Total synthesis of rhizopodin.

This is the peer reviewed version of the following article: Dalby, S.M, Goodwin-Tindall, J., Paterson, I. (2013), Total Synthesis of (−)-Rhizopodin. Angew. Chem. Int. Ed., which has been published in final form at http://dx.doi.org/‎10.1002/anie.201301978. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving http://olabout.wiley.com/WileyCDA/Section/id-815640.htmlCore assembly: The total synthesis of the myxobacterial metabolite rhizopodin, a potent actin-binding anticancer agent, has been achieved. The modular synthesis utilizes a common C1–C22 monomeric unit to assemble the dimeric 38-membered macrodiolide core, which was elaborated by a bidirectional boron-mediated aldol reaction to install the characteristic side-chains. The final global deprotection was critically dependent on the correct choice of silyl protecting groups at C16/C16′.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC)

Particle-seawater interaction of neodymium in the North Atlantic

Dissolved neodymium (Nd) isotopes (expressed as εNd) have been widely used as a water mass tracer in paleoceanography. However, one aspect of the modern biogeochemical cycle of Nd that has been sparsely investigated is the interplay between dissolved and particulate phases in seawater. We here present the first regional data set on particulate Nd isotope compositions (εNdp) and concentrations ([Nd]p) from five stations in the western North Atlantic Ocean along the GEOTRACES GA02 transect, in conjunction with previously published dissolved Nd isotope compositions (εNdd) and concentrations ([Nd]d)1. Key observations and interpretations from our new particulate data set include the following: (1) A low fractional contributions of [Nd]p to the total Nd inventory per volume unit of seawater (~5%), with significant increases of up to 45% in benthic boundary layers. (2) Increasing Nd concentrations in suspended particulate matter ([Nd]SPM) and fractions of lithogenic material with water depth, suggesting the removal of Nd poor phases. (3) Different provenances of particulates in the subpolar and subtropical gyres as evidenced by their Nd isotope fingerprints reaching from εNdp ≈ -20 near the Labrador Basin (old continental crust), over εNdp ≈ -4 between Iceland and Greenland (young mafic provenance), to values of εNdp ≈-13 in the subtropics (similar to African dust signal). (4) Vertical heterogeneity of εNdp, as well as large deviations from ambient seawater values in the subpolar gyre, indicate advection of lithogenic particles in this area. (5) Vertically homogenous εNdp values in the subtropical gyre, indistinguishable from εNdd values, are indicative of predominance of vertical particulate supply. The process of reversible scavenging only seems to influence particulate signatures below 3 km. Overall, we do not find evidence on enhanced particle dissolution, often invoked to explain the observed increase in dissolved Nd in the North Atlantic

Grain size effects on Th-230(xs) inventories in opal-rich and carbonate-rich marine sediments

Excess Thorium-230 (230Thxs) as a constant flux tracer is an essential tool for paleoceanographic studies, but its limitations for flux normalization are still a matter of debate. In regions of rapid sediment accumulation, it has been an open question if 230Thxs-normalized fluxes are biased by particle sorting effects during sediment redistribution. In order to study the sorting effect of sediment transport on 230Thxs, we analyzed the specific activity of 230Thxs in different particle size classes of carbonate-rich sediments from the South East Atlantic, and of opal-rich sediments from the Atlantic sector of the Southern Ocean. At both sites, we compare the 230Thxs distribution in neighboring high vs. low accumulation settings. Two grain-size fractionation methods are explored. We find that the 230Thxs distribution is strongly grain size dependent, and 5090% of the total 230Thxs inventory is concentrated in fine material smaller than 10 μm, which is preferentially deposited at the highaccumulation sites. This leads to an overestimation of the focusing factor Ψ, and consequently to an underestimation of the vertical flux rate at such sites. The distribution of authigenic uranium indicates that fine organic-rich material has also been re-deposited from lateral sources. If the particle sorting effect isconsidered in the flux calculations, it reduces the estimated extent of sediment focusing. In order to assess the maximum effect of particle sorting on Ψ, we present an extreme scenario, in which we assume a lateralsediment supply of only fine material (b10 μm). In this case, the focusing factor of the opal-rich core would be reduced from Ψ=5.9 to Ψ=3.2. In a more likely scenario, allowing silt-sized material to be transported, Ψ is reduced from 5.9 to 5.0 if particle sorting is taken into consideration. The bias introduced by particle sorting is most important for strongly focused sediments. Comparing 230Thxs-normalized mass fluxes biased by sorting effects with uncorrected mass fluxes, we suggest that 230Thxs-normalization is still a valid tool to correct for lateral sediment redistribution. However,differences in focusing factors between core locations have to be evaluated carefully, taking the grain size distributions into consideration

Strategies for a nearly Zero-Energy Building market transition in the European Union

European legislation makes nearly Zero-Energy Buildings (nZEBs) a standard by 2020. The technology is available and proven; however, the large-scale uptake of nZEB construction and renovation remains a challenge. ZEBRA2020 monitored the market uptake of nZEBs across Europe and provided data and knowledge on how to reach the nZEB standard. This information was structured and analysed to derive recommendations. ZEBRA2020 covers 17 European countries and almost 90% of the EU/EEA building stock and population. The online data tools provide unique information regarding nZEB market development and nZEB characteristics. New approaches have been developed in order to allow for a better comparability of national data. However, the absence or difficult accessibility to key data and in particular for non-residential and existing buildings as well as for renovations remains an important obstacle. The online nZEB tracker, based on a set of criteria, assesses the nZEB market maturity. On EU-level, the tracker shows a substantial gap of market maturity that still has to be closed by 2019/2021. A set of barriers and related recommendations have been identified both at national and EU level: The implementation of a common, shared long-term vision for the building stock is crucial. A quantitative comparison of national nZEB definitions is complex due to different system boundaries, calculation methodologies, applied factors etc. However, our analysis indicates that a significant share of nZEB definitions does not meet the intention of the EU directive on energy efficient buildings (EPBD) that the energy consumption should be “nearly zero or very low amount” and the remaining part “should be covered to a very significant extent by energy from renewable sources”. Thus, the new EPBD requires clear definitions of these terms and thresholds. Further, it is important to distinguish between new buildings and renovations – despite of a common nZEB definition for both cases. The nZEB compliance monitoring and sanctions regimes need improvement. Only about half of the covered Member States monitor the compliance of new buildings with energy performance requirements. The lack of professional skills continues to be an important barrier and should remain a focus, especially in case of new built. In many Member States, the reliability and credibility of Energy Performance Certificates (EPC) is often questioned by actors on the real estate market. Transforming EPCs into Building Certificates (“Passes”) for the whole lifetime of a building may increase credibility and serve as a key measure to foster building renovation towards an nZEB standard. Storage of building data in an electronically accessible national database may contribute to better data availability. Energy poverty and vulnerable consumers are a European-wide issue and need further attention. Shifting from fuel subsidy to energy efficiency support is required. Future-proof buildings will be highly-efficient micro energy-hubs consuming, producing, storing and supplying energy. A revised nZEB definition should be future-proofed to be a smart building and district-ready.publishedVersio

Epigenetic Control of the foxp3 Locus in Regulatory T Cells

Compelling evidence suggests that the transcription factor Foxp3 acts as a master switch governing the development and function of CD4(+) regulatory T cells (Tregs). However, whether transcriptional control of Foxp3 expression itself contributes to the development of a stable Treg lineage has thus far not been investigated. We here identified an evolutionarily conserved region within the foxp3 locus upstream of exon-1 possessing transcriptional activity. Bisulphite sequencing and chromatin immunoprecipitation revealed complete demethylation of CpG motifs as well as histone modifications within the conserved region in ex vivo isolated Foxp3(+)CD25(+)CD4(+) Tregs, but not in naïve CD25(−)CD4(+) T cells. Partial DNA demethylation is already found within developing Foxp3(+) thymocytes; however, Tregs induced by TGF-β in vitro display only incomplete demethylation despite high Foxp3 expression. In contrast to natural Tregs, these TGF-β–induced Foxp3(+) Tregs lose both Foxp3 expression and suppressive activity upon restimulation in the absence of TGF-β. Our data suggest that expression of Foxp3 must be stabilized by epigenetic modification to allow the development of a permanent suppressor cell lineage, a finding of significant importance for therapeutic applications involving induction or transfer of Tregs and for the understanding of long-term cell lineage decisions

Long-term effects of tongue piercing — a case control study

The aim of this study was to evaluate tooth and periodontal damage in subjects wearing a tongue piercing (TP) in comparison to matched control subjects without tongue piercing. Members of the German Federal Armed Forces who had TP (group TP) and a matched control group (group C) volunteered to take part in the study. The time in situ, localization and material of TP were documented. Dental examinations included DMF-T, oral hygiene, enamel fissures (EF), enamel cracks (EC) and recessions. Statistical analysis was determined by χ2 test and the t test. Both groups had 46 male subjects (mean age 22.1 years). The piercings had been in situ for 3.8 ± 3.1 years. Subjects in the TP group had a total of 1,260 teeth. Twenty-nine subjects had 115 teeth (9.1%) with EF (67% lingual). In group C (1,243 teeth), 30 subjects had 60 teeth with EF (4.8%, 78% vestibular) (p < 0.01). Thirty-eight subjects belonging to group TP had EC in 186 teeth (15%). In group C, 26 subjects with 56 teeth (4.5%) were affected by EC (p < 0.001). Twenty-seven subjects in group TP had 97 teeth (7.7%) with recessions. Lingual surfaces of anterior teeth in the lower jaw were affected most frequently (74%). In group C, 8 subjects had 19 teeth (1.5%) with recessions (65% vestibular). Differences between the two groups were statistically significant (p < 0.001). Tongue piercing is correlated with an increased occurrence of enamel fissures, enamel cracks and lingual recessions. Patients need better information on the potential complications associated with tongue piercing

The GEOTRACES Intermediate Data Product 2014

The GEOTRACES Intermediate Data Product 2014 (IDP2014) is the first publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2013. It consists of two parts: (1) a compilation of digital data for more than 200 trace elements and isotopes (TEIs) as well as classical hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing a strongly inter-linked on-line atlas including more than 300 section plots and 90 animated 3D scenes. The IDP2014 covers the Atlantic, Arctic, and Indian oceans, exhibiting highest data density in the Atlantic. The TEI data in the IDP2014 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at cross-over stations. The digital data are provided in several formats, including ASCII spreadsheet, Excel spreadsheet, netCDF, and Ocean Data View collection. In addition to the actual data values the IDP2014 also contains data quality flags and 1-? data error values where available. Quality flags and error values are useful for data filtering. Metadata about data originators, analytical methods and original publications related to the data are linked to the data in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2014 data providing section plots and a new kind of animated 3D scenes. The basin-wide 3D scenes allow for viewing of data from many cruises at the same time, thereby providing quick overviews of large-scale tracer distributions. In addition, the 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of observed tracer plumes, as well as for making inferences about controlling processes

230Thxs budgets in size-fractionated calcareous near-surface sediments from Walvis Ridge

Deep-sea sediments are composed of particles settling vertically through the water column, but often contain significant portions of laterally advected material. This laterally supplied material contributes to total sediment accumulation. However its deposition does not correspond to particle fluxes through the overlying water column. With 230Thxs-normalized particle flux calculations it is possible to quantify advective sediment supply. Bottom currents, that transport resuspended sediment, are likely to sort sediment particles according to grain size and sinking velocity. Thus it is reasonable to assume that the laterally supplied portion of the sediment is predominantly composed of fine-grained particles. However 230Thxs-based flux calculations rely on radionuclide measurements of bulk sediment samples. On the other hand, particle separation may lead to a decoupling of the particle-associated proxy records, which might result in over- or underestimation of the associated fluxes. To study the effects of lateral transport the objective of this study therefore is to perform particle flux estimations with grain size fractionated sediments. We present initial data from calcareous near-surface sediments from two sites at Walvis Ridge in water-depths of 2200 m and 2700 m. Both samples were grain size fractionated by sieving and settling using MilliQ water. Fractionated samples were acid-digested and radioisotopes of Uranium (234U, 235U, 238U) and Thorium (230Th, 232Th) were measured with an ICP-MS. 230Thxs data were calculated following standard procedures. The sediment is composed of 25 34 % clay-sized particles (63 µm). In contrast, 50 61 % of the excess Thorium inventory is contributed solely by the clay fraction. The silt fraction contributes to 230Thxs in a range of 28 38 %, whereas only less than 12 % of 230Thxs is residing in the sand fraction. This confirms results from Thomson et al. (1993). In almost all grain size fractions the ratio 238U/232Th is exceeding the range of 0.5 1.1, indicating an uptake of authigenic Uranium to the sediment as a result of reducing conditions (François et al. 1993). These results highlight the potential of miscalculating 230Thxs-normalized fluxes of certain sediment consitutents, e.g., of foraminifera using bulk radioisotope measurements

The Influence of Particle Size, Composition, and Transport on the Distribution of 230Thxs, 231Paxs, and 10Be in Marine Sediments

The study focuses on the grain-size dependent distribution of particle-reactive, natural radionuclides (230Th, 231Pa, 10Be) in marine sediments from the Southern Ocean, the South East Atlantic, and the Equatorial Pacific. Particle-size specific isotope analyses show that a large amount (53-89 %) of the total 230Th is concentrated in clay-size material. It is discussed to what extent a lateral transport of fine particles could generate a biasing to particle flux calculations based on 230Th. In the Southern Ocean sediment the distribution of 231Pa and 10Be strongly depends on the concentration of biogenic silica of particles. 231Pa/230Th and 10Be/230Th in opal-rich particles largely exceed their production ratio in seawater. This supports the application of bulk 231Pa/230Th as a proxy for past opal fluxes to Southern Ocean sediments. The study of compound-specific 231Pa/230Th and 10Be/230Th, as conducted here, allows a more detailed picture of the origin of the isotopic signatures