115 research outputs found
Pressure is not a state function for generic active fluids
Pressure is the mechanical force per unit area that a confined system exerts
on its container. In thermal equilibrium, it depends only on bulk properties
(density, temperature, etc.) through an equation of state. Here we show that in
a wide class of active systems the pressure depends on the precise interactions
between the active particles and the confining walls. In general, therefore,
active fluids have no equation of state, their mechanical pressures exhibit
anomalous properties that defy the familiar thermodynamic reasoning that holds
in equilibrium. The pressure remains a function of state, however, in some
specific and well-studied active models that tacitly restrict the character of
the particle-wall and/or particle-particle interactions.Comment: 8 pages + 9 SI pages, Nature Physics (2015
Continuation for thin film hydrodynamics and related scalar problems
This chapter illustrates how to apply continuation techniques in the analysis
of a particular class of nonlinear kinetic equations that describe the time
evolution through transport equations for a single scalar field like a
densities or interface profiles of various types. We first systematically
introduce these equations as gradient dynamics combining mass-conserving and
nonmass-conserving fluxes followed by a discussion of nonvariational amendmends
and a brief introduction to their analysis by numerical continuation. The
approach is first applied to a number of common examples of variational
equations, namely, Allen-Cahn- and Cahn-Hilliard-type equations including
certain thin-film equations for partially wetting liquids on homogeneous and
heterogeneous substrates as well as Swift-Hohenberg and Phase-Field-Crystal
equations. Second we consider nonvariational examples as the
Kuramoto-Sivashinsky equation, convective Allen-Cahn and Cahn-Hilliard
equations and thin-film equations describing stationary sliding drops and a
transversal front instability in a dip-coating. Through the different examples
we illustrate how to employ the numerical tools provided by the packages
auto07p and pde2path to determine steady, stationary and time-periodic
solutions in one and two dimensions and the resulting bifurcation diagrams. The
incorporation of boundary conditions and integral side conditions is also
discussed as well as problem-specific implementation issues
Scalar <i>Ο</i><sup>4</sup> field theory for active-particle phase separation
Recent theories predict phase separation among orientationally disordered
active particles whose propulsion speed decreases rapidly enough with density.
Coarse-grained models of this process show time-reversal symmetry (detailed
balance) to be restored for uniform states, but broken by gradient terms; hence
detailed-balance violation is strongly coupled to interfacial phenomena. To
explore the subtle generic physics resulting from such coupling we here
introduce `Active Model B'. This is a scalar field theory (or
phase-field model) that minimally violates detailed balance via a leading-order
square-gradient term. We find that this additional term has modest effects on
coarsening dynamics, but alters the static phase diagram by creating a jump in
(thermodynamic) pressure across flat interfaces. Both results are surprising,
since interfacial phenomena are always strongly implicated in coarsening
dynamics but are, in detailed-balance systems, irrelevant for phase equilibria.Comment: 15 pages, 7 figure
Chronic Respiratory Aeroallergen Exposure in Mice Induces Epithelial-Mesenchymal Transition in the Large Airways
Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM) extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-Ξ²1) levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (Ξ±-SMA) and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease
Review of Community Pharmacy Staff Educational Needs for Supporting Mental Health Consumers and Carers
Development of a mental health education package for community pharmacy staff should be informed by mental health consumers/carersβ needs, expectations and experiences, and staff knowledge, skills and attitudes. This review (1) explored research on community pharmacy practice and service provision for mental health consumers/carers, and (2) identified validated methods for assessing staff knowledge, skills and attitudes about mental illness to inform the development of a training questionnaire. A literature scan using key words knowledge, skills, attitudes, and beliefs combined with community pharmacy, pharmacist, and pharmacy support staff, and mental illness, depression, anxiety was conducted. A small number of studies were found that used reliable methods to assess pharmacistsβ training needs regarding mental illness and treatment options. There was little published specifically in relation to depression and anxiety in community pharmacy practice. No studies assessed the training needs of pharmacy support staff. A systematic analysis of pharmacy staff learning needs is warranted
An intranasal selective antisense oligonucleotide impairs lung cyclooxygenase-2 production and improves inflammation, but worsens airway function, in house dust mite sensitive mice
<p>Abstract</p> <p>Background</p> <p>Despite its reported pro-inflammatory activity, cyclooxygenase (COX)-2 has been proposed to play a protective role in asthma. Accordingly, COX-2 might be down-regulated in the airway cells of asthmatics. This, together with results of experiments to assess the impact of COX-2 blockade in ovalbumin (OVA)-sensitized mice in vivo, led us to propose a novel experimental approach using house dust mite (HDM)-sensitized mice in which we mimicked altered regulation of COX-2.</p> <p>Methods</p> <p>Allergic inflammation was induced in BALBc mice by intranasal exposure to HDM for 10 consecutive days. This model reproduces spontaneous exposure to aeroallergens by asthmatic patients. In order to impair, but not fully block, COX-2 production in the airways, some of the animals received an intranasal antisense oligonucleotide. Lung COX-2 expression and activity were measured along with bronchovascular inflammation, airway reactivity, and prostaglandin production.</p> <p>Results</p> <p>We observed impaired COX-2 mRNA and protein expression in the lung tissue of selective oligonucleotide-treated sensitized mice. This was accompanied by diminished production of mPGE synthase and PGE<sub>2 </sub>in the airways. In sensitized mice, the oligonucleotide induced increased airway hyperreactivity (AHR) to methacholine, but a substantially reduced bronchovascular inflammation. Finally, mRNA levels of hPGD synthase remained unchanged.</p> <p>Conclusion</p> <p>Intranasal antisense therapy against COX-2 in vivo mimicked the reported impairment of COX-2 regulation in the airway cells of asthmatic patients. This strategy revealed an unexpected novel dual effect: inflammation was improved but AHR worsened. This approach will provide insights into the differential regulation of inflammation and lung function in asthma, and will help identify pharmacological targets within the COX-2/PG system.</p
Budesonide and Formoterol Reduce Early Innate Anti-Viral Immune Responses In Vitro
Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC) from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16) in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10β6 M) when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNΞ± and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2β², 5β² oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits viral clearance in vivo remains to be determined
Allergen Uptake, Activation, and IL-23 Production by Pulmonary Myeloid DCs Drives Airway Hyperresponsiveness in Asthma-Susceptible Mice
Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs βpro-asthmaticβ, and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs) to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness
Painting with light-powered bacteria
External control of the swimming speed of `active particles' can be used to
self assemble designer structures in situ on the micrometer to millimeter
scale. We demonstrate such reconfigurable templated active self assembly in a
fluid environment using light powered strains of Escherichia coli. The physics
and biology controlling the sharpness and formation speed of patterns is
investigated using a bespoke fast-responding strain.Comment: 19 pages, 11 figure
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