Piecewise Linear Identification for the Rate-Independent and Rate-Dependent Duhem Hysteresis Models

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57843/1/HysteresisIDTACMarch2007.pd

Semilinear Duhem Model for Rate-Independent and Rate-Dependent Hysteresis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57865/1/HysteresisSemilinearDuhemTAC2005.pd

A GABAergic projection from the centromedial nuclei of the amygdala to ventromedial prefrontal cortex modulates reward behavior

The neural circuitry underlying mammalian reward behaviors involves several distinct nuclei throughout the brain. It is widely accepted that the midbrain dopamine (DA) neurons are critical for the reward-related behaviors. Recent studies have shown that the centromedial nucleus of the amygdala (CeMA) has a distinct role in regulating reward-related behaviors. However, the CeMA and ventromedial PFC (vmPFC) interaction in reward regulation remains poorly understood. Here, we identify and dissect a GABAergic projection that originates in the CeMA and terminates in the vmPFC (VGat-Cre(CeMA-vmPFC)) using viral-vector-mediated, cell-type-specific optogenetic techniques in mice. Pathway-specific optogenetic activation of the VGat-Cre(CeMA-vmPFC) circuit in awake, behaving animals produced a positive, reward-like phenotype in real-time place preference and increased locomotor activity in open-field testing. In sucrose operant conditioning, the photoactivation of these terminals increased nose-poking effort with no effect on licking behavior and robustly facilitated the extinction of operant behavior. However, photoactivation of these terminals did not induce self-stimulation in the absence of an external reward. The results described here suggest that the VGat-Cre(CeMA-vmPFC) projection acts to modulate existing reward-related behaviors. SIGNIFICANCE STATEMENT Many studies have shown that the interactions between the centromedial nucleus of the amygdala (CeMA) and ventromedial PFC (vmPFC) have critical roles for emotional regulation. However, most studies have associated this circuit with fear and anxiety behaviors and emphasized top-down processing from vmPFC to CeMA. Here, we provide new evidence for bottom-up CeMA to vmPFC influence on reward-related behaviors. Although previous work implicated the CeMA in incentive salience, our results isolate the investigation to a specific CeMA GABAergic projection to the vmPFC. This long-range GABAergic interaction between amygdala and frontal cortex adds a new dimension to the complex regulation of reward-related behaviors

Shaken and stirred: conduction and turbulence in clusters of galaxies

(abridged) Uninhibited radiative cooling in clusters of galaxies would lead to excessive mass accretion rates contrary to observations. One of the key proposals to offset radiative energy losses is thermal conduction from outer, hotter layers of cool core clusters to their centers. However, conduction is sensitive to magnetic field topology. In cool-core clusters the heat buoyancy instability (HBI) leads to B-fields ordered preferentially in the direction perpendicular to that of gravity, which significantly reduces the level of conduction below the classical Spitzer-Braginskii value. However, the cluster cool cores are rarely in perfect hydrostatic equilibrium. Sloshing motions due to minor mergers, galaxy motions or AGN can significantly perturb the gas and affect the level of thermal conduction. We perform 3D AMR MHD simulations of the effect of turbulence on the properties of the anisotropic thermal conduction in cool core clusters. We show that very weak subsonic motions, well within observational constraints, can randomize the magnetic field and significantly boost effective thermal conduction beyond the saturated values expected in the pure unperturbed HBI case. We find that the turbulent motions can essentially restore the conductive heat flow to the cool core to level comparable to the theoretical maximum of 1/3 Spitzer for a highly tangled field. Runs with radiative cooling show that the cooling catastrophe can be averted and the cluster core stabilized. Above a critical Froude number, these same turbulent motions also eliminate the tangential bias in the velocity and magnetic field that is otherwise induced by the trapped g-modes. Our results can be tested with future radio polarization measurements, and have implications for efficient metal dispersal in clusters.Comment: submitted to ApJ, references added, expanded Section

Galaxy Motions, Turbulence and Conduction in Clusters of Galaxies

Unopposed radiative cooling in clusters of galaxies results in excessive mass deposition rates. However, the cool cores of galaxy clusters are continuously heated by thermal conduction and turbulent heat diffusion due to minor mergers or the galaxies orbiting the cluster center. These processes can either reduce the energy requirements for AGN heating of cool cores, or they can prevent overcooling altogether. We perform 3D MHD simulations including field-aligned thermal conduction and self-gravitating particles to model this in detail. Turbulence is not confined to the wakes of galaxies but is instead volume-filling, due to the excitation of large-scale g-modes. We systematically probe the parameter space of galaxy masses and numbers. For a wide range of observationally motivated galaxy parameters, the magnetic field is randomized by stirring motions, restoring the conductive heat flow to the core. The cooling catastrophe either does not occur or it is sufficiently delayed to allow the cluster to experience a major merger that could reset conditions in the intracluster medium. Whilst dissipation of turbulent motions is negligible as a heat source, turbulent heat diffusion is extremely important; it predominates in the cluster center. However, thermal conduction becomes important at larger radii, and simulations without thermal conduction suffer a cooling catastrophe. Conduction is important both as a heat source and to reduce stabilizing buoyancy forces, enabling more efficient diffusion. Turbulence enables conduction, and conduction enables turbulence. In these simulations, the gas vorticity---which is a good indicator of trapped g-modes--increases with time. The vorticity growth is approximately mirrored by the growth of the magnetic field, which is amplified by turbulence.Comment: Submitted to MNRA

Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes

Background \ud Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin– like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud Caenorhabditis species. \ud \ud Methodology/Principal Findings \ud We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions \ud The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Phenotypic covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. \ud \ud Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

NCoR Repression of LXRs Restricts Macrophage Biosynthesis of Insulin-Sensitizing Omega 3 Fatty Acids

SummaryMacrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and ω3 fatty acids. Remarkably, the increased ω3 fatty acid levels primarily inhibit NF-κB-dependent inflammatory responses by uncoupling NF-κB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies