Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity

Citation: Ruan, X. S., Sack, D. A., & Zhang, W. P. (2015). Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity. Plos One, 10(3), 20. doi:10.1371/journal.pone.0121623Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2): 2439], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTa(A14Q)-dmLT or 3xSTa(N12S)-dmLT [IAI 2014, 82(5): 1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-(toxoid)-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-(toxoid)-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTa(N12S)-dmLT induced broadly protective anti-CFA and antitoxin immunity, suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development

Compressive behavior of luffa sponge material at high strain rate

The strain rate effect of luffa sponge material is an indispensable property for it to be used for acoustic, vibration, and impact energy absorption. Compressive tests at different strain rates on cylindrical column specimens of luffa sponge material were conducted over a wide density ranging from 24 to 64 kg/m3. A photographic technique was applied to measure the section area of the specimen with irregular shape. The mechanical properties of luffa sponge material at various strain rates were obtained based on this measurement. The dynamic data were compared to those of quasi-static experiments. It was found that compressive strength, plateau stress and specific energy absorption of luffa sponge material were sensitive to the rate of loading. Empirical formulae were developed for strength, densification strain and specific energy absorption at various strain rates in the macroscopic level by considering the luffa fiber as base material

Thermal Transport at the Nanoscale: A Fourier\u27s Law vs. Phonon Boltzmann Equation Study

Steady-state thermal transport in nanostructures with dimensions comparable to the phonon mean-free-path is examined. Both the case of contacts at different temperatures with no internal heat generation and contacts at the same temperature with internal heat generation are considered. Fourier’s Law results are compared to finite volume method solutions of the phonon Boltzmann equation in the gray approximation. When the boundary conditions are properly specified, results obtained using Fourier’s Law without modifying the bulk thermal conductivity are in essentially exact quantitative agreement with the phonon Boltzmann equation in the ballistic and diffusive limits. The errors between these two limits are examined in this paper. For the four cases examined, the error in the apparent thermal conductivity as deduced from a correct application of Fourier’s Law is less than 6%. We also find that the Fourier’s Law results presented here are nearly identical to those obtained from a widely used ballistic-diffusive approach, but analytically much simpler. Although limited to steady-state conditions with spatial variations in one dimension and to a gray model of phonon transport, the results show that Fourier’s Law can be used for linear transport from the diffusive to the ballistic limit. The results also contribute to an understanding of how heat transport at the nanoscale can be understood in terms of the conceptual framework that has been established for electron transport at the nanoscale

Inertia effect on buckling-induced auxetic metamaterials

Auxetic metamaterials have enhanced indentation and penetration resistance due to their high shear strength and modulus. Its auxetic performance under dynamic loading cases is an important property for shields and armour applications. In the present study, compressive tests at different impact velocities on buckling-induced auxetic metamaterials were conducted for two different initial geometries. A photographic technique was applied to measure the Poisson's ratio. When the dynamic data were compared with those of quasi-static experiments, it was found that the negative Poisson's ratio for the buckling-induced metamaterial is sensitive to the rate of loading, while the negative Poisson's ratio for the metamaterial with initial auxetic behaviour is insensitive to the loading rate. It was also found that the deformation pattern is similar to that in the quasi-static loading condition when the impact force measured by the test machine is dominated by the inertia force of the metamaterials

Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro

Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis

Nuclear modification at sqrt{s_{NN}}=17.3 GeV, measured at NA49

Transverse momentum spectra up to 4.5 GeV/c were measured around midrapidity in Pb+Pb reactions at sqrt{s_{NN}}=17.3 GeV, for pi^{+/-}, p, pbar and K^{+/-}, by the NA49 experiment. The nuclear modification factors R_{AA}, R_{AA/pA} and R_{CP} were extracted and are compared to RHIC results at sqrt{s_{NN}}=200 GeV. The modification factor R_{AA} shows a rapid increase with transverse momentum in the covered region. The modification factor R_{CP} shows saturation well below unity in the pi^{+/-} channel. The extracted R_{CP} values follow the 200 GeV RHIC results closely in the available transverse momentum range for all particle species. For pi^{+/-} above 2.5 GeV/c transverse momentum, the measured suppression is smaller than that observed at RHIC. The nuclear modification factor R_{AA/pA} for pi^{+/-} stays well below unity.Comment: Proceedings of Quark Matter 2008 conferenc

Petroleum generation timing and source in the Northern Longmen Shan Thrust Belt, Southwest China: Implications for multiple oil generation episodes and sources

The temporal evolution of hydrocarbons (∼500 million bbl) and its relationship to the orogenic events of the Longmen Shan thrust belt have been extensively debated. The hydrocarbons occur as solid bitumen, as dykes and/or coatings within/along faults/fractures, and as present-day oil seeps. Here, utilizing organic geochemistry, we demonstrate that all of the bitumen exhibit similar organo-geochemical characteristics, and were sourced from the upper Neoproterozoic–lower Cambrian Doushantuo and Qiongzhusi Formations. In contrast, the organic geochemistry of the present-day oil seeps are distinct from that of the bitumen, and suggest that the source is the Permian Dalong Formation. Bitumen Re-Os data indicate that the upper Neoproterozoic–lower Cambrian Doushantuo and Qiongzhusi Formations underwent two temporally distinct oil-generation events; initial oil generation occurred during the Late Cambrian/Early Ordovician prior to the Caledonian orogeny, and secondly during the Jurassic (∼165 Ma) coinciding with the Indosinian-Yanshan orogenies. In contrast, the Re-Os data of the present-day oil seeps are too similar to yield a meaningful age, although the source is considered to have undergone hydrocarbon maturation between the Triassic and Jurassic. The temporal hydrocarbon evolution in the Longmen Shan thrust belt also provides an understanding of the hydrocarbon evolution and future exploration of the adjacent petroliferous Sichuan Basin

Prospects of cold dark matter searches with an ultra-low-energy germanium detector

The report describes the research program on the development of ultra-low-energy germanium detectors, with emphasis on WIMP dark matter searches. A threshold of 100 eV is achieved with a 20 g detector array, providing a unique probe to the low-mas WIMP. Present data at a surface laboratory is expected to give rise to comparable sensitivities with the existing limits at the $\rm{5 - 10 GeV}$ WIMP-mass range. The projected parameter space to be probed with a full-scale, kilogram mass-range experiment is presented. Such a detector would also allow the studies of neutrino-nucleus coherent scattering and neutrino magnetic moments.Comment: 3 pages, 4 figures, Proceedings of TAUP-2007 Conferenc