145 research outputs found
Thermal Convection over Fractal Surfaces
We use well resolved numerical simulations with the Lattice Boltzmann Method
to study Rayleigh-B\'enard convection in cells with a fractal boundary in two
dimensions for and . The fractal
boundaries are functions characterized by power spectral densities that
decay with wavenumber, , as (). The degree of
roughness is quantified by the exponent with for smooth
(differentiable) surfaces and for rough surfaces with Hausdorff
dimension . By computing the exponent in power
law fits , where and are the Nusselt and the
Rayleigh numbers for , we observe that heat
transport scaling increases with roughness over the top two decades of . For , and we find and , respectively. We
also observe that the Reynolds number, , scales as ,
where over , for all
used in the study. For a given value of , the averaged and are
insensitive to the specific realization of the roughness.Comment: 15 pages, 13 figure
The transcription factor Pdr802 regulates Titan cell formation and pathogenicity of Cryptococcus neoformans
The pathogenic yeast
Cryptococcus neoformansC. neoforman
Minimal Brownian Ratchet: An Exactly Solvable Model
We develop an exactly-solvable three-state discrete-time minimal Brownian
ratchet (MBR), where the transition probabilities between states are
asymmetric. By solving the master equations we obtain the steady-state
probabilities. Generally the steady-state solution does not display detailed
balance, giving rise to an induced directional motion in the MBR. For a reduced
two-dimensional parameter space we find the null-curve on which the net current
vanishes and detailed balance holds. A system on this curve is said to be
balanced. On the null-curve, an additional source of external random noise is
introduced to show that a directional motion can be induced under the zero
overall driving force. We also indicate the off-balance behavior with biased
random noise.Comment: 4 pages, 4 figures, RevTex source, General solution added. To be
appeared in Phys. Rev. Let
Pre-surgical depression and anxiety and recovery following coronary artery bypass graft surgery
We aimed to explore the combined contribution of pre-surgical depression and anxiety symptoms for recovery following coronary artery bypass graft (CABG) using data from 251 participants. Participants were assessed prior to surgery for depression and anxiety symptoms and followed up at 12 months to assess pain and physical symptoms, while hospital emergency admissions and death/major adverse cardiac events (MACE) were monitored on average 2.68 years after CABG. After controlling for covariates, baseline anxiety symptoms, but not depression, were associated with greater pain (β = 0.231, p = 0.014) and greater physical symptoms (β = 0.194, p = 0.034) 12 months after surgery. On the other hand, after controlling for covariates, baseline depression symptoms, but not anxiety, were associated with greater odds of having an emergency admission (OR 1.088, CI 1.010–1.171, p = 0.027) and greater hazard of death/MACE (HR 1.137, CI 1.042–1.240, p = 0.004). These findings point to different pathways linking mood symptoms with recovery after CABG surgery
Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia
The application of immunotherapies such as chimeric antigen receptor (CAR) T therapy or bi-specific T cell engager (BiTE) therapy to manage myeloid malignancies has proven more challenging than for B-cell malignancies. This is attributed to a shortage of leukemia-specific cell-surface antigens that distinguish healthy from malignant myeloid populations, and the inability to manage myeloid depletion unlike B-cell aplasia. Therefore, the development of targeted therapeutics for myeloid malignancies, such as acute myeloid leukemia (AML), requires new approaches. Herein, we developed a ligand-based CAR and secreted bi-specific T cell engager (sBite) to target c-kit using its cognate ligand, stem cell factor (SCF). c-kit is highly expressed on AML blasts and correlates with resistance to chemotherapy and poor prognosis, making it an ideal candidate for which to develop targeted therapeutics. We utilize γδ T cells as a cytotoxic alternative to αβ T cells and a transient transfection system as both a safety precaution and switch to remove alloreactive modified cells that may hinder successful transplant. Additionally, the use of γδ T cells permits its use as an allogeneic, off-the-shelf therapeutic. To this end, we show mSCF CAR- and hSCF sBite-modified γδ T cells are proficient in killing c-kit+ AML cell lines and sca-1+ murine bone marrow cells in vitro. In vivo, hSCF sBite-modified γδ T cells moderately extend survival of NSG mice engrafted with disseminated AML, but therapeutic efficacy is limited by lack of γδ T-cell homing to murine bone marrow. Together, these data demonstrate preclinical efficacy and support further investigation of SCF-based γδ T-cell therapeutics for the treatment of myeloid malignancies
Social tipping points in animal societies
Animal social groups are complex systems that are likely to exhibit tipping points—which are defined as drastic shifts in the dynamics of systems that arise from small changes in environmental conditions—yet this concept has not been carefully applied to these systems. Here we summarize the concepts behind tipping points and describe instances in which they are likely to occur in animal societies. We also offer ways in which the study of social tipping points can open up new lines of inquiry in behavioral ecology and generate novel questions, methods, and approaches in animal behavior and other fields, including community and ecosystem ecology. While some behaviors of living systems are hard to predict, we argue that probing tipping points across animal societies and across tiers of biological organization—populations, communities, ecosystems—may help to reveal principles that transcend traditional disciplinary boundaries
Diminished macrophage apoptosis and reactive oxygen species generation after phorbol ester stimulation in Crohn's disease.
BACKGROUND: Crohn's Disease (CD) is a chronic relapsing disorder characterized by granulomatous inflammation of the gastrointestinal tract. Although its pathogenesis is complex, we have recently shown that CD patients have a systemic defect in macrophage function, which results in the defective clearance of bacteria from inflammatory sites. METHODOLOGY/PRINCIPAL FINDINGS: Here we have identified a number of additional macrophage defects in CD following diacylglycerol (DAG) homolog phorbol-12-myristate-13-acetate (PMA) activation. We provide evidence for decreased DNA fragmentation, reduced mitochondrial membrane depolarization, impaired reactive oxygen species production, diminished cytochrome c release and increased IL-6 production compared to healthy subjects after PMA exposure. The observed macrophage defects in CD were stimulus-specific, as normal responses were observed following p53 activation and endoplasmic reticulum stress. CONCLUSION: These findings add to a growing body of evidence highlighting disordered macrophage function in CD and, given their pivotal role in orchestrating inflammatory responses, defective apoptosis could potentially contribute to the pathogenesis of CD
Hybrid framework for the simulation of stochastic chemical kinetics
Stochasticity plays a fundamental role in various biochemical processes, such
as cell regulatory networks and enzyme cascades. Isothermal, well-mixed systems
can be modelled as Markov processes, typically simulated using the Gillespie
Stochastic Simulation Algorithm (SSA). While easy to implement and exact, the
computational cost of using the Gillespie SSA to simulate such systems can
become prohibitive as the frequency of reaction events increases. This has
motivated numerous coarse-grained schemes, where the "fast" reactions are
approximated either using Langevin dynamics or deterministically. While such
approaches provide a good approximation when all reactants are abundant, the
approximation breaks down when one or more species exist only in small
concentrations and the fluctuations arising from the discrete nature of the
reactions becomes significant. This is particularly problematic when using such
methods to compute statistics of extinction times for chemical species, as well
as simulating non-equilibrium systems such as cell-cycle models in which a
single species can cycle between abundance and scarcity. In this paper, a
hybrid jump-diffusion model for simulating well- mixed stochastic kinetics is
derived. It acts as a bridge between the Gillespie SSA and the chemical
Langevin equation. For low reactant reactions the underlying behaviour is
purely discrete, while purely diffusive when the concentrations of all species
is large, with the two different behaviours coexisting in the intermediate
region. A bound on the weak error in the classical large volume scaling limit
is obtained, and three different numerical discretizations of the
jump-diffusion model are described. The benefits of such a formalism are
illustrated using computational examples.Comment: 37 pages, 6 figure
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