2,478 research outputs found
Thermodynamic and dynamic anomalies for a three dimensional isotropic core-softened potential
Using molecular dynamics simulations and integral equations (Rogers-Young,
Percus-Yevick and hypernetted chain closures) we investigate the thermodynamic
of particles interacting with continuous core-softened intermolecular
potential. Dynamic properties are also analyzed by the simulations. We show
that, for a chosen shape of the potential, the density, at constant pressure,
has a maximum for a certain temperature. The line of temperatures of maximum
density (TMD) was determined in the pressure-temperature phase diagram.
Similarly the diffusion constant at a constant temperature, , has a maximum
at a density and a minimum at a density .
In the pressure-temperature phase-diagram the line of extrema in diffusivity is
outside of TMD line. Although in this interparticle potential lacks
directionality, this is the same behavior observed in SPC/E water.Comment: 16 page
Entropy, diffusivity and the energy landscape of a water-like fluid
Molecular dynamics simulations and instantaneous normal mode (INM) analysis
of a fluid with core-softened pair interactions and water-like liquid-state
anomalies are performed to obtain an understanding of the relationship between
thermodynamics, transport properties and the poten- tial energy landscape.
Rosenfeld-scaling of diffusivities with the thermodynamic excess and pair
correlation entropy is demonstrated for this model. The INM spectra are shown
to carry infor- mation about the dynamical consequences of the interplay
between length scales characteristic of anomalous fluids, such as bimodality of
the real and imaginary branches of the frequency distribu- tion. The INM
spectral information is used to partition the liquid entropy into two
contributions associated with the real and imaginary frequency modes; only the
entropy contribution from the imaginary branch captures the non-monotonic
behaviour of the excess entropy and diffusivity in the anomalous regime of the
fluid
Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory
Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling
Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1
Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density
Multiple stakeholdersâ perspectives of marine social ecological systems, a case study on the Barents Sea
The Barents Sea ecosystem components and services are under pressure from climate change and other
anthropogenic impacts. Following an Ecosystem-based management approach, multiple simultaneous pressures
are addressed by using integrative strategies, but regular prioritization of key issues is needed. Identification of
such priorities is typically done in a âscopingâ phase, where the characterization of the social-ecological system is
defined and discussed. We performed a scoping exercise using an open and flexible multi-stakeholder approach
to build conceptual models of the Barents Sea social-ecological system. After standardizing vocabulary, a com plex hierarchical model structure containing 155 elements was condensed to a simpler model structure con taining a maximum of 36 elements. To capture a common understanding across stakeholder groups, inputs from
the individual group models were compiled into a collective model. Stakeholdersâ representation of the Barents
Sea social-ecological system is complex and often group specific, emphasizing the need to include social scientific
methods to ensure the identification and inclusion of key stakeholders in the process. Any summary or simpli fication of the stakeholdersâ representation neglects important information. Some commonalities are highlighted
in the collective model, and additional information from the hierarchical model is provided by multicriteria
analysis. The collective conceptual stakeholder model provides input to an integrated overview and strengthens
prioritization in Ecosystem-based management by supporting the development of qualitative network models.
Such models allow for exploration of perturbations and can inform cross-sectoral management trade-offs and
prioritiespublishedVersio
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Low cost titanium--myth or reality
In 1998, approximately 57,000 tons of titanium metal was consumed in the form of mill products (1). Only about 5% of the 4 million tons of titanium minerals consumed each year is used to produce titanium metal, with the remainder primarily used to produce titanium dioxide pigment. Titanium metal production is primarily based on the direct chlorination of rutile to produce titanium tetrachloride, which is then reduced to metal using the Kroll magnesium reduction process. The use of titanium is tied to its high strength-to-weight ratio and corrosion resistance. Aerospace is the largest application for titanium, and titanium cost has prevented its use in non-aerospace applications including the automotive and heavy vehicle industries
Crowding of Polymer Coils and Demixing in Nanoparticle-Polymer Mixtures
The Asakura-Oosawa-Vrij (AOV) model of colloid-polymer mixtures idealizes
nonadsorbing polymers as effective spheres that are fixed in size and
impenetrable to hard particles. Real polymer coils, however, are intrinsically
polydisperse in size (radius of gyration) and may be penetrated by smaller
particles. Crowding by nanoparticles can affect the size distribution of
polymer coils, thereby modifying effective depletion interactions and
thermodynamic stability. To analyse the influence of crowding on polymer
conformations and demixing phase behaviour, we adapt the AOV model to mixtures
of nanoparticles and ideal, penetrable polymer coils that can vary in size. We
perform Gibbs ensemble Monte Carlo simulations, including trial
nanoparticle-polymer overlaps and variations in radius of gyration. Results are
compared with predictions of free-volume theory. Simulation and theory
consistently predict that ideal polymers are compressed by nanoparticles and
that compressibility and penetrability stabilise nanoparticle-polymer mixtures.Comment: 18 pages, 4 figure
Similarities between structural distortions under pressure and chemical doping in superconducting BaFe2As2
The discovery of a new family of high Tc materials, the iron arsenides
(FeAs), has led to a resurgence of interest in superconductivity. Several
important traits of these materials are now apparent, for example, layers of
iron tetrahedrally coordinated by arsenic are crucial structural ingredients.
It is also now well established that the parent non-superconducting phases are
itinerant magnets, and that superconductivity can be induced by either chemical
substitution or application of pressure, in sharp contrast to the cuprate
family of materials. The structure and properties of chemically substituted
samples are known to be intimately linked, however, remarkably little is known
about this relationship when high pressure is used to induce superconductivity
in undoped compounds. Here we show that the key structural features in
BaFe2As2, namely suppression of the tetragonal to orthorhombic phase transition
and reduction in the As-Fe-As bond angle and Fe-Fe distance, show the same
behavior under pressure as found in chemically substituted samples. Using
experimentally derived structural data, we show that the electronic structure
evolves similarly in both cases. These results suggest that modification of the
Fermi surface by structural distortions is more important than charge doping
for inducing superconductivity in BaFe2As2
TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.
HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion
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