Non-Blocking Signature of very large SOAP Messages

Data transfer and staging services are common components in Grid-based, or more generally, in service-oriented applications. Security mechanisms play a central role in such services, especially when they are deployed in sensitive application fields like e-health. The adoption of WS-Security and related standards to SOAP-based transfer services is, however, problematic as a straightforward adoption of SOAP with MTOM introduces considerable inefficiencies in the signature generation process when large data sets are involved. This paper proposes a non-blocking, signature generation approach enabling a stream-like processing with considerable performance enhancements.Comment: 13 pages, 5 figure

Non-Blocking Signature of very large SOAP Messages

Data transfer and staging services are common components in Grid-based, or more generally, in service-oriented applications. Security mechanisms play a central role in such services, especially when they are deployed in sensitive application fields like e-health. The adoption of WS-Security and related standards to SOAP-based transfer services is, however, problematic as a straightforward adoption of SOAP with MTOM introduces considerable inefficiencies in the signature generation process when large data sets are involved. This paper proposes a non-blocking, signature generation approach enabling a stream-like processing with considerable performance enhancements.Comment: 13 pages, 5 figure

The “systems approach” to treating the brain: opportunities in developmental psychopharmacology

The significance of early life for the long-term programming of mental health is increasingly being recognized. However, most psychotropic medications are currently intended for adult patients, and early psychopharmacological approaches aimed at reverting aberrant neurodevelopmental trajectories are missing. Psychopharmacologic intervention at an early age faces the challenge of operating in a highly plastic system and requires a comprehensive knowledge of neurodevelopmental mechanisms. Recently the systems biology approach has contributed to the understanding of neuroplasticity mechanisms from a new perspective that interprets them as the result of complex and dynamic networks of signals from different systems. This approach is creating opportunities for developmental psychopharmacology, suggesting novel targets that can modulate the course of development by interfering with neuroplasticity at an early age. We will discuss two interconnected systems—the immune and gut microbiota—that regulate neurodevelopment and that have been implicated in preclinical research as new targets in the prevention of aberrant brain development

Where are the horses? With the sheep or cows? Uncertain host location, vector-feeding preferences and the risk of African horse sickness transmission in Great Britain

Understanding the influence of non-susceptible hosts on vector-borne disease transmission is an important epidemiological problem. However, investigation of its impact can be complicated by uncertainty in the location of the hosts. Estimating the risk of transmission of African horse sickness (AHS) in Great Britain (GB), a virus transmitted by Culicoides biting midges, provides an insightful example because: (i) the patterns of risk are expected to be influenced by the presence of non-susceptible vertebrate hosts (cattle and sheep) and (ii) incomplete information on the spatial distribution of horses is available because the GB National Equine Database records owner, rather than horse, locations. Here, we combine land-use data with available horse owner distributions and, using a Bayesian approach, infer a realistic distribution for the location of horses. We estimate the risk of an outbreak of AHS in GB, using the basic reproduction number (R0), and demonstrate that mapping owner addresses as a proxy for horse location significantly underestimates the risk. We clarify the role of non-susceptible vertebrate hosts by showing that the risk of disease in the presence of many hosts (susceptible and non-susceptible) can be ultimately reduced to two fundamental factors: first, the abundance of vectors and how this depends on host density, and, second, the differential feeding preference of vectors among animal species

Molecular mechanisms of mitotane action in adrenocortical cancer based on in vitro studies

SIMPLE SUMMARY: Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and for postoperative adjuvant therapy. It is known that mitotane destroys the adrenal cortex impairing steroidogenesis, although its exact molecular mechanism is still unclear. However, confounding factors affecting in vitro experiments could reduce the relevance of the studies. In this review, we explore in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. On this basis, it may be necessary to re-evaluate the experiments taking into account their potential confounding factors such as cell strains, culture serum, lipoprotein concentration, and culture passages, which could hide important molecular results. As a consequence, the identification of novel pharmacological molecular pathways might be used in the future to implement personalized therapy, maximizing the benefit of mitotane treatment while minimizing its toxicity. ABSTRACT: Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. Although it is known that mitotane destroys the adrenal cortex and impairs steroidogenesis, its exact mechanism of action is still unclear. The most used cell models are H295-derived cell strains and SW13 cell lines. The diverging results obtained in presumably identical cell lines highlight the need for a stable in vitro model and/or a standard methodology to perform experiments on H295 strains. The presence of several enzymatic targets responsive to mitotane in mitochondria and mitochondria-associated membranes causes progressive alteration in mitochondrial structure when cells were exposed to mitotane. Confounding factors of culture affecting in vitro experiments could reduce the significance of any molecular mechanism identified in vitro. To ensure experimental reproducibility, particular care should be taken in the choice of culture conditions: aspects such as cell strains, culture serum, lipoproteins concentration, and culture passages should be carefully considered and explicated in the presentation of results. We aimed to review in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. If the concerns pointed out in this review will be overcome, the new insights into mitotane mechanism of action observed in-vitro could allow the identification of novel pharmacological molecular pathways to be used to implement personalized therapy

Elevated miR-34a expression and altered transcriptional profile are associated with adverse electromechanical remodeling in the heart of male rats exposed to social stress

This study investigated epigenetic risk factors that may contribute to stress-related cardiac disease in a rodent model. Experiment 1 was designed to evaluate the expression of microRNA-34a (miR-34a), a known modulator of both stress responses and cardiac pathophysiology, in the heart of male adult rats exposed to a single or repeated episodes of social defeat stress. Moreover, RNA sequencing was conducted to identify transcriptomic profile changes in the heart of repeatedly stressed rats. Experiment 2 was designed to assess cardiac electromechanical changes induced by repeated social defeat stress that may predispose rats to cardiac dysfunction. Results indicated a larger cardiac miR-34a expression after repeated social defeat stress compared to a control condition. This molecular modification was associated with increased vulnerability to pharmacologically induced arrhythmias and signs of systolic left ventricular dysfunction. Gene expression analysis identified clusters of differentially expressed genes in the heart of repeatedly stressed rats that are mainly associated with morphological and functional properties of the mitochondria and may be directly regulated by miR-34a. These results suggest the presence of an association between miR-34a overexpression and signs of adverse electromechanical remodeling in the heart of rats exposed to repeated social defeat stress, and point to compromised mitochondria efficiency as a potential mediator of this link. This rat model may provide a useful tool for investigating the causal relationship between miR-34a expression, mitochondrial (dys)function, and cardiac alterations under stressful conditions, which could have important implications in the context of stress-related cardiac disease