Thermal equilibrium and statistical thermometers in special relativity

There is an intense debate in the recent literature about the correct generalization of Maxwell's velocity distribution in special relativity. The most frequently discussed candidate distributions include the Juettner function as well as modifications thereof. Here, we report results from fully relativistic one-dimensional (1D) molecular dynamics (MD) simulations that resolve the ambiguity. The numerical evidence unequivocally favors the Juettner distribution. Moreover, our simulations illustrate that the concept of 'thermal equilibrium' extends naturally to special relativity only if a many-particle system is spatially confined. They make evident that 'temperature' can be statistically defined and measured in an observer frame independent way.Comment: version accepted for publication (5 pages), part of the introduction modified, new figures, additional reference

IL-28 Supplants Requirement for Treg Cells in Protein σ1-Mediated Protection against Murine Experimental Autoimmune Encephalomyelitis (EAE)

Conventional methods to induce tolerance in humans have met with limited success. Hence, efforts to redirect tolerogen uptake using reovirus adhesin, protein sigma 1 (pσ1), may circumvent these shortcomings based upon the recent finding that when reovirus pσ1 is engineered to deliver chicken ovalbumin (OVA) mucosally, tolerance is obtained, even with a single dose. To test whether single-dose tolerance can be induced to treat EAE, proteolipid protein (PLP130–151) was genetically fused to OVA to pσ1 (PLP:OVA-pσ1) and shown to significantly ameliorate EAE, suppressing proinflammatory cytokines by IL-10+ forkhead box P3 (FoxP3)+ CD25+CD4+ Treg and IL-4+CD25−CD4+ Th2 cells. IL-10R or IL-4 neutralization reversed protection to EAE conferred by PLP:OVA-pσ1, and adoptive transfer of Ag-specific Treg or Th2 cells restored protection against EAE in recipients. Upon assessment of each relative participant, functional inactivation of CD25 impaired PLP:OVA-pσ1's protective capacity, triggering TGF-β-mediated inflammation; however, concomitant inactivation of TGF-β and CD25 reestablished PLP:OVA-pσ1-mediated protection by IL-28-producing FoxP3+CD25−CD4+ T cells. Thus, pσ1-based therapy can resolve EAE independently of or dependently upon CD25 and assigns IL-28 as an alternative therapy for autoimmunity

Delivery of IL-35 by Lactococcus lactis Ameliorates Collagen-Induced Arthritis in Mice

IL-35, a relatively newly discovered cytokine belonging to the larger IL-12 family, shows unique anti-inflammatory properties, believed to be associated with dedicated receptors and signaling pathways. IL-35 plays a pivotal role in the development and the function of both regulatory B (Bregs) and T cells (Tregs). In order to further its therapeutic potential, a dairy Lactococcus lactis strain was engineered to express murine IL-35 (LL-IL35), and this recombinant strain was applied to suppress collagen-induced arthritis (CIA). Oral administration of LL-IL35 effectively reduced the incidence and disease severity of CIA. When administered therapeutically, LL-IL35 abruptly halted CIA progression with no increase in disease severity by reducing neutrophil influx into the joints. LL-IL35 treatment reduced IFN-γ and IL-17 3.7- and 8.5-fold, respectively, and increased IL-10 production compared to diseased mice. Foxp3+ and Foxp3− CD39+ CD4+ T cells were previously shown to be the Tregs responsible for conferring protection against CIA. Inquiry into their induction revealed that both CCR6+ and CCR6− Foxp3+or− CD39+ CD4+ T cells act as the source of the IL-10 induced by LL-IL35. Thus, this study demonstrates the feasibility and benefits of engineered probiotics for treating autoimmune diseases

A Polymer/Oil Based Nanovaccine as a Single-Dose Immunization Approach

The recognized necessity for new antigen delivery carriers with the capacity to boost, modulate and prolong neutralizing immune responses prompted our approach, in which we describe a multifunctional nanocarrier consisting of an oily nanocontainer protected by a polymeric shell made of chitosan (CS), named CS nanocapsules (CSNC). The CS shell can associate the antigen on its surface, whereas the oily core might provide additional immunostimulating properties. In this first characterization of the system, we intended to study the influence of different antigen organizations on the nanocarrier's surface (using the recombinant hepatitis B surface antigen –rHBsAg– as a model antigen) on their long-term immunopotentiating effect, without any additional immunostimulant. Thus, two prototypes of antigen-loaded CSNC (CSNC+ and CSNC−), exhibiting similar particle size (200 nm) and high antigen association efficiency (>80%), were developed with different surface composition (polymer/antigen ratios) and surface charge (positive/negative, respectively). The biological evaluation of these nanovaccines evidenced the superiority of the CSNC+ as compared to CSNC- and alum-rHBsAg in terms of neutralizing antibody responses, following intramuscular vaccination. Moreover, a single dose of CSNC+ led to similar IgG levels to the positive control. The IgG1/IgG2a ratio suggested a mixed Th1/Th2 response elicited by CSNC+, in contrast to the typical Th2-biased response of alum. Finally, CSNC+ could be freeze-dried without altering its physicochemical properties and adjuvant effect in vivo. In conclusion, the evaluation of CSNC+ confirms its interesting features for enhancing, prolonging and modulating the type of immune response against subunit antigens, such as rHBsAgThis work was supported by a grant from the Bill and Melinda Gates Foundation (www.gatesfoundation.org), Consolider Ingenio 2010 CSD2006-00012 (Ministry of Science and Innovation, Spain) and Competitive Reference Groups SUDOE-FEDER (SOE1/P1/E014). SV and MP acknowledge a fellowship from the Spanish Ministry of Education (FPU predoctoral grants). DWP was in part supported by Montana Agricultural Experiment Station and US Department of Agriculture Formula FundsS

Quantum entropy source on an InP photonic integrated circuit for random number generation

[EN] Random number generators are essential to ensuring performance in information technologies, including cryptography, stochastic simulations, and massive data processing. The quality of random numbers ultimately determines the security and privacy that can be achieved, while the speed at which they can be generated poses limits to the utilization of the available resources. In this work we propose and demonstrate a quantum entropy source for random number generation on an indium phosphide photonic integrated circuit made possible by a new design using two-laser interference and heterodyne detection. The resulting device offers high-speed operation with unprecedented security guarantees and reduced form factor. It is also compatible with complementary metal-oxide semiconductor technology, opening the path to its integration in computation and communication electronic cards, which is particularly relevant for the intensive migration of information processing and storage tasks from local premises to cloud data centers. (C) 2016 Optical Society of AmericaEuropean Regional Development Fund (FEDER) (TEC2013-46168-R); Ministerio de Economia y Competitividad (MINECO) Qu-CARD (SRTC1400C002844XV0); Severo Ochoa (SEV-2015-0522); XPLICA (FIS2014-62181-EXP); European Research Council (ERC) (AQUMET 280169, ERIDIAN 713682); European Union QUIC (641122); Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) (2014 LLAV 00078, 2014-SGR-1295, 2014-SGR-1623); Fundacion CELLEX.Abellan, C.; Amaya Ocampo, WA.; Doménech Gómez, JD.; Muñoz Muñoz, P.; Capmany Francoy, J.; Longhi, S.; Mitchell, MW.... (2016). Quantum entropy source on an InP photonic integrated circuit for random number generation. 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F., Fröhlich, B., Plews, A., & Shields, A. J. (2014). Robust random number generation using steady-state emission of gain-switched laser diodes. Applied Physics Letters, 104(26), 261112. doi:10.1063/1.4886761Nie, Y.-Q., Huang, L., Liu, Y., Payne, F., Zhang, J., & Pan, J.-W. (2015). The generation of 68 Gbps quantum random number by measuring laser phase fluctuations. Review of Scientific Instruments, 86(6), 063105. doi:10.1063/1.4922417Abellán, C., Amaya, W., Mitrani, D., Pruneri, V., & Mitchell, M. W. (2015). Generation of Fresh and Pure Random Numbers for Loophole-Free Bell Tests. Physical Review Letters, 115(25). doi:10.1103/physrevlett.115.250403Heck, M. J. R., Bauters, J. F., Davenport, M. L., Doylend, J. K., Jain, S., Kurczveil, G., … Bowers, J. E. (2013). Hybrid Silicon Photonic Integrated Circuit Technology. 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Equine Arteritis Virus Elicits a Mucosal Antibody Response in the Reproductive Tract of Persistently Infected Stallions

Equine arteritis virus (EAV) has the ability to establish persistent infection in the reproductive tract of the stallion (carrier) and is continuously shed in its semen. We have recently demonstrated that EAV persists within stromal cells and a subset of lymphocytes in the stallion accessory sex glands in the presence of a significant local inflammatory response. In the present study, we demonstrated that EAV elicits a mucosal antibody response in the reproductive tract during persistent infection with homing of plasma cells into accessory sex glands. The EAV-specific immunoglobulin isotypes in seminal plasma included IgA, IgG1, IgG3/5, and IgG4/7. Interestingly, seminal plasma IgG1 and IgG4/7 possessed virus-neutralizing activity, while seminal plasma IgA and IgG3/5 did not. However, virus-neutralizing IgG1 and IgG4/7 in seminal plasma were not effective in preventing viral infectivity. In addition, the serological response was primarily mediated by virus-specific IgM and IgG1, while virus-specific serum IgA, IgG3/5, IgG4/7, and IgG6 isotype responses were not detected. This is the first report characterizing the immunoglobulin isotypes in equine serum and seminal plasma in response to EAV infection. The findings presented herein suggest that while a broader immunoglobulin isotype diversity is elicited in seminal plasma, EAV has the ability to persist in the reproductive tract, in spite of local mucosal antibody and inflammatory responses. This study provides further evidence that EAV employs complex immune evasion mechanisms during persistence in the reproductive tract that warrant further investigation

Distortions of Subjective Time Perception Within and Across Senses

Background: The ability to estimate the passage of time is of fundamental importance for perceptual and cognitive processes. One experience of time is the perception of duration, which is not isomorphic to physical duration and can be distorted by a number of factors. Yet, the critical features generating these perceptual shifts in subjective duration are not understood. Methodology/Findings: We used prospective duration judgments within and across sensory modalities to examine the effect of stimulus predictability and feature change on the perception of duration. First, we found robust distortions of perceived duration in auditory, visual and auditory-visual presentations despite the predictability of the feature changes in the stimuli. For example, a looming disc embedded in a series of steady discs led to time dilation, whereas a steady disc embedded in a series of looming discs led to time compression. Second, we addressed whether visual (auditory) inputs could alter the perception of duration of auditory (visual) inputs. When participants were presented with incongruent audio-visual stimuli, the perceived duration of auditory events could be shortened or lengthened by the presence of conflicting visual information; however, the perceived duration of visual events was seldom distorted by the presence of auditory information and was never perceived shorter than their actual durations. Conclusions/Significance: These results support the existence of multisensory interactions in the perception of duration and, importantly, suggest that vision can modify auditory temporal perception in a pure timing task. Insofar as distortions in subjective duration can neither be accounted for by the unpredictability of an auditory, visual or auditory-visual event, we propose that it is the intrinsic features of the stimulus that critically affect subjective time distortions

Nuclear receptors in vascular biology

Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

Swift Observations of the highly X-ray variable Narrow Line Seyfert 1 galaxy RX J0148.3-2758

We report on Swift observations of the Narrow-Line Seyfert 1 galaxy (NLS1) RX J0148.3--2758. It was observed for 41.6 ks in 2005 May and for 15.8 ks in 2005 December. On short as well as on long timescales RX J0148.3--2758 is a highly variable source. It doubles its X-ray flux within 18-25 ks. The observation of 2005 December 09, which had a flux 4 times lower than during the 2005 May observations, shows a significant hardening of the X-ray hardness ratio compared with the 2005-May and 2005-December 20/21 observations. A detailed analysis of the X-ray spectra shows that we actually observe two spectral changes in RX J0148.3-2758: First a decrease of the soft X-ray component between 2005 May and December 09, which is most likely due to an increase of the intrinsic absorber column, and second a decrease of the hard X-ray flux in the December 20/21 observations. The soft X-ray spectral slope $\alpha_{\rm X, soft}$=2.58$^{+0.15}_{-0.12}$ during the high state in 2005 May agrees well with that measured by ROSAT (\axs=2.54\plm0.82). In contrast to the strong X-ray variability, the analysis of the Swift UVOT photometry from December 2005 of RX J0148.3--2758 shows no significant variability in any of the 6 UVOT filters. From the simultaneous X-ray and UV observations in 2005 December we measured the X-ray loudness alpha-ox varies between alpha-ox=1.5 and 1.8. Our Swift observations of RX J0148.3-2758 demonstrate the great potential the multi-wavelength observatory Swift has for AGN science. (shortened)Comment: 19 pages; accepted for publication the Astronomical Journa

Temperature and Malaria Trends in Highland East Africa

There has been considerable debate on the existence of trends in climate in the highlands of East Africa and hypotheses about their potential effect on the trends in malaria in the region. We apply a new robust trend test to mean temperature time series data from three editions of the University of East Anglia's Climatic Research Unit database (CRU TS) for several relevant locations. We find significant trends in the data extracted from newer editions of the database but not in the older version for periods ending in 1996. The trends in the newer data are even more significant when post-1996 data are added to the samples. We also test for trends in the data from the Kericho meteorological station prepared by Omumbo et al. We find no significant trend in the 1979-1995 period but a highly significant trend in the full 1979-2009 sample. However, although the malaria cases observed at Kericho, Kenya rose during a period of resurgent epidemics (1994-2002) they have since returned to a low level. A large assembly of parasite rate surveys from the region, stratified by altitude, show that this decrease in malaria prevalence is not limited to Kericho