CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy

Targeting T cell malignancies with universal CD7-targeting chimeric antigen receptor T cells (UCART7) can lead to profound immune deficiency due to loss of normal T and NK cells. While a small population of endogenous CD7- T cells exists, these cells are unlikely to be able to repopulate the entire immune repertoire after UCART7 treatment, as they are limited in number and proliferative capacity. To rescue T and NK cells after UCART7, we created hematopoietic stem cells genetically deleted for CD7 (CD7-KO HSCs). CD7-KO HSCs were able to engraft immunodeficient mice and differentiate into T and NK cells lacking CD7 expression. CD7-KO T and NK cells could perform effector functions as robustly as control T and NK cells. Furthermore, CD7-KO T cells were phenotypically and functionally distinct from endogenous CD7- T cells, indicating that CD7-KO T cells can supplement immune functions lacking in CD7- T cells. Mice engrafted with CD7-KO HSCs maintained T and NK cell numbers after UCART7 treatment, while these were significantly decreased in control mice. These studies support the development of CD7-KO HSCs to augment host immunity in patients with T cell malignancies after UCART7 treatment

The TOMCAT global chemical transport model v1.6: description of chemical mechanism and model evaluation

This paper documents the tropospheric chemical mechanism scheme used in the TOMCAT 3-D chemical transport model. The current scheme includes a more detailed representation of hydrocarbon chemistry than previously included in the model, with the inclusion of the emission and oxidation of ethene, propene, butane, toluene and monoterpenes. The model is evaluated against a range of surface, balloon, aircraft and satellite measurements. The model is generally able to capture the main spatial and seasonal features of high and low concentrations of carbon monoxide (CO), ozone (O3), volatile organic compounds (VOCs) and reactive nitrogen. However, model biases are found in some species, some of which are common to chemistry models and some that are specific to TOMCAT and warrant further investigation. The most notable of these biases are (1) a negative bias in Northern Hemisphere (NH) winter and spring CO and a positive bias in Southern Hemisphere (SH) CO throughout the year, (2) a positive bias in NH O3 in summer and a negative bias at high latitudes during SH winter and (3) a negative bias in NH winter C2 and C3 alkanes and alkenes. TOMCAT global mean tropospheric hydroxyl radical (OH) concentrations are higher than estimates inferred from observations of methyl chloroform but similar to, or lower than, multi-model mean concentrations reported in recent model intercomparison studies. TOMCAT shows peak OH concentrations in the tropical lower troposphere, unlike other models which show peak concentrations in the tropical upper troposphere. This is likely to affect the lifetime and transport of important trace gases and warrants further investigation

Legal origin and social solidarity: the continued relevance of Durkheim to comparative institutional analysis

By using the classic works of Durkheim as a theoretical platform, this research explores the relationship between legal systems and social solidarity. We found that certain types of civil law system, most notably those of Scandinavia, are associated with higher levels of social capital and better welfare state provision. However, we found the relationship between legal system and societal outcomes is considerably more complex than suggested by currently fashionable economistic legal origin approaches, and more in line with the later writings of Durkheim, and, indeed, the literature on comparative capitalisms. Relative communitarianism was strongly affected by relative development, reflecting the complex relationship between institutions, state capabilities and informal social ties and networks

Hygrothermal durability of bond in FRP-strengthened masonry

Fiber reinforced polymers (FRPs) are accepted as an efficient material for external strengthening of masonry structures. Previous researches have shown that the bond between FRP and the substrate plays an important role in the effectiveness of this strengthening technique. Extensive investigations have been devoted to the characterization of the short-term bond behavior, while its durability and long-term performance requires further studies. In this regard, a full experimental program for investigating the environmental durability of bond in FRP-strengthened masonry is crucial for understanding the degrading mechanisms. This paper presents the results of an experimental program aimed at investigating the hygrothermal durability of bond in FRP-strengthened bricks. Accelerated ageing tests were performed on the FRP-strengthened brick elements and the bond degradation was periodically investigated by visual inspection and by conventional single-lap shear bond tests. The changes in the properties of material constituents have also been monitored. The obtained results are presented and critically discussed.This work was developed within the framework of the RILEM Technical Committee "223-MSC: Masonry Strengthening with Composite Materials". The financial support from the project FP7-ENV-2009-1-244123-NIKER of the 7th Framework Program of the European Commission is gratefully acknowledged. The first author also acknowledges the financial support of the Portuguese Science Foundation (Fundacao de Ciencia e Tecnologia, FCT), through grant SFRH/BD/80697/2011

Determining the effect of drying time on phosphorus solubilization from three agricultural soils under climate change scenarios

Climate projections for the future indicate that the United Kingdom will experience hotter, drier summers and warmer, wetter winters, bringing longer dry periods followed by rewetting. This will result in changes in phosphorus (P) mobilization patterns that will influence the transfer of P from land to water. We tested the hypothesis that changes in the future patterns of drying–rewetting will affect the amount of soluble reactive phosphorus (SRP) solubilized from soil. Estimations of dry period characteristics (duration and temperature) under current and predicted climate were determined using data from the UK Climate Projections (UKCP09) Weather Generator tool. Three soils (sieved 25°C are predicted in some places and dry periods of 30 to 90 d extremes are predicted. Combining the frequency of projected dry periods with the SRP concentration in leachate suggests that this may result overall in increased mobilization of P; however, critical breakpoints of 6.9 to 14.5 d dry occur wherein up to 28% more SRP can be solubilized following a rapid rewetting event. The precise cause of this increase could not be identified and warrants further investigation as the process is not currently included in P transfer models

Introduction to the special issue "in-depth study of air pollution sources and processes within Beijing and its surrounding region (APHH-Beijing)"

© 2019 Author(s). The Atmospheric Pollution and Human Health in a Chinese Megacity (APHH-Beijing) programme is an international collaborative project focusing on understanding the sources, processes and health effects of air pollution in the Beijing megacity. APHH-Beijing brings together leading China and UK research groups, state-of-the-art infrastructure and air quality models to work on four research themes: (1) sources and emissions of air pollutants; (2) atmospheric processes affecting urban air pollution; (3) air pollution exposure and health impacts; and (4) interventions and solutions. Themes 1 and 2 are closely integrated and support Theme 3, while Themes 1-3 provide scientific data for Theme 4 to develop cost-effective air pollution mitigation solutions. This paper provides an introduction to (i) the rationale of the APHH-Beijing programme and (ii) the measurement and modelling activities performed as part of it. In addition, this paper introduces the meteorology and air quality conditions during two joint intensive field campaigns-a core integration activity in APHH-Beijing. The coordinated campaigns provided observations of the atmospheric chemistry and physics at two sites: (i) the Institute of Atmospheric Physics in central Beijing and (ii) Pinggu in rural Beijing during 10 November-10 December 2016 (winter) and 21 May-22 June 2017 (summer). The campaigns were complemented by numerical modelling and automatic air quality and low-cost sensor observations in the Beijing megacity. In summary, the paper provides background information on the APHH-Beijing programme and sets the scene for more focused papers addressing specific aspects, processes and effects of air pollution in Beijing

Environment and Rural Affairs Monitoring & Modelling Programme - ERAMMP Report-60: ERAMMP Integrated Modelling Platform (IMP) Land Use Scenarios

Six scenarios consisting of changes in farm-gate prices (T1 to T6) have been applied to the ERAMMP Integrated Modelling Platform (IMP) to simulate impacts on land use change, biodiversity and ecosystem services (carbon, water quality and air quality). The scenarios were based on discussions held between stakeholders in the Evidence and Scenario subgroup (Roundtable Wales and Brexit1) and Welsh Government (WG) policy officials. These discussions took place in late 2020 before the arrangements for the UK leaving the EU were agreed, therefore are based on broad assumptions around the detail of the trade agreement with the EU as well as other third countries including Australia, New Zeland and USA. It is important to note that the outputs of these discussions which were used as inputs into the ERAMMP IMP may therefore not accurately reflect the outcomes achieved within the finalised trade agreements. The T1 scenario assumes no EU trade deal and trade liberalisation, with no tariffs applied to imported products and T2 an EU trade deal with no change to the trade arrangements with third countries. These two scenarios used the changes to farm-gate prices modelled by FAPRI2. The assumptions used in the T3 to T6 scenarios were based on expert opinion from the stakeholder group, and include impacts on farm-gate prices which potentially could have resulted from different combinations of trade deals with New Zealand, Australia and USA. Scenarios which include “no EU deal” options (T1 and T4) are no longer relevant. In no way whatsoever do T1, T3, T4, T5 and T6 represent a WG position; our understanding of the nature and impact of new and emerging trade deals has evolved significantly and the WG Trade Policy Team lead in this area. The objective of this work was to gain an early understanding of how changes in farm-gate prices potentially resulting from trading relationships may influence land use and subsequently effect entry into the Sustainable Farming Scheme. We note that many other factors are also likely to influence Welsh farmgate prices, such as (but not limited to), currency exchange rates, energy prices and extreme weather events in other parts of the world. This report provides an overview of the land use implications of all these scenarios, but focuses on the T2 scenario, which represents an EU Trade Deal. This T2 scenario is being used as the counterfactual scenario against which the costs and benefits of the land use implications of the proposed Sustainable Farming Scheme will be assessed in the Regulatory Impact Assessment for the proposed Agricultural Bill. This includes the estimated environmental outcomes of the EU Trade Deal scenario and, where the ERAMMP IMP has attached monetary valuations to these, the value of these outcomes to society. In the Cost Benefit Analysis, these monetary values will inform the overall estimated Net Present Value (NPV) of this business-as-usual counterfactual. The IMP involves many assumptions and these need to be borne in mind when interpreting and using its outcomes. By necessity, all models are a simplification of the real situation, but can still provide very useful insights if applied for a specific purpose and with caution. The collaborative and iterative consortium-based approach to co-designing the IMP has meant that Welsh Government and IMP teams have clear, open channels of communication for asking questions. This ensures that the modelling represents government aspirations as well as possible and the limits of the approach are well understood. IMP outputs for the T2 scenario show that some simulated full-time farms (>1 FTE labour) come under economic pressure (7%) and are simulated to be unable to produce a sufficient Farm Business Income to be economically viable. For these farm types, no options to transition to a more alternative profitable farm type are available and they are assumed to leave full-time agriculture. A greater number of farms transition to dairying resulting in a 75% increase in the number of dairy farms. This is associated with large increases in the number of dairy cattle (73%) and reductions in sheep (-34%). A general intensification of grassland systems is simulated resulting from the farm type transitions, with a 66% increase in temporary grasslands and a 21% decrease in permanent grasslands. Overall, these changes in agriculture and land use are simulated to lead to mixed, but predominantly negative, effects on biodiversity, increases in GHG emissions and deterioration in air and water quality. The T2 scenario predicts the least change in agriculture out of the six scenarios. T1 simulates the greatest impacts on agriculture due to significant farm-gate price reductions across dairy, beef and sheep systems, with a large number of full-time farms leaving agriculture. This leads to large increases in woodland area and generally positive effects on biodiversity and ecosystem services. T3 and T4 also simulate large impacts on agriculture. These are associated with significant farm transitions to dairy (due to increases in milk prices and significant decreases in beef and lamb prices) resulting in larger increases in GHG emissions and greater declines in air and water quality, compared to the T2 scenario. The T5 and T6 scenarios fall between these extremes, with T6 projecting the second greatest impacts on agriculture (after T1) in terms of farms under pressure. These simulated changes in agriculture are associated with net benefits for air and water quality, but net costs for GHG emissions; although these costs are lower than for scenarios T3-T5