Lentiviral vectors with amplified beta cell-specific gene expression.

An important goal of gene therapy is to be able to deliver genes, so that they express in a pattern that recapitulates the expression of an endogenous cellular gene. Although tissue-specific promoters confer selectivity, in a vector-based system, their activity may be too weak to mediate detectable levels in gene-expression studies. We have used a two-step transcriptional amplification system to amplify gene expression from lentiviral vectors using the human insulin promoter. In this system, the human insulin promoter drives expression of a potent synthetic transcription activator (the yeast GAL4 DNA-binding domain fused to the activation domain of the Herpes simplex virus-1 VP16 activator), which in turn activates a GAL4-responsive promoter, driving the enhanced green fluorescent protein reporter gene. Vectors carrying the human insulin promoter did not express in non-beta-cell lines, but expressed in murine insulinoma cell lines, indicating that the human insulin promoter was capable of conferring cell specificity of expression. The insulin-amplifiable vector was able to amplify gene expression five to nine times over a standard insulin-promoter vector. In primary human islets, gene expression from the insulin-promoted vectors was coincident with insulin staining. These vectors will be useful in gene-expression studies that require a detectable signal and tissue specificity

Childhood and the politics of scale: Descaling children's geographies?

This is the post-print version of the final published paper that is available from the link below. Copyright @ 2008 SAGE Publications.The past decade has witnessed a resurgence of interest in the geographies of children's lives, and particularly in engaging the voices and activities of young people in geographical research. Much of this growing body of scholarship is characterized by a very parochial locus of interest — the neighbourhood, playground, shopping mall or journey to school. In this paper I explore some of the roots of children's geographies' preoccupation with the micro-scale and argue that it limits the relevance of research, both politically and to other areas of geography. In order to widen the scope of children's geographies, some scholars have engaged with developments in the theorization of scale. I present these arguments but also point to their limitations. As an alternative, I propose that the notion of a flat ontology might help overcome some difficulties around scalar thinking, and provide a useful means of conceptualizing sociospatiality in material and non-hierarchical terms. Bringing together flat ontology and work in children's geographies on embodied subjectivity, I argue that it is important to examine the nature and limits of children's spaces of perception and action. While these spaces are not simply `local', they seldom afford children opportunities to comment on, or intervene in, the events, processes and decisions that shape their own lives. The implications for the substance and method of children's geographies and for geographical work on scale are considered

Modeling the red sequence: Hierarchical growth yet slow luminosity evolution

We explore the effects of mergers on the evolution of massive early-type galaxies by modeling the evolution of their stellar populations in a hierarchical context. We investigate how a realistic red sequence population set up by z~1 evolves under different assumptions for the merger and star formation histories, comparing changes in color, luminosity and mass. The purely passive fading of existing red sequence galaxies, with no further mergers or star formation, results in dramatic changes at the bright end of the luminosity function and color-magnitude relation. Without mergers there is too much evolution in luminosity at a fixed space density compared to observations. The change in color and magnitude at a fixed mass resemble that of a passively evolving population that formed relatively recently, at z~2. Mergers amongst the red sequence population ("dry mergers") occurring after z=1 build up mass, counteracting the fading of the existing stellar populations to give smaller changes in both color and luminosity for massive galaxies. By allowing some galaxies to migrate from the blue cloud onto the red sequence after z=1 through gas-rich mergers, younger stellar populations are added to the red sequence. This manifestation of the progenitor bias increases the scatter in age and results in even smaller changes in color and luminosity between z=1 and z=0 at a fixed mass. The resultant evolution appears much slower, resembling the passive evolution of a population that formed at high redshift (z~3-5) and is in closer agreement with observations. Measurements of the luminosity and color evolution alone are not sufficient to distinguish between the purely passive evolution of an old population and cosmologically motivated hierarchical growth, although these scenarios have very different implications for the mass growth of early-type galaxies over the last half of cosmic history.Comment: 14 pages, 4 figures. Final version accepted for publication in ApJ (2012, ApJ 753, 44

The Evolution of the Fractions of Quiescent and Star-forming Galaxies as a Function of Stellar Mass Since z=3: Increasing Importance of Massive, Dusty Star-forming Galaxies in the Early Universe

Using the UltraVISTA DR1 and 3D-HST catalogs, we construct a stellar-mass-complete sample, unique for its combination of surveyed volume and depth, to study the evolution of the fractions of quiescent galaxies, moderately unobscured star-forming galaxies, and dusty star-forming galaxies as a function of stellar mass over the redshift interval $0.2 \le z \le 3.0$. We show that the role of dusty star-forming galaxies within the overall galaxy population becomes more important with increasing stellar mass, and grows rapidly with increasing redshift. Specifically, dusty star-forming galaxies dominate the galaxy population with $\log{(M_{\rm star}/M_{\odot})} \gtrsim 10.3$ at $z\gtrsim2$. The ratio of dusty and non-dusty star-forming galaxies as a function of stellar mass changes little with redshift. Dusty star-forming galaxies dominate the star-forming population at $\log{(M_{\rm star}/M_{\odot})} \gtrsim 10.0-10.5$, being a factor of $\sim$3-5 more common, while unobscured star-forming galaxies dominate at $\log{(M_{\rm star}/M_{\odot})} \lesssim 10$. At $\log{(M_{\rm star}/M_{\odot})} > 10.5$, red galaxies dominate the galaxy population at all redshift $z<3$, either because they are quiescent (at late times) or dusty star-forming (in the early universe).Comment: 7 pages, 4 figures, 1 table. Accepted by Astrophysical Journal Letters after minor revisio

Direct Observation of Dynamic Symmetry Breaking above Room Temperature in Methylammonium Lead Iodide Perovskite

Lead halide perovskites such as methylammonium lead triiodide (MAPI) have outstanding optical and electronic properties for photovoltaic applications, yet a full understanding of how this solution processable material works so well is currently missing. Previous research has revealed that MAPI possesses multiple forms of static disorder regardless of preparation method, which is surprising in light of its excellent performance. Using high energy resolution inelastic X-ray (HERIX) scattering, we measure phonon dispersions in MAPI and find direct evidence for another form of disorder in single crystals: large amplitude anharmonic zone-edge rotational instabilities of the PbI_6 octahedra that persist to room temperature and above, left over from structural phase transitions that take place tens to hundreds of degrees below. Phonon calculations show that the orientations of the methylammonium couple strongly and cooperatively to these modes. The result is a non-centrosymmetric, instantaneous local structure, which we observe in atomic pair distribution function (PDF) measurements. This local symmetry breaking is unobservable by Bragg diffraction, but can explain key material properties such as the structural phase sequence, ultra low thermal transport, and large minority charge carrier lifetimes despite moderate carrier mobility.Comment: 30 pages, 11 figure

Visual activism and social justice: using visual methods to make young people’s complex lives visible across ‘public’ and ‘private’ spaces

Much critical social justice research, including work employing visual methods, focuses on young people&rsquo;s use of public spaces leaving domestic spaces relatively unexplored. Such research tacitly maintains modernist notions of the public/private distinction in which the private sphere is considered less relevant to concerns of social justice. However, UK crime and social justice policy has increasingly intervened in the home lives of the poorest British families. Further, such policies have been legitimated by drawing on (or not contesting) media imagery that constructs these family lives almost entirely negatively, obscuring their complexity. Drawing on childhood studies research, and a project that employed visual methods to explore belonging among young people in foster, kinship or residential care, this paper examines participants&rsquo; often fragile efforts to find or forge places in which they could feel at &lsquo;home&rsquo; and imagine a future. In so doing, it invites visual activists to reconsider their understanding of public and private spaces in order to contest prevalent unsympathetic policy representations of poorer young people&rsquo;s lives, to focus greater attention on their need for support, and to extend imaginations of their futures

Calcite/aragonite ratio fluctuations in Aptian rudist bivalves: Correlation with changing temperatures

Understanding how bivalves responded to past temperature fluctuations may help us to predict specific responses of complex calcifiers to future climate change. During the late-Early Aptian, aragonite-rich rudist bivalves decreased in abundance in northern Tethyan carbonate platforms, while rudists with a thickened calcitic outer shell layer came to dominate those of Iberia. Seawater cooling and variations in calcium carbonate saturation states may have controlled this faunal turnover. However, our understanding of how rudist lineages responded to changing environmental conditions is constrained by a lack of quantitative data on the evolution of thickness, size, and mineralogy of the shell. This study is based on volumetric measurements of the shell and shows the transition in lineages of the family Polyconitidae from aragonite-rich mineralogy in the earliest Aptian, to low-Mg calcite-dominated mineralogy in the middle Aptian, returning to aragonite-dominated composition in the latest Aptian. The platform biocalcification crisis that occurred at the Early-Late Aptian boundary in the Tethys was marked by a relative increase of calcite and a decrease in skeletal thickness and commissural diameters. The highest calcite/aragonite (Cc/A) ratios in polyconitid rudists accompanied the late Aptian cold episode, and the lowest values were reached during the warmer intervals of the earliest and latest Aptian. These results imply a correlation between Cc/A ratio values and temperature and suggest that some bivalves adapted to less favorable calcification conditions by changing calcite and aragonite proportions of their bimineralic shells and decreasing skeletal thickness, thereby reducing the metabolic cost of shell growth. GeoRef Subjec

Gamma ray monitoring of a AGN and galactic black hole candidates by the Compton Gamma Ray Observatory

The Compton Gamma-Ray Observatory's Burst and Transient Source Experiment (BATSE) has a powerful capability to provide nearly uninterrupted monitoring in the 25 keV-10 MeV range of both active galactic nuclei (AGN) and galactic black hole candidates (GBHC) such as Cygnus X-1, using the occultation of cosmic sources by the Earth. Since the Crab is detected by the BATSE Large Area Detectors with roughly 25(sigma) significance in the 15-125 keV range in a single rise or set, a variation by a factor of two of a source having one-tenth the strength of Cygnus X-1 should be detectable within a day. Methods of modeling the background are discussed which will increase the accuracy, sensitivity, and reliability of the results beyond those obtainable from a linear background fit with a single rise or set discontinuity