Synthetic studies toward the brasilinolides: controlled assembly of a protected C1-C38 polyol based on fragment union by complex aldol reactions.

The brasilinolides are an architecturally complex family of 32-membered macrolides, characterised by potent immunosuppressant and antifungal properties, which represent challenging synthetic targets. By adopting a highly convergent strategy, a range of asymmetric aldol/reduction sequences and catalytic protocols were employed to assemble a series of increasingly elaborate fragments. The controlled preparation of suitable C1-C19 and C20-C38 acyclic fragments 5 and 6, containing seven and 12 stereocentres respectively, was first achieved. An adventurous C19-C20 fragment union was then explored to construct the entire carbon chain of the brasilinolides. This pivotal coupling step could be performed in a complex boron-mediated aldol reaction to install the required C19 hydroxyl stereocentre when alternative Mukaiyama-type aldol protocols proved unrewarding. A protected C1-C38 polyol 93 was subsequently prepared, setting the stage for future late-stage diversification toward the various brasilinolide congeners. Throughout this work, asymmetric boron-mediated aldol reactions of chiral ketones with aldehydes proved effective both for controlled fragment assembly and coupling with predictable stereoinduction from the enolate component.We thank the EPSRC (EP/F025734/1) and Syngenta for support, the Isaac Newton–Mays Wild Research Fellowship at Downing College (M.P.H.), the Herchel Smith Postdoctoral Fellowships Fund at Cambridge (C.J.C.) and the Deutsche Akademie der Naturforser Leopoldina (F.A.M.; BMBF-LPD 9901/8-148) for additional funding, and the EPSRC National Mass Spectrometry Centre (Swansea) for mass spectra.This is the final published version of the article. It was originally published in Organic & Biomolecular Chemistry (Paterson I, Housden MP, Cordier CJ, Burton PM, Mühlthau FA, Loiseleur O, Organic & Biomolecular Chemistry, 2015,13, 5716-5733 doi:10.1039/C5OB00498E). The final version is available at http://dx.doi.org/10.1039/C5OB00498

Patrones de diversidad de poliquetos en hábitats intermareales tropicales selectos

Few studies have quantitatively compared benthic macrofaunal assemblages between different tropical intertidal habitats over differing spatial scales. The present study uses spatially nested material from vegetated (seagrass) and non-vegetated (mudflat) habitats in SW Thailand to address this issue. Polychaetes were the numerically dominant component of benthic assemblages throughout the region, comprising over 74% of the total macrofauna. Despite great within-site and sample variation, based on species diversity, polychaete assemblages were mostly site-specific. Not so visibly obvious were the evident differences in polychaete assemblages between habitats. The spatial pattern of polychaete diversity is explored.Pocos estudios han comparado cuantitativamente el macrozoobentos entre diferentes hábitats intermareales tropicales a diferentes escalas espaciales. Para remediar esta situación, esta investigación utiliza y compara material colectado en praderas marinas y zonas sin vegetación en la costa suroeste de Tailandia a diferentes escalas espaciales. Los poliquetos formaron la mayor parte del zoobentos, constituyendo el 74% del total. Pese al alto nivel de variación entre muestras, basado en la diversidad de especies, los conjuntos de poliquetos mostraron mayor afinidad a su lugar de colecta. Diferencias entre cada hábitat, aunque difíciles de apreciar a simple vista, son corroboradas estadísticamente. Se exploran cambios en la diversidad asociados con cambios en la escala espacial. &nbsp

Lake surface temperature [in “State of the Climate in 2017”]

Observed lake surface water temperature anomalies in 2017 are placed in the context of the recent warming observed in global surface air temperature by collating long-term in situ lake surface temperature observations from some of the world’s best-studied lakes and a satellite-derived global lake surface water temperature dataset. The period 1996–2015, 20 years for which satellite-derived lake temperatures are available, is used as the base period for all lake temperature anomaly calculations

Revisiting the rigor-relevance relationship: An institutional logics perspective

The question of whether academic research should emphasize scientific rigor, practical relevance, or both simultaneously has been hotly debated in HRM research and other related disciplines for much of the past century. That said, empirical investigations of whether these values are mutually exclusive or compatible are surprisingly rare. Moreover, the perspective of the end consumers of research-practitioners-as to what research is relevant has been almost completely ignored. In the present study, we adopt an institutional logics perspective to assess the perceived relevance of common management research findings with two samples of 298 and 143 practicing managers, respectively. Further, we examine whether objective indicators of rigor and manager-rated relevance impact academic legitimacy. The results indicate a positive relationship between rigor and relevance. Interestingly, practitioner ratings of relevance were stronger predictors of academic legitimacy than methodological rigor. Finally, research findings that deal with leadership topics are rated as most relevant to practitioners, whereas job characteristics, demographics, and human resource practices are seen as the least relevant to managers. The contributions of this study and implications for future research conclude the article

Infrared spectra and fragmentation dynamics of isotopologue-selective mixed-ligand complexes †

Isolated mixed-ligand complexes provide tractable model systems in which to study competitive and cooperative binding effects as well as controlled energy flow. Here, we report spectroscopic and isotopologue-selective infrared photofragmentation dynamics of mixed gas-phase Au(12/13CO)n(N2O)m+ complexes. The rich infrared action spectra, which are reproduced well using simulations of calculated lowest energy structures, clarify previous ambiguities in the assignment of vibrational bands, especially accidental coincidence of CO and N2O bands. The fragmentation dynamics exhibit the same unexpected behaviour as reported previously in which, once CO loss channels are energetically accessible, these dominate the fragmentation branching ratios, despite the much lower binding energy of N2O. We have investigated the dynamics computationally by considering anharmonic couplings between a relevant subset of normal modes involving both ligand stretch and intermolecular modes. Discrepancies between correlated and uncorrelated model fit to the ab initio potential energy curves are quantified using a Boltzmann sampled root mean squared deviation providing insight into efficiency of vibrational energy transfer between high frequency ligand stretches and the softer intermolecular modes which break during fragmentation

Chiral Hierarchies, Compositeness and the Renormalization Group

A wide class of models involve the fine--tuning of significant hierarchies between a strong--coupling ``compositeness'' scale, and a low energy dynamical symmetry breaking scale. We examine the issue of whether such hierarchies are generally endangered by Coleman--Weinberg instabilities. A careful study using perturbative two--loop renormalization group methods finds that consistent large hierarchies are not generally disallowed.Comment: 22 pp + 5 figs (uuencoded and submitted separately), SSCL-Preprint-490; FERMI-PUB-93/035-

Caenorhabditis elegans Maintains Highly Compartmentalized Cellular Distribution of Metals and Steep Concentration Gradients of Manganese

Bioinorganic chemistry is critical to cellular function. Homeostasis of manganese (Mn), for example, is essential for life. A lack of methods for direct in situ visualization of Mn and other biological metals within intact multicellular eukaryotes limits our understanding of management of these metals. We provide the first quantitative subcellular visualization of endogenous Mn concentrations (spanning two orders of magnitude) associated with individual cells of the nematode, Caenorhabditis elegans

The photochemical mediated ring contraction of 4H-1,2,6-thiadiazines to afford 1,2,5-thiadiazol-3(2H)-one 1-oxides

E.B. and C.G.T. are grateful to Heriot-Watt University and the EPSRC CRITICAT Centre for Doctoral Training (E.B. Ph.D. Studentship: EP/L016419/1, C.G.T Ph.D. Studentship: EP/LO14419/1) for funding and training. C.G.T. is grateful to the Heriot-Watt Annual Fund for financial support. P.A.K. and A.S.K. thank the University of Cyprus for the Internal Grant “Thiadiazine-Based Organic Photovoltaics”, and the Cyprus Research Promotion Foundation (Grant Nos. ΣΤΡΑΤΗΙΙ/0308/06, NEKYP/0308/02 ΥΓΕΙΑ/0506/19, and ΕΝΙΣΧ/0308/83). M.J.P. thanks the EPSRC for funding (Grant Nos. EP/T021675 and EP/V006746), and the Leverhulme Trust (Grant No. PG-2020-208). S.A.M. thanks the EPSRC for funding (Grant No. EP/T019867/1).1,2,6-Thiadiazines treated with visible light and 3O2 under ambient conditions are converted into difficult-to-access 1,2,5-thiadiazole 1-oxides (35 examples, yields of 39–100%). Experimental and theoretical studies reveal that 1,2,6-thiadiazines act as triplet photosensitizers that produce 1O2 and then undergo a chemoselective [3 + 2] cycloaddition to give an endoperoxide that ring contracts with selective carbon atom excision and complete atom economy. The reaction was optimized under both batch and continuous-flow conditions and is also efficient in green solvents.Publisher PDFPeer reviewe

Exploring the measurement of markedness and its relationship with other linguistic variables

Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse

Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection, and reproduction in a wild rodent

The genotype of an individual is an important predictor of their immune function, and subsequently, their ability to control or avoid infection and ultimately contribute offspring to the next generation. However, the same genotype, subjected to different intrinsic and/or extrinsic environments, can also result in different phenotypic outcomes, which can be missed in controlled laboratory studies. Natural wildlife populations, which capture both genotypic and environmental variability, provide an opportunity to more fully understand the phenotypic expression of genetic variation. We identified a synonymous polymorphism in the high-affinity Immunoglobulin E (IgE) receptor (GC and non-GC haplotypes) that has sex-dependent effects on immune gene expression, susceptibility to infection, and reproductive success of individuals in a natural population of field voles (Microtus agrestis). We found that the effect of the GC haplotype on the expression of immune genes differed between sexes. Regardless of sex, both pro-inflammatory and anti-inflammatory genes were more highly relatively expressed in individuals with the GC haplotype than individuals without the haplotype. However, males with the GC haplotype showed a stronger signal for pro-inflammatory genes, while females showed a stronger signal for anti-inflammatory genes. Furthermore, we found an effect of the GC haplotype on the probability of infection with a common microparasite, Babesia microti, in females – with females carrying the GC haplotype being more likely to be infected. Finally, we found an effect of the GC haplotype on reproductive success in males – with males carrying the GC haplotype having a lower reproductive success. This is a rare example of a polymorphism whose consequences we are able to follow across immunity, infection, and reproduction for both males and females in a natural population