Languages generated by P systems with active membranes

We propose an alternative approach to generate languages by means of P systems: building up an appropriate representation for a string by means of a corresponding membrane structure and then generating the string by visiting the membrane structure according to a well-specified strategy. To this aim, we consider P systems with active membranes, allowing membrane creation or division or duplication and dissolution, where the output of a computation may be obtained either by visiting the tree associated with the membrane structure, or by following the traces of a specific object, called traveller, or sending out the objects. For each of these approaches, we provide characterizations of recursively enumerable languages based on P systems that use different sets of operations for modifying the membrane structure. Francesco Bernardini: He started his Ph.D. at the University of Sheffield in December 2002 after having previously got a master degree in Computer Science from the University of Pisa in Italy. His research is dedicated to the study of theoretical aspects of membrane computing (P systems) and discrete models of biological systems based on P systems. Marian Gheorghe, Ph.D.: His main research interests are in computational models and their applications to software modelling and testing, formal specifications of agent based systems, software engineering. He was investigating computational power of various generative devices (regular, context-free, fully initial; grammar systems; L-systems and variants). He is currently interested in natural computing (membrane calculus) and biological modelling.     

Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay

Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay. Both ectopic expression and platelet MV-mediated delivery of miR-126-3p downregulated AKT2 expression, thus suppressing proliferating and invading properties, in either triple negative (BT549 cells) or less aggressive Luminal A (MCF-7 cells) BC subtypes. Accordingly, as shown by bioinformatic analysis, both high miR-126 and low AKT2 levels were associated with favorable long-term prognosis in BC patients. Our results, together with the literature data, indicate that miR-126-3p exerts suppressor activity by specifically targeting components of the PIK3/AKT signaling cascade. Therefore, management of platelet-derived MV production and selective delivery of miR-126-3p to tumor cells may represent a useful tool in multimodal therapeutic approaches in BC patients.     

Characterisation of Progressive Skeletal Muscle Fibrosis in the Mdx Mouse Model of Duchenne Muscular Dystrophy: An In Vivo and In Vitro Study

Duchenne muscular dystrophy (DMD) is a rare genetic disease leading to progressive muscle wasting, respiratory failure, and cardiomyopathy. Although muscle fibrosis represents a DMD hallmark, the organisation of the extracellular matrix and the molecular changes in its turnover are still not fully understood. To define the architectural changes over time in muscle fibrosis, we used an mdx mouse model of DMD and analysed collagen and glycosaminoglycans/proteoglycans content in skeletal muscle sections at different time points during disease progression and in comparison with age-matched controls. Collagen significantly increased particularly in the diaphragm, quadriceps, and gastrocnemius in adult mdx, with fibrosis significantly correlating with muscle degeneration. We also analysed collagen turnover pathways underlying fibrosis development in cultured primary quadriceps-derived fibroblasts. Collagen secretion and matrix metalloproteinases (MMPs) remained unaffected in both young and adult mdx compared to wt fibroblasts, whereas collagen cross-linking and tissue inhibitors of MMP (TIMP) expression significantly increased. We conclude that, in the DMD model we used, fibrosis mostly affects diaphragm and quadriceps with a higher collagen cross-linking and inhibition of MMPs that contribute differently to progressive collagen accumulation during fibrotic remodelling. This study offers a comprehensive histological and molecular characterisation of DMD-associated muscle fibrosis; it may thus provide new targets for tailored therapeutic interventions.     

Primary Aldosteronism and Resistant Hypertension: A Pathophysiological Insight

Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of “non-classical” effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.     

Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

A proportional share allocation mechanism for coordination of plug-in electric vehiclecharging

The near-future penetration of plug-in electric vehicles is expected to be large enough to have a significant impact on the power grid. If PEVs were allowed to charge simultaneously at the maximum power rate, the distribution grid would face serious problems of stability. Therefore, mechanisms are needed to coordinate various PEVs that charge simultaneously. In this paper we propose an allocation mechanism that aims at balancing allocative efficiency and fairness, providing preferential treatment to the PEVs that have a high valuation of the available power, while guaranteeing a fair share of this power to all thePEVs.     

Gene regulatory networks reconstruction from time series datasets using genetic programming: a comparison between tree-based and graph-based approaches

Genetic programming researchers have shown a growing interest in the study of gene regulatory networks in the last few years. Our team has also contributed to the field, by defining two systems for the automatic reverse engineering of gene regulatory networks called GRNGen and GeNet. In this paper, we revise this work by describing in detail the two approaches and empirically comparing them. The results we report, and in particular the fact that GeNet can be used on large networks while GRNGen cannot, encourage us to pursue the study of GeNet in the future. We conclude the paper by discussing the main research directions that we are planning to investigate to improve GeNet.     

Two-dimensional synthetic aperture images over a land surface scene

The Soil Moisture and Ocean Salinity (SMOS) space mission is currently undergoing phase-B studies at the European Space Agency. The SMOS payload is an L-band interferometric radiometer based on a two-dimensional aperture synthesis concept. This paper presents the first images obtained by a demonstrator of the SMOS instrument over land surfaces at the Avignon test site in 1999     

Self-Adaptive Fault Tolerance in Multi-/Many-Core Systems

This paper presents a novel approach to the design of multi-/many-core systems with an adaptive level of reliability. The approach defines a layer at the operating system level that achieves fault detection/tolerance/diagnosis properties by means of thread replication and re-execution mechanisms. The layer applies the most convenient hardening mechanism to achieve the desired trade-off between reliability and performance by adapting at run-time to the changes of the working scenario. The proposed strategy has been applied in a set of experimental sessions considering a real-world parallel application, to evaluate its benefits on the final system with respect to various strategies selected at design time.