Trigger release liposome systems:local and remote controlled delivery?

Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

Reporting and managing risk:a look at current practice at Tesco, RBS, local and central government

These case studies from CIMA highlight the need to embed risk management within more easily understood behaviours, consistent with the overall organisational culture. In each case, some form of internal audit team provides either an oversight function or acts as an expert link in that feedback loop. Frontline staff, managers and specialists should be completely aligned on risk, in part just to ensure that there is a consistency of approach. They should understand instinctively that good performance includes good risk management. Tesco has continued to thrive during the recession and remains a robust and efficient group of businesses despite the emergence of potential threats around consumer spending and the supply chain. RBS, by contrast, has suffered catastrophic and very public failures of risk management despite a large in-house function and stiff regulation of risk controls. Birmingham City Council, like all local authorities, is adapting to more commercial modes of operation and is facing diverse threats and opportunities emerging as a result of social change. And DCMS, like many other public sector organisations, has to handle an incredibly complex network of delivery partners within the context of a relatively recent overhaul of central government risk management processes. Key Findings: •Risk management is no longer solely a financial discipline, nor is it simply a concern for the internal control function. •Where organisations retain a discrete risk management cadre – often specialists at monitoring and evaluating a range of risks – their success is dependent on embedding risk awareness in the wider culture of the enterprise. •Risk management is most successful when it is explicitly linked to operational performance. •Clear leadership, specific goals, excellent influencing skills and open-mindedness to potential threats and opportunities are essential for effective risk management. •Bureaucratic processes and systems can hamper good risk management – either as a result of a ‘box-ticking mentality’ or because managers and staff believe they do not need to consider risk themselves.

Analysis and comparison of network performance with different network parameters

The purpose of this study was to analyze the network performance by observing the effect of varying network size and data link rate on one of the most commonly found network configurations. Computer networks have been growing explosively. Networking is used in every aspect of business, including advertising, production, shipping, planning, billing, and accounting. Communication takes place through networks that form the basis of transfer of information. The number and type of components may vary from network to network depending on several factors such as requirement and actual physical placement of the networks. There is no fixed size of the networks and they can be very small consisting of say five to six nodes or very large consisting of over two thousand nodes. The varying network sizes make it very important to study the network performance so as to be able to predict the functioning and the suitability of the network. The findings demonstrated that the network performance parameters such as global delay, load, router processor utilization, router processor delay, etc. are affected. The findings demonstrated that the network performance parameters such as global delay, load, router processor utilization, router processor delay, etc. are affected significantly due to the increase in the size of the network and that there exists a correlation between the various parameters and the size of the network. These variations are not only dependent on the magnitude of the change in the actual physical area of the network but also on the data link rate used to connect the various components of the network.

Scotland's Marine Protected Area network : Reviewing progress towards achieving commitments for marine conservation

Acknowledgements This research was supported and funded by Climate XChange (reference no: A10431853). Climate XChange is a collaborative initiative between Scottish research and higher education institutes and is funded by the Scottish Government. The authors would like to thank Marine Scotland, JNCC and SNH for their permission to reproduce their figures of the Scottish MPA process and maps of the Scottish MPA network.

Dialogue, partnership and empowerment for network and information security:the changing role of the private sector from objects of regulation to regulation shapers

The protection of cyberspace has become one of the highest security priorities of governments worldwide. The EU is not an exception in this context, given its rapidly developing cyber security policy. Since the 1990s, we could observe the creation of three broad areas of policy interest: cyber-crime, critical information infrastructures and cyber-defence. One of the main trends transversal to these areas is the importance that the private sector has come to assume within them. In particular in the area of critical information infrastructure protection, the private sector is seen as a key stakeholder, given that it currently operates most infrastructures in this area. As a result of this operative capacity, the private sector has come to be understood as the expert in network and information systems security, whose knowledge is crucial for the regulation of the field. Adopting a Regulatory Capitalism framework, complemented by insights from Network Governance, we can identify the shifting role of the private sector in this field from one of a victim in need of protection in the first phase, to a commercial actor bearing responsibility for ensuring network resilience in the second, to an active policy shaper in the third, participating in the regulation of NIS by providing technical expertise. By drawing insights from the above-mentioned frameworks, we can better understand how private actors are involved in shaping regulatory responses, as well as why they have been incorporated into these regulatory networks.

RF MIMO Systems for Wide-Area Indoor Human Motion Monitoring

Human motion monitoring is an important function in numerous applications. In this dissertation, two systems for monitoring motions of multiple human targets in wide-area indoor environments are discussed, both of which use radio frequency (RF) signals to detect, localize, and classify different types of human motion. In the first system, a coherent monostatic multiple-input multiple-output (MIMO) array is used, and a joint spatial-temporal adaptive processing method is developed to resolve micro-Doppler signatures at each location in a wide-area for motion mapping. The downranges are obtained by estimating time-delays from the targets, and the crossranges are obtained by coherently filtering array spatial signals. Motion classification is then applied to each target based on micro-Doppler analysis. In the second system, multiple noncoherent multistatic transmitters (Tx's) and receivers (Rx's) are distributed in a wide-area, and motion mapping is achieved by noncoherently combining bistatic range profiles from multiple Tx-Rx pairs. Also, motion classification is applied to each target by noncoherently combining bistatic micro-Doppler signatures from multiple Tx-Rx pairs. For both systems, simulation and real data results are shown to demonstrate the ability of the proposed methods for monitoring patient repositioning activities for pressure ulcer prevention.

Comparing Remote Data Transfer Rates of Compact Muon Solenoid Jobs with Xrootd and Lustre

To explore the feasibility of processing Compact Muon Solenoid (CMS) analysis jobs across the wide area network, the FIU CMS Tier-3 center and the Florida CMS Tier-2 center designed a remote data access strategy. A Kerberized Lustre test bed was installed at the Tier-2 with the design to provide storage resources to private-facing worker nodes at the Tier-3. However, the Kerberos security layer is not capable of authenticating resources behind a private network. As a remedy, an xrootd server on a public-facing node at the Tier-3 was installed to export the file system to the private-facing worker nodes. We report the performance of CMS analysis jobs processed by the Tier-3 worker nodes accessing data from a Kerberized Lustre file. The processing performance of this configuration is benchmarked against a direct connection to the Lustre file system, and separately, where the xrootd server is near the Lustre file system.

Integrated Optimal Power Flow for Distribution Networks in Local and Urban Scales

This paper develops an integrated optimal power flow (OPF) tool for distribution networks in two spatial scales. In the local scale, the distribution network, the natural gas network, and the heat system are coordinated as a microgrid. In the urban scale, the impact of natural gas network is considered as constraints for the distribution network operation. The proposed approach incorporates unbalance three-phase electrical systems, natural gas systems, and combined cooling, heating, and power systems. The interactions among the above three energy systems are described by energy hub model combined with components capacity constraints. In order to efficiently accommodate the nonlinear constraint optimization problem, particle swarm optimization algorithm is employed to set the control variables in the OPF problem. Numerical studies indicate that by using the OPF method, the distribution network can be economically operated. Also, the tie-line power can be effectively managed.

Letting the managers manage: analyzing capacity to conserve biodiversity in a cross-border protected area network

Biodiversity loss is one of the most significant drivers of ecosystem change and is projected to continue at a rapid rate. While protected areas, such as national parks, are seen as important refuges for biodiversity, their effectiveness in stemming biodiversity decline has been questioned. Public agencies have a critical role in the governance of many such areas, but there are tensions between the need for these agencies to be more “adaptive” and their current operating environment. Our aim is to analyze how institutions enable or constrain capacity to conserve biodiversity in a globally significant cross-border network of protected areas, the Australian Alps. Using a novel conceptual framework for diagnosing biodiversity institutions, our research examined institutional adaptive capacity and more general capacity for conserving biodiversity. Several intertwined issues limit public agencies’ capacity to fulfill their conservation responsibilities. Narrowly defined accountability measures constrain adaptive capacity and divert attention away from addressing key biodiversity outcomes. Implications for learning were also evident, with protected area agencies demonstrating successful learning for on-ground issues but less success in applying this learning to deeper policy change. Poor capacity to buffer political and community influences in managing significant cross-border drivers of biodiversity decline signals poor fit with the institutional context and has implications for functional fit. While cooperative federalism provides potential benefits for buffering through diversity, it also means protected area agencies have restricted authority to address cross-border threats. Restrictions on staff authority and discretion, as public servants, have further implications for deploying capacity. This analysis, particularly the possibility of fostering “ambidexterity”—creatively responding to political pressures in a way that also achieves a desirable outcome for biodiversity conservation—is one promising way of building capacity to buffer both political influences and ecological pressures. The findings and the supporting analysis provide insight into how institutional capacity to conserve biodiversity can be enhanced in protected areas in Australia and elsewhere, especially those governed by public agencies and/or multiple organizations and across jurisdictions.

Catalogue of data and platforms at Network GDAC level, including the example of Copernicus In Situ TAC

This document presents catalogue techniques used at network GDAC level to facilitate the discovery of platforms and data files. Some AtlantOS networks are organized as DAC-GDACs that continuously update a catalogue of metadata on observation datasets and platforms: • A DAC is a Data Assembly Centre operating at national or regional scale. It manages data and metadata for its area with a direct link to Scientifics and Operators. The DAC pushes observations to the network GDAC. • A GDAC is a Global Data Assembly Centre. It is designed for a global observation network such as Argo, OceanSITES, DBCP, EGO, Gosud, etc… The GDAC aggregates data and metadata of an observation network, in real-time and delayed mode, provided by DACs.

Consumers motivations for buying local and organic products in developing vs developed countries.

Despite numerous studies reporting on organic consumer profiles, little is known on consumers motivations for buying local and organic products. More precisely, do consumers prefer local products because they want to support local producers or do environment and the question of food miles matter in their choice ? Besides, very little is known about organic consumers in developing countries, since most surveys are generally conducted in developed countries. Our purpose is to fill this double gap. By conducting qualitative surveys based on individual interviews in four developing countries (Brazil, Egypt, Uganda and China) and two European countries, France and Denmark, we plan to study consumers choice for organic products from supermarkets, farmers markets or local organic food network respectively. Products are selected to cover examples of imported organic products that compete with comparable products of local origin. First results from Brazil and France show that French consumers are more concerned by the environment than Brazilian consumers, but that most consumers in both samples are not concerned by food miles and their subsequent environmental impacts. Results also shed light on different patterns related to commitment of supporting small or local farmers, and suggest implications for policy makers.

Design and Development of Network Monitoring Strategies in P4-enabled Programmable Switches

Network monitoring is of paramount importance for effective network management: it allows to constantly observe the network’s behavior to ensure it is working as intended and can trigger both automated and manual remediation procedures in case of failures and anomalies. The concept of SDN decouples the control logic from legacy network infrastructure to perform centralized control on multiple switches in the network, and in this context, the responsibility of switches is only to forward packets according to the flow control instructions provided by controller. However, as current SDN switches only expose simple per-port and per-flow counters, the controller has to do almost all the processing to determine the network state, which causes significant communication overhead and excessive latency for monitoring purposes. The absence of programmability in the data plane of SDN prompted the advent of programmable switches, which allow developers to customize the data-plane pipeline and implement novel programs operating directly in the switches. This means that we can offload certain monitoring tasks to programmable data planes, to perform fine-grained monitoring even at very high packet processing speeds. Given the central importance of network monitoring exploiting programmable data planes, the goal of this thesis is to enable a wide range of monitoring tasks in programmable switches, with a specific focus on the ones equipped with programmable ASICs. Indeed, most network monitoring solutions available in literature do not take computational and memory constraints of programmable switches into due account, preventing, de facto, their successful implementation in commodity switches. This claims that network monitoring tasks can be executed in programmable switches. Our evaluations show that the contributions in this thesis could be used by network administrators as well as network security engineers, to better understand the network status depending on different monitoring metrics, and thus prevent network infrastructure and service outages.

Whole Cortical And Default Mode Network Mean Functional Connectivity As Potential Biomarkers For Mild Alzheimer's Disease.

The search for an Alzheimer's disease (AD) biomarker is one of the most relevant contemporary research topics due to the high prevalence and social costs of the disease. Functional connectivity (FC) of the default mode network (DMN) is a plausible candidate for such a biomarker. We evaluated 22 patients with mild AD and 26 age- and gender-matched healthy controls. All subjects underwent resting functional magnetic resonance imaging (fMRI) in a 3.0 T scanner. To identify the DMN, seed-based FC of the posterior cingulate was calculated. We also measured the sensitivity/specificity of the method, and verified a correlation with cognitive performance. We found a significant difference between patients with mild AD and controls in average z-scores: DMN, whole cortical positive (WCP) and absolute values. DMN individual values showed a sensitivity of 77.3% and specificity of 70%. DMN and WCP values were correlated to global cognition and episodic memory performance. We showed that individual measures of DMN connectivity could be considered a promising method to differentiate AD, even at an early phase, from normal aging. Further studies with larger numbers of participants, as well as validation of normal values, are needed for more definitive conclusions.

Bay 41-2272 Activates Host Defence Against Local And Disseminated Candida Albicans Infections.

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C) ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.