377 research outputs found
Localized states in strong magnetic field: resonant scattering and the Dicke effect
We study the energy spectrum of a system of localized states coupled to a 2D
electron gas in strong magnetic field. If the energy levels of localized states
are close to the electron energy in the plane, the system exhibits a kind of
collective behavior analogous to the Dicke effect in optics. The latter
manifests itself in ``trapping'' of electronic states by localized states. At
the same time, the electronic density of states develops a gap near the
resonance. The gap and the trapping of states appear to be complementary and
reflect an intimate relation between the resonant scattering and the Dicke
effect. We reveal this relation by presenting the exact solution of the problem
for the lowest Landau level. In particular, we show that in the absence of
disorder the system undergoes a phase transition at some critical concentration
of localized states.Comment: 28 pages + 9 fig
Broad-Spectrum Antiviral Therapeutics
Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.National Institute of Allergy and Infectious Diseases (U.S.) (grant AI057159)New England Regional Center of Excellence for Biodefense and Emerging Infectious DiseasesUnited States. Dept. of Defense (Director of Defense Research & Engineering)United States. Defense Threat Reduction AgencyUnited States. Defense Advanced Research Projects Agenc
Active Brownian Particles. From Individual to Collective Stochastic Dynamics
We review theoretical models of individual motility as well as collective
dynamics and pattern formation of active particles. We focus on simple models
of active dynamics with a particular emphasis on nonlinear and stochastic
dynamics of such self-propelled entities in the framework of statistical
mechanics. Examples of such active units in complex physico-chemical and
biological systems are chemically powered nano-rods, localized patterns in
reaction-diffusion system, motile cells or macroscopic animals. Based on the
description of individual motion of point-like active particles by stochastic
differential equations, we discuss different velocity-dependent friction
functions, the impact of various types of fluctuations and calculate
characteristic observables such as stationary velocity distributions or
diffusion coefficients. Finally, we consider not only the free and confined
individual active dynamics but also different types of interaction between
active particles. The resulting collective dynamical behavior of large
assemblies and aggregates of active units is discussed and an overview over
some recent results on spatiotemporal pattern formation in such systems is
given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte
Quantum dynamics in strong fluctuating fields
A large number of multifaceted quantum transport processes in molecular
systems and physical nanosystems can be treated in terms of quantum relaxation
processes which couple to one or several fluctuating environments. A thermal
equilibrium environment can conveniently be modelled by a thermal bath of
harmonic oscillators. An archetype situation provides a two-state dissipative
quantum dynamics, commonly known under the label of a spin-boson dynamics. An
interesting and nontrivial physical situation emerges, however, when the
quantum dynamics evolves far away from thermal equilibrium. This occurs, for
example, when a charge transferring medium possesses nonequilibrium degrees of
freedom, or when a strong time-dependent control field is applied externally.
Accordingly, certain parameters of underlying quantum subsystem acquire
stochastic character. Herein, we review the general theoretical framework which
is based on the method of projector operators, yielding the quantum master
equations for systems that are exposed to strong external fields. This allows
one to investigate on a common basis the influence of nonequilibrium
fluctuations and periodic electrical fields on quantum transport processes.
Most importantly, such strong fluctuating fields induce a whole variety of
nonlinear and nonequilibrium phenomena. A characteristic feature of such
dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres
Experimentally Guided Computational Model Discovers Important Elements for Social Behavior in Myxobacteria
Identifying essential factors in cellular interactions and organized movement of cells is important in predicting behavioral phenotypes exhibited by many bacterial cells. We chose to study Myxococcus xanthus, a soil bacterium whose individual cell behavior changes while in groups, leading to spontaneous formation of aggregation center during the early stage of fruiting body development. In this paper, we develop a cell-based computational model that solely relies on experimentally determined parameters to investigate minimal elements required to produce the observed social behaviors in M. xanthus. The model verifies previously known essential parameters and identifies one novel parameter, the active turning, which we define as the ability and tendency of a cell to turn to a certain angle without the presence of any obvious external factors. The simulation is able to produce both gliding pattern and spontaneous aggregation center formation as observed in experiments. The model is tested against several known M. xanthus mutants and our modification of parameter values relevant for the individual mutants produces good phenotypic agreements. This outcome indicates the strong predictive potential of our model for the social behaviors of uncharacterized mutants and their expected phenotypes during development
A systematic review and meta-analysis of haematological malignancies in residents living near petrochemical facilities
Background
The petrochemical industry is a major source of hazardous and toxic air pollutants that are recognised to have mutagenic and carcinogenic properties. A wealth of occupational epidemiology literature exists around the petrochemical industry, with adverse haematological effects identified in employees exposed to ‘low’ concentrations of aromatic hydrocarbons (benzene, toluene, ethylbenzene, and xylene). Releases from the petrochemical industry are also thought to increase the risk of cancer incidence in fenceline communities. However, this emerging and at times inconclusive evidence base remains fragmented. The present study’s aim was to conduct a systematic review and meta-analysis of epidemiological studies investigating the association between incidences of haematological malignancy and residential exposure to the petrochemical industry.
Methods
Epidemiological studies reporting the risk of haematological malignancies (Leukaemia, Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, and Multiple myeloma) were included where the following criteria were met: (i) Cancer incidence is diagnosed by a medical professional and coded in accordance to the International Classification of Diseases; (ii) A clear definition of fenceline communities is provided, indicating the proximity between exposed residents and petrochemical activities; and (iii) Exposure is representative of normal operating conditions, not emergency events. Two investigators independently extracted information on study characteristics and outcomes in accordance with PRISMA and MOOSE guidelines. Relative risks and their 95% confidence intervals were pooled across studies for the four categories of haematological malignancy, using a random effects meta-analysis.
Results
The systematic review identified 16 unique studies, which collectively record the incidence of haematological malignancies across 187,585 residents living close to a petrochemical operation. Residents from fenceline communities, less than 5 km from a petrochemical facility (refinery or manufacturer of commercial chemicals), had a 30% higher risk of developing Leukaemia than residents from communities with no petrochemical activity. Meanwhile, the association between exposure and rarer forms of haematological malignancy remains uncertain, with further research required.
Conclusions
The risk of developing Leukaemia appears higher in individuals living near a petrochemical facility. This highlights the need for further policy to regulate the release of carcinogens by industry
Boundary-layer turbulence as a kangaroo process
A nonlocal mixing-length theory of turbulence transport by finite size eddies is developed by means of a novel evaluation of the Reynolds stress. The analysis involves the contruct of a sample path space and a stochastic closure hypothesis. The simplifying property of exhange (strong eddies) is satisfied by an analytical sampling rate model. A nonlinear scaling relation maps the path space onto the semi-infinite boundary layer. The underlying near-wall behavior of fluctuating velocities perfectly agrees with recent direct numerical simulations. The resulting integro-differential equation for the mixing of scalar densities represents fully developed boundary-layer turbulence as a nondiffusive (Kubo-Anderson or kangaroo) type of stochastic process. The model involves a scaling exponent (with → in the diffusion limit). For the (partly analytical) solution for the mean velocity profile, excellent agreement with the experimental data yields 0.58. © 1995 The American Physical Society
The Coxiella burnetii Dot/Icm System Delivers a Unique Repertoire of Type IV Effectors into Host Cells and Is Required for Intracellular Replication
Coxiella burnetii, the causative agent of human Q fever, is an intracellular pathogen that replicates in an acidified vacuole derived from the host lysosomal network. This pathogen encodes a Dot/Icm type IV secretion system that delivers bacterial proteins called effectors to the host cytosol. To identify new effector proteins, the functionally analogous Legionella pneumophila Dot/Icm system was used in a genetic screen to identify fragments of C. burnetii genomic DNA that when fused to an adenylate cyclase reporter were capable of directing Dot/Icm-dependent translocation of the fusion protein into mammalian host cells. This screen identified Dot/Icm effectors that were proteins unique to C. burnetii, having no overall sequence homology with L. pneumophila Dot/Icm effectors. A comparison of C. burnetii genome sequences from different isolates revealed diversity in the size and distribution of the genes encoding many of these effectors. Studies examining the localization and function of effectors in eukaryotic cells provided evidence that several of these proteins have an affinity for specific host organelles and can disrupt cellular functions. The identification of a transposon insertion mutation that disrupts the dot/icm locus was used to validate that this apparatus was essential for translocation of effectors. Importantly, this C. burnetii Dot/Icm-deficient mutant was found to be defective for intracellular replication. Thus, these data indicate that C. burnetii encodes a unique subset of bacterial effector proteins translocated into host cells by the Dot/Icm apparatus, and that the cumulative activities exerted by these effectors enables C. burnetii to successfully establish a niche inside mammalian cells that supports intracellular replication
Somatic Variants in SVIL in Cerebral Aneurysms
Publisher Copyright: © American Academy of Neurology.Background and ObjectivesWhile somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.MethodsWe performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.ResultsSomatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway.DiscussionWe propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.Peer reviewe
- …