Infection control and meticillin-resistant Staphylococcus aureus decolonization:the perspective of nursing home staff

Infection control and meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes have started to assume greater importance in practice and policy.

‘Darkened surfaces’: camouflage and the nocturnal observation of Britain, 1941–45

Positioned in relation to an emerging geographical interest into the effects of different atmospheric and observational conditions in shaping sensory engagements with the Earth's surfaces, this paper considers how a critical examination of the practices of camouflage can open up new dialogues into how the Earth's surfaces become known, are interacted with, and transformed in the conditions of darkness. With an empirical focus on the cultural and historical geographies of nocturnal camouflage practised during the Second World War, the paper examines the systematic attempts of civil camoufleurs to understand how natural and artificial landforms were visibly 'present' in the nocturnal landscape, despite darkness often being conceived as producing an environment of 'visual absence' through diminished sensory engagement. Furthermore, the paper highlights how the tensions between visual presence/absence that shape both the nocturnal experience and the 'knowing' of landscape can often be exploited for social, cultural, and political ends, in this case, to enable protection against aerial attack. © 2013 Pion and its Licensors.

Electrochemical versus gas-phase oxidation of ru single-crystal surfaces

The electrochemical uptake of oxygen on a Ru(0001) electrode was investigated by electron diffraction, Auger spectroscopy, and cyclic voltammetry. An ordered (2 × 2)-O overlayer forms at a potential close to the hydrogen region. At +0.42 and +1.12 V vs Ag/AgCl, a (3 × 1) phase and a (1 × 1)-O phase, respectively, emerge. When the Ru electrode potential is maintained at +1.12 V for 2 min, RuO2 grows epitaxially with its (100) plane parallel to the Ru(0001) surface. In contrast to the RuO domains, the non-oxidized regions of the Ru electrode surface are flat. If, however, the electrode potential is increased to +1.98 V for 2 min, the remaining non-oxidized Ru area also becomes rough. These findings are compared with O overlayers and oxides on the Ru(0001) and Ru(101¯1) surfaces created by exposure to gaseous O under UHV conditions. On the other hand, gas-phase oxidation of the Ru(101¯0) surface leads to the formation of RuO with a (100) orientation. It is concluded that the difference in surface energy between RuO(110) and RuO(100) is quite small. RuO again grows epitaxially on Ru(0001), but with the (110) face oriented parallel to the Ru(0001) surface. The electrochemical oxidation of the Ru(0001) electrode surface proceeds via a 3-dimensional growth mechanism with a mean cluster size of 1.6 nm, whereas under UHV conditions, a 2-dimensional oxide film (1-2 nm thick) is epitaxially formed with an average domain size of 20 µm. © 2000 American Chemical Society.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism. © 2012 Macmillan Publishers Limited

Increased susceptibility of a triclabendazole (TCBZ)-resistant isolate of Fasciola hepatica to TCBZ following co-incubation in vitro with the P-glycoprotein inhibitor, R(+)-verapamil

SUMMARY A study was carried out to investigate whether the action of triclabendazole sulphoxide (TCBZ.SO) against the liver fluke, Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible fluke isolates were used for this in vitro study and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL]. For experiments with the Oberon isolate, flukes were incubated for 24 h with either R(+)-VPL (1×10-4 m) on its own, TCBZ.SO (15 µg mL-1) alone, a combination of R(+)-VPL (1×10-4 m) plus TCBZ.SO (15 µg mL-1), TCBZ.SO (50 µg mL-1) on its own, or a combination of TCBZ.SO (50 µg mL-1) plus R(+)-VPL (1×10-4 m). They were also incubated in TCBZ.SO (50 µg mL-1) alone or in combination with R(+)-VPL (1×10-4 m) until they became inactive; and in TCBZ.SO (50 µg mL-1) alone for a time to match that of the combination inactivity time. Flukes from the Cullompton isolate were treated with either TCBZ.SO (50 µg mL-1) alone or in combination with R(+)-VPL (1×10-4 m) until they became inactive, or with TCBZ.SO (50 µg mL-1) alone time-matched to the combination inactivity time. Morphological changes resulting from drug treatment and following Pgp inhibition were assessed by means of scanning electron microscopy. Incubation in R(+)-VPL alone had a minimal effect on either isolate. TCBZ.SO treatment had a relatively greater impact on the TCBZ-susceptible Cullompton isolate. When R(+)-VPL was combined with TCBZ.SO in the incubation medium, however, the surface disruption to both isolates was more severe than that seen after TCBZ.SO treatment alone; also, the time taken to reach inactivity was shorter. More significantly, though, the potentiation of drug activity was greater in the Oberon isolate; also, it was more distinct at the higher concentration of TCBZ.SO. So, the Oberon isolate appears to be particularly sensitive to efflux pump inhibition. The results of this study suggest that enhanced drug efflux in the Oberon isolate may be involved in the mechanism of resistance to TCBZ.

Effect of the P-glycoprotein inhibitor, R(+)-verapamil on the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by the inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Sligo TCBZ-resistant and Cullompton TCBZ-susceptible fluke isolates were used for these experiments and the Pgp inhibitor selected was R(+)-verapamil [R-VPL]. In the first experiment, flukes were initially incubated for 2 h in R-VPL (100 µM), then incubated for a further 22 h in R-VPL+triclabendazole sulphoxide (TCBZ.SO) (50 µg/ml, or 0.1327 µM). For controls, flukes were incubated for 24 h in R-VPL and TCBZ.SO on their own. In a second experiment, flukes were removed from the incubation media following cessation of movement. In the third experiment, Sligo flukes were incubated in lower concentrations of R-VPL (10 µM) and TCBZ.SO (15 µg/ml, or 0.0398 µM). Morphological changes resulting from drug treatment and following Pgp inhibition were assessed by means of scanning electron microscopy. Incubation in R-VPL alone had minimal effect on either isolate. After treatment with TCBZ.SO alone, there was greater surface disruption to the Cullompton than Sligo isolate. However, combined treatment of R-VPL+TCBZ.SO led to more severe surface changes to the Sligo isolate than with TCBZ.SO on its own; this potentiation of drug activity was not seen with the Cullompton isolate. The phenomenon was evident at both concentrations of TCBZ.SO. Inclusion of R-VPL in the incubation medium also reduced the time taken for the flukes to become inactive; again, this effect was more distinct with the Sligo isolate. The results of this study support the concept of altered drug efflux in TCBZ-resistant flukes and indicate that drug transporters may play a role in the development of drug resistance.

Influence of surface structures, subsurface carbon and hydrogen, and surface alloying on the activity and selectivity of acetylene hydrogenation on Pd surfaces: A density functional theory study

The selective hydrogenation of acetylene to ethylene on several Pd surfaces (Pd(111), Pd(100), Pd(211), and Pd(211)-defect) and Pd surfaces with subsurface species (carbon and hydrogen) as well as a number of Pd-based alloys (Pd-M/Pd(111) and Pd-M/Pd(211) (M = Cu, Ag and Au)) are investigated using density functional theory calculations to understand both the acetylene hydrogenation activity and the selectivity of ethylene formation. All the hydrogenation barriers are calculated, and the reaction rates on these surfaces are obtained using a two-step model. Pd(211) is found to have the highest activity for acetylene hydrogenation while Pd(100) gives rise to the lowest activity. In addition, more open surfaces result in over-hydrogenation to form ethane, while the close-packed surface (Pd(111)) is the most selective. However, we also find that the presence of subsurface carbon and hydrogen significantly changes the reactivity and selectivity of acetylene toward hydrogenation on Pd surfaces. On forming surface alloys of Pd with Cu, Ag and Au, the selectivity for ethylene is also found to be changed. A new energy decomposition method is used to quantitatively analyze the factors in determining the changes in selectivity. These surface modifiers are found to block low coordination unselective sites, leading to a decreased ethane production. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Synergistic effects of proteasome inhibitor carfilzomib in combination with tyrosine kinase inhibitors in imatinib-sensitive and -resistant chronic myeloid leukemia models

The tyrosine kinase inhibitor (TKI) imatinib has transformed the treatment and outlook of chronic myeloid leukemia (CML); however, the development of drug resistance and the persistence of TKI-resistant stem cells remain obstacles to eradicating the disease. Inhibition of proteasome activity with bortezomib has been shown to effectively induce apoptosis in TKI-resistant cells. In this study, we show that exposure to the next generation proteasome inhibitor carfilzomib is associated with a decrease in ERK signaling and increased expression of Abelson interactor proteins 1 and 2 (ABI-1/2). We also investigate the effect of carfilzomib in models of imatinib-sensitive and -resistant CML and demonstrate a potent reduction in proliferation and induction of apoptosis in a variety of models of imatinib-resistant CML, including primitive CML stem cells. Carfilzomib acts synergistically with the TKIs imatinib and nilotinib, even in imatinib-resistant cell lines. In addition, we found that the presence of immunoproteasome subunits is associated with an increased sensitivity to carfilzomib. The present findings provide a rational basis to examine the potential of carfilzomib in combination with TKIs as a potential therapy for CML, particularly in imatinib-resistant disease.

Corrosion resistant fibre reinforced polymer (FRP) reinforcement for bridge deck slabs

This paper discusses the beneficial influence of compressive membrane action in fibre reinforced polymer (FRP)reinforced in-plane restrained slabs in bridge deck slabs and the improved service performance when archingaction occurs. Bridge deck slabs that are exposed to extreme environmental conditions can experience severecorrosion damage. Expansive corrosion in steel reinforcement significantly reduces the design life and durabilityof concrete structures; for example, on one short section of the M1 in Northern Ireland, nearly £1 million was spent last year on the maintenance and repair of bridges due to corrosion. Corrosion-resistant compositereinforcement such as basalt fibre reinforced polymer (BFRP) and glass fibre reinforced polymer (GFRP) provides adurable alternative to reinforcing steel. In this research, two BFRP reinforced slabs and two GFRP reinforced slabswere constructed using high-strength concrete with a target cube compressive strength of 65 N/mm2. The slabsrepresented typical full-scale dimensions of a real bridge deck slab 475 mm wide by 1425 mm long and 150 mmdeep. The service and ultimate behaviour of the slabs are discussed and the results are compared with the relevantdesign guidelines.

Disruption of vitellogenesis and spermatogenesis by triclabendazole (TCBZ) in a TCBZ-resistant isolate of Fasciola hepatica following incubation in vitro with a P-glycoprotein inhibitor

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Sligo TCBZ-resistant fluke isolate was used for these experiments and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL]. In the first experiment, flukes were initially incubated for 2 h in R(+)-VPL (100 μ m), then incubated in R(+)-VPL+triclabendazole sulphoxide (TCBZ.SO) (50 μg mL-1, or 133·1 μ m) until flukes ceased movement (at 9 h post-treatment). In a second experiment, flukes were incubated in TCBZ.SO alone and removed from the incubation medium following cessation of motility (after 15 h). In the third experiment, flukes were incubated for 24 h in R(+)-VPL on its own. Changes to the testis tubules and vitelline follicles following drug treatment and following Pgp inhibition were assessed by means of light microscope histology and transmission electron microscopy. Incubation of the Sligo isolate in either R(+)-VPL or TCBZ.SO on their own had a limited impact on the morphology of the two tissues. Greater disruption was observed when the drugs were combined, in terms of the block in development of the spermatogenic and vitelline cells and the apoptotic breakdown of the remaining cells. Sperm formation was severely affected and abnormal. Large spaces appeared in the vitelline follicles and synthesis of shell protein was disrupted. The results of this study support the concept of altered drug efflux in TCBZ-resistant flukes and indicate that drug transporters may play a role in the development of drug resistance.

Ultrashort Cationic Naphthalene-Derived Self-Assembled Peptides as Antimicrobial Nanomaterials

Self-assembling dipeptides conjugated to naphthalene show considerable promise as nanomaterial structures, biomaterials, and drug delivery devices. Biomaterial infections are responsible for high rates of patient mortality and morbidity. The presence of biofilm bacteria, which thrive on implant surfaces, are a huge burden on healthcare budgets, as they are highly resistant to current therapeutic strategies. Ultrashort cationic self-assembled peptides represent a highly innovative and cost-effective strategy to form antibacterial nanomaterials. Lysine conjugated variants display the greatest potency with 2% w/v NapFFKK hydrogels significantly reducing the viable Staphylococcus epidermidis biofilm by 94%. Reducing the size of the R-group methylene chain on cationic moieties resulted in reduction of antibiofilm activity. The primary amine of the protruding R-group tail may not be as readily available to interact with negatively charged bacterial membranes. Cryo-SEM, FTIR, CD spectroscopy, and oscillatory rheology provided evidence of supramolecular hydrogel formation at physiological pH (pH 7.4). Cytotoxicity assays against murine fibroblast (NCTC 929) cell lines confirmed the gels possessed reduced cytotoxicity relative to bacterial cells, with limited hemolysis upon exposure to equine erythrocytes. The results presented in this paper highlight the significant potential of ultrashort cationic naphthalene peptides as future biomaterials.

The effects of stepped sites and ruthenium adatom decoration on methanol dehydrogenation over platinum-based catalyst surfaces

A density functional theory study of methanol dehydrogenation over stepped Pt(2 1 1) surfaces without and with Ru modification was carried out to understand fuel catalytic reactions on Pt-based catalysts. Two main pathways of the CH3OH dehydrogenation were examined: the O–H pathway which was initiated by O–H bond scission to form the methoxy (CH3O) intermediate followed by sequential cleavage of C–H bonds to CO, and the C–H pathway which was initiated by C–H bond scission to form the hydroxymethyl (CH2OH) followed by two C–H bond cleavages to COH and then CO. Possible crossover reactions between the O–H and C–H pathways were also computed. Compared to flat Pt(1 1 1), stepped Pt(2 1 1) increases the adsorption energies of intermediates, making no significant contribution to decreasing the reaction barriers of most elementary steps involved, except in the first hydrogen scission. However, on the Ru-modified surface, a significant reduction was found in reaction barriers for the first step of the C–H bond scission and a number of further dehydrogenation steps crossing over to the O–H pathway, with the most facile paths identified. Our data reveals the complexity of methanol catalytic reaction processes at the atomic level and contributes to a fundamental understanding of fuel reactions on Pt-based catalysts.

Electrowetting movement of an aqueous droplet between two three-dimensional electrode surfaces

In an effort to develop a novel electronic paper image display technology based on the electrowetting principle, a 3-D electrowetting cell is designed and fabricated, which consists of two 3-D bent electrodes, each having a horizontal surface made of gold and a vertical surface made of indium tin oxide (ITO) glass as a color display window, a layer of dielectric material on the 3-D electrodes, and a highly fluorinated hydrophobic layer on the surface of the dielectric layer. Results of this work show that an electrowetting-induced motion of an aqueous droplet in immiscible oils can be achieved reversibly across the boundary of the horizontal and vertical surfaces of the 3-D electrode surface. It is also shown that the droplet can maintain its wetting state on a vertical sidewall electrode free of a power supplier when the voltage is removed. This phenomenon may form the basis for color contrast modulation applications, where a power-free image display is required, such as electronic paper display technology in the future. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3100201]