Ultrahigh energy neutrinos at the Pierre Auger observatory

The observation of ultrahigh energy neutrinos (UHEνs) has become a priority in experimental astroparticle physics. UHEνs can be detected with a variety of techniques. In particular, neutrinos can interact in the atmosphere (downward-going ν) or in the Earth crust (Earth-skimming ν), producing air showers that can be observed with arrays of detectors at the ground. With the surface detector array of the Pierre Auger Observatory we can detect these types of cascades. The distinguishing signature for neutrino events is the presence of very inclined showers produced close to the ground (i.e., after having traversed a large amount of atmosphere). In this work we review the procedure and criteria established to search for UHEνs in the data collected with the ground array of the Pierre Auger Observatory. This includes Earth-skimming as well as downward-going neutrinos. No neutrino candidates have been found, which allows us to place competitive limits to the diffuse flux of UHEνs in the EeV range and above.P. Abreu ... K. B. Barber ... J. A. Bellido ... R. W. Clay ... M. J. Cooper ... B. R. Dawson ... T. A. Harrison ... A. E. Herve ... V. C. Holmes ... J. Sorokin ... P. Wahrlich ... B. J. Whelan ... et al

A new application of confocal scanning microscopy to characterize liposomes lamellarity.

none5Purpose: Lamellarity of liposomes is an important parameter that may influence the entrapment efficacy of vesicles. In order to characterize the number of lamellas of a minoxidil (Mx) liposome system, a new application of Confocal Laser Scanning Microscopy (CLSM) was developped. Methods: Different minoxidil liposomes systems were prepared by mechanical dispersion. MLV (Multilamellar vesicles) dipalmitoylphosphatidylcholine - cholesterol (DPPC – CHOL) liposomes containing Mx or fluorescent probe b-carotene (bC) were obtained. All systems investigated were characterize with regard to its entrapment efficacy, by dynamic dialysis and assayed by HPLC (Mx) or spectrofotometrically (bC). Lamellarity was analized by means of a Confocal Laser Scanning Microscope using both, fluorescence and transmitted light channels. Results: Dynamic dialysis assays revealed high entrapment efficacies both for liposomes containing Mx or bC when a certain amount of cholesterol is present in the formulation. It existed a good correlation between entrapment efficacies of Mx or bC, as not significant differences were observed for both kinds of systems. Lamellarity studies of the vesicles showed a major distribution of multilamellar vesicles for all systems studied, with a number of concentric bilayers ranged between 3 and 6. Sonicated vesicles showed a clear tendency to diminish their lamellarity, finding out a representative number of unilamellar vesicles in the formulation. Conclusion: A new technique is presented for characterization of liposomes lamellarity. CLSM constitutes a new procedure that allows to visualize number and morphology of lamellas in liposomes. CLSM provide a great imaging quality of the formulation in its aqueous medium. Non sonicated liposomes showed a multillamelar distribution, while sonication of MLV introduce a number of unilamellar vesicles in the formulation.noneJ.M. López-Pinto; J. Palma; M.L. González-Rodríguez; A. Fini; A.M. RabascoJ.M. López-Pinto; J. Palma; M.L. González-Rodríguez; A. Fini; A.M. Rabasc

DPPC vesicles containing minoxidil II: application of experimental and Taguchi design to improve formulations.

none5Purpose: The aim of this study was to optimize the minoxidil (Mx) liposome / ethosome formulations obtained by mechanical dispersion method. The (statistical) design of experiments (DOE) is an efficient procedure for planning experiments so that the data obtained can be analized to yield valid and objective conclusions. Taguchi method uses the signal-to-noise (SN) ratio, which is directly transformed from the quadratic quality loss function, as a measure to determine the robustness of a process. Methods: The effects of membrane composition, liposome size, amount of drug and number of vortexing cycles on the efficacy entrapment were studied in a 25 complete factorial design, made up of 32 runs. Based on the results from the factorial design, a new design was applied to find the optimum condition and to analyse how sensitive the reponse were to variations in the settings of the experimental variables. The SN ratio (h) was used to estimate the quality variation. The variability characteristic is inversely proportional to the SN ratio, so the larger the h is, the more robust is the system. Results: Cholesterol, ethanol and the amount of drug exerted statistical significance, while number of vortexing cycles and time did not. The optimization study carried out leaded to a ethosomal system with a high content in cholesterol. Conclusion: Experimental and Taguchi designs are two valid strategies to improve formulations of liposomes and ethosomes by optimizing the composition of the vesicles and reaction conditions. Cholesterol and ethanol constitute the most importants factors that provide high stability, flux properties and entrapment efficacy of Mx.noneJ.M. López-Pinto; J. Palma; M.L. González-Rodríguez; A. Fini; A.M. RabascoJ.M. López-Pinto; J. Palma; M.L. González-Rodríguez; A. Fini; A.M. Rabasc

PPC vesicles containing minoxidil I: characterization and in vitro permeation studies through rat skin

Purpose: Characterization of liposomes and ethosomes containing hidrophobic minoxidil (Mx) for topical administration was carried out in order to investigate the effect of preparation method and composition variables in flux properties of minoxidil through rat skin and its targeting to pilosebaceous structures. Methods: MLV liposomes and ethosomes were prepared by mechanical dispersion or Bangham method. Characterization was carried out attending to size, as a measure of stability, entrapment efficacy, morphology and lamellarity of the vesicles. Permeation studies through rat skin were conducted by means of Franz diffusion cells for all the batches investigated. In order to analize the preferential pathway of Mx across the stratum corneum toward the pilosebaceus unity, a fluorescent probe (b-carotene, bC) was used as a model drug for Confocal Laser Scanning Microscopy (CLSM) assays. Results: Mean size, entrapment efficacy, outer morphology and lamellarity were strongly influenced by the relative amount of cholesterol in the composition of the vesicles and by the presence or absence of ethanol in the medium. Flux properties of minoxidil from all systems depended as well on the cholesterol amount and the presence of ethanol in the formulation. In all cases, ethosomes exhibit better values of flux through rat skin than liposomes. All systems investigated by CLSM were compared with regard to the penetration depth of the fluorescent probe into the stratum corneum and the relative intensity of fluorescence at the pilosebaceous level. Ethosome formulation with 40 % of cholesterol (total lipid weight) showed the highest values for flux of Mx and the best targeting ability. Conclusions: DPPC vesicles were effective in delivering Mx through stratum corneum of rat skin, showing a strongly increase with regard to the drug as such. Ethosomes demonstrated to be the best formulation assayed in the targeting of the drug to the pilosebaceous structures

DPPC vesicles containing minoxidil II: application of experimental and Taguchi design to improve formulations

Purpose: The aim of this study was to optimize the minoxidil (Mx) liposome / ethosome formulations obtained by mechanical dispersion method. The (statistical) design of experiments (DOE) is an efficient procedure for planning experiments so that the data obtained can be analized to yield valid and objective conclusions. Taguchi method uses the signal-to-noise (SN) ratio, which is directly transformed from the quadratic quality loss function, as a measure to determine the robustness of a process. Methods: The effects of membrane composition, liposome size, amount of drug and number of vortexing cycles on the efficacy entrapment were studied in a 25 complete factorial design, made up of 32 runs. Based on the results from the factorial design, a new design was applied to find the optimum condition and to analyse how sensitive the reponse were to variations in the settings of the experimental variables. The SN ratio (h) was used to estimate the quality variation. The variability characteristic is inversely proportional to the SN ratio, so the larger the h is, the more robust is the system. Results: Cholesterol, ethanol and the amount of drug exerted statistical significance, while number of vortexing cycles and time did not. The optimization study carried out leaded to a ethosomal system with a high content in cholesterol. Conclusion: Experimental and Taguchi designs are two valid strategies to improve formulations of liposomes and ethosomes by optimizing the composition of the vesicles and reaction conditions. Cholesterol and ethanol constitute the most importants factors that provide high stability, flux properties and entrapment efficacy of Mx

First report from the excavations at De Nadale Cave, a single layered Mousterian site in the North of Italy.

none8sinoneJéquier C.; Delpiano D.; López-García J.M.; Lembo G.; Livraghi A.; Obradović M.; Romandini M.; Peresani M.Jéquier, C.; Delpiano, Davide; López García, J. M.; Lembo, G.; Livraghi, A.; Obradović, M.; Romandini, Matteo; Peresani, Marc