Daily Plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage

<p>Abstract</p> <p>Background</p> <p>Human populations that are naturally subjected to <it>Plasmodium </it>infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure. However, sterile immunity against <it>Plasmodium </it>liver stage can be achieved after repeated exposure to radiation attenuated sporozoites. The reasons for this different response remain largely unknown, but a suppressive effect of blood stage <it>Plasmodium </it>infection has been proposed as a cause for the lack of liver stage protection.</p> <p>Methods</p> <p>Using <it>Plasmodium yoelii </it>17XNL, the response generated in mice subjected to daily infective bites from normal or irradiated mosquitoes was compared. The effect of daily-infected mosquito bites on mice that were previously immunized against <it>P. yoelii </it>liver stage was also studied.</p> <p>Results</p> <p>It was observed that while the bites of normal infected mosquitoes do not generate strong antibody responses and protection, the bites of irradiated mosquitoes result in high levels of anti-sporozoite antibodies and protection against liver stage <it>Plasmodium </it>infection. Exposure to daily infected mosquito bites did not eliminate the protection acquired previously with a experimental liver stage vaccine.</p> <p>Conclusions</p> <p>Liver stage immunity generated by irradiated versus normal <it>P. yoelii </it>infected mosquitoes is essentially different, probably because of the blood stage infection that follows normal mosquito bites, but not irradiated. While infective mosquito bites do not induce a protective liver stage response, they also do not interfere with previously acquired liver stage protective responses, even if they induce a complete blood stage infection. Considering that the recently generated anti-malaria vaccines induce only partial protection against infection, it is encouraging that, at least in mouse models, immunity is not negatively affected by subsequent exposure and infection with the parasite.</p

Biodegradable polyesters reinforced with triclosan loaded polylactide micro/nanofibers: Properties, release and biocompatibility

Mechanical properties and drug release behavior were studied for three biodegradable polyester matrices (polycaprolactone, poly(nonamethylene azelate) and the copolymer derived from 1,9-nonanediol and an equimolar mixture of azelaic and pimelic acids) reinforced with polylactide (PLA) fibers. Electrospinning was used to produce suitable mats constituted by fibers of different diameters (i.e. from micro- to nanoscale) and a homogeneous dispersion of a representative hydrophobic drug (i.e. triclosan). Fabrics were prepared by a molding process, which allowed cold crystallization of PLA micro/nanofibers and hot crystallization of the polyester matrices. The orientation of PLA molecules during electrospinning favored the crystallization process, which was slightly enhanced when the diameter decreased. Incorporation of PLA micro/nanofibers led to a significant increase in the elastic modulus and tensile strength, and in general to a decrease in the strain at break. The brittle fracture was clearer when high molecular weight samples with high plastic deformation were employed. Large differences in the release behavior were detected depending on the loading process, fiber diameter size and hydrophobicity of the polyester matrix. The release of samples with the drug only loaded into the reinforcing fibers was initially fast and then became slow and sustained, resulting in longer lasting antimicrobial activity. Biocompatibility of all samples studied was demonstrated by adhesion and proliferation assays using HEp-2 cell cultures

Lowering the background level and the energy threshold of Micromegas x-ray detectors for axion searches

Axion helioscopes search for solar axions by their conversion in x-rays in the presence of high magnetic fields. The use of low background x-ray detectors is an essential component contributing to the sensitivity of these searches. In this work, we review the recent advances on Micromegas detectors used in the CERN Axion Solar Telescope (CAST) and proposed for the future International Axion Observatory (IAXO). The actual setup in CAST has achieved background levels below 10$^{-6}$ keV$^{-1}$ cm$^{-2}$ s$^{-1}$, a factor 100 lower than the first generation of Micromegas detectors. This reduction is based on active and passive shielding techniques, the selection of radiopure materials, offline discrimination techniques and the high granularity of the readout. We describe in detail the background model of the detector, based on its operation at CAST site and at the Canfranc Underground Laboratory (LSC), as well as on Geant4 simulations. The best levels currently achieved at LSC are low than 10$^{-7}$ keV$^{-1}$ cm$^{-2}$ s$^{-1}$ and show good prospects for the application of this technology in IAXO. Finally, we present some ideas and results for reducing the energy threshold of these detectors below 1 keV, using high-transparent windows, autotrigger electronics and studying the cluster shape at different energies. As a high flux of axion-like-particles is expected in this energy range, a sub-keV threshold detector could enlarge the physics case of axion helioscopes.Comment: Proceedings of 3rd International Conference on Technology and Instrumentation in Particle Physics (TIPP 2014

Towards a new generation axion helioscope

We study the feasibility of a new generation axion helioscope, the most ambitious and promising detector of solar axions to date. We show that large improvements in magnetic field volume, x-ray focusing optics and detector backgrounds are possible beyond those achieved in the CERN Axion Solar Telescope (CAST). For hadronic models, a sensitivity to the axion-photon coupling of \gagamma\gtrsim {\rm few} \times 10^{-12} GeV$^{-1}$ is conceivable, 1--1.5 orders of magnitude beyond the CAST sensitivity. If axions also couple to electrons, the Sun produces a larger flux for the same value of the Peccei-Quinn scale, allowing one to probe a broader class of models. Except for the axion dark matter searches, this experiment will be the most sensitive axion search ever, reaching or surpassing the stringent bounds from SN1987A and possibly testing the axion interpretation of anomalous white-dwarf cooling that predicts $m_a$ of a few meV. Beyond axions, this new instrument will probe entirely unexplored ranges of parameters for a large variety of axion-like particles (ALPs) and other novel excitations at the low-energy frontier of elementary particle physics.Comment: 37 pages, 11 figures, accepted for publication in JCA

The International Axion Observatory (IAXO)

The International Axion Observatory (IAXO) is a new generation axion helioscope aiming at a sensitivity to the axion-photon coupling of a few 10$^{12}$ GeV$^{-1}$, i.e. 1 - 1.5 orders of magnitude beyond the one currently achieved by CAST. The project relies on improvements in magnetic field volume together with extensive use of x-ray focusing optics and low background detectors, innovations already successfully tested in CAST. Additional physics cases of IAXO could include the detection of electron-coupled axions invoked to solve the white dwarfs anomaly, relic axions, and a large variety of more generic axion-like particles (ALPs) and other novel excitations at the low-energy frontier of elementary particle physics. This contribution is a summary of our paper [1] to which we refer for further details.Comment: 4 pages, 2 figures. To appear in the proceedings of the 7th Patras Workshop on Axions, WIMPs and WISPs, Mykonos, Greece, 201

The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS

OBJECTIVE: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. METHODS: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). RESULTS: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28–95) versus 7 (1–19) and 3 (1–24) versus 0 (0–1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. CONCLUSION: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS

CAST constraints on the axion-electron coupling

In non-hadronic axion models, which have a tree-level axion-electron interaction, the Sun produces a strong axion flux by bremsstrahlung, Compton scattering, and axio-recombination, the "BCA processes." Based on a new calculation of this flux, including for the first time axio-recombination, we derive limits on the axion-electron Yukawa coupling g_ae and axion-photon interaction strength g_ag using the CAST phase-I data (vacuum phase). For m_a < 10 meV/c2 we find g_ag x g_ae< 8.1 x 10^-23 GeV^-1 at 95% CL. We stress that a next-generation axion helioscope such as the proposed IAXO could push this sensitivity into a range beyond stellar energy-loss limits and test the hypothesis that white-dwarf cooling is dominated by axion emission

CAST solar axion search with 3^He buffer gas: Closing the hot dark matter gap

The CERN Axion Solar Telescope (CAST) has finished its search for solar axions with 3^He buffer gas, covering the search range 0.64 eV < m_a <1.17 eV. This closes the gap to the cosmological hot dark matter limit and actually overlaps with it. From the absence of excess X-rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of g_ag < 3.3 x 10^{-10} GeV^{-1} at 95% CL, with the exact value depending on the pressure setting. Future direct solar axion searches will focus on increasing the sensitivity to smaller values of g_a, for example by the currently discussed next generation helioscope IAXO.Comment: 5 pages, 2 figures. Last version uploade

Biodegradable free-standing nanomembranes of conducting polymer:polyester blends as bioactive platforms for tissue engineering

The present study reports the fabrication of free-standing nanomembranes with semiconducting and biodegradable properties. Nanomembranes have been prepared by spin-coating mixtures of a semiconducting polythiophene derivative, poly(3-thiophene methyl acetate), and a biodegradable polyester, poly(tetramethylene succinate). Both the roughness and thickness of the nanomembranes, which ranged from 3 to 20 nm and from 20 to 80 nm, respectively, were precisely controlled through the spin-coater speed and the solvent evaporation properties. Nanomembranes made of conducting polymer/polyester blends, which are able to retain the properties of the individual polymers, are stable in air and in ethanol solution for more than one year, facilitating their manipulation. Enzymatic degradation essays indicated that the ultra-thin films are biodegradable due to the presence of the aliphatic polyester. Interestingly, adhesion and proliferation assays with epithelial cells revealed that the behavior of the blend as cellular matrix is superior to that of the two individual polymers, validating the use of the nanomembranes as bioactive substrates for tissue regeneration.222585594MICINNFEDER [MAT2009-09138, MAT2009-11513]DIUE of the Generalitat de Catalunya [2009SGR925, 2009SGR1208, XRQTC]Euro Brazilian Windows agency [41309-EM-1-2008-PT-ERAMUNDUS-ECW-L16]FPU-UPCGeneralitat de CatalunyaFEDER [MAT2009-09138, MAT2009-11513]DIUE of the Generalitat de Catalunya [2009SGR925, 2009SGR1208, XRQTC]Euro Brazilian Windows agency [41309-EM-1-2008-PT-ERAMUNDUS-ECW-L16