Electrosynthesis has much to offer to the synthetic organic chemist. But in order to be widely accepted as a routine procedure in an organic synthesis laboratory, electrosynthesis needs to be ...presented in a much more user-friendly way. The literature is largely based on electrolysis in a glass beaker or H-cells that often give poor performance for synthesis with a very slow rate of conversion and, often, low selectivity and reproducibility. Flow cells can lead to much improved performance. Electrolysis is participating in the trend toward continuous flow synthesis, and this has led to a number of innovations in flow cell design that make possible selective syntheses with high conversion of reactant to product with a single passage of the reactant solution through the cell. In addition, the needs of the synthetic organic chemist can often be met by flow cells operating with recycle of the reactant solution. These cells give a high rate of product formation while the reactant concentration is high, but they perform best at low conversion. Both approaches are considered in this review and the important features of each cell design are discussed. Throughout, the application of the cell designs is illustrated with syntheses that have been reported.
There is growing interest in diffusion models to represent the cognitive and neural processes of speeded decision making. Sequential-sampling models like the diffusion model have a long history in ...psychology. They view decision making as a process of noisy accumulation of evidence from a stimulus. The standard model assumes that evidence accumulates at a constant rate during the second or two it takes to make a decision. This process can be linked to the behaviors of populations of neurons and to theories of optimality. Diffusion models have been used successfully in a range of cognitive tasks and as psychometric tools in clinical research to examine individual differences. In this review, we relate the models to both earlier and more recent research in psychology.
Chitin is an essential structural polysaccharide of fungal pathogens and parasites, but its role in human immune responses remains largely unknown. It is the second most abundant polysaccharide in ...nature after cellulose and its derivatives today are widely used for medical and industrial purposes. We analysed the immunological properties of purified chitin particles derived from the opportunistic human fungal pathogen Candida albicans, which led to the selective secretion of the anti-inflammatory cytokine IL-10. We identified NOD2, TLR9 and the mannose receptor as essential fungal chitin-recognition receptors for the induction of this response. Chitin reduced LPS-induced inflammation in vivo and may therefore contribute to the resolution of the immune response once the pathogen has been defeated. Fungal chitin also induced eosinophilia in vivo, underpinning its ability to induce asthma. Polymorphisms in the identified chitin receptors, NOD2 and TLR9, predispose individuals to inflammatory conditions and dysregulated expression of chitinases and chitinase-like binding proteins, whose activity is essential to generate IL-10-inducing fungal chitin particles in vitro, have also been linked to inflammatory conditions and asthma. Chitin recognition is therefore critical for immune homeostasis and is likely to have a significant role in infectious and allergic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) ...over the next 10 years is to undertake broad-based phenotyping of 20,000 mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale mouse phenotyping and provides an overview of the aims and processes involved in IMPC mouse production and phenotyping.
Using a sample of 68 planet-hosting stars, I carry out a comparison of isochrone fitting and gyrochronology to investigate whether tidal interactions between the stars and their planets are leading ...to underestimated ages using the latter method. I find a slight tendency for isochrones to produce older age estimates but find no correlation with tidal time-scale, although for some individual systems the effect of tides might be leading to more rapid rotation than expected from the stars’ isochronal age, and therefore an underestimated gyrochronology age. By comparing to planetary systems in stellar clusters, I also find that in some cases isochrone fitting can overestimate the age of the star. The evidence for any bias on a sample-wide level is inconclusive. I also consider the subset of my sample for which the sky-projected alignment angle between the stellar rotation axis and the planet's orbital axis has been measured, finding similar patterns to those identified in the full sample. However, small sample sizes for both the misaligned and aligned systems prevent strong conclusions from being drawn.
Summary Background The decision of whether to treat incidental intracranial saccular aneurysms is complicated by limitations in current knowledge of their natural history. We combined individual ...patient data from prospective cohort studies to determine predictors of aneurysm rupture and to construct a risk prediction chart to estimate 5-year aneurysm rupture risk by risk factor status. Methods We did a systematic review and pooled analysis of individual patient data from 8382 participants in six prospective cohort studies with subarachnoid haemorrhage as outcome. We analysed cumulative rupture rates with Kaplan-Meier curves and assessed predictors with Cox proportional-hazard regression analysis. Findings Rupture occurred in 230 patients during 29 166 person-years of follow-up. The mean observed 1-year risk of aneurysm rupture was 1·4% (95% CI 1·1–1·6) and the 5-year risk was 3·4% (2·9–4·0). Predictors were age, hypertension, history of subarachnoid haemorrhage, aneurysm size, aneurysm location, and geographical region. In study populations from North America and European countries other than Finland, the estimated 5-year absolute risk of aneurysm rupture ranged from 0·25% in individuals younger than 70 years without vascular risk factors with a small-sized (<7 mm) internal carotid artery aneurysm, to more than 15% in patients aged 70 years or older with hypertension, a history of subarachnoid haemorrhage, and a giant-sized (>20 mm) posterior circulation aneurysm. By comparison with populations from North America and European countries other than Finland, Finnish people had a 3·6-times increased risk of aneurysm rupture and Japanese people a 2·8-times increased risk. Interpretation The PHASES score is an easily applicable aid for prediction of the risk of rupture of incidental intracranial aneurysms. Funding Netherlands Organisation for Health Research and Development.
Highlights • CLRs play an essential role in immunity to fungi and mycobacteria. • CLRs are involved in the regulation of homeostasis, autoimmunity and allergy. • CLRs recognise and trigger cellular ...responses to dead and cancerous cells.
On the abundance of circumbinary planets Armstrong, D. J; Osborn, H. P; Brown, D. J. A ...
Monthly notices of the Royal Astronomical Society,
10/2014, Letnik:
444, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We present here the first observationally based determination of the rate of occurrence of circumbinary planets. This is derived from the publicly available Kepler data, using an automated search ...algorithm and debiasing process to produce occurrence rates implied by the seven systems already known. These rates depend critically on the planetary inclination distribution: if circumbinary planets are preferentially coplanar with their host binaries, as has been suggested, then the rate of occurrence of planets with Rp
> 6R⊕ orbiting with P
p
< 300 d is
$10.0 ^{+18}_{-6.5}$
per cent (95 per cent confidence limits), higher than but consistent with single star rates. If on the other hand the underlying planetary inclination distribution is isotropic, then this occurrence rate rises dramatically, to give a lower limit of 47 per cent. This implies that formation and subsequent dynamical evolution in circumbinary discs must either lead to largely coplanar planets, or proceed with significantly greater ease than in circumstellar discs. As a result of this investigation, we also show that giant planets ( > 10R⊕) are significantly less common in circumbinary orbits than their smaller siblings, and confirm that the proposed shortfall of circumbinary planets orbiting the shorter period binaries in the Kepler sample is a real effect.
The Chinese medicinal plant Artemisia annua L. (Qinghao) is the only known source of the sesquiterpene artemisinin (Qinghaosu), which is used in the treatment of malaria. Artemisinin is a highly ...oxygenated sesquiterpene, containing a unique 1,2,4-trioxane ring structure, which is responsible for the antimalarial activity of this natural product. The phytochemistry of A. annua is dominated by both sesquiterpenoids and flavonoids, as is the case for many other plants in the Asteraceae family. However, A. annua is distinguished from the other members of the family both by the very large number of natural products which have been characterised to date (almost six hundred in total, including around fifty amorphane and cadinane sesquiterpenes), and by the highly oxygenated nature of many of the terpenoidal secondary metabolites. In addition, this species also contains an unusually large number of terpene allylic hydroperoxides and endoperoxides. This observation forms the basis of a proposal that the biogenesis of many of the highly oxygenated terpene metabolites from A. annua - including artemisinin itself - may proceed by spontaneous oxidation reactions of terpene precursors, which involve these highly reactive allyllic hydroperoxides as intermediates. Although several studies of the biosynthesis of artemisinin have been reported in the literature from the 1980s and early 1990s, the collective results from these studies were rather confusing because they implied that an unfeasibly large number of different sesquiterpenes could all function as direct precursors to artemisinin (and some of the experiments also appeared to contradict one another). As a result, the complete biosynthetic pathway to artemisinin could not be stated conclusively at the time. Fortunately, studies which have been published in the last decade are now providing a clearer picture of the biosynthetic pathways in A. annua. By synthesising some of the sesquiterpene natural products which have been proposed as biogenetic precursors to artemisinin in such a way that they incorporate a stable isotopic label, and then feeding these precursors to intact A. annua plants, it has now been possible to demonstrate that dihydroartemisinic acid is a late-stage precursor to artemisinin and that the closely related secondary metabolite, artemisinic acid, is not (this approach differs from all the previous studies, which used radio-isotopically labelled precursors that were fed to a plant homogenate or a cell-free preparation). Quite remarkably, feeding experiments with labeled dihydroartemisinic acid and artemisinic acid have resulted in incorporation of label into roughly half of all the amorphane and cadinane sesquiterpenes which were already known from phytochemical studies of A. annua. These findings strongly support the hypothesis that many of the highly oxygenated sesquiterpenoids from this species arise by oxidation reactions involving allylic hydroperoxides, which seem to be such a defining feature of the chemistry of A. annua. In the particular case of artemisinin, these in vivo results are also supported by in vitro studies, demonstrating explicitly that the biosynthesis of artemisinin proceeds via the tertiary allylic hydroperoxide, which is derived from oxidation of dihydroartemisinic acid. There is some evidence that the autoxidation of dihydroartemisinic acid to this tertiary allylic hydroperoxide is a non-enzymatic process within the plant, requiring only the presence of light; and, furthermore, that the series of spontaneous rearrangement reactions which then convert this allylic hydroperoxide to the 1,2,4-trioxane ring of artemisinin are also non-enzymatic in nature.
We report the discovery of rising X-ray emission from the binary neutron star merger event GW170817. This is the first detection of X-ray emission from a gravitational-wave (GW) source. Observations ...acquired with the Chandra X-ray Observatory (CXO) at t 2.3 days post-merger reveal no significant emission, with L x 3.2 × 10 38 erg s − 1 (isotropic-equivalent). Continued monitoring revealed the presence of an X-ray source that brightened with time, reaching L x 9 × 10 38 erg s − 1 at 15.1 days post-merger. We interpret these findings in the context of isotropic and collimated relativistic outflows (both on- and off-axis). We find that the broadband X-ray to radio observations are consistent with emission from a relativistic jet with kinetic energy E k ∼ 10 49 − 50 erg , viewed off-axis with θ obs ∼ 20 ° - 40 ° . Our models favor a circumbinary density n ∼ 10 − 4 - 10 − 2 cm − 3 , depending on the value of the microphysical parameter ϵ B = 10 − 4 - 10 − 2 . A central-engine origin of the X-ray emission is unlikely. Future X-ray observations at t 100 days, when the target will be observable again with the CXO, will provide additional constraints to solve the model degeneracies and test our predictions. Our inferences on θ obs are testable with GW information on GW170817 from advanced LIGO/Virgo on the binary inclination.
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