Optical assessment of impact and recovery of sedimentary pH profiles in ocean acidification and carbon capture and storage research

Available methods for measuring the impact of ocean acidification (OA) and leakage from carbon capture and storage (CCS) on marine sedimentary pH profiles are unsuitable for replicated experimental setups. To overcome this issue, a novel optical sensor application is presented, using off-the-shelf optode technology (MOPP). The application is validated using microprofiling, during a CCS leakage experiment, where the impact and recovery from a high CO2 plume was investigated in two types of natural marine sediment. MOPP offered user-friendliness, speed of data acquisition, robustness to sediment type, and large sediment depth range. This ensemble of characteristics overcomes many of the challenges found with other pH measuring methods, in OA and CCS research. The impact varied greatly between sediment types, depending on baseline pH variability and sediment permeability. Sedimentary pH profile recovery was quick, with profiles close to control conditions 24 h after the cessation of the leak. However, variability of pH within the finer sediment was still apparent 4 days into the recovery phase. Habitat characteristics need therefore to be considered, to truly disentangle high CO2 perturbation impacts on benthic systems. Impacts on natural communities depend not only on the pH gradient caused by perturbation, but also on other processes that outlive the perturbation, adding complexity to recovery.

A Quantitative and Mechanistic Assessment of Activated Thrombin-Activatable Fibrinolysis Inhibitor and its Role in Pathological Bleeding and Thrombosis

The coagulation and fibrinolytic systems are linked by the thrombin-thrombomodulin complex which regulates each system through activation of protein C and TAFI, respectively. We have used novel assays and techniques to study the enzymology and biochemistry of TAFI and TAFIa, to measure TAFI activation in hemophilia A and protein C deficiency and to determine if enhancing TAFI activation can improve hemostasis in hemophilic plasma and whole blood. We show that TAFIa not TAFI attenuates fibrinolysis in vitro and this is supported by a relatively high catalytic efficiency (16.41μM-1s-1) of plasminogen binding site removal from fibrin degradation products (FDPs) by TAFIa. Since the catalytic efficiency of TAFIa in removing these sites is ~60-fold higher than that for inflammatory mediators such as bradykinin it is likely that FDPs are a physiological substrate of TAFIa. The high catalytic efficiency is primarily a result of a low Km which can be explained by a novel mechanism where TAFIa forms a binary complex with plasminogen and is recruited to the surface of FDPs. The low Km also suggests that TAFIa would effectively cleave lysines from FDPs during the early stages of fibrinolysis (i.e. at low concentrations of FDPs). Since individuals with hemophilia suffer from premature fibrinolysis as a result of insufficient TAFI activation we quantified TAFI activation in whole blood from hemophilic subjects. Both the rate of activation and the area under the TAFI activation time course (termed TAFIa potential) was determined to be reduced in hemophilia A and the TAFIa potential was significantly and inversely correlated with the clinical bleeding iii phenotype. Using a novel therapeutic strategy, we used soluble thrombomodulin to increase TAFI activation which improved the clot lysis time in factor VIII deficient human plasma and hemophilic dog plasma as well as hemophilic dog blood. Finally, we briefly show in a biochemical case study that TAFI activation is enhanced in protein C deficiency and when afflicted individuals are placed on Warfarin anticoagulant therapy, TAFI activation is reduced. Since TAFIa stabilizes blood clots, this suggests that reducing TAFI activation or inhibiting TAFIa may help restore blood flow in vessels with pathological thrombosis.

Performance assessment of nanoscale double- and triple- gate FinFETs

This is the first paper to describe performance assessment of triple and double gate FinFETs for High Performance (HP), Low Operating Power (LOP) and Low Standby Power (LSTP) logic technologies is investigated. The impact of gate work-function, spacer width, lateral source/drain doping gradient, fin aspect ratio, fin thickness on device performance, has been analysed in detail and guidelines are presented to meet ITRS specification at 65 and 45 nm nodes. Optimal design of lateral source/drain doping profile can not only effectively control short channel effects, yielding low off-current, but also achieve low values of intrinsic gate delay.

Unraveling EU Policies: the ““Common Basic Principles”” and the ““European Integration Fund”” as a technology of government

this paper is about EU “soft policies” on immigrant integration. It analyzes the “Common Basic Principles” (CBPs) and the “European Integration Fund” (EIF), two devices that have been recently established within this framework. It adopts the theoretical perspective of the “anthropology of policy” and “governmentality studies”. It shows the context of birth of the aforementioned devices, as well as their functioning and the assessment done by the actors implied in the elaboration/implementation/evaluation of the related policies. It is based both on documentary research as well as direct observation and interviews done to the actors implied. It concludes that the PBC and the EIF should be considered as a “technology of government”, that strives to align the conduct of the actors with the governmental aims, as well as it produces specific practices and knowledge. It also underlines an intrinsic feature of many policies: their “congenital failure”, since they are (often) disputed and resignified by situated actors, who are embedded in asymmetrical power relations.

Value-oriented impact assessment: the economics of a new approach to impact assessment

Environmental Impact Assessment has gained a prominent position as a tool to evaluate the environmental effects of economic activities. However, all approaches proposed so far use a burden-oriented logic. They concentrate on the different environmental impacts in order to ascertain the overall environmental damage caused by economic activity. This paper argues that such a burden-oriented view is (a) hampered by a series of methodological shortcomings which hinders its widespread use in practice; and (b) is analytically incomplete. The paper proposes a value-oriented approach to impact assessment. For this purpose an economic analysis of the optimal use of environmental and social resources is conducted from both a burden-oriented and a value-oriented standpoint. The basic logic of a value-oriented impact assessment is explained, as well as the resulting economic conditions for an optimal use of resources. In addition, it is shown that value- and burden-oriented approaches are complementary to achieve optimality. Finally, the paper discusses the conditions under which the use of burden- or value-oriented impact assessments is appropriate, respectively.

Microporation Techniques for Enhanced Delivery of Therapeutic Agents

Perhaps the greatest barrier to development of the field of transmembrane drug delivery is that only a limited number of drugs are amenable to administration by this route. The highly lipophilic nature and barrier function of the uppermost layer of the skin, the stratum corneum, for example, restricts the permeation of hydrophilic, high molecular weight and charged compounds into the systemic circulation. Other membranes in the human body can also present significant barriers to drug permeation. In order to successfully deliver hydrophilic drugs, and macromolecular agents of interest, including peptides, DNA and small interfering RNA, many research groups and pharmaceutical companies Worldwide are focusing on the use of microporation methods and devices. Whilst there are a variety of microporation techniques, including the use of laser, thermal ablation, electroporation, radiofrequency, ultrasound, high pressure jets, and microneedle technology, they share the common goal of enhancing the permeability of a biological membrane through the creation of transient aqueous transport pathways of micron dimensions across that membrane. Once created, these micropores are orders of magnitude larger than molecular dimensions and, therefore, should readily permit the transport of hydrophilic macromolecules. Additionally, microporation devices also enable minimally-invasive sampling and monitoring of biological fluids. This review deals with the innovations relating to microporation-based methods and devices for drug delivery and minimally invasive monitoring, as disclosed in recent patent literature. © 2010 Bentham Science Publishers Ltd.

Multi-Study Assessment of Vaginal Cytokines and Microflora in the Safety Evaluation of Intravaginal Rings in Pig-Tailed Macaques

BACKGROUND: HIV microbicide trials have emphasized the need to evaluate the safety of topical microbicides and delivery platforms in an animal model prior to conducting clinical efficacy trials. An ideal delivery device should provide sustainable and sufficient concentrations of effective products to prevent HIV transmission while not increasing transmission risk by either local mucosal inflammation and/or disruption of the normal vaginal microflora.

METHODS: Safety analyses of macaque-sized elastomeric silicone and polyurethane intravaginal rings (IVRs) loaded with candidate antiretroviral (ARV) drugs were tested in four studies ranging in duration from 49 to 73 days with retention of the IVR being 28 days in each study. Macaques were assigned to 3 groups; blank IVR, ARV-loaded IVR, and naïve. In sequential studies, the same macaques were used but rotated into different groups. Mucosal and systemic levels of cytokines were measured from vaginal fluids and plasma, respectively, using multiplex technology. Changes in vaginal microflora were also monitored. Statistical analysis (Mann-Whitney test) was used to compare data between two groups of unpaired samples (with and without IVR, and IVR with and without ARV) for the groups collectively, and also for individual macaques.

RESULTS: There were few statistically significant differences in mucosal and systemic cytokine levels measured longitudinally when the ring was present or absent, with or without ARVs. Of the 8 proinflammatory cytokines assayed a significant increase (p = 0.015) was only observed for IL8 in plasma with the blank and ARV loaded IVR (median of 9.2 vs. 5.7 pg/ml in the absence of IVR). There were no significant differences in the prevalence of H2O2-producing lactobacilli or viridans streptococci, or other microorganisms indicative of healthy vaginal microflora. However, there was an increase in the number of anaerobic gram negative rods in the presence of the IVR (p= < 0.0001).

CONCLUSIONS: IVRs with or without ARVs neither significantly induce the majority of potentially harmful proinflammatory cytokines locally or systemically, nor alter the lactobacillus or G. vaginalis levels. The increase in anaerobic gram negative rods alone suggests minimal disruption of normal vaginal microflora. The use of IVRs as a long-term sustained delivery device for ARVs is promising and preclinical studies to demonstrate the prevention of transmission in the HIV/SHIV nonhuman primate model should continue.

Assessment framework for construction supply chain relationships: Development and evaluation

The change of supply chain relationships from the traditional adversarial to the collaborative has been increasing in the UK construction industry. To reflect this change, some attempts have been made to establish models for measuring and improving supply chain relationships in construction. However, there are obvious deficiencies in these existing models. This highlights the need for a systematic model for the assessment of construction supply chain relationships. Based on a review of the literature and an expert group discussion, an assessment framework is developed in this paper, which consists of assessment criteria, relationship levels, detailed descriptions, assessment classes and assessment procedures. The proposed framework is evaluated through expert interviews and case studies. This framework provides a roadmap for the improvement of supply chain relationships. It can help construction organisations to position their current relationship and identify key areas for relationship improvement in the future.