lDDT: a local superposition-free score for comparing protein structures and models using distance difference tests

Motivation: The assessment of protein structure prediction techniques requires objective criteria to measure the similarity between a computational model and the experimentally determined reference structure. Conventional similarity measures based on a global superposition of carbon α atoms are strongly influenced by domain motions and do not assess the accuracy of local atomic details in the model. Results: The Local Distance Difference Test (lDDT) is a superposition-free score that evaluates local distance differences of all atoms in a model, including validation of stereochemical plausibility. The reference can be a single structure, or an ensemble of equivalent structures. We demonstrate that lDDT is well suited to assess local model quality, even in the presence of domain movements, while maintaining good correlation with global measures. These properties make lDDT a robust tool for the automated assessment of structure prediction servers without manual intervention. Availability and implementation: Source code, binaries for Linux and MacOSX, and an interactive web server are available at http://swissmodel.expasy.org/lddt Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Comparison between Conventional and Non-Conventional Computer Methods to Define Antiknock Properties of Fuel Mixtures

Research Octane Number (RON) is one of the primary indicators for the determination of the resistance of gasoline fuels to autoignition. This parameter is usually determined with a test procedure involving a standardized engine that requires expensive hardware and time-consuming tests. In this work, a set of different methods with which to determine the RON of gasoline fuel surrogates is presented, considering only computer simulations, which allows to reduce both cost and time for the evaluation. A palette of 11 chemical species has been chosen as the basis for the surrogates’ database, which will be investigated in the work, allowing the representation of the complex chemical formulation of fuels in an easier way. A simplified zero-dimensional engine model of the standard variable compression ratio is used to provide pressure and temperature, then employed to calculate RON. This is done first by means of existing methods, and then by introducing new processes concerning a simplified chemical reactor built on kinetic schemes. Finally, these different methodologies are tested against a molar weighted sum of RONs of each chemical specie, allowing to have a criterion for comparison and evaluating their real prediction capabilities

Possible predicative role of electrical risk score on transcatheter aortic valve replacement outcomes in older patients. preliminary data

Background:Transcatheter aortic valve replacement (TAVR) is an effective procedure capable to change the natural history of the degenerative aortic valve stenosis. Despite the TAVR, the patients with advanced valve disease and severe myocardial damage (low flow, gradient and ejection fraction)show high mortality level. Aim of this study was toevaluate the predicative power of a noninvasive and inexpensive test obtained by means of a simple standard 12-leads electrocardiogram,known as the Electrical Risk Score (ERS). Methods: ERS was composed by seven simple ECG markers: heart rate (>75 bpm); QRS duration (>110 ms), left ventricular hypertrophy (Sokolow-Lyon criteria), delayed QRS transition zone (≥ V4), frontal QRS-T angle (>90°), long QTBazett (>450 ms for men and >460 in women) or JTBazett(330 ms for men and > 340 ms for women);long T peak to T end interval (Tp-e)( >89 ms). An ERS ≥ 4was considered high risk for all-cause or cardiovascular mortality.We calculated retrospectively the pre-procedure ERS in 40 TAVR patients after one year of follow-up. Results: In the follow up the all-cause and cardiovascular mortality were respectively 25% and 15%.None of survivors reported ERS ≥ 4,moreover, the ERS was the strongest predictor of all-cause (odd ratio 3.73, 95% CI: 1.44-9.66, p<0.05) or cardiovascular (odd ratio 3.95, 95% CI: 1.09-14.27, p<0.05) mortality.ROC curves showed that ERS had the widest significant sensitivity-specificity area under the curve (auc) predicting all-cause (auc: 0.855, p<0.05) or cardiovascular mortality (auc: 0.908, p<0.05). Conclusions:In this pivotal study, ERS resulted an useful tool to stratify the risk of mortality in one-year follow-up TAVR patients. Obviously, it is necessary to confirm these data in large prospective studies

Triggers for atrial fibrillation. the role of anxiety

Atrial fibrillation (AF) is the most widely recognized arrhythmia. Systemic arterial hypertension, diabetes, obesity, heart failure, and valvular heart diseases are major risk factors for the onset and progression of AF. Various studies have emphasized the augmented anxiety rate among AF patients due to the poor quality of life; however, little information is known about the possibility of triggering atrial fibrillation by anxiety. +e present review sought to underline the possible pathophysiological association between AF and anxiety disorders and suggests that anxiety can be an independent risk factor for AF, acting as atrigger, creating an arrhythmogenic substrate, and modulating the autonomic nervous system.+e awareness of the role of anxietydisorders as a risk factor for AF may lead to the development of new clinical strategies for the management of AF

OpenStructure: a flexible software framework for computational structural biology

Motivation: Developers of new methods in computational structural biology are often hampered in their research by incompatible software tools and non-standardized data formats. To address this problem, we have developed OpenStructure as a modular open source platform to provide a powerful, yet flexible general working environment for structural bioinformatics. OpenStructure consists primarily of a set of libraries written in C++ with a cleanly designed application programmer interface. All functionality can be accessed directly in C++ or in a Python layer, meeting both the requirements for high efficiency and ease of use. Powerful selection queries and the notion of entity views to represent these selections greatly facilitate the development and implementation of algorithms on structural data. The modular integration of computational core methods with powerful visualization tools makes OpenStructure an ideal working and development environment. Several applications, such as the latest versions of IPLT and QMean, have been implemented based on OpenStructure—demonstrating its value for the development of next-generation structural biology algorithms. Availability: Source code licensed under the GNU lesser general public license and binaries for MacOS X, Linux and Windows are available for download at http://www.openstructure.org. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

OpenStructure: a flexible software framework for computational structural biology

Motivation: Developers of new methods in computational structural biology are often hampered in their research by incompatible software tools and non-standardized data formats. To address this problem, we have developed OpenStructure as a modular open source platform to provide a powerful, yet flexible general working environment for structural bioinformatics. OpenStructure consists primarily of a set of libraries written in C++ with a cleanly designed application programmer interface. All functionality can be accessed directly in C++ or in a Python layer, meeting both the requirements for high efficiency and ease of use. Powerful selection queries and the notion of entity views to represent these selections greatly facilitate the development and implementation of algorithms on structural data. The modular integration of computational core methods with powerful visualization tools makes OpenStructure an ideal working and development environment. Several applications, such as the latest versions of IPLT and QMean, have been implemented based on OpenStructure—demonstrating its value for the development of next-generation structural biology algorithms

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 &lt; 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p &lt; 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p &lt; 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 &lt; 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p &lt; 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

A proposed strategy for anticoagulation therapy in noncompaction cardiomyopathy

Noncompaction cardiomyopathy (NCCM) is a rare condition characterized by prominent trabeculae, deep intertrabecular recesses, and a left ventricular myocardium with a two-layered structure, characterized by a spongy endocardial layer and a thinner and compacted epicardial one. NCCM can be isolated or associated with other congenital heart diseases and complex syndromes involving neuromuscular disorders and facial dysmorphisms. To date, more than 40 genes coding for sarcomeric, cytoskeletal, ion channels, and desmosomal proteins have been identified. Clinical presentation is also highly variable, ranging from no symptoms to end-stage heart failure (HF), lethal arrhythmias, sudden cardiac death, or thromboembolic events. In particular, the prevalence of thromboembolism in NCCM patients appears to be higher than that of a similar, age-matched population without NCCM. Thromboembolism has a multifactorial aetiology, which is linked to genetic, as well as traditional cardiovascular risk factors. In previous studies, atrial fibrillation (AF) was observed in approximately 25-30% of adult NCCM patients and embolism had a cardiac source in ~63-69% of cases; therefore, AF represents a strong predictor of adverse events, especially if associated to HF and neuromuscular disorders. Left ventricular dysfunction is another risk factor for thromboembolism, as a result of blood stagnation and local myocardial injury. Moreover, it is not completely clarified if the presence of deep intertrabecular recesses causing stagnant blood flow can constitute per se a thrombogenic substrate even in absence of ventricular dysfunction. For the clinical management of NCCM patients, an appropriate stratification of the thromboembolic risk is of utmost importance for a timely initiation of anticoagulant therapy. The aim of the present study is to review the available literature on NCCM with particular attention on thromboembolic risk stratification and prevention and the current evidence for oral anticoagulation therapy. The use of direct oral anticoagulants vs. vitamin K antagonists is also discussed with important implications for patient treatment and prognosis

Preliminary Assessment of Radiolysis for the Cooling Water System in the Rotating Target of {SORGENTINA}-{RF}

The SORGENTINA-RF project aims at developing a 14 MeV fusion neutron source featuring an emission rate in the order of 5-7 x 10(13) s(-1). The plant relies on a metallic water-cooled rotating target and a deuterium (50%) and tritium (50%) ion beam. Beyond the main focus of medical radioisotope production, the source may represent a multi-purpose neutron facility by implementing a series of neutron-based techniques. Among the different engineering and technological issues to be addressed, the production of incondensable gases and corrosion product into the rotating target deserves a dedicated investigation. In this study, a preliminary analysis is carried out, considering the general layout of the target and the present choice of the target material

Genetic Structure of Bluefin Tuna in the Mediterranean Sea Correlates with Environmental Variables

Abstract Background Atlantic Bluefin Tuna (ABFT) shows complex demography and ecological variation in the Mediterranean Sea. Genetic surveys have detected significant, although weak, signals of population structuring; catch series analyses and tagging programs identified complex ABFT spatial dynamics and migration patterns. Here, we tested the hypothesis that the genetic structure of the ABFT in the Mediterranean is correlated with mean surface temperature and salinity. Methodology We used six samples collected from Western and Central Mediterranean integrated with a new sample collected from the recently identified easternmost reproductive area of Levantine Sea. To assess population structure in the Mediterranean we used a multidisciplinary framework combining classical population genetics, spatial and Bayesian clustering methods and a multivariate approach based on factor analysis. Conclusions FST analysis and Bayesian clustering methods detected several subpopulations in the Mediterranean, a result also supported by multivariate analyses. In addition, we identified significant correlations of genetic diversity with mean salinity and surface temperature values revealing that ABFT is genetically structured along two environmental gradients. These results suggest that a preference for some spawning habitat conditions could contribute to shape ABFT genetic structuring in the Mediterranean. However, further studies should be performed to assess to what extent ABFT spawning behaviour in the Mediterranean Sea can be affected by environmental variation.(undefined