Modeling of 2D self-drifting flame-balls in Hele-Shaw cells

The disintegration of near limit flames propagating through the gap of Hele-Shaw cells has recently become a subject of active research. In this paper, the flamelets resulting from the disintegration of the continuous front a reinterpreted in terms of the Zeldovich flame-balls stabilized by volumetric heat losses. A complicated free-boundary problem for 2D self-drifting near circular flamelets is reduced to a 1D model. The 1D formulation is then utilized to obtain the locus of the flamelet velocity, radius, heat losses and Lewis numbers at which the self-drifting flamelet exists.Comment: 19 pages, 22 figure

Au nanostructured surfaces for electrochemical and localized surface plasmon resonance-based monitoring of α-synuclein-small molecule interactions.

In this proof-of-concept study, the fabrication of novel Au nanostructured indium tin oxide (Au-ITO) surfaces is described for the development of a dual-detection platform with electrochemical and localized surface plasmon resonance (LSPR)-based biosensing capabilities. Nanosphere lithography (NSL) was applied to fabricate Au-ITO surfaces. Oligomers of α-synuclein (αS) were covalently immobilized to determine the electrochemical and LSPR characteristics of the protein. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were performed using the redox probe [Fe(CN)6](3-/4-) to detect the binding of Cu(II) ions and (-)-epigallocatechin-3-gallate (EGCG) to αS on the Au-ITO surface. Electrochemical and LSPR data were complemented by Thioflavin-T (ThT) fluorescence, surface plasmon resonance imaging (SPRi), and transmission electron microscopy (TEM) studies. EGCG was shown to induce the formation of amorphous aggregates that decreased the electrochemical signals. However, the binding of EGCG with αS increased the LSPR absorption band with a bathochromic shift of 10-15 nm. The binding of Cu(II) to αS enhanced the DPV peak current intensity. NSL fabricated Au-ITO surfaces provide a promising dual-detection platform to monitor the interaction of small molecules with proteins using electrochemistry and LSPR

Characterization of a far-red analog of ghrelin for imaging GHS-R in P19-derived cardiomyocytes.

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as measured in HEK293 cells overexpressing GHS-R1a was within an order of magnitude of that of fluorescein-ghrelin and native human ghrelin, while the des-acyl Cy5-ghrelin did not bind GHS-R1a. Live cell imaging in HEK293/GHS-R1a cells showed cell surface labeling that was displaced by excess ghrelin. Interestingly, Cy5-ghrelin, but not the des-acyl analog, showed concentration-dependent binding in mouse heart tissue sections. We then used Cy5-ghrelin to track GHS-R expression in P19-derived cardiomyocytes. Live cell imaging at different time points after DMSO-induced differentiation showed that GHS-R expression preceded that of the differentiation marker aMHC and tracked with the contractility marker SERCA 2a. Our far-red analog of ghrelin adds to the tools we are developing to map GHS-R in developing and diseased cardiac tissues

SPARK Linking Ready Kids to Ready Schools: A Report on Policy Insights from the Governors' Forum Series

Each year too many children start kindergarten unprepared to learn. Many will never catch up. The reasons for this are complex, but this much is clear: The multiple systems – from family to schools to government – that should be supporting young children too often are failing to do so. The W.K. Kellogg Foundation seeks to change that, and to permanently improve systems that affect children's learning.As policymakers look for ways to improve student outcomes by creating "seamless" systems of education starting at preschool, communities have been getting it done. SPARK (Supporting Partnerships to Assure Ready Kids) — a fiveyear initiative funded by the Kellogg Foundation — has contributed a unique, community-based perspective to the national conversation on what it takes to effectively link learning systems. In particular, SPARK examines what it takes at the beginning of the education pipeline to link early learning to the early grades. The goal is to make sure that children are ready for school and that schools are ready for them — a formula critical for a lifetime of successful learning.SPARK efforts are deeply anchored in the community and are designed to assure that children are successful both before and after they enter school. The strategy of working with schools, early care and education providers, families and community partners has yielded a set of proven ways to align local systems of education — approaches that have been tested in diverse rural and urban communities in Florida, Georgia, Hawaii, Mississippi, New Mexico, North Carolina, Ohio and Washington, D.C. What SPARK community-based sites have done to create connections across local systems of learning stands to influence larger school reform issues and state policy discussions about what is needed to create a more holistic learning experience for children — one that results in academic success at grade three and beyond

Is rat a good model for assessment of particulate-based taste-masked formulations?

Recently there has been an increased interest to develop specialised dosage forms that are better suited to specific patient populations, such as paediatrics and geriatrics. In these patient populations the acceptability of the oral dosage form can be paramount to the products success. However, many active pharmaceutical Ingredients (APIs) are known to cause an aversive taste response. One way to increase the acceptability and to enhance the palatability of the formulation is to design coated taste-masked particulate-based dosage forms. The masking of poorly tasting drugs with physical barriers such as polymer coatings can be utilised to prevent the release of drug within the oral cavity, thus preventing a taste response. However, currently, there are few assessment tools and models available to test the efficiency of these particulate-based taste-masked formulations. The rat brief access taste aversion model has been shown to be useful in assessment of taste for liquid dosage forms. However, the applicability of the rat model for particulate-based taste masked formulations is yet to be assessed. It is not understood whether dissolution, solubility and thus exposure of the drug to taste receptors would be the same in rat and human. Therefore, rat saliva must be compared to human saliva to determine the likelihood that drug release would be similar within the oral cavity for both species. In this study rat saliva was characterised for parameters known to be important for drug dissolution, such as pH, buffer capacity, surface tension, and viscosity. Subsequently dissolution of model bitter tasting compounds, sildenafil citrate and efavirenz, in rat saliva was compared to dissolution in human saliva. For all parameters characterised and for the dissolution of both drugs in rat saliva, a substantial difference was observed when compared to human saliva. This discrepancy in saliva parameters and dissolution of model drugs suggests that preclinical taste evaluation of particulate-based taste-masked formulations suggests rat is not a good model for predicting taste of solid dosage forms or undissolved drug where dissolution is required. Alternative preclinical in vivo models in other species, or improved biorelevant in vitro models should be considered instead

Innate recognition of apoptotic cells:novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies

Cells dying by apoptosis are normally cleared by phagocytes through mechanisms that can suppress inflammation and immunity. Molecules of the innate immune system, the pattern recognition receptors (PRRs), are able to interact not only with conserved structures on microbes (pathogen-associated molecular patterns, PAMPs) but also with ligands displayed by apoptotic cells. We reasoned that PRRs might therefore interact with structures on apoptotic cells-apoptotic cell-associated molecular patterns (ACAMPs)-that are analogous to PAMPs. Here we show that certain monoclonal antibodies raised against the prototypic PAMP, lipopolysaccharide (LPS), can crossreact with apoptotic cells. We demonstrate that one such antibody interacts with a constitutively expressed intracellular protein, laminin-binding protein, which translocates to the cell surface during apoptosis and can interact with cells expressing the prototypic PRR, mCD14 as well as with CD14-negative cells. Anti-LPS cross reactive epitopes on apoptotic cells colocalised with annexin V-and C1q-binding sites on vesicular regions of apoptotic cell surfaces and were released associated with apoptotic cell-derived microvesicles (MVs). These results confirm that apoptotic cells and microbes can interact with the immune system through common elements and suggest that anti-PAMP antibodies could be used strategically to characterise novel ACAMPs associated not only with apoptotic cells but also with derived MVs

Perspectives on the ‘silent period’ for emergent bilinguals in England

This paper draws together the research findings from two ethnographic studies (Drury, 2007; Bligh, 2011) as a means to problematize the ‘silent period’ as experienced by young bilingual learners in two English speaking early years settings in England. Most teachers and senior early years practitioners in England are monolingual English speakers. The children (regardless of their mother tongue) are taught through the medium of spoken and written English in and through all subject areas. Bilingual learning through the mother tongue is not only disregarded in most schools in England but is actively discouraged in some. Three emergent bilingual learners were re-examined as case studies. Suki and Adyta (Bligh, 2011) of Japanese and Punjabi decent and Nazma (Drury, 2007) of Kashmiri descent were observed whilst they each negotiated new ways of knowing within and through an English pre-school setting. Sociocultural insights into how these young children employ their silenced mother tongue to negotiate their learning creates a fuller and richer portrait of the emergent bilingual learner both in and outside of preschool. These collaborative research findings present the silent period as agentive (Drury, 2007) and as a crucial time for self-mediated learning (Bligh, 2011) within the early years community of practice