Static and Dynamic Optical Analysis of Micro Wrinkle Formation on a Liquid Surface.

A spatially periodic voltage was used to create a dielectrophoresis induced periodic micro wrinkle deformation on the surface of a liquid film. Optical Coherence Tomography provided the equilibrium wrinkle profile at submicron accuracy. The dynamic wrinkle amplitude was derived from optical diffraction analysis during sub-millisecond wrinkle formation and decay, after abruptly increasing or reducing the voltage, respectively. The decay time constant closely followed the film thickness dependence expected for surface tension driven viscous levelling. Modelling of the system using numerical solution of the Stokes flow equations with electrostatic forcing predicted that wrinkle formation was faster than decay, in accord with observations.

A study of planar anchor groups for graphene-based single-molecule electronics.

To identify families of stable planar anchor groups for use in single molecule electronics, we report detailed results for the binding energies of two families of anthracene and pyrene derivatives adsorbed onto graphene. We find that all the selected derivatives functionalized with either electron donating or electron accepting substituents bind more strongly to graphene than the parent non-functionalized anthracene or pyrene. The binding energy is sensitive to the detailed atomic alignment of substituent groups over the graphene substrate leading to larger than expected binding energies for -OH and -CN derivatives. Furthermore, the ordering of the binding energies within the anthracene and pyrene series does not simply follow the electron affinities of the substituents. Energy barriers to rotation or displacement on the graphene surface are much lower than binding energies for adsorption and therefore at room temperature, although the molecules are bound to the graphene, they are almost free to move along the graphene surface. Binding energies can be increased by incorporating electrically inert side chains and are sensitive to the conformation of such chains.

A boundary integral formalism for stochastic ray tracing in billiards.

Determining the flow of rays or non-interacting particles driven by a force or velocity field is fundamental to modelling many physical processes. These include particle flows arising in fluid mechanics and ray flows arising in the geometrical optics limit of linear wave equations. In many practical applications, the driving field is not known exactly and the dynamics are determined only up to a degree of uncertainty. This paper presents a boundary integral framework for propagating flows including uncertainties, which is shown to systematically interpolate between a deterministic and a completely random description of the trajectory propagation. A simple but efficient discretisation approach is applied to model uncertain billiard dynamics in an integrable rectangular domain.

Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis.

There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B12 can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B12 deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B12 levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B12 of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B12 did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B12, from which it can be concluded that the usual dietary source of vitamin B12 is animal products and those who choose to omit or restrict these products are destined to become vitamin B12 deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.

Novel polyvinylpyrrolidones to improve delivery of poorly water-soluble drugs: from design to synthesis and evaluation.

Polyvinylpyrrolidone is widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant, whereas the cross-linked form is a superdisintegrant. We have previously reported that simply mixing the commercial cross-linked polymer with ibuprofen disrupted drug crystallinity with consequent improvements in drug dissolution behavior. In this study, we have designed and synthesized novel cross-linking agents containing a range of oligoether moieties that have then been polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in the most common solvents and in water, properties that suggest their value as disintegrants. The polymers were evaluated in simple physical mixtures with ibuprofen as a model poorly water-soluble drug. The results show that the novel PVPs induce the drug to become "X-ray amorphous", which increased dissolution to a greater extent than that seen with commercial cross-linked PVP. The polymers stabilize the amorphous drug with no evidence for recrystallization seen after 20 weeks of storage.

Healable polymeric materials: a tutorial review.

Given the extensive use of polymers in the modern age with applications ranging from aerospace components to microcircuitry, the ability to regain the mechanical and physical characteristics of complex pristine materials after damage is an attractive proposition. This tutorial review focusses upon the key chemical concepts that have been successfully utilised in the design of healable polymeric materials.

Mechanisms for the formation of organic acids in the gas-phase ozonolysis of 3-carene.

This paper describes experimental studies aimed at elucidating mechanisms for the formation of low-volatility organic acids in the gas-phase ozonolysis of 3-carene. Experiments were carried out in a static chamber under 'OH-free' conditions. A range of multifunctional acids-which are analogous to those observed from alpha-pinene ozonolysis-were identified in the condensed phase using gas chromatography coupled to mass spectrometry after derivation. Product yields were determined as a function of different OH radical scavengers and relative humidities to give mechanistic information about their routes of formation. Furthermore, an enone and an enal derived from 3-carene were ozonised in order to probe the early mechanistic steps in the reaction and, in particular, which of the two initially formed Criegee intermediates gives rise to which products. Branching ratios for the formation of the two Criegee Intermediates are determined. Similarities and differences in product formation from 3-carene and alpha-pinene ozonolysis are discussed and possible mechanisms-supported by experimental evidence-are developed for all acids investigated.

From alpha-cedrene to crinipellin B and onward: 25 years of the alkene-arene meta-photocycloaddition reaction in natural product synthesis.

Wender and Howbert's remarkable synthesis of alpha-cedrene in 1981 brought the attention of the synthetic community to the alkene-arene meta-photocycloaddition reaction. Here we review the natural product syntheses that have been achieved, over the last 25 years, utilising this strategic level reaction.

Molecular and genetic studies imply Akt-mediated signaling promotes protein kinase CbetaII alternative splicing via phosphorylation of serine/arginine-rich splicing factor SRp40.

Insulin regulates alternative splicing of PKCbetaII mRNA by phosphorylation of SRp40 via a phosphatidylinositol 3-kinase pathway (Patel, N. A., Chalfant, C. E., Watson, J. E., Wyatt, J. R., Dean, N. M., Eichler, D. C., and Cooper, D. C. (2001) J. Biol. Chem. 276, 22648-22654). Transient transfection of constitutively active Akt2 kinase promotes PKCbetaII exon inclusion. Serine/arginine-rich (SR) RNA-binding proteins regulating the selection of alternatively spliced exons are potential substrates of Akt kinase because many of them contain RXRXX(S/T) motifs. Here we show that Akt2 kinase phosphorylated SRp40 in vivo and in vitro. Mutation of Ser86 on SRp40 blocked in vitro phosphorylation. In control Akt2(+/+) fibroblasts, insulin treatment increased the phosphorylation of endogenous SR proteins, but their phosphorylation state remained unaltered by insulin in fibroblasts from Akt2(-/-) mice. Levels of PKCbetaII protein were up-regulated by insulin in Akt2(+/+) cells; however, only very low levels of PKCbetaII were detected in Akt2(-/-) cells and did not change following insulin treatment. Endogenous PKCbetaI and -betaII mRNA levels in Akt2(+/+) and Akt2(-/-) gastrocnemius muscle tissues were compared using quantitative real time PCR. The results indicated a 54% decrease in the expression of PKCbetaII levels in Akt(-/-), whereas PKCbetaI levels remained unchanged in both samples. Further, transfection of Akt2(-/-) cells with a PKCbetaII splicing minigene revealed defective betaII exon inclusion. Co-transfection of the mutated SRp40 attenuated betaII exon inclusion. This study provides in vitro and in vivo evidence showing Akt2 kinase directly phosphorylated SRp40, thereby connecting the insulin, PI 3-kinase/Akt pathway with phosphorylation of a site on a nuclear splicing protein promoting exon inclusion. This model is upheld in Akt2-deficient mice with insulin resistance leading to diabetes mellitus.

Differential regulation of SOCS genes in normal and transformed erythroid cells.

The SOCS family of genes are negative regulators of cytokine signalling with SOCS-1 displaying tumor suppressor activity. SOCS-1, CIS and SOCS-3 have been implicated in the regulation of red blood cell production. In this study, a detailed examination was conducted on the expression patterns of these three SOCS family members in normal erythroid progenitors and a panel of erythroleukemic cell lines. Unexpectedly, differences in SOCS gene expression were observed during maturation of normal red cell progenitors, viz changes to CIS were inversely related to the alterations of SOCS-1 and SOCS-3. Similarly, these SOCS genes were differentially expressed in transformed erythoid cells - erythroleukemic cells immortalized at an immature stage of differentiation expressed SOCS-1 and SOCS-3 mRNA constitutively, whereas in more mature cell lines SOCS-1 and CIS were induced only after exposure to erythropoietin (Epo). Significantly, when ectopic expression of the tyrosine kinase Lyn was used to promote differentiation of immature cell lines, constitutive expression of SOCS-1 and SOCS-3 was completely suppressed. Modulation of intracellular signalling via mutated Epo receptors in mature erythroleukemic lines also highlighted different responses by the three SOCS family members. Close scrutiny of SOCS-1 revealed that, despite large increases in mRNA levels, the activity of the promoter did not alter after erythropoietin stimulation; in addition, erythroid cells from SOCS-1-/- mice displayed increased sensitivity to Epo. These observations indicate complex, stage-specific regulation of SOCS genes during normal erythroid maturation and in erythroleukemic cells.

The protein kinase C beta II exon confers mRNA instability in the presence of high glucose concentrations.

Previous studies showed that short term exposure of cells to high glucose destabilized protein kinase C (PKC) betaII mRNA, whereas PKCbetaI mRNA levels remained unaltered. Because PKCbeta mRNAs share common sequences other than the PKCbetaII exon encoding a different carboxyl terminus, we examined PKCbetaII mRNA for a cis-acting region that could confer glucose-induced destabilization. A beta-globin/growth hormone reporter con struct containing the PKCbetaII exon was transfected into human aorta and rat vascular smooth muscle cells (A10) to follow glucose-induced destabilization. Glucose (25 mm) exposure destabilized PKCbetaII chimeric mRNA but not control mRNA. Deletion analysis and electrophoretic mobility shift assays followed by UV cross-linking experiments demonstrated that a region introduced by inclusion of the betaII exon was required to confer destabilization. Although a cis-acting element mapped to 38 nucleotides within the betaII exon was necessary to bestow destabilization, it was not sufficient by itself to confer complete mRNA destabilization. Yet, in intact cells antisense oligonucleotides complementary to this region blocked glucose-induced destabilization. These results suggest that this region must function in context with other sequence elements created by exon inclusion involved in affecting mRNA stability. In summary, inclusion of an exon that encodes PKCbetaII mRNA introduces a cis-acting region that confers destabilization to the mRNA in response to glucose.

Phosphoinositide 3-kinase mediates protein kinase C beta II mRNA destabilization in rat A10 smooth muscle cell cultures exposed to high glucose.

High-glucose exposure down-regulates protein kinaseC beta II posttranscriptionally in rat and human vascular smooth muscle cells and contributes to increased cell proliferation. High-glucose-induced mRNA destabilization is specific for PKC beta II mRNA, while PKC beta I and other PKC mRNA are not affected. This study focused on whether glucose metabolism was required. The effect was blocked by cytochalasin B, suggesting a requirement for glucose uptake. Glucosamine did not mimic the effect, indicating that metabolism via hexosamine pathway was not involved. The effect was hexokinase-independent since 3-O-methylglucose, in a dose-dependent manner, mimicked high-glucose effects. Cycloheximide did not block the effect excluding dependency on new protein synthesis. Wortmannin and LY294002, phosphoinositide 3-kinase (PI3-kinase) inhibitors, blocked glucose effects in the presence of 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole. Glucose and 3-O-methylglucose activated PI3-kinase, and LY294002 blocked glucose effects on Akt phosphorylation. In these cells, high-glucose concentrations activated a metabolically linked signaling pathway independent of glucose metabolism to regulate mRNA processing.