Counting statistics for mesoscopic conductors with internal degrees of freedom

We consider the transport of electrons passing through a mesoscopic device possessing internal dynamical quantum degrees of freedom. The mutual interaction between the system and the conduction electrons contributes to the current fluctuations, which we describe in terms of full counting statistics. We identify conditions where this discriminates coherent from incoherent internal dynamics, and also identify and illustrate conditions under which the device acts to dynamically bunch transmitted or reflected electrons, thereby generating super-Poissonian noise.Comment: 4 pages, 2 figure

Accelerating topical anaesthesia using microneedles

Background/Aims: Topical anaesthetics reduce pain during venous access procedures in children. However, clinical use is hindered by a significant anaesthetic onset time. Restricted diffusion of the topical anaesthetic through the stratum corneum barrier is the principal reason for the delayed onset. Microneedles can painlessly pierce the skin. This study evaluated microneedle pre-treatment of ex vivo human skin as a means to increase the rate of tetracaine permeation, in order to accelerate the onset of anaesthesia. Methods: Franz-type diffusion cells were used to determine permeation of a commercial tetracaine formulation, Ametop gel, through human skin epidermis. Microneedle-assisted permeation was compared to untreated epidermis. Upon completion of permeation studies the epidermal membranes were visually characterised. Results: At 30 minutes 5.43 μg/cm2 of tetracaine had permeated through untreated membrane compared to 12.13 μg/cm2 in microneedle treated membrane. Insertion of a hypodermic needle created a large single channel in the epidermis (approximately 4250μm2) whilst the punctured surface area following microneedle treatments was estimated to be 75,000μm2. Conclusion: Pre-treatment of skin with microneedles significantly enhances the permeation of tetracaine. Microneedles have the potential to more than halve the onset time for anaesthesia when applying Ametop gel

FlgN is required for flagellum based motility by <em>Bacillus subtilis</em>

The assembly of the bacterial flagellum is exquisitely controlled. Flagellar biosynthesis is underpinned by a specialized type III secretion system that allows export of proteins from the cytoplasm to the nascent structure. Bacillus subtilis regulates flagellar assembly using both conserved and species-specific mechanisms. Here, we show that YvyG is essential for flagellar filament assembly. We define YvyG as an orthologue of the Salmonella enterica serovar Typhimurium type III secretion system chaperone, FlgN, which is required for the export of the hook-filament junction proteins, FlgK and FlgL. Deletion of flgN (yvyG) results in a nonmotile phenotype that is attributable to a decrease in hag translation and a complete lack of filament polymerization. Analyses indicate that a flgK-flgL double mutant strain phenocopies deletion of flgN and that overexpression of flgK-flgL cannot complement the motility defect of a ΔflgN strain. Furthermore, in contrast to previous work suggesting that phosphorylation of FlgN alters its subcellular localization, we show that mutation of the identified tyrosine and arginine FlgN phosphorylation sites has no effect on motility. These data emphasize that flagellar biosynthesis is differentially regulated in B. subtilis from classically studied Gram-negative flagellar systems and questions the biological relevance of some posttranslational modifications identified by global proteomic approaches

Coupling flagellar gene expression to flagellar assembly in Caulobacter crescentus

PhD ThesisBacterial flagellar filaments are long cell surface appendages that generate propulsion for movement. They also play key roles in surface attachment and host-bacterial interactions. The filament is made from a single protein species flagellin. Approximately 45 % of annotated flagellar systems possess multiple flagellin genes. We have investigated the ability of Caulobacter crescentus to build a flagellar filament using six flagellins: FljJ, FljK, FljL, FljM, FljN and FljO. Our analysis showed that this flagellar system exhibits extensive structural redundancy, in that one species of flagellin is sufficient to sustain motility. However, when that flagellin is FljJ cells are non motile. Distinct flagellar assembly checkpoints are utilised by bacteria in order to coordinate and couple flagellar gene expression to the assembly pathway. One of these checkpoints, hook-basal-body completion, is sensed and overcome by the secretion of a flagellar-associated secretion substrate. This mechanism results in a system switch to the export of proteins, which are needed for filament assembly. In C. crescentus the post-transcriptional regulators FlbT and FlaF have been implicated to function at this switch. As the flagellins themselves are being secreted we asked the logical question: are the flagellins involved in subunit feedback control of the regulation of filament assembly? In a bacterial two-hybrid assay, FljJ was the only flagellin able to interact with FlbT and FlaF. Furthermore, FljJ along with FlbT was found to interact with flagellin mRNA. In light of our data we a propose model for the regulation of flagellar filament assembly in C. crescentus and discuss the implications with respect to other flagellar system

Understanding large scale public political conversation online in austerity Britain through an iterative, quali-quanti investigation.

This study investigated online public political conversation in the UK. Drawing on theories of deliberative democracy, it emphasised the importance of inter-ideological discussion between citizens in the formation of informed opinion and preferences, focussing on the potential of the internet to facilitate this through large scale, ideologically diverse conversations. A multivariate analysis investigated the roles of interface design, institutional linkage and participant community dynamics in the formation of online political conversation. The investigation of conversation from across the internet required a very large scale approach, situating the study within the big data paradigm. However, it also required deeper understanding of human communication, gained through more qualitative analysis. Therefore the study utilised a novel, iterative, quali-quanti approach featuring initial, large scale quantitative analysis – involving bespoke software to automate the collection and analysis of conversation data – that was used to direct further iterations of increasingly smaller scale and qualitative analysis. Reflections on the successful application of the methodology are significant in themselves, but the study also generated novel observations of online public political conversation. The findings illustrated participatory spaces as unique online niches, each with specific communities and goals, and described how participant agency allows citizens to contribute according to various democratic models. For example, an action-oriented approach existed in policy related spaces, in which participants sought only to express a preference, rather than engage in discussion. In more discursive spaces, non-political social bonds between participants were seen to be particularly important in the facilitation of civil, productive, inter-ideological debate and certain participatory roles were important in facilitating these bonds. The design of spaces exerted a significant, but not determining effect on conversation, being used to present conversation in particular ways. However, certain features, notably active facilitation, helped to shape conversation through enabling some of the important community roles to be performed

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Himic Anhydride: A Retro Diels–Alder Reaction for the Organic Laboratory and an Accompanying NMR Study

The thermal equilibration of himic anhydride [IUPAC (2-endo,3-endo)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid anhydride] to (2-exo,3-exo)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid anhydride and subsequent recrystallization of the exo-product can be performed as a standard undergraduate laboratory experiment requiring minimal equipment. The interpretation of the 1H NMR spectra for these norbornene carboxylic anhydride molecules promotes an appreciation of constrained ring systems and factors that affect chemical shifts and coupling constants

Retreat into scientism, paradoxes of transparency, and corruption in education

Um dos sintomas da razão indolente (SANTOS, 2006) é o recuo ao cientificismo, o qual tem sido, particularmente, acentuado nas políticas, cada vez mais hegemônicas, de avaliação, de prestação de contas e de responsabilização. Por isso, um dos objetivos deste texto é o de colocar em causa este aparente consenso cientificista (ou este consenso supostamente transideológico) e fazer uma breve incursão exploratória ao que aqui se designa de paradoxos da transparência. Considera-se que esses paradoxos traduzem a existência de tensões e contradições relativas a uma dimensão central dos discursos políticos e educacionais contemporâneos. Com isso, o artigo pretende dar continuidade a uma linha de pesquisa que tem procurado sublinhar a relevância da necessidade de complexificar e dar maior rigor teórico-conceptual à accountability em educação. Finalmente, tentando abrir caminho para o desenvolvimento de novas articulações e análises, chama-se a atenção para a corrupção na educação cuja complexidade ainda é insuficientemente conhecida e pesquisada, nomeadamente, nas suas relações com as problemáticas da transparência e da accountability. Admite-se que as práticas de corrupção em educação, em muitas situações, são (paradoxalmente) induzidas pela necessidade de dar resposta à governação baseada nos números, nos rankings e nas (supostas) evidências, anulando completamente as expectativas legítimas em torno da transparência dos processos educacionais e das decisões políticas.One symptom of “indolent reason” (SANTOS, 2006) is the retreat into scientism, which is especially marked in the increasingly hegemonic policies surrounding assessment, reporting and accountability. As such, one of the aims of this paper is to call into question this apparent consensus on scientism (a supposedly trans-ideological consensus), and briefly explore what we define as the paradoxes of transparency. These paradoxes are found to reveal the existence of tensions and contradictions concerning a central aspect of current political and educational discourse. In doing so, the article seeks to continue a line of study which has aimed to emphasize the significance of the need for a more complex, and theoretically and conceptually rigorous understanding of accountability in education. Finally, in an attempt to pave the way for further discussion and analysis, attention is drawn to corruption in education, the complex nature of which remains insufficiently understood and studied, notably in terms of its relationship with the problems of transparency and accountability. It is acknowledged that practices of corruption within education are, in many situations, (paradoxically) caused by the need to answer to a system of governance based on numbers, league tables, and (supposed) truths, completely nullifying legitimate expectations about the transparency of educational processes and policy decisions.Trabalho financiado por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia – no âmbito do Projeto PEst-OE/CED/UI1661/2014.info:eu-repo/semantics/publishedVersio

Development and evaluation of topical gabapentin formulations

Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations