The ciliary machinery is repurposed for T cell immune synapse trafficking of LCK

Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B. The UNC119A N terminus acts as a “regulatory arm” by binding the LCK kinase domain, an interaction inhibited by LCK Y394 phosphorylation, thus together with the ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose that the ciliary machinery has been repurposed by T cells to generate and maintain polarized segregation of signals such as activated LCK at the immune synapse

Diagnosis for ecological intensification of maize-based smallholder farming systems in the Costa Chica, Mexico

Enhanced utilization of ecological processes for food and feed production as part of the notion of ecological intensification starts from location-specific knowledge of production constraints. A diagnostic systems approach which combined social-economic and production ecological methods at farm and field level was developed and applied to diagnose extent and causes of the perceived low productivity of maize-based smallholder systems in two communities of the Costa Chica in South West Mexico. Social-economic and production ecological surveys were applied and complemented with model-based calculations. The results demonstrated that current nutrient management of crops has promoted nutrition imbalances, resulting in K- and, less surprisingly N-limited production conditions, reflected in low yields of the major crops maize and roselle and low resource use efficiencies. Production on moderate to steep slopes was estimated to result in considerable losses of soil and organic matter. Poor crop production, lack of specific animal fodder production systems and strong dependence on animal grazing within communal areas limited recycling of nutrients through manure. In combination with low prices for the roselle cash crop, farmers are caught in a vicious cycle of cash shortage and resource decline. The production ecological findings complemented farmers opinions by providing more insight in background and extent of livelihood constraints. Changing fertilizer subsidies and rethinking animal fodder production as well as use of communal lands requires targeting both formal and informal governance structures. The methodology has broader applicability in smallholder systems in view of its low demand on capital intensive resource

Magnetic properties of photospheric regions having very low magnetic flux

The magnetic properties of the quiet Sun are investigated using a novel inversion code, FATIMA, based on the Principal Component Analysis of the observed Stokes profiles. The stability and relatively low noise sensitivity of this inversion procedure allows for the systematic inversion of large data sets with very weak polarization signal. Its application to quiet Sun observations of network and internetwork regions reveals that a significant fraction of the quiet Sun contains kilogauss fields (usually with very small filling factors) and confirms that the pixels with weak polarization account for most of the magnetic flux. Mixed polarities in the resolution element are also found to occur more likely as the polarization weakens.Comment: To apapear in ApJ. 39 pages, 12 figures (2 of them are color figures

Bayesian Inversion of Stokes Profiles

[abridged] Inversion techniques are the most powerful methods to obtain information about the thermodynamical and magnetic properties of solar and stellar atmospheres. In the last years, we have witnessed the development of highly sophisticated inversion codes that are now widely applied to spectro-polarimetric observations. The majority of these inversion codes are based on the optimization of a complicated non-linear merit function. However, no reliable and statistically well-defined confidence intervals can be obtained for the parameters inferred from the inversions. A correct estimation of the confidence intervals for all the parameters that describe the model is mandatory. Additionally, it is fundamental to apply efficient techniques to assess the ability of models to reproduce the observations and to what extent the models have to be refined or can be simplified. Bayesian techniques are applied to analyze the performance of the model to fit a given observed Stokes vector. The posterior distribution, is efficiently sampled using a Markov Chain Monte Carlo method. For simplicity, we focus on the Milne-Eddington approximate solution of the radiative transfer equation and we only take into account the generation of polarization through the Zeeman effect. However, the method is extremely general and other more complex forward models can be applied. We illustrate the ability of the method with the aid of academic and realistic examples. We show that the information provided by the posterior distribution turns out to be fundamental to understand and determine the amount of information available in the Stokes profiles in these particular cases.Comment: 15 pages, 12 figures, accepted for publication in A&

A GPU-Computing Approach to Solar Stokes Profile Inversion

We present a new computational approach to the inversion of solar photospheric Stokes polarization profiles, under the Milne-Eddington model, for vector magnetography. Our code, named GENESIS (GENEtic Stokes Inversion Strategy), employs multi-threaded parallel-processing techniques to harness the computing power of graphics processing units GPUs, along with algorithms designed to exploit the inherent parallelism of the Stokes inversion problem. Using a genetic algorithm (GA) engineered specifically for use with a GPU, we produce full-disc maps of the photospheric vector magnetic field from polarized spectral line observations recorded by the Synoptic Optical Long-term Investigations of the Sun (SOLIS) Vector Spectromagnetograph (VSM) instrument. We show the advantages of pairing a population-parallel genetic algorithm with data-parallel GPU-computing techniques, and present an overview of the Stokes inversion problem, including a description of our adaptation to the GPU-computing paradigm. Full-disc vector magnetograms derived by this method are shown, using SOLIS/VSM data observed on 2008 March 28 at 15:45 UT

Current profiles and AC losses of a superconducting strip with elliptic cross-section in perpendicular magnetic field

The case of a hard type II superconductor in the form of strip with elliptic cross-section when placed in transverse magnetic field is studied. We approach the problem in two steps, both based on the critical-state model. First we calculate numerically the penetrated current profiles that ensure complete shielding in the interior, without assuming an a priori form for the profiles. In the second step we introduce an analytical approximation that asumes that the current profiles are ellipses. Expressions linking the sample magnetization to the applied field are derived covering the whole range of applied fields. The theoretical predictions are tested by the comparison with experimental data for the imaginary part of AC susceptibility.Comment: 12 pages; 3 figure

Influence of health literacy on acceptance of influenza and pertussis vaccinations: a cross-sectional study among Spanish pregnant women.

OBJECTIVES: Immunisations against influenza and Bordetella pertussis infection are recommended to pregnant women in Valencia (Spain), yet vaccination rates remain low. Health literacy (HL) appears as a crucial factor in vaccination decision-making. We explored the relation between HL of pregnant women and decisions to receive influenza and pertussis immunisations. SETTING: University hospital in Valencia (Spain). PARTICIPANTS: 119 women who gave birth at a hospital in Valencia (Spain) between November 2015 and May 2016. Women in the immediate postpartum period (more than 27 weeks of gestation), between November 2015 and May 2016 were included in the study. Women with impairments, language barriers or illiteracy which prevented completion of the questionnaires, or those who were under 18 years were excluded from enrolment. PRIMARY AND SECONDARY OUTCOME MEASURES: HL level; influenza and pertussis immunisation rate; reasons for rejection of vaccination. RESULTS: 119 participants were included (mean age 32.3±5.5 years, 52% primiparous, 95% full-term deliveries). A higher education level was associated with Short Assessment of Health Literacy for Spanish Adults _50 (adjusted R2=0.22, p=0.014) and Newest Vital Sign (adjusted R2=0.258, p=0.001) scores. Depending on the scale, 56%-85% of participants had adequate HL. 52% (62/119) and 94% (112/119) of women received influenza and pertussis immunisation, respectively. Women rejecting influenza vaccine had a higher HL level (measured by SALHSA_50 tool) than those accepting it (Kruskal-Wallis test p=0.022). 24% of women who declined influenza vaccination felt the vaccine was unnecessary, and 23% claimed to have insufficient information. CONCLUSIONS: Influenza vaccination rate was suboptimal in our study. Women with high HL were more likely to decline immunisation. Information from professionals needs to match patients' HL levels to reduce negative perceptions of vaccination

On the generation of asymmetric warps in disk galaxies

The warps in many spiral galaxies are now known to asymmetric. Recent sensitive observations have revealed that asymmetry of warps may be the norm rather than exception. However there exists no generic mechanism to generate these asymmetries in warps. We have derived the dispersion relation in a compact form for the S-shaped warps(described by the m=1 mode) and the bowl-shaped distribution(described by the m=0 mode) in galactic disk embedded in a dark matter halo. We then performed the numerical modal analysis and used the linear and time-dependent superposition principle to generate asymmetric warps in the disk. On doing the modal analysis we find the frequency of the $m=0$ mode is much larger than that of the $m=1$ mode. The linear and time-dependent superposition of these modes with their unmodulated amplitudes(that is, the coefficients of superposition being unity) results in an asymmetry in warps of ~ 20 - 40 %, whereas a smaller coefficient for the m=0 mode results in a smaller asymmetry. The resulting values agree well with the recent observations. We study the dependence of the asymmetry index on the dark matter halo parameters. This approach can also naturally produce U-shaped warps and L-shaped warps. We show that a rich variety of possible asymmetries in the z-distribution of the spiral galaxies can naturally arise due to a dynamical wave interference between the first two bending modes(i.e. m=0 and m=1) in the disk. This is a simple but general method for generating asymmetric warps that is independent of how the individual modes arise in the disk.Comment: Accepted for publication in A &

Toxicological evaluation of lactose and chitosan delivered by inhalation

These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione ( GSSG), myeloperoxidase ( MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 +/- 2.27 versus 15.10 +/- 7.27 ( P = 0.011) for MPO and 0.89 +/- 0.68 versus 2.02 +/- 0.22 ( P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators

Constraints on dark matter particles from theory, galaxy observations and N-body simulations

Mass bounds on dark matter (DM) candidates are obtained for particles decoupling in or out of equilibrium with {\bf arbitrary} isotropic and homogeneous distribution functions. A coarse grained Liouville invariant primordial phase space density $\mathcal D$ is introduced. Combining its value with recent photometric and kinematic data on dwarf spheroidal satellite galaxies in the Milky Way (dShps), the DM density today and $N$-body simulations, yields upper and lower bounds on the mass, primordial phase space densities and velocity dispersion of the DM candidates. The mass of the DM particles is bound in the few keV range. If chemical freeze out occurs before thermal decoupling, light bosonic particles can Bose-condense. Such Bose-Einstein {\it condensate} is studied as a dark matter candidate. Depending on the relation between the critical($T_c$)and decoupling($T_d$)temperatures, a BEC light relic could act as CDM but the decoupling scale must be {\it higher} than the electroweak scale. The condensate tightens the upper bound on the particle's mass. Non-equilibrium scenarios that describe particle production and partial thermalization, sterile neutrinos produced out of equilibrium and other DM models are analyzed in detail obtaining bounds on their mass, primordial phase space density and velocity dispersion. Light thermal relics with $m \sim \mathrm{few} \mathrm{keV}$ and sterile neutrinos lead to a primordial phase space density compatible with {\bf cored} dShps and disfavor cusped satellites. Light Bose condensed DM candidates yield phase space densities consistent with {\bf cores} and if $T_c\gg T_d$ also with cusps. Phase space density bounds from N-body simulations suggest a potential tension for WIMPS with $m \sim 100 \mathrm{GeV},T_d \sim 10 \mathrm{MeV}$.Comment: 27 pages 8 figures. Version to appear in Phys. Rev.