Empowering precision medicine through high performance computing clusters

The role of High Performance Computing (HPC) in Medicine is greatly increase in these last years, moving from basic research to the clinics. With the advent of Next Generation Sequencing (NGS) technologies, diverse areas of human health have been investigated through different omics techniques. The extensive use of these NGS platforms to high throughput profile human health issues in a cost-efficient manner, is generating huge amount of sequencing data pushing " (https://www.facebook.com/pages/Oatext/1439466783004774) # $ % (https://www.youtube.com/user/users/oatext) ○ ○ ○ Article Article Info Author Info Figures & Data bioinformatic research in the big-data field. Speed, accuracy and reproducibility of massively sequencing analysis have allowed to transfer molecular biology knowledge into precision medicine. Furthermore, Molecular Dynamics (MD) earned a great importance in aiding genome research. Sequencing studies of cancer have allowed to detect and characterize mutated genes that drive tumorigenesis. As a complementary approach, from a biophysical perspective, MD simulations, executed on HPC architectures, have permitted to investigate the role played by pathological mutations on the molecular mechanism of activation

The Need for Speed and Judicial Notice: New York\u27s Admissibility of Lidar Technology in Law Enforcement

(Excerpt) Focusing at the state level, this Note proposes to establish uniformity within New York State by means of judicial notice or legislative action. Part I provides a history, background, and the development of LIDAR, commencing with its predecessor, radar. It discusses LIDAR’s technical workings and the importance of its current usage to law enforcement. Part I also compares LIDAR to radar, which is nationally accepted. Part II explores New York’s adherence to the admissibility standard set forth in Frye v. United States, and shows how New York’s lower courts have been approaching the issue by analyzing several court decisions in which the courts have differed in approach. Part II likewise explores how several other states have approached the issue of LIDAR reliability and explains why New York should follow suit. Part III offers two proposed solutions to the admissibly question. The first is through the normal channels of obtaining judicial notice, a ruling from the New York Court of Appeals, which establishes the reliability and admissibility of LIDAR. The second, more favorable, approach requires that the New York State legislature pass a law proclaiming the reliability of all speed detection devices. Part III proposes a model statute that the New York State legislature could pass to resolve the issue. It also explores the advantages of legislative action over judicial notice and the public policy justifications

The Need for Speed and Judicial Notice: New York\u27s Admissibility of Lidar Technology in Law Enforcement

(Excerpt) Focusing at the state level, this Note proposes to establish uniformity within New York State by means of judicial notice or legislative action. Part I provides a history, background, and the development of LIDAR, commencing with its predecessor, radar. It discusses LIDAR’s technical workings and the importance of its current usage to law enforcement. Part I also compares LIDAR to radar, which is nationally accepted. Part II explores New York’s adherence to the admissibility standard set forth in Frye v. United States, and shows how New York’s lower courts have been approaching the issue by analyzing several court decisions in which the courts have differed in approach. Part II likewise explores how several other states have approached the issue of LIDAR reliability and explains why New York should follow suit. Part III offers two proposed solutions to the admissibly question. The first is through the normal channels of obtaining judicial notice, a ruling from the New York Court of Appeals, which establishes the reliability and admissibility of LIDAR. The second, more favorable, approach requires that the New York State legislature pass a law proclaiming the reliability of all speed detection devices. Part III proposes a model statute that the New York State legislature could pass to resolve the issue. It also explores the advantages of legislative action over judicial notice and the public policy justifications

Survival of farms in Veneto Region 1999-2004.

We model at a micro level farms’ survival in Veneto Region (Italy) for the period 1999- 2004. We use a new database which links information on survival histories contained in the Official Registers of the Chamber of Commerce with information on socio-economic and structural characteristics of farms and farmers collected in the 2000 Census of Agriculture. First, we consider the cohort of farms born in year 1999, then we extend the analysis to all farms registered at the end of year 1999. We find that the model performs quite well in selecting farms with a high probability of survival

The open state of human topoisomerase I as probed by molecular dynamics simulation

The open state of human topoisomerase I has been probed by molecular dynamics simulation, starting from the coordinates of the closed structure of the protein complexed with DNA, after elimination of the 22-bp DNA duplex oligonucleotide. A repulsion force between the two lips of the protein has been introduced for a short time to induce destabilization of the local minimum, after which an unperturbed simulation has been carried out for 10 ns. The simulation shows that the protein undergoes a large conformational change due to rearrangements in the orientation of the protein domains, which however move as a coherent unit, fully maintaining their secondary and tertiary structures. Despite movements between the domains as large as 80–90 Å, the catalytic pentad remains preassembled, the largest deviation of the active site backbone atoms from the starting crystallographic structure being only 1.7 Å. Electrostatic calculation of the open protein structure shows that the protein displays a vast positive region with the active site residues located nearly at its center, in a conformation perfectly suited to interact with the negatively charged supercoiled DNA substrate

Sexual enhancement products for sale online : raising awareness of the psychoactive effects of Yohimbine, Maca, Horny Goat Weed and Ginkgo Biloba

Copyright © 2014 Ornella Corazza et al.This is an open access article distributed under theCreativeCommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedIntroduction. The use of unlicensed food and herbal supplements to enhance sexual functions is drastically increasing. This phenomenon, combined with the availability of these products over the Internet, represents a challenge from a clinical and a public health perspective. Methods. A comprehensive multilingual assessment of websites, drug fora, and other online resources was carried out between February and July 2013 with exploratory qualitative searches including 203 websites. Additional searches were conducted using the Global Public Health Intelligence Network (GPHIN). Once the active constitutes of the products were identified, a comprehensive literature search was carried out using PsycInfo and PubMed. Results. The most common sexual enhancement products available on the Internet were identified. Their active ingredients included yohimbine, maca, horny goat weed and Ginkgo biloba. These four substances were reported with the occurrence of adverse events and the induction of psychological symptoms, such as mood changes, anxiety, and hallucinations as well as addictive behaviours. Conclusions. Uncontrolled availability of sexual enhancement products that contain potentially harmful substances is a major public healthconcern.Thepossible impact on population health, particularly among subjects with psychiatric disorders, usually at risk for sexual dysfunction, may be significant. This new trend needs to be extensively studied and monitoredPeer reviewedFinal Published versio

Massive NGS data analysis reveals hundreds of potential novel gene fusions in human cell lines

Background: Gene fusions derive from chromosomal rearrangements and the resulting chimeric transcripts are often endowed with oncogenic potential. Furthermore, they serve as diagnostic tools for the clinical classification of cancer subgroups with different prognosis and, in some cases, they can provide specific drug targets. So far, many efforts have been carried out to study gene fusion events occurring in tumor samples. In recent years, the availability of a comprehensive Next Generation Sequencing dataset for all the existing human tumor cell lines has provided the opportunity to further investigate these data in order to identify novel and still uncharacterized gene fusion events. Results: In our work, we have extensively reanalyzed 935 paired-end RNA-seq experiments downloaded from "The Cancer Cell Line Encyclopedia" repository, aiming at addressing novel putative cell-line specific gene fusion events in human malignancies. The bioinformatics analysis has been performed by the execution of four different gene fusion detection algorithms. The results have been further prioritized by running a bayesian classifier which makes an in silico validation. The collection of fusion events supported by all of the predictive softwares results in a robust set of ∼ 1,700 in-silico predicted novel candidates suitable for downstream analyses. Given the huge amount of data and information produced, computational results have been systematized in a database named LiGeA. The database can be browsed through a dynamical and interactive web portal, further integrated with validated data from other well known repositories. Taking advantage of the intuitive query forms, the users can easily access, navigate, filter and select the putative gene fusions for further validations and studies. They can also find suitable experimental models for a given fusion of interest. Conclusions: We believe that the LiGeA resource can represent not only the first compendium of both known and putative novel gene fusion events in the catalog of all of the human malignant cell lines, but it can also become a handy starting point for wet-lab biologists who wish to investigate novel cancer biomarkers and specific drug targets

Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations

The role of Thr729 in modulating the enzymatic function of human topoisomerase I has been characterized by molecular dynamics (MD) simulation. In detail, the structural–dynamical behaviour of the Thr729Lys and the Thr729Pro mutants have been characterized because of their in vivo and in vitro functional properties evidenced in the accompanying paper. Both mutants can bind to the DNA substrate and are enzymatically active, but while Thr729Lys is resistant even at high concentration of the camptothecin (CPT) anti-cancer drug, Thr729Pro shows only a mild reduction in drug sensitivity and in DNA binding. MD simulations show that the Thr729Lys mutation provokes a structural perturbation of the CPT-binding pocket. On the other hand, the Thr729Pro mutant maintains the wild-type structural scaffold, only increasing its rigidity. The simulations also show the complete abolishment, in the Thr729Lys mutant, of the protein communications between the C-terminal domain (where the active Tyr723 is located) and the linker domain, that plays an essential role in the control of the DNA rotation, thus explaining the distributive mode of action displayed by this mutant