12 research outputs found
Nonequilibrium Stationary States of Harmonic Chains with Bulk Noises : Harmonic Chains with Bulk Noises
We consider a chain composed of coupled harmonic oscillators in contact with heat baths at temperature and at sites and respectively. The oscillators are also subjected to non-momentum conserving bulk stochastic noises. These make the heat conductivity satisfy Fourier's law. Here we describe some new results about the hydrodynamical equations for typical macroscopic energy and displacement profiles, as well as their fluctuations and large deviations, in two simple models of this type
Nonequilibrium stationary states of harmonic chains with bulk noises
We consider a chain composed of coupled harmonic oscillators in contact with heat baths at temperature and at sites 1 and respectively. The oscillators are also subjected to non-momentum conserving bulk stochastic noises. These make the heat conductivity satisfy Fourier's law. Here we describe some new results about the hydrodynamical equations for typical macroscopic energy and displacement profiles, as well as their fluctuations and large deviations, in two simple models of this type.Peer reviewe
TGF-β affects the differentiation of human GM-CSF+ CD4+ T cells in an activation- and sodium-dependent manner
The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is involved in
the pathogenesis of chronic inflammatory diseases such as multiple sclerosis. However,
the environmental cues promoting differentiation of GM-CSF producing T cells are
unclear. Herein, we performed a broad experimental screening of cytokines and datadriven
analysis assessing their ability to induce human GM-CSF+ CD4+ T cells and their
subpopulations. TGF-β was discovered to induce GM-CSF production independently of
proliferation and IL-2 signaling including STAT5. In contrast, IL-6 and IL-23 decreased
GM-CSF production. On the population level, GM-CSF induction was highly correlated
with expression of FOXP3 across cytokine stimulations but not with that of IL-17.
However, on single-cell level GM-CSF and IFN-γ expression were most correlated,
independently of the cytokine environment. Importantly, under low sodium conditions
in the medium or upon stimulation with plate-bound instead of bead-bound anti-CD3
and anti-CD28 antibodies, the effects of TGF-β on GM-CSF, but not on FOXP3, were
reversed. Our analysis indicates a novel role for TGF-β in generating GM-CSF+ subsets
of human CD4+ T cells. These results are important for understanding of autoimmune
disease and therapeutic considerations.FP7Publishe
Inferring causal molecular networks: empirical assessment through a community-based effort
Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks
Inferring causal molecular networks: empirical assessment through a community-based effort
It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense
Heat conduction in low dimensional lattice systems
We study heat conduction and other nonequilibrium properties of one dimensional chain of particles, ordered and disordered, harmonic and anharmonic. Our results include derivation of oscillatory temperature profile for harmonic alternating mass chains, demonstration of finite heat conductivity for disordered harmonic chains with velocity-flipping noise, description of fluctuations for ordered harmonic systems with noise, and understanding the behavior of systems with noise and anharmonicity. We provide a comparative analysis of the effects of the various dynamics and system parameters on the characteristics of the nonequilibrium steady state of the chain.Ph. D.Includes bibliographical referencesby Venkateshan Kanna
Nonequilibrium stationary state of a harmonic crystal with alternating masses
We analyze the nonequilibrium steady states (NESS) of a one-dimensional harmonic chain of N atoms with alternating masses connected to heat reservoirs at unequal temperatures. We find that the temperature profile defined through the local kinetic energy T(j)≡〈p<sub>j</sub><sup>2</sup>〉/m<sub>j</sub> oscillates with period two in the bulk of the system. Depending on boundary conditions, either the heavier or the lighter particles in the bulk are hotter. We obtain explicit integral expressions for the bulk temperature profile and steady state current in the limit N→∞. These depend on whether N is odd or even. We also study similar temperature oscillations in the NESS of systems with noise in the dynamics. These die out as N→∞
Elevated ATP, cytokines and potential microglial inflammation distinguish exfoliation glaucoma from exfoliation syndrome
Glaucoma is the second leading cause of blindness. Exfoliation syndrome (XFN) is a risk factor for exfoliation glaucoma (XFG) which is a secondary open angle glaucoma. XFG is difficult to manage with a worse prognosis. Though 40% of the XFN progress to XFG, there are no predictive markers to identify the susceptible patients. Herein, we analyze clinical data, ATP levels in aqueous humor and cytokines in plasma to identify alteration that help distinguish XFN from XFG. Our results show characteristic clinical features of XFG compared to XFN and controls. Elevated levels of ATP in aqueous humor were observed in XFG compared to XFN and cataract controls while elevated levels of plasma cytokines were observed in XFG compared to XFN, cataract controls and healthy controls. Microglia are immune cells in the retina implicated in glaucoma. TNFα plays a predominant role in microglial inflammation and is implicated in neurodegeneration. Using in vitro N9 microglial cell culture model, we demonstrate that TNFα modulated expression of cytokines and chemotaxis is dependent on P2 receptors like P2X7, P2Y12 and P2Y6. In addition, ATP also induce expression of TNFα which might act as a feed forward loop. The TNFα induced inflammation is dependent on downstream signaling modules like PI3K, JNK and ROS. Taken together, our results show that elevated ATP in aqueous humor, plasma cytokines and inflammation potentially involving microglia distinguish XFG from XFN. Purinergic receptors might be potential therapeutic targets in XFG