The synthesis of chiral N-heterocyclic carbene–borane and –diorganoborane complexes and their use in the asymmetric reduction of ketones

Chiral N-heterocyclic carbene–borane complexes have been synthesised, and have been shown to reduce ketones with Lewis acid promotion. Chiral N-heterocyclic carbene–borane and –diorganoborane complexes can reduce ketones with enantioselectivities up to 75% and 85% ee, respectively.

A dialkylborenium ion via reaction of N-heterocyclic carbene–organoboranes with Brønsted acids—synthesis and DOSY NMR studies

A dialkylborenium ion stabilized by an N-heterocyclic carbene has been prepared for the first time by reaction of IMes-9-BBN-H with triflic acid. The ion-separated nature of the borenium ion was confirmed by 1H and 19F diffusion ordered NMR spectroscopy.

Atmospheric composition of West Africa: highlights from the AMMA program

The atmospheric composition of West Africa reflects the interaction of various dynamical and chemical systems (i.e. biogenic, urban, convective and long-range transport) with signatures from local to continental scales. Recent measurements performed during the African Monsoon Multidisciplinary Analyses (AMMA) observational periods in 2005 and 2006 provide new data which has allowed new insight into the processes within these systems that control the distribution of ozone and its precursors. Using these new data and recently published results, we provide an overview of these systems with a particular emphasis on ozone distributions over West Africa during the wet season.

Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?

Objective: The objective of this study was to explore the relationship between low density lipoprotein (LDL) and dendritic cell (DC) activation, based upon the hypothesis that reactive oxygen species (ROS)-mediated modification of proteins that may be present in local DC microenvironments could be important as mediators of this activation. Although LDL are known to be oxidised in vivo, and taken up by macrophages during atherogenesis; their effect on DC has not been explored previously. Methods: Human DCs were prepared from peripheral blood monocytes using GM-CSF and IL-4. Plasma LDLs were isolated by sequential gradient centrifugation, oxidised in CuSO4, and oxidation arrested to yield mild, moderate and highly oxidised LDL forms. DCs exposed to these LDLs were investigated using combined phenotypic, functional (autologous T cell activation), morphological and viability assays. Results: Highly-oxidised LDL increased DC HLA-DR, CD40 and CD86 expression, corroborated by increased DC-induced T cell proliferation. Both native and oxidised LDL induced prominent DC clustering. However, high concentrations of highly-oxidised LDL inhibited DC function, due to increased DC apoptosis. Conclusions: This study supports the hypothesis that oxidised LDL are capable of triggering the transition from sentinel to messenger DC. Furthermore, the DC clustering–activation–apoptosis sequence in the presence of different LDL forms is consistent with a regulatory DC role in immunopathogenesis of atheroma. A sequence of initial accumulation of DC, increasing LDL oxidation, and DC-induced T cell activation, may explain why local breach of tolerance can occur. Above a threshold level, however, supervening DC apoptosis limits this, contributing instead to the central plaque core.

Exploring homeless people’s use of outreach services: applying a social psychological perspective

A number of critiques have been published drawing attention to the gaps in research methods applied to issues surrounding homelessness and service utilisation in Britain. This paper discusses the use of social identity, a theory drawn from the field of applied social psychology, and synthesises it with the pathways model, thereby providing a framework to further explore service utilisation. The synthesised framework was used to predict the uptake of outreach services in a prospective study of 121 homeless people in a major UK city. In general, homeless people's use of intervention services was affected by the extent to which they identified with the support services themselves. The study demonstrates the central role of social identity in understanding service utilisation patterns, and shows the importance of applying fresh techniques to fine-tune our understanding of uptake in the long term.

The ocean’s role in setting the mean position of the Inter-Tropical Convergence Zone

Through study of observations and coupled climate simulations, it is argued that the mean position of the Inter-Tropical Convergence Zone (ITCZ) north of the equator is a consequence of a northwards heat transport across the equator by ocean circulation. Observations suggest that the hemispheric net radiative forcing of climate at the top of the atmosphere is almost perfectly symmetric about the equator, and so the total (atmosphere plus ocean) heat transport across the equator is small (order 0.2 PW northwards). Due to the Atlantic ocean’s meridional overturning circulation, however, the ocean carries significantly more heat northwards across the equator (order 0.4 PW) than does the coupled system. There are two primary consequences. First, atmospheric heat transport is southwards across the equator to compensate (0.2 PW southwards), resulting in the ITCZ being displaced north of the equator. Second, the atmosphere, and indeed the ocean, is slightly warmer (by perhaps 2 °C) in the northern hemisphere than in the southern hemisphere. This leads to the northern hemisphere emitting slightly more outgoing longwave radiation than the southern hemisphere by virtue of its relative warmth, supporting the small northward heat transport by the coupled system across the equator. To conclude, the coupled nature of the problem is illustrated through study of atmosphere–ocean–ice simulations in the idealized setting of an aquaplanet, resolving the key processes at work.

Family-based association analysis with ordered categorical phenotypes, covariates and interactions

Genetic association analyses of family-based studies with ordered categorical phenotypes are often conducted using methods either for quantitative or for binary traits, which can lead to suboptimal analyses. Here we present an alternative likelihood-based method of analysis for single nucleotide polymorphism (SNP) genotypes and ordered categorical phenotypes in nuclear families of any size. Our approach, which extends our previous work for binary phenotypes, permits straightforward inclusion of covariate, gene-gene and gene-covariate interaction terms in the likelihood, incorporates a simple model for ascertainment and allows for family-specific effects in the hypothesis test. Additionally, our method produces interpretable parameter estimates and valid confidence intervals. We assess the proposed method using simulated data, and apply it to a polymorphism in the c-reactive protein (CRP) gene typed in families collected to investigate human systemic lupus erythematosus. By including sex interactions in the analysis, we show that the polymorphism is associated with anti-nuclear autoantibody (ANA) production in females, while there appears to be no effect in males.

Syk and Src family kinases regulate C-type lectin receptor 2 (CLEC-2)-mediated clustering of podoplanin and platelet adhesion to lymphatic endothelial cells

The interaction of C-type lectin receptor 2 (CLEC-2) on platelets with Podoplanin on lymphatic endothelial cells initiates platelet signaling events that are necessary for prevention of blood-lymph mixing during development. In the present study, we show that CLEC-2 signaling via Src family and Syk tyrosine kinases promotes platelet adhesion to primary mouse lymphatic endothelial cells at low shear. Using supported lipid bilayers containing mobile Podoplanin, we further show that activation of Src and Syk in platelets promotes clustering of CLEC-2 and Podoplanin. Clusters of CLEC-2-bound Podoplanin migrate rapidly to the center of the platelet to form a single structure. Fluorescence lifetime imaging demonstrates that molecules within these clusters are within 10 nm of one another and that the clusters are disrupted by inhibition of Src and Syk family kinases. CLEC-2 clusters are also seen in platelets adhered to immobilized Podoplanin using direct stochastic optical reconstruction microscopy. These findings provide mechanistic insight by which CLEC-2 signaling promotes adhesion to Podoplanin and regulation of Podoplanin signaling, thereby contributing to lymphatic vasculature development.

The COnvective Precipitation Experiment (COPE): investigating the origins of heavy precipitation in the southwestern UK

A recent field campaign in southwest England used numerical modeling integrated with aircraft and radar observations to investigate the dynamic and microphysical interactions that can result in heavy convective precipitation. The COnvective Precipitation Experiment (COPE) was a joint UK-US field campaign held during the summer of 2013 in the southwest peninsula of England, designed to study convective clouds that produce heavy rain leading to flash floods. The clouds form along convergence lines that develop regularly due to the topography. Major flash floods have occurred in the past, most famously at Boscastle in 2004. It has been suggested that much of the rain was produced by warm rain processes, similar to some flash floods that have occurred in the US. The overarching goal of COPE is to improve quantitative convective precipitation forecasting by understanding the interactions of the cloud microphysics and dynamics and thereby to improve NWP model skill for forecasts of flash floods. Two research aircraft, the University of Wyoming King Air and the UK BAe 146, obtained detailed in situ and remote sensing measurements in, around, and below storms on several days. A new fast-scanning X-band dual-polarization Doppler radar made 360-deg volume scans over 10 elevation angles approximately every 5 minutes, and was augmented by two UK Met Office C-band radars and the Chilbolton S-band radar. Detailed aerosol measurements were made on the aircraft and on the ground. This paper: (i) provides an overview of the COPE field campaign and the resulting dataset; (ii) presents examples of heavy convective rainfall in clouds containing ice and also in relatively shallow clouds through the warm rain process alone; and (iii) explains how COPE data will be used to improve high-resolution NWP models for operational use.