579 research outputs found
Reinterpreting the development of extensive air showers initiated by nuclei and photons
Ultra-high energy cosmic rays (UHECRs) interacting with the atmosphere
generate extensive air showers (EAS) of secondary particles. The depth
corresponding to the maximum development of the shower, \Xmax, is a
well-known observable for determining the nature of the primary cosmic ray
which initiated the cascade process. In this paper, we present an empirical
model to describe the distribution of \Xmax for EAS initiated by nuclei, in
the energy range from eV up to eV, and by photons, in the
energy range from eV up to eV. Our model adopts the
generalized Gumbel distribution motivated by the relationship between the
generalized Gumbel statistics and the distribution of the sum of
non-identically distributed variables in dissipative stochastic systems. We
provide an analytical expression for describing the \Xmax distribution for
photons and for nuclei, and for their first two statistical moments, namely
\langle \Xmax\rangle and \sigma^{2}(\Xmax). The impact of the hadronic
interaction model is investigated in detail, even in the case of the most
up-to-date models accounting for LHC observations. We also briefly discuss the
differences with a more classical approach and an application to the
experimental data based on information theory.Comment: 21 pages, 4 tables, 8 figure
Transport proteins determine drug sensitivity and resistance in a protozoan parasite, Trypanosoma brucei
Drug resistance in pathogenic protozoa is very often caused by changes to the âtransportomeâ of the parasites. In Trypanosoma brucei, several transporters have been implicated in uptake of the main classes of drugs, diamidines and melaminophenyl arsenicals. The resistance mechanism had been thought to be due to loss of a transporter known to carry both types of agents: the aminopurine transporter P2, encoded by the gene TbAT1. However, although loss of P2 activity is well-documented as the cause of resistance to the veterinary diamidine diminazene aceturate (BerenilÂź), cross-resistance between the human-use arsenical melarsoprol and the diamidine pentamidine (MPXR) is the result of loss of a separate High Affinity Pentamidine Transporter (HAPT1). A genome-wide RNAi library screen for resistance to pentamidine, published in 2012, gave the key to the genetic identity of HAPT1 by linking the phenomenon to a locus that contains the closely related T. brucei aquaglyceroporin genes TbAQP2 and TbAQP3. Further analysis determined that knockdown of only one pore, TbAQP2, produced the MPXR phenotype. TbAQP2 is an unconventional aquaglyceroporin with unique residues in the âselectivity regionâ of the pore, and it was found that in several MPXR lab strains the WT gene was either absent or replaced by a chimeric protein, recombined with parts of TbAQP3. Importantly, wild-type AQP2 was also absent in field isolates of T. b. gambiense, correlating with the outcome of melarsoprol treatment. Expression of a wild-type copy of TbAQP2 in even the most resistant strain completely reversed MPXR and re-introduced HAPT1 function and transport kinetics. Expression of TbAQP2 in Leishmania mexicana introduced a pentamidine transport activity indistinguishable from HAPT1. Although TbAQP2 has been shown to function as a classical aquaglyceroporin it is now clear that it is also a high affinity drug transporter, HAPT1. We discuss here a possible structural rationale for this remarkable ability
Entropy of L-fuzzy sets
The notion of âentropyâ of a fuzzy set, introduced in a previous paper in the case of generalized characteristic functions whose range is the interval [0, 1] of the real line, is extended to the case of maps whose range is a poset L (or, in particular, a lattice).Some of the reasons giving rise to the non-comparability of the truth values and then the necessity of considering poset structures as range of the maps are discussed.The interpretative problems of the given mathematical definitions regarding the connections with decision theory are briefly analyzed
Gramine derivatives targeting Ca2+ channels and Ser/Thr phosphatases: A new dual strategy for the treatment of neurodegenerative diseases
This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Journal of Medicinal Chemistry , copyright © American Chemical Society after peer review. To access the final edited and published work, see http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00478We describe the synthesis of gramine derivatives and their pharmacological evaluation as multipotent drugs for the treatment of Alzheimerâs disease. An innovative multitarget approach is presented, targeting both voltage-gated Ca2+ channels, classically studied for neurodegenerative diseases, and Ser/Thr phosphatases, which have been marginally aimed, even despite their key role in protein Ï dephosphorylation. Twenty-five compounds were synthesized, and mostly their neuroprotective profile exceeded that offered by the head compound gramine. In general, these compounds reduced the entry of Ca2+ through VGCC, as measured by Fluo-4/AM and patch clamp techniques, and protected in Ca2+ overload-induced models of neurotoxicity, like glutamate or veratridine exposures. Furthermore, we hypothesize that these compounds decrease Ï hyperphosphorylation based on the maintenance of the Ser/Thr phosphatase activity and their neuroprotection against the damage caused by okadaic acid. Hence, we propose this multitarget approach as a new and promising strategy for the treatment of neurodegenerative diseasesThis work was supported by the following grant: Proyectos de InvestigaciĂłn en Salud (PI13/00789, IS Carlos III). R.L.C is granted by Universidad AutĂłnoma de Madri
The Air Microwave Yield (AMY) experiment - A laboratory measurement of the microwave emission from extensive air showers
The AMY experiment aims to measure the microwave bremsstrahlung radiation
(MBR) emitted by air-showers secondary electrons accelerating in collisions
with neutral molecules of the atmosphere. The measurements are performed using
a beam of 510 MeV electrons at the Beam Test Facility (BTF) of Frascati INFN
National Laboratories. The goal of the AMY experiment is to measure in
laboratory conditions the yield and the spectrum of the GHz emission in the
frequency range between 1 and 20 GHz. The final purpose is to characterise the
process to be used in a next generation detectors of ultra-high energy cosmic
rays. A description of the experimental setup and the first results are
presented.Comment: 3 pages -- EPS-HEP'13 European Physical Society Conference on High
Energy Physics (July, 18-24, 2013) at Stockholm, Swede
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