Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

<p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p> <p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p> <p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p> <p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p&gt

A genetic algorithm

Castelli, M., Dondi, R., Manzoni, S., Mauri, G., & Zoppis, I. (2019). Top k 2-clubs in a network: A genetic algorithm. In J. J. Dongarra, J. M. F. Rodrigues, P. J. S. Cardoso, J. Monteiro, R. Lam, V. V. Krzhizhanovskaya, M. H. Lees, ... P. M. A. Sloot (Eds.), Computational Science. ICCS 2019: 19th International Conference, 2019, Proceedings (Vol. 5, pp. 656-663). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 11540 LNCS). Springer Verlag. https://doi.org/10.1007/978-3-030-22750-0_63The identification of cohesive communities (dense sub-graphs) is a typical task applied to the analysis of social and biological networks. Different definitions of communities have been adopted for particular occurrences. One of these, the 2-club (dense subgraphs with diameter value at most of length 2) has been revealed of interest for applications and theoretical studies. Unfortunately, the identification of 2-clubs is a computationally intractable problem, and the search of approximate solutions (at a reasonable time) is therefore fundamental in many practical areas. In this article, we present a genetic algorithm based heuristic to compute a collection of Top k 2-clubs, i.e., a set composed by the largest k 2-clubs which cover an input graph. In particular, we discuss some preliminary results for synthetic data obtained by sampling Erdös-Rényi random graphs.authorsversionpublishe

Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies

Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein–Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes

Latin American immigrants in Indianapolis: Perceptions of prejudice and discrimination

The article focuses on immigrants’ interactions with the Indiana natives, with emphasis in the city of Indianapolis and its suburbs. More specifically, this study aims at providing an understanding of the experiences of Latin American immigrants with special attention to perceptions of prejudice and discrimination and to feelings of social exclusion. A substantial proportion of Latin American immigrants interviewed indicated that they considered Indiana natives to be prejudiced and that they had personally experienced discrimination. The study reveals specific examples of discrimination experienced by the immigrants at the work place, in housing, in stores, restaurants and by various service providers. The results of the study demonstrate the relevance of the normative and power resource theories to explain prejudice and discrimination

GenomeBlast: a web tool for small genome comparison

BACKGROUND: Comparative genomics has become an essential approach for identifying homologous gene candidates and their functions, and for studying genome evolution. There are many tools available for genome comparisons. Unfortunately, most of them are not applicable for the identification of unique genes and the inference of phylogenetic relationships in a given set of genomes. RESULTS: GenomeBlast is a Web tool developed for comparative analysis of multiple small genomes. A new parameter called "coverage" was introduced and used along with sequence identity to evaluate global similarity between genes. With GenomeBlast, the following results can be obtained: (1) unique genes in each genome; (2) homologous gene candidates among compared genomes; (3) 2D plots of homologous gene candidates along the all pairwise genome comparisons; and (4) a table of gene presence/absence information and a genome phylogeny. We demonstrated the functions in GenomeBlast with an example of multiple herpesviral genome analysis and illustrated how GenomeBlast is useful for small genome comparison. CONCLUSION: We developed a Web tool for comparative analysis of small genomes, which allows the user not only to identify unique genes and homologous gene candidates among multiple genomes, but also to view their graphical distributions on genomes, and to reconstruct genome phylogeny. GenomeBlast runs on a Linux server with 4 CPUs and 4 GB memory. The online version of GenomeBlast is available to public by using a Web browser with the URL

Intrecci linguistici. Lingue e dialetti italiani tra i giovani italoamericani nella grande area di New York

Da quando furono introdotti dai primi immigrati che si insediarono sul suolo americano, la lingua e i dialetti italiani negli Stati Uniti si sono continuamente trasformati. Sui comportamenti linguistici degli emigrati italiani all\u2019estero incisero fattori di natura sociale, culturale, geografica ed economica, nonch\ue9 le diverse ondate migratorie. In particolare, nelle comunit\ue0 italoamericane, la lingua e i dialetti italiani andarono a comporre un continuum linguistico che si accompagn\uf2 all\u2019inglese secondo combinazioni diverse e con un variegato ventaglio di forme. Questo saggio si propone di ripercorrere le tappe che hanno segnato questi cambiamenti, analizzando alcune ricerche svolte a partire dagli anni Ottanta nonch\ue9 i dati della condizione in cui versa attualmente la lingua italiana negli Stati Uniti. Vengono, inoltre, presentati i risultati legati all\u2019uso della lingua e dei dialetti, frutto di una survey condotta nel 2013 su un campione di giovani italoamericani residenti nella grande area di New York. Nonostante le differenze tra le diverse generazioni d\u2019immigrazione dei giovani partecipanti allo studio, emerge come vi sia, soprattutto nelle nuove generazioni di italoamericani, una tendenza alla ripresa di interesse verso la lingua delle origini e i dialetti, espressa anche attraverso la volont\ue0 di trasmetterla ai propri figli

Experimental realization of on-chip topological nanoelectromechanical metamaterials

Topological mechanical metamaterials translate condensed matter phenomena, like non-reciprocity and robustness to defects, into classical platforms. At small scales, topological nanoelectromechanical metamaterials (NEMM) can enable the realization of on-chip acoustic components, like unidirectional waveguides and compact delay-lines for mobile devices. Here, we report the experimental realization of NEMM phononic topological insulators, consisting of two-dimensional arrays of free-standing silicon nitride (SiN) nanomembranes that operate at high frequencies (10-20 MHz). We experimentally demonstrate the presence of edge states, by characterizing their localization and Dirac cone-like frequency dispersion. Our topological waveguides also exhibit robustness to waveguide distortions and pseudospin-dependent transport. The suggested devices open wide opportunities to develop functional acoustic systems for high-frequency signal processing applications