Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Energy-saving scheduling on IaaS HPC cloud environments based on a multi-objective genetic algorithm

The Journal of Supercomputing - Nowadays, cloud computing is a growing scenario applied to many scientific and manufacturing areas due to its flexibility for adapting to highly demanding computing...     

Linear regression-based multifidelity surrogate for disturbance amplification in multiphase explosion

Structural and Multidisciplinary Optimization - When simulations are very expensive and many are required, as for optimization or uncertainty quantification, a way to reduce cost is using...     

On the efficiency of quantization-based integration methods for building simulation

Models describing energy consumption, heating, and cooling of buildings usually impose difficulties to the numerical integration algorithms used to simulate them. Stiffness and the presence of frequent discontinuities are among the main causes of those difficulties, that become critical when the models grow in size. Quantized State Systems (QSS) methods are a family of numerical integration algorithms that can efficiently handle discontinuities and stiffness in large models. For this reason, they are promising candidates for overcoming the mentioned problems. Based on this observation, this article studies the performance of QSS methods in some systems that are relevant to the field of building simulation. The study includes a performance comparison of different QSS algorithms against state-of-the-art classic numerical solvers, showing that the former can be more than one order of magnitude faster.     

Hierarchical micro-nanostructured albite-based glass-ceramic for high dielectric strength insulators

A novel glass-ceramic material based on albite type Na-rich feldspar has been synthesized by conventional ceramic process. High crystallinity, >94%?Vol.% is obtained by fast sintering which allows energy saving processing. Albite is the main crystalline phase and tetragonal SiO₂ is a secondary phase. Electrical properties were examined by complex impedance, DC measurements, and dielectric breakdown test. Dielectric characterization shows a non-Debye type dielectric behavior with low dielectric constant, 4.6 at 1?MHz, low dielectric losses, (～10^?3 at 1?MHz, and a large dielectric strength, ～60?kV/mm), that it is the largest value reported in ceramic insulators. Those dielectric properties are attained by the low glassy phase content in the samples and their unique micro-nanostructure. All these properties make this novel material a very promising candidate in the market of ceramic electrical insulator, highlighting for high-voltage applications.     

Microbial Fuel Cell Application for Azoic Dye Decolorization with Simultaneous Bioenergy Production Using Stenotrophomonas sp.

A single‐chamber air‐cathode microbial fuel cell (MFC) was successfully applied for decolorization of the diazoic dye Reactive Black 5 (RB5) with simultaneous production of electricity. An innovative low‐cost medium, the marine water‐glucose‐yeast extract medium (MWGY), was developed which appears as a textile marine effluent in terms of salinity. The anode compartment containing a single bacterial strain of Stenotrophomonas sp. showed almost complete dye decolorization with different RB5 concentrations after seven days of treatment. For the four dye concentrations used, a correlation between dye removal and production of electrical energy was found. The comparison of the decolorization process in the MFC with that in a batch reactor as control experiment highlights the efficiency of the single‐chamber air‐cathode MFC technology which improved the dye removal by the same bacterial strain.