Using human induced pluripotent stem cells to treat retinal disease

AbstractThe eye is an ideal target for exploiting the potential of human induced pluripotent stem cell (hiPSC) technology in order to understand disease pathways and explore novel therapeutic strategies for inherited retinal disease. The aim of this article is to map the pathway from state-of-the art laboratory-based discoveries to realising the translational potential of this emerging technique. We describe the relevance and routes to establishing hiPSCs in selected models of human retinal disease. Additionally, we define pathways for applying hiPSC technology in treating currently incurable, progressive and blinding retinal disease

Hydrogen on venus: Exospheric distribution and escape

Charge exchange between H and H+ and momentum transfer between fast O and H provide comparable sources for suprathermal H atoms in Venus' exosphere. The fast O atoms are produced by dissociative recombination of O2 +. The spatial distribution of suprathermal H was calculated using an approximate numerical solution of the time-independent Boltzmann equation. Sources of suprathermal H atoms were specified on the basis of measurements by Pioneer Venus. Reactions involving H2 were neglected in the absence of direct experimental information on the concentration of H2 and on the grounds of indirect arguments suggesting its mixing ratio should be less than 0.5 ppmv. Computed densities of suprathermal H are in satisfactory agreement with profiles derived earlier from analysis of Lyman-α airglow by Mariners 5 and 10, and Veneras 11 and 12. The dayside emission at radial distances larger than 18,000 km is attributed to scattering of solar photons by fast H atoms produced primarily on the nightside near midnight. The nightside ionosphere, and consequently the source of suprathermal H, are expected to vary in response to changes in the solar wind. Observations of the variability of Lyman-α emission on the dayside could provide a useful test of the model, in particular its description of conditions in the nightside ionosphere and its neglect of fast H produced by reactions involving H2. Charge transfer of H with nightside H+ accounts for approximately 70% of the hydrogen escaping from Venus. The total escape rate is estimated to be between 0.4 and 1 × 107atoms cm−2s−1

Ozone, water vapor, and temperature in the upper tropical troposphere: Variations over a decade of MOZAIC measurements

[1] The MOZAIC ( Measurement of Ozone and Water Vapor by Airbus In-service Aircraft) program (Marenco et al., 1998) has archived in situ measurements of temperature, water vapor, and ozone from August 1994 to December 2003. We analyze the trends, seasonality, and interannual variability of these quantities at aircraft cruise levels (7.7 - 11.3 km) within the tropics ( 20 degrees S - 20 degrees N). Mean lapse rates for temperature and log( water vapor) are nearly identical in both tropics. The root-mean-square variance in temperature over cruise levels, seasons, and years is small, <= 1 degrees C. The seasonal range in water vapor, a factor of 2.5, is much larger than expected from the seasonal range in temperature (1.7 degrees C) if the two scale with the lapse rate relation or the Clausius-Clapeyron equation. The mean ozone abundance in the region sampled is 45 ppb in the north tropics and 50 ppb in the south tropics. This 112- month period shows a clearly linear increase in ozone over the north tropics with a trend fit of 1.12 +/- 0.05 ppb/yr. In the south tropics, which has a large seasonal range of over 25 ppb, the trend is less obvious but still robust, 1.03 +/- 0.08 ppb/yr. These trends in the upper troposphere are twice as large as reported for surface ozone over the tropical Atlantic (Lelieveld et al., 2004), but this pattern of ozone increases is consistent with projected increases driven by industrial emissions

Transport impacts on atmosphere and climate: Aviation

Aviation alters the composition of the atmosphere globally and can thus drive climate change and ozone depletion. The last major international assessment of these impacts was made by the Intergovernmental Panel on Climate Change (IPCC) in 1999. Here, a comprehensive updated assessment of aviation is provided. Scientific advances since the 1999 assessment have reduced key uncertainties, sharpening the quantitative evaluation, yet the basic conclusions remain the same. The climate impact of aviation is driven by long-term impacts from CO2 emissions and shorter-term impacts from non-CO2 emissions and effects, which include the emissions of water vapour, particles and nitrogen oxides (NOx). The presentday radiative forcing from aviation (2005) is estimated to be 55 mW m2 (excluding cirrus cloud enhancement), which represents some 3.5% (range 1.3–10%, 90% likelihood range) of current anthropogenic forcing, or 78 mW m2 including cirrus cloud enhancement, representing 4.9% of current forcing (range 2–14%, 90% likelihood range). According to two SRES-compatible scenarios, future forcings may increase by factors of 3–4 over 2000 levels, in 2050. The effects of aviation emissions of CO2 on global mean surface temperature last for many hundreds of years (in common with other sources), whilst its non-CO2 effects on temperature last for decades. Much progress has been made in the last ten years on characterizing emissions, although major uncertainties remain over the nature of particles. Emissions of NOx result in production of ozone, a climate warming gas, and the reduction of ambient methane (a cooling effect) although the overall balance is warming, based upon current understanding. These NOx emissions from current subsonic aviation do not appear to deplete stratospheric ozone. Despite the progress made on modelling aviation’s impacts on tropospheric chemistry, there remains a significant spread in model results. The knowledge of aviation’s impacts on cloudiness has also improved: a limited number of studies have demonstrated an increase in cirrus cloud attributable to aviation although the magnitude varies: however, these trend analyses may be impacted by satellite artefacts. The effect of aviation particles on clouds (with and without contrails) may give rise to either a positive forcing or a negative forcing: the modelling and the underlying processes are highly uncertain, although the overall effect of contrails and enhanced cloudiness is considered to be a positive forcing and could be substantial, compared with other effects. The debate over quantification of aviation impacts has also progressed towards studying potential mitigation and the technological and atmospheric tradeoffs. Current studies are still relatively immature and more work is required to determine optimal technological development paths, which is an aspect that atmospheric science has much to contribute. In terms of alternative fuels, liquid hydrogen represents a possibility and may reduce some of aviation’s impacts on climate if the fuel is produced in a carbon-neutral way: such fuel is unlikely to be utilized until a ‘hydrogen economy’ develops. The introduction of biofuels as a means of reducing CO2 impacts represents a future possibility. However, even over and above land-use concerns and greenhouse gas budget issues, aviation fuels require strict adherence to safety standards and thus require extra processing compared with biofuels destined for other sectors, where the uptake of such fuel may be more beneficial in the first instance

The influence of future non-mitigated road transport emissions on regional ozone exceedences at global scale

Road Transport emissions (RTE) are a significant anthropogenic global NOx source responsible for enhancing the chemical production of tropospheric ozone (O3) in the lower troposphere. Here we analyse a multi-model ensemble which adopts the realistic SRES A1B emission scenario and a “policy-failure” scenario for RTE (A1B_HIGH) for the years 2000, 2025 and 2050. Analysing the regional trends in RTE NOx estimates shows by 2025 that differences of 0.2–0.3 Tg N yr−1 occur for most of the world regions between the A1B and A1B_HIGH estimates, except for Asia where there is a larger difference of ∼1.4 Tg N yr−1. For 2050 these differences fall to ∼0.1 Tg N yr−1, with shipping emissions becoming as important as RTE. Analysing the seasonality in near-surface O3 from the multi-model ensemble monthly mean values shows a large variability in the projected changes between different regions. For Western Europe and the Eastern US although the peak O3 mixing ratios decrease by ∼10% in 2050, there is an associated degradation during wintertime due to less direct titration from nitric oxide. For regions such as Eastern China, although total anthropogenic NOx emissions are reduced from 2025 to 2050, there is no real improvement in peak O3 levels. By normalizing the seasonal ensemble means of near-surface O3 (0–500 m) with the recommended European Commission (EC) exposure limit to derive an exceedence ratio (ER), we show that ER values greater than 1.0 occur across a wide area in the Northern Hemisphere for boreal summer using the year 2000 emissions. When adopting the future A1B_HIGH estimates, the Middle East exhibits the worst regional air quality, closely followed by Asia. For these regions the area of exceedence (ER > 1.0) for 2025 is ∼40% and ∼25% of the total area of each region, respectively. Comparing simulations employing the various scenarios shows that unmitigated RTE increases the area of exceedence in the Middle East by ∼6% and, for Asia, by ∼2% of the total regional areas. For the USA the area of exceedence approximately doubles in 2025 as a result of unmitigated RTE, with the most exceedences occurring in the southern USA. The effects across the various regions implies that unmitigated RTE would have a detrimental effect on regional health for 2025, and potentially offset the benefits introduced by mitigating e.g. international shipping emissions. By 2050 the further mitigation of non-transport emissions results in much cleaner air meaning that mitigation of RTE is not critical for achieving the defined limits in many world regions

Transport impacts on atmosphere and climate: Aviation

Aviation alters the composition of the atmosphere globally and can thus drive climate change and ozone depletion. The last major international assessment of these impacts was made by the Intergovernmental Panel on Climate Change (IPCC) in 1999. Here, a comprehensive updated assessment of aviation is provided. Scientific advances since the 1999 assessment have reduced key uncertainties, sharpening the quantitative evaluation, yet the basic conclusions remain the same. The climate impact of aviation is driven by long-term impacts from CO2 emissions and shorter-term impacts from non-CO2 emissions and effects, which include the emissions of water vapour, particles and nitrogen oxides (NOx). The present-day radiative forcing from aviation (2005) is estimated to be 55 mW m−2 (excluding cirrus cloud enhancement), which represents some 3.5% (range 1.3–10%, 90% likelihood range) of current anthropogenic forcing, or 78 mW m−2 including cirrus cloud enhancement, representing 4.9% of current forcing (range 2–14%, 90% likelihood range). According to two SRES-compatible scenarios, future forcings may increase by factors of 3–4 over 2000 levels, in 2050. The effects of aviation emissions of CO2 on global mean surface temperature last for many hundreds of years (in common with other sources), whilst its non-CO2 effects on temperature last for decades. Much progress has been made in the last ten years on characterizing emissions, although major uncertainties remain over the nature of particles. Emissions of NOx result in production of ozone, a climate warming gas, and the reduction of ambient methane (a cooling effect) although the overall balance is warming, based upon current understanding. These NOx emissions from current subsonic aviation do not appear to deplete stratospheric ozone. Despite the progress made on modelling aviation's impacts on tropospheric chemistry, there remains a significant spread in model results. The knowledge of aviation's impacts on cloudiness has also improved: a limited number of studies have demonstrated an increase in cirrus cloud attributable to aviation although the magnitude varies: however, these trend analyses may be impacted by satellite artefacts. The effect of aviation particles on clouds (with and without contrails) may give rise to either a positive forcing or a negative forcing: the modelling and the underlying processes are highly uncertain, although the overall effect of contrails and enhanced cloudiness is considered to be a positive forcing and could be substantial, compared with other effects. The debate over quantification of aviation impacts has also progressed towards studying potential mitigation and the technological and atmospheric tradeoffs. Current studies are still relatively immature and more work is required to determine optimal technological development paths, which is an aspect that atmospheric science has much to contribute. In terms of alternative fuels, liquid hydrogen represents a possibility and may reduce some of aviation's impacts on climate if the fuel is produced in a carbon-neutral way: such fuel is unlikely to be utilized until a ‘hydrogen economy’ develops. The introduction of biofuels as a means of reducing CO2impacts represents a future possibility. However, even over and above land-use concerns and greenhouse gas budget issues, aviation fuels require strict adherence to safety standards and thus require extra processing compared with biofuels destined for other sectors, where the uptake of such fuel may be more beneficial in the first instance

Radiative forcing due to changes in ozone and methane caused by the transport sector

The year 2000 radiative forcing (RF) due to changes in O3 and CH4 (and the CH4-induced stratospheric water vapour) as a result of emissions of short-lived gases (oxides of nitrogen (NOx), carbon monoxide and non-methane hydrocarbons) from three transport sectors (ROAD, maritime SHIPping and AIRcraft) are calculated using results from five global atmospheric chemistry models. Using results from these models plus other published data, we quantify the uncertainties. The RF due to short-term O3 changes (i.e. as an immediate response to the emissions without allowing for the long-term CH4 changes) is positive and highest for ROAD transport (31mWm-2) compared to SHIP (24 mWm-2) and AIR (17 mWm-2) sectors in four of the models. All five models calculate negative RF from the CH4 perturbations, with a larger impact from the SHIP sector than for ROAD and AIR. The net RF of O3 and CH4 combined (i.e. including the impact of CH4 on ozone and stratospheric water vapour) is positive for ROAD (+16(±13)(one standard deviation) mWm-2) and AIR (+6(±5) mWm-2) traffic sectors and is negative for SHIP (-18(±10) mWm-2) sector in all five models. Global Warming Potentials (GWP) and Global Temperature change Potentials (GTP) are presented for AIR NOx emissions; there is a wide spread in the results from the 5 chemistry models, and it is shown that differences in the methane response relative to the O3 response drive much of the spread