Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/µm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately following irradiation in a dose-dependent manner. The analysis of repair capability showed that the cells irradiated with 1 and 2 Gy almost completely recovered from the damage, but not, however, 3 Gy treated cells in which DNA damage was not recovered. In addition, the results indicate the importance of the use of an appropriate control in radiobiological in vitro analysis.

Adaptive Measurement-Based Policy-Driven QoS Management with Fuzzy-Rule-based Resource Allocation

Fixed and wireless networks are increasingly converging towards common connectivity with IP-based core networks. Providing effective end-to-end resource and QoS management in such complex heterogeneous converged network scenarios requires unified, adaptive and scalable solutions to integrate and co-ordinate diverse QoS mechanisms of different access technologies with IP-based QoS. Policy-Based Network Management (PBNM) is one approach that could be employed to address this challenge. Hence, a policy-based framework for end-to-end QoS management in converged networks, CNQF (Converged Networks QoS Management Framework) has been proposed within our project. In this paper, the CNQF architecture, a Java implementation of its prototype and experimental validation of key elements are discussed. We then present a fuzzy-based CNQF resource management approach and study the performance of our implementation with real traffic flows on an experimental testbed. The results demonstrate the efficacy of our resource-adaptive approach for practical PBNM systems

Induction of alloxan/streptozotocin diabetes in dogs: a revised experimental technique

The diabetic dog represents an excellent model for use in many aspects of diabetic research. The present paper describes, in detail, a reproducible experimental protocol for the successful induction of chemical diabetes in beagles using a combination of the 2 pancreatic beta-cell cytoxic agents alloxan and streptozotocin.

Rule-Based Intrusion Detection System for SCADA Networks

Increased complexity and interconnectivity of Supervisory Control and Data Acquisition (SCADA) systems in Smart Grids potentially means greater susceptibility to malicious attackers. SCADA systems with legacy communication infrastructure have inherent cyber-security vulnerabilities as these systems were originally designed with little consideration of cyber threats. In order to improve cyber-security of SCADA networks, this paper presents a rule-based Intrusion Detection System (IDS) using a Deep Packet Inspection (DPI) method, which includes signature-based and model-based approaches tailored for SCADA systems. The proposed signature-based rules can accurately detect several known suspicious or malicious attacks. In addition, model-based detection is proposed as a complementary method to detect unknown attacks. Finally, proposed intrusion detection approaches for SCADA networks are implemented and verified using a ruled based method.

Incubation or Induction? Gendered Identity Work in the Context of Technology Business Incubation

While there is a substantial body of literature exploring the influence of business incubation upon early stage firms, this debate remains almost entirely gender blind. This article challenges this assumption by adopting a feminist perspective to reveal business incubation as a gendered process shaping the identity work undertaken by women seeking legitimacy as technology venturers. In so doing, we critically evaluate prevailing normative analyses of the business incubation process and entrepreneurial legitimation. To illustrate this argument, we draw upon empirical evidence which reveals technology incubation as a legitimating induction process encouraging women to reproduce masculinized representations of the normative technology entrepreneur.

Induction of signalling in non-erythroid cells by pharmacological levels of erythropoietin

Erythropoiesis is maintained by the hormone erythropoietin (Epo) binding to its cognate receptor (EpoR) on erythroid progenitor cells. The Epo-EpoR interaction initiates a signal transduction process that regulates the survival, growth and differentiation of these cells. Originally perceived as highly lineage-restricted, Epo is now recognised to have pleiotropic effects extending beyond the maintenance of red cell mass. Functional interactions between Epo and EpoR have been demonstrated in numerous cells and tissues. EpoR expression on neoplastic cells leads to concern that recombinant human erythropoietin, used to treat anaemia in cancer patients, may augment tumour growth. Here we demonstrate that EPO, at pharmacological concentrations, can activate three major signalling cascades, viz. the Jak2/STAT5, Ras/ERK and PI3K/Akt pathways in non-small cell lung carcinoma (NSCLC) cell lines. EpoR synthesis is normally under the control of GATA-1, but NSCLC cells exhibit decreased GATA-1 levels compared to GATA-2, -3 and -6, suggesting that GATA-1 is not essential for EpoR production. The increased Epo-induced signalling was not associated with a growth advantage for the NSCLC cells.

Scotland, Renewable Energy and the Independence Debate: Will Head or Heart Rule the Roost?

Political support for renewable energy development, especially offshore renewables, is particularly conspicuous in Scotland and is a centrepiece of SNP policy. However, this is built on something of a paradox because, put simply, without the subsidies paid by electricity consumers in the rest of the UK, the Scottish Government's ambitious targets for renewable energy would be politically unachievable. We argue in this paper that if Scotland does move towards independence, then there could be little reason for the UK to continue paying (much) of the subsidies since the resulting renewable generation would no longer contribute towards UK renewable energy targets. We suggest that the potential scenarios, and their implications, needs to be far better considered in the arguments around the Scottish constitutional position and the broader aims of UK energy policy.

Efficient Drug Delivery and Induction of Apoptosis in Colorectal Tumors Using a Death Receptor 5-Targeted Nanomedicine

Death Receptor 5 (DR5) is a pro-apoptotic cell-surface receptor that is a potential therapeutic target in cancer. Despite the potency of DR5-targeting agents in preclinical models, the translation of these effects into the clinic remains disappointing. Herein, we report an alternative approach to exploiting DR5 tumor expression using antibody-targeted, chemotherapy-loaded nanoparticles. We describe the development of an optimized polymer-based nanotherapeutic incorporating both a functionalized polyethylene glycol (PEG) layer and targeting antibodies to limit premature phagocytic clearance whilst enabling targeting of DR5-expressing tumor cells. Using the HCT116 colorectal cancer model, we show that following binding to DR5, the nanoparticles activate caspase 8, enhancing the anti-tumor activity of the camptothecin payload both in vitro and in vivo. Importantly, the combination of nanoparticle-induced DR5 clustering with camptothecin delivery overcomes resistance to DR5-induced apoptosis caused by loss of BAX or overexpression of anti-apoptotic FLIP. This novel approach may improve the clinical activity of DR5-targeted therapeutics while increasing tumor-specific delivery of systemically toxic chemotherapeutics.Molecular Therapy (2014); doi:10.1038/mt.2014.137.

Biogas reforming using renewable wind energy and induction heating

While the benefits of renewable energy are well known and used to influence government policy there are a number of problems which arise from having significant quantities of renewable energies on an electricity grid. The most notable problem stems from their intermittent nature which is often out of phase with the demands of the end users. This requires the development of either efficient energy storage systems, e.g. battery technology, compressed air storage etc. or through the creation of demand side management units which can utilise power quickly for manufacturing operations. Herein a system performing the conversion of synthetic biogas to synthesis gas using wind power and an induction heating system is shown. This approach demonstrates the feasibility of such techniques for stabilising the electricity grid while also providing a robust means of energy storage. This exemplar is also applicable to the production of hydrogen from the steam reforming of natural gas.