Immunogenicity of a truncated enterovirus 71 VP1 protein fused to a Newcastle disease virus nucleocapsid protein fragment in mice.

Enterovirus 71 (EV71) is one of the viruses that cause hand, foot and mouth disease. Its viral capsid protein 1 (VP1), which contains many neutralization epitopes, is an ideal target for vaccine development. Recently, we reported the induction of a strong immune response in rabbits to a truncated VP1 fragment (Nt-VP1t) displayed on a recombinant Newcastle disease virus (NDV) capsid protein. Protective efficacy of this vaccine, however, can only be tested in mice, since all EV71 animal models thus far were developed in mouse systems. In this study, we evaluated the type of immune responses against the protein developed by adult BALB/c mice. Nt-VP1t protein induced high levels of VP1 IgG antibody production in mice. Purified VP1 antigen stimulated activation, proliferation and differentiation of splenocytes harvested from these mice. They also produced significant levels of IFN-γ, a Th1-related cytokine. Taken together, Nt-VP1t protein is a potent immunogen in adult mice and our findings provide the data needed for testing of its protective efficacy in mouse models of EV71 infections

Detection of pathological myopia by PAMELA with texture-based features through an SVM approach

10.1260/2040-2295.1.1.1Journal of Healthcare Engineering111-1

Fine particulate matter in the tropical environment: monsoonal effects, source apportionment, and health risk assessment

The health implications of PM2:5 in the tropical region of Southeast Asia (SEA) are significant as PM2:5 can pose serious health concerns. PM2:5 concentration and sources here are strongly influenced by changes in the monsoon regime from the south-west quadrant to the north-east quadrant in the region. In this work, PM2:5 samples were collected at a semi-urban area using a high-volume air sampler at different seasons on 24 h basis. Analysis of trace elements and water-soluble ions was performed using inductively coupled plasma mass spectroscopy (ICP-MS) and ion chromatography (IC), respectively. Apportionment analysis of PM2:5 was carried out using the United States Environmental Protection Agency (US EPA) positive matrix factorization (PMF) 5.0 and a mass closure model. We quantitatively characterized the health risks posed to human populations through the inhalation of selected heavy metals in PM2:5. 48% of the samples collected exceeded the World Health Organization (WHO) 24 h PM2:5 guideline but only 19% of the samples exceeded 24 h US EPA National Ambient Air Quality Standard (NAAQS). The PM2:5 concentration was slightly higher during the north-east monsoon compared to south-west monsoon. The main trace metals identified were As, Pb, Cd, Ni, Mn, V, and Cr while the main ions were SO

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

Analysis of Density Changes in Plutonium Observed from Accelerated Aging Using Pu-238 Enrichment

We present dimensional and density changes in an aging plutonium alloy enriched with 7.3 at.% of {sup 238}Pu and reference alloys of various ages. After 45 equivalent years of aging, the enriched alloys at 35 C have swelled in volume by 0.14 to 0.16% and now exhibit a near linear volume increase, without void swelling. Based on X-ray diffraction measurements, the lattice expansion by self-irradiation appears to be the primary cause for dimensional changes during the initial 2-3 years of aging. Following the initial transient, the density change is primarily cause by a constant helium in-growth rate as a result of {alpha}-particle decay

Incidence, presenting features, and diagnosis of cicatrising conjunctivitis in the United Kingdom

Cicatrising conjunctival disorders are uncommon, and are difficult to diagnose and manage. This study was designed to assess the annual incidence and underlying diagnosis of patients with cicatrising conjunctivitis (CC) within the United Kingdom

The Corrosion Resistance of Fe-Based Amorphous Metals: Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4 and Other Compositions

Several Fe-based amorphous metals were developed with good corrosion resistance. These materials have been produced as melt-spun ribbons, ingots, and thermal-spray coatings. Cyclic polarization has been conducted in several aggressive environments, at ambient temperature, as well as temperatures approaching the boiling points of the test solutions. The hypothesis that the corrosion resistance of iron-based amorphous metals can be enhanced through application of heuristic principles related to the additions of chromium, molybdenum, tungsten has been tested and found to have merit. Chromium (Cr), molybdenum (Mo) and tungsten (W) provide corrosion resistance; boron (B) enables glass formation; and rare earths such as yttrium (Y) lower critical cooling rate (CCR). The high boron content of this particular amorphous metal makes this amorphous alloy an effective neutron absorber, and suitable for criticality control applications. In general, the corrosion resistance of such iron-based amorphous metals is maintained at operating temperatures up to the glass transition temperature

Corrosion Resistances of Iron-Based Amorphous Metals with Yttrium and Tungsten Additions in Hot Calcium Chloride Brine & Natural Seawater: Fe48Mo14Cr15Y2C15B6 and W-Containing Variants

Yttrium-containing SAM1651 (Fe{sub 48.0}Cr{sub 15.0}Mo{sub 14.0}B{sub 6.0}C{sub 15.0}Y{sub 2.0}), has a critical cooling rate (CCR) of approximately 80 Kelvin per second, while SAM2X5 (Fe{sub 49.7}Cr{sub 17.7}Mn{sub 1.9}Mo{sub 7.4}W{sub 1.6}B{sub 15.2}C{sub 3.8}Si{sub 2.4}) with no yttrium has a higher critical cooling rate of approximately 600 Kelvin per second. SAM1651's low CCR enables it to be rendered as a completely amorphous material in practical materials processes. Chromium (Cr), molybdenum (Mo) and tungsten (W) provide corrosion resistance; boron (B) enables glass formation; and rare earths such as yttrium (Y) lower critical cooling rate (CCR). The passive film stability of these Fe-based amorphous metal formulations have been found to be superior to that of conventional stainless steels, and comparable to that of Ni-based alloys, based on electrochemical measurements of the passive film breakdown potential and general corrosion rates

Genetic Variants on Chromosome 1q41 Influence Ocular Axial Length and High Myopia

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = −0.16 mm per minor allele, Pmeta = 2.69×10−10). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68–0.84, Pmeta = 4.38×10−7) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia

Turbophoresis in forced inhomogeneous turbulence

We show, by direct numerical simulations, that heavy inertial particles (characterized by Stokes number St) in inhomogeneously forced statistically stationary isothermal turbulent flows cluster at the minima of mean-square turbulent velocity. Two turbulent transport processes, turbophoresis and turbulent diffusion together determine the spatial distribution of the particles. If the turbulent diffusivity is assumed to scale with turbulent root-mean-square velocity, as is the case for homogeneous turbulence, the turbophoretic coefficient can be calculated. Indeed, for the above assumption, the non-dimensional product of the turbophoretic coefficient and the rms velocity is shown to increase with St for small St, reach a maxima for St ≈ 10 and decrease as ∼ St - 0. 33 for large St. © 2018, The Author(s).publishedVersio