Nano-Structured Carbide-Derived Carbon Films and Their Tribology

Carbide-derived carbon （CDC） is a form of carbon produced by reacting metal carbides, such as SiC or TiC, with halogens at temperatures high enough to produce fast kinetics, but too low to permit the rearrangement of the carbon atoms into an equilibrium graphitic structure. The structure of CDC is derivative of the original carbide structure and contains nanoscale porosity and both sp2 and sp3 bonded carbon in a variety of nanoscale structures. CDC can be produced as a thin film on hard carbides to improve their tribological performance. CDC coatings are distinguished by their low friction coefficients and high wear resistance in many important industrial environments and by their resistance to spallation and delamination. The tribology of CDC coatings on SiC surfaces is described in detail.     

Tunable gold catalysts for selective hydrocarbon oxidation under mild conditions

Oxidation is an important method for the synthesis of chemical intermediates in the manufacture of high-tonnage commodities, high-value fine chemicals, agrochemicals and pharmaceuticals: but oxidations are often inefficient. The introduction of catalytic systems using oxygen from air is preferred for 'green' processing. Gold catalysis is now showing potential in selective redox processes, particularly for alcohol oxidation and the direct synthesis of hydrogen peroxide. However, a major challenge that persists is the synthesis of an epoxide by the direct electrophilic addition of oxygen to an alkene. Although ethene is epoxidized efficiently using molecular oxygen with silver catalysts in a large-scale industrial process, this is unique because higher alkenes can only be effectively epoxidized using hydrogen peroxide, hydroperoxides or stoichiometric oxygen donors. Here we show that nanocrystalline gold catalysts can provide tunable active catalysts for the oxidation of alkenes using air, with exceptionally high selectivity to partial oxidation products ( approximately 98%) and significant conversions. Our finding significantly extends the discovery by Haruta that nanocrystalline gold can epoxidize alkenes when hydrogen is used to activate the molecular oxygen; in our case, no sacrificial reductant is needed. We anticipate that our finding will initiate attempts to understand more fully the mechanism of oxygen activation at gold surfaces, which might lead to commercial exploitation of the high redox activity of gold nanocrystals.     

Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis

Haploinsufficiency of Dll4, a vascular-specific Notch ligand, has shown that it is essential for embryonic vascular development and arteriogenesis. Mechanistically, it is unclear how the Dll4-mediated Notch pathway contributes to complex vascular processes that demand meticulous coordination of multiple signalling pathways. Here we show that Dll4-mediated Notch signalling has a unique role in regulating endothelial cell proliferation and differentiation. Neutralizing Dll4 with a Dll4-selective antibody rendered endothelial cells hyperproliferative, and caused defective cell fate specification or differentiation both in vitro and in vivo. In addition, blocking Dll4 inhibited tumour growth in several tumour models. Remarkably, antibodies against Dll4 and antibodies against vascular endothelial growth factor (VEGF) had paradoxically distinct effects on tumour vasculature. Our data also indicate that Dll4-mediated Notch signalling is crucial during active vascularization, but less important for normal vessel maintenance. Furthermore, unlike blocking Notch signalling globally, neutralizing Dll4 had no discernable impact on intestinal goblet cell differentiation, supporting the idea that Dll4-mediated Notch signalling is largely restricted to the vascular compartment. Therefore, targeting Dll4 might represent a broadly efficacious and well-tolerated approach for the treatment of solid tumours.     

PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

Large subglacial lakes in East Antarctica at the onset of fast-flowing ice streams

Water plays a crucial role in ice-sheet stability and the onset of ice streams. Subglacial lake water moves between lakes and rapidly drains, causing catastrophic floods. The exact mechanisms by which subglacial lakes influence ice-sheet dynamics are unknown, however, and large subglacial lakes have not been closely associated with rapidly flowing ice streams. Here we use satellite imagery and ice-surface elevations to identify a region of subglacial lakes, similar in total area to Lake Vostok, at the onset region of the Recovery Glacier ice stream in East Antarctica and predicted by ice-sheet models. We define four lakes through extensive, flat, featureless regions of ice surface bounded by upstream troughs and downstream ridges. Using ice velocities determined using interferometric synthetic aperture radar (InSAR), we find the onset of rapid flow (moving at 20 to 30 m yr(-1)) of the tributaries to the Recovery Glacier ice stream in a 280-km-wide segment at the downslope margins of these four subglacial lakes. We conclude that the subglacial lakes initiate and maintain rapid ice flow through either active modification of the basal thermal regime of the ice sheet by lake accretion or through scouring bedrock channels in periodic drainage events. We suggest that the role of subglacial lakes needs to be considered in ice-sheet mass balance assessments.     

Charge- and size-based separation of macromolecules using ultrathin silicon membranes

Commercial ultrafiltration and dialysis membranes have broad pore size distributions and are over 1,000 times thicker than the molecules they are designed to separate, leading to poor size cut-off properties, filtrate loss within the membranes, and low transport rates. Nanofabricated membranes have great potential in molecular separation applications by offering more precise structural control, yet transport is also limited by micrometre-scale thicknesses. This limitation can be addressed by a new class of ultrathin nanostructured membranes where the membrane is roughly as thick (approximately 10 nm) as the molecules being separated, but membrane fragility and complex fabrication have prevented the use of ultrathin membranes for molecular separations. Here we report the development of an ultrathin porous nanocrystalline silicon (pnc-Si) membrane using straightforward silicon fabrication techniques that provide control over average pore sizes from approximately 5 nm to 25 nm. Our pnc-Si membranes can retain proteins while permitting the transport of small molecules at rates an order of magnitude faster than existing materials, separate differently sized proteins under physiological conditions, and separate similarly sized molecules carrying different charges. Despite being only 15 nm thick, pnc-Si membranes that are free-standing over 40,000 microm2 can support a full atmosphere of differential pressure without plastic deformation or fracture. By providing efficient, low-loss macromolecule separations, pnc-Si membranes are expected to enable a variety of new devices, including membrane-based chromatography systems and both analytical and preparative microfluidic systems that require highly efficient separations.     

Genetic cost of reproductive assurance in a self-fertilizing plant

The transition from outcrossing to self-fertilization is one of the most common evolutionary trends in plants. Reproductive assurance, where self-fertilization ensures seed production when pollinators and/or potential mates are scarce, is the most long-standing and most widely accepted explanation for the evolution of selfing, but there have been few experimental tests of this hypothesis. Moreover, many apparently adaptive floral mechanisms that ensure the autonomous production of selfed seed might use ovules that would have otherwise been outcrossed. This seed discounting is costly if selfed offspring are less viable than their outcrossed counterparts, as often happens. The fertility benefit of reproductive assurance has never been examined in the light of seed discounting. Here we combine experimental measures of reproductive assurance with marker-gene estimates of self-fertilization, seed discounting and inbreeding depression to show that, during 2 years in 10 Ontario populations of Aquilegia canadensis (Ranunculaceae), reproductive assurance through self-fertilization increases seed production, but this benefit is greatly outweighed by severe seed discounting and inbreeding depression.