Characterisation of lnc-G4, a long noncoding RNA that regulates skeletal muscle differentiation through translational repression of G-quadruplex containing mRNAs

Long non-coding RNAs are crucial regulators of the fine tuning of gene expression. Their role has been widely studied especially in developmental processes such as skeletal muscle differentiation. In particular, a novel cytoplasmic long non-coding RNA, called lnc- G4, has a relevant role in promoting murine C2C12 myoblast differentiation. The analysis of the interactors of this long non- coding RNA showed its ability to base-pair with many mRNAs thanks to a repeated element embedded in its sequence; among the interactors, we focused on MLX mRNA, which encodes for a myogenic transcription factor. We demonstrated that lnc-G4 directly interacts with the three splicing isoforms of MLX mRNA, while it is able to specifically inhibit the translation of only MLX g isoform; this translational regulation could depend on the recruitment of the RNA helicase DHX36. Interestingly, the effect of lnc-G4 on MLX g regulates the subcellular localization of the other isoforms, and this has an impact on the transcriptional activation of MLX targets. Taken together, these evidences suggest that lnc-G4 could be a key factor in post-transcriptional gene regulation during the early phases of myogenesis through the translational regulation of MLX g. Moreover, lnc-G4 interacts with other mRNAs, and the regulation mechanism could be extended to many other targets

Info-Struttura. Algoritmi generativi per interventi site specific: il viadotto dei Navicelli

L’area al di sotto del viadotto dei Navicelli del porto di Livorno costituisce un’amnesia urbana ignorata da un’espansione della città regolata dal semplice criterio dell’addizione di elementi. In opposizione al consumo di territorio, si vogliono sfruttare le pieghe dell’esistente con un intervento site specific. Non solo l’area di interesse, ma l’intera città viene analizzata per trovare punti di intensità e riconoscere il patrimonio genetico che ha generato le sue forme e le sue dinamiche. Il processo progettuale, quindi, si avvicina ad una sorta di ricerca di laboratorio, nella quale i vari componenti (forme, processi, eventi e relazioni) vengono individuati, separati e ricombinati. Lo sviluppo tecnologico contemporaneo, fatto di simulazioni e di potenze di calcolo tali da consentire la gestione di un numero sempre maggiore di informazioni, consente un controllo del progetto perfettamente in linea con tali considerazioni. L’utilizzo di software generativi e parametrici, la programmazione di algoritmi e la creazione di diagrammi digitali consente di gestire dinamicamente i sistemi di dati dall’analisi territoriale e relazionale, alla creazione di geometrie complesse, fino alla fase di dimensionamento strutturale di massima. Utilizzando Grasshopper® (plug-in di Rhinoceros®) viene costituita una specifica pipeline di software, allo scopo di collegare in modo bidirezionale e senza soluzione di continuità la parte di indagine e modellazione generativa (Rhinoceros® + Grasshopper®) con quella di analisi e dimensionamento dei profili in acciaio (Grasshopper® + GeometryGym® + SAP 2000®), riconducendo i dati nella stessa struttura d’informazione attraverso cicli di feedback. In ogni punto di tale struttura (o, se si preferisce, in ogni fase del processo progettuale), è possibile effettuare variazioni sui parametri ed osservarne immediatamente gli effetti sull’intero sistema, consentendo la ricerca della miglior combinazione tra processo architettonico generativo e soluzione tecnica

Empowering Games. Meaning Making by Designing and Playing Location Based Mobile Games.

The article analyses and discusses the use of Location Based Mobile Games to raise awareness on sensitive issues connected to illness and disability. We report on a study grounded on higher education didactic experiences. By means of a multi-methodological approach we analysed the experience of designing and playing games and their fallouts in terms of learning and awareness about the topics addressed. The study is conducted from a design perspective and aims to understand whether designing and playing LBMGs can sensitise designers and players on sensitive topic

La Musealizzazione dello studio d'artista: il caso dello scultore Gavino Tilocca (1911-1999)

Historical houses and artist's studios represent an immense cultural heritage and are considered universally real theatres of historical memory thanks to their ability to provide valuable information about life and works of those inhabited them. Considering this panorama of studies, this paper aims to reconstruct the artistic career of the sculptor Gavino Tilocca (Sassari, 1911-1999) - a significant presence of Sardinian art scene after World War II, and a prominent figure of Italian ceramics between the Fifties and the Sixties - starting from its studio in Sassari to trace then a musealization project of his place of work. To better understand the dynamics that lie behind the conversion from private spaces in public ones, four case studies will be considered: the reconstruction of Constantin Brancusi’s studio in Paris and the relocation of the Francis Bacon’s studio in Dublin as well as the redevelopment of Giorgio Marandi's house in Bologna and Carlo Zauli’s laboratory in Faenza. These experiences form the basis of the reflections will lead to the realization of the transformation project of the Gavino Tilocca's studio in a museum, whose goal is to create a public centre of study and research, education and entertainment and at the same time to give rise to a place of affection for the regional community

A Comprehensive Study of Code-removal Patches in Automated Program Repair

Automatic Program Repair (APR) techniques can promisingly help reducing the cost of debugging. Many relevant APR techniques follow the generate-and-validate approach, that is, the faulty program is iteratively modified with different change operators and then validated with a test suite until a plausible patch is generated. In particular, Kali is a generate-and-validate technique developed to investigate the possibility of generating plausible patches by only removing code. Former studies show that indeed Kali successfully addressed several faults. This paper addresses the case of code-removal patches in automated program repair investigating the reasons and the scenarios that make their creation possible, and the relationship with patches implemented by developers. Our study reveals that code-removal patches are often insufficient to fix bugs, and proposes a comprehensive taxonomy of code-removal patches that provides evidence of the problems that may affect test suites, opening new opportunities for researchers in the field of automatic program repair.Comment: New version of the manuscrip

Comparison of the calorimetric and kinematic methods of neutrino energy reconstruction in disappearance experiments

To be able to achieve their physics goals, future neutrino-oscillation experiments will need to reconstruct the neutrino energy with very high accuracy. In this work, we analyze how the energy reconstruction may be affected by realistic detection capabilities, such as energy resolutions, efficiencies, and thresholds. This allows us to estimate how well the detector performance needs to be determined a priori in order to avoid a sizable bias in the measurement of the relevant oscillation parameters. We compare the kinematic and calorimetric methods of energy reconstruction in the context of two muon-neutrino disappearance experiments operating in different energy regimes. For the calorimetric reconstruction method, we find that the detector performance has to be estimated with a ~10% accuracy to avoid a significant bias in the extracted oscillation parameters. On the other hand, in the case of kinematic energy reconstruction, we observe that the results exhibit less sensitivity to an overestimation of the detector capabilities.Comment: 16 pages, 14 figures, matches the version published in Phys. Rev.

GHItaly'17: 1st Workshop on Games-Human Interaction

The 1st Workshop on Games-Human Interaction (GHItaly ‘17) aims at bringing together scholars and industry practitioners to establish a common ground on the topic

Nocturnal Arrhythmias and Heart-Rate Swings in Patients With Obstructive Sleep Apnea Syndrome Treated With Beta Blockers

Background: The higher cardiovascular variability and the increased prevalence of arrhythmias in patients with obstructive sleep apneas may contribute to their higher rate of fatal events during sleep. In this regard, the use of beta blockers (BB) is debated because they may induce bradyarrhythmias and alter the pattern of heart rate changes induced by apneas. Thus, the aim of our study is to quantify peri-apneic heart-rate swings and prevalence of nocturnal bradyarrhythmias in BB-treated and BB-naive patients with obstructive sleep apnea. Methods and Results: Our real-life, retrospective, cohort study analyzed data from patients with obstructive sleep apnea after a basal cardiorespiratory polysomnography. Among 228 eligible participants, we enrolled 78 BB-treated and 88 BB-naive patients excluding those treated with antiarrhythmic drugs or pacemakers, or with uninterpretable ECG traces during polysomnography. In each patient, type and frequency of arrhythmias were identified and peri-apneic changes of RR intervals were evaluated for each apnea. BB-treated patients were older and with more comorbidities than BB-naive patients, but had similar obstructive sleep apnea severity, similar frequency of arrhythmic episodes, and similar prevalence of bradyarrhythmias. Apnea-induced heart-rate swings, unadjusted for age, showed lower RR interval changes in BB-treated (133.5 +/- 63.8 ms) than BB-naive patients (171.3 +/- 87.7 ms, P=0.01), lower RR interval increases during apneas (58.5 +/- 28.5 versus 74.6 +/- 40.2 ms, P=0.01), and lower RR interval decreases after apneas (75.0 +/- 42.4 versus 96.7 +/- 55.5 ms, P0.05). Conclusions: BB appear to be safe in patients with obstructive sleep apnea because they are not associated with worse episodes of nocturnal bradyarrhythmias and even seem protective in terms of apnea-induced changes of heart rate

Arrhythmic risk in elderly patients candidates to transcatheter aortic valve replacement. predicative role of repolarization temporal dispersion

Degenerative aortic valve stenosis (AS) is associated to ventricular arrhythmias and sudden cardiac death, as well as mental stress in specific patients. In such a context, substrate, autonomic imbalance as well as repolarization dispersion abnormalities play an undoubted role. Aim of the study was to evaluate the increase of premature ventricular contractions (PVC) and complex ventricular arrhythmias during mental stress in elderly patients candidate to the transcatheter aortic valve replacement (TAVR). In eighty-one elderly patients with AS we calculated several short-period RRand QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE). All the myocardial repolarization dispersion markers worsened during mental stress (p < 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p < 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p < 0.05). Eventually, twenty-four (30%) and twelve (15%) patients increased significantly PVC and, respectively, complex ventricular arrhythmias during the MMSE administration. At multivariate logistic regression analysis, the standard deviation of QTend (QTesd), obtained at rest, was predictive of increased PVC (odd ratio: 1.54, 95% CI 1.14–2.08; p = 0.005) and complex ventricular arrhythmias (odd ratio: 2.31, 95% CI 1.40–3.83; p = 0.001) during MMSE. The QTesd showed the widest sensitive-specificity area under the curve for the increase of PVC (AUC: 0.699, 95% CI: 0.576–0.822, p < 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p < 0.05). In elderly with AS ventricular arrhythmias worsened during a simple cognitive assessment, this events being a possible further burden on the outcome of TAVR. QTesd might be useful to identify those patients with the highest risk of ventricular arrhythmias. Whether the TAVR could led to a QTesd reduction and, hence, to a reductionof thearrhythmicburdenin thissettingofpatients isworthytobe investigated