Characterising small solutions in delay differential equations through numerical approximations

This paper discusses how the existence of small solutions for delay differential equations can be predicted from the behaviour of the spectrum of the finite dimensional approximations.Manchester Centre for Computational Mathematic

The Formation, Structure, and Stability of a Shear Layer in a Fluid with Temperature-Dependent Viscosity

The presence of viscosity normally has a stabilizing effect on the flow of a fluid. However, experiments show that the flow of a fluid might form shear bands or shear layers, narrow bands in which the velocity of the fluid changes sharply. In general, adiabatic shear layers are observed not only in fluids but also in thermo-plastic materials subject to shear at a high-strain rate and in combustion. Therefore there is widespread interest in modeling the formation of shear layers. In this paper we investigate the basic system of conservation laws for a one-dimensional flow with temperature-dependent viscosity using a combination of analytical and numerical tools. We present results to substantiate the claim that the formation of shear layers is due to teh fact that viscosity decreases sufficiently quickly as temperature increases and analyze the structure and stability properties of the layers

The numerical solution of forward–backward differential equations: Decomposition and related issues

NOTICE: this is the author’s version of a work that was accepted for publication in Journal of computational and applied mathematics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of computational and applied mathematics, 234,(2010), doi: 10.1016/j.cam.2010.01.039This journal article discusses the decomposition, by numerical methods, of solutions to mixed-type functional differential equations (MFDEs) into sums of “forward” solutions and “backward” solutions

Analysis of Shear Layers in a Fluid with Temperature-Dependent Viscosity

The presence of viscosity normally has a stabilizing effect on the flow of a fluid. Howerver, experiments show that the flow of a fluid in which viscosity decreases as temperature increases tends to form shear layers, narrow regions in which the velocity of the fluid changes sharply. In general, adiabatic shear layers are observed not only in fluids but also in thermo-plastic materials subject to shear at a high-strain rate and in combustion and there is widespread interest in modeling their formation. In this paper, we investigate a well-known model representing a basic system of conservation laws for a one-dimensional flow with temperature-dependent viscosity using a combination of analytical and numerical tools. We present results to substantiate the claim that the formation of shear layers can only occur in solutions of the model when the viscosity decreases sufficiently quickly as temperature increases and we further analyze the structure and stability properties of the layers

Interferon-stimulated gene (ISG)-expression screening reveals the specific antibunyaviral activity of ISG20

Bunyaviruses pose a significant threat to human health, prosperity and food security. In response to viral infections, interferons (IFNs) upregulate the expression of hundreds of interferon stimulated genes (ISGs) whose cumulative action can potently inhibit the replication of bunyaviruses. We used a flow cytometry-based method to screen the ability of ∼500 unique ISGs from humans and rhesus macaques to inhibit the replication of Bunyamwera orthobunyavirus (BUNV), the prototype of both the Peribunyaviridae family and Bunyavirales order. Candidates possessing antibunyaviral activity were further examined using a panel of divergent bunyaviruses. Interestingly, one candidate, ISG20, exhibited potent antibunyaviral activity against most viruses examined from the Peribunyaviridae, Hantaviridae and Nairoviridae families, whereas phleboviruses (Phenuiviridae) largely escaped inhibition. Similar to other viruses known to be targeted by ISG20, the antibunyaviral activity of ISG20 is dependent upon its functional ribonuclease activity. Through use of an infectious VLP assay (based on the BUNV minigenome system), we confirmed that gene expression from all 3 viral segments is strongly inhibited by ISG20. Using in vitro evolution, we generated a substantially ISG20-resistant BUNV and mapped the determinants of ISG20 sensitivity/resistance. Taken together, we report that ISG20 is a broad and potent antibunyaviral factor yet some bunyaviruses are remarkably ISG20 resistant. Thus, ISG20 sensitivity/resistance could influence the pathogenesis of bunyaviruses, many of which are emerging viruses of clinical or veterinary significance

Viral markers of hepatitis B, C and D and HB vaccination status of a health care team in a rural district of Cameroon

UNLABELLED: Ninety-three health care workers (HCW) in the Tokombere sahelian district volunteered to participate in a trial to investigate viral markers of hepatitis B, C, and D and HB vaccination status. METHODS: . Sera were tested using the Vikia HBsAg kit followed by CMIA for detection of HBsAg, anti-HBs, anti-HBc, and anti-HCV. HBsAg-positive HCW were tested for HBV-DNA, anti-HDV, and, if positive for anti-HDV, HDV-RNA.RESULTS: Analysis of anti-HBc positivity indicated that 91% of HCW had been infected by HBV, regardless of vaccination history. Vikia HBsAg results were confirmed by chemiluminescent microparticle immunoassay (CMIA) in all HCW and were positive in 17 HCW with virus load >2000 IU/mL in 6 and HDV co-infection in 6. Anti-HCV was found in 6 HCW. Among the 55 HCW that had not been vaccinated, only 3 needed vaccination because of anti-HBc negativity. Among HCW considered for HBV treatment, one patient presenting HBV/HDV co-infection was excluded after diagnosis of hepatocarcinoma. CONCLUSION: Systematic HB vaccination of new HCW appears unnecessary in this rural region of Africa. Anti-HBc screening is cost-effective for identifying HCW requiring vaccination. Vikia HBsAg is effective for point-of-care screening. We underline the need for universal early (preferably neonatal) HB vaccination and for availability of anti-HBV drug in limited-resource countries

Willin/FRMD6 influences mechanical phenotype and neuronal differentiation in mammalian cells by regulating ERK1/2 activity

This research was financially supported by an Engineering and Physical Sciences Research Council (EPSRC) Programme Grant (EP/P030017/1) and by the Biotechnology and Biological Sciences Research Council (BBSRC) Tools and Resources Development Fund (BB/P027148/1).Willin/FRMD6 is part of a family of proteins with a 4.1 ezrin-radixin-moesin (FERM) domain. It has been identified as an upstream activator of the Hippo pathway and, when aberrant in its expression, is associated with human diseases and disorders. Even though Willin/FRMD6 was originally discovered in the rat sciatic nerve, most studies have focused on its functional roles in cells outside of the nervous system, where Willin/FRMD6 is involved in the formation of apical junctional cell-cell complexes and in regulating cell migration. Here, we investigate the biochemical and biophysical role of Willin/FRMD6 in neuronal cells, employing the commonly used SH-SY5Y neuronal model cell system and combining biochemical measurements with Elastic Resonator Interference Stress Micropscopy (ERISM). We present the first direct evidence that Willin/FRMD6 expression influences both the cell mechanical phenotype and neuronal differentiation. By investigating cells with increased and decreased Willin/FRMD6 expression levels, we show that Willin/FRMD6 not only affects proliferation and migration capacity of cells but also leads to changes in cell morphology and an enhanced formation of neurite-like membrane extensions. These changes were accompanied by alterations of biophysical parameters such as cell force, the organization of actin stress fibers and the formation of focal adhesions. At the biochemical level, changes in Willin/FRMD6 expression inversely affected the activity of the extracellular signal-regulated kinases (ERK) pathway and downstream transcriptional factor NeuroD1, which seems to prime SH-SY5Y cells for retinoic acid (RA)-induced neuronal differentiation.Publisher PDFPeer reviewe

Improved fibrosis staging by elastometry and blood test in chronic hepatitis C.

AIMS: Our main objective was to improve non-invasive fibrosis staging accuracy by resolving the limits of previous methods via new test combinations. Our secondary objectives were to improve staging precision, by developing a detailed fibrosis classification, and reliability (personalized accuracy) determination. METHODS: All patients (729) included in the derivation population had chronic hepatitis C, liver biopsy, 6 blood tests and Fibroscan. Validation populations included 1584 patients. RESULTS: The most accurate combination was provided by using most markers of FibroMeter and Fibroscan results targeted for significant fibrosis, i.e. \u27E-FibroMeter\u27. Its classification accuracy (91.7%) and precision (assessed by F difference with Metavir: 0.62 ± 0.57) were better than those of FibroMeter (84.1%, P < 0.001; 0.72 ± 0.57, P < 0.001), Fibroscan (88.2%, P = 0.011; 0.68 ± 0.57, P = 0.020), and a previous CSF-SF classification of FibroMeter + Fibroscan (86.7%, P < 0.001; 0.65 ± 0.57, P = 0.044). The accuracy for fibrosis absence (F0) was increased, e.g. from 16.0% with Fibroscan to 75.0% with E-FibroMeter (P < 0.001). Cirrhosis sensitivity was improved, e.g. E-FibroMeter: 92.7% vs. Fibroscan: 83.3%, P = 0.004. The combination improved reliability by deleting unreliable results (accuracy <50%) observed with a single test (1.2% of patients) and increasing optimal reliability (accuracy ≥85%) from 80.4% of patients with Fibroscan (accuracy: 90.9%) to 94.2% of patients with E-FibroMeter (accuracy: 92.9%), P < 0.001. The patient rate with 100% predictive values for cirrhosis by the best combination was twice (36.2%) that of the best single test (FibroMeter: 16.2%, P < 0.001). CONCLUSION: The new test combination increased: accuracy, globally and especially in patients without fibrosis, staging precision, cirrhosis prediction, and even reliability, thus offering improved fibrosis staging