All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium ...adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium
. Here, using whole-genome sequencing, we show that normal human endometrial glands are clonal cell populations with total mutation burdens that increase at about 29 base substitutions per year and that are many-fold lower than those of endometrial cancers. Normal endometrial glands frequently carry 'driver' mutations in cancer genes, the burden of which increases with age and decreases with parity. Cell clones with drivers often originate during the first decades of life and subsequently progressively colonize the epithelial lining of the endometrium. Our results show that mutational landscapes differ markedly between normal tissues-perhaps shaped by differences in their structure and physiology-and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Surface ozone is a secondary air pollutant produced during the atmospheric photochemical degradation of emitted volatile organic compounds (VOCs) in the presence of sunlight and nitrogen oxides ...(NOx). Temperature directly influences ozone production through speeding up the rates of chemical reactions and increasing the emissions of VOCs, such as isoprene, from vegetation. In this study, we used an idealised box model with different chemical mechanisms (Master Chemical Mechanism, MCMv3.2; Common Representative Intermediates, CRIv2; Model for OZone and Related Chemical Tracers, MOZART-4; Regional Acid Deposition Model, RADM2; Carbon Bond Mechanism, CB05) to examine the non-linear relationship between ozone, NOx and temperature, and we compared this to previous observational studies. Under high-NOx conditions, an increase in ozone from 20 to 40°C of up to 20ppbv was due to faster reaction rates, while increased isoprene emissions added up to a further 11ppbv of ozone. The largest inter-mechanism differences were obtained at high temperatures and high-NOx emissions. CB05 and RADM2 simulated more NOx-sensitive chemistry than MCMv3.2, CRIv2 and MOZART-4, which could lead to different mitigation strategies being proposed depending on the chemical mechanism. The increased oxidation rate of emitted VOC with temperature controlled the rate of Ox production; the net influence of peroxy nitrates increased net Ox production per molecule of emitted VOC oxidised. The rate of increase in ozone mixing ratios with temperature from our box model simulations was about half the rate of increase in ozone with temperature observed over central Europe or simulated by a regional chemistry transport model. Modifying the box model set-up to approximate stagnant meteorological conditions increased the rate of increase of ozone with temperature as the accumulation of oxidants enhanced ozone production through the increased production of peroxy radicals from the secondary degradation of emitted VOCs. The box model simulations approximating stagnant conditions and the maximal ozone production chemical regime reproduced the 2ppbv increase in ozone per degree Celsius from the observational and regional model data over central Europe. The simulated ozone-temperature relationship was more sensitive to mixing than the choice of chemical mechanism. Our analysis suggests that reductions in NOx emissions would be required to offset the additional ozone production due to an increase in temperature in the future.
The potential of emissions from urban vegetation combined with anthropogenic emissions to produce ozone and particulate matter has long been recognized. This potential increases with rising ...temperatures and may lead to severe problems with air quality in densely populated areas during heat waves. Here, we investigate how heat waves affect emissions of volatile organic compounds from urban/suburban vegetation and corresponding ground-level ozone and particulate matter. We use the Weather Research and Forecasting Model with atmospheric chemistry (WRF-Chem) with emissions of volatile organic compounds (VOCs) from vegetation simulated with MEGAN to quantify some of these feedbacks in Berlin, Germany, during the heat wave in 2006. The highest ozone concentration observed during that period was ∼200 μg/m3 (∼101 ppbV). The model simulations indicate that the contribution of biogenic VOC emissions to ozone formation is lower in June (9–11%) and August (6–9%) than in July (17–20%). On particular days within the analyzed heat wave period, this contribution increases up to 60%. The actual contribution is expected to be even higher as the model underestimates isoprene concentrations over urban forests and parks by 0.6–1.4 ppbv. Our study demonstrates that biogenic VOCs can considerably enhance air pollution during heat waves. We emphasize the dual role of vegetation for air quality and human health in cities during warm seasons, which is removal and lessening versus enhancement of air pollution. The results of our study suggest that reduction of anthropogenic sources of NOx, VOCs, and PM, for example, reduction of the motorized vehicle fleet, would have to accompany urban tree planting campaigns to make them really beneficial for urban dwellers.
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IJS, KILJ, NUK, PNG, UL, UM
For Gentrification? Butler, Tim
Environment and planning. A,
01/2007, Volume:
39, Issue:
1
Journal Article
Peer reviewed
In this paper I argue that gentrification, despite the many arguments over its continuing validity as a concept, retains its key importance in understanding processes of class change. For some it is ...a process of colonising the city, for others a manifestation of belonging; for some the concept can be used as a radical critique of neoliberalism whilst for others this very critique is an exemplar of the hegemonising tendencies amongst (often radical) North American urban scholars. I argue that the concept has grown somewhat middle-aged and overendowed with its own history. I suggest that it needs to retain a focus on the implications of macro social change for individuals and social groups. In particular, gentrification needs to decouple itself from its original association with the deindustrialisation of metropolitan centres such as London and from its associations with working-class displacement. Recently, gentrification has occurred across the spatial scale—in second-order cities and in hitherto suburban locations as well as in the countryside. Processes such as ‘greentrification’, ‘gated communities’, and ‘studentification’ often coexist in quite close proximity to each other; the influence London exerts over the southern half of England is a good example of this. I argue that the concept of gentrification functions as an important way of understanding the mediations between global processes and flows, on the one hand, and the construction of identities in particular localities, on the other. With the decline of social class as providing an overall explanation of cultural, social, and spatial behaviour, this notion of gentrification as a form of ‘elective belonging’ has considerable potential for uniting geographical and sociological approaches to agency and structure. I illustrate this by drawing on three recent studies on the relationship between people and places.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
This article is based on a study of Docklands in London, which was undertaken as part of a larger study of gentrification in inner London. Using interview and survey data, the article compares ...Docklands with the gentrification that has taken place elsewhere in inner London. Whilst there were important differences between these inner‐London study areas, all differ qualitatively from the process in Docklands. The article questions whether the distinction that is normally drawn between ‘gentrification by capital’ and ‘gentrification by collective social action’ is appropriate and argues that this disguises the nature of the urban regeneration being undertaken in Docklands. It is suggested that this is more a process of re‐urbanization in which some of the characteristics normally associated with suburban development are being brought to an area near the centre of the city, but in a context more normally reserved for gentrification. The data from the survey show that for many of the respondents in Docklands, the kind of life they are seeking is often associated with some conceptions of suburban life. It is suggested that both gentrification and suburbanization as concepts need to be used with care in understanding contemporary processes of re‐urbanization such as are occurring in Docklands and the central areas of other British cities.
Résumé
Cet article s'appuie sur une étude du quartier des Docks de Londres, menée dans le cadre de travaux plus vastes relatifs à l'embourgeoisement du centre londonien. Des données provenant d'entretiens et d'enquêtes permettent une comparaison entre cette zone et d'autres quartiers centraux ayant connu un embourgeoisement. S'il existe d'importantes différences entre ces quartiers du centre‐ville, tous divergent au plan qualitatif du processus des Docks. En s'interrogeant sur la pertinence de la distinction entre ‘embourgeoisement par le capital’ et ‘embourgeoisement par l'action sociale collective’, l'article avance que cette vision dissimule la nature de la régénération urbaine entreprise dans le quartier des Docks. Il s'agit davantage d'un processus de ré‐urbanisation dans lequel des caractéristiques associées habituellement à l'aménagement des banlieues sont apportées dans une zone située près du centre‐ville, bien que dans un contexte plus normalement réservéà l'embourgeoisement. Les résultats d'enquête montrent que, pour bon nombre des personnes interrogées, le genre de vie recherché dans le quartier des Docks se rapproche de certaines conceptions de la vie suburbaine. Il convient donc d'utiliser avec prudence les concepts d'embourgeoisement et de suburbanisation si l'on veut comprendre les processus contemporains de ré‐urbanisation, tels que ceux qui ont lieu dans le quartier des Docks et dans le centre d'autres grandes villes britanniques.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A gridded, geographically extended weather type classification has been developed based on the Jenkinson–Collison (JC) classification system and used to evaluate the representation of weather types ...over Europe in a suite of climate model simulations. To this aim, a set of models participating in the Coupled Model Intercomparison Project Phase 5 (CMIP5) is compared with the circulation from two reanalysis products. Furthermore, we examine seasonal changes between simulated frequencies of weather types at present and future climate conditions. The models are in reasonably good agreement with the reanalyses, but some discrepancies occur in cyclonic days being overestimated over North, and underestimated over South Europe, while anticyclonic situations were overestimated over South, and underestimated over North Europe. Low flow conditions were generally underestimated, especially in summer over South Europe, and Westerly conditions were generally overestimated. The projected frequencies of weather types in the late twenty-first century suggest an increase of Anticyclonic days over South Europe in all seasons except summer, while Westerly days increase over North and Central Europe, particularly in winter. We find significant changes in the frequency of Low flow conditions and the Easterly type that become more frequent during the warmer seasons over Southeast and Southwest Europe, respectively. Our results indicate that in winter the Westerly type has significant impacts on positive anomalies of maximum and minimum temperature over most of Europe. Except in winter, the warmer temperatures are linked to Easterlies, Anticyclonic and Low Flow conditions, especially over the Mediterranean area. Furthermore, we show that changes in the frequency of weather types represent a minor contribution of the total change of European temperatures, which would be mainly driven by changes in the temperature anomalies associated with the weather types themselves.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
High penetrations of domestic electric vehicles (EVs) in U.K. low voltage (LV) networks may result in significant technical problems. This paper proposes an implementable, centralized control ...algorithm, currently being trialed in 9 U.K. residential LV networks, that uses limited information to manage EV charging points to mitigate these technical problems. Two real U.K. LV networks are used to quantify the potential impacts of different EV penetration levels and to demonstrate the effectiveness of the control algorithm (using different control cycles) for simultaneous thermal and voltage management. Monte Carlo simulations (adopting 1-min resolution data) are undertaken to cater for domestic and EV demand uncertainties. Results for these LV networks show that problems may occur for EV penetrations higher than 20%. More importantly, they highlight that even for a 100% penetration and control cycles of up to 10 min, the control algorithm successfully mitigates problems on the examined LV networks. Crucially, to determine effects on the comfort of EV users, a metric is introduced and discussed. The results of different control settings are presented to analyze potential adaptations of the control strategy. Finally, a comparison with an optimization framework highlights that the proposed algorithm is as effective while using limited information.
Ambient air pollution poses a major risk for the development and aggravation of respiratory diseases. Evidence suggests that even in low-level air pollution environments there is a risk for an ...increase in adverse respiratory symptoms. We examined whether variations in daily air pollution levels of nitrogen dioxide, ozone, or particulate matter in Berlin, Germany were associated with hospital admissions of chronic obstructive pulmonary disease (COPD) and asthma patients in a time series analysis.
We calculated single and multi-pollutant models, investigated possible lags in effect, and analysed the influence of meteorological variables on the results. Data from January 2005 through December 2015 were used to quantify the concentration-response.
The risk ratio for asthma patients to be hospitalised on the same day of NO
exposure was 1.101 per 10 µg/m
NO
increase (95% CI: 1.013 to 1.195), for COPD patients 1.123 (95% CI: 1.081 to 1.168). Neither the exposure to ozone (95% CI: 0.904 to 1.020), PM
(95% CI: 0.990 to 1.127), nor PM
(95% CI: 0.981 to 1.148) was associated with an increased risk ratio for asthma patients to be hospitalised. Risk ratios for the hospital admission of COPD patients were also not increased due to ozone (95% CI: 0.981 to 1.033), PM
(95% CI: 0.988 to 1.032), or PM
(95% CI: 0.966 to 1.019) exposure. The presented risk ratios and confidence intervals relate to the day of exposure. We found no increased hospitalisation risks with a delayed occurrence on subsequent days.
A quantifiable, statistically significant increase in risk for asthma and COPD exacerbations owing to NO
exposure at levels well below European regulatory limit values was observed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Coloboma mouse carries a ∼2 cM deletion encompassing the SNAP25 gene and has a hyperactive phenotype similar to that of ADHD. Such mice are 3 fold more active compared to their control ...littermates. Genetic association studies support a role for allelic variants of the human SNAP25 gene in predisposing to ADHD.
We performed association analysis across the SNAP25 gene in 1,107 individuals (339 ADHD trios). To assess the functional relevance of the SNAP25-ADHD associated allele, we performed quantitative PCR on post-mortem tissue derived from the inferior frontal gyrus of 89 unaffected adults. Significant associations with the A allele of SNP rs362990 (χ(2) = 10, p-corrected = 0.019, OR = 1.5) and three marker haplotypes (rs6108461, rs362990 and rs362998) were observed. Furthermore, a significant additive decrease in the expression of the SNAP25 transcript as a function of the risk allele was also observed. This effect was detected at the haplotype level, where increasing copies of the ADHD-associated haplotype reduced the expression of the transcript.
Our data show that DNA variation at SNAP25 confers risk to ADHD and reduces the expression of the transcript in a region of the brain that is critical for the regulation of attention and inhibition.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With NO2 limit values being frequently exceeded in European cities, complying with the European air quality regulations still poses a problem for many cities. Traffic is typically a major source of ...NOx emissions in urban areas. High-resolution chemistry transport modelling can help to assess the impact of high urban NOx emissions on air quality inside and outside of urban areas. However, many modelling studies report an underestimation of modelled NOx and NO2 compared with observations. Part of this model bias has been attributed to an underestimation of NOx emissions, particularly in urban areas. This is consistent with recent measurement studies quantifying underestimations of urban NOx emissions by current emission inventories, identifying the largest discrepancies when the contribution of traffic NOx emissions is high. This study applies a high-resolution chemistry transport model in combination with ambient measurements in order to assess the potential underestimation of traffic NOx emissions in a frequently used emission inventory. The emission inventory is based on officially reported values and the Berlin–Brandenburg area in Germany is used as a case study. The WRF-Chem model is used at a 3 km × 3 km horizontal resolution, simulating the whole year of 2014. The emission data are downscaled from an original resolution of ca. 7 km × 7 km to a resolution of 1 km × 1 km. An in-depth model evaluation including spectral decomposition of observed and modelled time series and error apportionment suggests that an underestimation in traffic emissions is likely one of the main causes of the bias in modelled NO2 concentrations in the urban background, where NO2 concentrations are underestimated by ca. 8 µg m−3 (−30 %) on average over the whole year. Furthermore, a diurnal cycle of the bias in modelled NO2 suggests that a more realistic treatment of the diurnal cycle of traffic emissions might be needed. Model problems in simulating the correct mixing in the urban planetary boundary layer probably play an important role in contributing to the model bias, particularly in summer. Also taking into account this and other possible sources of model bias, a correction factor for traffic NOx emissions of ca. 3 is estimated for weekday daytime traffic emissions in the core urban area, which corresponds to an overall underestimation of traffic NOx emissions in the core urban area of ca. 50 %. Sensitivity simulations for the months of January and July using the calculated correction factor show that the weekday model bias can be improved from −8.8 µg m−3 (−26 %) to −5.4 µg m−3 (−16 %) in January on average in the urban background, and −10.3 µg m−3 (−46 %) to −7.6 µg m−3 (−34 %) in July. In addition, the negative bias of weekday NO2 concentrations downwind of the city in the rural and suburban background can be reduced from −3.4 µg m−3 (−12 %) to −1.2 µg m−3 (−4 %) in January and from −3.0 µg m−3 (−22 %) to −1.9 µg m−3 (−14 %) in July. The results and their consistency with findings from other studies suggest that more research is needed in order to more accurately understand the spatial and temporal variability in real-world NOx emissions from traffic, and apply this understanding to the inventories used in high-resolution chemical transport models.
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