are optically thin to the driving UV resonance lines will cause absorption at an increasingly blueshifted line-of-sight velocity as they are accelerated. This behavior will imprint an identifiable signature on the line profile if warm absorbers are enshrouded in an even broader absorption line produced by a high column of intercloud gas. Interestingly, we show that it is possible to develop a spectral diagnostic for cloud acceleration by differencing the absorption components of a doublet line, a result that can be qualitatively understood using a simple partial covering model. Our calculations also permit us to comment on the spectral differences between cloud disruption and ionization changes driven by flux variability. Notably, cloud disruption offers another possibility for explaining absorption line variability.

Plantar-Plate Disruptions: “The Severe Turf-Toe Injury.” Three Cases in Contact Athletes

PubMed Central

Drakos, Mark C.; Fiore, Russell; Murphy, Conor; DiGiovanni, Christopher W.

2015-01-01

Objective: To present 3 cases of plantar-plate rupture and turf-toe injury in contact athletes at 1 university and to discuss appropriate diagnosis and treatment algorithms for each case. Background: Turf toe is a common injury in athletes participating in outdoor cutting sports. However, it has been used as an umbrella term to describe many different injuries of the great toe. In some cases, the injury can be so severe that the plantar plate and sesamoid apparatus may be ruptured. These patients may be better managed with surgery than with traditional nonoperative interventions. Differential Diagnosis: Turf toe, plantar-plate disruption, sesamoid fracture. Treatment: For stable injuries in which the plantar plate is not completely disrupted, nonoperative treatment with casting or a stiff-soled shoe, gradual weight bearing, and rehabilitation is the best practice. Unstable injuries require surgical intervention and plantar-plate repair. Uniqueness: Turf toe and injury to the first metatarsophalangeal joint are relatively common injuries in athletes, but few researchers have detailed the operative and nonoperative treatments of plantar-plate disruption in these patients. We examine 3 cases that occurred over 4 seasons on a collegiate football team. Conclusions: Turf toe represents a wide array of pathologic conditions involving the first metatarsophalangeal joint. Stress and instability testing are key components to assess in determining whether surgical intervention is warranted to restore optimal function. Stiffer-soled shoes or shoes with steel-plate insertions may help to prevent these injuries and are useful tools for protection during the rehabilitation period. PMID:25695855

1I/‘Oumuamua as a Tidal Disruption Fragment from a Binary Star System

NASA Astrophysics Data System (ADS)

Ćuk, Matija

2018-01-01

1I/‘Oumuamua is the first known interstellar small body, probably being only about 100 m in size. Against expectations based on comets, ‘Oumuamua does not show any activity and has a very elongated figure, and it also exhibits undamped rotational tumbling. In contrast, ‘Oumuamua’s trajectory indicates that it was moving with the local stars, as expected from a low-velocity ejection from a relatively nearby system. Here, I assume that ‘Oumuamua is typical of 100 m interstellar objects and speculate on its origins. I find that giant planets are relatively inefficient at ejecting small bodies from inner solar systems of main-sequence stars, and that binary systems offer a much better opportunity for ejections of non-volatile bodies. I also conclude that ‘Oumuamua is not a member of a collisional population, which could explain its dramatic difference from small asteroids. I observe that 100 m small bodies are expected to carry little mass in realistic collisional populations and that occasional events, when whole planets are disrupted in catastrophic encounters, may dominate the interstellar population of 100 m fragments. Unlike the Sun or Jupiter, red dwarf stars are very dense and are capable of thoroughly tidally disrupting terrestrial planets. I conclude that ‘Oumuamua may have originated as a fragment from a planet that was tidally disrupted and then ejected by a dense member of a binary system, which could explain its peculiarities.

Recovery of postural equilibrium control following spaceflight

NASA Technical Reports Server (NTRS)

Paloski, W. H.; Reschke, M. F.; Black, F. O.; Doxey, D. D.; Harm, D. L.

1992-01-01

Decreased postural stability is observed in most astronauts immediately following spaceflight. Because ataxia may present postflight operational hazards, it is important to determine the incidence of postural instability immediately following landing and the dynamics of recovery of normal postural equilibrium control. It is postulated that postflight postural instability results from in-flight adaptive changes in central nervous system (CNS) processing of sensory information from the visual, vestibular, and proprioceptive systems. The purpose of the present investigation was to determine the magnitude and time course of postflight recovery of postural equilibrium control and, hence, readaptation of CNS processing of sensory information. Thirteen crew members from six spaceflight missions were studied pre- and postflight using a modified commercial posturography system. Postural equilibrium control was found to be seriously disrupted immediately following spaceflight in all subjects. Readaptation to the terrestrial environment began immediately upon landing, proceeded rapidly for the first 10-12 hours, and then proceeded much more slowly for the subsequent 2-4 days until preflight stability levels were reachieved. It is concluded that the overall postflight recovery of postural stability follows a predictable time course.

TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish

PubMed Central

Reverendo, Marisa; Soares, Ana R; Pereira, Patrícia M; Carreto, Laura; Ferreira, Violeta; Gatti, Evelina; Pierre, Philippe; Moura, Gabriela R; Santos, Manuel A

2014-01-01

Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through proteome instability and saturation of the proteostasis network. To test this hypothesis we have induced mistranslation in zebrafish embryos using mutant tRNAs that misincorporate Serine (Ser) at various non-cognate codon sites. Embryo viability was affected and malformations were observed, but a significant proportion of embryos survived by activating the unfolded protein response (UPR), the ubiquitin proteasome pathway (UPP) and downregulating protein biosynthesis. Accumulation of reactive oxygen species (ROS), mitochondrial and nuclear DNA damage and disruption of the mitochondrial network, were also observed, suggesting that mistranslation had a strong negative impact on protein synthesis rate, ER and mitochondrial homeostasis. We postulate that mistranslation promotes gradual cellular degeneration and disease through protein aggregation, mitochondrial dysfunction and genome instability. PMID:25483040

Predictors of social instability stress effects on social interaction and anxiety in adolescent male rats.

PubMed

Hodges, Travis E; Baumbach, Jennet L; McCormick, Cheryl M

2018-06-21

Adolescence is an important phase of development of social behaviors, which may be disrupted by the experience of stressors. We previously reported that exposure to social instability stress in adolescence (SS; postnatal day [PND] 30-45) in rats reduced social interactions with unfamiliar peers compared with non-stressed controls (CTL). In experiment 1, we replicated the effect of SS on social interaction and found that the pattern of neural activations based on Fos immunohistochemistry in brain regions during social interactions differed for SS and CTL rats. In experiment 2, we found that individual differences in novelty-seeking behavior on PND 30 and SS exposure were unique predictors of anxiety in the elevated plus maze on PND 46, and interacted to predict social interaction on PND 47; among high novelty-seeking rats, SS and CTL rats do not differ, whereas among low-novelty seeking rats, SS rats engaged in less social interaction than did CTL rats. Thus, high novelty-seeking may be a resilience factor against the effects of social stressors in adolescence. © 2018 Wiley Periodicals, Inc.

Magnetorotational Instability in Eccentric Disks

NASA Astrophysics Data System (ADS)

Chan, Chi-Ho; Krolik, Julian H.; Piran, Tsvi

2018-03-01

Eccentric disks arise in such astrophysical contexts as tidal disruption events, but it is unknown whether the magnetorotational instability (MRI), which powers accretion in circular disks, operates in eccentric disks as well. We examine the linear evolution of unstratified, incompressible MRI in an eccentric disk orbiting a point mass. We consider vertical modes of wavenumber k on a background flow with uniform eccentricity e and vertical Alfvén speed {v}{{A}} along an orbit with mean motion n. We find two mode families, one with dominant magnetic components, the other with dominant velocity components. The former is unstable at {(1-e)}3 {f}2≲ 3, where f\\equiv {{kv}}{{A}}/n, and the latter at e ≳ 0.8. For f 2 ≲ 3, MRI behaves much like in circular disks, but the growth per orbit declines slowly with increasing e; for f 2 ≳ 3, modes grow by parametric amplification, which is resonant for 0 < e ≪ 1. MRI growth and the attendant angular momentum and energy transport happen chiefly near pericenter, where orbital shear dominates magnetic tension.

Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation.

PubMed

Sun, Guoqiang; Yu, Ruth T; Evans, Ronald M; Shi, Yanhong

2007-09-25

TLX is a transcription factor that is essential for neural stem cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated neural stem cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates neural stem cell proliferation. TLX interacts with HDAC3 and HDAC5 in neural stem cells. The HDAC5-interaction domain was mapped to TLX residues 359-385, which contains a conserved nuclear receptor-coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in neural stem cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21(CIP1/WAF1)(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX-interacting HDACs play an important role in neural stem cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX-HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of neural stem cell proliferation. Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX-HDAC interactions.

Aging Does Not Alter Tendon Mechanical Properties During Homeostasis, but does Impair Flexor Tendon Healing

PubMed Central

Ackerman, Jessica E.; Bah, Ibrahima; Jonason, Jennifer H.; Buckley, Mark R.; Loiselle, Alayna E.

2017-01-01

Aging is an important factor in disrupted homeostasis of many tissues. While an increased incidence of tendinopathy and tendon rupture are observed with aging, it is unclear whether this is due to progressive changes in tendon cell function and mechanics over time, or an impaired repair reaction from aged tendons in response to insult or injury. In the present study we examined changes in the mechanical properties of Flexor Digitorum Longus (FDL), Flexor Carpi Ulnaris (FCU), and tail fascicles in both male and female C57Bl/6 mice between 3-27 months of age to better understand the effects of sex and age on tendon homeostasis. No change in max load at failure was observed in any group over the course of aging, although there were significant decreases in toe and linear stiffness in female mice from 3-months to 15, and to 22-27-months. No changes in cell proliferation were observed with aging, although an observable decrease in cellularity occurred in 31-month old tendons. Given that aging did not dramatically alter tendon mechanical homeostasis we hypothesized that a disruption in tendon homeostasis, via acute injury would result in an impaired healing response. Significant decreases in max load, stiffness, and yield load were observed in repairs of 22-month old mice, relative to 4-month old mice. No changes in cell proliferation were observed between young and aged, however a dramatic loss of bridging collagen extracellular matrix was observed in aged repairs suggest that matrix production, but not cell proliferation leads to impaired tendon healing with aging. PMID:28419543

A non-linear theory of the parallel firehose and gyrothermal instabilities in a weakly collisional plasma

NASA Astrophysics Data System (ADS)

Rosin, M. S.; Schekochihin, A. A.; Rincon, F.; Cowley, S. C.

2011-05-01

Weakly collisional magnetized cosmic plasmas have a dynamical tendency to develop pressure anisotropies with respect to the local direction of the magnetic field. These anisotropies trigger plasma instabilities at scales just above the ion Larmor radius ρi and much below the mean free path λmfp. They have growth rates of a fraction of the ion cyclotron frequency, which is much faster than either the global dynamics or even local turbulence. Despite their microscopic nature, these instabilities dramatically modify the transport properties and, therefore, the macroscopic dynamics of the plasma. The non-linear evolution of these instabilities is expected to drive pressure anisotropies towards marginal stability values, controlled by the plasma beta βi. Here this non-linear evolution is worked out in an ab initio kinetic calculation for the simplest analytically tractable example - the parallel (k⊥= 0) firehose instability in a high-beta plasma. An asymptotic theory is constructed, based on a particular physical ordering and leading to a closed non-linear equation for the firehose turbulence. In the non-linear regime, both the analytical theory and the numerical solution predict secular (∝t) growth of magnetic fluctuations. The fluctuations develop a k-3∥ spectrum, extending from scales somewhat larger than ρi to the maximum scale that grows secularly with time (∝t1/2); the relative pressure anisotropy (p⊥-p∥)/p∥ tends to the marginal value -2/βi. The marginal state is achieved via changes in the magnetic field, not particle scattering. When a parallel ion heat flux is present, the parallel firehose mutates into the new gyrothermal instability (GTI), which continues to exist up to firehose-stable values of pressure anisotropy, which can be positive and are limited by the magnitude of the ion heat flux. The non-linear evolution of the GTI also features secular growth of magnetic fluctuations, but the fluctuation spectrum is eventually dominated by modes around a maximal scale ˜ρilT/λmfp, where lT is the scale of the parallel temperature variation. Implications for momentum and heat transport are speculated about. This study is motivated by our interest in the dynamics of galaxy cluster plasmas (which are used as the main astrophysical example), but its relevance to solar wind and accretion flow plasmas is also briefly discussed.

Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome

PubMed Central

Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

2014-01-01

Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress. PMID:24932421

Submesoscale currents in the ocean

PubMed Central

2016-01-01

This article is a perspective on the recently discovered realm of submesoscale currents in the ocean. They are intermediate-scale flow structures in the form of density fronts and filaments, topographic wakes and persistent coherent vortices at the surface and throughout the interior. They are created from mesoscale eddies and strong currents, and they provide a dynamical conduit for energy transfer towards microscale dissipation and diapycnal mixing. Consideration is given to their generation mechanisms, instabilities, life cycles, disruption of approximately diagnostic force balance (e.g. geostrophy), turbulent cascades, internal-wave interactions, and transport and dispersion of materials. At a fundamental level, more questions remain than answers, implicating a programme for further research. PMID:27279778

Premature aging of the hippocampal neurogenic niche in adult Bmal1-deficient mice.

PubMed

Ali, Amira A H; Schwarz-Herzke, Beryl; Stahr, Anna; Prozorovski, Timour; Aktas, Orhan; von Gall, Charlotte

2015-06-01

Hippocampal neurogenesis undergoes dramatic age-related changes. Mice with targeted deletion of the clock geneBmal1 (Bmal1(-/-)) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1(-/-) mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1(-/-) mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70 kDa and expression of the cell cycle inhibitor p21(Waf1/CIP1) were increased in adult Bmal1(-/-) mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age-dependent decline in adult neurogenesis presumably as a consequence of oxidative stress.

Essential Role of Cyclin-G–associated Kinase (Auxilin-2) in Developing and Mature Mice

PubMed Central

Lee, Dong-won; Zhao, Xiaohong; Yim, Yang-In; Eisenberg, Evan

2008-01-01

Hsc70 with its cochaperone, either auxilin or GAK, not only uncoats clathrin-coated vesicles but also acts as a chaperone during clathrin-mediated endocytosis. However, because synaptojanin is also involved in uncoating, it is not clear whether GAK is an essential gene. To answer this question, GAK conditional knockout mice were generated and then mated to mice expressing Cre recombinase under the control of the nestin, albumin, or keratin-14 promoters, all of which turn on during embryonic development. Deletion of GAK from brain, liver, or skin dramatically altered the histology of these tissues, causing the mice to die shortly after birth. Furthermore, by expressing a tamoxifen-inducible promoter to express Cre recombinase we showed that deletion of GAK caused lethality in adult mice. Mouse embryonic fibroblasts in which the GAK was disrupted showed a lack of clathrin-coated pits and a complete block in clathrin-mediated endocytosis. We conclude that GAK deletion blocks development and causes lethality in adult animals by disrupting clathrin-mediated endocytosis. PMID:18434600

The Genomic Landscape of Balanced Cytogenetic Abnormalities Associated with Human Congenital Anomalies

PubMed Central

Redin, Claire; Brand, Harrison; Collins, Ryan L.; Kammin, Tammy; Mitchell, Elyse; Hodge, Jennelle C.; Hanscom, Carrie; Pillalamarri, Vamsee; Seabra, Catarina M.; Abbott, Mary-Alice; Abdul-Rahman, Omar A.; Aberg, Erika; Adley, Rhett; Alcaraz-Estrada, Sofia L.; Alkuraya, Fowzan S.; An, Yu; Anderson, Mary-Anne; Antolik, Caroline; Anyane-Yeboa, Kwame; Atkin, Joan F.; Bartell, Tina; Bernstein, Jonathan A.; Beyer, Elizabeth; Blumenthal, Ian; Bongers, Ernie M.H.F.; Brilstra, Eva H.; Brown, Chester W.; Brüggenwirth, Hennie T.; Callewaert, Bert; Chiang, Colby; Corning, Ken; Cox, Helen; Cuppen, Edwin; Currall, Benjamin B.; Cushing, Tom; David, Dezso; Deardorff, Matthew A.; Dheedene, Annelies; D’Hooghe, Marc; de Vries, Bert B.A.; Earl, Dawn L.; Ferguson, Heather L.; Fisher, Heather; FitzPatrick, David R.; Gerrol, Pamela; Giachino, Daniela; Glessner, Joseph T.; Gliem, Troy; Grady, Margo; Graham, Brett H.; Griffis, Cristin; Gripp, Karen W.; Gropman, Andrea L.; Hanson-Kahn, Andrea; Harris, David J.; Hayden, Mark A.; Hill, Rosamund; Hochstenbach, Ron; Hoffman, Jodi D.; Hopkin, Robert J.; Hubshman, Monika W.; Innes, A. Micheil; Irons, Mira; Irving, Melita; Jacobsen, Jessie C.; Janssens, Sandra; Jewett, Tamison; Johnson, John P.; Jongmans, Marjolijn C.; Kahler, Stephen G.; Koolen, David A.; Korzelius, Jerome; Kroisel, Peter M.; Lacassie, Yves; Lawless, William; Lemyre, Emmanuelle; Leppig, Kathleen; Levin, Alex V.; Li, Haibo; Li, Hong; Liao, Eric C.; Lim, Cynthia; Lose, Edward J.; Lucente, Diane; Macera, Michael J.; Manavalan, Poornima; Mandrile, Giorgia; Marcelis, Carlo L.; Margolin, Lauren; Mason, Tamara; Masser-Frye, Diane; McClellan, Michael W.; Zepeda Mendoza, Cinthya J.; Menten, Björn; Middelkamp, Sjors; Mikami, Liya R.; Moe, Emily; Mohammed, Shehla; Mononen, Tarja; Mortenson, Megan E.; Moya, Graciela; Nieuwint, Aggie W.; Ordulu, Zehra; Parkash, Sandhya; Pauker, Susan P.; Pereira, Shahrin; Perrin, Danielle; Phelan, Katy; Piña Aguilar, Raul E.; Poddighe, Pino J.; Pregno, Giulia; Raskin, Salmo; Reis, Linda; Rhead, William; Rita, Debra; Renkens, Ivo; Roelens, Filip; Ruliera, Jayla; Rump, Patrick; Schilit, Samantha L.P.; Shaheen, Ranad; Sparkes, Rebecca; Spiegel, Erica; Stevens, Blair; Stone, Matthew R.; Tagoe, Julia; Thakuria, Joseph V.; van Bon, Bregje W.; van de Kamp, Jiddeke; van Der Burgt, Ineke; van Essen, Ton; van Ravenswaaij-Arts, Conny M.; van Roosmalen, Markus J.; Vergult, Sarah; Volker-Touw, Catharina M.L.; Warburton, Dorothy P.; Waterman, Matthew J.; Wiley, Susan; Wilson, Anna; Yerena-de Vega, Maria de la Concepcion A.; Zori, Roberto T.; Levy, Brynn; Brunner, Han G.; de Leeuw, Nicole; Kloosterman, Wigard P.; Thorland, Erik C.; Morton, Cynthia C.; Gusella, James F.; Talkowski, Michael E.

2017-01-01

Despite their clinical significance, characterization of balanced chromosomal abnormalities (BCAs) has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and revealed complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. This study proposes that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements, and provides insight into novel pathogenic mechanisms such as altered regulation due to changes in chromosome topology. PMID:27841880

SCFSlimb ubiquitin ligase suppresses condensin II–mediated nuclear reorganization by degrading Cap-H2

PubMed Central

Buster, Daniel W.; Daniel, Scott G.; Nguyen, Huy Q.; Windler, Sarah L.; Skwarek, Lara C.; Peterson, Maureen; Roberts, Meredith; Meserve, Joy H.; Hartl, Tom; Klebba, Joseph E.; Bilder, David; Bosco, Giovanni

2013-01-01

Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCFSlimb ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCFSlimb function reorganized interphase chromosomes into dense, compact domains and disrupted homologue pairing in both cultured Drosophila cells and in vivo, but these effects were rescued by condensin II inactivation. Furthermore, Cap-H2 stabilization distorted nuclear envelopes and dispersed Cid/CENP-A on interphase chromosomes. Therefore, SCFSlimb-mediated down-regulation of condensin II is required to maintain proper organization and morphology of the interphase nucleus. PMID:23530065

Dynamics of Multiple Trafficking Behaviors of Individual Synaptic Vesicles Revealed by Quantum-Dot Based Presynaptic Probe

PubMed Central

Lee, Suho; Jung, Kyung Jin; Jung, Hyun Suk; Chang, Sunghoe

2012-01-01

Although quantum dots (QDs) have provided invaluable information regarding the diffusive behaviors of postsynaptic receptors, their application in presynaptic terminals has been rather limited. In addition, the diffraction-limited nature of the presynaptic bouton has hampered detailed analyses of the behaviors of synaptic vesicles (SVs) at synapses. Here, we created a quantum-dot based presynaptic probe and characterized the dynamic behaviors of individual SVs. As previously reported, the SVs exhibited multiple exchanges between neighboring boutons. Actin disruption induced a dramatic decrease in the diffusive behaviors of SVs at synapses while microtubule disruption only reduced extrasynaptic mobility. Glycine-induced synaptic potentiation produced significant increases in synaptic and inter-boutonal trafficking of SVs, which were NMDA receptor- and actin-dependent while NMDA-induced synaptic depression decreased the mobility of the SVs at synapses. Together, our results show that sPH-AP-QD revealed previously unobserved trafficking properties of SVs around synapses, and the dynamic modulation of SV mobility could regulate presynaptic efficacy during synaptic activity. PMID:22666444

Bcl-2 prevents loss of mitochondria in CCCP-induced apoptosis.

PubMed

de Graaf, Aniek O; van den Heuvel, Lambert P; Dijkman, Henry B P M; de Abreu, Ronney A; Birkenkamp, Kim U; de Witte, Theo; van der Reijden, Bert A; Smeitink, Jan A M; Jansen, Joop H

2004-10-01

Bcl-2 family proteins regulate apoptosis at the level of mitochondria. To examine the mechanism of Bcl-2 function, we investigated the effects of the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on two hematopoietic cell lines and Bcl-2 overexpressing transfectants. CCCP directly interferes with mitochondrial function and induces apoptosis. We show that Bcl-2 inhibits apoptosis and that the antiapoptotic effect of Bcl-2 takes place upstream of caspase activation and nuclear changes associated with apoptosis, since these were markedly inhibited in cells overexpressing Bcl-2. Bcl-2 does not prevent the decrease in mitochondrial membrane potential nor the alterations in cellular ATP content induced by CCCP in FL5.12 and Jurkat cells. A higher number of mitochondria was observed in untreated Bcl-2 transfected cells compared to parental cells, as shown by electron microscopy. Exposure to CCCP induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, with apparent swelling and loss of cristae in parental cells. Bcl-2 clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. These data suggest that CCCP induces apoptosis by structural disruption of mitochondria and that Bcl-2 prevents apoptosis and mitochondrial degeneration by preserving mitochondrial integrity.

Reversing resistance to vascular-disrupting agents by blocking late mobilization of circulating endothelial progenitor cells.

PubMed

Taylor, Melissa; Billiot, Fanny; Marty, Virginie; Rouffiac, Valérie; Cohen, Patrick; Tournay, Elodie; Opolon, Paule; Louache, Fawzia; Vassal, Gilles; Laplace-Builhé, Corinne; Vielh, Philippe; Soria, Jean-Charles; Farace, Françoise

2012-05-01

The prevailing concept is that immediate mobilization of bone marrow-derived circulating endothelial progenitor cells (CEP) is a key mechanism mediating tumor resistance to vascular-disrupting agents (VDA). Here, we show that administration of VDA to tumor-bearing mice induces 2 distinct peaks in CEPs: an early, unspecific CEP efflux followed by a late yet more dramatic tumor-specific CEP burst that infiltrates tumors and is recruited to vessels. Combination with antiangiogenic drugs could not disrupt the early peak but completely abrogated the late VDA-induced CEP burst, blunted bone marrow-derived cell recruitment to tumors, and resulted in striking antitumor efficacy, indicating that the late CEP burst might be crucial to tumor recovery after VDA therapy. CEP and circulating endothelial cell kinetics in VDA-treated patients with cancer were remarkably consistent with our preclinical data. These findings expand the current understanding of vasculogenic "rebounds" that may be targeted to improve VDA-based strategies. Our findings suggest that resistance to VDA therapy may be strongly mediated by late, rather than early, tumor-specific recruitment of CEPs, the suppression of which resulted in increased VDA-mediated antitumor efficacy. VDA-based therapy might thus be significantly enhanced by combination strategies targeting late CEP mobilization. © 2012 AACR

Paths and wakes of deformable nearly spheroidal rising bubbles close to the transition to path instability

NASA Astrophysics Data System (ADS)

Cano-Lozano, José Carlos; Martínez-Bazán, Carlos; Magnaudet, Jacques; Tchoufag, Joël

2016-09-01

We report on a series of results provided by three-dimensional numerical simulations of nearly spheroidal bubbles freely rising and deforming in a still liquid in the regime close to the transition to path instability. These results improve upon those of recent computational studies [Cano-Lozano et al., Int. J. Multiphase Flow 51, 11 (2013), 10.1016/j.ijmultiphaseflow.2012.11.005; Phys. Fluids 28, 014102 (2016), 10.1063/1.4939703] in which the neutral curve associated with this transition was obtained by considering realistic but frozen bubble shapes. Depending on the dimensionless parameters that characterize the system, various paths geometries are observed by letting an initially spherical bubble starting from rest rise under the effect of buoyancy and adjust its shape to the surrounding flow. These include the well-documented rectilinear axisymmetric, planar zigzagging, and spiraling (or helical) regimes. A flattened spiraling regime that most often eventually turns into either a planar zigzagging or a helical regime is also frequently observed. Finally, a chaotic regime in which the bubble experiences small horizontal displacements (typically one order of magnitude smaller than in the other regimes) is found to take place in a region of the parameter space where no standing eddy exists at the back of the bubble. The discovery of this regime provides evidence that path instability does not always result from a wake instability as previously believed. In each regime, we examine the characteristics of the path, bubble shape, and vortical structure in the wake, as well as their couplings. In particular, we observe that, depending on the fluctuations of the rise velocity, two different vortex shedding modes exist in the zigzagging regime, confirming earlier findings with falling spheres. The simulations also reveal that significant bubble deformations may take place along zigzagging or spiraling paths and that, under certain circumstances, they dramatically alter the wake structure. The instability thresholds that can be inferred from the computations compare favorably with experimental data provided by various sets of recent experiments guaranteeing that the bubble surface is free of surfactants.

Social stars: Modeling the interactive lives of stars in dense clusters and binary systems in the era of time domain astronomy

NASA Astrophysics Data System (ADS)

MacLeod, Morgan Elowe

This thesis uses computational modeling to study of phases of dramatic interaction that intersperse stellar lifetimes. In galactic centers stars trace dangerously wandering orbits dictated by the combined gravitational force of a central, supermassive black hole and all of the surrounding stars. In binary systems, stars' evolution -- which causes their radii to increase substantially -- can bring initially non-interacting systems into contact. Moments of strong stellar interaction transform stars, their subsequent evolution, and the stellar environments they inhabit. In tidal disruption events, a star is partially or completely destroyed as tidal forces from a supermassive black hole overwhelm the star's self gravity. A portion of the stellar debris falls back to the black hole powering a luminous flare as it accretes. This thesis studies the relative event rates and properties of tidal disruption events for stars across the stellar evolutionary spectrum. Tidal disruptions of giant stars occur with high specific frequency; these objects' extended envelopes make them vulnerable to disruption. More-compact white dwarf stars are tidally disrupted relatively rarely. Their transients are also of very different duration and luminosity. Giant star disruptions power accretion flares with timescales of tens to hundreds of years; white dwarf disruption flares take hours to days. White dwarf tidal interactions can additionally trigger thermonuclear burning and lead to transients with signatures similar to type I supernovae. In binary star systems, a phase of hydrodynamic interaction called a common envelope episode occurs when one star evolves to swallow its companion. Dragged by the surrounding gas, the companion star spirals through the envelope to tighter orbits. This thesis studies accretion and flow morphologies during this phase. Density gradients across the gravitationally-focussed material lead to a strong angular momentum barrier to accretion during common envelope. Typical accretion efficiencies are in the range of 1 percent the Hoyle-Lyttleton accretion rate. This implies that compact objects embedded in common envelopes do not grow significantly during this phase, increasing their mass by at most a few percent. This thesis models the properties of a recent stellar-merger powered transient to derive constraints on this long-uncertain phase of binary star evolution.

Epigenetic remodelling and dysregulation of DLGAP4 is linked with early-onset cerebellar ataxia

PubMed Central

Minocherhomji, Sheroy; Hansen, Claus; Kim, Hyung-Goo; Mang, Yuan; Bak, Mads; Guldberg, Per; Papadopoulos, Nickolas; Eiberg, Hans; Doh, Gerald Dayebga; Møllgård, Kjeld; Hertz, Jens Michael; Nielsen, Jørgen E.; Ropers, Hans-Hilger; Tümer, Zeynep; Tommerup, Niels; Kalscheuer, Vera M.; Silahtaroglu, Asli

2014-01-01

Genome instability, epigenetic remodelling and structural chromosomal rearrangements are hallmarks of cancer. However, the coordinated epigenetic effects of constitutional chromosomal rearrangements that disrupt genes associated with congenital neurodevelopmental diseases are poorly understood. To understand the genetic–epigenetic interplay at breakpoints of chromosomal translocations disrupting CG-rich loci, we quantified epigenetic modifications at DLGAP4 (SAPAP4), a key post-synaptic density 95 (PSD95) associated gene, truncated by the chromosome translocation t(8;20)(p12;q11.23), co-segregating with cerebellar ataxia in a five-generation family. We report significant epigenetic remodelling of the DLGAP4 locus triggered by the t(8;20)(p12;q11.23) translocation and leading to dysregulation of DLGAP4 expression in affected carriers. Disruption of DLGAP4 results in monoallelic hypermethylation of the truncated DLGAP4 promoter CpG island. This induced hypermethylation is maintained in somatic cells of carriers across several generations in a t(8;20) dependent-manner however, is erased in the germ cells of the translocation carriers. Subsequently, chromatin remodelling of the locus-perturbed monoallelic expression of DLGAP4 mRNAs and non-coding RNAs in haploid cells having the translocation. Our results provide new mechanistic insight into the way a balanced chromosomal rearrangement associated with a neurodevelopmental disorder perturbs allele-specific epigenetic mechanisms at breakpoints leading to the deregulation of the truncated locus. PMID:24986922

Kondo interactions from band reconstruction in YbInCu 4

DOE PAGES

Jarrige, I.; Kotani, A.; Yamaoka, H.; ...

2015-03-27

We combine resonant inelastic X-ray scattering (RIXS) and model calculations in the Kondo lattice compound YbInCu₄, a system characterized by a dramatic increase in Kondo temperature and associated valence fluctuations below a first-order valence transition at T≃42 K. In this study, the bulk-sensitive, element-specific, and valence-projected charge excitation spectra reveal an unusual quasi-gap in the Yb-derived state density which drives an instability of the electronic structure and renormalizes the low-energy effective Hamiltonian at the transition. Our results provide long-sought experimental evidence for a link between temperature-driven changes in the low-energy Kondo scale and the higher-energy electronic structure of this system.

Late Glacial to Early Holocene socio-ecological responses to climatic instability within the Mediterranean basin

NASA Astrophysics Data System (ADS)

Fernández-López de Pablo, Javier; Jones, Samantha E.; Burjachs, Francesc

2018-03-01

The period spanning the Late Glacial and the Early Holocene (≈19-8.2 ka) witnessed a dramatic sequence of climate and palaeoenvironmental changes (Rasmussen et al., 2014). Interestingly, some of the most significant transformations ever documented in human Prehistory took place during this period such as the intensification of hunter-gatherer economic systems, the domestication process of wild plants and animals, and the spread of farming across Eurasia. Understanding the role of climate and environmental dynamics on long-term cultural and economic trajectories, as well as specific human responses to episodes of rapid climate change, still remains as one of the main challenges of archaeological research (Kintigh et al., 2014).

Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits.

PubMed Central

Mossman, K; Lee, S F; Barry, M; Boshkov, L; McFadden, G

1996-01-01

Myxoma virus is a pathogenic poxvirus that induces a lethal myxomatosis disease profile in European rabbits, which is characterized by fulminating lesions at the primary site of inoculation, rapid dissemination to secondary internal organs and peripheral external sites, and supervening gram-negative bacterial infection. Here we describe the role of a novel myxoma virus protein encoded by the M-T5 open reading frame during pathogenesis. The myxoma virus M-T5 protein possesses no significant sequence homology to nonviral proteins but is a member of a larger poxviral superfamily designated host range proteins. An M-T5- mutant virus was constructed by disruption of both copies of the M-T5 gene followed by insertion of the selectable marker p7.5Ecogpt. Although the M-T5- deletion mutant replicated with wild-type kinetics in rabbit fibroblasts, infection of a rabbit CD4+ T-cell line (RL5) with the myxoma virus M-T5- mutant virus resulted in the rapid and complete cessation of both host and viral protein synthesis, accompanied by the manifestation of all the classical features of programmed cell death. Infection of primary rabbit peripheral mononuclear cells with the myxoma virus M-T5-mutant virus resulted in the apoptotic death of nonadherent lymphocytes but not adherent monocytes. Within the European rabbit, disruption of the M-T5 open reading frame caused a dramatic attenuation of the rapidly lethal myxomatosis infection, and none of the infected rabbits displayed any of the characteristic features of myxomatosis. The two most significant histological observations in rabbits infected with the M-T5-mutant virus were (i) the lack of progression of the infection past the primary site of inoculation, coupled with the establishment of a rapid and effective inflammatory reaction, and (ii) the inability of the virus to initiate a cellular reaction within secondary immune organs. We conclude that M-T5 functions as a critical virulence factor by allowing productive infection of immune cells such as peripheral lymphocytes, thus facilitating virus dissemination to secondary tissue sites via the lymphatic channels. PMID:8676463

Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits.

PubMed

Mossman, K; Lee, S F; Barry, M; Boshkov, L; McFadden, G

1996-07-01

Myxoma virus is a pathogenic poxvirus that induces a lethal myxomatosis disease profile in European rabbits, which is characterized by fulminating lesions at the primary site of inoculation, rapid dissemination to secondary internal organs and peripheral external sites, and supervening gram-negative bacterial infection. Here we describe the role of a novel myxoma virus protein encoded by the M-T5 open reading frame during pathogenesis. The myxoma virus M-T5 protein possesses no significant sequence homology to nonviral proteins but is a member of a larger poxviral superfamily designated host range proteins. An M-T5- mutant virus was constructed by disruption of both copies of the M-T5 gene followed by insertion of the selectable marker p7.5Ecogpt. Although the M-T5- deletion mutant replicated with wild-type kinetics in rabbit fibroblasts, infection of a rabbit CD4+ T-cell line (RL5) with the myxoma virus M-T5- mutant virus resulted in the rapid and complete cessation of both host and viral protein synthesis, accompanied by the manifestation of all the classical features of programmed cell death. Infection of primary rabbit peripheral mononuclear cells with the myxoma virus M-T5-mutant virus resulted in the apoptotic death of nonadherent lymphocytes but not adherent monocytes. Within the European rabbit, disruption of the M-T5 open reading frame caused a dramatic attenuation of the rapidly lethal myxomatosis infection, and none of the infected rabbits displayed any of the characteristic features of myxomatosis. The two most significant histological observations in rabbits infected with the M-T5-mutant virus were (i) the lack of progression of the infection past the primary site of inoculation, coupled with the establishment of a rapid and effective inflammatory reaction, and (ii) the inability of the virus to initiate a cellular reaction within secondary immune organs. We conclude that M-T5 functions as a critical virulence factor by allowing productive infection of immune cells such as peripheral lymphocytes, thus facilitating virus dissemination to secondary tissue sites via the lymphatic channels.

Histone demethylase JARID1C inactivation triggers genomic instability in sporadic renal cancer

PubMed Central

Rondinelli, Beatrice; Rosano, Dalia; Antonini, Elena; Frenquelli, Michela; Montanini, Laura; Huang, DaChuan; Segalla, Simona; Yoshihara, Kosuke; Amin, Samir B.; Lazarevic, Dejan; The, Bin Tean; Verhaak, Roel G.W.; Futreal, P. Andrew; Di Croce, Luciano; Chin, Lynda; Cittaro, Davide; Tonon, Giovanni

2015-01-01

Mutations in genes encoding chromatin-remodeling proteins are often identified in a variety of cancers. For example, the histone demethylase JARID1C is frequently inactivated in patients with clear cell renal cell carcinoma (ccRCC); however, it is largely unknown how JARID1C dysfunction promotes cancer. Here, we determined that JARID1C binds broadly to chromatin domains characterized by the trimethylation of lysine 9 (H3K9me3), which is a histone mark enriched in heterochromatin. Moreover, we found that JARID1C localizes on heterochromatin, is required for heterochromatin replication, and forms a complex with established players of heterochromatin assembly, including SUV39H1 and HP1α, as well as with proteins not previously associated with heterochromatin assembly, such as the cullin 4 (CUL4) complex adaptor protein DDB1. Transcription on heterochromatin is tightly suppressed to safeguard the genome, and in ccRCC cells, JARID1C inactivation led to the unrestrained expression of heterochromatic noncoding RNAs (ncRNAs) that in turn triggered genomic instability. Moreover, ccRCC patients harboring JARID1C mutations exhibited aberrant ncRNA expression and increased genomic rearrangements compared with ccRCC patients with tumors endowed with other genetic lesions. Together, these data suggest that inactivation of JARID1C in renal cancer leads to heterochromatin disruption, genomic rearrangement, and aggressive ccRCCs. Moreover, our results shed light on a mechanism that underlies genomic instability in sporadic cancers. PMID:26551685

The Crucial Role of Additive Manufacturing at NASA

NASA Technical Reports Server (NTRS)

Vickers, John

2016-01-01

At NASA, the first steps of the Journey to Mars are well underway with the development of NASA's next generation launch system and investments in research and technologies that should increase the affordability, capability, and safety of exploration activities. Additive Manufacturing presents a disruptive opportunity for NASA to design and manufacture hardware with new materials at dramatically reduced cost and schedule. Opportunities to incorporate additive manufacturing align very well with NASA missions and with most NASA programs related to space, science, and aeronautics. The Agency also relies on many partnerships with other government agencies, industry and academia.

NASA's Additive Manufacturing Development Materials Science to Technology Infusion - Connecting the Digital Dots

NASA Technical Reports Server (NTRS)

Vickers, John

2017-01-01

At NASA, the first steps of the Journey to Mars are well underway with the development of NASA's next generation launch system and investments in research and technologies that should increase the affordability, capability, and safety of exploration activities. Additive Manufacturing presents a disruptive opportunity for NASA to design and manufacture hardware with new materials at dramatically reduced cost and schedule. Opportunities to incorporate additive manufacturing align very well with NASA missions and with most NASA programs related to space, science, and aeronautics. The Agency also relies on many partnerships with other government agencies, industry and academia.

Africa's Great Lakes in peril

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

Ryan, J.C.

Three of the great lakes in East Africa are in serious danger. Over the last two decades, overfishing, pollution, and the introduction of the Nile perch, have combined to push into extinction as many as 200 fish species found in Lake Victoria. The recycling of nutrients and oxygen through living and non-living matter has been disrupted and large area of the lake are now depleted of oxygen. Overfishing has had dramatic consequences in Lake Malawi, while Lake Tanganyika's most serious problem is with sedimentation from raw sewage, soil and chemicals. International cooperation will be required to restore these lakes.

Dreaming and immanence: rejecting the dogmatic image of thought in science education

NASA Astrophysics Data System (ADS)

Bazzul, Jesse; Wallace, Maria F. G.; Higgins, Marc

2018-02-01

In this article, we, a multivocal-thinking-assemblage, trouble what we feel is the dogmatic image of thought in science education. Beginning with Lars Bang's (Cult Stud Sci Educ, 2017) dramatic and disruptive imagery of the Ouroboros as a means to challenge scientific literacy we explore the importance of dreams, thinking with both virtual and actual entities, and immanent thinking to science education scholarship. Dreaming as movement away from a dogmatic image of thought takes the authors in multiple directions as they attempt to open Deleuzian horizons of difference, immanence, and self-exploration.

Destroying Gadofullerene Aggregates by Salt Addition in Aqueous Solution of Gd@C60(OH)x and Gd@C60[C(COOH2)]10

PubMed Central

Laus, Sabrina; Sitharaman, Balaji; Tóth, Éva; Bolskar, Robert D.; Helm, Lothar; Asokan, Subashini; Wong, Michael S.; Wilson, Lon J.

2008-01-01

A combined proton relaxivity and dynamic light scattering study has shown that aggregates formed in aqueous solution of water-soluble gadofullerenes can be disrupted by addition of salts. The salt content of fullerene-based materials will strongly influence properties related to aggregation phenomena, therefore their behavior in biological or medical applications. In particular, the relaxivity of gadofullerenes decreases dramatically with phosphate addition. Moreover, real biological fluids present a rather high salt concentration which will have consequences on fullerene aggregation and influence fullerene-based drug delivery. PMID:15984854

Lessons learned from the disruption of dental training of Malaysian students studying in Egypt during the Arab spring.

PubMed

Simon, Sibu Sajjan; Ramachandra, Srinivas Sulugodu; Abdullah, Datuk Dr Fawzia; Islam, Md Nurul; Kalyan, C G

2016-01-01

Political crisis and worsening security situation in Egypt in late 2013 resulted in Malaysian students who were pursuing their dental education in Egypt being recalled home to Malaysia. The Ministry of Higher Education in Malaysia took steps to integrate these students into public and private universities in Malaysia. We used a questionnaire and informal interviews to learn from students returning from Egypt about their experiences transitioning from dental schools in Egypt to Malaysia. We discuss the challenges students faced with regards to credit transfer, pastoral care, the differences in the curriculum between the dental faculties of the two nations, and the financial implications of this disruption of their training. We live in a fragile world where similar political situations will surely arise again. The approaches used by the Malaysian government and the lessons learned from these students may help others. The perspectives of these students may help educators reintegrate expatriate students who are displaced by political instability back into the education system of their own countries.

Error field optimization in DIII-D using extremum seeking control

NASA Astrophysics Data System (ADS)

Lanctot, M. J.; Olofsson, K. E. J.; Capella, M.; Humphreys, D. A.; Eidietis, N.; Hanson, J. M.; Paz-Soldan, C.; Strait, E. J.; Walker, M. L.

2016-07-01

DIII-D experiments have demonstrated a new real-time approach to tokamak error field control based on maximizing the toroidal angular momentum. This approach uses extremum seeking control theory to optimize the error field in real time without inducing instabilities. Slowly-rotating n  =  1 fields (the dither), generated by external coils, are used to perturb the angular momentum, monitored in real-time using a charge-exchange spectroscopy diagnostic. Simple signal processing of the rotation measurements extracts information about the rotation gradient with respect to the control coil currents. This information is used to converge the control coil currents to a point that maximizes the toroidal angular momentum. The technique is well-suited for multi-coil, multi-harmonic error field optimizations in disruption sensitive devices as it does not require triggering locked tearing modes or plasma current disruptions. Control simulations highlight the importance of the initial search direction on the rate of the convergence, and identify future algorithm upgrades that may allow more rapid convergence that projects to convergence times in ITER on the order of tens of seconds.

Stabilizing Effect of Sweep on Low-Frequency STBLI Unsteadiness

NASA Astrophysics Data System (ADS)

Adler, Michael; Gaitonde, Datta

2017-11-01

A Large-Eddy Simulation database is generated to examine unsteady shock/turbulent boundary-layer-interaction (STBLI) mechanisms in a Mach 2 swept-compression-corner. Such interactions exhibit open separation, with separation relief from the sweep, and lack the closed mean recirculation found in spanwise-homogeneous STBLIs. We find that the swept interaction lacks the low-frequency coherent shock unsteadiness, two-decades below incoming turbulent boundary layer scales, that is a principal feature of comparable closed separation STBLIs. Rather, the prominent unsteady content is a mid-frequency regime that develops in the separated shear layer and scales weakly with the local separation length. Additionally, a linear perturbation analysis of the unsteady flow indicates that the feedback pathway (associated with an absolute instability in spanwise-homogeneous interactions) is absent in swept-compression-corner interactions. This suggests that 1) the linear oscillator is an essential component of low-frequency unsteadiness in interactions with closed separation. 2) Low-frequency control efforts should be focused on disrupting this oscillator. 3) Introduction of 3D effects constitute one mechanism to disrupt the oscillator.

Numerical Experiments with a Turbulent Single-Mode Rayleigh-Taylor Instability

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

Cloutman, L.D.

2000-04-01

Direct numerical simulation is a powerful tool for studying turbulent flows. Unfortunately, it is also computationally expensive and often beyond the reach of the largest, fastest computers. Consequently, a variety of turbulence models have been devised to allow tractable and affordable simulations of averaged flow fields. Unfortunately, these present a variety of practical difficulties, including the incorporation of varying degrees of empiricism and phenomenology, which leads to a lack of universality. This unsatisfactory state of affairs has led to the speculation that one can avoid the expense and bother of using a turbulence model by relying on the grid andmore » numerical diffusion of the computational fluid dynamics algorithm to introduce a spectral cutoff on the flow field and to provide dissipation at the grid scale, thereby mimicking two main effects of a large eddy simulation model. This paper shows numerical examples of a single-mode Rayleigh-Taylor instability in which this procedure produces questionable results. We then show a dramatic improvement when two simple subgrid-scale models are employed. This study also illustrates the extreme sensitivity to initial conditions that is a common feature of turbulent flows.« less

Achieving Stable Radiation Pressure Acceleration of Heavy Ions via Successive Electron Replenishment from Ionization of a High-Z Material Coating

NASA Astrophysics Data System (ADS)

Qiao, Bin; Shen, X. F.; Zhang, H.; Kar, S.; Zhou, C. T.; Chang, H. X.; Borghesi, M.; He, X. T.

2017-10-01

Among various laser-driven acceleration schemes, radiation pressure acceleration (RPA) is regarded as one of the most promising schemes to obtain high-quality ion beams. Although RPA is very attractive in principle, it is difficult to be achieved experimentally. One of the most important reasons is the dramatic growth of the multi-dimensional Rayleigh-Taylor-like (RT) instabilities. In this talk, we report a novel method to achieve stable RPA of ions from laser-irradiated ultrathin foils, where a high-Z material coating in front is used. The coated high-Z material, acting as a moving electron repository, continuously replenishes the accelerating ion foil with comoving electrons in the light-sail acceleration stage due to its successive ionization under laser fields with Gaussian temporal profile. As a result, the detrimental effects such as electron loss induced by the RT and other instabilities are significantly offset and suppressed so that stable acceleration of ions are maintained. Supported by the NSAF, Grant No. U1630246; the NNSF China Grants No. 11575298; and the National Key Program of S&T Research and Development, Grant No. 2016YFA0401100.

Numerical study on the effect of temperature oscillations on the crystallization front shape during Czochralski growth of gadolinium gallium garnet crystal

NASA Astrophysics Data System (ADS)

Faiez, Reza; Rezaei, Yazdan

2017-10-01

Time-dependent, finite volume method calculations of momentum and heat transfer were carried out to investigate the correlation between oscillatory convection and the crystallization front dynamics during the Czochralski (Cz) growth of an oxide material. The present modeling allows us to illustrate the modification of the interface shape during the time period of oscillation of the flow manifesting as the formation of a cold plume beneath the phase boundary. It was shown that the instability mechanism is associated with an irreversible dramatic change in the interface shape, which occurs at a critical Reynolds number significantly lower than that is predicted by the quasi-stationary global model analysis of the Cz growth system. The baroclinic term which appears in the vorticity equation in a rotating stratified fluid is used to describe the numerical results of the model. The properties of the thermal waves were studied in the monitoring points located nearby the interface. The waves are regular but not in fact vertically correlated as observed in the case of baroclinic waves. The Rayleigh-Benard dynamics is suggested to be the predominant mechanism even though the instability is primarily baroclinic.

Earthquakes initiation and thermal shear instability in the Hindu Kush intermediate depth nest

NASA Astrophysics Data System (ADS)

Poli, Piero; Prieto, German; Rivera, Efrain; Ruiz, Sergio

2016-02-01

Intermediate depth earthquakes often occur along subducting lithosphere, but despite their ubiquity the physical mechanism responsible for promoting brittle or brittle-like failure is not well constrained. Large concentrations of intermediate depth earthquakes have been found to be related to slab break-off, slab drip, and slab tears. The intermediate depth Hindu Kush nest is one of the most seismically active regions in the world and shows the correlation of a weak region associated with ongoing slab detachment process. Here we study relocated seismicity in the nest to constraint the geometry of the shear zone at the top of the detached slab. The analysis of the rupture process of the Mw 7.5 Afghanistan 2015 earthquake and other several well-recorded events over the past 25 years shows an initially slow, highly dissipative rupture, followed by a dramatic dynamic frictional stress reduction and corresponding large energy radiation. These properties are typical of thermal driven rupture processes. We infer that thermal shear instabilities are a leading mechanism for the generation of intermediated-depth earthquakes especially in presence of weak zone subjected to large strain accumulation, due to ongoing detachment process.

Self-induced temporal instability from a neutrino antenna

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

Capozzi, Francesco; INFN - Sezione di Padova,Via Marzolo 8, 35131 Padova; Dasgupta, Basudeb

2016-04-21

It has been recently shown that the flavor composition of a self-interacting neutrino gas can spontaneously acquire a time-dependent pulsating component during its flavor evolution. In this work, we perform a more detailed study of this effect in a model where neutrinos are assumed to be emitted in a two-dimensional plane from an infinite line that acts as a neutrino antenna. We consider several examples with varying matter and neutrino densities and find that temporal instabilities with various frequencies are excited in a cascade. We compare the numerical calculations of the flavor evolution with the predictions of linearized stability analysismore » of the equations of motion. The results obtained with these two approaches are in good agreement in the linear regime, while a dramatic speed-up of the flavor conversions occurs in the non-linear regime due to the interactions among the different pulsating modes. We show that large flavor conversions can take place if some of the temporal modes are unstable for long enough, and that this can happen even if the matter and neutrino densities are changing, as long as they vary slowly.« less

Effects of geometry and fluid elasticity during polymeric droplet pinch-off in microfluidic environments

NASA Astrophysics Data System (ADS)

Steinhaus, Ben; Shen, Amy; Sureshkumar, Radhakrishna

2006-11-01

We investigate the effects of fluid elasticity and channel geometry on polymeric droplet pinch-off by performing systematic experiments using viscoelastic polymer solutions which possess practically shear rate-independent viscosity (Boger fluids). Four different geometric sizes (width and depth are scaled up proportionally at the ratio of 0.5, 1, 2, 20) are used to study the effect of the length scale, which in turn influences the ratio of elastic to viscous forces as well as the Rayleigh time scale associated with the interfacial instability of a cylindrical column of liquid. We observe a power law relationship between the dimensionless (scaled with respect to the Rayleigh time scale) capillary pinch-off time, T, and the elasticity number, E, defined as the ratio of the fluid relaxation time to the time scale of viscous diffusion. In general, T increases dramatically with increasing E. The inhibition of ``bead-on-a-string'' formation is observed for flows with effective Deborah number, De, defined as the ratio of the fluid relaxation time to the Rayleigh time scale becomes greater than 10. For sufficiently large values of De, the Rayleigh instability may be modified substantially by fluid elasticity.

Serial population extinctions in a small mammal indicate Late Pleistocene ecosystem instability

PubMed Central

Brace, Selina; Palkopoulou, Eleftheria; Dalén, Love; Lister, Adrian M.; Miller, Rebecca; Otte, Marcel; Germonpré, Mietje; Blockley, Simon P. E.; Stewart, John R.; Barnes, Ian

2012-01-01

The Late Pleistocene global extinction of many terrestrial mammal species has been a subject of intensive scientific study for over a century, yet the relative contributions of environmental changes and the global expansion of humans remain unresolved. A defining component of these extinctions is a bias toward large species, with the majority of small-mammal taxa apparently surviving into the present. Here, we investigate the population-level history of a key tundra-specialist small mammal, the collared lemming (Dicrostonyx torquatus), to explore whether events during the Late Pleistocene had a discernible effect beyond the large mammal fauna. Using ancient DNA techniques to sample across three sites in North-West Europe, we observe a dramatic reduction in genetic diversity in this species over the last 50,000 y. We further identify a series of extinction-recolonization events, indicating a previously unrecognized instability in Late Pleistocene small-mammal populations, which we link with climatic fluctuations. Our results reveal climate-associated, repeated regional extinctions in a keystone prey species across the Late Pleistocene, a pattern likely to have had an impact on the wider steppe-tundra community, and one that is concordant with environmental change as a major force in structuring Late Pleistocene biodiversity. PMID:23185018

Modeling self-excited combustion instabilities using a combination of two- and three-dimensional simulations

NASA Astrophysics Data System (ADS)

Harvazinski, Matthew Evan

Self-excited combustion instabilities have been studied using a combination of two- and three-dimensional computational fluid dynamics (CFD) simulations. This work was undertaken to assess the ability of CFD simulations to generate the high-amplitude resonant combustion dynamics without external forcing or a combustion response function. Specifically, detached eddy simulations (DES), which allow for significantly coarser grid resolutions in wall bounded flows than traditional large eddy simulations (LES), were investigated for their capability of simulating the instability. A single-element laboratory rocket combustor which produces self-excited longitudinal instabilities is used for the configuration. The model rocket combustor uses an injector configuration based on practical oxidizer-rich staged-combustion devices; a sudden expansion combustion section; and uses decomposed hydrogen peroxide as the oxidizer and gaseous methane as the fuel. A better understanding of the physics has been achieved using a series of diagnostics. Standard CFD outputs like instantaneous and time averaged flowfield outputs are combined with other tools, like the Rayleigh index to provide additional insight. The Rayleigh index is used to identify local regions in the combustor which are responsible for driving and damping the instability. By comparing the Rayleigh index to flowfield parameters it is possible to connect damping and driving to specific flowfield conditions. A cost effective procedure to compute multidimensional local Rayleigh index was developed. This work shows that combustion instabilities can be qualitatively simulated using two-dimensional axisymmetric simulations for fuel rich operating conditions. A full three-dimensional simulation produces a higher level of instability which agrees quite well with the experimental results. In addition to matching the level of instability the three-dimensional simulation also predicts the harmonic nature of the instability that is observed in experiments. All fuel rich simulations used a single step global reaction for the chemical kinetic model. A fuel lean operating condition is also studied and has a lower level of instability. The two-dimensional results are unable to provide good agreement with experimental results unless a more expensive four-step chemical kinetic model is used. The three-dimensional simulation is able to predict the harmonic behavior but fails to capture the amplitude of the instability observed in the companion experiment, instead predicting lower amplitude oscillations. A detailed analysis of the three-dimensional results on a single cycle shows that the periodic heat release commonly associated with combustion instability can be interpreted to be a result of the time lag between the instant the fuel is injected and when it is burned. The time lag is due to two mechanisms. First, methane present near the backstep can become trapped and transported inside shed vortices to the point of combustion. The second aspect of the time lag arises due to the interaction of the fuel with upstream-running pressure waves. As the wave moves past the injection point the flow is temporarily disrupted, reducing the fuel flow into the combustor. A comparison between the fuel lean and fuel rich cases shows several differences. Whereas both cases can produce instability, the fuel-rich case is measurably more unstable. Using the tools developed differences in the location of the damping, and driving regions are evident. By moving the peak driving area upstream of the damping region the level of instability is lower in the fuel lean case. The location of the mean heat release is also important; locating the mean heat release adjacent to the vortex impingement point a higher level of instability is observed for the fuel rich case. This research shows that DES instability modeling has the ability to be a valuable tool in the study of combustion instability. The lower grid size requirement makes the use of DES based modeling a potential candidate in the modeling of full-scale rocket engines. Whereas three-dimensional simulations may be necessary for very good agreement, two-dimensional simulations allow efficient parametric investigation and tool development. The insights obtained from the simulations offer the possibility that their results can be used in the design of future engines to exploit damping and reduce driving.

A Quasar Turns On

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2017-02-01

The intermediate Palomar Transient Factory (iPTF) has discovered a quasar the brightly-shining, active nucleus of a galaxy abruptly turning on in what appears to be the fastest such transition ever seen in such an object.A Rapid TransitionQuasars are expected to show variations in brightness on timescales of hours to millions of years, but its not often that we get to study their major variability in real time! So far, weve discovered only a dozen changing-look quasars active galactic nuclei that exhibit major changes in their spectral class and brightness between observations. Roughly half of these were quasars that turned on and half were quasars that turned off, generally on timescales of maybe 5 or 10 years.The dramatic change in spectrum of iPTF 16bco between the archival SDSS data from 2004 (bottom) and the follow-up spectroscopy from Keck 2+DEIMOS in 2016 (top). [Adapted from Gezari et al. 2017]In June 2016, however, a team of scientists led by Suvi Gezari (University of Maryland) discovered iPTF 16bco, a nuclear transient that wasnt there the last time Palomar checked in 2012. A search through archival Sloan Digital Sky Survey and GALEX data in addition to some follow-up X-ray imaging and spectroscopic observations told the team what they needed to know: iPTF 16bco is a quasar that only just turned on within the 500 days preceding the iPTF observations.This source, in fact, is a 100-million-solar-mass black hole located at the center of a galaxy at a redshift of z= 0.237. In just over a year, the source changed classification from a galaxy with weak narrow-line emission to a quasar with characteristic strong, broad emission lines and a ten-fold increase in continuum brightness! What caused this sudden transition?Instabilities at Fault?iPTF 16bco and the other known changing-look quasars with disappearing (red circles) and appearing (blue circles) broad-line emission. [Adapted from Gezari et al. 2017]Gezari and collaborators used the large number of recent and archival observations of the galaxy to explore several scenarios that might be responsible for the rapid change in its brightness and spectral appearance. They found that the data disfavor variable obscuration by an absorber between us and the galaxy, microlensing of a background object, and tidal disruption of a star.Instead, the authors conclude that the best-fitting explanation is one in which thegalaxys nucleus already had a preexisting accretion disk, but the disk recently developed an instability. That instability caused more gas to rapidly feed onto the black hole, bumping the accretion rate up a notch and resulting in the quasar suddenlybrightening.Continued observations ofiPTF 16bcowill certainly help us to better understand whats happening in this unusual source. In the meantime, itsrapid change of state pushes the limits of accretion disk theory and presents us with an intriguing challenge to our understanding of quasars.CitationS. Gezari et al 2017 ApJ 835 144. doi:10.3847/1538-4357/835/2/144

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

Spurzem, R.; Giersz, M.; Heggie, D. C.

At least 10%-15% of nearby Sunlike stars have known Jupiter-mass planets. In contrast, very few planets are found in mature open and globular clusters such as the Hyades and 47 Tuc. We explore here the possibility that this dichotomy is due to the postformation disruption of planetary systems associated with the stellar encounters in long-lived clusters. One supporting piece of evidence for this scenario is the discovery of freely floating low-mass objects in star forming regions. We use two independent numerical approaches, a hybrid Monte Carlo and a direct N-body method, to simulate the impact of the encounters. We showmore » that the results of numerical simulations are in reasonable agreement with analytical determinations in the adiabatic and impulsive limits. They indicate that distant stellar encounters generally do not significantly modify the compact and nearly circular orbits. However, moderately close stellar encounters, which are likely to occur in dense clusters, can excite planets' orbital eccentricity and induce dynamical instability in systems that are closely packed with multiple planets. The disruption of planetary systems occurs primarily through occasional nearly parabolic, nonadiabatic encounters, though eccentricity of the planets evolves through repeated hyperbolic adiabatic encounters that accumulate small-amplitude changes. The detached planets are generally retained by the potential of their host clusters as free floaters in young stellar clusters such as {sigma} Orionis. We compute effective cross sections for the dissolution of planetary systems and show that, for all initial eccentricities, dissolution occurs on timescales that are longer than the dispersion of small stellar associations, but shorter than the age of typical open and globular clusters. Although it is much more difficult to disrupt short-period planets, close encounters can excite modest eccentricity among them, such that subsequent tidal dissipation leads to orbital decay, tidal inflation, and even disruption of the close-in planets.« less

LAD Early Career Prize Talk:Laboratory astrophysics experiments investigating the effects of high energy fluxes on Rayleigh-Taylor instability growth relevant to young supernova remnants

NASA Astrophysics Data System (ADS)

Kuranz, Carolyn C.; Drake, R. Paul; Park, Hye Sook; Huntington, Channing; Miles, Aaron R.; Remington, Bruce A.; Plewa, Tomek; Trantham, Matt; Shvarts, Dov; Raman, Kumar; MacLaren, Steven; Wan, Wesley; Doss, Forrest; Kline, John; Flippos, Kirk; Malamud, Guy; Handy, Timothy; Prisbey, Shon; Grosskopf, Michael; Krauland, Christine; Klein, Sallee; Harding, Eric; Wallace, Russell; Marion, Donna; Kalantar, Dan

2017-06-01

Energy-transport effects can alter the structure that develops as a supernova evolves into a supernova remnant. The Rayleigh Taylor (RT) instability is thought to produce structure at the interface between the stellar ejecta and the circumstellar matter (CSM), based on simple models and hydrodynamic simulations. When a blast wave emerges from an exploding star, it drives a forward shock into the CSM and a reverse shock forms in the expanding stellar ejecta, creating a young supernova remnant (SNR). As mass accumulates in the shocked layers, the interface between these two shocks decelerates, becoming unstable to the RT instability. Simulations predict that RT produces structures at this interface, having a range of spatial scales. When the CSM is dense enough, as in the case of SN 1993J, the hot shocked matter can produce significant radiative fluxes that affect the emission from the SNR. Here we report experimental results from the National Ignition Facility (NIF) to explore how large energy fluxes, which are present in supernovae such as SN 1993J, might affect this structure. The experiment used NIF to create a RT unstable interface subject to a high energy flux by the emergence of a blast wave into lower-density matter, in analogy to the SNR. We also preformed and with a low energy flux to compare the affect of the energy flux on the instability growth. We found that the RT growth was reduced in the experiments with a high energy flux. In analyzing the comparison with SN 1993J, we discovered that the energy fluxes produced by heat conduction appear to be larger than the radiative energy fluxes, and large enough to have dramatic consequences. No reported astrophysical simulations have included radiation and heat conduction self-consistently in modeling SNRs.

The Stability of Radiatively Cooling Jets. 2: Nonlinear Evolution

NASA Technical Reports Server (NTRS)

Stone, James M.; Xu, Jianjun; Hardee, Philip

1997-01-01

We use two-dimensional time-dependent hydrodynamical simulations to follow the growth of the Kelvin-Helmholtz (K-H) instability in cooling jets into the nonlinear regime. We focus primarily on asymmetric modes that give rise to transverse displacements of the jet beam. A variety of Mach numbers and two different cooling curves are studied. The growth rates of waves in the linear regime measured from the numerical simulations are in excellent agreement with the predictions of the linear stability analysis presented in the first paper in this series. In the nonlinear regime, the simulations show that asymmetric modes of the K-H instability can affect the structure and evolution of cooling jets in a number of ways. We find that jets in which the growth rate of the sinusoidal surface wave has a maximum at a so-called resonant frequency can be dominated by large-amplitude sinusoidal oscillations near this frequency. Eventually, growth of this wave can disrupt the jet. On the other hand, nonlinear body waves tend to produce low-amplitude wiggles in the shape of the jet but can result in strong shocks in the jet beam. In cooling jets, these shocks can produce dense knots and filaments of cooling gas within the jet. Ripples in the surface of the jet beam caused by both surface and body waves generate oblique shock "spurs" driven into the ambient gas. Our simulations show these shock "spurs" can accelerate ambient gas at large distances from the jet beam to low velocities, which represents a new mechanism by which low-velocity bipolar outflows may be driven by high-velocity jets. Rapid entrainment and acceleration of ambient gas may also occur if the jet is disrupted. For parameters typical of protostellar jets, the frequency at which K-H growth is a maximum (or highest frequency to which the entire jet can respond dynamically) will be associated with perturbations with a period of - 200 yr. Higher frequency (shorter period) perturbations excite waves associated with body modes that produce internal shocks and only small-amplitude wiggles within the jet. The fact that most observed systems show no evidence for large-amplitude sinusoidal oscillation leading to disruption is indicative that the perturbation frequencies are generally large, consistent with the suggestion that pro- tostellar jets arise from the inner regions (r less than 1 AU) of accretion disks.

Computational Modeling of Semiconductor Dynamics at Femtosecond Time Scales

NASA Technical Reports Server (NTRS)

Agrawal, Govind P.; Goorjian, Peter M.

1998-01-01

The main objective of the Joint-Research Interchange NCC2-5149 was to develop computer codes for accurate simulation of femtosecond pulse propagation in semiconductor lasers and semiconductor amplifiers [I]. The code should take into account all relevant processes such as the interband and intraband carrier relaxation mechanisms and the many-body effects arising from the Coulomb interaction among charge carriers [2]. This objective was fully accomplished. We made use of a previously developed algorithm developed at NASA Ames [3]-[5]. The new algorithm was tested on several problems of practical importance. One such problem was related to the amplification of femtosecond optical pulses in semiconductors. These results were presented in several international conferences over a period of three years. With the help of a postdoctoral fellow, we also investigated the origin of instabilities that can lead to the formation of femtosecond pulses in different kinds of lasers. We analyzed the occurrence of absolute instabilities in lasers that contain a dispersive host material with third-order nonlinearities. Starting from the Maxwell-Bloch equations, we derived general multimode equations to distinguish between convective and absolute instabilities. We find that both self-phase modulation and intensity-dependent absorption can dramatically affect the absolute stability of such lasers. In particular, the self-pulsing threshold (the so-called second laser threshold) can occur at few times the first laser threshold even in good-cavity lasers for which no self-pulsing occurs in the absence of intensity-dependent absorption. These results were presented in an international conference and published in the form of two papers.

Why Buckling Stellar Bars Weaken in Disk Galaxies

NASA Astrophysics Data System (ADS)

Martinez-Valpuesta, Inma; Shlosman, Isaac

2004-09-01

Young stellar bars in disk galaxies experience a vertical buckling instability that terminates their growth and thickens them, resulting in a characteristic peanut/boxy shape when viewed edge-on. Using N-body simulations of galactic disks embedded in live halos, we have analyzed the bar structure throughout this instability and found that the outer (approximately) third of the bar dissolves completely while the inner part (within the vertical inner Lindblad resonance) becomes less oval. The bar acquires the frequently observed peanut/boxy-shaped isophotes. We also find that the bar buckling is responsible for a mass injection above the plane, which is subsequently trapped by specific three-dimensional families of periodic orbits of particular shapes explaining the observed isophotes, in line with previous work. Using a three-dimensional orbit analysis and surfaces of sections, we infer that the outer part of the bar is dissolved by a rapidly widening stochastic region around its corotation radius-a process related to the bar growth. This leads to a dramatic decrease in the bar size, decrease in the overall bar strength, and a mild increase in its pattern speed but is not expected to lead to a complete bar dissolution. The buckling instability appears primarily responsible for shortening the secular diffusion timescale to a dynamical one when building the boxy isophotes. The sufficiently long timescale of the described evolution, ~1 Gyr, can affect the observed bar fraction in the local universe and at higher redshifts, both through reduced bar strength and the absence of dust offset lanes in the bar.

Changes in the Transnational Family Structures of Mexican Farm Workers in the Era of Border Militarization.

PubMed

Hamilton, Erin R; Hale, Jo Mhairi

2016-10-01

Historically, undocumented Mexican farm workers migrated circularly, leaving family behind in Mexico on short trips to the United States. Scholars have argued that border militarization has disrupted circular migration as the costs of crossing the border lead to longer stays, increased settlement, and changing transnational family practices. Yet, no study has explored changes in the transnational family structures of Mexico-U.S. migrants that span the era of border militarization. Using data from the National Agricultural Workers Survey, we document a dramatic shift away from transnational family life (as measured by location of residence of dependent children) among undocumented Mexican farm workers and a less dramatic shift among documented Mexican farm workers in the United States between 1993 and 2012. These trends are not explained by changes in the sociodemographic characteristics of farm workers or by changing demographic conditions or rising violence in Mexico. One-half of the trend can be accounted for by lengthened duration of stay and increased connections to the United States among the undocumented, but none of the trend is explained by these measures of settlement among the documented, suggesting that some Mexican farm workers adopt new family migration strategies at first migration. Increases in border control are associated with lower likelihood that children reside in Mexico-a finding that holds up to instrumental variable techniques. Our findings confirm the argument that U.S. border militarization-a policy designed to deter undocumented migration-is instead disrupting transnational family life between Mexico and the United States and, in doing so, is creating a permanent population of undocumented migrants and their children in the United States.

Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation

PubMed Central

Sun, GuoQiang; Yu, Ruth T.; Evans, Ronald M.; Shi, Yanhong

2007-01-01

TLX is a transcription factor that is essential for neural stem cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated neural stem cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates neural stem cell proliferation. TLX interacts with HDAC3 and HDAC5 in neural stem cells. The HDAC5-interaction domain was mapped to TLX residues 359–385, which contains a conserved nuclear receptor–coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in neural stem cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21CIP1/WAF1(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX-interacting HDACs play an important role in neural stem cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX–HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of neural stem cell proliferation. Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX–HDAC interactions. PMID:17873065

Aqueous magnesium as an environmental selection pressure in the evolution of phospholipid membranes on early earth

NASA Astrophysics Data System (ADS)

Dalai, Punam; Ustriyana, Putu; Sahai, Nita

2018-02-01

Early compartmentalization of simple biomolecules by membrane bilayers was, presumably, a critical step in the emergence of the first cell-like entities, protocells. Their membranes were likely composed of single chain amphiphiles (SCAs), but pure SCA membranes especially those with short-chains are highly unstable towards divalent cations, which are ubiquitous in aqueous environments. The prebiotic synthesis of phospholipids (PLs), even in only trace amounts, may also have been possible. PL membranes are much more stable towards divalent cations. Here, we show the transition of fatty acid membranes to mixed fatty acid-PL and, finally, to PL membranes in the presence of Mg2+, which acts as an environmental selection pressure, and we propose different mechanisms for the observed increased Mg2+-immunity. The "fatal" concentration ([Mg2+]fatal) at which vesicles are disrupted increased dramatically by an order of magnitude from OA to mixed to POPC vesicles. Two mechanisms for the increasing immunity were determined. The negative charge density of the vesicles decreased with increasing POPC content, so more Mg2+ was required for disruption. More interestingly, Mg2+ preferentially bound to and abstracted OA from mixed lipid membranes, resulting in relatively POPC-enriched vesicles compared to the initial ratio. The effect was the most dramatic for the largest initial OA-POPC ratio representing the most primitive protocells. Thus, Mg2+ acted to evolve the mixed membrane composition towards PL enrichment. To the best of our knowledge, this is the first report of selective lipid abstraction from mixed SCA-PL vesicles. These results may hold implications for accommodating prebiotic Mg2+-promoted processes such as non-enzymatic RNA polymerization on early Earth.

Selective alterations of the host cell architecture upon infection with parvovirus minute virus of mice

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

Nueesch, Juerg P.F.; Lachmann, Sylvie; Rommelaere, Jean

During a productive infection, the prototype strain of parvovirus minute virus of mice (MVMp) induces dramatic morphological alterations to the fibroblast host cell A9, resulting in cell lysis and progeny virus release. In order to understand the mechanisms underlying these changes, we characterized the fate of various cytoskeletal filaments and investigated the nuclear/cytoplasmic compartmentalization of infected cells. While most pronounced effects could be seen on micro- and intermediate filaments, manifest in dramatic rearrangements and degradation of filamentous (F-)actin and vimentin structures, only little impact could be seen on microtubules or the nuclear envelope during the entire monitored time of infection.more » To further analyze the disruption of the cytoskeletal structures, we investigated the viral impact on selective regulatory pathways. Thereby, we found a correlation between microtubule stability and MVM-induced phosphorylation of {alpha}/{beta} tubulin. In contrast, disassembly of actin filaments late in infection could be traced back to the disregulation of two F-actin associated proteins gelsolin and Wiscott-Aldrich Syndrome Protein (WASP). Thereby, an increase in the amount of gelsolin, an F-actin severing protein was observed during infection, accounting for the disruption of stress fibers upon infection. Concomitantly, the actin polymerization activity also diminished due to a loss of WASP, the activator protein of the actin polymerization machinery the Arp2/3 complex. No effects could be seen in amount and distribution of other F-actin regulatory factors such as cortactin, cofilin, and profilin. In summary, the selective attack of MVM towards distinct host cell cytoskeletal structures argues for a regulatory feature during infection, rather than a collapse of the host cell as a mere side effect of virus production.« less

Acute dietary zinc deficiency before conception compromises oocyte epigenetic programming and disrupts embryonic development.

PubMed

Tian, X; Diaz, F J

2013-04-01

Recent findings show that zinc is an important factor necessary for regulating the meiotic cell cycle and ovulation. However, the role of zinc in promoting oocyte quality and developmental potential is not known. Using an in vivo model of acute dietary zinc deficiency, we show that feeding a zinc deficient diet (ZDD) for 3-5 days before ovulation (preconception) dramatically disrupts oocyte chromatin methylation and preimplantation development. There was a dramatic decrease in histone H3K4 trimethylation and global DNA methylation in zinc deficient oocytes. Moreover, there was a 3-20 fold increase in transcript abundance of repetitive elements (Iap, Line1, Sineb1, Sineb2), but a decrease in Gdf9, Zp3 and Figla mRNA. Only 53% and 8% of mature eggs reached the 2-cell stage after IVF in animals receiving a 3 and 5 days ZDD, respectively, while a 5 day ZDD in vivo reduced the proportion of 2-cells to 49%. In vivo fertilized 2-cell embryos cultured in vitro formed fewer (38%) blastocysts compared to control embryos (74%). Likewise, fewer blastocyst and expanded blastocyst were collected from the reproductive tract of zinc deficient animals on day 3.5 of pregnancy. This could be due to a decrease in Igf2 and H19 mRNA in ZDD blastocyst. Supplementation with a methyl donor (SAM) during IVM restored histone H3K4me3 and doubled the IVF success rate from 17% to 43% in oocytes from zinc deficient animals. Thus, the terminal period of oocyte development is extremely sensitive to perturbation in dietary zinc availability. Copyright © 2013 Elsevier Inc. All rights reserved.

Amplifying recombination genome-wide and reshaping crossover landscapes in Brassicas

PubMed Central

Falque, Matthieu; Trotoux, Gwenn; Eber, Frédérique; Nègre, Sylvie; Gilet, Marie; Huteau, Virginie; Lodé, Maryse; Jousseaume, Thibaut; Dechaumet, Sylvain; Morice, Jérôme; Coriton, Olivier; Rousseau-Gueutin, Mathieu

2017-01-01

Meiotic recombination by crossovers (COs) is tightly regulated, limiting its key role in producing genetic diversity. However, while COs are usually restricted in number and not homogenously distributed along chromosomes, we show here how to disrupt these rules in Brassica species by using allotriploid hybrids (AAC, 2n = 3x = 29), resulting from the cross between the allotetraploid rapeseed (B. napus, AACC, 2n = 4x = 38) and one of its diploid progenitors (B. rapa, AA, 2n = 2x = 20). We produced mapping populations from different genotypes of both diploid AA and triploid AAC hybrids, used as female and/or as male. Each population revealed nearly 3,000 COs that we studied with SNP markers well distributed along the A genome (on average 1 SNP per 1.25 Mbp). Compared to the case of diploids, allotriploid hybrids showed 1.7 to 3.4 times more overall COs depending on the sex of meiosis and the genetic background. Most surprisingly, we found that such a rise was always associated with (i) dramatic changes in the shape of recombination landscapes and (ii) a strong decrease of CO interference. Hybrids carrying an additional C genome exhibited COs all along the A chromosomes, even in the vicinity of centromeres that are deprived of COs in diploids as well as in most studied species. Moreover, in male allotriploid hybrids we found that Class I COs are mostly responsible for the changes of CO rates, landscapes and interference. These results offer the opportunity for geneticists and plant breeders to dramatically enhance the generation of diversity in Brassica species by disrupting the linkage drag coming from limits on number and distribution of COs. PMID:28493942

Binary Black Holes, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Centrella, Joan

2008-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of very strong gravitational fields. We need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities, causing them to crash well before the black holes in the binary could complete even a single orbit. Recently this situation has changed dramatically, with a series of amazing breakthroughs. This talk will take you on this quest for the holy grail of numerical relativity, showing how a spacetime is constructed on a computer to build a simulation laboratory for binary black hole mergers. We will focus on the recent advances that are revealing these waveforms, and the dramatic new potential for discoveries that arises when these sources will be observed by LIGO and LISA.

Binary Black Holes, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Centrella, Joan

2008-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of very strong gravitational fields, we need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities. causing them to crash well before the black hole:, in the binary could complete even a single orbit. Recently this situation has changed dramatically, with a series of amazing breakthroughs. This talk will take you on this quest for the holy grail of numerical relativity, showing how a spacetime is constructed on a computer to build a simulation laboratory for binary black hole mergers. We will focus on the recent advances that are revealing these waveforms, and the dramatic new potential for discoveries that arises when these sources will be observed by LIGO and LISA.

Binary Black Holes, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Centrella, Joan

2008-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of very strong gravitational fields, we need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities, causing them to crash well before the black holes in the binary could complete even a single orbit. Recently this situation has changed dramatically, with a series of amazing breakthroughs. This talk will take you on this quest for the holy grail of numerical relativity, showing how a spacetime is constructed on a computer to build a simulation laboratory for binary black hole mergers. We will focus on the recent advances that are revealing these waveforms, and the dramatic new potential for discoveries that arises when these sources will be observed by LIGO and LISA.

Binary Black Holes, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Centrella, Joan

2009-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of very strong gravitational fields, we need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities, causing them to crash well before the black holes in the binary could complete even a single orbit. Recently this situation has changed dramatically, with a series of amazing breakthroughs. This talk will take you on this quest for the holy grail of numerical relativity, showing how a spacetime is constructed on a computer to build a simulation laboratory for binary black hole mergers. We will focus on the recent advances that are revealing these waveforms, and the dramatic new potential for discoveries that arises when these sources will be observed by LIGO and LISA.

Binary Black Holes, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Centrella, Joan

2007-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of very strong gravitational fields, we need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities, causing them to crash well before the black holes in the binary could complete even a single orbit. Recently this situation has changed dramatically, with a series of amazing breakthroughs. This talk will take you on this quest for the holy grail of numerical relativity, showing how a spacetime is constructed on a computer to build a simulation laboratory for binary black hole mergers. We will focus on the recent advances that are revealing these waveforms, and the dramatic new potential for discoveries that arises when these sources will be observed by LIGO and LISA

Binary Black Holes, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Centrella, Joan

2007-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of very strong gravitational fields, we need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities, causing them to crash well before the black holes in the binary could complete even a single orbit. Recently this situation has changed dramatically, with a series of amazing breakthroughs. This talk will take you on this quest for the holy grail of numerical relativity, showing how a spacetime is constructed on a computer to build a simutation laboratory for binary black hole mergers. We will focus on the recent advances that are revealing these waveforms, and the dramatic new potential for discoveries that arises when these sources will be observed by LIGO and LISA.

Binary Black Holes, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Centrella, Joan

2006-01-01

The final merger of two black holes releases a tremendous amount of energy and is one of the brightest sources in the gravitational wave sky. Observing these sources with gravitational wave detectors requires that we know the radiation waveforms they emit. Since these mergers take place in regions of extreme gravity, we need to solve Einstein's equations of general relativity on a computer in order to calculate these waveforms. For more than 30 years, scientists have tried to compute these waveforms using the methods of numerical relativity. The resulting computer codes have been plagued by instabilities, causing them to crash well before the black holes in the binary could complete even a single orbit. This situation has changed dramatically in the past year, with a series of amazing breakthroughs. This talk will take you on this quest for the holy grail of numerical relativity, showing how a spacetime is constructed on a computer to build a simulation laboratory for binary black hole mergers. We will focus on the recent advances that are revealing these waveforms, and the dramatic new potential for discoveries that arises when these sources will be observed by LISA and LIGO.

The Resilience of Kepler Multi-systems to Stellar Obliquity

NASA Astrophysics Data System (ADS)

Spalding, Christopher; Marx, Noah W.; Batygin, Konstantin

2018-04-01

The Kepler mission and its successor K2 have brought forth a cascade of transiting planets. Many of these planetary systems exhibit multiple transiting members. However, a large fraction possesses only a single transiting planet. This high abundance of singles, dubbed the "Kepler Dichotomy," has been hypothesized to arise from significant mutual inclinations between orbits in multi-planet systems. Alternatively, the single-transiting population truly possesses no other planets in the system, but the true origin of the overabundance of single systems remains unresolved. In this work, we propose that planetary systems typically form with a coplanar, multiple-planetary architecture, but that quadrupolar gravitational perturbations from their rapidly-rotating host star subsequently disrupt this primordial coplanarity. We demonstrate that, given sufficient stellar obliquity, even systems beginning with 2 planetary constituents are susceptible to dynamical instability soon after planet formation, as a result of the stellar quadrupole moment. This mechanism stands as a widespread, yet poorly explored pathway toward planetary system instability. Moreover, by requiring that observed multi-systems remain coplanar on Gyr timescales, we are able to place upper limits on the stellar obliquity in systems such as K2-38 (obliquity < 20 degrees), where other methods of measuring spin-orbit misalignment are not currently available.

Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers

PubMed Central

Udugama, Maheshi; Sanij, Elaine; Voon, Hsiao P. J.; Son, Jinbae; Hii, Linda; Henson, Jeremy D.; Chan, F. Lyn; Chang, Fiona T. M.; Liu, Yumei; Pearson, Richard B.; Kalitsis, Paul; Mann, Jeffrey R.; Collas, Philippe; Hannan, Ross D.; Wong, Lee H.

2018-01-01

ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers. PMID:29669917

Traumatic abdominal hernia complicated by necrotizing fasciitis.

PubMed

Martínez-Pérez, Aleix; Garrigós-Ortega, Gonzalo; Gómez-Abril, Segundo Ángel; Martí-Martínez, Eva; Torres-Sánchez, Teresa

2014-11-01

Necrotizing fasciitis is a critical illness involving skin and soft tissues, which may develop after blunt abdominal trauma causing abdominal wall hernia and representing a great challenge for physicians. A 52-year-old man was brought to the emergency department after a road accident, presenting blunt abdominal trauma with a large non-reducible mass in the lower-right abdomen. A first, CT showed abdominal hernia without signs of complication. Three hours after ICU admission, he developed hemodynamic instability. Therefore, a new CT scan was requested, showing signs of hernia complication. He was moved to the operating room where a complete transversal section of an ileal loop was identified. Five hours after surgery, he presented a new episode of hemodynamic instability with signs of skin and soft tissue infection. Due to the high clinical suspicion of necrotizing fasciitis development, wide debridement was performed. Following traumatic abdominal wall hernia (TAWH), patients can present unsuspected injuries in abdominal organs. Helical CT can be falsely negative in the early moments, leading to misdiagnosis. Necrotizing fasciitis is a potentially fatal infection and, consequently, resuscitation measures, wide-spectrum antibiotics, and early surgical debridement are required. This type of fasciitis can develop after blunt abdominal trauma following wall hernia without skin disruption.

Reshocks, rarefactions, and the generalized Layzer model for hydrodynamic instabilities

NASA Astrophysics Data System (ADS)

Mikaelian, Karnig O.

2009-02-01

We report numerical simulations and analytic modeling of shock tube experiments on Rayleigh-Taylor and Richtmyer-Meshkov instabilities. We examine single interfaces of the type A /B where the incident shock is initiated in A and the transmitted shock proceeds into B. Examples are He/air and air/He. In addition, we study finite-thickness or double-interface A /B/A configurations such as air/SF6/air gas-curtain experiments. We first consider conventional shock tubes that have a "fixed" boundary: A solid endwall which reflects the transmitted shock and reshocks the interface(s). Then we focus on new experiments with a "free" boundary—a membrane disrupted mechanically or by the transmitted shock, sending back a rarefaction toward the interface(s). Complex acceleration histories are achieved, relevant for inertial confinement fusion implosions. We compare our simulation results with a generalized Layzer model for two fluids with time-dependent densities and derive a new freeze-out condition whereby accelerating and compressive forces cancel each other out. Except for the recently reported failures of the Layzer model, the generalized Layzer model and hydrocode simulations for reshocks and rarefactions agree well with each other and remain to be verified experimentally.

Multi-region approach to free-boundary three-dimensional tokamak equilibria and resistive wall instabilities

NASA Astrophysics Data System (ADS)

Ferraro, N. M.; Jardin, S. C.; Lao, L. L.; Shephard, M. S.; Zhang, F.

2016-05-01

Free-boundary 3D tokamak equilibria and resistive wall instabilities are calculated using a new resistive wall model in the two-fluid M3D-C1 code. In this model, the resistive wall and surrounding vacuum region are included within the computational domain. This implementation contrasts with the method typically used in fluid codes in which the resistive wall is treated as a boundary condition on the computational domain boundary and has the advantage of maintaining purely local coupling of mesh elements. This new capability is used to simulate perturbed, free-boundary non-axisymmetric equilibria; the linear evolution of resistive wall modes; and the linear and nonlinear evolution of axisymmetric vertical displacement events (VDEs). Calculated growth rates for a resistive wall mode with arbitrary wall thickness are shown to agree well with the analytic theory. Equilibrium and VDE calculations are performed in diverted tokamak geometry, at physically realistic values of dissipation, and with resistive walls of finite width. Simulations of a VDE disruption extend into the current-quench phase, in which the plasma becomes limited by the first wall, and strong currents are observed to flow in the wall, in the SOL, and from the plasma to the wall.

Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects, and genomic instability

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Brooks, A. L.; Chatterjee, A. (Principal Investigator)

2001-01-01

Cell growth, differentiation and death are directed in large part by extracellular signaling through the interactions of cells with other cells and with the extracellular matrix; these interactions are in turn modulated by cytokines and growth factors, i.e. the microenvironment. Here we discuss the idea that extracellular signaling integrates multicellular damage responses that are important deterrents to the development of cancer through mechanisms that eliminate abnormal cells and inhibit neoplastic behavior. As an example, we discuss the action of transforming growth factor beta (TGFB1) as an extracellular sensor of damage. We propose that radiation-induced bystander effects and genomic instability are, respectively, positive and negative manifestations of this homeostatic process. Bystander effects exhibited predominantly after a low-dose or a nonhomogeneous radiation exposure are extracellular signaling pathways that modulate cellular repair and death programs. Persistent disruption of extracellular signaling after exposure to relatively high doses of ionizing radiation may lead to the accumulation of aberrant cells that are genomically unstable. Understanding radiation effects in terms of coordinated multicellular responses that affect decisions regarding the fate of a cell may necessitate re-evaluation of radiation dose and risk concepts and provide avenues for intervention.

Further evidences for sleep instability and impaired spindle-delta dynamics in schizophrenia: a whole-night polysomnography study with neuroloop-gain and sleep-cycle analysis.

PubMed

Sasidharan, Arun; Kumar, Sunil; Nair, Ajay Kumar; Lukose, Ammu; Marigowda, Vrinda; John, John P; Kutty, Bindu M

2017-10-01

Sleep offers a unique window into the brain dysfunctions in schizophrenia. Many past sleep studies have reported abnormalities in both macro-sleep architecture (like increased awakenings) as well as micro-sleep-architecture (like spindle deficits) in patients with schizophrenia (PSZ). The present study attempts to replicate previous reports of macro- and micro-sleep-architectural abnormalities in schizophrenia. In addition, the study also examined sleep-stage changes and spindle-delta dynamics across sleep-cycles to provide further evidence in support of the dysfunctional thalamocortical mechanisms causing sleep instability and poor sleep maintenance associated with schizophrenia pathophysiology. Whole-night polysomnography was carried out among 45 PSZ and 39 age- and gender-matched healthy control subjects. Sleep-stage dynamics were assessed across sleep-cycles using a customized software algorithm. Spindle-delta dynamics across sleep-cycles were determined using neuroloop-gain analysis. PSZ showed macro-sleep architecture abnormalities such as prolonged sleeplessness, increased intermittent-awakenings, long sleep-onset latency, reduced non-rapid eye movement (NREM) stage 2 sleep, increased stage transitions, and poor sleep efficiency. They also showed reduced spindle density (sigma neuroloop-gain) but comparable slow wave density (delta neuroloop-gain) throughout the sleep. Sleep-cycle-wise analysis revealed transient features of sleep instability due to significantly increased intermittent awakenings especially in the first and third sleep-cycles, and unstable and recurrent stage transitions in both NREM (first sleep-cycle) and rapid eye movement (REM) sleep-periods (second sleep-cycle). Spindle deficits were persistent across the first three cycles and were positively correlated with sleep disruption during the subsequent REM sleep. In addition to replicating previously reported sleep deficits in PSZ, the current study showed subtle deficits in NREM-REM alterations across whole-night polysomnography. These results point towards a possible maladaptive interplay between unstable thalamocortical networks, resulting in sleep-cycle-specific instability patterns associated with schizophrenia pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

Understanding the stability of the low torque ITER Baseline Scenario in DIII-D

NASA Astrophysics Data System (ADS)

Turco, Francesca

2017-10-01

Analysis of the evolving current density (J), pedestal and rotation profiles in a database of 200 ITER Baseline Scenario discharges in the DIII-D tokamak sheds light on the cause of the disruptive instability limiting both high and low torque operation of these plasmas. The m =2/n =1 tearing modes, occurring after several pressure-relaxation times, are related to the shape of the current profile in the outer region of the plasma. The q =2 surface is located just inside the current pedestal, near a minimum in J. This well in J deepens at constant betaN and at lower rotation, causing the equilibrium to evolve towards a classically unstable state. Lack of core-edge differential rotation likely biases the marginal point towards instability during the secular trend in J. New results from the 2017 experimental campaign establish the first reproducible, stable operation at T =0 Nm for this scenario. A new ramp-up recipe with delayed heating keeps the discharges stable without the need for ECCD stabilization. The J profile shape in the new shots is consistent with an expansion of the previous ``shallow well'' stable operational space. Realtime Active MHD Spectroscopy (AMS) has been applied to IBS plasmas for the first time, and the plasma response measurements show that the AMS can help sense the approach to instability during the discharges. The AMS data shows the trend towards instability at low rotation, and MARS-K modelling partially reproduces the experimental trend if collisionality and resistivity are included. The modelling results are sensitive to the edge resistivity, and this can indicate that the AMS is measuring the changes in ideal (kink) stability, to which the tearing stability index delta' is correlated. Together these results constitute a crucial step to acquire physical understanding and sensing capability for the MHD stability in the Q =10 ITER scenario. Work supported by US DOE under DE-FC02-04ER54698 and DE-FG02-04ER54761.

Endocrine-disrupting chemicals and oil and natural gas operations: Potential environmental contamination and recommendations to assess complex environmental mixtures

USGS Publications Warehouse

Kassotis, Christopher D.; Tillitt, Donald E.; Lin, Chung-Ho; McElroy, Jane A.; Nagel, Susan C.

2016-01-01

Background: Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. While these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals used throughout the process, including many known or suspected endocrine-disrupting chemicals.Objectives: We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and anti-hormonal activities for chemicals used.Methods: We discuss the literature on 1) surface and ground water contamination by oil and gas extraction operations, and 2) potential human exposure, particularly in context of the total hormonal and anti-hormonal activities present in surface and ground water from natural and anthropogenic sources, with initial analytical results and critical knowledge gaps discussed.Discussion: In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures.Conclusions: We describe a need for an endocrine-centric component for overall health assessments and provide supporting information that using this may help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

Identification and Validation of Novel Small Molecule Disruptors of HuR-mRNA Interaction

PubMed Central

Wu, Xiaoqing; Lan, Lan; Wilson, David Michael; Marquez, Rebecca T.; Tsao, Wei-chung; Gao, Philip; Roy, Anuradha; Turner, Benjamin Andrew; McDonald, Peter; Tunge, Jon A; Rogers, Steven A; Dixon, Dan A.; Aubé, Jeffrey; Xu, Liang

2015-01-01

HuR, an RNA binding protein, binds to adenine- and uridine-rich elements (ARE) in the 3′-untranslated region (UTR) of target mRNAs, regulating their stability and translation. HuR is highly abundant in many types of cancer, and it promotes tumorigenesis by interacting with cancer-associated mRNAs, which encode proteins that are implicated in different tumor processes including cell proliferation, cell survival, angiogenesis, invasion, and metastasis. Drugs that disrupt the stabilizing effect of HuR upon mRNA targets could have dramatic effects on inhibiting cancer growth and persistence. In order to identify small molecules that directly disrupt the HuR–ARE interaction, we established a fluorescence polarization (FP) assay optimized for high throughput screening (HTS) using HuR protein and an ARE oligo from Musashi RNA-binding protein 1 (Msi1) mRNA, a HuR target. Following the performance of an HTS of ~6000 compounds, we discovered a cluster of potential disruptors, which were then validated by AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay), surface plasmon resonance (SPR), ribonucleoprotein immunoprecipitation (RNP IP) assay, and luciferase reporter functional studies. These compounds disrupted HuR–ARE interactions at the nanomolar level and blocked HuR function by competitive binding to HuR. These results support future studies toward chemical probes for a HuR function study and possibly a novel therapy for HuR-overexpressing cancers. PMID:25750985

Impact of deformation on the atomic structures and dynamics of a Cu-Zr metallic glass: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Zhang, Y.; Mendelev, M. I.; Wang, C. Z.; Ott, R.; Zhang, F.; Besser, M. F.; Ho, K. M.; Kramer, M. J.

2014-11-01

Despite numerous studies on the atomic structures of Cu-Zr metallic glasses (MGs), their inherent structural ordering, e.g., medium-range order (MRO), remains difficult to describe. Specifically lacking is an understanding of how the MRO responds to deformation and the associated changes in atomic mobility. In this paper, we focus on the impact of deformation on MRO and associated effect on diffusion in a well-relaxed C u64.5Z r35.5 MG by molecular dynamics simulations. The Cu-Zr MG exhibits a larger elastic limit of 0.035 and a yield stress of 3.5 GPa. The cluster alignment method was employed to characterize the icosahedral short-range order (ISRO) and Bergman-type medium-range order (BMRO) in the models upon loading and unloading. From this analysis, we find the disruption of both ISRO and BMRO occurs as the strain reaches about 0.02, well below the elastic limit. Within the elastic limit, the total fractions of ISRO or BMRO can be fully recovered upon unloading. The diffusivity increases six to eight times in regions undergoing plastic deformation, which is due to the dramatic disruption of the ISRO and BMRO. By mapping the spatial distributions of the mobile atoms, we demonstrate the increase in atomic mobility is due to the extended regions of disrupted ISRO and more importantly BMRO.

Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures.

PubMed

Kassotis, Christopher D; Tillitt, Donald E; Lin, Chung-Ho; McElroy, Jane A; Nagel, Susan C

2016-03-01

Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals. We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used. We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps. In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures. We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

Testing synaptic plasticity in dynamic mate choice decisions: N-methyl d-aspartate receptor blockade disrupts female preference

PubMed Central

Ramsey, Mary E.; Vu, Wendy; Cummings, Molly E.

2014-01-01

Social behaviours such as mate choice require context-specific responses, often with evolutionary consequences. Increasing evidence indicates that the behavioural plasticity associated with mate choice involves learning. For example, poeciliids show age-dependent changes in female preference functions and express synaptic-plasticity-associated molecular markers during mate choice. Here, we test whether social cognition is necessary for female preference behaviour by blocking the central player in synaptic plasticity, NMDAR (N-methyl d-aspartate receptor), in a poeciliid fish, Xiphophorus nigrensis. After subchronic exposure to NMDAR antagonist MK-801, female preference behaviours towards males were dramatically reduced. Overall activity levels were unaffected, but there was a directional shift from ‘social’ behaviours towards neutral activity. Multivariate gene expression patterns significantly discriminated between females with normal versus disrupted plasticity processes and correlated with preference behaviours—not general activity. Furthermore, molecular patterns support a distinction between ‘preference’ (e.g. neuroserpin, neuroligin-3, NMDAR) and ‘sociality’ (isotocin and vasotocin) gene clusters, highlighting a possible conservation between NMDAR disruption and nonapeptides in modulating behaviour. Our results suggest that mate preference may involve greater social memory processing than overall sociality, and that poeciliid preference functions integrate synaptic-plasticity-oriented ‘preference’ pathways with overall sociality to invoke dynamic, context-specific responses towards favoured males and away from unfavoured males. PMID:24807251

Organization of cytoskeleton controls the changes in cytosolic calcium of cold-shocked Nicotiana plumbaginifolia protoplasts.

PubMed

Mazars, C; Thion, L; Thuleau, P; Graziana, A; Knight, M R; Moreau, M; Ranjeva, R

1997-11-01

Using Nicotiana plumbaginifolia constitutively expressing the recombinant bioluminescent calcium indicator, aequorin, it has been previously demonstrated that plant cells react to cold-shock by an immediate rise in cytosolic calcium. Such an opportune system has been exploited to address the regulatory pathway involved in the calcium response. For this purpose, we have used protoplasts derived from N. plumbaginifolia leaves that behave as the whole plant but with a better reproducibility. By both immunodetecting cytoskeletal components on membrane ghosts and measuring the relative change in cytosolic calcium, we demonstrate that the organization of the cytoskeleton has profound influences on the calcium response. The disruption of the microtubule meshwork by various active drugs, such as colchicin, oryzalin and vinblastin, leads to an important increase in the cytosolic calcium (up to 400 nM) in cold-shocked protoplasts over control. beta-Lumicolchicin, an inactive analogue of colchicin, is ineffective either on cytoplasmic calcium increase or on microtubule organization. A microfilament disrupting drug, cytochalasin D, exerts a slight stimulatory effect, whereas the simultaneous disruption of microtubule and microfilament meshworks results in a dramatic increase in the calcium response to cold-shock. The results described in the present paper illustrate the role of the intracellular organization and, more specifically, the role of cytoskeleton in controlling the intensity of calcium response to an extracellular stimulus.

Binary black holes, gravitational waves, and numerical relativity

NASA Astrophysics Data System (ADS)

Centrella, Joan M.; Baker, John G.; Boggs, William D.; Kelly, Bernard J.; McWilliams, Sean T.; van Meter, James R.

2007-07-01

The final merger of comparable mass binary black holes produces an intense burst of gravitational radiation and is one of the strongest sources for both ground-based and space-based gravitational wave detectors. Since the merger occurs in the strong-field dynamical regime of general relativity, numerical relativity simulations of the full Einstein equations in 3-D are required to calculate the resulting gravitational dynamics and waveforms. While this problem has been pursued for more than 30 years, the numerical codes have long been plagued by various instabilities and, overall, progress was incremental. Recently, however, dramatic breakthrough have occurred, resulting in robust simulations of merging black holes. In this paper, we examine these developments and the exciting new results that are emerging.

Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA

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

Knappenberger, Andrew John; Reiss, Caroline Wetherington; Strobel, Scott A.

Two classes of riboswitches related to the ykkC guanidine-I riboswitch bind phosphoribosyl pyrophosphate (PRPP) and guanosine tetraphosphate (ppGpp). Here we report the co-crystal structure of the PRPP aptamer and its ligand. We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with a dramatic 40,000-fold switch in specificity. The ends of the aptamer form a helix that is not present in the guanidine aptamer and is involved in the expression platform. In the mutant, the base of ppGpp replaces G96 in three-dimensional space. This disrupts the S-turn, which is a primary structural feature of themore » ykkC RNA motif. These dramatic differences in ligand specificity are achieved with minimal mutations. ykkC aptamers are therefore a prime example of an RNA fold with a rugged fitness landscape. The ease with which the ykkC aptamer acquires new specificity represents a striking case of evolvability in RNA.« less

Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA.

PubMed

Knappenberger, Andrew John; Reiss, Caroline Wetherington; Strobel, Scott A

2018-06-07

Two classes of riboswitches related to the ykkC guanidine-I riboswitch bind phosphoribosyl pyrophosphate (PRPP) and guanosine tetraphosphate (ppGpp). Here we report the co-crystal structure of the PRPP aptamer and its ligand. We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with a dramatic 40,000-fold switch in specificity. The ends of the aptamer form a helix that is not present in the guanidine aptamer and is involved in the expression platform. In the mutant, the base of ppGpp replaces G96 in three-dimensional space. This disrupts the S-turn, which is a primary structural feature of the ykkC RNA motif. These dramatic differences in ligand specificity are achieved with minimal mutations. ykkC aptamers are therefore a prime example of an RNA fold with a rugged fitness landscape. The ease with which the ykkC aptamer acquires new specificity represents a striking case of evolvability in RNA. © 2018, Knappenberger et al.

Optical/UV-to-X-Ray Echoes from the Tidal Disruption Flare ASASSN-14li

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

Pasham, Dheeraj R.; Sadowski, Aleksander; Cenko, S. Bradley

We carried out the first multi-wavelength (optical/UV and X-ray) photometric reverberation mapping of a tidal disruption flare (TDF) ASASSN-14li. We find that its X-ray variations are correlated with and lag the optical/UV fluctuations by 32 ± 4 days. Based on the direction and the magnitude of the X-ray time lag, we rule out X-ray reprocessing and direct emission from a standard circular thin disk as the dominant source of its optical/UV emission. The lag magnitude also rules out an AGN disk-driven instability as the origin of ASASSN-14li and thus strongly supports the tidal disruption picture for this event and similarmore » objects. We suggest that the majority of the optical/UV emission likely originates from debris stream self-interactions. Perturbations at the self-interaction sites produce optical/UV variability and travel down to the black hole where they modulate the X-rays. The time lag between the optical/UV and the X-rays variations thus correspond to the time taken by these fluctuations to travel from the self-interaction site to close to the black hole. We further discuss these time lags within the context of the three variants of the self-interaction model. High-cadence monitoring observations of future TDFs will be sensitive enough to detect these echoes and would allow us to establish the origin of optical/UV emission in TDFs in general.« less

Kinetic electron and ion instability of the lunar wake simulated at physical mass ratio

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

Haakonsen, Christian Bernt, E-mail: chaako@mit.edu; Hutchinson, Ian H., E-mail: ihutch@mit.edu; Zhou, Chuteng, E-mail: ctzhou@mit.edu

2015-03-15

The solar wind wake behind the moon is studied with 1D electrostatic particle-in-cell (PIC) simulations using a physical ion to electron mass ratio (unlike prior investigations); the simulations also apply more generally to supersonic flow of dense magnetized plasma past non-magnetic objects. A hybrid electrostatic Boltzmann electron treatment is first used to investigate the ion stability in the absence of kinetic electron effects, showing that the ions are two-stream unstable for downstream wake distances (in lunar radii) greater than about three times the solar wind Mach number. Simulations with PIC electrons are then used to show that kinetic electron effectsmore » can lead to disruption of the ion beams at least three times closer to the moon than in the hybrid simulations. This disruption occurs as the result of a novel wake phenomenon: the non-linear growth of electron holes spawned from a narrow dimple in the electron velocity distribution. Most of the holes arising from the dimple are small and quickly leave the wake, approximately following the unperturbed electron phase-space trajectories, but some holes originating near the center of the wake remain and grow large enough to trigger disruption of the ion beams. Non-linear kinetic-electron effects are therefore essential to a comprehensive understanding of the 1D electrostatic stability of such wakes, and possible observational signatures in ARTEMIS data from the lunar wake are discussed.« less

Complement factor C5a induces atherosclerotic plaque disruptions

PubMed Central

Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

2014-01-01

Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

A Medial Malleolar "Fleck Sign" May Predict Ankle Instability in Ligamentous Supination External Rotation Ankle Fractures.

PubMed

Nwosu, Kenneth; Schneiderman, Brian Andrew; Shymon, Stephen Joseph; Harris, Thomas

2018-06-01

Ankle joint stability dictates treatment in ligamentous supination external rotation ankle injuries (LSERAI). Investigation of the medial structures that support the ankle mortise is critical, and a small avulsion fracture, or "fleck", of the medial malleolus is occasionally encountered. This study aimed to assess the utility of this medial malleolus fleck sign (MMFS) in diagnosing instability requiring surgery in LSERAI. This retrospective observational study examined 166 LSERAI at a single level I trauma center. A standardized diagnostic and treatment protocol for ankle fractures was followed. LSERAI at presentation were reported as having a normal, dynamically wide, or statically wide medial clear space. Patient demographics, MMFS characteristics, and the use of operative management were recorded. MMFS incidence in the cohort was 16 (10%) of 166 and was present in 25% of patients with unstable LSERAI. Fifteen (94%) of 16 patients with a MMFS were deemed to have an unstable LSERAI (P < .005). MMFS had a 25% sensitivity and 99% specificity in diagnosing an unstable LSERAI. For the subgroup of patients without a statically wide medial clear space, MMFS had a 50% sensitivity and 99% specificity in determining instability. A MMFS may be indicative of an unstable LSERAI. With previous MRI studies demonstrating complete deltoid disruption in unstable LSERAI, we deduce the MMFS may be associated with extensive deltoid incompetence. The MMFS may help to diagnose a complete deltoid injury in LSERAI with a normal medial clear space, which could influence treatment and reduce patient morbidity, radiation exposure, and healthcare costs. Level III: Retrospective Cohort Study.

Future of antibody purification.

PubMed

Low, Duncan; O'Leary, Rhona; Pujar, Narahari S

2007-03-15

Antibody purification seems to be safely ensconced in a platform, now well-established by way of multiple commercialized antibody processes. However, natural evolution compels us to peer into the future. This is driven not only by a large, projected increase in the number of antibody therapies, but also by dramatic improvements in upstream productivity, and process economics. Although disruptive technologies have yet escaped downstream processes, evolution of the so-called platform is already evident in antibody processes in late-stage development. Here we perform a wide survey of technologies that are competing to be part of that platform, and provide our [inherently dangerous] assessment of those that have the most promise.

A dominant mutation in mediator of paramutation2, one of three second-largest subunits of a plant-specific RNA polymerase, disrupts multiple siRNA silencing processes.

PubMed

Sidorenko, Lyudmila; Dorweiler, Jane E; Cigan, A Mark; Arteaga-Vazquez, Mario; Vyas, Meenal; Kermicle, Jerry; Jurcin, Diane; Brzeski, Jan; Cai, Yu; Chandler, Vicki L

2009-11-01

Paramutation involves homologous sequence communication that leads to meiotically heritable transcriptional silencing. We demonstrate that mop2 (mediator of paramutation2), which alters paramutation at multiple loci, encodes a gene similar to Arabidopsis NRPD2/E2, the second-largest subunit of plant-specific RNA polymerases IV and V. In Arabidopsis, Pol-IV and Pol-V play major roles in RNA-mediated silencing and a single second-largest subunit is shared between Pol-IV and Pol-V. Maize encodes three second-largest subunit genes: all three genes potentially encode full length proteins with highly conserved polymerase domains, and each are expressed in multiple overlapping tissues. The isolation of a recessive paramutation mutation in mop2 from a forward genetic screen suggests limited or no functional redundancy of these three genes. Potential alternative Pol-IV/Pol-V-like complexes could provide maize with a greater diversification of RNA-mediated transcriptional silencing machinery relative to Arabidopsis. Mop2-1 disrupts paramutation at multiple loci when heterozygous, whereas previously silenced alleles are only up-regulated when Mop2-1 is homozygous. The dramatic reduction in b1 tandem repeat siRNAs, but no disruption of silencing in Mop2-1 heterozygotes, suggests the major role for tandem repeat siRNAs is not to maintain silencing. Instead, we hypothesize the tandem repeat siRNAs mediate the establishment of the heritable silent state-a process fully disrupted in Mop2-1 heterozygotes. The dominant Mop2-1 mutation, which has a single nucleotide change in a domain highly conserved among all polymerases (E. coli to eukaryotes), disrupts both siRNA biogenesis (Pol-IV-like) and potentially processes downstream (Pol-V-like). These results suggest either the wild-type protein is a subunit in both complexes or the dominant mutant protein disrupts both complexes. Dominant mutations in the same domain in E. coli RNA polymerase suggest a model for Mop2-1 dominance: complexes containing Mop2-1 subunits are non-functional and compete with wild-type complexes.

Merger of a white dwarf-neutron star binary to 1029 carat diamonds: origin of the pulsar planets

NASA Astrophysics Data System (ADS)

Margalit, Ben; Metzger, Brian D.

2017-03-01

We show that the merger and tidal disruption of a carbon/oxygen (C/O) white dwarf (WD) by a neutron star (NS) binary companion provides a natural formation scenario for the PSR B1257+12 planetary system. Starting with initial conditions for the debris disc produced of the disrupted WD, we model its long-term viscous evolution, including for the first time the effects of mass and angular momentum loss during the early radiatively inefficient accretion flow (RIAF) phase and accounting for the unusual C/O composition on the disc opacity. For plausible values of the disc viscosity α ∼ 10-3-10-2 and the RIAF mass-loss efficiency, we find that the disc mass remaining near the planet formation radius at the time of solid condensation is sufficient to explain the pulsar planets. Rapid rocky planet formation via gravitational instability of the solid carbon dominated disc is facilitated by the suppression of vertical shear instabilities due to the high solid-to-gas ratio. Additional evidence supporting a WD-NS merger scenario includes (1) the low observed occurrence rate of pulsar planets (≲1 per cent of NS birth), comparable to the expected WD-NS merger rate; (2) accretion by the NS during the RIAF phase is sufficient to spin PSR B1257+12 up to its observed 6 ms period; (3) similar models of 'low angular momentum' discs, such as those produced from supernova fallback, find insufficient mass reaching the planet formation radius. The unusually high space velocity of PSR B1257+12 of ≳326 km s-1 suggests a possible connection to the calcium-rich transients, dim supernovae which occur in the outskirts of their host galaxies and were proposed to result from mergers of WD-NS binaries receiving supernova kicks. The C/O disc composition implied by our model likely results in carbon-rich planets with diamond interiors.

Disturbed Dreaming and the Instability of Sleep: Altered Nonrapid Eye Movement Sleep Microstructure in Individuals with Frequent Nightmares as Revealed by the Cyclic Alternating Pattern

PubMed Central

Simor, Péter; Bódizs, Róbert; Horváth, Klára; Ferri, Raffaele

2013-01-01

Study Objectives: Nightmares are disturbing mental experiences during sleep that usually result in abrupt awakenings. Frequent nightmares are associated with poor subjective sleep quality, and recent polysomnographic data suggest that nightmare sufferers exhibit impaired sleep continuity during nonrapid eye movement (NREM) sleep. Because disrupted sleep might be related to abnormal arousal processes, the goal of this study was to examine polysomnographic arousal-related activities in a group of nightmare sufferers and a healthy control group. Design: Sleep microstructure analysis was carried out by scoring the cyclic alternating pattern (CAP) in NREM sleep and the arousal index in rapid eye movement (REM) sleep on the second night of the polysomnographic examination. Setting: Hospital-based sleep research laboratory. Participants: There were 17 in the nightmare (NMs) group and 23 in the healthy control (CTLs) group. Interventions: N/A. Measurements and Results: The NMs group exhibited reduced amounts of CAP A1 subtype and increased CAP A2 and A3 subtypes, as well as longer duration of CAP A phases in comparison with CTLs. Moreover, these differences remained significant after controlling for the confounding factors of anxious and depressive symptoms. The absolute number and frequency of REM arousals did not differ significantly between the two groups. Conclusions: The results of our study indicate that NREM sleep microstructure is altered during nonsymptomatic nights of nightmares. Disrupted sleep in the NMs group seems to be related to abnormal arousal processes, specifically an imbalance in sleep-promoting and arousing mechanisms during sleep. Citation: Simor P; Bódizs R; Horváth K; Ferri R. Disturbed dreaming and the instability of sleep: altered nonrapid eye movement sleep microstructure in individuals with frequent nightmares as revealed by the cyclic alternating pattern. SLEEP 2013;36(3):413-419. PMID:23449753

Instability of the insertional mutation in CftrTgH(neoim)Hgu cystic fibrosis mouse model

PubMed Central

Charizopoulou, Nikoletta; Jansen, Silke; Dorsch, Martina; Stanke, Frauke; Dorin, Julia R; Hedrich, Hans-Jürgen; Tümmler, Burkhard

2004-01-01

Background A major boost to the cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search for modifier genes. From the original CftrTgH(neoim)Hgu CF mouse model we have generated using strict brother × sister mating two inbred CftrTgH(neoim)Hgu mouse lines (CF/1 and CF/3). Thereafter, the insertional mutation was introgressed from CF/3 into three inbred backgrounds (C57BL/6, BALB/c, DBA/2J) generating congenic animals. In every backcross cycle germline transmission of the insertional mutation was monitored by direct probing the insertion via Southern RFLP. In order to bypass this time consuming procedure we devised an alternative PCR based protocol whereby mouse strains are differentiated at the Cftr locus by Cftr intragenic microsatellite genotypes that are tightly linked to the disrupted locus. Results Using this method we were able to identify animals carrying the insertional mutation based upon the differential haplotypic backgrounds of the three inbred strains and the mutant CftrTgH(neoim)Hgu at the Cftr locus. Moreover, this method facilitated the identification of the precise vector excision from the disrupted Cftr locus in two out of 57 typed animals. This reversion to wild type status took place without any loss of sequence revealing the instability of insertional mutations during the production of congenic animals. Conclusions We present intragenic microsatellite markers as a tool for fast and efficient identification of the introgressed locus of interest in the recipient strain during congenic animal breeding. Moreover, the same genotyping method allowed the identification of a vector excision event, posing questions on the stability of insertional mutations in mice. PMID:15102331

Elongated Nanoparticle Aggregates in Cancer Cells for Mechanical Destruction with Low Frequency Rotating Magnetic Field.

PubMed

Shen, Yajing; Wu, Congyu; Uyeda, Taro Q P; Plaza, Gustavo R; Liu, Bin; Han, Yu; Lesniak, Maciej S; Cheng, Yu

2017-01-01

Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells.

Silencing the HaHR3 Gene by Transgenic Plant-mediated RNAi to Disrupt Helicoverpa armigera Development

PubMed Central

Xiong, Yehui; Zeng, Hongmei; Zhang, Yuliang; Xu, Dawei; Qiu, Dewen

2013-01-01

RNA interference (RNAi) caused by exogenous double-stranded RNA (dsRNA) has developed into a powerful technique in functional genomics, and to date it is widely used to down-regulate crucial physiology-related genes to control pest insects. A molt-regulating transcription factor gene, HaHR3, of cotton bollworm (Helicoverpa armigera) was selected as the target gene. Four different fragments covering the coding sequence (CDS) of HaHR3 were cloned into vector L4440 to express dsRNAs in Escherichia coli. The most effective silencing fragment was then cloned into a plant over-expression vector to express a hairpin RNA (hpRNA) in transgenic tobacco (Nicotiana tabacum). When H. armigera larvae were fed the E. coli or transgenic plants, the HaHR3 mRNA and protein levels dramatically decreased, resulting developmental deformity and larval lethality. The results demonstrate that both recombinant bacteria and transgenic plants could induce HaHR3 silence to disrupt H. armigera development, transgenic plant-mediated RNAi is emerging as a powerful approach for controlling insect pests. PMID:23630449

Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon.

PubMed

Gil-Sanz, Cristina; Landeira, Bruna; Ramos, Cynthia; Costa, Marcos R; Müller, Ulrich

2014-08-06

Radial glial cells (RGCs) in the ventricular neuroepithelium of the dorsal telencephalon are the progenitor cells for neocortical projection neurons and astrocytes. Here we show that the adherens junction proteins afadin and CDH2 are critical for the control of cell proliferation in the dorsal telencephalon and for the formation of its normal laminar structure. Inactivation of afadin or CDH2 in the dorsal telencephalon leads to a phenotype resembling subcortical band heterotopia, also known as "double cortex," a brain malformation in which heterotopic gray matter is interposed between zones of white matter. Adherens junctions between RGCs are disrupted in the mutants, progenitor cells are widely dispersed throughout the developing neocortex, and their proliferation is dramatically increased. Major subtypes of neocortical projection neurons are generated, but their integration into cell layers is disrupted. Our findings suggest that defects in adherens junctions components in mice massively affects progenitor cell proliferation and leads to a double cortex-like phenotype. Copyright © 2014 the authors 0270-6474/14/3410475-13$15.00/0.

Altered gene expression patterns during the initiation and promotion stages of neonatally diethylstilbestrol-induced hyperplasia/dysplasia/neoplasia in the hamster uterus.

PubMed

Hendry, William J; Hariri, Hussam Y; Alwis, Imala D; Gunewardena, Sumedha S; Hendry, Isabel R

2014-12-01

Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: (1) immunoblot analyses and (2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and (3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: (1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and (2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

Elongated Nanoparticle Aggregates in Cancer Cells for Mechanical Destruction with Low Frequency Rotating Magnetic Field

PubMed Central

Shen, Yajing; Wu, Congyu; Uyeda, Taro Q. P.; Plaza, Gustavo R.; Liu, Bin; Han, Yu; Lesniak, Maciej S.; Cheng, Yu

2017-01-01

Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells. PMID:28529648

Small-molecule inhibitors directly target CARD9 and mimic its protective variant in inflammatory bowel disease.

PubMed

Leshchiner, Elizaveta S; Rush, Jason S; Durney, Michael A; Cao, Zhifang; Dančík, Vlado; Chittick, Benjamin; Wu, Huixian; Petrone, Adam; Bittker, Joshua A; Phillips, Andrew; Perez, Jose R; Shamji, Alykhan F; Kaushik, Virendar K; Daly, Mark J; Graham, Daniel B; Schreiber, Stuart L; Xavier, Ramnik J

2017-10-24

Advances in human genetics have dramatically expanded our understanding of complex heritable diseases. Genome-wide association studies have identified an allelic series of CARD9 variants associated with increased risk of or protection from inflammatory bowel disease (IBD). The predisposing variant of CARD9 is associated with increased NF-κB-mediated cytokine production. Conversely, the protective variant lacks a functional C-terminal domain and is unable to recruit the E3 ubiquitin ligase TRIM62. Here, we used biochemical insights into CARD9 variant proteins to create a blueprint for IBD therapeutics and recapitulated the mechanism of the CARD9 protective variant using small molecules. We developed a multiplexed bead-based technology to screen compounds for disruption of the CARD9-TRIM62 interaction. We identified compounds that directly and selectively bind CARD9, disrupt TRIM62 recruitment, inhibit TRIM62-mediated ubiquitinylation of CARD9, and demonstrate cellular activity and selectivity in CARD9-dependent pathways. Taken together, small molecules targeting CARD9 illustrate a path toward improved IBD therapeutics. Published under the PNAS license.

Diminished self-conscious emotional responding in frontotemporal lobar degeneration patients.

PubMed

Sturm, Virginia E; Ascher, Elizabeth A; Miller, Bruce L; Levenson, Robert W

2008-12-01

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that dramatically alters social and emotional behavior. Recent work has suggested that self-conscious emotions (e.g., embarrassment) may be particularly vulnerable to disruption in this disease. Self-conscious emotions require the ability to monitor the self in relation to others. These abilities are thought to be subserved by brain regions (e.g., medial prefrontal, anterior cingulate, and insula) that are particularly vulnerable to damage in FTLD. This study examined emotional responding (expressive behavior, peripheral physiology, and subjective experience) in 24 FTLD patients and 16 cognitively normal control participants using a karaoke task known to elicit self-conscious emotion reliably and a nonemotional control task (isometric handgrip). Results indicated that FTLD patients showed diminished self-conscious emotional behavior (embarrassment and amusement) and diminished physiological responding while watching themselves singing. No differences were found between patients and controls in the nonemotional control task. These findings offer evidence of marked disruption of self-conscious emotional responding in FTLD. Diminished self-conscious emotional responding likely contributes significantly to social inappropriateness and other behavioral abnormalities in FTLD. 2008 APA, all rights reserved

Diminished Self-Conscious Emotional Responding in Frontotemporal Lobar Degeneration Patients

PubMed Central

Sturm, Virginia E.; Ascher, Elizabeth A.; Miller, Bruce L.; Levenson, Robert W.

2009-01-01

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that dramatically alters social and emotional behavior. Recent work has suggested that self-conscious emotions (e.g., embarrassment) may be particularly vulnerable to disruption in this disease. Self-conscious emotions require the ability to monitor the self in relation to others. These abilities are thought to be subserved by brain regions (e.g., medial prefrontal, anterior cingulate, and insula) that are particularly vulnerable to damage in FTLD. This study examined emotional responding (expressive behavior, peripheral physiology, and subjective experience) in 24 FTLD patients and 16 cognitively normal control participants using a karaoke task known to elicit self-conscious emotion reliably and a nonemotional control task (isometric handgrip). Results indicated that FTLD patients showed diminished self-conscious emotional behavior (embarrassment and amusement) and diminished physiological responding while watching themselves singing. No differences were found between patients and controls in the nonemotional control task. These findings offer evidence of marked disruption of self-conscious emotional responding in FTLD. Diminished self-conscious emotional responding likely contributes significantly to social inappropriateness and other behavioral abnormalities in FTLD. PMID:19102597

Bisphenol A disrupts gene expression in human placental trophoblast cells.

PubMed

Rajakumar, Chandrew; Guan, Haiyan; Langlois, David; Cernea, Maria; Yang, Kaiping

2015-06-01

This study examined the effect of bisphenol A (BPA) on human placental gene expression using primary trophoblast cells as an in vitro model system. Trophoblast cells were isolated from human placentas at term, cultured and then exposed to environmentally relevant concentrations of BPA (0.1-2 μg/ml) for up to 24h, after which levels of 11β-HSD2 mRNA, protein and activity were determined by standard radiometric conversion assay, western blotting, and qRT-PCR, respectively. The mRNA levels of several other prominent placental hormones/factors were also assessed by qRT-PCR. BPA dramatically increased levels of 11β-HSD2 activity, protein and mRNA in a time- and concentration-dependent manner (> 4-fold). BPA also augmented aromatase, glucose transporter-1, CRH, and hCG mRNA levels while reducing the level of leptin mRNA. These findings demonstrate that BPA severely disrupts human placental gene expression in vitro, which suggests that exposure to BPA may contribute to altered placental function and consequent pregnancy complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Loss of Mitochondrial Fission Depletes Axonal Mitochondria in Midbrain Dopamine Neurons

PubMed Central

Berthet, Amandine; Margolis, Elyssa B.; Zhang, Jue; Hsieh, Ivy; Zhang, Jiasheng; Hnasko, Thomas S.; Ahmad, Jawad; Edwards, Robert H.; Sesaki, Hiromi; Huang, Eric J.

2014-01-01

Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics—mitochondrial fission—in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp1). Drp1 loss rapidly eliminates the DA terminals in the caudate–putamen and causes cell bodies in the midbrain to degenerate and lose α-synuclein. Without Drp1, mitochondrial mass dramatically decreases, especially in axons, where the mitochondrial movement becomes uncoordinated. However, in the ventral tegmental area (VTA), a subset of midbrain DA neurons characterized by small hyperpolarization-activated cation currents (Ih) is spared, despite near complete loss of their axonal mitochondria. Drp1 is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons. PMID:25339743

Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons.

PubMed

Berthet, Amandine; Margolis, Elyssa B; Zhang, Jue; Hsieh, Ivy; Zhang, Jiasheng; Hnasko, Thomas S; Ahmad, Jawad; Edwards, Robert H; Sesaki, Hiromi; Huang, Eric J; Nakamura, Ken

2014-10-22

Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics-mitochondrial fission-in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp1). Drp1 loss rapidly eliminates the DA terminals in the caudate-putamen and causes cell bodies in the midbrain to degenerate and lose α-synuclein. Without Drp1, mitochondrial mass dramatically decreases, especially in axons, where the mitochondrial movement becomes uncoordinated. However, in the ventral tegmental area (VTA), a subset of midbrain DA neurons characterized by small hyperpolarization-activated cation currents (Ih) is spared, despite near complete loss of their axonal mitochondria. Drp1 is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons. Copyright © 2014 the authors 0270-6474/14/3414304-14$15.00/0.

Fast Time Response Electromagnetic Particle Injection System for Disruption Mitigation

NASA Astrophysics Data System (ADS)

Raman, Roger; Lay, W.-S.; Jarboe, T. R.; Menard, J. E.; Ono, M.

2017-10-01

Predicting and controlling disruptions is an urgent issue for ITER. In this proposed method, a radiative payload consisting of micro spheres of Be, BN, B, or other acceptable low-Z materials would be injected inside the q =2 surface for thermal and runaway electron mitigation. The radiative payload would be accelerated to the required velocities (0.2 to >1km/s) in an Electromagnetic Particle Injector (EPI). An important advantage of the EPI system is that it could be positioned very close to the reactor vessel. This has the added benefit that the external field near a high-field tokamak dramatically improves the injector performance, while simultaneously reducing the system response time. A NSTX-U / DIII-D scale system has been tested off-line to verify the critical parameters - the projected system response time and attainable velocities. Both are consistent with the model calculations, giving confidence that an ITER-scale system could be built to ensure safety of the ITER device. This work is supported by U.S. DOE Contracts: DE-AC02-09CH11466, DE-FG02-99ER54519 AM08, and DE-SC0006757.

Disrupting effects of polychlorinated biphenyls on gonadal development and reproductive functions in chickens.

PubMed

Zhang, Caiqiao; Fang, Changge; Liu, Li; Xia, Guoliang; Qiao, Huili

2002-01-01

Polychlorinated biphenyls (PCBs) are worldwide persistent pollutants that have produced detrimental effects on endocrine function and reproduction in a variety of species. The present study revealed effects of PCBs on gonadal development and functions in chickens of different ages. Aroclor 1254 (0-100 microg/egg) was injected into Hyline chicken eggs before incubation. The adult chickens received Aroclor 1254 by gavage (50 mg/kg BW). It was observed that in day 5 embryos, PCBs resulted in a dose-dependent decrease of primordial germ cell (PGC) numbers, and caused PGCs pyknosis and vacuolation. Clomiphen failed to block the effects of PCBs. In the newly hatched chicken, PCBs induced a marked decrease in area of the transverse sections, diameter and relative area of the testicular tubules. The differentiation of germ cells was retarded after PCB treatment. In contrast, the area of the left ovarian transverse sections, the thickness of ovarian cortex and the number of oocytes increased dramatically in the female chickens after PCB exposure. In the adult chickens, PCBs caused no significant changes in body weight, respiration, heart rate, body temperature, red and white blood cell number, but induced a marked decrease in the testicular weight, and severe damage of the seminiferous tubules. The number of the spermatogenic cells and serum testosterone level were decreased significantly by PCBs. On the contrary, in the laying hens there was no significant effect of PCB on egg quality except a slight decrease in egg weight. These results indicated that PCBs exerted its disrupting effects on chicken reproduction with a sex and stage-related pattern, and in vivo disruption of gonadal development represents a possible model for risk assessment of environmental endocrine disrupters by in ovo treatment.

Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures

PubMed Central

Kassotis, Christopher D.; Tillitt, Donald E.; Lin, Chung-Ho; McElroy, Jane A.; Nagel, Susan C.

2015-01-01

Background Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals. Objectives We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used. Methods We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps. Discussion In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures. Conclusions We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs. Citation Kassotis CD, Tillitt DE, Lin CH, McElroy JA, Nagel SC. 2016. Endocrine-disrupting chemicals and oil and natural gas operations: potential environmental contamination and recommendations to assess complex environmental mixtures. Environ Health Perspect 124:256–264; http://dx.doi.org/10.1289/ehp.1409535 PMID:26311476

Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses

PubMed Central

2014-01-01

Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL). MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number 24 hours after exposure to 0.024, 0.24, 2.4 and 24 μg/cm2 MWCNT. Monopolar mitotic spindles comprised 95% of disrupted mitoses. Three-dimensional reconstructions of 0.1 μm optical sections showed carbon nanotubes integrated with microtubules, DNA and within the centrosome structure. Cell cycle analysis demonstrated a greater number of cells in S-phase and fewer cells in the G2 phase in MWCNT-treated compared to diluent control, indicating a G1/S block in the cell cycle. The monopolar phenotype of the disrupted mitotic spindles and the G1/S block in the cell cycle is in sharp contrast to the multi-polar spindle and G2 block in the cell cycle previously observed following exposure to SWCNT. One month following exposure to MWCNT there was a dramatic increase in both size and number of colonies compared to diluent control cultures, indicating a potential to pass the genetic damage to daughter cells. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant exposure levels. PMID:24479647

“Seeing the Life”: Redefining self-worth and family roles among Iraqi refugee families resettled in the United States

PubMed Central

Nelson, Matthew; Hess, Julia Meredith; Isakson, Brian; Goodkind, Jessica

2017-01-01

Social and geographic displacement is a global phenomenon that precipitates novel stressors and disruptions that intersect with longstanding familial and social roles. Among the displaced are war-torn Iraqi refugee families, who must address these new obstacles in unconventional ways. This study explores how such disruptions have influenced associations between gender and apparent self-worth experienced by Iraqi refugee families upon relocation to the United States. Further, the psychosocial mechanisms requisite of any novel approach to a new social construct are explored and reveal that production in the family is at the core of instability and shifting power dynamics during resettlement, preventing family members from “seeing the life” in the United States that they had envisioned prior to immigration. Over 200 semi-structured qualitative interviews with Iraqi participants and mental health providers were conducted over the course of the study, and demonstrate a plasticity among social roles in the family and community that transcends the notion of a simple role reversal, and illustrate the complex positionalities that families under stress must approximate during such physical and social displacement. PMID:28966556

Crossing the LINE toward genomic instability: LINE-1 retrotransposition in cancer

NASA Astrophysics Data System (ADS)

Kemp, Jacqueline; Longworth, Michelle

2015-12-01

Retrotransposons are repetitive DNA sequences that are positioned throughout the human genome. Retrotransposons are capable of copying themselves and mobilizing new copies to novel genomic locations in a process called retrotransposition. While most retrotransposon sequences in the human genome are incomplete and incapable of mobilization, the LINE-1 retrotransposon, which comprises approximately 17% of the human genome, remains active. The disruption of cellular mechanisms that suppress retrotransposon activity is linked to the generation of aneuploidy, a potential driver of tumor development. When retrotransposons insert into a novel genomic region, they have the potential to disrupt the coding sequence of endogenous genes and alter gene expression, which can lead to deleterious consequences for the organism. Additionally, increased LINE-1 copy numbers provide more chances for recombination events to occur between retrotransposons, which can lead to chromosomal breaks and rearrangements. LINE-1 activity is increased in various cancer cell lines and in patient tissues resected from primary tumors. LINE-1 activity also correlates with increased cancer metastasis. This review aims to give a brief overview of the connections between LINE-1 retrotransposition and the loss of genome stability. We will also discuss the mechanisms that repress retrotransposition in human cells and their links to cancer.

Gene disruption of dematin causes precipitous loss of erythrocyte membrane stability and severe hemolytic anemia.

PubMed

Lu, Yunzhe; Hanada, Toshihiko; Fujiwara, Yuko; Nwankwo, Jennifer O; Wieschhaus, Adam J; Hartwig, John; Huang, Sha; Han, Jongyoon; Chishti, Athar H

2016-07-07

Dematin is a relatively low abundance actin binding and bundling protein associated with the spectrin-actin junctions of mature erythrocytes. Primary structure of dematin includes a loosely folded core domain and a compact headpiece domain that was originally identified in villin. Dematin's actin binding properties are regulated by phosphorylation of its headpiece domain by cyclic adenosine monophosphate-dependent protein kinase. Here, we used a novel gene disruption strategy to generate the whole body dematin gene knockout mouse model (FLKO). FLKO mice, while born at a normal Mendelian ratio, developed severe anemia and exhibited profound aberrations of erythrocyte morphology and membrane stability. Having no apparent effect on primitive erythropoiesis, FLKO mice show significant enhancement of erythroblast enucleation during definitive erythropoiesis. Using membrane protein analysis, domain mapping, electron microscopy, and dynamic deformability measurements, we investigated the mechanism of membrane instability in FLKO erythrocytes. Although many membrane and cytoskeletal proteins remained at their normal levels, the major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLKO erythrocytes. Our results demonstrate that dematin plays a critical role in maintaining the fundamental properties of the membrane cytoskeleton complex. © 2016 by The American Society of Hematology.

Gene disruption of dematin causes precipitous loss of erythrocyte membrane stability and severe hemolytic anemia

PubMed Central

Lu, Yunzhe; Hanada, Toshihiko; Fujiwara, Yuko; Nwankwo, Jennifer O.; Wieschhaus, Adam J.; Hartwig, John; Huang, Sha; Han, Jongyoon

2016-01-01

Dematin is a relatively low abundance actin binding and bundling protein associated with the spectrin–actin junctions of mature erythrocytes. Primary structure of dematin includes a loosely folded core domain and a compact headpiece domain that was originally identified in villin. Dematin’s actin binding properties are regulated by phosphorylation of its headpiece domain by cyclic adenosine monophosphate–dependent protein kinase. Here, we used a novel gene disruption strategy to generate the whole body dematin gene knockout mouse model (FLKO). FLKO mice, while born at a normal Mendelian ratio, developed severe anemia and exhibited profound aberrations of erythrocyte morphology and membrane stability. Having no apparent effect on primitive erythropoiesis, FLKO mice show significant enhancement of erythroblast enucleation during definitive erythropoiesis. Using membrane protein analysis, domain mapping, electron microscopy, and dynamic deformability measurements, we investigated the mechanism of membrane instability in FLKO erythrocytes. Although many membrane and cytoskeletal proteins remained at their normal levels, the major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLKO erythrocytes. Our results demonstrate that dematin plays a critical role in maintaining the fundamental properties of the membrane cytoskeleton complex. PMID:27073223

Non-axisymmetric equilibrium reconstruction and suppression of density limit disruptions in a current-carrying stellarator

NASA Astrophysics Data System (ADS)

Ma, Xinxing; Ennis, D. A.; Hanson, J. D.; Hartwell, G. J.; Knowlton, S. F.; Maurer, D. A.

2017-10-01

Non-axisymmetric equilibrium reconstructions have been routinely performed with the V3FIT code in the Compact Toroidal Hybrid (CTH), a stellarator/tokamak hybrid. In addition to 50 external magnetic measurements, 160 SXR emissivity measurements are incorporated into V3FIT to reconstruct the magnetic flux surface geometry and infer the current distribution within the plasma. Improved reconstructions of current and q profiles provide insight into understanding the physics of density limit disruptions observed in current-carrying discharges in CTH. It is confirmed that the final scenario of the density limit of CTH plasmas is consistent with classic observations in tokamaks: current profile shrinkage leads to growing MHD instabilities (tearing modes) followed by a loss of MHD equilibrium. It is also observed that the density limit at a given current linearly increases with increasing amounts of 3D shaping fields. Consequently, plasmas with densities up to two times the Greenwald limit are attained. Equilibrium reconstructions show that addition of 3D fields effectively moves resonance surfaces towards the edge of the plasma where the current profile gradient is less, providing a stabilizing effect. This work is supported by US Department of Energy Grant No. DE-FG02-00ER54610.

Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

PubMed

Kamiya, Nobuhiro; Shuxian, Lin; Yamaguchi, Ryosuke; Phipps, Matthew; Aruwajoye, Olumide; Adapala, Naga Suresh; Yuan, Hui; Kim, Harry K W; Feng, Jian Q

2016-10-01

Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the β-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is proposed to explain how BMPR1A controls bone remodeling by inhibiting cell proliferation and stimulating differentiation. It is reported that RANKL and SOST are abundantly expressed by osteocytes. Thus, BMP signaling through BMPR1A plays important roles in osteocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Overexpression of dominant negative PARP interferes with tumor formation of HeLa cells in nude mice: evidence for increased tumor cell apoptosis in vivo.

PubMed

Hans, M A; Müller, M; Meyer-Ficca, M; Bürkle, A; Küpper, J H

1999-11-25

Poly(ADP-ribose) polymerase (PARP4) catalyzes the formation of ADP-ribose polymers covalently attached to proteins by using NAD+ as substrate. PARP is strongly activated by DNA single- or double-strand breaks and is thought to be involved in cellular responses to DNA damage. We characterized a dominant negative PARP mutant, i.e. the DNA-binding domain of this enzyme, whose overexpression in cells leads to increased genetic instability following DNA damage. In order to study whether PARP activity is also implicated in the process of tumorigenesis, we generated stably transfected HeLa cell clones with constitutive overexpression of dominant negative PARP and investigated tumor formation of these clones in nude mice. We found that inhibition of PARP activity dramatically reduces tumor forming ability of HeLa cells. Moreover, we provide strong evidence that the observed reduction in tumor forming ability is due to increased tumor cell apoptosis in vivo. Viewed together, our data and those from other groups show that inhibition of PARP enzyme activity interferes with DNA base excision repair and leads to increased genetic instability and recombination but, on the other hand, can sensitize cells to apoptotic stimuli and by this mechanism may prevent tumor formation.

Controlling Rayleigh-Taylor Instabilities in Magnetically Driven Solid Metal Shells by Means of a Dynamic Screw Pinch

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

Schmit, P. F.; Velikovich, A. L.; McBride, R. D.

Magnetically driven implosions of solid metal shells are an effective vehicle to compress materials to extreme pressures and densities. Rayleigh-Taylor instabilities (RTI) are ubiquitous, yet typically undesired features in all such experiments where solid materials are rapidly accelerated to high velocities. In cylindrical shells (“liners”), the magnetic field driving the implosion can exacerbate the RTI. Here, we suggest an approach to implode solid metal liners enabling a remarkable reduction in the growth of magnetized RTI (MRTI) by employing a magnetic drive with a tilted, dynamic polarization, forming a dynamic screw pinch. Our calculations, based on a self-consistent analytic framework, demonstratemore » that the cumulative growth of the most deleterious MRTI modes may be reduced by as much as 1 to 2 orders of magnitude. One key application of this technique is to generate increasingly stable, higher-performance implosions of solid metal liners to achieve fusion [M. R. Gomez et al., Phys. Rev. Lett. 113, 155003 (2014)]. Finally, we weigh the potentially dramatic benefits of the solid liner dynamic screw pinch against the experimental tradeoffs required to achieve the desired drive field history and identify promising designs for future experimental and computational studies.« less

Controlling Rayleigh-Taylor Instabilities in Magnetically Driven Solid Metal Shells by Means of a Dynamic Screw Pinch

DOE PAGES

Schmit, P. F.; Velikovich, A. L.; McBride, R. D.; ...

2016-11-11

Magnetically driven implosions of solid metal shells are an effective vehicle to compress materials to extreme pressures and densities. Rayleigh-Taylor instabilities (RTI) are ubiquitous, yet typically undesired features in all such experiments where solid materials are rapidly accelerated to high velocities. In cylindrical shells (“liners”), the magnetic field driving the implosion can exacerbate the RTI. Here, we suggest an approach to implode solid metal liners enabling a remarkable reduction in the growth of magnetized RTI (MRTI) by employing a magnetic drive with a tilted, dynamic polarization, forming a dynamic screw pinch. Our calculations, based on a self-consistent analytic framework, demonstratemore » that the cumulative growth of the most deleterious MRTI modes may be reduced by as much as 1 to 2 orders of magnitude. One key application of this technique is to generate increasingly stable, higher-performance implosions of solid metal liners to achieve fusion [M. R. Gomez et al., Phys. Rev. Lett. 113, 155003 (2014)]. Finally, we weigh the potentially dramatic benefits of the solid liner dynamic screw pinch against the experimental tradeoffs required to achieve the desired drive field history and identify promising designs for future experimental and computational studies.« less

Combinatorial screening of organic electronic materials: thin film stability

NASA Astrophysics Data System (ADS)

Chattopadhyay, Santanu; Carson Meredith, J.

2005-01-01

Dewetting of thin polymeric semiconducting-insulating (and conducting-insulating) bilayers is a serious fundamental problem facing the fabrication of organic electronic devices such as transistors, light-emitting diodes and supercapacitors. This paper describes a high-throughput characterization method that utilizes orthogonal thickness-gradient libraries of the bilayer components poly(3-octylthiophene) (semiconductor) and poly(styrene) (insulator). The technique allows simultaneous observation of hundreds of combinations of thicknesses and has permitted rapid discovery of a previously-unknown VDW instability transition. We observe that the onset of VDW instability in the PS-P3OT bilayer is a complex function of P3OT thickness that cannot be predicted by Hamaker constant models for free energy. At low P3OT thickness, the semiconductor acts to stabilize the PS insulator. But above a P3OT thickness of 175 nm, this behaviour is switched and P3OT destabilizes the PS. These thickness-dependent effects are correlated very well with dramatic transitions in P3OT optical spectra and the P3OT-AFM tip interaction forces. This unusual behaviour places critical limitations on practical device thicknesses and interfacial combinations, and points to the need for a thin-film stability theory that accounts for thickness-dependent molecular-electronic effects.

Numerical Simulation of Rotation-Driven Plasma Transport In the Jovian Magnetosphere

NASA Technical Reports Server (NTRS)

Wolf, Richard A.

1997-01-01

A Jupiter version of the Rice Convection Model (RCM-J) was developed with support of an earlier NASA SR&T grant. The conversion from Earth to Jupiter included adding currents driven by centrifugal force, reversing the planetary magnetic field, and rescaling various parameters. A series of informative runs was carried out, all of them solving initial value problems. The simulations followed an initial plasma torus configuration as it fell apart by interchange instability. Some conclusions from the simulations were the following: 1. We confirmed that, for conventional values of the torus density and ionospheric conductance, the torus disintegrates by interchange instability on a time scale of approx. one day, which is 1-2 orders of magnitude shorter than the best estimates of the average residence time of plasma in the torus. 2. In the model, the instability could be slowed to an arbitrary degree by the addition of sufficient impounding energetic particles, as suggested earlier by Siscoe et al (1981). However, the observed energetic particles do not seem sufficient to guarantee impoundment (e.g., Mauk et al., 1996). 3. Whether inhibited by impoundment or not, the interchange was found to proceed by the formation of long fingers, which get thinner as they get longer. This picture differed dramatically from the conventional radial-diffusion picture (e.g., Siscoe and Summers (1981)), more superficially with the outward-moving-blob picture (Pontius and Hill, 1989). The obvious limitation of the original RCM-J was that it could not represent a plasma source. We could represent the decay of a pre-existing torus, but we could not represent the way ionization of material from Io continually replenishes the plasma. We consequently were precluded from studying a whole set of fundamental issues of torus theory, including whether the system can come to a steady state.

Extreme precipitation events and related weather patterns over Iraq

NASA Astrophysics Data System (ADS)

raheem Al-nassar, Ali; Sangrà, Pablo; Alarcón, Marta

2016-04-01

This study aims to investigate the extreme precipitation events and the associated weather phenomena in the Middle East and particularly in Iraq. For this purpose we used Baghdad daily precipitation records from the Iraqi Meteorological and Seismology Organization combined with ECMWF (ERA-Interim) reanalysis data for the period from January 2002 to December 2013. Extreme events were found statistically at the 90% percentile of the recorded precipitation, and were highly correlated with hydrological flooding in some cities of Iraq. We identified fifteen extreme precipitation events. The analysis of the corresponding weather patterns (500 hPa and 250 hPa geopotential and velocity field distribution) indicated that 5 events were related with cut off low causing the highest precipitation (180 mm), 3 events related with rex block (158 mm), 3 events related with jet streak occurrence (130 mm) and 4 events related with troughs (107 mm). . Five of these events caused flash floods and in particular one of them related with a rex block was the most dramatic heavy rain event in Iraq in 30 years. We investigated for each case the convective instability and dynamical forcing together with humidity sources. For convective instability we explored the distribution of the K index and SWEAT index. For dynamical forcing we analyzed at several levels Q vector, divergence, potential and relative vorticity advection and omega vertical velocity. Source of humidity was investigated through humidity and convergence of specific humidity distribution. One triggering factor of all the events is the advection and convergence of humidity from the Red Sea and the Persian Gulf. Therefore a necessary condition for extreme precipitation in Iraq is the advection and convergence of humidity from the Red Sea and Persian Gulf. Our preliminary analysis also indicates that extreme precipitation events are primary dynamical forced playing convective instability a secondary role.

Interleukin 6-dependent genomic instability heralds accelerated carcinogenesis following liver regeneration on a background of chronic hepatitis.

PubMed

Lanton, Tali; Shriki, Anat; Nechemia-Arbely, Yael; Abramovitch, Rinat; Levkovitch, Orr; Adar, Revital; Rosenberg, Nofar; Paldor, Mor; Goldenberg, Daniel; Sonnenblick, Amir; Peled, Amnon; Rose-John, Stefan; Galun, Eithan; Axelrod, Jonathan H

2017-05-01

Liver cancer, which typically develops on a background of chronic liver inflammation, is now the second leading cause of cancer mortality worldwide. For patients with liver cancer, surgical resection is a principal treatment modality that offers a chance of prolonged survival. However, tumor recurrence after resection, the mechanisms of which remain obscure, markedly limits the long-term survival of these patients. We have shown that partial hepatectomy in multidrug resistance 2 knockout (Mdr2 -/- ) mice, a model of chronic inflammation-associated liver cancer, significantly accelerates hepatocarcinogenesis. Here, we explore the postsurgical mechanisms that drive accelerated hepatocarcinogenesis in Mdr2 -/- mice by perioperative pharmacological inhibition of interleukin-6 (IL6), which is a crucial liver regeneration priming cytokine. We demonstrate that inhibition of IL6 signaling dramatically impedes tumorigenesis following partial hepatectomy without compromising survival or liver mass recovery. IL6 blockade significantly inhibited hepatocyte cell cycle progression while promoting a hypertrophic regenerative response, without increasing apoptosis. Mdr2 -/- mice contain hepatocytes with a notable persistent DNA damage response (γH2AX, 53BP1) due to chronic inflammation. We show that liver regeneration in this microenvironment leads to a striking increase in hepatocytes bearing micronuclei, a marker of genomic instability, which is suppressed by IL6 blockade. Our findings indicate that genomic instability derived during the IL6-mediated liver regenerative response within a milieu of chronic inflammation links partial hepatectomy to accelerated hepatocarcinogenesis; this suggests a new therapeutic approach through the usage of an anti-IL6 treatment to extend the tumor-free survival of patients undergoing surgical resection. (Hepatology 2017;65:1600-1611). © 2016 by the American Association for the Study of Liver Diseases.

Sodium Lidar-observed Strong Inertia-gravity Wave Activities in the Mesopause Region over Fort Collins, Colorado (41 deg N, 105 deg W)

NASA Technical Reports Server (NTRS)

Li, Tao; She, C. -Y.; Liu, Han-Li; Leblanc, Thierry; McDermid, I. Stuart

2007-01-01

In December 2004, the Colorado State University sodium lidar system at Fort Collins, Colorado (41 deg N, 105 deg W), conducted an approximately 80-hour continuous campaign for the simultaneous observations of mesopause region sodium density, temperature, and zonal and meridional winds. This data set reveals the significant inertia-gravity wave activities with a period of approximately 18 hours, which are strong in both wind components since UT day 338 (second day of the campaign), and weak in temperature and sodium density. The considerable variability of wave activities was observed with both wind amplitudes growing up to approximately 40 m/s at 95-100 km in day 339 and then decreasing dramatically in day 340. We also found that the sodium density wave perturbation is correlated in phase with temperature perturbation below 90 km, and approximately 180 deg out of phase above. Applying the linear wave theory, we estimated the wave horizontal propagation direction, horizontal wavelength, and apparent horizontal phase speed to be approximately 25 deg south of west, approximately 1800 +/- 150 km, and approximately 28 +/- 2 m/s, respectively of wave intrinsic period, intrinsic phase speed, and vertical wavelength were also estimated. While the onset of enhanced inertia-gravity wave amplitude in the night of 338 was observed to be in coincidence with short-period gravity wave breaking via convective instability, the decrease of inertia-gravity wave amplitude after noon of day 339 was also observed to coincide with the development of atmospheric dynamical instability layers with downward phase progression clearly correlated with the 18-hour inertia-gravity wave, suggesting likely breaking of this inertia-gravity wave via dynamical (shear) instability.

Ilizarov ring fixator for a difficult case of ankle syndesmosis disruption.

PubMed

Relwani, Jaikumar; Lahoti, Om; Orakwe, Sam

2002-01-01

Syndesmotic stabilization is recommended for tibiofibular diastasis, a Maisonneuve fracture, or syndesmotic instability after fixation of distal tibia-fibula fractures. In the case presented, a syndesmotic stabilization was performed with a screw inserted 2 cm above the tibiotalar joint Subsequent failure occurred due to the weight of the patient and a lack of compliance with the necessary nonweight bearing protocol. The Ilizarov frame was used to reduce and maintain a stable syndesmosis with a simple two-ring construct which allowed the patient to bear weight on the injured limb while his syndesmosis healed. This is not recommend as a routine method of treatment, but is presented as an extended indication of the Ilizarov frame for difficult cases.

Super-Alfvénic translation of a field-reversed configuration into a large-bore dielectric chamber

NASA Astrophysics Data System (ADS)

Sekiguchi, J.; Asai, T.; Takahashi, T.

2018-01-01

An experimental device to demonstrate additional heating and control methods for a field-reversed configuration (FRC) has been developed. The newly developed device, named FRC Amplification via Translation (FAT), has a field-reversed theta-pinch plasma source and a low-elongation dielectric (transparent quartz) confinement chamber with quasi-static confinement field. In the initial experiments on the FAT device, FRC translation and trapping were successfully demonstrated. Although the typical elongation of the trapped FRC in the confinement region was roughly three, no disruptive global instability, such as tilt, was observed. The FAT device increases the latitude to perform translation-related experiments, such as those concerning inductive current drive, equivalent neutral beam injection effects, and wave applications.

Quasi-linear analysis of the extraordinary electron wave destabilized by runaway electrons

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

Pokol, G. I.; Kómár, A.; Budai, A.

2014-10-15

Runaway electrons with strongly anisotropic distributions present in post-disruption tokamak plasmas can destabilize the extraordinary electron (EXEL) wave. The present work investigates the dynamics of the quasi-linear evolution of the EXEL instability for a range of different plasma parameters using a model runaway distribution function valid for highly relativistic runaway electron beams produced primarily by the avalanche process. Simulations show a rapid pitch-angle scattering of the runaway electrons in the high energy tail on the 100–1000 μs time scale. Due to the wave-particle interaction, a modification to the synchrotron radiation spectrum emitted by the runaway electron population is foreseen, exposing amore » possible experimental detection method for such an interaction.« less

Kinetics of relativistic runaway electrons

NASA Astrophysics Data System (ADS)

Breizman, B. N.; Aleynikov, P. B.

2017-12-01

This overview covers recent developments in the theory of runaway electrons in tokamaks. Its main purpose is to outline the intuitive basis for first-principle advancements in runaway electron physics. The overview highlights the following physics aspects of the runaway evolution: (1) survival and acceleration of initially hot electrons during thermal quench, (2) effect of magnetic perturbations on runaway confinement, (3) multiplication of the runaways via knock-on collisions with the bulk electrons, (4) slow decay of the runaway current, and (5) runaway-driven micro-instabilities. The scope of the reported studies is governed by the need to understand the behavior of runaway electrons as an essential physics element of the disruption events in ITER in order to develop an effective runaway mitigation scheme. ).

An Interesting Presentation About Cyclical Menstrual Psychosis with an Updated Review of Literature.

PubMed

Thippaiah, Srinagesh Mannekote; Nagaraja, Soumya; Birur, Badari; Cohen, Arnold W

2018-03-13

Cyclical menstrual psychosis is an uncommon, generally a self-limiting mental illness that occurs only in females. It is associated with other menstruation-related disorders and stressful psychogenic factors. Nonetheless, many cases remain unrecognized due to poor awareness of its presence. A young female who presented with psychotic and mood symptoms during each cycle of menstruation was admitted to the psychiatric inpatient unit. There was severe disruption in her activities of daily living and socio-occupational functioning. Treatment involved bio-psycho-social approach in collaboration with Ob-Gyn team with symptoms responding well to a combination of valproic acid and risperidone. Severe affective instability with evident psychosis during menstrual cycle should be evaluated for cyclical menstrual psychosis.

Disruption of current filaments and isotropization of magnetic field in counter-streaming plasmas

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

Fiuza, Frederico

We study the stability of current filaments produced by the Weibel, or current filamentation, instability in weakly magnetized counter-streaming plasmas. It is shown that a resonance exists between the current-carrying ions and a longitudinal drift-kink mode that strongly deforms and eventually breaks the current filaments. Analytical estimates of the wavelength, growth rate and saturation level of the resonant mode are derived and validated by three-dimensional particle-in-cell simulations. Furthermore, self-consistent simulations of counter-streaming plasmas indicate that this drift-kink mode is dominant in the slow down of the flows and in the isotropization of the magnetic field, playing an important role inmore » the formation of collision less shocks.« less

Viscous shear heating instabilities in a 1-D viscoelastic shear zone

NASA Astrophysics Data System (ADS)

Homburg, J. M.; Coon, E. T.; Spiegelman, M.; Kelemen, P. B.; Hirth, G.

2010-12-01

Viscous shear instabilities may provide a possible mechanism for some intermediate depth earthquakes where high confining pressure makes it difficult to achieve frictional failure. While many studies have explored the feedback between temperature-dependent strain rate and strain-rate dependent shear heating (e.g. Braeck and Podladchikov, 2007), most have used thermal anomalies to initiate a shear instability or have imposed a low viscosity region in their model domain (John et al., 2009). By contrast, Kelemen and Hirth (2007) relied on an initial grain size contrast between a predetermined fine-grained shear zone and coarse grained host rock to initiate an instability. This choice is supported by observations of numerous fine grained ductile shear zones in shallow mantle massifs as well as the possibility that annealed fine grained fault gouge, formed at oceanic transforms, subduction related thrusts and ‘outer rise’ faults, could be carried below the brittle/ductile transition by subduction. Improving upon the work of Kelemen and Hirth (2007), we have developed a 1-D numerical model that describes the behavior of a Maxwell viscoelastic body with the rheology of dry olivine being driven at a constant velocity at its boundary. We include diffusion and dislocation creep, dislocation accommodated grain boundary sliding, and low-temperature plasticity (Peierls mechanism). Initial results suggest that including low-temperature plasticity inhibits the ability of the system to undergo an instability, similar to the results of Kameyama et al. (1999). This is due to increased deformation in the background allowing more shear heating to take place, and thus softening the system prior to reaching the peak stress. However if the applied strain rate is high enough (e.g. greater than 0.5 x 10-11 s-1 for a domain size of 2 km, an 8 m wide shear zone, a background grain size of 1 mm, a shear zone grain size of 150 μm, and an initial temperature of 650°C) dramatic instabilities can occur. The instability is enhanced by the development of a self-localizing thermal perturbation in the fine grained zone that is narrower than the original width of the fine-grained zone. To examine the effect of melting, we include a parameterization of partially molten rock viscosity as a function of temperature assuming a simple relationship between melt fraction and temperature. At T > ~1400°C, all other deformation mechanisms are deactivated but shear heating continues, allowing for continued temperature evolution. In addition a strain rate cap proportional to the shear wave velocity in olivine has been imposed, reflecting the maximum rate that changes in stress can be communicated through the system. While Kelemen and Hirth (2007) allowed for grain size evolution, this has not yet been implemented in our model. Adding grain size evolution as an additional strain softening mechanism would probably allow instabilities to develop at more geologically reasonable applied strain rates. In addition to discussing the stability of the olivine only system, we will explore grain size evolution during system evolution and evaluate the consequences that the grain size evolution and lithology have on the stability of the system.

The Air-Sea Interface and Surface Stress under Tropical Cyclones

NASA Astrophysics Data System (ADS)

Soloviev, Alexander; Lukas, Roger; Donelan, Mark; Ginis, Isaac

2013-04-01

Air-sea interaction dramatically changes from moderate to very high wind speed conditions (Donelan et al. 2004). Unresolved physics of the air-sea interface are one of the weakest components in tropical cyclone prediction models. Rapid disruption of the air-water interface under very high wind speed conditions was reported in laboratory experiments (Koga 1981) and numerical simulations (Soloviev et al. 2012), which resembled the Kelvin-Helmholtz instability at an interface with very large density difference. Kelly (1965) demonstrated that the KH instability at the air-sea interface can develop through parametric amplification of waves. Farrell and Ioannou (2008) showed that gustiness results in the parametric KH instability of the air-sea interface, while the gusts are due to interacting waves and turbulence. The stochastic forcing enters multiplicatively in this theory and produces an exponential wave growth, augmenting the growth from the Miles (1959) theory as the turbulence level increases. Here we complement this concept by adding the effect of the two-phase environment near the mean interface, which introduces additional viscosity in the system (turning it into a rheological system). The two-phase environment includes air-bubbles and re-entering spray (spume), which eliminates a portion of the wind-wave wavenumber spectrum that is responsible for a substantial part of the air sea drag coefficient. The previously developed KH-type interfacial parameterization (Soloviev and Lukas 2010) is unified with two versions of the wave growth model. The unified parameterization in both cases exhibits the increase of the drag coefficient with wind speed until approximately 30 m/s. Above this wind speed threshold, the drag coefficient either nearly levels off or even slightly drops (for the wave growth model that accounts for the shear) and then starts again increasing above approximately 65 m/s wind speed. Remarkably, the unified parameterization reveals a local minimum of the drag coefficient wind speed dependence around 65 m/s. This minimum may contribute to the rapid intensification of storms to major tropical cyclones. The subsequent slow increase of the drag coefficient with wind above 65 m/s serves as an obstacle for further intensification of tropical cyclones. Such dependence may explain the observed bi-modal distribution of tropical cyclone intensity. Implementation of the new parameterization into operational models is expected to improve predictions of tropical cyclone intensity and the associated wave field. References: Donelan, M. A., B. K. Haus, N. Reul, W. Plant, M. Stiassnie, H. Graber, O. Brown, and E. Saltzman, 2004: On the limiting aerodynamic roughness of the ocean in very strong winds, Farrell, B.F, and P.J. Ioannou, 2008: The stochastic parametric mechanism for growth of wind-driven surface water waves. Journal of Physical Oceanography 38, 862-879. Kelly, R.E., 1965: The stability of an unsteady Kelvin-Helmholtz flow. J. Fluid Mech. 22, 547-560. Koga, M., 1981: Direct production of droplets from breaking wind-waves-Its observation by a multi-colored overlapping exposure technique, Tellus 33, 552-563. Miles, J.W., 1959: On the generation of surface waves by shear flows, part 3. J. Fluid. Mech. 6, 583-598. Soloviev, A.V. and R. Lukas, 2010: Effects of bubbles and sea spray on air-sea exchanges in hurricane conditions. Boundary-Layer Meteorology 136, 365-376. Soloviev, A., A. Fujimura, and S. Matt, 2012: Air-sea interface in hurricane conditions. J. Geophys. Res. 117, C00J34.

Generation of Caustics and Rogue Waves from Nonlinear Instability.

PubMed

Safari, Akbar; Fickler, Robert; Padgett, Miles J; Boyd, Robert W

2017-11-17

Caustics are phenomena in which nature concentrates the energy of waves and may exhibit rogue-type behavior. Although they are known mostly in optics, caustics are intrinsic to all wave phenomena. As we demonstrate in this Letter, the formation of caustics and consequently rogue events in linear systems requires strong phase fluctuations. We show that nonlinear phase shifts can generate sharp caustics from even small fluctuations. Moreover, in that the wave amplitude increases dramatically in caustics, nonlinearity is usually inevitable. We perform an experiment in an optical system with Kerr nonlinearity, simulate the results based on the nonlinear Schrödinger equation, and achieve perfect agreement. As the same theoretical framework is used to describe other wave systems such as large-scale water waves, our results may also aid the understanding of ocean phenomena.

Black Hole Mergers, Gravitational Waves, and Multi-Messenger Astronomy

NASA Technical Reports Server (NTRS)

Centrella, Joan M.

2010-01-01

The final merger of two black holes is expected to be the strongest source of gravitational waves for both ground-based detectors such as LIGO and VIRGO, as well as the space-based LISA. Since the merger takes place in the regime of strong dynamical gravity, computing the resulting gravitational waveforms requires solving the full Einstein equations of general relativity on a computer. Although numerical codes designed to simulate black hole mergers were plagued for many years by a host of instabilities, recent breakthroughs have conquered these problems and opened up this field dramatically. This talk will focus on the resulting gold rush of new results that is revealing the dynamics and waveforms of binary black hole mergers, and their applications in gravitational wave detection, astrophysics, and testing general relativity.

Generation of Caustics and Rogue Waves from Nonlinear Instability

NASA Astrophysics Data System (ADS)

Safari, Akbar; Fickler, Robert; Padgett, Miles J.; Boyd, Robert W.

2017-11-01

Caustics are phenomena in which nature concentrates the energy of waves and may exhibit rogue-type behavior. Although they are known mostly in optics, caustics are intrinsic to all wave phenomena. As we demonstrate in this Letter, the formation of caustics and consequently rogue events in linear systems requires strong phase fluctuations. We show that nonlinear phase shifts can generate sharp caustics from even small fluctuations. Moreover, in that the wave amplitude increases dramatically in caustics, nonlinearity is usually inevitable. We perform an experiment in an optical system with Kerr nonlinearity, simulate the results based on the nonlinear Schrödinger equation, and achieve perfect agreement. As the same theoretical framework is used to describe other wave systems such as large-scale water waves, our results may also aid the understanding of ocean phenomena.

Linear stability of compressible Taylor-Couette flow

NASA Technical Reports Server (NTRS)

Kao, Kai-Hsiung; Chow, Chuen-Yen

1992-01-01

A temporal stability analysis of compressible Taylor-Couette flow is presented. The viscous flow studied in this paper is contained between two concentric cylinders of infinite length, which are rotating with different angular velocities and are kept at different surface temperatures. The effects of differential rotation and temperature difference on the stability of Taylor-Couette flow are contrasted for a range of Mach numbers ranging from incompressible to Mach 3.0. The relative motion of the cylinders dramatically affects the characteristics of the Couette flow at the onset of instability. The flow is stabilized or destabilized depending upon the temperature ratio and speeds of the two cylinders. Independent of Mach number and temperature ratio, increasing Reynolds number generally promotes a destabilizing effect, indicating the inviscid nature of the Taylor-Couette flow.

Time varying moments, regime switch, and crisis warning: The birth-death process with changing transition probability

NASA Astrophysics Data System (ADS)

Tang, Yinan; Chen, Ping

2014-06-01

The sub-prime crisis in the U.S. reveals the limitation of diversification strategy based on mean-variance analysis. A regime switch and a turning point can be observed using a high moment representation and time-dependent transition probability. Up-down price movements are induced by interactions among agents, which can be described by the birth-death (BD) process. Financial instability is visible by dramatically increasing 3rd to 5th moments one-quarter before and during the crisis. The sudden rising high moments provide effective warning signals of a regime-switch or a coming crisis. The critical condition of a market breakdown can be identified from nonlinear stochastic dynamics. The master equation approach of population dynamics provides a unified theory of a calm and turbulent market.

Numerical investigation of the spreading of self-excited stratified jets

NASA Technical Reports Server (NTRS)

Batcho, P. F.; Karniadakis, G. E.; Orszag, S. A.

1990-01-01

The structure and evolution of self-excited subsonic periodic arrays of jets of constant and variable density are studied using spectral-element direct numerical simulations. The governing equation of motion is presented, and a method based on spectral element discretizations appropriate for simulating arbitrarily complex geometry jets and large density variations for subsonic flows is developed. Variable density fields are found to be more unstable than the corresponding uniform density fields with much higher rms values; as a result, their spreading is also considerably larger. There is a dramatic increase in spreading after a few pairings occur. Findings presented for low and high side-momentum flux reveal a shifting of the origin of instability from the near-field to the far-field, respectively, and suggest possible routes of stabilization.

Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein

NASA Astrophysics Data System (ADS)

Agarwal, Sonya; Döring, Kristina; Gierusz, Leszek A.; Iyer, Pooja; Lane, Fiona M.; Graham, James F.; Goldmann, Wilfred; Pinheiro, Teresa J. T.; Gill, Andrew C.

2015-10-01

The β2-α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2-α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2-α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region.

HIV and Bone Metabolism

PubMed Central

Ofotokun, Ighovwerha; Weitzmann, M. Neale

2013-01-01

The skeleton is an organ whose integrity is maintained by constant lifelong renewal involving coordinated removal of worn bone by osteoclasts and resynthesis of new bone by osteoblasts. In young adult humans and animals this process is homeostatic with no net gain or loss of bone mass. With natural aging and exacerbated by numerous pathological conditions, bone removal exceeds bone formation, disrupting homeostasis and resulting in bone loss. Over time, skeletal decline reaches clinical significance with development of osteopenia and eventually osteoporosis, conditions that dramatically increase bone fragility and the risk of fracture. Bone fractures can be devastating with significant morbidity and mortality. Over the last decade, it has become clear that skeletal renewal is strongly influenced by the immune system, a consequence of deep integration and centralization of common cell types and cytokine mediators, which we have termed the “immuno-skeletal interface.” Consequently, dysregulated skeletal renewal and bone loss is a common feature of inflammatory conditions associated with immune activation. Interestingly, bone loss is also associated with conditions of immunodeficiency, including infection by the human immunodeficiency virus (HIV) that leads to acquired immunodeficiency syndrome (AIDS). Disruptions to the immuno-skeletal interface drive skeletal deterioration contributing to a high rate of bone fracture in HIV infection. This review examines current knowledge concerning the prevalence and etiology of skeletal complications in HIV infection, the effect of antiretroviral therapies (ART) on the skeleton, and how disruption of the immuno-skeletal interface may underlie bone loss in HIV infection and ART. PMID:21616037

Hyperconnectivity is a fundamental response to neurological disruption.

PubMed

Hillary, Frank G; Roman, Cristina A; Venkatesan, Umesh; Rajtmajer, Sarah M; Bajo, Ricardo; Castellanos, Nazareth D

2015-01-01

In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Induction of Cytoprotective Pathways Is Central to the Extension of Lifespan Conferred by Multiple Longevity Pathways

PubMed Central

Shore, David E.; Carr, Christopher E.; Ruvkun, Gary

2012-01-01

Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60), the ER UPR (hsp-4), ROS response (sod-3, gst-4), and xenobiotic detoxification (gst-4). We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors. PMID:22829775

A decade after the first full human genome sequencing: when will we understand our own genome?

PubMed

Eisenhaber, Frank

2012-10-01

The contrast between the pomp of celebrating the first full human genome sequencing in 2000 and the cautious tone of recollections a decade thereafter could hardly be greater. The promises with regard to medical cures and biotechnology applications have been realized not even nearly to the expectations. Understanding the human genomes means knowing the genes' and proteins' functions and their interconnectedness via biomolecular mechanisms. This articles estimates how long will it take to achieve this goal if we extrapolate from the previous decade (indeed, a century!) and the possible disruptive trends in science, technology and society that may accelerate the pace of progress dramatically.

A Mitochondrial Mutator System in Maize1[w

PubMed Central

Kuzmin, Evgeny V.; Duvick, Donald N.; Newton, Kathleen J.

2005-01-01

The P2 line of maize (Zea mays) is characterized by mitochondrial genome destabilization, initiated by recessive nuclear mutations. These alleles alter copy number control of mitochondrial subgenomes and disrupt normal transfer of mitochondrial genomic components to progeny, resulting in differences in mitochondrial DNA profiles among sibling plants and between parents and progeny. The mitochondrial DNA changes are often associated with variably defective phenotypes, reflecting depletion of essential mitochondrial genes. The P2 nuclear genotype can be considered a natural mutagenesis system for maize mitochondria. It dramatically accelerates mitochondrial genomic divergence by increasing low copy-number subgenomes, by rapidly amplifying aberrant recombination products, and by causing the random loss of normal components of the mitochondrial genomes. PMID:15681663

Reengineering Translational Science: The Time Is Right

PubMed Central

Collins, Francis S.

2011-01-01

Despite dramatic advances in the molecular pathogenesis of disease, translation of basic biomedical research into safe and effective clinical applications remains a slow, expensive, and failure-prone endeavor. To pursue opportunities for disruptive translational innovation, the U.S. National Institutes of Health (NIH) intends to establish a new entity, the National Center for Advancing Translational Sciences (NCATS). The mission of NCATS is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of diseases and conditions. The new center’s activities will complement, and not compete with, translational research being carried out at NIH and elsewhere in the public and private sectors. PMID:21734173

From Ions to Wires to the Grid: The Transformational Science of LANL Research in High-Tc Superconducting Tapes and Electric Power Applications

ScienceCinema

Marken, Ken

2018-01-09

The Department of Energy (DOE) Office of Electricity Delivery and Energy Reliability (OE) has been tasked to lead national efforts to modernize the electric grid, enhance security and reliability of the energy infrastructure, and facilitate recovery from disruptions to energy supplies. LANL has pioneered the development of coated conductors – high-temperature superconducting (HTS) tapes – which permit dramatically greater current densities than conventional copper cable, and enable new technologies to secure the national electric grid. Sustained world-class research from concept, demonstration, transfer, and ongoing industrial support has moved this idea from the laboratory to the commercial marketplace.

ROSSBY WAVE INSTABILITY AT DEAD ZONE BOUNDARIES IN THREE-DIMENSIONAL RESISTIVE MAGNETOHYDRODYNAMICAL GLOBAL MODELS OF PROTOPLANETARY DISKS

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

Lyra, Wladimir; Mac Low, Mordecai-Mark, E-mail: wlyra@jpl.nasa.gov, E-mail: mordecai@amnh.org

It has been suggested that the transition between magnetorotationally active and dead zones in protoplanetary disks should be prone to the excitation of vortices via Rossby wave instability (RWI). However, the only numerical evidence for this has come from alpha disk models, where the magnetic field evolution is not followed, and the effect of turbulence is parameterized by Laplacian viscosity. We aim to establish the phenomenology of the flow in the transition in three-dimensional resistive-magnetohydrodynamical models. We model the transition by a sharp jump in resistivity, as expected in the inner dead zone boundary, using the PENCIL CODE to simulatemore » the flow. We find that vortices are readily excited in the dead side of the transition. We measure the mass accretion rate finding similar levels of Reynolds stress at the dead and active zones, at the {alpha} Almost-Equal-To 10{sup -2} level. The vortex sits in a pressure maximum and does not migrate, surviving until the end of the simulation. A pressure maximum in the active zone also triggers the RWI. The magnetized vortex that results should be disrupted by parasitical magneto-elliptic instabilities, yet it subsists in high resolution. This suggests that either the parasitic modes are still numerically damped or that the RWI supplies vorticity faster than they can destroy it. We conclude that the resistive transition between the active and dead zones in the inner regions of protoplanetary disks, if sharp enough, can indeed excite vortices via RWI. Our results lend credence to previous works that relied on the alpha-disk approximation, and caution against the use of overly reduced azimuthal coverage on modeling this transition.« less

Orbital Perturbations of the Galilean Satellites during Planetary Encounters

NASA Astrophysics Data System (ADS)

Deienno, Rogerio; Nesvorný, David; Vokrouhlický, David; Yokoyama, Tadashi

2014-08-01

The Nice model of the dynamical instability and migration of the giant planets can explain many properties of the present solar system, and can be used to constrain its early architecture. In the jumping-Jupiter version of the Nice model, required from the terrestrial planet constraint and dynamical structure of the asteroid belt, Jupiter has encounters with an ice giant. Here, we study the survival of the Galilean satellites in the jumping-Jupiter model. This is an important concern because the ice-giant encounters, if deep enough, could dynamically perturb the orbits of the Galilean satellites and lead to implausible results. We performed numerical integrations where we tracked the effect of planetary encounters on the Galilean moons. We considered three instability cases from Nesvorný & Morbidelli that differed in the number and distribution of encounters. We found that in one case, where the number of close encounters was relatively small, the Galilean satellite orbits were not significantly affected. In the other two, the orbital eccentricities of all moons were excited by encounters, Callisto's semimajor axis changed, and, in a large fraction of trials, the Laplace resonance of the inner three moons was disrupted. The subsequent evolution by tides damps eccentricities and can recapture the moons in the Laplace resonance. A more important constraint is represented by the orbital inclinations of the moons, which can be excited during the encounters and not appreciably damped by tides. We find that one instability case taken from Nesvorný & Morbidelli clearly does not meet this constraint. This shows how the regular satellites of Jupiter can be used to set limits on the properties of encounters in the jumping-Jupiter model, and help us to better understand how the early solar system evolved.

Minimal Invasive Surgical Treatment of Fragility Fractures of the Pelvis.

PubMed

Rommens, Pol Maria; Wagner, Daniel; Hofmann, Alex

2017-01-01

The incidence of fragility fractures of the pelvis is increasing quickly. The characteristics of these fractures are different from pelvic ring disruptions in adults. Fragility fractures of the pelvis are the consequence of a low-energy trauma which occurs in a patient with an important decrease of bone mineral density. Due to a consistent pattern of alteration of bone mass distribution in the sacrum, other fracture morphologies occur than in younger adults. The leading symptom is immobilizing pain in the lower back, in the buttocks, in the inguinal region and/or at the pubic symphysis. Conventional radiographs and CT will show the presence and localization of the fractures in the anterior and posterior pelvic ring. A new, comprehensive classification system distinguishes four categories of instability. This first criterion is most important, because it also gives hints for the preferred type of treatment. The second criterion, leading to the subtypes in the four categories, is the localization of the instability in the posterior pelvic ring. This criterion points the way towards the type of the surgical procedure to be used. When a surgical treatment is chosen, the procedure should be as minimal invasive as possible. Different techniques for percutaneous or less invasive fixation of the posterior pelvic ring have been developed. Their advantages and limitations are presented: sacroplasty, iliosacral screw osteosynthesis, cement augmentation, transiliac internal fixation, trans-sacral osteosynthesis, lumbopelvic fixation. Fractures of the anterior pelvic ring also need special attention. Retrograde transpubic screw fixation is recommended for pubic rami fractures. Fractures of the pubic body and instabilities of the pubic symphysis need bridging plate osteosynthesis. We do not recommend anterior pelvic external fixation in elderly because of the risk of pin track infection and pin loosening. Celsius.

Electron-cloud build-up in hadron machines

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

Furman, M.A.

2004-08-09

The first observations of electron-proton coupling effect for coasting beams and for long-bunch beams were made at the earliest proton storage rings at the Budker Institute of Nuclear Physics (BINP) in the mid-60's [1]. The effect was mainly a form of the two-stream instability. This phenomenon reappeared at the CERN ISR in the early 70's, where it was accompanied by an intense vacuum pressure rise. When the ISR was operated in bunched-beam mode while testing aluminum vacuum chambers, a resonant effect was observed in which the electron traversal time across the chamber was comparable to the bunch spacing [2]. Thismore » effect (''beam-induced multipacting''), being resonant in nature, is a dramatic manifestation of an electron cloud sharing the vacuum chamber with a positively-charged beam. An electron-cloud-induced instability has been observed since the mid-80's at the PSR (LANL) [3]; in this case, there is a strong transverse instability accompanied by fast beam losses when the beam current exceeds a certain threshold. The effect was observed for the first time for a positron beam in the early 90's at the Photon Factory (PF) at KEK, where the most prominent manifestation was a coupled-bunch instability that was absent when the machine was operated with an electron beam under otherwise identical conditions [4]. Since then, with the advent of ever more intense positron and hadron beams, and the development and deployment of specialized electron detectors [5-9], the effect has been observed directly or indirectly, and sometimes studied systematically, at most lepton and hadron machines when operated with sufficiently intense beams. The effect is expected in various forms and to various degrees in accelerators under design or construction. The electron-cloud effect (ECE) has been the subject of various meetings [10-15]. Two excellent reviews, covering the phenomenology, measurements, simulations and historical development, have been recently given by Frank Zimmermann [16,17]. In this article we focus on the mechanisms of electron-cloud buildup and dissipation for hadronic beams, particularly those with very long, intense, bunches.« less

VizieR Online Data Catalog: Adiabatic mass loss in binary stars. II. (Ge+, 2015)

NASA Astrophysics Data System (ADS)

Ge, H.; Webbink, R. F.; Chen, X.; Han, Z.

2016-02-01

In the limit of extremely rapid mass transfer, the response of a donor star in an interacting binary becomes asymptotically one of adiabatic expansion. We survey here adiabatic mass loss from Population I stars (Z=0.02) of mass 0.10M⊙-100M⊙ from the zero-age main sequence to the base of the giant branch, or to central hydrogen exhaustion for lower main sequence stars. The logarithmic derivatives of radius with respect to mass along adiabatic mass-loss sequences translate into critical mass ratios for runaway (dynamical timescale) mass transfer, evaluated here under the assumption of conservative mass transfer. For intermediate- and high-mass stars, dynamical mass transfer is preceded by an extended phase of thermal timescale mass transfer as the star is stripped of most of its envelope mass. The critical mass ratio qad (throughout this paper, we follow the convention of defining the binary mass ratio as q{equiv}Mdonor/Maccretor) above which this delayed dynamical instability occurs increases with advancing evolutionary age of the donor star, by ever-increasing factors for more massive donors. Most intermediate- or high-mass binaries with nondegenerate accretors probably evolve into contact before manifesting this instability. As they approach the base of the giant branch, however, and begin developing a convective envelope, qad plummets dramatically among intermediate-mass stars, to values of order unity, and a prompt dynamical instability occurs. Among low-mass stars, the prompt instability prevails throughout main sequence evolution, with qad declining with decreasing mass, and asymptotically approaching qad=2/3, appropriate to a classical isentropic n=3/2 polytrope. Our calculated qad values agree well with the behavior of time-dependent models by Chen & Han (2003MNRAS.341..662C) of intermediate-mass stars initiating mass transfer in the Hertzsprung gap. Application of our results to cataclysmic variables, as systems that must be stable against rapid mass transfer, nicely circumscribes the range in qad as a function of the orbital period in which they are found. These results are intended to advance the verisimilitude of population synthesis models of close binary evolution. (3 data files).

Stochastic events may lead to accretion in Saturn's rings

NASA Astrophysics Data System (ADS)

Esposito, Larry W.

Stochastic events may lead to accretion in Saturn's rings Larry W. Esposito LASP, University of Colorado UVIS occultations indicate accretion is triggered at the B ring edge, in strong density waves in ring A and in the F ring. Moons may trigger accretion by streamline crowding (Lewis & Stewart); which enhances collisions, leading to accretion; increasing random velocities; leading to more collisions and more accretion. Cassini occultations of these strongly perturbed locations show not only accretion but also disaggregation, with time scales of hours to weeks. The collisions may lead to temporary aggregations via stochastic events: collisions can compress unconsolidated objects, trigger adhesion or bring small pieces into contact with larger or higher-density seeds. Disaggregation then can follow from disruptive collisions or tidal shedding. In the accretion/disruption balance, increased random motions could eventually give the upper hand to disruption. . . just as `irrational exuberance' can lead to financial panic in the economy; or the overpopulation of hares can lead to boom-and-bust in the population of foxes. I present a simple predator-prey model. This system's unstable equilibrium can similarly give rise to episodic cycles in accretion: explaining why the observable ring features that indicate embedded objects have been increasing since the beginning of Cassini's observations of Saturn in 2004. Unlike other interpretations of the peculiar events seen near Saturn Equinox, I emphasize the kinetic description of particle interactions rather than a fluid instability approach; and the dominance of stochastic events involving individual aggregates over free and/or driven modes in a flat disk.

Three-dimensional structure of the curved mixing layer using image reconstruction and volume rendering

NASA Astrophysics Data System (ADS)

Karasso, P. S.; Mungal, M. G.

1991-05-01

This study investigates the structure and mixing of the two-dimensional turbulent mixing layer when subjected to longitudinal streamwise curvature. The straight layer is now well known to be dominated by the primary Kelvin-Helmholtz (KH) instability as well as the secondary Taylor-Goertler (TG) instability. For equal density fluids, placing the high-speed fluid on the inside of a streamwise bend causes the TG instability to be enhanced (unstable case), while placing the low-speed fluid on the inside of the same bend leads to the suppression of the TG instability (stable case). The location of the mixing transition is correspondingly altered. Our goal is to study the changes to the mixing field and growth rate resulting from the competition between instabilities. Our studies are performed in a newly constructed blow-down water facility capable of high Reynolds numbers and excellent optical access. Maximum flow speeds are 2 and 0.25 m/sec for the high- and low-speed sides, respectively, leading to maximum Reynolds numbers of 80 000 based on velocity difference and the width of the layer. We are able to dye one stream with a fluorescent dye, thus providing several planar views of the flow under laser sheet illumination. These views are superior to conventional approaches as they are free of wall effects and are not spatially integrating. However, our most useful diagnostic of the structure of the flow is the ability to record high-speed images of the end view of the flow that are then reconstructed by computer using the volume rendering technique of Jiménez et al.1 This approach is especially useful as it allows us to compare the structural changes to the flow resulting from the competition between the KH and TG instabilities. Another advantage is the fact that several hundred frames, covering many characteristic times, are incorporated into the rendered image and thus capture considerably more flow physics than do still images. We currently have our rendering techniques fully operational,2 and are presently acquiring high quality high-speed movies of the various flow cases. Our findings to date, based on planar time-averaged and instantaneous views, show the following: (1) a 50% increase in growth rate from the stable to the unstable case resulting from mild curvature; (2) an enhancement of the TG vortices in the unstable case, but without major disruption of the KH instability which remains relatively intact; and (3) the occurrence of the KH instability at angles tilted with respect to the splitter plate tip, in agreement with the predictions of linear stability theory. This final observation has not been reported to date, primarily because sheet techniques have not been used at Reynolds numbers as high as the present study. The presentation will provide detailed views of the changes between the stable, straight, and unstable cases using our volume rendering approach, and will provide statistical measures such as changes to vortex spacing and size, to quantify such changes.

Interfacial instability of amorphous LiPON against lithium: A combined Density Functional Theory and spectroscopic study

NASA Astrophysics Data System (ADS)

Sicolo, Sabrina; Fingerle, Mathias; Hausbrand, René; Albe, Karsten

2017-06-01

The chemical instability of the glassy solid electrolyte LiPON against metallic lithium and the occurrence of side reactions at their interface is investigated by combining a surface science approach and quantum-mechanical calculations. Using an evolutionary structure search followed by a melt-quenching protocol, a model for the disordered structure of LiPON is generated and put into contact with lithium. Even the static optimization of a simple model interface suggests that the diffusion of lithium into LiPON is driven by a considerable driving force that could easily take place under experimental conditions. Calculated reaction energies indicate that the reduction and decomposition of LiPON is thermodynamically favorable. By monitoring the evolution of the LiPON core levels as a function of lithium exposure, the disruption of the LiPON network alongside the occurrence of new phases is observed. The direct comparison between UV photoelectron spectroscopy measurements and calculated electronic densities of states for increasing stages of lithiation univocally identifies the new phases as Li2O, Li3P and Li3N. These products are stable against Li metal and form a passivation layer which shields the electrolyte from further decomposition while allowing for the diffusion of Li ions.

Nonlinear Evolution of Rayleigh-Taylor Instability in a Radiation-supported Atmosphere

NASA Astrophysics Data System (ADS)

Jiang, Yan-Fei; Davis, Shane W.; Stone, James M.

2013-02-01

The nonlinear regime of Rayleigh-Taylor instability (RTI) in a radiation supported atmosphere, consisting of two uniform fluids with different densities, is studied numerically. We perform simulations using our recently developed numerical algorithm for multi-dimensional radiation hydrodynamics based on a variable Eddington tensor (VET) as implemented in Athena, focusing on the regime where scattering opacity greatly exceeds absorption opacity. We find that the radiation field can reduce the growth and mixing rate of RTI, but this reduction is only significant when radiation pressure significantly exceeds gas pressure. Small-scale structures are also suppressed in this case. In the nonlinear regime, dense fingers sink faster than rarefied bubbles can rise, leading to asymmetric structures about the interface. By comparing the calculations that use a VET versus the Eddington approximation, we demonstrate that anisotropy in the radiation field can affect the nonlinear development of RTI significantly. We also examine the disruption of a shell of cold gas being accelerated by strong radiation pressure, motivated by models of radiation driven outflows in ultraluminous infrared galaxies. We find that when the growth timescale of RTI is smaller than acceleration timescale, the amount of gas that would be pushed away by the radiation field is reduced due to RTI.

Injuries of the Sternoclavicular Joint - An Innovative Approach in the Management of a Rare Injury: Tight Rope Fixation of the Costo-Clavicular Ligament.

PubMed

Unterkofler, Jan; Merschin, David; Langenbach, Andreas; Ekkernkamp, Axel; Schulz-Drost, Stefan

2017-01-01

Background: The costoclavicular ligament (CCL) provides the most tight stability within the sternoclavicular joint (SCJ), followed by the most cited sternoclavicular ligaments (SCL). Their disruption may cause severe instability of the SCJ. Different treatment options, such as the use of plates, wires or autologous tendons are associated with mainly limited functional outcome. Could a stabilization of CCL next to an anatomic fixation of the SCL provide sufficient reconstruction of the SCJ? Methods: A 58-year-old male showed severe anterior and painful instability of the SCJ following a fall on his shoulder 8 weeks ago. The SCJ had been reconstructed in an open procedure with stabilization of the CCL employing 2 tight ropes and anatomical suture of the SCL. Follow-up was carried out 78 weeks after operation. Results: The reduction of the SCJ was successful. X-ray proved the anatomic position of the SCJ. Pain was decreased in between the first 6 weeks. The patient showed uneventful follow-up and returned to work 6 months after the procedureas a hard working farmer. Conclusions: Innovative stabilization of the CCL with tight ropes additional to a suture of the SCL may enable anatomic reconstruction of the SCJ considering cosmetic and functional results. Celsius.

Multi-region approach to free-boundary three-dimensional tokamak equilibria and resistive wall instabilities

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

Ferraro, N. M.; Jardin, S. C.; Lao, L. L.

Free-boundary 3D tokamak equilibria and resistive wall instabilities are calculated using a new resistive wall model in the two-fluid M3D-C1 code. In this model, the resistive wall and surround- ing vacuum region are included within the computational domain. Our implementation contrasts with the method typically used in fluid codes in which the resistive wall is treated as a boundary condition on the computational domain boundary and has the advantage of maintaining purely local coupling of mesh elements. We use this new capability to simulate perturbed, free-boundary non- axisymmetric equilibria; the linear evolution of resistive wall modes; and the linear andmore » nonlinear evolution of axisymmetric vertical displacement events (VDEs). Calculated growth rates for a resistive wall mode with arbitrary wall thickness are shown to agree well with the analytic theory. Equilibrium and VDE calculations are performed in diverted tokamak geometry, at physically real- istic values of dissipation, and with resistive walls of finite width. Simulations of a VDE disruption extend into the current-quench phase, in which the plasma becomes limited by the first wall, and strong currents are observed to flow in the wall, in the SOL, and from the plasma to the wall.« less

Multi-region approach to free-boundary three-dimensional tokamak equilibria and resistive wall instabilities

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

Ferraro, N. M., E-mail: nferraro@pppl.gov; Lao, L. L.; Jardin, S. C.

Free-boundary 3D tokamak equilibria and resistive wall instabilities are calculated using a new resistive wall model in the two-fluid M3D-C1 code. In this model, the resistive wall and surrounding vacuum region are included within the computational domain. This implementation contrasts with the method typically used in fluid codes in which the resistive wall is treated as a boundary condition on the computational domain boundary and has the advantage of maintaining purely local coupling of mesh elements. This new capability is used to simulate perturbed, free-boundary non-axisymmetric equilibria; the linear evolution of resistive wall modes; and the linear and nonlinear evolutionmore » of axisymmetric vertical displacement events (VDEs). Calculated growth rates for a resistive wall mode with arbitrary wall thickness are shown to agree well with the analytic theory. Equilibrium and VDE calculations are performed in diverted tokamak geometry, at physically realistic values of dissipation, and with resistive walls of finite width. Simulations of a VDE disruption extend into the current-quench phase, in which the plasma becomes limited by the first wall, and strong currents are observed to flow in the wall, in the SOL, and from the plasma to the wall.« less

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice.

PubMed

Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

2010-02-01

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice

PubMed Central

Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

2010-01-01

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target. PMID:20093778

The effects of differential flow between rational surfaces on toroidal resistive MHD modes

NASA Astrophysics Data System (ADS)

Brennan, Dylan; Halfmoon, Michael; Rhodes, Dov; Cole, Andrew; Okabayashi, Michio; Paz-Soldan, Carlos; Finn, John

2016-10-01

Differential flow between resonant surfaces can strongly affect the coupling and penetration of resonant components of resistive modes, and yet this mechanism is not yet fully understood. This study focuses on the evolution of tearing instabilities and the penetration of imposed resonant magnetic perturbations (RMPs) in tokamak configurations relevant to DIII-D and ITER, including equilibrium flow shear. It has been observed on DIII-D that the onset of tearing instabilities leading to disruption is often coincident with a loss of differential rotation between a higher m/n tearing surface (normally the 4/3 or 3/2) and a lower m/n tearing surface (normally the 2/1). Imposing RMPs can strongly affect this coupling and the torques between the modes. We apply the nonlinear 3-D resistive magnetohydrodynamic (MHD) code NIMROD to study the mechanisms by which these couplings occur. Reduced MHD analyses are applied to study the effects of differential flow between resonant surfaces in the simulations. Interaction between resonant modes can cause significant energy transfer between them, effectively stabilizing one mode while the other grows. The flow mitigates this transfer, but also affects the individual modes. The combination of these effects determines the nonlinear outcome. Supported by US DOE Grants DE-SC0014005 and DE-SC0014119.

Multi-region approach to free-boundary three-dimensional tokamak equilibria and resistive wall instabilities

DOE PAGES

Ferraro, N. M.; Jardin, S. C.; Lao, L. L.; ...

2016-05-20

Free-boundary 3D tokamak equilibria and resistive wall instabilities are calculated using a new resistive wall model in the two-fluid M3D-C1 code. In this model, the resistive wall and surround- ing vacuum region are included within the computational domain. Our implementation contrasts with the method typically used in fluid codes in which the resistive wall is treated as a boundary condition on the computational domain boundary and has the advantage of maintaining purely local coupling of mesh elements. We use this new capability to simulate perturbed, free-boundary non- axisymmetric equilibria; the linear evolution of resistive wall modes; and the linear andmore » nonlinear evolution of axisymmetric vertical displacement events (VDEs). Calculated growth rates for a resistive wall mode with arbitrary wall thickness are shown to agree well with the analytic theory. Equilibrium and VDE calculations are performed in diverted tokamak geometry, at physically real- istic values of dissipation, and with resistive walls of finite width. Simulations of a VDE disruption extend into the current-quench phase, in which the plasma becomes limited by the first wall, and strong currents are observed to flow in the wall, in the SOL, and from the plasma to the wall.« less

Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

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

Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy

Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murinemore » lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. Finally, this multi-omic view provides a unique resource and deeper insight into normal pulmonary development.« less

Germline Cas9 expression yields highly efficient genome engineering in a major worldwide disease vector, Aedes aegypti

PubMed Central

Li, Ming; Bui, Michelle; Yang, Ting; Bowman, Christian S.; White, Bradley J.; Akbari, Omar S.

2017-01-01

The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito disease vector Aedes aegypti. Here, we describe the generation of multiple stable, transgenic Ae. aegypti strains expressing Cas9 in the germline, resulting in dramatic improvements in both the consistency and efficiency of genome modifications using CRISPR. Using these strains, we disrupted numerous genes important for normal morphological development, and even generated triple mutants from a single injection. We have also managed to increase the rates of homology-directed repair by more than an order of magnitude. Given the exceptional mutagenic efficiency and specificity of the Cas9 strains we engineered, they can be used for high-throughput reverse genetic screens to help functionally annotate the Ae. aegypti genome. Additionally, these strains represent a step toward the development of novel population control technologies targeting Ae. aegypti that rely on Cas9-based gene drives. PMID:29138316

Germline Cas9 expression yields highly efficient genome engineering in a major worldwide disease vector, Aedes aegypti.

PubMed

Li, Ming; Bui, Michelle; Yang, Ting; Bowman, Christian S; White, Bradley J; Akbari, Omar S

2017-12-05

The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito disease vector Aedes aegypti Here, we describe the generation of multiple stable, transgenic Ae. aegypti strains expressing Cas9 in the germline, resulting in dramatic improvements in both the consistency and efficiency of genome modifications using CRISPR. Using these strains, we disrupted numerous genes important for normal morphological development, and even generated triple mutants from a single injection. We have also managed to increase the rates of homology-directed repair by more than an order of magnitude. Given the exceptional mutagenic efficiency and specificity of the Cas9 strains we engineered, they can be used for high-throughput reverse genetic screens to help functionally annotate the Ae. aegypti genome. Additionally, these strains represent a step toward the development of novel population control technologies targeting Ae. aegypti that rely on Cas9-based gene drives. Copyright © 2017 the Author(s). Published by PNAS.

Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

DOE PAGES

Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy; ...

2017-02-01

Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murinemore » lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. Finally, this multi-omic view provides a unique resource and deeper insight into normal pulmonary development.« less

Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood-Brain Barrier Disruption during Japanese Encephalitis Virus Infection.

PubMed

Li, Fang; Wang, Yueyun; Yu, Lan; Cao, Shengbo; Wang, Ke; Yuan, Jiaolong; Wang, Chong; Wang, Kunlun; Cui, Min; Fu, Zhen F

2015-05-01

Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate that JEV gains entry into the CNS prior to BBB disruption. Furthermore, it is not JEV infection per se, but the inflammatory cytokines/chemokines induced by JEV infection that inhibit the expression of TJ proteins and ultimately result in the enhancement of BBB permeability. Neutralization of gamma interferon (IFN-γ) ameliorated the enhancement of BBB permeability in JEV-infected mice, suggesting that IFN-γ could be a potential therapeutic target. This study would lead to identification of potential therapeutic avenues for the treatment of JEV infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Root-driven Weathering Impacts on Mineral-Organic Associations in Deep Soil

NASA Astrophysics Data System (ADS)

Keiluweit, M.; Garcia Arredondo, M.; Tfaily, M. M.; Kukkadapu, R. K.; Schulz, M. S.; Lawrence, C. R.

2017-12-01

Plant roots dramatically reshape the soil environments through the release of organic compounds. While root-derived organic compounds are recognized as an important source of soil C, their role in promoting weathering reactions has largely been overlooked. On the one hand, root-driven weathering may generate mineral-organic associations, which can protect soil C for centuries to millennia. On the other hand, root-driven weathering also transforms minerals, potentially disrupting protective mineral-organic associations in the process. Hence root-derived C may not only initiate C accumulation, but also diminish C stocks through disruption of mineral-organic associations. Here we determined the impact of rhizogenic weathering on mineral-organic associations, and associated changes in C storage, across the Santa Cruz Marine Terrace chronosequence (65ka-226ka). Using a combination of high-resolution mass spectrometry, Mössbauer, and X-ray (micro)spectroscopy, we examined mineral-organic associations of deep soil horizons characterized by intense rhizogenic weathering gradients. Initial rhizogenic weathering dramatically increased C stocks, which is directly linked to an increase of microbially-derived C bound to monomeric Fe and Al and nano-goethite. As weathering proceeded, the soil C stocks declined concurrent with an increasingly plant-derived C signature and decreasing crystallinity. X-ray spectromicroscopic analyses revealed strong spatial associations between C and Fe during initial weathering stages, indicative of protective mineral-organic associations. In contrast, later weathering stages showed weaker spatial relationships between C and Fe. We conclude that rhizogenic weathering enhance C storage by creating protective mineral-organic associations in the initial weathering stages. As root-driven weathering proceeds, minerals are transformed into more crystalline phases that retain lower amounts of C. Our results demonstrate that root-induced weathering reactions are primary drivers of the dynamics of mineral-organic associations, and are thus critical for future predictions of the vulnerability of deep soil carbon to climate change.

Humeral Avulsion of the Glenohumeral Ligament: Indications for Surgical Treatment and Outcomes—A Systematic Review

PubMed Central

Bozzo, Anthony; Oitment, Colby; Thornley, Patrick; Yan, James; Habib, Anthony; Hoppe, Daniel J.; Athwal, George S.; Ayeni, Olufemi R.

2017-01-01

Background: The inferior glenohumeral ligament, the most important static anterior stabilizer of the shoulder, becomes disrupted in humeral avulsion of the glenohumeral ligament (HAGL) lesions. Unfortunately, HAGL lesions commonly go unrecognized. A missed HAGL during an index operation to treat anterior shoulder instability may lead to persistent instability. Currently, there are no large studies describing the indications for surgical repair or the outcomes of patients with HAGL lesions. Purpose: To search the literature to identify surgical indications for the treatment of HAGL lesions and discuss reported outcomes. Study Design: Systematic review; Level of evidence, 4. Methods: Two reviewers completed a comprehensive literature search of 3 online databases (MEDLINE, EMBASE, and Cochrane Library) from inception until May 25, 2016, using the keywords “humeral avulsion of the glenohumeral ligament” or “HAGL” to generate a broad search. Systematic screening of eligible studies was undertaken in duplicate. Abstracted data were organized in table format, with descriptive statistics presented. Results: After screening, 18 studies comprising 118 patients were found that described surgical intervention and outcomes for HAGL lesions. The mean patient was 22 years (range, 12-50 years), and 82% were male. Sports injuries represented 72% of all HAGL injuries. The main surgical indication was primary anterior instability, followed by pain and failed nonoperative management. Commonly associated injuries in patients with identified HAGL lesions included a Bankart lesion (15%), Hill-Sachs lesions (13%), and glenoid bone loss (7%). Reporting of outcome scores varied among the included studies. Meta-analysis was not possible, but all included studies reported significantly improved postoperative stability and function. There were no demonstrated differences in outcomes for patients treated with open versus arthroscopic surgical techniques. All but 2 patients undergoing operative management for HAGL lesions were able to return to sport at their previous levels; these included Olympians and professional athletes. Conclusion: HAGL lesions typically occur in younger male patients and are often associated with Bankart lesions and bone loss. Open and arthroscopic management techniques are both effective in preventing recurrent instability. PMID:28840152

Experimental Observations on a Low Strain Counter-Flow Diffusion Flame: Flow and Bouyancy Effects

NASA Technical Reports Server (NTRS)

Sutula, J. A.; Torero, J. L.; Ezekoye, O. A.

1999-01-01

Diffusion flames are of great interest in fire safety and many industrial processes. The counter-flow configuration provides a constant strain flow, and therefore is ideal to study the structure of diffusion flames. Most studies have concentrated on the high velocity, high strain limit, since buoyantly induced instabilities will disintegrate the planar flame as the velocity decreases. Only recently, experimental studies in microgravity conditions have begun to explore the low strain regimes. Numerical work has shown the coupling between gas phase reaction rates, soot reaction rates, and radiation. For these programs, size, geometry and experimental conditions have been chosen to keep the flame unaffected by the physical boundaries. When the physical boundaries can not be considered infinitely far from the reaction zone discrepancies arise. A computational study that includes boundary effects and accounts for the deviations occurring when the major potential flow assumptions are relaxed was presented by Borlik et al. This development properly incorporates all heat loss terms and shows the possibility of extinction in the low strain regime. A major constraint of studying the low strain regime is buoyancy. Buoyant instabilities have been shown to have a significant effect on the nature of reactants and heat transport, and can introduce instabilities on the flow that result in phenomena such as flickering or fingering. The counter-flow configuration has been shown to provide a flame with no symmetry disrupting instabilities for inlet velocities greater than 50 mm/s. As the velocity approaches this limit, the characteristic length of the experiment has to be reduced to a few millimetres so as to keep the Rayleigh number (Ra(sub L) = (Beta)(g(sub 0))(L(exp 3) del T)/(alpha(v))) below 2000. In this work, a rectangular counter-flow burner was used to study a two-dimensional counter-flow diffusion flame. Flow visualisation and Particle Image Velocimetry served to describe the nature of the stagnation plane for strain rates smaller than 100 (1/s). These experiments were conducted with a non-reacting flow. Video images of a propane air diffusion flame were used to describe the behaviour of a diffusion flame in this regime. Flame geometry and pulsation frequency are described.

Sources and Losses of Ring Current Ions

NASA Technical Reports Server (NTRS)

Chen, Sheng-Hsien; Fok, Mei-Ching H.; Angeloupoulos, Vassilis

2010-01-01

During geomagnetic quiet times, in-situ measurements of ring current energetic ions (few to few tens of keVs) from THEMIS spacecraft often exhibit multiple ion populations at discrete energies that extend from the inner magnetosphere to the magnetopause at dayside or plasma sheet at nightside. During geomagnetic storm times, the levels of fluxes as well as the mean energies of these ions elevated dramatically and the more smooth distributions in energies and distances during quiet times are disrupted into clusters of ion populations with more confined spatial extends. This reveals local plasma heating processes that might have come into play. Several processes have been proposed. Magnetotail dipolarization, sudden enhancement of field-aligned current, local current disruptions, and plasma waves are possible mechanisms to heat the ions locally as well as strong convections of energetic ions directly from the magnetotail due to reconnections. We will examine two geomagnetic storms on October 11, 2008 and July 22, 2009 to reveal possible heating mechanisms. We will analyze in-situ plasma and magnetic field measurements from THEMIS, GOES, and DMSP for the events to study the ion pitch angle distributions and magnetic field perturbations in the auroral ionosphere and inner magnetosphere where the plasma heating processes occur.

Smoke pollution disrupted biodiversity during the 2015 El Niño fires in Southeast Asia

NASA Astrophysics Data System (ADS)

Y-H Lee, Benjamin P.; Davies, Zoe G.; Struebig, Matthew J.

2017-09-01

Forest and peatland fires during the 2015 El Niño drought were amongst the worst on record in Southeast Asia. They were a major contributor of carbon emissions across the region, with the associated smoke-induced haze causing an air pollution crisis that affected millions of people. We present evidence of air pollution impacts on biodiversity. Using daily acoustic recordings in central Singapore, we monitored the dawn chorus before, during and after the haze event. We demonstrate that levels of ecological community acoustic activity dropped dramatically during the haze, and that this decline was significantly associated with levels of air pollution considered ‘unhealthy’ to the human population. Acoustic disruption was apparent across four common indices of soundscape activity, with only a partial recovery to pre-haze levels observed 16 weeks after the smoke had dissipated. These impacts on ecological communities were likely to be even more severe closer to the fires, where air pollution levels were reported to be 15-fold greater than those recorded in Singapore. Our results indicate that large-scale air pollution crises may have hitherto underestimated and potentially far-reaching impacts on biodiversity, especially in parts of the world prone to extensive forest fires.

Re-Shuffling of Species with Climate Disruption: A No-Analog Future for California Birds?

PubMed Central

Stralberg, Diana; Jongsomjit, Dennis; Howell, Christine A.; Snyder, Mark A.; Alexander, John D.; Wiens, John A.; Root, Terry L.

2009-01-01

By facilitating independent shifts in species' distributions, climate disruption may result in the rapid development of novel species assemblages that challenge the capacity of species to co-exist and adapt. We used a multivariate approach borrowed from paleoecology to quantify the potential change in California terrestrial breeding bird communities based on current and future species-distribution models for 60 focal species. Projections of future no-analog communities based on two climate models and two species-distribution-model algorithms indicate that by 2070 over half of California could be occupied by novel assemblages of bird species, implying the potential for dramatic community reshuffling and altered patterns of species interactions. The expected percentage of no-analog bird communities was dependent on the community scale examined, but consistent geographic patterns indicated several locations that are particularly likely to host novel bird communities in the future. These no-analog areas did not always coincide with areas of greatest projected species turnover. Efforts to conserve and manage biodiversity could be substantially improved by considering not just future changes in the distribution of individual species, but including the potential for unprecedented changes in community composition and unanticipated consequences of novel species assemblages. PMID:19724641

Potent Nematicidal Activity and New Hybrid Metabolite Production by Disruption of a Cytochrome P450 Gene Involved in the Biosynthesis of Morphological Regulatory Arthrosporols in Nematode-Trapping Fungus Arthrobotrys oligospora.

PubMed

Song, Tian-Yang; Xu, Zi-Fei; Chen, Yong-Hong; Ding, Qiu-Yan; Sun, Yu-Rong; Miao, Yang; Zhang, Ke-Qin; Niu, Xue-Mei

2017-05-24

Types of polyketide synthase-terpenoid synthase (PKS-TPS) hybrid metabolites, including arthrosporols with significant morphological regulatory activity, have been elucidated from nematode-trapping fungus Arthrobotrys oligospora. A previous study suggested that the gene cluster AOL_s00215 in A. oligospora was involved in the production of arthrosporols. Here, we report that disruption of one cytochrome P450 monooxygenase gene AOL_s00215g280 in the cluster resulted in significant phenotypic difference and much aerial hyphae. A further bioassay indicated that the mutant showed a dramatic decrease in the conidial formation but developed numerous traps and killed 85% nematodes within 6 h in contact with prey, in sharp contrast to the wild-type strain with no obvious response. Chemical investigation revealed huge accumulation of three new PKS-TPS epoxycyclohexone derivatives with different oxygenated patterns around the epoxycyclohexone moiety and the absence of arthrosporols in the cultural broth of the mutant ΔAOL_s00215g280. These findings suggested that a study on the biosynthetic pathway for morphological regulatory metabolites in nematode-trapping fungus would provide an efficient way to develop new fungal biocontrol agents.

How Listening to Music Affects Reading: Evidence From Eye Tracking.

PubMed

Zhang, Han; Miller, Kevin; Cleveland, Raymond; Cortina, Kai

2018-02-01

The current research looked at how listening to music affects eye movements when college students read natural passages for comprehension. Two studies found that effects of music depend on both frequency of the word and dynamics of the music. Study 1 showed that lexical and linguistic features of the text remained highly robust predictors of looking times, even in the music condition. However, under music exposure, (a) readers produced more rereading, and (b) gaze duration on words with very low frequency were less predicted by word length, suggesting disrupted sublexical processing. Study 2 showed that these effects were exacerbated for a short period as soon as a new song came into play. Our results suggested that word recognition generally stayed on track despite music exposure and that extensive rereading can, to some extent, compensate for disruption. However, an irrelevant auditory signal may impair sublexical processing of low-frequency words during first-pass reading, especially when the auditory signal changes dramatically. These eye movement patterns are different from those observed in some other scenarios in which reading comprehension is impaired, including mindless reading. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Epithelial toxicity of alkylglycoside surfactants.

PubMed

Vllasaliu, Driton; Shubber, Saif; Fowler, Robyn; Garnett, Martin; Alexander, Cameron; Stolnik, Snow

2013-01-01

Alkylglycoside surfactants have been proposed as drug delivery excipients with the potential to enhance mucosal drug absorption of therapeutic macromolecules. Previous work reported their drug absorption-promoting potential by demonstrating that several compounds within this class of surfactants improve mucosal absorption of peptides, proteins and other macromolecules. However, detailed investigation of their toxicity has not been conducted. Using Calu-3 epithelial cell layers as a model of the airway mucosa, and liposomes as models of cell membranes, this work investigates the cytotoxicity of dodecylmaltoside, tridecylmaltoside and tetradecylmaltoside, as representative alkylglycosides. A combination of different toxicity assays and other tests indicating cell membrane disruption were used to assess cytotoxicity. The alkylglycosides tested induced a dramatic reduction in cell viability, cell membrane and liposome-disruptive effects, as well as abrogation of transepithelial electrical resistance that did not recover completely. Importantly, these phenomena were noted at concentrations markedly lower than those typically used in the literature studies demonstrating the absorption-enhancing properties of alkylglycosides. This work therefore demonstrates that alkylglycosides exhibit significant toxicity towards airway epithelial cells, most likely resulting from a membrane-damaging effect, highlighting a need for further evaluation of their safety as absorption-enhancing excipients. Copyright © 2012 Wiley Periodicals, Inc.

Mechanisms of DNA damage, repair and mutagenesis

PubMed Central

Chatterjee, Nimrat; Walker, Graham C.

2017-01-01

Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease-states. However, robust DNA repair and damage-bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine-tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating their use have become important. In this introductory review, we will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue. PMID:28485537

Current Saturation Avoidance with Real-Time Control using DPCS

NASA Astrophysics Data System (ADS)

Ferrara, M.; Hutchinson, I.; Wolfe, S.; Stillerman, J.; Fredian, T.

2008-11-01

Tokamak ohmic-transformer and equilibrium-field coils need to be able to operate near their maximum current capabilities. However if they reach their upper limit during high-performance discharges or in the presence of a strong off-normal event, shape control is compromised, and instability, even plasma disruptions can result. On Alcator C-Mod we designed and tested an anti-saturation routine which detects the impending saturation of OH and EF currents and interpolates to a neighboring safe equilibrium in real-time. The routine was implemented with a multi-processor, multi-time-scale control scheme, which is based on a master process and multiple asynchronous slave processes. The scheme is general and can be used for any computationally-intensive algorithm. USDoE award DE- FC02-99ER545512.

THE DROP DURING LESS THAN 300 DAYS OF A DUSTY WHITE DWARF'S INFRARED LUMINOSITY

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

Xu, S.; Jura, M., E-mail: sxu@astro.ucla.edu, E-mail: jura@astro.ucla.edu

2014-09-10

We report Spitzer/Infrared Array Camera photometry of WD J0959–0200, a white dwarf that displays excess infrared radiation from a disk, likely produced by a tidally disrupted planetesimal. We find that in 2010, the fluxes in both 3.6 μm and 4.5 μm decreased by ∼35% in less than 300 days. The drop in the infrared luminosity is likely due to an increase of the inner disk radius from one of two scenarios: (1) a recent planetesimal impact; (2) instability in the circumstellar disk. The current situation is tantalizing; high-sensitivity, high-cadence infrared studies will be a new tool to study the interplay between a diskmore » and its host white dwarf star.« less

Induction of virus resistance by exogenous application of double-stranded RNA.

PubMed

Mitter, Neena; Worrall, Elizabeth A; Robinson, Karl E; Xu, Zhi Ping; Carroll, Bernard J

2017-10-01

Exogenous application of double-stranded RNA (dsRNA) for virus resistance in plants represents a very attractive alternative to virus resistant transgenic crops or pesticides targeting virus vectors. However, the instability of dsRNA sprayed onto plants is a major challenge as spraying naked dsRNA onto plants provides protection against homologous viruses for only 5 days. Innovative approaches, such as the use of nanoparticles as carriers of dsRNA for improved stability and sustained release, are emerging as key disruptive technologies. Knowledge is still limited about the mechanism of entry, transport and processing of exogenously applied dsRNA in plants. Cost of dsRNA and regulatory framework will be key influencers towards practical adoption of this technology. Copyright © 2017 Elsevier B.V. All rights reserved.

Toroidal band limiter for a plasma containment device

DOEpatents

Kelley, George G.

1978-01-01

This invention relates to a toroidal plasma confinement device having poloidal and toroidal magnetic fields for confining a toroidal plasma column with a plasma current induced therein along an endless, circular equilibrium axis in a torus vacuum cavity wherein the improvement comprises the use of a toroidal plasma band limiter mounted within the vacuum cavity in such a manner as to ensure that the plasma energy is distributed more uniformly over the limiter surface thereby avoiding intense local heating of the limiter while at the same time substantially preventing damage to the plasma containment wall of the cavity by the energetic particles diffusing out from the confined plasma. A plurality of poloidal plasma ring limiters are also utilized for containment wall protection during any disruptive instability that might occur during operation of the device.

Interface width effect on the classical Rayleigh-Taylor instability in the weakly nonlinear regime

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

Wang, L. F.; State Key Laboratory for Geomechanics and Deep Underground Engineering, China University of Mining and Technology, Beijing 100083; Ye, W. H.

2010-05-15

In this paper, the interface width effects (i.e., the density gradient effects or the density transition layer effects) on the Rayleigh-Taylor instability (RTI) in the weakly nonlinear (WN) regime are investigated by numerical simulation (NS). It is found that the interface width effects dramatically influence the linear growth rate in the linear growth regime and the mode coupling process in the WN growth regime. First, the interface width effects decrease the linear growth rate of the RTI, particularly for the short perturbation wavelengths. Second, the interface width effects suppress (reduce) the third-order feedback to the fundamental mode, which induces themore » nonlinear saturation amplitude (NSA) to exceed the classical prediction, 0.1lambda. The wider the density transition layer is, the larger the NSA is. The NSA in our NS can reach a half of its perturbation wavelength. Finally, the interface width effects suppress the generation and the growth of the second and the third harmonics. The ability to suppress the harmonics' growth increases with the interface width but decreases with the perturbation wavelength. On the whole, in the WN regime, the interface width effects stabilize the RTI, except for an enhancement of the NSA, which is expected to improve the understanding of the formation mechanism for the astrophysical jets, and for the jetlike long spikes in the high energy density physics.« less

Ghrelin inhibits atherosclerotic plaque angiogenesis and promotes plaque stability in a rabbit atherosclerotic model.

PubMed

Wang, Li; Chen, Qingwei; Ke, Dazhi; Li, Guiqiong

2017-04-01

Intraplaque angiogenesis associates with the instability of atherosclerotic plaques. In the present study, we investigated the effects of ghrelin on intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. The rabbits were randomly divided into three groups, namely, the control group, atherosclerotic model group, and ghrelin-treated group, with treatments lasting for 4 weeks. We found that the thickness ratio of the intima to media in rabbits of the ghrelin-treated group was significantly lower than that in rabbits of the atherosclerotic model group. The number of neovessels and the levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) decreased dramatically in rabbits of the ghrelin-treated group compared to those of the atherosclerotic model group. Ghrelin significantly decreased the plaque content of macrophages, matrix metalloproteinase (MMP)-2, and MMP-9, in a rabbit model of atherosclerosis. In addition, the level of the pro-inflammatory factor monocyte chemoattractant protein (MCP)-1 was significantly lower in rabbits of the ghrelin-treated group than in rabbits of the atherosclerotic model group. In summary, ghrelin can inhibit intraplaque angiogenesis and promote plaque stability by down-regulating VEGF and VEGFR2 expression, inhibiting the plaque content of macrophages, and reducing MCP-1 expression at an advanced stage of atherosclerosis in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical instability of graphene oxide following exposure to highly reactive radicals in advanced oxidation processes.

PubMed

Wang, Zhaohui; Sun, Linyan; Lou, Xiaoyi; Yang, Fei; Feng, Min; Liu, Jianshe

2017-12-01

The rapidly increasing and widespread use of graphene oxide (GO) as catalyst supports, requires further understanding of its chemical stability in advanced oxidation processes (AOPs). In this study, UV/H 2 O 2 and UV/persulfate (UV/PS) processes were selected to test the chemical instability of GO in terms of their performance in producing highly reactive hydroxyl radicals (OH) and sulfate radicals (SO 4 - ), respectively. The degradation intermediates were characterized using UV-visible absorption spectra (UV-vis), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), Raman spectroscopy, and matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Experimental data indicate that UV/PS process was more effective in enhancing GO degradation than the UV/H 2 O 2 system. The overall oxygen-containing functionalities (e.g. CO, CO and OCO groups) dramatically declined. After radical attack, sheet-like GO was destructed into lots of flakes and some low-molecular-weight molecules were detected. The results suggest GO is most vulnerable against SO 4 - radical attack, which deserves special attention while GO acts as a catalyst support or even as a catalyst itself. Therefore, stability of GO and its derivatives should be carefully assessed before they are applied to SO 4 - -based AOPs. Copyright © 2017 Elsevier Inc. All rights reserved.

Surface currents associated with external kink modes in tokamak plasmas during a major disruption

NASA Astrophysics Data System (ADS)

Ng, C. S.; Bhattacharjee, A.

2017-10-01

The surface current on the plasma-vacuum interface during a disruption event involving kink instability can play an important role in driving current into the vacuum vessel. However, there have been disagreements over the nature or even the sign of the surface current in recent theoretical calculations based on idealized step-function background plasma profiles. We revisit such calculations by replacing step-function profiles with more realistic profiles characterized by a strong but finite gradient along the radial direction. It is shown that the resulting surface current is no longer a delta-function current density, but a finite and smooth current density profile with an internal structure, concentrated within the region with a strong plasma pressure gradient. Moreover, this current density profile has peaks of both signs, unlike the delta-function case with a sign opposite to, or the same as the plasma current. We show analytically and numerically that such current density can be separated into two parts, with one of them, called the convective current density, describing the transport of the background plasma density by the displacement, and the other part that remains, called the residual current density. It is argued that consideration of both types of current density is important and can resolve past controversies.

Heart rate variability alters cardiac repolarization and electromechanical dynamics.

PubMed

Phadumdeo, Vrishti M; Weinberg, Seth H

2018-04-07

Heart rate continuously varies due to autonomic regulation, stochasticity in pacemaking, and circadian rhythm, collectively termed heart rate variability (HRV), during normal physiological conditions. Low HRV is clinically associated with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat alternation in action potential duration (APD) and/or intracellular calcium (Ca) transient, is a well-known risk factor associated with cardiac arrhythmias that is typically studied under conditions of a constant pacing rate, i.e., the absence of HRV. In this study, we investigate the effects of HRV on the interplay between APD, Ca, and electromechanical properties, employing a nonlinear discrete-time map model that governs APD and intracellular Ca cycling with a stochastic pacing period. We find that HRV can decrease variation in APD and peak Ca at fast pacing rates for which alternans is present. Further, increased HRV typically disrupts the alternating pattern for both APD and peak Ca and weakens the correlation between APD and peak Ca, thus decoupling Ca-mediated instabilities from repolarization alternation. We find that the efficacy of these effects is regulated by the sarcoplasmic reticulum Ca uptake rate. Overall, these results demonstrate that HRV disrupts arrhythmogenic alternans and suggests that HRV may be a significant factor in preventing life-threatening arrhythmias. Copyright © 2018 Elsevier Ltd. All rights reserved.

Planetary Engulfment as a Trigger for White Dwarf Pollution

NASA Astrophysics Data System (ADS)

Petrovich, Cristobal; Muñoz, Diego J.

2017-01-01

The presence of a planetary system can shield a planetesimal disk from the secular gravitational perturbations due to distant outer massive objects (planets or stellar companions). As the host star evolves off the main sequence to become a white dwarf, these planets can be engulfed during the giant phase, triggering secular instabilities and leading to the tidal disruptions of small rocky bodies. These disrupted bodies can feed the white dwarfs with rocky material and possibly explain the high-metallicity material in their atmospheres. We illustrate how this mechanism can operate when the gravitational perturbations are due to the KL mechanism from a stellar binary companion, a process that is activated only after the planet has been removed/engulfed. We show that this mechanism can explain the observed accretion rates if: (1) the planetary engulfment happens rapidly compared to the secular timescale, which is generally the case for wide binaries (> 100 au) and planetary engulfment during the asymptotic giant branch; (2) the planetesimal disk has a total mass of ˜ {10}-4-{10}-2{M}\\oplus . We show that this new mechanism can provide a steady supply of material throughout the entire life of the white dwarfs for all cooling ages and can account for a large fraction (up to nearly half) of the observed polluted white dwarfs.

Cooling of the magma ocean due to accretional disruption of the surface insulating layer

NASA Technical Reports Server (NTRS)

Sasaki, Sho

1992-01-01

Planetary accretion has been considered as a process to heat planets. Some fraction of the kinetic energy of incoming planetesimals is trapped to heat the planetary interior (Kaula, 1979; Davies, 1984). Moreover, blanketing effect of a primary atmosphere (Hayashi et al., 1979; Sasaki, 1990) or a degassed atmosphere (Abe and Matsui, 1986; Zahnle et al., 1988) would raise the surface temperature of the Earth-size planets to be higher than the melting temperature. The primordial magma ocean was likely to be formed during accretion of terrestrial planets. In the magma ocean, if crystallized fractions were heavier than melt, they would sink. But if solidified materials were lighter than the melt (like anorthosite of the lunar early crust) they would float to form a solid shell surrounding the planet. (In an icy satellite, solidified water ice should easily float on liquid water because of its small density.) The surface solid lid would prevent efficient convective heat transfer and slow the interior cooling. Consider that the accretion of planetesimals still continues in this cooling stage. Shock disruption at planetesimal impact events may destroy the solid insulating layer. Even if the layer survives impacts, the surface layer is finally overturned by Rayleigh-Taylor instability, since accreting materials containing metals are heavier than the surface solidified lid of silicates.

Disruption of PCNA-lamins A/C interactions by prelamin A induces DNA replication fork stalling.

PubMed

Cobb, Andrew M; Murray, Thomas V; Warren, Derek T; Liu, Yiwen; Shanahan, Catherine M

2016-09-02

The accumulation of prelamin A is linked to disruption of cellular homeostasis, tissue degeneration and aging. Its expression is implicated in compromised genome stability and increased levels of DNA damage, but to date there is no complete explanation for how prelamin A exerts its toxic effects. As the nuclear lamina is important for DNA replication we wanted to investigate the relationship between prelamin A expression and DNA replication fork stability. In this study we report that the expression of prelamin A in U2OS cells induced both mono-ubiquitination of proliferating cell nuclear antigen (PCNA) and subsequent induction of Pol η, two hallmarks of DNA replication fork stalling. Immunofluorescence microscopy revealed that cells expressing prelamin A presented with high levels of colocalisation between PCNA and γH2AX, indicating collapse of stalled DNA replication forks into DNA double-strand breaks. Subsequent protein-protein interaction assays showed prelamin A interacted with PCNA and that its presence mitigated interactions between PCNA and the mature nuclear lamina. Thus, we propose that the cytotoxicity of prelamin A arises in part, from it actively competing against mature lamin A to bind PCNA and that this destabilises DNA replication to induce fork stalling which in turn contributes to genomic instability.

Drift resonance and stability of the Io plasma torus

NASA Astrophysics Data System (ADS)

Zhan, Jie; Hill, T. W.

2000-03-01

The observed local time asymmetry of the Io plasma torus is generally attributed to the presence of a persistent dawn-to-dusk electric field in the Jovian magnetosphere. The local time asymmetry is modulated at the System 3 rotation period of Jupiter's magnetic field, suggesting that the dawn-to-dusk electric field may be similarly modulated. We argue that such a System 3 modulation would have a profound disruptive effect on the observed torus structure if the torus were to corotate at exactly the System 3 rate: the torus would be a resonantly forced harmonic oscillator, and would disintegrate in a few rotation periods, contrary to observations. This destabilizing effect is independent of, and in addition to, the more familiar effect of the centrifugal interchange instability, which is also capable of disrupting the torus in a few rotation periods in the absence of other effects. We conclude that the observed (few percent) corotation lag of the torus is essential to preserving the observed long-lived torus structure by detuning the resonant frequency (the torus drift frequency) relative to the forcing frequency (System 3). A possible outcome of this confinement mechanism is a residual radial oscillation of the torus at the beat period (~10 days) between System 3 and the torus drift period.