Finite-difference methods for simulation models incorporating non-conservative forces

We discuss algorithms applicable to the numerical solution of second-order ordinary differential equations by finite-differences. We make particular reference to the solution of the dissipative particle dynamics fluid model, and present extensive results comparing one of the algorithms discussed with the standard method of solution. These results show the successful modeling of phase separation and surface tension in a binary immiscible fluid mixture.Comment: 27 pages RevTeX, 9 figures, J. Chem. Phys. (in press

Quantification of neurodegeneration by measurement of brain-specific proteins

Quantification of neurodegeneration in animal models is typically assessed by time-consuming and observer-dependent immunocytochemistry. This study aimed to investigate if newly developed ELISA techniques could provide an observer-independent, cost-effective and time-saving tool for this purpose. Neurofilament heavy chain (NfH(SM135)), astrocytic glial fibrillary acidic protein (GFAP), S100B and ferritin, markers of axonal loss, gliosis, astrocyte activation and microglial activation, respectively, were quantified in the spinal cord homogenates of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE, n=8) and controls (n=7). Levels of GFAP were found to be threefold elevated in CREAE (13 ng/mg protein) when compared to control animals (4.5 ng/mg protein, p<0.001). The inverse was observed for NfH(SM135) (21 ng/mg protein vs. 63 ng/mg protein, p<0.001), ferritin (542 ng/mg protein vs. 858 ng/mg protein, p<0.001) and S100B (786 ng/mg protein vs. 2080 ng/mg protein, N.S.). These findings were confirmed by immunocytochemistry, which demonstrated intense staining for GFAP and decreased staining for NfH(SM135) in CREAE compared to control animals. These findings indicate that axonal loss and gliosis can be estimated biochemically using the newly developed ELISA assays for NfH(SM135) and GFAP. These assays may facilitate the quantification of pathological features involved in neurodegeneration

SILC: a new Planck Internal Linear Combination CMB temperature map using directional wavelets

We present new clean maps of the CMB temperature anisotropies (as measured by Planck) constructed with a novel internal linear combination (ILC) algorithm using directional, scale-discretised wavelets --- Scale-discretised, directional wavelet ILC or SILC. Directional wavelets, when convolved with signals on the sphere, can separate the anisotropic filamentary structures which are characteristic of both the CMB and foregrounds. Extending previous component separation methods, which use the frequency, spatial and harmonic signatures of foregrounds to separate them from the cosmological background signal, SILC can additionally use morphological information in the foregrounds and CMB to better localise the cleaning algorithm. We test the method on Planck data and simulations, demonstrating consistency with existing component separation algorithms, and discuss how to optimise the use of morphological information by varying the number of directional wavelets as a function of spatial scale. We find that combining the use of directional and axisymmetric wavelets depending on scale could yield higher quality CMB temperature maps. Our results set the stage for the application of SILC to polarisation anisotropies through an extension to spin wavelets.Comment: 15 pages, 13 figures. Minor changes to match version published in MNRAS. Map products available at http://www.silc-cmb.or

Spin-SILC: CMB polarisation component separation with spin wavelets

We present Spin-SILC, a new foreground component separation method that accurately extracts the cosmic microwave background (CMB) polarisation $E$ and $B$ modes from raw multifrequency Stokes $Q$ and $U$ measurements of the microwave sky. Spin-SILC is an internal linear combination method that uses spin wavelets to analyse the spin-2 polarisation signal $P = Q + iU$. The wavelets are additionally directional (non-axisymmetric). This allows different morphologies of signals to be separated and therefore the cleaning algorithm is localised using an additional domain of information. The advantage of spin wavelets over standard scalar wavelets is to simultaneously and self-consistently probe scales and directions in the polarisation signal $P = Q + iU$ and in the underlying $E$ and $B$ modes, therefore providing the ability to perform component separation and $E$-$B$ decomposition concurrently for the first time. We test Spin-SILC on full-mission Planck simulations and data and show the capacity to correctly recover the underlying cosmological $E$ and $B$ modes. We also demonstrate a strong consistency of our CMB maps with those derived from existing component separation methods. Spin-SILC can be combined with the pseudo- and pure $E$-$B$ spin wavelet estimators presented in a companion paper to reliably extract the cosmological signal in the presence of complicated sky cuts and noise. Therefore, it will provide a computationally-efficient method to accurately extract the CMB $E$ and $B$ modes for future polarisation experiments.Comment: 13 pages, 9 figures. Minor changes to match version published in MNRAS. Map products available at http://www.silc-cmb.org. Companion paper: arXiv:1605.01414 "Wavelet reconstruction of pure E and B modes for CMB polarisation and cosmic shear analyses" (B. Leistedt et al.

The development of magmatism along the Cameroon Volcanic Line: evidence from seismicity and seismic anisotropy

The Cameroon Volcanic Line (CVL) straddles the continent-ocean boundary in West Africa but exhibits no clear age progression. This renders it difficult to explain by traditional plume/plate motion hypotheses; thus, there remains no consensus on the processes responsible for its development. To understand better the nature of asthenospheric flow beneath the CVL, and the effects of hotspot tectonism on the overlying lithosphere, we analyze mantle seismic anisotropy and seismicity. Cameroon is relatively aseismic compared to hotspots elsewhere, with little evidence for magmatism-related crustal deformation away from Mount Cameroon, which last erupted in 2000. Low crustal Vp/Vs ratios (?1.74) and a lack of evidence for seismically anisotropic aligned melt within the lithosphere both point toward a poorly developed magmatic plumbing system beneath the CVL. Null SKS splitting observations dominate the western continental portion of the CVL; elsewhere, anisotropic fast polarization directions parallel the strike of the Precambrian Central African Shear Zone (CASZ). The nulls may imply that the convecting upper mantle beneath the CVL is isotropic, or characterized by a vertically oriented olivine lattice preferred orientation fabric, perhaps due to a mantle plume or the upward limb of a small-scale convection cell. Precambrian CASZ fossil lithospheric fabrics along the CVL may have been thermomechanically eroded during Gondwana breakup ?130?Ma, with an isotropic lower lithosphere subsequently reforming due to cooling of the slow-moving African plate. Small-scale lithospheric delamination during the 30?Ma recent development of the line may also have contributed to the erosion of the CASZ lithospheric fossil anisotropy, at the same time as generating the low-volume alkaline basaltic volcanism along the CV

Neutrophil extracellular traps in chronic lung disease:implications for pathogenesis and therapy

Neutrophilic inflammation has a key role in the pathophysiology of multiple chronic lung diseases. The formation of neutrophil extracellular traps (NETs) has emerged as a key mechanism of disease in neutrophilic lung diseases including asthma, COPD, cystic fibrosis and, most recently, bronchiectasis. NETs are large, web-like structures composed of DNA and anti-microbial proteins that are able to bind pathogens, prevent microbial dissemination and degrade bacterial virulence factors. The release of excess concentrations of proteases, antimicrobial proteins, DNA and histones, however, also leads to tissue damage, impaired mucociliary clearance, impaired bacterial killing and increased inflammation. A number of studies have linked airway NET formation with greater disease severity, increased exacerbations and overall worse disease outcomes across the spectrum of airway diseases. Treating neutrophilic inflammation has been challenging in chronic lung disease because of the delicate balance between reducing inflammation and increasing the risk of infections through immunosuppression. Novel approaches to suppressing NET formation or the associated inflammation are in development and represent an important therapeutic target. This review will discuss the relationship between NETs and the pathophysiology of cystic fibrosis, asthma, COPD and bronchiectasis, and explore the current and future development of NET-targeting therapies

Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis

BACKGROUND: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. METHODS: In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays. RESULTS: There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL). CONCLUSION: Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta

Inhaled corticosteroids and the lung microbiome in copd

The Global Initiative for Chronic Obstructive Lung Disease 2021 Report recommends inhaled corticosteroid (ICS)-containing regimens as part of pharmacological treatment in patients with chronic obstructive lung disease (COPD) and frequent exacerbations, particularly with eosinophilic inflammation. However, real-world studies reveal overprescription of ICS in COPD, irrespective of disease presentation and inflammatory endotype, leading to increased risk of side effects, mainly respiratory infections. The optimal use of ICS in COPD therefore remains an area of intensive research, and additional biomarkers of benefit and risk are needed. Although the interplay between inflammation and infection in COPD is widely acknowledged, the role of the microbiome in shaping lower airway inflammation has only recently been explored. Next-generation sequencing has revealed that COPD disease progression and exacerbation frequency are associated with changes in the composition of the lung microbiome, and that the immunosuppressive effects of ICS can contribute to potentially deleterious airway microbiota changes by increasing bacterial load and the abundance of potentially pathogenic taxa such as Streptococcus and Haemophilus. Here, we explore the relationship between microbiome, inflammation, ICS use and disease phenotype. This relationship may inform the benefit:risk assessment of ICS use in patients with COPD and lead to more personalised pharmacological management