Cell Therapy for Type 1 Diabetes

Acknowledgements The work described in this review was supported by a grant from the MRC. K.R.M. is supported by a fellowship from the Scottish Translational Medicines and Therapeutics Initiative through the Wellcome Trust.Peer reviewedPublisher PD

Inhibition of activin/nodal signalling is necessary for pancreatic differentiation of human pluripotent stem cells

Peer reviewedPublisher PD

Origins and composition of fine atmospheric carbonaceous aerosol in the Sierra Nevada Mountains, California

In this paper we report chemically resolved measurements of organic aerosol (OA) and related tracers during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX) at the Blodgett Forest Research Station, California from 15 August–10 October 2007. OA contributed the majority of the mass to the fine atmospheric particles and was predominately oxygenated (OOA). The highest concentrations of OA were during sporadic wildfire influence when aged plumes were impacting the site. In situ measurements of particle phase molecular markers were dominated by secondary compounds and along with gas phase compounds could be categorized into six factors or sources: (1) aged biomass burning emissions and oxidized urban emissions, (2) oxidized urban emissions (3) oxidation products of monoterpene emissions, (4) monoterpene emissions, (5) anthropogenic emissions and (6) local methyl chavicol emissions and oxidation products. There were multiple biogenic components that contributed to OA at this site whose contributions varied diurnally, seasonally and in response to changing meteorological conditions, e.g. temperature and precipitation events. Concentrations of isoprene oxidation products were larger when temperatures were higher during the first half of the campaign (15 August–12 September) due to more substantial emissions of isoprene and enhanced photochemistry. The oxidation of methyl chavicol, an oxygenated terpene emitted by ponderosa pine trees, contributed similarly to OA throughout the campaign. In contrast, the abundances of monoterpene oxidation products in the particle phase were greater during the cooler conditions in the latter half of the campaign (13 September–10 October), even though emissions of the precursors were lower, although the mechanism is not known. OA was correlated with the anthropogenic tracers 2-propyl nitrate and carbon monoxide (CO), consistent with previous observations, while being comprised of mostly non-fossil carbon (>75%). The correlation between OA and an anthropogenic tracer does not necessarily identify the source of the carbon as being anthropogenic but instead suggests a coupling between the anthropogenic and biogenic components in the air mass that might be related to the source of the oxidant and/or the aerosol sulfate. Observations of organosulfates of isoprene and α-pinene provided evidence for the likely importance of aerosol sulfate in spite of neutralized aerosol although acidic plumes might have played a role upwind of the site. This is in contrast to laboratory studies where strongly acidic seed aerosols were needed in order to form these compounds. These compounds together represented only a minor fraction (<1%) of the total OA mass, which may be the result of the neutralized aerosol at the site or because only a small number of organosulfates were quantified. The low contribution of organosulfates to total OA suggests that other mechanisms, e.g. NO_x enhancement of oxidant levels, are likely responsible for the majority of the anthropogenic enhancement of biogenic secondary organic aerosol observed at this site

Apportionment of primary and secondary organic aerosols in Southern California during the 2005 Study of Organic Aerosols in Riverside (SOAR-1)

Ambient sampling was conducted in Riverside, California during the 2005 Study of Organic Aerosols in Riverside to characterize the composition and sources of organic aerosol using a variety of state-of-the-art instrumentation and source apportionment techniques. The secondary organic aerosol (SOA) mass is estimated by elemental carbon and carbon monoxide tracer methods, water soluble organic carbon content, chemical mass balance of organic molecular markers, and positive matrix factorization of high-resolution aerosol mass spectrometer data. Estimates obtained from each of these methods indicate that the organic fraction in ambient aerosol is overwhelmingly secondary in nature during a period of several weeks with moderate ozone concentrations and that SOA is the single largest component of PM1 aerosol in Riverside. Average SOA/OA contributions of 70−90% were observed during midday periods, whereas minimum SOA contributions of ~45% were observed during peak morning traffic periods. These results are contrary to previous estimates of SOA throughout the Los Angeles Basin which reported that, other than during severe photochemical smog episodes, SOA was lower than primary OA. Possible reasons for these differences are discussed

Scenario planning for the Edinburgh city region

This paper examines the application of scenario planning techniques to the detailed and daunting challenge of city re-positioning when policy makers are faced with a heavy history and a complex future context. It reviews a process of scenario planning undertaken in the Edinburgh city region, exploring the scenario process and its contribution to strategies and policies for city repositioning. Strongly rooted in the recent literature on urban and regional economic development, the text outlines how key individuals and organisations involved in the process participated in far-reaching analyses of the possible future worlds in which the Edinburgh city region might find itself

Major components of atmospheric organic aerosol in southern California as determined by hourly measurements of source marker compounds

We report the first hourly in-situ measurements of speciated organic aerosol (OA) composition in an urban environment. Field measurements were made in southern California at the University of California–Riverside during the 2005 Study of Organic Aerosol at Riverside (SOAR), which included two separate measurement periods: a summer study (15 July–15 August) and a fall study (31 October–28 November). Hourly measurements of over 300 semivolatile and nonvolatile organic compounds were made using the thermal desorption aerosol gas chromatograph (TAG). Positive matrix factorization (PMF) was performed on a subset of these compounds to identify major components contributing to submicron (i.e., PM₁) OA at the site, as measured by an aerosol mass spectrometer (AMS). PMF analysis was performed on an 11-day focus period in each season, representing average seasonal conditions during the summer and a period of urban influence during the fall. As a result of this analysis, we identify multiple types of primary and secondary OA (POA and SOA). Secondary sources contribute substantially to fine OA mass at Riverside, which commonly receives regional air masses that pass through metropolitan Los Angeles during the summer. Four individual summertime SOA components are defined, and when combined, they are estimated to contribute an average 88% of the total fine OA mass during summer afternoons according to PMF results. These sources appear to be mostly from the oxidation of anthropogenic precursor gases, with one SOA component having contributions from oxygenated biogenics. During the fall, three out of four aerosol components that contain SOA are inseparable from covarying primary emissions, and therefore we cannot estimate the fraction of total OA that is secondary in nature during the fall study. Identified primary OA components are attributed to vehicle emissions, food cooking, primary biogenics, and biomass burning aerosol. While a distinction between local and regional vehicle emissions is made, a combination of these two factors accounted for approximately 11% of observed submicron OA during both sampling periods. Food cooking operations contributed ~10% of submicron OA mass during the summer, but was not separable from SOA during the fall due to high covariance of sources. Biomass burning aerosol contributed a larger fraction of fine OA mass during the fall (~11%) than compared to summer (~7%). Primary biogenic aerosol was also identified during the summer, contributing ~1% of the OA, but not during the fall. While the contribution of both local and regional primary vehicle OA accounts for only ~11% of total OA during both seasons, gas-phase vehicle emissions likely create a substantial fraction of the observed SOA as a result of atmospheric processing

Genome-wide association study of receptive language ability of 12 year olds

Purpose: We have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. The current study attempted to identify some of the genes responsible for the heritability of receptive language ability using a genome-wide association (GWA) approach. Method: We administered four internet-based measures of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample of 2329 12-year-olds for whom DNA and genome-wide genotyping were available. Nearly 700,000 single-nucleotide polymorphisms (SNPs) and one million imputed SNPs were included in a GWA analysis of receptive language composite scores. Results: No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p < 5 ×10-8). The strongest SNP association did not replicate in an additional sample of 2639 12-year-olds. Conclusion: These results indicate that individual differences in receptive language ability in the general population do not reflect common genetic variants that account for >3% of the phenotypic variance. The search for genetic variants associated with language skill will require larger samples and additional methods to identify and functionally characterize the full spectrum of risk variants

Pancreatic Transcription Factors Containing Protein Transduction Domains Drive Mouse Embryonic Stem Cells towards Endocrine Pancreas

Protein transduction domains (PTDs), such as the HIV1-TAT peptide, have been previously used to promote the uptake of proteins into a range of cell types, including stem cells. Here we generated pancreatic transcription factors containing PTD sequences and administered these to endoderm enriched mouse embryonic stem (ES) cells under conditions that were designed to mimic the pattern of expression of these factors in the developing pancreas. The ES cells were first cultured as embryoid bodies and treated with Activin A and Bone morphogenetic protein 4 (BMP4) to promote formation of definitive endoderm. Cells were subsequently plated as a monolayer and treated with different combinations of the modified recombinant transcription factors Pdx1 and MafA. The results demonstrate that each transcription factor was efficiently taken up by the cells, where they were localized in the nuclei. RT-qPCR was used to measure the expression levels of pancreatic markers. After the addition of Pdx1 alone for a period of five days, followed by the combination of Pdx1 and TAT-MafA in a second phase, up-regulation of insulin 1, insulin 2, Pdx1, Glut2, Pax4 and Nkx6.1 was observed. As assessed by immunocytochemistry, double positive insulin and Pdx1 cells were detected in the differentiated cultures. Although the pattern of pancreatic markers expression in these cultures was comparable to that of a mouse transformed β-cell line (MIN-6) and human islets, the expression levels of insulin observed in the differentiated ES cell cultures were several orders of magnitude lower. This suggests that, although PTD-TFs may prove useful in studying the role of exogenous TFs in the differentiation of ES cells towards islets and other pancreatic lineages, the amount of insulin generated is well below that required for therapeutically useful cells

Competing Ultrafast Energy Relaxation Pathways in Photoexcited Graphene

For most optoelectronic applications of graphene a thorough understanding of the processes that govern energy relaxation of photoexcited carriers is essential. The ultrafast energy relaxation in graphene occurs through two competing pathways: carrier-carrier scattering -- creating an elevated carrier temperature -- and optical phonon emission. At present, it is not clear what determines the dominating relaxation pathway. Here we reach a unifying picture of the ultrafast energy relaxation by investigating the terahertz photoconductivity, while varying the Fermi energy, photon energy, and fluence over a wide range. We find that sufficiently low fluence ($\lesssim$ 4 $\mu$J/cm$^2$) in conjunction with sufficiently high Fermi energy ($\gtrsim$ 0.1 eV) gives rise to energy relaxation that is dominated by carrier-carrier scattering, which leads to efficient carrier heating. Upon increasing the fluence or decreasing the Fermi energy, the carrier heating efficiency decreases, presumably due to energy relaxation that becomes increasingly dominated by phonon emission. Carrier heating through carrier-carrier scattering accounts for the negative photoconductivity for doped graphene observed at terahertz frequencies. We present a simple model that reproduces the data for a wide range of Fermi levels and excitation energies, and allows us to qualitatively assess how the branching ratio between the two distinct relaxation pathways depends on excitation fluence and Fermi energy.Comment: Nano Letters 201

Physical modeling of unsteady turbulence in breaking tidal bores

A tidal bore is an unsteady flow motion generated by the rapid water level rise at the river mouth during the early flood tide under macrotidal and appropriate bathymetric conditions. This paper presents a study that physically investigates the turbulent properties of tidal bores. Results from some experimental measurements of free-surface fluctuations and turbulent velocities conducted on smooth and rough beds are reported. The free-surface measurements were conducted with Froude numbers of 1-1.7. Both undular and breaking bores were observed. Using an ensemble-averaging technique, the free-surface fluctuations of breaking tidal bores are characterized. Immediately before the roller, the free-surface curves gradually upwards. The passage of the bore roller is associated with some large water elevation fluctuations; the largest free-surface fluctuations are observed during the first half of the bore roller. The turbulent velocity measurements were performed at several vertical elevations during and shortly after the passage of breaking bores. Both the instantaneous and ensemble-averaged velocity data highlight a strong flow deceleration at all elevations during the bore passage. Close to the bed, the longitudinal velocity component becomes negative immediately after the roller passage, implying the existence of a transient recirculation. The height and duration of the transient are a function of the bed roughness, with a higher and longer recirculation region above the rough bed. The vertical velocity data presented some positive, upward motion beneath the front with increasing maximum vertical velocity with increasing distance from the bed. The transverse velocity data show some large fluctuations with nonzero ensemble average after the roller passage that highlight some intense secondary motion advected behind the bore front. DOI: 10.1061/(ASCE)HY.1943-7900.0000542. (C) 2012 American Society of Civil Engineers