Engineering the vaccinia virus L1 protein for increased neutralizing antibody response after DNA immunization

<p>Abstract</p> <p>Background</p> <p>The licensed smallpox vaccine, comprised of infectious vaccinia virus, has associated adverse effects, particularly for immunocompromised individuals. Therefore, safer DNA and protein vaccines are being investigated. The L1 protein, a component of the mature virion membrane that is conserved in all sequenced poxviruses, is required for vaccinia virus entry into host cells and is a target for neutralizing antibody. When expressed by vaccinia virus, the unglycosylated, myristoylated L1 protein attaches to the viral membrane via a C-terminal transmembrane anchor without traversing the secretory pathway. The purpose of the present study was to investigate modifications of the gene expressing the L1 protein that would increase immunogenicity in mice when delivered by a gene gun.</p> <p>Results</p> <p>The L1 gene was codon modified for optimal expression in mammalian cells and potential N-glycosylation sites removed. Addition of a signal sequence to the N-terminus of L1 increased cell surface expression as shown by confocal microscopy and flow cytometry of transfected cells. Removal of the transmembrane domain led to secretion of L1 into the medium. Induction of binding and neutralizing antibodies in mice was enhanced by gene gun delivery of L1 containing the signal sequence with or without the transmembrane domain. Each L1 construct partially protected mice against weight loss caused by intranasal administration of vaccinia virus.</p> <p>Conclusion</p> <p>Modifications of the vaccinia virus L1 gene including codon optimization and addition of a signal sequence with or without deletion of the transmembrane domain can enhance the neutralizing antibody response of a DNA vaccine.</p

Classical and Quantum Cosmology of Multigravity

Recently, a multigraviton theory on a simple closed circuit graph corresponding to the discretization of $S^1$ compactification of the Kaluza-Klein (KK) theory has been considered. In the present paper, we extend this theory to that on a general graph and study what modes of particles are included. Furthermore, we generalize it in a possible nonlinear theory based on the vierbein formalism and study classical and quantum cosmological solutions in the theory. We found that scale factors in a solution for this theory repeat acceleration and deceleration.Comment: 17 pages, 15 figures, RevTeX4.1, revised versio

Virtual Adversarial Ladder Networks For Semi-supervised Learning

Semi-supervised learning (SSL) partially circumvents the high cost of labeling data by augmenting a small labeled dataset with a large and relatively cheap unlabeled dataset drawn from the same distribution. This paper offers a novel interpretation of two deep learning-based SSL approaches, ladder networks and virtual adversarial training (VAT), as applying distributional smoothing to their respective latent spaces. We propose a class of models that fuse these approaches. We achieve near-supervised accuracy with high consistency on the MNIST dataset using just 5 labels per class: our best model, ladder with layer-wise virtual adversarial noise (LVAN-LW), achieves 1.42%±0.12 average error rate on the MNIST test set, in comparison with 1.62%±0.65 reported for the ladder network. On adversarial examples generated with L2-normalized fast gradient method, LVAN-LW trained with 5 examples per class achieves average error rate 2.4%±0.3 compared to 68.6%±6.5 for the ladder network and 9.9%±7.5 for VAT

High correlation of scotopic and photopic electroretinogram components with severity of central retinal artery occlusion

Celso S Matsumoto1,2, Kei Shinoda1, Kazuo Nakatsuka21Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, Faculty of Medicine, Oita University, Oita, JapanPurpose: The aim of this study was to determine whether a significant correlation exists between the scotopic and photopic components of electroretinograms (ERGs) and the degree of circulation disturbances caused by a central retinal artery occlusion (CRAO).Design: Observational clinical study.Participants: Sixteen patients with a CRAO (16 eyes).Methods: The circulatory disturbance in eyes with CRAO was graded as mild (group 1) when the arm-to-retina transmission time was &amp;lt;30 sec and severe (group 2) when the arm-to-retina transmission time was &amp;ge;30 sec. Scotopic and photopic ERG components in eyes with CRAO were compared with those in healthy fellow eyes with respect to the degree of circulation disturbance.Results: The scotopic and photopic b-waves were significantly reduced only in group 2, whereas the amplitudes of the photopic negative response (PhNR) of the photopic cone ERGs were significantly reduced in both groups. The amplitudes of each ERG component, except for the a-wave of the mixed rod-cone ERG, were significantly smaller in group 2 than in group 1.Conclusions: The PhNR was reduced even in group 1 with minimal circulatory disturbance and thus may be a good functional indicator.Keywords: scotopic electroretinogram, photopic electroretinogram, photopic negative response, central retinal artery occlusion, fluorescein angiograph

Ocean temperature and salinity components of the Madden-Julian oscillation observed by Argo floats

New diagnostics of the Madden-Julian Oscillation (MJO) cycle in ocean temperature and, for the first time, salinity are presented. The MJO composites are based on 4 years of gridded Argo float data from 2003 to 2006, and extend from the surface to 1,400 m depth in the tropical Indian and Pacific Oceans. The MJO surface salinity anomalies are consistent with precipitation minus evaporation fluxes in the Indian Ocean, and with anomalous zonal advection in the Pacific. The Argo sea surface temperature and thermocline depth anomalies are consistent with previous studies using other data sets. The near-surface density changes due to salinity are comparable to, and partially offset, those due to temperature, emphasising the importance of including salinity as well as temperature changes in mixed-layer modelling of tropical intraseasonal processes. The MJO-forced equatorial Kelvin wave that propagates along the thermocline in the Pacific extends down into the deep ocean, to at least 1,400 m. Coherent, statistically significant, MJO temperature and salinity anomalies are also present in the deep Indian Ocean

Percolation on the average and spontaneous magnetization for q-states Potts model on graph

We prove that the q-states Potts model on graph is spontaneously magnetized at finite temperature if and only if the graph presents percolation on the average. Percolation on the average is a combinatorial problem defined by averaging over all the sites of the graph the probability of belonging to a cluster of a given size. In the paper we obtain an inequality between this average probability and the average magnetization, which is a typical extensive function describing the thermodynamic behaviour of the model

Recent Results on the Anomalous X-ray Pulsars

The ''Anomalous X-ray Pulsars'' (AXPs) are a small group of X-ray pulsars characterized by periods in the 5-10 s range and by the absence of massive companion stars. There are now 7 possible members of this class of objects. We review recent observational results on their X-ray spectra, spin period evolution, and searches for orbital motion and discuss the implications for possible models.Comment: 4 pages, 1 figures. To appear in The Active X-ray Sky: Results from BeppoSAX and Rossi-XTE, Nuclear Physics B Proceedings Supplements, L. Scarsi, H. Bradt, P. Giommi and F. Fiore (eds.), Elsevier Science B.

Thermal stress induces glycolytic beige fat formation via a myogenic state.

Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival

Measurement of forward photon production cross-section in proton-proton collisions at s\sqrt{s} = 13 TeV with the LHCf detector

In this paper, we report the production cross-section of forward photons in the pseudorapidity regions of $\eta\,>\,10.94$ and $8.99\,>\,\eta\,>\,8.81$, measured by the LHCf experiment with proton--proton collisions at $\sqrt{s}$ = 13 TeV. The results from the analysis of 0.191 $\mathrm{nb^{-1}}$ of data obtained in June 2015 are compared to the predictions of several hadronic interaction models that are used in air-shower simulations for ultra-high-energy cosmic rays. Although none of the models agree perfectly with the data, EPOS-LHC shows the best agreement with the experimental data among the models.Comment: 21 pages, 4 figure

Measurement of the cosmic-ray antiproton spectrum at solar minimum with a long-duration balloon flight over Antarctica

The energy spectrum of cosmic-ray antiprotons from 0.17 to 3.5 GeV has been measured using 7886 antiprotons detected by BESS-Polar II during a long-duration flight over Antarctica near solar minimum in December 2007 and January 2008. This shows good consistency with secondary antiproton calculations. Cosmologically primary antiprotons have been investigated by comparing measured and calculated antiproton spectra. BESS-Polar II data show no evidence of primary antiprotons from evaporation of primordial black holes.Comment: 4 pages, 4 figures, submitted to Physical Review Letter