Transthyretin familial amyloid polyneuropathy impact on health-related quality of life

info:eu-repo/semantics/publishedVersio

Micromegas operation in high pressure xenon: charge and scintillation readout

The operational characteristics of a Micromegas operating in pure xenon at the pressure range of 1 to 10 bar are investigated. The maximum charge gain achieved in each pressure is approximately constant, around 4x10^2, for xenon pressures up to 5 bar and decreasing slowly above this pressure down to values somewhat above 10^2 at 10 bar. The MM presents the highest gains for xenon pressures above 4 bar, when compared to other micropattern gaseous multipliers. The lowest energy resolution obtained for X-rays of 22.1 keV exhibits a steady increase with pressure, from 12% at 1bar to about 32% at 10 bar. The effective scintillation yield, defined as the number of photons exiting through the MM mesh holes per primary electron produced in the conversion region was calculated. This yield is about 2x10^2 photons per primary electron at 1 bar, increasing to about 6x10^2 at 5 bar and, then, decreasing again to 2x10^2 at 10 bar. The readout of this scintillation by a suitable photosensor will result in higher gains but with increased statistical fluctuations.Comment: 22 pages, 11 figure

Solving the multi-period water distribution network design problem with a hybrid simulated anealling

This work presents an optimization technique based on Simulated Annealing (SA) to solve the Water Distribution Network Design problem, considering multi-period restrictions with time varying demand patterns. The design optimization of this kind of networks is an important issue in modern cities, since a safe, adequate, and accessible supply of potable water is one of the basic necessities of any human being. Given the complexity of this problem, the SA is improved with a local search procedure, yielding a hybrid SA, in order to obtain good quality networks designs. Additionally, four variants of this algorithm based on different cooling schemes are introduced and analyzed. A broad experimentation using different benchmark networks is carried out to test our proposals. Moreover, a comparison with an approach from the literature reveals the goodness to solve this network design problem.Fil: Bermudez, Carlos Alberto. Universidad Nacional de la Pampa. Facultad de Ingeniería; ArgentinaFil: Salto, Carolina. Universidad Nacional de la Pampa. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: Minetti, Gabriela Fabiana. Universidad Nacional de la Pampa. Facultad de Ingeniería; Argentin

Whole-genome analysis uncovers loss of blaZ associated with carriage isolates belonging to methicillin-resistant Staphylococcus aureus (MRSA) clone ST5-VI in Cape Verde

Objectives: Surveillance studies for Staphylococcus aureus carriage are a primary tool to survey the prevalence of methicillin-resistant S. aureus (MRSA) in the general population, patients and healthcare workers. We have previously reported S. aureus carriage in various African countries, including Cape Verde. Methods: Whole-genome sequences of 106 S. aureus isolates from Cape Verde were determined. Results: Staphylococcus aureus carriage isolates in Cape Verde show high genetic variability, with the detection of 27 sequence types (STs) and three primary genetic clusters associated with ST152, ST15 and ST5. One transmission event with less than eight core-genome single nucleotide polymorphisms (cgSNP) differences was detected among the ST5-VI MRSA lineage. Genetic analysis confirmed the phenotypic resistance and allowed the identification of six independent events of plasmid or transposon loss associated with the deletion of blaZ in nine isolates. In the four ST5 MRSA isolates, loss of the blaZ plasmid coincided with the acquisition of SCCmec type VI and an unusual penicillin phenotype with a minimum inhibitory concentration (MIC) at the breakpoint, indicating an adaptation trend in this endemic lineage. Similar events of blaZ plasmid loss, with concomitant acquisition SCCmec elements, were detected among ST5 isolates from different geographical origins. Conclusion: Overall, the genome data allowed to place isolates in a phylogenetic context and to identify different blaZ gene deletions associated with plasmid or transposon loss. Genomic analysis unveiled adaptation and evolution trends, namely among emerging MRSA lineages in the country, which deserve additional consideration in the design of future infection control protocols

Engineered extracellular vesicle decoy receptor-mediated modulation of the IL6 trans-signalling pathway in muscle

The cytokine interleukin 6 (IL6) is a key mediator of inflammation that contributes to skeletal muscle pathophysiology. IL6 activates target cells by two main mechanisms, the classical and trans-signalling pathways. While classical signalling is associated with the anti-inflammatory activities of the cytokine, the IL6 trans-signalling pathway mediates chronic inflammation and is therefore a target for therapeutic intervention. Extracellular vesicles (EVs) are natural, lipid-bound nanoparticles, with potential as targeted delivery vehicles for therapeutic macromolecules. Here, we engineered EVs to express IL6 signal transducer (IL6ST) decoy receptors to selectively inhibit the IL6 trans-signalling pathway. The potency of the IL6ST decoy receptor EVs was optimized by inclusion of a GCN4 dimerization domain and a peptide sequence derived from syntenin-1 which targets the decoy receptor to EVs. The resulting engineered EVs were able to efficiently inhibit activation of the IL6 trans-signalling pathway in reporter cells, while having no effect on the IL6 classical signalling. IL6ST decoy receptor EVs, were also capable of blocking the IL6 trans-signalling pathway in C2C12 myoblasts and myotubes, thereby inhibiting the phosphorylation of STAT3 and partially reversing the anti-differentiation effects observed when treating cells with IL6/IL6R complexes. Treatment of a Duchenne muscular dystrophy mouse model with IL6ST decoy receptor EVs resulted in a reduction in STAT3 phosphorylation in the quadriceps and gastrocnemius muscles of these mice, thereby demonstrating in vivo activity of the decoy receptor EVs as a potential therapy. Taken together, this study reveals the IL6 trans-signalling pathway as a promising therapeutic target in DMD, and demonstrates the therapeutic potential of IL6ST decoy receptor EVs

Verification and Diagnostics Framework in ATLAS Trigger/DAQ

Trigger and data acquisition (TDAQ) systems for modern HEP experiments are composed of thousands of hardware and software components depending on each other in a very complex manner. Typically, such systems are operated by non-expert shift operators, which are not aware of system functionality details. It is therefore necessary to help the operator to control the system and to minimize system down-time by providing knowledge-based facilities for automatic testing and verification of system components and also for error diagnostics and recovery. For this purpose, a verification and diagnostic framework was developed in the scope of ATLAS TDAQ. The verification functionality of the framework allows developers to configure simple low-level tests for any component in a TDAQ configuration. The test can be configured as one or more processes running on different hosts. The framework organizes tests in sequences, using knowledge about components hierarchy and dependencies, and allowing the operator to verify the functionality of any subset of the system. The diagnostics functionality includes the possibility to analyze the test results and diagnose detected errors, e.g. by starting additional tests and understanding reasons of failures. A conclusion about system functionality, error diagnosis and recovery advice are presented to the operator in a GUI. The current implementation uses the CLIPS expert system shell for knowledge representation and reasoning.Comment: Paper for the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003 (presented as poster). Format: PDF, using MSWord template, 5 pages, 6 figures. PSN TUGP00