Preclinical Tests for Cerebral Stroke

Stroke is the second single highest cause of death in Europe. The low reliability of animal models in replicating the human disease is one of the most serious problems in the field of medical and pharmaceutical research about stroke. The standard models for the study of ischemic stroke are often poorly predictive as they simulate only partially the human disease. This work aims at investigating animal models with diseases typically associated with the onset of stroke in human patients. We have designed and realised a knowledge base for collecting, elaborating, and extracting analytical results of genomic, proteomic, biochemical, morphological investigations from animal models of cerebral stroke. Data analysis techniques are tailored to make the data available for processing and correlation, in order to increase the predictive value of the preclinical data, to perform biosimulation studies, and to support both academic and industrial research in the area of cerebral stroke therapy. A first statistical analysis of the retrieved information leads to the validation of our animal models and suggests a predictive and translational value for parameters related to a specific model. In particular, concerning gene expression data, we have applied a data analysis pipeline that initially takes into account an initial set of 64,000 genes and brings down the focus on a few tens of them

MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences.

Double minutes (dmin), homogeneously staining regions, and ring chromosomes are vehicles of gene amplification in cancer. The underlying mechanism leading to their formation as well as their structure and function in acute myeloid leukemia (AML) remain mysterious. We combined a range of high-resolution genomic methods to investigate the architecture and expression pattern of amplicons involving chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different MYC-dmin architectures can coexist within the same leukemic cell population, indicating a step-wise evolution rather than a single event origin, such as through chromothripsis. This was supported also by the analysis of the chromothripsis criteria, that poorly matched the model in our samples. Furthermore, we found that dmin could evolve toward ring chromosomes stabilized by neocentromeres. Surprisingly, amplified genes (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs

An Accurate Model for Steady-State and Dynamic Analysis of the Sicilian Network with HVDC Interconnections

Sicily is one of the first Italian regions for installed power from renewable energy plants, especially photovoltaic and wind plants, and a crucial point for the Mediterranean energy hub. Its role as nexus between the European and the African Continents is becoming more and more significant due to the realization in a short time of the so called Tyrrhenian link and the High Voltage Direct Current (HVDC) connection with Tunisia. In this framework, the paper presents a model of the Sicily power generation and transmission system, including the Tyrrhenian link and two equivalent buses representing the Sardinian power network and the rest of the Continental Europe (CE) synchronous area, for both steady-state and dynamic analysis. The model is developed in Neplan and it is based on the actual structure of the Sicilian power system. The rest of the CE system is represented in the model and validated by a comparison with the large-scale dynamic model of the CE provided by the European Network of Transmission System Operators for Electricity (ENTSO-E). Finally, some simulations of the Sicilian grid in future energy scenarios are presented, and the behaviour of the system is discussed considering different transient conditions