Cause and Effect of Feedback: Multiphase Gas in Cluster Cores Heated by AGN Jets

Multiwavelength data indicate that the X-ray-emitting plasma in the cores of galaxy clusters is not cooling catastrophically. To a large extent, cooling is offset by heating due to active galactic nuclei (AGNs) via jets. The cool-core clusters, with cooler/denser plasmas, show multiphase gas and signs of some cooling in their cores. These observations suggest that the cool core is locally thermally unstable while maintaining global thermal equilibrium. Using high-resolution, three-dimensional simulations we study the formation of multiphase gas in cluster cores heated by collimated bipolar AGN jets. Our key conclusion is that spatially extended multiphase filaments form only when the instantaneous ratio of the thermal instability and free-fall timescales (t(TI)/t(ff)) falls below a critical threshold of approximate to 10. When this happens, dense cold gas decouples from the hot intracluster medium (ICM) phase and generates inhomogeneous and spatially extended Ha filaments. These cold gas clumps and filaments ``rain'' down onto the central regions of the core, forming a cold rotating torus and in part feeding the supermassive black hole. Consequently, the self-regulated feedback enhances AGN heating and the core returns to a higher entropy level with t(TI)/t(ff) > 10. Eventually, the core reaches quasi-stable global thermal equilibrium, and cold filaments condense out of the hot ICM whenever t(TI)/t(ff) less than or similar to 10. This occurs despite the fact that the energy from AGN jets is supplied to the core in a highly anisotropic fashion. The effective spatial redistribution of heat is enabled in part by the turbulent motions in the wake of freely falling cold filaments. Increased AGN activity can locally reverse the cold gas flow, launching cold filamentary gas away from the cluster center. Our criterion for the condensation of spatially extended cold gas is in agreement with observations and previous idealized simulations.

Mutations in Drosophila Myosin Rod Cause Defects in Myofibril Assembly

The roles of myosin during muscle contraction are well studied, but how different domains of this protein are involved in myofibril assembly in vivo is far less understood. The indirect flight muscles (IFMs) of Drosophila melanogaster provide a good model for understanding muscle development and function in vivo. We show that two missense mutations in the rod region of the myosin heavy-chain gene, Mhc, give rise to IFM defects and abnormal myofibrils. These defects likely result from thick filament abnormalities that manifest during early sarcomere development or later by hypercontraction. The thick filament defects are accompanied by marked reduction in accumulation of flightin, a myosin binding protein, and its phosphorylated forms, which are required to stabilise thick filaments. We investigated with purified rod fragments whether the mutations affect the coiled-coil structure, rod aggregate size or rod stability. No significant changes in these parameters were detected, except for rod thermodynamic stability in one mutation. Molecular dynamics simulations suggest that these mutations may produce localised rod instabilities. We conclude that the aberrant myofibrils are a result of thick filament defects, but that these in vivo effects cannot be detected in vitro using the biophysical techniques employed. The in vivo investigation of these mutant phenotypes in IFM development and function provides a useful platform for studying myosin rod and thick filament formation generically, with application to the aetiology of human myosin rod myopathies. (C) 2012 Elsevier Ltd. All rights reserved.

Valley splitting in Si/Si1-xGex heterostructures

We show that the alloy disorder potential can be a possible cause for the valley splitting observed in the Si/Si1-xGex heterostructures at high magnetic fields and low electron densities.

The physics of ENSO-monsoon connection

The physical mechanism through which Ei-Nino and Southern Oscillation (ENSO) tends to produce deficient precipitation over Indian continent is investigated using both observations as well as a general circulation model. Both analysis of observations and atmospheric general circulation model (AGCM) study show that the planetary scale response associated with ENSO primarily influences the equatorial Indian Ocean region. Through this interaction it tends to favour the equatorial heat source, enhance precipitation over the equatorial Indian Ocean and indirectly cause a decrease in continental precipitation through induced subsidence. This situation is further complicated by the fact the regional tropospheric quasi biennial oscillation (QBO) has a bimodal structure over this region with large amplitude over the Indian continent. While the ENSO response has a quasi-four year periodicity and tends peak during beginning of the calendar year, the QBO mode tends to peak during northern summer. Thus, the QBO mode exerts a stronger influence on the interannual variability of the monsoon. The strength of the Indian monsoon in a given year depends on the combined effect of the ENSO and the QBO mode. Sines the two oscillations have disparate time scales, exact phase information of the two modes during northern summer is important in determining the Indian summer monsoon. The physical mechanism of the interannual variations of the Indian monsoon precipitation associated with ENSO presented here is similar to the physical process that cause intraseasonal 'active', 'break' oscillations of the monsoon.

Dynamics of a dilute sheared inelastic fluid. II. The effect of correlations

The effect of correlations on the viscosity of a dilute sheared inelastic fluid is analyzed using the ring-kinetic equation for the two-particle correlation function. The leading-order contribution to the stress in an expansion in epsilon=(1-e)(1/2) is calculated, and it is shown that the leading-order viscosity is identical to that obtained from the Green-Kubo formula, provided the stress autocorrelation function in a sheared steady state is used in the Green-Kubo formula. A systemmatic extension of this to higher orders is also formulated, and the higher-order contributions to the stress from the ring-kinetic equation are determined in terms of the terms in the Chapman-Enskog solution for the Boltzmann equation. The series is resummed analytically to obtain a renormalized stress equation. The most dominant contributions to the two-particle correlation function are products of the eigenvectors of the conserved hydrodynamic modes of the two correlated particles. In Part I, it was shown that the long-time tails of the velocity autocorrelation function are not present in a sheared fluid. Using those results, we show that correlations do not cause a divergence in the transport coefficients; the viscosity is not divergent in two dimensions, and the Burnett coefficients are not divergent in three dimensions. The equations for three-particle and higher correlations are analyzed diagrammatically. It is found that the contributions due to the three-particle and higher correlation functions to the renormalized viscosity are smaller than those due to the two-particle distribution function in the limit epsilon -> 0. This implies that the most dominant correlation effects are due to the two-particle correlations.

Mutations in STIL, Encoding a Pericentriolar and Centrosomal Protein, Cause Primary Microcephaly

Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterized by smaller-than-normal brain size and mental retardation. MCPH is genetically heterogeneous with six known loci: MCPH1-MCPH6. We report mapping of a novel locus, MCPH7, to chromosome 1p32.3-p33 between markers D1S2797 and D1S417, corresponding to a physical distance of 8.39 Mb. Heterogeneity analysis of 24 families previously excluded from linkage to the six known MCPH loci suggested linkage of five families (20.83%) to the MCPH7 locus. In addition, four families were excluded from linkage to the MCPH7 locus as well as all of the six previously known loci, whereas the remaining 15 families could not be conclusively excluded or included. The combined maximum two-point LOD score for the linked families was 5.96 at marker D1S386 at theta = 0.0. The combined multipoint LOD score was 6.97 between markers D1S2797 and D1S417. Previously, mutations in four genes, MCPH1, CDK5RAP2, ASPM, and CENPJ, that code for centrosomal proteins have been shown to cause this disorder. Three different homozygous mutations in STIL, which codes for a pericentriolar and centrosomal protein, were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the STIL protein. Further, another recently ascertained family was homozygous for the same mutation as one of the original families. There was no evidence for a common haplotype. These results suggest that the centrosome and its associated structures are important in the control of neurogenesis in the developing human brain.

Focused Prefetching: Performance Oriented Prefetching Based On Commit Stalls

Loads that miss in L1 or L2 caches and waiting for their data at the head of the ROB cause significant slow down in the form of commit stalls. We identify that most of these commit stalls are caused by a small set of loads, referred to as LIMCOS (Loads Incurring Majority of COmmit Stalls). We propose simple history-based classifiers that track commit stalls suffered by loads to help us identify this small set of loads. We study an application of these classifiers to prefetching. The classifiers are used to train the prefetcher to focus on the misses suffered by LIMCOS. This, referred to as focused prefetching, results in a 9.8% gain in IPC over naive GHB based delta correlation prefetcher along with a 20.3% reduction in memory traffic for a set of 17 memory-intensive SPEC2000 benchmarks. Another important impact of focused prefetching is a 61% improvement in the accuracy of prefetches. We demonstrate that the proposed classification criterion performs better than other existing criteria like criticality and delinquent loads. Also we show that the criterion of focusing on commit stalls is robust enough across cache levels and can be applied to any prefetcher without any modifications to the prefetcher.

EXAFS studies of arsenic chalcogenide glasses

An EXAFS study at the AsK edge of the ternary glasses As2(S, Se)3 and As2(Se, Te)3 and the binary As2S3, As2Se3 and As2Te3 glasses has been carried out. Radial structure functions show that the environment of As in glasses of intermediate compositions is quite different from that in the binary glasses. In the As2(S, Se)3 system, this might arise from chemical disorder in the network while in the As2(Se, Te)3 system increased ionicity could be the cause of this behaviour. Glasses where the constituent atoms are of similar size seem to exhibit fewer peaks in the radial structure function.

Mesospheric influences on linkages between solar activity and lower atmospheric phenomena

Analyses of rocket data at mid- and high-latitude locations over the American Continent show a solar activity-dependent mesospheric heating effect in the 60 to 90 km altitude region. A study of the altitude dependence of the effect shows that the heating and associated processes propagating downwards through the mesosphere do not cause discernible effects, below the 50 to 60 km layer. At Thumba, a significant short-term heating effect attributable to varying solar ultraviolet fluxes causing variable heating of atmospheric ozone is observed. This effect does not seem to propagate downwards into the upper stratosphere.

The effect of radiation on the electron pairing in a multiband system

The possible occurrence of a generalized (1-wave) nonequilibrium superconducting state in a multiband system under certain conditions is studied. In the model the radiation field causes interband mixing, and phonons of an appropriate mode (branch) are involved in the interband scattering of electrons of two conduction bands of the system. The strength of the generalized 1-wave pairing interaction between quasiparticles belonging to new radiation admixed states depends on the density (n o/V) of quanta in the system. The coupling constant has the form Xl= AiB(n o/V)/[C + B(no/V)], where A1, B, and C are parameters. For C > B(n0/V), the transition temperature T1* increases with (no/V) in the initial stages. It levels off with higher power. With further increase of power, the transition temperature is expected to drop sharply due to heating effects which cause pair breaking. Estimates show that p-wave (triplet state) pairing may be possible under radiation-induced nonequilibrium situations in appropriate systems. Estimates for lifetimes of various processes quasiparticle, phonon, pair relaxation, and photon-induced mixing) show that the coherence required for the mixing and pairing effects will be maintained for the temperature range and photon density considered.

Comprehensive Path-sensitive Data-flow Analysis

Data-flow analysis is an integral part of any aggressive optimizing compiler. We propose a framework for improving the precision of data-flow analysis in the presence of complex control-flow. W initially perform data-flow analysis to determine those control-flow merges which cause the loss in data-flow analysis precision. The control-flow graph of the program is then restructured such that performing data-flow analysis on the resulting restructured graph gives more precise results. The proposed framework is both simple, involving the familiar notion of product automata, and also general, since it is applicable to any forward data-flow analysis. Apart from proving that our restructuring process is correct, we also show that restructuring is effective in that it necessarily leads to more optimization opportunities. Furthermore, the framework handles the trade-off between the increase in data-flow precision and the code size increase inherent in the restructuring. We show that determining an optimal restructuring is NP-hard, and propose and evaluate a greedy strategy. The framework has been implemented in the Scale research compiler, and instantiated for the specific problem of Constant Propagation. On the SPECINT 2000 benchmark suite we observe an average speedup of 4% in the running times over Wegman-Zadeck conditional constant propagation algorithm and 2% over a purely path profile guided approach.

Damage assessment of structures with uncertainty by using mode-shape curvatures and fuzzy logic

Uncertainties associated with the structural model and measured vibration data may lead to unreliable damage detection. In this paper, we show that geometric and measurement uncertainty cause considerable problem in damage assessment which can be alleviated by using a fuzzy logic-based approach for damage detection. Curvature damage factor (CDF) of a tapered cantilever beam are used as damage indicators. Monte Carlo simulation (MCS) is used to study the changes in the damage indicator due to uncertainty in the geometric properties of the beam. Variation in these CDF measures due to randomness in structural parameter, further contaminated with measurement noise, are used for developing and testing a fuzzy logic system (FLS). Results show that the method correctly identifies both single and multiple damages in the structure. For example, the FLS detects damage with an average accuracy of about 95 percent in a beam having geometric uncertainty of 1 percent COV and measurement noise of 10 percent in single damage scenario. For multiple damage case, the FLS identifies damages in the beam with an average accuracy of about 94 percent in the presence of above mentioned uncertainties. The paper brings together the disparate areas of probabilistic analysis and fuzzy logic to address uncertainty in structural damage detection.

Farnesyltransferase Inhibitors Reduce Ras Activation and Ameliorate Acetaminophen-Induced Liver Injury in Mice

Hepatotoxicity due to overdose of the analgesic and antipyretic acetaminophen (A-PAIP) is a major cause of liver failure in adults. To better understand the contributions of different signaling pathways, the expression and role of Ras activation was evaluated after oral dosing of mice with APAP (400-500 mg/kg). Ras-guanosine triphosphate (GTP) is induced early and in an oxidative stress-dependent manner. The functional role of Ras activation was studied by a single intraperitoneal injection of the neutral sphingomyelinase and farnesyltransferase inhibitor (FTI) manumycin A (I mg/kg), which lowers induction of Ras-GTP and serum amounts of alanine aminotransferase (ALT). APAP dosing decreases hepatic glutathione amounts, which are not affected by manumycin A treatment. However, APAP-induced activation of c-Jun N-terminal kinase, which plays an important role, is reduced by manumycin A. Also, APAP-induced mitochondrial reactive oxygen species are reduced by manumycin A at a later time point during liver injury. Importantly, the induction of genes involved in the inflammatory response (including iNos, gp91phox, and Fasl) and serum amounts of proinflammatory cytokines interferon-gamma (IFN gamma) and tumor necrosis factor alpha, which increase greatly with APAP challenge, are suppressed with manumycin A. The FTI ctivity of manumycin A is most likely involved in reducing APAP-induced liver injury, because a specific neutral sphingomyelinase inhibitor, GW4869 (I mg/kg), did not show any hepatoprotective effect. Notably, a structurally distinct FTI, gliotoxin (I mg/kg), also inhibits Ras activation and reduces serum amounts of ALT and IFN-gamma after APAP dosing. Finally, histological analysis confirmed the hepatoprotective effect f manumycin A and gliotoxin during APAP-induced liver damage. Conclusion: This study identifies a key role for Ras activation and demonstrates the therapeutic efficacy of FTIs during APAP-induced liver injury.

Phenotypic plasticity and longevity in plants and animals: cause and effect?

Immobile plants and immobile modular animals outlive unitary animals. This paper discusses competing but not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of phenotypic plasticity. Stem cell immortality, vascular autonomy, and epicormic branching are some important features of the phenotypic plasticity of plants that contribute to their longevity. Monocarpy versus polycarpy can also influence the kind of senescent processes experienced by plants. How density-dependent phenomena affecting the establishment of juveniles in these immobile organisms can influence the evolution of senescence, and consequently longevity, is reviewed and discussed. Whether climate change scenarios will favour long-lived or short-lived organisms, with their attendant levels of plasticity, is also presented.

Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action

Neutral and cationic organometallic ruthenium(II) piano stool complexes of the type [(eta(6)-cymene)R-uCl(X)(Y)] (complexes R1-R8) has been synthesized and characterized. In cationic complexes, X, Y is either a eta(2) phosphorus ligand such as 1,1-bis(diphenylphosphino)methane (DPPM) and 1,2-bis(diphenylphosphino)ethane (DPPE) or partially oxidized ligands such as 1,2-bis(diphenylphosphino)methane monooxide (DPPMO) and 1,2-bis(diphenylphosphino)ethane monooxide (DPPEO) which are strong hydrogen bond acceptors. In neutral complexes. X is chloride and Y is a monodentate phosphorous donor. Complexes with DPPM and DPPMO ligands ([(eta(6)-cymene)Ru(eta(2)-DPPM)Cl]PF6 (R2), [(eta(6)-cymene)Ru(eta(2)-DPPMO)Cl]PF6 (R3), [(eta(6)-cymene)Ru(eta(1)-DPPM)Cl-2] (R5) and [(eta(6)-cymene)Ru(eta(1)-DPPMO)Cl-2] (R6) show good cytotoxicity. Growth inhibition study of several human cancer cell lines by these complexes has been carried out. Mechanistic studies for R5 and R6 show that inhibition of cancer cell growth involves both cell cycle arrest and apoptosis induction. Using an apoptosis PCR array, we identified the sets of antiapoptotic genes that were down regulated and pro-apoptotic genes that were up regulated. These complexes were also found to be potent metastasis inhibitors as they prevented cell invasion through matrigel. The complexes were shown to bind DNA in a non intercalative fashion and cause unwinding of plasmid DNA in cell-free medium by competitive ethidium bromide binding, viscosity measurements, thermal denaturation and gel mobility shift assays.