At the advent of cross-coupling chemistry, carbon electrophiles based on halides or pseudohalides were the only suitable electrophilic coupling partners. Almost two decades passed before the first ...cross-coupling reaction of heteroatom-based electrophiles was reported. Early work by Murai and Tanaka initiated investigations into silicon electrophiles. Narasaka and Johnson pioneered the way in the use of nitrogen electrophiles, while Suginome began the exploration of boron electrophiles. The chemistry reviewed within provides perspective on the use of heteroatomic electrophiles, specifically silicon-, nitrogen-, boron-, oxygen-, and phosphorus-based electrophiles in transition-metal catalyzed cross-coupling. For the purposes of this review, a loose definition of cross-coupling is utilized; all reactions minimally proceed via an oxidative addition event. Although not cross-coupling in a traditional sense, we have also included catalyzed reactions that join a heteroatomic electrophile with an in situ generated nucleophile. However, for brevity, those involving hydroamination or C–H activation as a key step are largely excluded. This work includes primary references published up to and including October 2018.
During the past 10 years, preclinical studies implicating sustained androgen receptor (AR) signalling as the primary driver of castration-resistant prostate cancer (CRPC) have led to the development ...of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong the survival of patients with late-stage prostate cancer but are not curative. In this Review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signalling, AR bypass signalling and complete AR independence. This diverse range of resistance mechanisms presents new challenges for long-term disease control, which may be addressable through early use of combination therapies guided by recent insights from genomic landscape studies of CRPC.
A long-standing paradigm in astrophysics is that collisions- or mergers-of two neutron stars form highly relativistic and collimated outflows (jets) that power Y-ray bursts of short (less than two ...seconds) duration. The observational support for this model, however, is only indirect. A hitherto outstanding prediction is that gravitational-wave events from such mergers should be associated with Y-ray bursts, and that a majority of these bursts should be seen off-axis, that is, they should point away from Earth. Here we report the discovery observations of the X-ray counterpart associated with the gravitational-wave event GW170817. Although the electromagnetic counterpart at optical and infrared frequencies is dominated by the radioactive glow (known as a 'kilonova') from freshly synthesized rapid neutron capture (r-process) material in the merger ejecta, observations at X-ray and, later, radio frequencies are consistent with a short Y-ray burst viewed off-axis. Our detection of X-ray emission at a location coincident with the kilonova transient provides the missing observational link between short Y-ray bursts and gravitational waves from neutron-star mergers, and gives independent confirmation of the collimated nature of the Y-ray-burst emission.
The nanopattern on the surface of Clanger cicada (Psaltoda claripennis) wings represents the first example of a new class of biomaterials that can kill bacteria on contact based solely on their ...physical surface structure. The wings provide a model for the development of novel functional surfaces that possess an increased resistance to bacterial contamination and infection. We propose a biophysical model of the interactions between bacterial cells and cicada wing surface structures, and show that mechanical properties, in particular cell rigidity, are key factors in determining bacterial resistance/sensitivity to the bactericidal nature of the wing surface. We confirmed this experimentally by decreasing the rigidity of surface-resistant strains through microwave irradiation of the cells, which renders them susceptible to the wing effects. Our findings demonstrate the potential benefits of incorporating cicada wing nanopatterns into the design of antibacterial nanomaterials.
Chickens are a highly important source of protein for a large proportion of the human population. The caecal microbiota plays a crucial role in chicken nutrition through the production of short-chain ...fatty acids, nitrogen recycling, and amino acid production. In this study, we sequence DNA from caecal content samples taken from 24 chickens belonging to either a fast or a slower growing breed consuming either a vegetable-only diet or a diet containing fish meal.
We utilise 1.6 T of Illumina data to construct 469 draft metagenome-assembled bacterial genomes, including 460 novel strains, 283 novel species, and 42 novel genera. We compare our genomes to data from 9 European Union countries and show that these genomes are abundant within European chicken flocks. We also compare the abundance of our genomes, and the carbohydrate active enzymes they produce, between our chicken groups and demonstrate that there are both breed- and diet-specific microbiomes, as well as an overlapping core microbiome.
This data will form the basis for future studies examining the composition and function of the chicken caecal microbiota.
The self-cleaning function of superhydrophobic surfaces is conventionally attributed to the removal of contaminating particles by impacting or rolling water droplets, which implies the action of ...external forces such as gravity. Here, we demonstrate a unique self-cleaning mechanism whereby the contaminated superhydrophobic surface is exposed to condensing water vapor, and the contaminants are autonomously removed by the self-propelled jumping motion of the resulting liquid condensate, which partially covers or fully encloses the contaminating particles. The jumping motion off the superhydrophobic surface is powered by the surface energy released upon coalescence of the condensed water phase around the contaminants. The jumping-condensate mechanism is shown to spontaneously clean superhydrophobic cicada wings, where the contaminating particles cannot be removed by gravity, wing vibration, or wind flow. Our findings offer insights for the development of self-cleaning materials.
Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss ...during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD.
Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease.
Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively.
Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.
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Geckos, and specifically their feet, have attracted significant attention in recent times with the focus centred around their remarkable adhesional properties. Little attention ...however has been dedicated to the other remaining regions of the lizard body. In this paper we present preliminary investigations into a number of notable interfacial properties of the gecko skin focusing on solid and aqueous interactions. We show that the skin of the box-patterned gecko (Lucasium sp.) consists of dome shaped scales arranged in a hexagonal patterning. The scales comprise of spinules (hairs), from several hundred nanometres to several microns in length, with a sub-micron spacing and a small radius of curvature typically from 10 to 20nm. This micro and nano structure of the skin exhibited ultralow adhesion with contaminating particles. The topography also provides a superhydrophobic, anti-wetting barrier which can self clean by the action of low velocity rolling or impacting droplets of various size ranges from microns to several millimetres. Water droplets which are sufficiently small (10–100μm) can easily access valleys between the scales for efficient self-cleaning and due to their dimensions can self-propel off the surface enhancing their mobility and cleaning effect. In addition, we demonstrate that the gecko skin has an antibacterial action where Gram-negative bacteria (Porphyromonas gingivalis) are killed when exposed to the surface however eukaryotic cell compatibility (with human stem cells) is demonstrated. The multifunctional features of the gecko skin provide a potential natural template for man-made applications where specific control of liquid, solid and biological contacts is required.
Nature's molecular machines are a constant source of inspiration to the chemist. Many of these molecular machines function within lipid membranes, allowing them to exploit potential gradients between ...spatially close, but chemically distinct environments to fuel their work cycle. Indeed, the realisation of such principles in synthetic transmembrane systems remains a tantalising goal. This tutorial review opens by highlighting seminal examples of synthetic molecular machines. We illustrate the importance of surfaces for facilitating the extraction of work from molecular switches and motors. We chart the development of man-made transmembrane systems; from passive to machine-like stimuli-responsive channels, to fully autonomous transmembrane molecular machines. Finally, we highlight higher-order compartmentalised systems that exhibit emergent properties. We suggest that such higher-order architectures could serve as platforms for sophisticated devices that co-ordinate the activity of numerous transmembrane molecular machines.
The Give and Take of Alcohol Activation Watson, Andrew J. A.; Williams, Jonathan M. J.
Science (American Association for the Advancement of Science),
08/2010, Letnik:
329, Številka:
5992
Journal Article
Recenzirano
Catalysts make alcohols more reactive by taking away hydrogen to create carbonyl compounds and then returning the hydrogen to the final products.
Alcohols are relatively common starting materials for ...chemical reactions, even though they are quite unreactive. For example, reactions that would substitute another functional group (a nucleophile) for OH often fail because the hydroxide group (HO
−
) is difficult to displace—it is a poor leaving group. Alcohols are usually activated by turning the hydroxide into a better leaving group, either by protonating the alcohol or by converting it into a sulfonate or halide. However, both of these activation methods have some disadvantages (
1
). The acidic environment required for protonating the alcohol also protonates and deactivates the incoming nucleophile, especially amines. Conversion of the alcohol into a sulfonate or halide can lead to toxicity problems; many alkyl halides and alkyl sulfonates are mutagenic.
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