Mantra 2.0: An online collaborative resource for drug mode of action and repurposing by network analysis

Elucidation of molecular targets of a compound (mode of action, MoA) and of its off-targets is a crucial step in drug development. We developed an online collaborative resource (MANTRA 2.0) that supports this process by exploiting similarities between drug-induced transcriptional profiles. Drugs are organised in a network of nodes (drugs) and edges (similarities) highlighting “communities” of drugs sharing a similar MoA. A user can upload gene expression profiles (GEPs) before and after drug treatment in one or multiple cell types. An automated processing pipeline transforms the GEPs into a unique drug ”node” embedded in the drug-network. Visual inspection of the neighbouring drugs and communities helps in revealing its MoA, and to suggest new applications of known drugs (drug repurposing). MANTRA 2.0 allows storing and sharing user-generated network nodes, thus making MANTRA 2.0 a collaborative ever-growing resource

SoNeUCON_{ABC}Pro: an access control model for social networks with translucent user provenance

Proceedings of: SecureComm 2017 International Workshops, ATCS and SePrIoT, Niagara Falls, ON, Canada, October 22–25, 2017Web-Based Social Networks (WBSNs) are used by millions of people worldwide. While WBSNs provide many benefits, privacy preservation is a concern. The management of access control can help to assure data is accessed by authorized users. However, it is critical to provide sufficient flexibility so that a rich set of conditions may be imposed by users. In this paper we coin the term user provenance to refer to tracing users actions to supplement the authorisation decision when users request access. For example restricting access to a particular photograph to those which have “liked” the owners profile. However, such a tracing of actions has the potential to impact the privacy of users requesting access. To mitigate this potential privacy loss the concept of translucency is applied. This paper extends SoNeUCONABC model and presents SoNeUCONABCPro, an access control model which includes translucent user provenance. Entities and access control policies along with their enforcement procedure are formally defined. The evaluation demonstrates that the system satisfies the imposed goals and supports the feasibility of this model in different scenarios.This work was supported by the MINECO grants TIN2013-46469-R (SPINY: Security and Privacy in the Internet of You) and TIN2016-79095-C2-2-R (SMOG-DEV); by the CAM grant S2013/ICE-3095 (CIBERDINE: Cybersecurity, Data, and Risks); and by the Programa de Ayudas para la Movilidad of Carlos III University of Madrid, Spain (J. M. de Fuentes and L. Gonzalez-Manzano grants)

Effect of opiate receptor blockade on the insulin response to oral glucose load in polycystic ovarian disease

In order to test the hypothesis that endogenous opiates are at least partially responsible for hyperinsulinaemia in patients with polycystic ovarian disease (PCOD), the effect of naloxone (an opiate receptor blocker) on the insulin response to oral glucose load (OGTT) was studied in 20 women with PCOD and 17 control subjects at days 5-8 of their follicular phase. After fasting overnight for 10-12 h, each woman received an i.v. bolus injection (2 mg) of naloxone or an equal volume of saline infusion followed by a constant infusion of naloxone or saline solution at a rate of 8 ml/h (1 mg/h of naloxone) for 5 h. OGTT (75 g) was performed 1 h after the bolus injection. The naloxone study was performed 48 h after the saline study. Naloxone did not modify the insulin response to OGTT in either group. When the data were related to the insulin response, in PCOD hyperinsulinaemic patients, naloxone significantly reduced (P less than 0.02) the insulin response to OGTT without any change in glycaemic response curves. In control and PCOD normoinsulinaemic patients, naloxone did not change significantly either the glycaemia or the insulin levels after OGTT. No change of gonadotrophin and steroid secretion was found in any patient receiving naloxone. In conclusion, endogenous opiates may play a significant role in hyperinsulinaemia in PCO

BATS: a Bayesian user-friendly software for Analyzing Time Series microarray experiments

BATS is a user-friendly software for Bayesian Analysis of Time Series microarray experiments based on the novel, truly functional and fully Bayesian approach proposed in Angelini et at. (2006). The software is specifically designed for time series data. It allows an user to automatically identify and rank differentially expressed genes and to estimate their expression profiles. BATS successfully manages various technical difficulties which arise in microarray time-course experiments, such as a small number of observations, non-uniform sampling intervals, and presence of missing or multiple data. BATS can carry out analysis with both simulated and real experimental data. It also handles data from different platforms. 1 Availability: BATS is written in Matlab and executable in Windows (Macintosh and Linux version are currently under development). It is freely available upon request from the authors.

Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments

The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure.Based on the ability of adeno-associated viral (AAV) vectors to transduce heart together with skeletal muscle following systemic administration, we delivered human delta-sarcoglycan cDNA into male BIO14.6 hamsters by testing different ages of injection, routes of administration and AAV serotypes. Body-wide restoration of delta-SG expression was associated with functional reconstitution of the sarcoglycan complex and with significant lowering of centralized nuclei and fibrosis in skeletal muscle. Motor ability and cardiac functions were completely rescued. However, BIO14.6 hamsters having less than 70% of fibers recovering sarcoglycan developed cardiomyopathy, even if the total rescued protein was normal. When we used serotype 2/8 in combination with serotype 2/1, lifespan was extended up to 22 months with sustained heart function improvement.Our data support multiple systemic administrations of AAV as a general therapeutic strategy for clinical trials in cardiomyopathies and muscle disorders

Managing A Software System And Keeping It Internally Consistent During Its Evolution

1 The production and the maintenance of a software system require that many components and relationships between them, all describing the system, be managed. Many descriptions of these components are produced and maintained by automatic tools. During the whole software life cycle many tools are needed and usually each of them manages only a subset of the required information. This creates several difficulties in managing the software system's information and a great risk of redundancy, reducing software understandability and transferability. This paper proposes a tool for managing a repository that implements the software system model and federates the repositories of all the tools used in the software production and maintenance processes. It is independent from the ones it federates and is able to eliminate all the redundancies in the information collected in their repositories. It also effectively manages the software system's evolution preserving the repository's internal consistenc..