Field emission from single-, double-, and multi-walled carbon nanotubes chemically attached to silicon

The chemical attachment and field emission (FE) properties of single-walled carbon nanotubes (SWCNTs), double-walled carbon nanotubes (DWCNTs), and multi-walled carbon nanotubes (MWCNTs) chemically attached to a silicon substrate have been investigated. A high density of CNTs was revealed by atomic force microscopy imaging with orientation varying with CNT type. Raman spectroscopy was used to confirm the CNT type and diameter on the surfaces. The field emission properties of the surfaces were studied and both current-voltage and Fowler-Nordheim plots were obtained. The SWCNTs exhibited superior FE characteristics with a turn-on voltage (Eto) of 1.28 V μm−1 and electric field enhancement factor (β) of 5587. The DWCNT surface showed an Eto of 1.91 V μm−1 and a β of 4748, whereas the MWCNT surface exhibited an Eto of 2.79 V μm−1 and a β of 3069. The emission stability of each CNT type was investigated and it was found that SWCNTs produced the most stable emission. The differences between the FE characteristics and stability are explained in terms of the CNT diameter, vertical alignment, and crystallinity. The findings suggest that strength of substrate adhesion and CNT crystallinity play a major role in FE stability. Comparisons to other FE studies are made and the potential for device application is discussed

Developing a comparative marine socio-economic framework for the European Atlantic Area

Availability and easy access to a wide range of natural and human-activity data on the oceans and coastal regions of Europe is the basis for strategic decision-making on coastal and marine policy. Strategies within Europe’s Integrated Maritime Policy, including the Maritime Strategy for the Atlantic Area, Blue Growth, Maritime Spatial Planning and Marine Data and Knowledge, require coherent and comparable socio-economic data across European countries. Similarly, the Marine Strategy Framework Directive requires member states to carry out economic and social analysis of their waters and the reformed Common Fisheries Policy includes a social dimension requiring socio-economic data. However, the availability of consistent, accessible marine socio-economic data for the European Atlantic Arc regions is limited. Ocean economy studies have been undertaken in some countries (for example, Ireland, France, and UK) but timescales and methodologies are not necessarily comparable. Marnet is an EU transnational co-operation project involving eight partners from five member states of the Atlantic Area (Ireland, Spain, UK, France and Portugal). Marnet has developed a methodology to collate comparable marine socio-economic data across the Atlantic regions. The comparative marine socio-economic information system developed by Marnet could provide a template for other European States to follow that could potentially facilitate the construction of a Europe-wide marine economic information system as envisaged under the EU Integrated Maritime Policy

Sigma-2 receptor ligands potentiate conventional chemotherapies and improve survival in models of pancreatic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>We have previously reported that the sigma-2 receptor is highly expressed in pancreas cancer. Furthermore, we have demonstrated that sigma-2 receptor specific ligands induce apoptosis in a dose-dependent fashion. Here, we examined whether sigma-2 receptor ligands potentiate conventional chemotherapies such as gemcitabine and paclitaxel.</p> <p>Methods</p> <p>Mouse (Panc-02) and human (CFPAC-1, Panc-1, AsPC-1) pancreas cancer cell lines were used in this study. Apoptosis was determined by FACS or immunohistochemical analysis after TUNEL and Caspase-3 staining. Combination therapy with the sigma-2 ligand SV119 and the conventional chemotherapies gemcitabine and paclitaxel was evaluated in an allogenic animal model of pancreas cancer.</p> <p>Results</p> <p>SV119, gemcitabine, and paclitaxel induced apoptosis in a dose-dependent fashion in all pancreas cancer cell lines tested. Combinations demonstrated increases in apoptosis. Mice were treated with SV119 (1 mg/day) which was administered in combination with paclitaxel (300 μg/day) over 7 days to mice with established tumors. A survival benefit was observed with combination therapy (p = 0.0002). Every other day treatment of SV119 (1 mg/day) in combination with weekly treatment of gemcitabine (1.5 mg/week) for 2 weeks also showed a survival benefit (p = 0.046). Animals tolerated the combination therapy and no gross toxicity was noted in serum biochemistry data or on necropsy.</p> <p>Conclusion</p> <p>SV119 augments tumoricidal activity of paclitaxel and gemcitabine without major side effects. These results highlight the potential utility of the sigma-2 ligand as an adjuvant treatment in pancreas cancer.</p

Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish

During inflammation, dysregulated neutrophil behaviour can play a major role in a range of chronic inflammatory diseases, for many of which current treatments are generally ineffective. Recently, specific naturally occurring tanshinones have shown promising anti-inflammatory effects by targeting neutrophils in vivo, yet such tanshinones, and moreover, their isomeric isotanshinone counterparts, are still a largely underexplored class of compounds, both in terms of synthesis and biological effects. To explore the anti-inflammatory effects of isotanshinones, and the tanshinones more generally, a series of substituted tanshinone and isotanshinone analogues was synthesised, alongside other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of neutrophilic inflammation revealed differential anti-inflammatory profiles in vivo, with a number of compounds exhibiting promising effects. Several compounds reduce initial neutrophil recruitment and/or promote resolution of neutrophilic inflammation, of which two also result in increased apoptosis of human neutrophils. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting the recruitment of neutrophils to inflammatory sites, making this a particularly attractive candidate for potential pro-resolution therapeutics, as well as a possible lead for future development of functionalised tanshinones as molecular tools and/or chemical probes. The structurally related β-lapachones promote neutrophil recruitment but do not affect resolution. We also observed notable differences in toxicity profiles between compound classes. Overall, we provide new insights into the in vivo anti-inflammatory activities of several novel tanshinones, isotanshinones, and structurally related compounds

Thermal Burn Injury Induced Microvesicle Particle Release

Microvesicle particles (MVP) are found to be important for cellular communication because they contain many bioactive proteins, lipids, cytokines, and nucleic acids. We have previously found that ultraviolet B radiation (UVB) and a Platelet-activating factor agonist (CPAF) can stimulate the release of MVP in keratinocytes. We hypothesized that there may also be an increase in MVP released after thermal burn and that could be involved in pathogenesis of the systemic effects found in some patients. In this thesis various keratinocyte cell lines, mice and human ex vivo skin were used as model systems to test our hypotheses. It was determined that thermal burn significantly increases the release of MVP compared to the untreated groups. UVB, CPAF and thermal burn all seemed to involve acid sphingomyelinase (aSMase), but different MAP kinase pathways. There was also a significant decrease in the cytokine concentration inside MVP after thermal burn, suggesting a possible defense mechanism to prevent cytokine storm

Injury-Induced Microvesicle Particle Release in Human Skin Explant Tissue

Microvesicle particles (MVP) are 100-1000 nm vesicles that bud from the cell membrane and transmit intercellular signals locally and systemically via their bioactive cargo (e.g. cytokines). We have previously shown that thermal burn injury or UVB radiation result in the formation Platelet Activating Factor (PAF), and UVB or a PAF agonist (CPAF) can promote MVP formation in keratinocytes. Thermal burn and UVB radiation can result in systemic effects, even though their injury is localized to the skin. We therefore propose that PAF-producing injuries, UVB irradiation or thermal burn injury, result in the formation of MVPs that can potentially transport cytokines through the blood stream and induce systemic effects. This study, in-part, addresses that proposed mechanism by demonstrating increased MVP release after thermal burn injury in vivo and ex vivo. In vivo there was a significant increase in MVP concentration in mouse skin that received thermal burn injury compared to untreated skin. This demonstrates that there is an increase in MVP release after injury in living models. Human skin explants that received suction blisters to separate the epidermis from the dermis exhibited increased MVP release into the blister fluid in response to CPAF, UVB or thermal burn injury as compared to controls, suggesting epidermal MVPs are mobile and can exit the epidermis. Acid Sphingomyelinase (aSMase), an enzyme that breaks sphingomyelin into ceramide and phosphorylcholine, has been found to be involved in MVP release in other cell types. Utilizing an FDA approved aSMase inhibitor, Imipramine, we found that UVB, CPAF and thermal burn-mediated MVP release is completely dependent on aSMase in keratinocyte cell lines and human explant skin. These results suggest that PAF-producing skin injuries (thermal burn and UVB) can induce MVP release, and the release can be therapeutically inhibited by imipramine

Expression of the NKCC2A Cotransporter in Mouse Central Nervous System

Na-K-2Cl cotransporter 2A (NKCC2A), also known as the bumetanide-sensitive cotransporter 1 (BSC1), transports Na+, K+ and Cl- with a stoichiometry of 1:1:2. NKCC2A is considered a kidney specific cotransporter. It is abundantly expressed in apical membrane of the tubular cells in the thick ascending limb of the loop of Henle (TALH) and in the macula densa. However, NKCC2 has also been found at low levels in different cells, including insulin-secreting ones. This secondary active transporter uses the energy stored in the electrochemical gradients of Na and K maintained by the Na/K-ATPase located on the basolateral membrane of the TALH. The gene encoding NKCC2 is Slc12a1, solute carrier family 12 member 1 located on chromosome 2. Mice lacking NKCC2A (NKCC2A-KO) exhibit mild kidney dysfunction. In this lab it was noted that NKCC2A-KO mice express atypical muscle movements, slight tremors and subtle muscle dyscontrol, endure exceptionally well in the forced swim test and had changes in neurotransmitter levels. These observations led to the hypothesis that NKCC2A may be also found in the central nervous system (CNS).https://corescholar.libraries.wright.edu/urop_celebration/1013/thumbnail.jp

UVB Induces Release of Bioactive Microvesicle Particles in Keratinocytes via Platelet-Activating Factor and Acid Sphingomyelinase

Ultraviolet-B (UVB) radiation is only appreciably absorbed by the epidermis, yet induces both acute inflammation and delayed immunosuppression. These UVB effects are due to keratinocyte-derived factors. Our lab has previously determined that UVB induces the production of the lipid mediator, Platelet-activating factor (PAF), which is involved in mediating both acute pro-inflammatory and immunosuppressive UVB responses. PAF has been reported to contribute to acid sphingomyelinase (aSMase)-dependent generation of ceramide, a key regulator of the lipid releasing pathway of microvesicle particles (MVP), which are small membrane-derived vesicles released from the plasma membrane that can facilitate intercellular transport of bioactive molecules. We have previously reported that UVB induces MVP, but the mechanism of MVP production and MVP contents have not been characterized. In this study, we found that both UVB and the stable PAF-R agonist C-PAF generated MVP release in various skin-derived epithelial cell lines, human skin and WT mice skin. The PAF dependence of UVB-mediated MVP release was confirmed utilizing a PAF-R antagonist, PAF-R negative cell lines and PAFR -/- mice. Interestingly, we found that UVB induced MVP do not contain protein cytokines, but contain large amounts of PAF agonists that can stimulate PAF-R activation in recipient cells. A small-molecule inhibitor of aSMase effectively blocked CPAF- and UVB-mediated MVP release in epithelial cells, human skin ex vivo and murine skin in vivo, suggesting that aSMase is required for the UVB induced, PAF-R-dependent release of MVP. This study suggests that keratinocyte-derived MVP are involved in transferring PAF, likely by protecting this labile lipid from metabolism. The targeting of UVB-mediated MVP release could serve as a potential therapeutic target in mitigating UVB-induced acute inflammation and systemic immunosuppression