AcT-2: A Novel Myotropic and Antimicrobial Type 2 Tryptophyllin from the Skin Secretion of the Central American Red-Eyed Leaf Frog, Agalychnis callidryas

Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure—GMRPPWF-NH2—was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50 = 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50 = 9.3 μM). The peptide could also inhibit the growth of the microorganisms, Staphylococcus aureus, (MIC = 256 mg/L) Escherichia coli (MIC = 512 mg/L), and Candida albicans (128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

La governance degli enti locali sulle aziende di gestione dei servizi pubblici. Strumenti di programmazione e controllo in ottica di gruppo

Lo scopo del presente lavoro è delineare un nuovo modello inerente l'organizzazione, i processi e gli strumenti di programmazione e controllo a supporto della governance degli enti locali sulle loro aziende di gestione dei servizi pubblici, con particolare attenzione per la variabile strumentale. E' stata adottata una metodologia mista, deduttivo-induttiva. Nella fase deduttiva è stata analizzata la normativa italiana nonché la dottrina economico aziendale nazionale ed internazionale in tema di gestione dei servizi pubblici locali: in tal modo è stato estrapolato un modello normativo-dottrinale inerente l'organizzazione, i processi e gli strumenti di programmazione e controllo a supporto della governance degli enti locali sulle loro aziende di gestione dei servizi pubblici. Nella fase induttiva è stata realizzata un'indagine empirica che ha coinvolto i comuni capoluogo di Emilia-Romagna e Toscana, in modo tale da testare il livello di utilizzo del modello normativo-dottrinale precedentemente estrapolato Nella fase di feedback sono stati delineati i punti di forza e di debolezza del succitato modello emergenti dalla ricerca. Si è così cercato di proporre un nuovo modello, con particolare attenzione per la variabile strumentale, in grado di porre rimedio ai punti di debolezza e di potenziare i punti di forza del modello normativo-dottrinale.

Il performance measurement negli enti locali. Strumenti innovativi nella prospettiva economico-aziendale

In un'epoca di risorse scarse e di crescente disaffezione verso la politica, l'azione degli enti locali ha un impatto sempre più rilevante sulla qualità della vita del cittadino. A tal fine, l'adozione di sistemi di programmazione e controllo, supportati da idonei strumenti, diviene essenziale per il perseguimento dell'efficienza e dell'efficacia e dunque per riconquistare la fiducia del cittadino stesso. Il volume, sulla base di un'analisi della normativa (dai primi anni Novanta fino al DL 174/2012 e s.m.i.) e della letteratura nazionale ed internazionale in tema di performance measurement, identifica un Modello ottimale (Modello PerformEL) per la redazione di due documenti che possono avere un ruolo centrale nel sistema di programmazione e controllo locale: il Piano e la Relazione sulla Performance. La capacità informativa di questi ultimi è testata tramite un'indagine empirica che ha coinvolto i comuni con almeno 50.000 abitanti, comparando struttura, forma e contenuti di tali documenti con quelli ritenuti ottimali e quindi inseriti nel Modello. Sulla base dei risultati dell'indagine, che mostrano una diffusa inadeguatezza informativa degli strumenti analizzati, viene proposto un percorso evolutivo per la graduale realizzazione di documenti di programmazione e controllo che, al di là della loro 'etichetta formale' (Piano della Performance piuttosto che Piano Esecutivo di Gestione, Relazione sulla Performance o Report dei Controlli interni) permetta di semplificare l'architettura informativa dell'ente locale (nel rispetto del DL 174/2012) e parimenti di trasformare i molteplici inutili adempimenti in utili documenti di performance measurement.

Robust visual tracking using structurally random projection and weighted least squares

Sparse representation based visual tracking approaches have attracted increasing interests in the community in recent years. The main idea is to linearly represent each target candidate using a set of target and trivial templates while imposing a sparsity constraint onto the representation coefficients. After we obtain the coefficients using L1-norm minimization methods, the candidate with the lowest error, when it is reconstructed using only the target templates and the associated coefficients, is considered as the tracking result. In spite of promising system performance widely reported, it is unclear if the performance of these trackers can be maximised. In addition, computational complexity caused by the dimensionality of the feature space limits these algorithms in real-time applications. In this paper, we propose a real-time visual tracking method based on structurally random projection and weighted least squares techniques. In particular, to enhance the discriminative capability of the tracker, we introduce background templates to the linear representation framework. To handle appearance variations over time, we relax the sparsity constraint using a weighed least squares (WLS) method to obtain the representation coefficients. To further reduce the computational complexity, structurally random projection is used to reduce the dimensionality of the feature space while preserving the pairwise distances between the data points in the feature space. Experimental results show that the proposed approach outperforms several state-of-the-art tracking methods.

Updating Credal Networks is Approximable in Polynomial Time

Credal networks relax the precise probability requirement of Bayesian networks, enabling a richer representation of uncertainty in the form of closed convex sets of probability measures. The increase in expressiveness comes at the expense of higher computational costs. In this paper, we present a new variable elimination algorithm for exactly computing posterior inferences in extensively specified credal networks, which is empirically shown to outperform a state-of-the-art algorithm. The algorithm is then turned into a provably good approximation scheme, that is, a procedure that for any input is guaranteed to return a solution not worse than the optimum by a given factor. Remarkably, we show that when the networks have bounded treewidth and bounded number of states per variable the approximation algorithm runs in time polynomial in the input size and in the inverse of the error factor, thus being the first known fully polynomial-time approximation scheme for inference in credal networks.

An unbiased genetic screen reveals the polygenic nature of the influenza virus anti-interferon response

UNLABELLED: Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space.

IMPORTANCE: In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response.

On the statistical memory architecture exploration and optimization

The worsening of process variations and the consequent increased spreads in circuit performance and consumed power hinder the satisfaction of the targeted budgets and lead to yield loss. Corner based design and adoption of design guardbands might limit the yield loss. However, in many cases such methods may not be able to capture the real effects which might be way better than the predicted ones leading to increasingly pessimistic designs. The situation is even more severe in memories which consist of substantially different individual building blocks, further complicating the accurate analysis of the impact of variations at the architecture level leaving many potential issues uncovered and opportunities unexploited. In this paper, we develop a framework for capturing non-trivial statistical interactions among all the components of a memory/cache. The developed tool is able to find the optimum memory/cache configuration under various constraints allowing the designers to make the right choices early in the design cycle and consequently improve performance, energy, and especially yield. Our, results indicate that the consideration of the architectural interactions between the memory components allow to relax the pessimistic access times that are predicted by existing techniques.

Dynamics and structure of self-generated magnetics fields on solids following high contrast, high intensity laser irradiation

The dynamics of self-generated magnetic B-fields produced following the interaction of a high contrast, high intensity (I > 10¹⁹W cm^-2) laser beam with thin (3 μm thick) solid (Al or Au) targets is investigated experimentally and numerically. Two main sources drive the growth of B-fields on the target surfaces. B-fields are first driven by laser-generated hot electron currents that relax over ∼10-20 ps. Over longer timescales, the hydrodynamic expansion of the bulk of the target into vacuum also generates B-field induced by non-collinear gradients of density and temperature. The laser irradiation of the target front side strongly localizes the energy deposition at the target front, in contrast to the target rear side, which is heated by fast electrons over a much larger area. This induces an asymmetry in the hydrodynamic expansion between the front and rear target surfaces, and consequently the associated B-fields are found strongly asymmetric. The sole long-lasting (>30 ps) B-fields are the ones growing on the target front surface, where they remain of extremely high strength (∼8-10 MG). These B-fields have been recently put by us in practical use for focusing laser-accelerated protons [B. Albertazzi et al., Rev. Sci. Instrum. 86, 043502 (2015)]; here we analyze in detail their dynamics and structure.

Development of open models and tools for seismic risk assessment: application to Portugal

The exponential growth of the world population has led to an increase of settlements often located in areas prone to natural disasters, including earthquakes. Consequently, despite the important advances in the field of natural catastrophes modelling and risk mitigation actions, the overall human losses have continued to increase and unprecedented economic losses have been registered. In the research work presented herein, various areas of earthquake engineering and seismology are thoroughly investigated, and a case study application for mainland Portugal is performed. Seismic risk assessment is a critical link in the reduction of casualties and damages due to earthquakes. Recognition of this relation has led to a rapid rise in demand for accurate, reliable and flexible numerical tools and software. In the present work, an open-source platform for seismic hazard and risk assessment is developed. This software is capable of computing the distribution of losses or damage for an earthquake scenario (deterministic event-based) or earthquake losses due to all the possible seismic events that might occur within a region for a given interval of time (probabilistic event-based). This effort has been developed following an open and transparent philosophy and therefore, it is available to any individual or institution. The estimation of the seismic risk depends mainly on three components: seismic hazard, exposure and vulnerability. The latter component assumes special importance, as by intervening with appropriate retrofitting solutions, it may be possible to decrease directly the seismic risk. The employment of analytical methodologies is fundamental in the assessment of structural vulnerability, particularly in regions where post-earthquake building damage might not be available. Several common methodologies are investigated, and conclusions are yielded regarding the method that can provide an optimal balance between accuracy and computational effort. In addition, a simplified approach based on the displacement-based earthquake loss assessment (DBELA) is proposed, which allows for the rapid estimation of fragility curves, considering a wide spectrum of uncertainties. A novel vulnerability model for the reinforced concrete building stock in Portugal is proposed in this work, using statistical information collected from hundreds of real buildings. An analytical approach based on nonlinear time history analysis is adopted and the impact of a set of key parameters investigated, including the damage state criteria and the chosen intensity measure type. A comprehensive review of previous studies that contributed to the understanding of the seismic hazard and risk for Portugal is presented. An existing seismic source model was employed with recently proposed attenuation models to calculate probabilistic seismic hazard throughout the territory. The latter results are combined with information from the 2011 Building Census and the aforementioned vulnerability model to estimate economic loss maps for a return period of 475 years. These losses are disaggregated across the different building typologies and conclusions are yielded regarding the type of construction more vulnerable to seismic activity.

Orizzonte Cina: le sfide dell’urbanizzazione al 2020

A metà marzo 2014 il governo cinese ha reso pubblico un documento di indirizzo per le politiche urbane che potrebbe determinare una correzione di rotta nell’attuale processo di rapida urbanizzazione che il paese attraversa ormai da qualche decennio. Si tratta del National New-Type Urbanization Plan – Guojia Xinxing Chengzhenhua Guihua 2014-2020 (SCPRC, 2014), ovvero il primo piano nazionale per un nuovo modello people-centred di urbanizzazione del paese. Compito di questo saggio breve è quello di riflettere sulle sfide future del processo di urbanizzazione cinese che tale documento lascia intravedere, alla luce di una serie di nodi irrisolti del processo non finito di opening-up della società cinese al modello capitalista occidentale.

Influência de um programa de exercícios específicos em estudantes de violino

Introdução: A elevada prevalência de problemas musculosqueléticos relacionados com a performance musical (PMRPM) em estudantes universitários de música, sobretudo violinistas, justifica uma abordagem preventiva junto destes, nomeadamente, através do exercício. Este deve ser específico e baseado nos padrões de movimento durante a performance musical do violinista. Objetivos: verificar a influência de um programa de exercícios específicos (PEE) nos sintomas relacionados com a prática musical, na incapacidade funcional e na autoperceção da performance física e musical, em estudantes universitários de violino. Métodos: estudo quase-experimental baseado num estudo piloto com 24 estudantes para pesquisa da sintomatologia, e 4 para análise cinemática e cinética do gesto técnico. No estudo principal participaram 22 violinistas divididos equitativamente, e por disponibilidade, entre grupo experimental (GE) e grupo de controlo (GC). O GE realizou o PEE bissemanalmente, durante 8 semanas. No momento inicial e após 8 semanas, os participantes preencheram: Questionário de Performance (incluiu Escala Visual Analógica), Disabilities of the Arm, Shoulder and Hand, Oswestry Disability Index versão 2.0, Pain Catastrophizing Scale e Escala de Borg Modificada. Resultados: do estudo piloto constatou-se que os sintomas mais frequentes, dor e fadiga, localizavam-se na cintura escapular, ombros e coluna lombar; os ombros aparentavam maior risco de PMRPM; era necessário aumentar a endurance dos mobilizadores dos membros superiores (principalmente deltóide) e relaxar os estabilizadores da coluna cervical (sobretudo trapézio superior). No final do PEE, o GE apresentou significativamente melhores pontuações do que o GC na percentagem de violinistas com “dor na coluna lombar esquerda” (p=0,007), frequência da dor (U=8,5; W=29,5; p=0,016), número de locais com sintomas (U=18; W=84; p=0,003) e amplificação (U=26; W=92; p=0,021). Conclusão: Um PEE pode produzir efeitos positivos na diminuição dos sintomas relacionados com a prática musical e incapacidade funcional, e na melhoria de alguns parâmetros da performance física autoreportada, em estudantes universitários de violino.

Comparação do efeito da técnica de facilitação neuromuscular proprioceptiva com a técnica de músculo energia no alongamento muscular dos isquiotibiais a curto prazo

Introdução: A aplicação das técnicas de Contrair-Relaxar com Contracção do Antagonista (CRCA) e de Músculo Energia (TME) promovem um aumento da flexibilidade muscular, contudo poucos estudos comparam a eficácia de ambas. Apresentam aspectos comuns como a contracção prévia do músculo a alongar sendo esta máxima na CRCA e uma percentagem da máxima na TME. Contudo, alguma evidência sugere que não existe correspondência entre a força produzida e a desejada pelo que este aspecto da TME carece de explicação. Objectivos: Confirmar se a técnica CRCA e a TME são efectivas no alongamento muscular dos isquiotibiais a curto prazo, caso sejam determinar qual a mais efectiva. Pretende-se ainda avaliar se a percepção ao esforço durante a aplicação da TME corresponde à força efectivamente realizada. Métodos: Efectuou-se um estudo experimental com 45 voluntários distribuídos aleatoriamente pelos grupos CRCA, TME e Controlo. Avaliou-se a amplitude articular passiva de extensão do joelho antes e depois de aplicar as técnicas, utilizando um goniómetro. Nos participantes submetidos à TME avaliou-se a percepção ao esforço, solicitando uma contracção submáxima isométrica de 40% medida através do dinamómetro de mão. Resultados: Verificou-se um efeito das técnicas entre as avaliações (Teste ANOVA medidas repetidas factor tempo: p<0,001) e entre os grupos (tempo*grupo: p<0,001). Comparando os grupos dois a dois, verificaram-se diferenças entre o grupo CRCA e o grupo Controlo (Teste Post Hoc Games-Howell: p=0,001) e entre o grupo TME e o grupo Controlo (p=0,009), não existindo diferenças entre os grupos CRCA e TME (p=0,376). Os grupos CRCA e TME obtiveram um ganho de 10,7º e de 11,4º respectivamente, não havendo diferenças significativas entre os ganhos (Teste T-Student Independente: p=0,599). Existiram diferenças significativas entre os 40% CMVI produzida e desejada (Teste Wilcoxon: p=0,018). Conclusão: Ambas foram efectivas no aumento da flexibilidade muscular dos isquiotibiais a curto prazo. Os efeitos foram comparáveis, mas dada a menor complexidade e menor solicitação a TME foi considerada mais eficiente. A percepção ao esforço durante a aplicação da TME não correspondeu ao esforço desejado, existindo uma tendência para a produção de intensidades de contracções maiores.

How to attract central and Northeneuropeans to a rural tourism establishment in the center of Portugal

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Patient satisfaction after biofeedback for constipation and pelvic floor dyssynergia.

Patients referred for chronic constipation frequently report symptoms of straining, feeling of incomplete evacuation, or the need to facilitate defecation digitally (dyschezia). When such patients show manometric evidence of inappropriate contraction or failure to relax the pelvic floor muscles during attempts to defecate, they are diagnosed as having pelvic floor dyssynergia (Rome I). To evaluate long-term satisfaction of patients with pelvic floor dyssynergia after biofeedback. Forty-one consecutive patients referred for chronic constipation at an outpatient gastrointestinal unit and diagnosed as having pelvic floor dyssynergia who completed a full course of biofeedback. Data have been collected using a standardised questionnaire. A questionnaire survey of patients' satisfaction rate and requirement of aperients was undertaken. Mean age and symptom duration were respectively 41 and 20 years. Half of patients reported fewer than 3 bowel motions per week. Patients were treated with a mean of 5 biofeedback sessions. At the end of the therapy pelvic floor dyssynergia was alleviated in 85% of patients and 49% were able to stop all aperients. Satisfaction was maintained at follow-up telephone interviews undertaken after a mean period of 2 years, as biofeedback was helpful for 79% of patients and 47% still abstained from intake of aperients. Satisfaction after biofeedback is high for patients referred for chronic constipation and diagnosed with pelvic floor dyssynergia. Biofeedback improves symptoms related to dyschezia and reduces use of aperients.

Life design: Un paradigma per la costruzione della vita professionale nel XXI secolo

In questo inizio di secolo, la nuova organizzazione sociale del lavoro pone una serie di domande e di sfide ai ricercatori che intendono aiutare le persone a progettare la loro vita lavorativa. Nell'era della globalizzazione anche per quanto riguarda il career counseling, abbiamo deciso di affrontare queste problematiche e di dare delle risposte che si caratterizzassero come innovative attraverso la costituzione di un forum di discussione internazionale. Si è proceduto in questo modo per evitare le difficoltà che generalmente si incontrano quando si mettono a punto dei modelli e dei metodi in un Paese e poi si esportano in altre culture con l'intento di adattarli alle stesse. Questo articolo presenta i primi risultati della collaborazione che si è registrata - un modello e dei metodi per la consulenza di orientamento. Il modello per l'intervento nell'ambito dell'approccio Life Design si caratterizza per cinque presupposti relativi al modo di vedere le persone e la loro vita lavorativa. Essi riguardano le possibilità contestuali, i processi dinamici, i progressi non-lineari, le molteplici prospettive e la presenza di pattern personali. Partendo da questi cinque presupposti abbiamo messo a punto un modello basato sull'epistemologia del costruzionismo sociale, che sostiene che la conoscenza e l'identità di un individuo sono i prodotti dell'interazione sociale e che il significato è costruito attraverso il discorso. Questo approccio fa riferimento anche alla teoria della costruzione di sé di Guichard (2005) e della costruzione della vita professionale di Savickas (2005), che descrivono le azioni utili a facilitare la progettazione del proprio futuro. Particolare attenzione viene data agli interventi nel corso dell'arco di vita, olistici, contestuali e preventivi.