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.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

HRTEM observation of the monoclinic-to-tetragonal m-t) phase transition in nanocrystalline ZrO2

The orientation relations m(100) || t(001), m[001] || t[110]; m(011) || t(100), m[100] || t[001]; m(100) || t(110), m[001] || t[001]; m(013) || t(116), m[001] || t[001] (indices for the primitive tetragonal cell) have been found between the tetragonal (t) and monoclinic (m) domains during the electron irradiation-induced m-t phase transition observed in-situ with HREM within isolated zirconia nanoparticles. Geometric models of the m-t interfaces are proposed.     

Building kernels from binary strings for image matching.

In the statistical learning framework, the use of appropriate kernels may be the key for substantial improvement in solving a given problem. In essence, a kernel is a similarity measure between input points satisfying some mathematical requirements and possibly capturing the domain knowledge. In this paper, we focus on kernels for images: we represent the image information content with binary strings and discuss various bitwise manipulations obtained using logical operators and convolution with nonbinary stencils. In the theoretical contribution of our work, we show that histogram intersection is a Mercer's kernel and we determine the modifications under which a similarity measure based on the notion of Hausdorff distance is also a Mercer's kernel. In both cases, we determine explicitly the mapping from input to feature space. The presented experimental results support the relevance of our analysis for developing effective trainable systems.     

Study of phase equilibria in the Al - Pd - Re system

Scanning and transmission electron microscopy have been combined with x-ray diffraction to examine the phase equilibria in the Al - Pd - Re system at 1000°C for compositions from 50 to 100 at.% Al, and the corresponding isothermal section has been constructed. The binary monoclinic Al₃ Re phase has been observed for the first time. It is confirmed that there is a stable icosahedral phase in this system. The boundaries to its homogeneity region have been determined and the phase equilibria in which it participates.     

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds

The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.     

Line balancing in a just-in-time production environment: balancing multiple U-lines

The introduction of multiple, independent production lines has helped many firms to increase their production flexibility, provide for redundancy when equipment breaks down, reduce idle time and labor costs, and achieve many other benefits. This paper introduces and formalizes the multiple U-line balancing problem. Optimal solution methodologies are provided for Type I (minimize the number of stations for a given cycle time), Type II (minimize the cycle time for a given number of stations), and cost-minimization line-balancing problems. A branch-and-bound algorithm is also developed for the situation in which equipment requirements are dependent on the line configuration and the task assignment to stations. Computational results indicate that the greatest benefit of exploiting multiple lines occurs for smaller cycle-time problems that require higher output.     

Object-oriented query language access to relational databases: A semantic framework for query translation

This research investigates and approach to query processing in a multidatabase system that uses an objectoriented model to capture the semantics of other data models. The object-oriented model is used to construct a global schema, defining an integrated view of the different schemas in the environment. The model is also used as a self-describing model to build a meta-database for storing information about the global schema. A unique aspect of this work is that the object-oriented model is used to describe the different data models of the multidatabase environment, thereby extending the meta database with semantic information about the local schemas. With the global and local schemas all represented in an object-oriented form, structural mappings between the global schema and each local schema are then easily supported. An object algebra then provides a query language for expressing global queries, using the structural mappings to translate object algebra queries into SQL queries over local relational schema. The advantage of using an object algebra is that the object-oriented database can be viewed as a blackboard for temporary storage of local data and for establishing relationships between different databases. The object algebra can be used to directly retrieve temporarily-stored data from the object-oriented database or to transparently retrieve data from local sources using the translation process described in this paper.     

Antimicrobial activity of dogwood fruits (Cornus drummondii) from winter food caches of eastern woodrats (Neotoma floridana)

Post-harvest loss of resources to microbial competitors affects a number of species of animals, and many of them have evolved behaviors that reduce the likelihood of such loss. We previously described the inhibition ofBacillus psychrophilus by dogwood fruits (Cornus drummondii), which can comprise a significant portion of the winter food cache of the eastern woodrat (Neotoma floridana). The present study is a further investigation of the ability of dogwood fruits to inhibit growth ofB. psychrophilus. Additionally, we tested the antimicrobial activity of dogwood fruits onEscherichia coli andStaphlococcus aureus. Results of our study indicate that fresh fruits inhibit the growth ofB. psychrophilus andS. aureus but notE. coli. However, fruits taken from woodrat dens after four and six months storage inhibited growth of all three species of bacteria. Further, the strength of inhibition increased over the test period. We suggest the presence of an inhibitor allows woodrats to compete effectively for a valuable and limited food resource.