Using the Mechanical Bond to Tune the Performance of a Thermally Activated Delayed Fluorescence Emitter**

We report the characterization of rotaxanes based on a carbazole-benzophenone thermally activated delayed fluorescence luminophore. We find that the mechanical bond leads to an improvement in key photophysical properties of the emitter, notably an increase in photoluminescence quantum yield and a decrease in the energy difference between singlet and triplet states, as well as fine tuning of the emission wavelength, a feat that is difficult to achieve when using covalently bound substituents. Computational simulations, supported by X-ray crystallography, suggest that this tuning of properties occurs due to weak interactions between the axle and the macrocycle that are enforced by the mechanical bond. This work highlights the benefits of using the mechanical bond to refine existing luminophores, providing a new avenue for emitter optimization that can ultimately increase the performance of these molecules

Recurrent Chromosomal Copy Number Alterations in Sporadic Chordomas

The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/ brachyury for proliferation

Chronic obstructive pulmonary disease guidelines in Europe: a look into the future.

Clinical practice guidelines are ubiquitous and are developed to provide recommendations for the management of many diseases, including chronic obstructive pulmonary disease. The development of these guidelines is burdensome, demanding a significant investment of time and money. In Europe, the majority of countries develop their own national guidelines, despite the potential for overlap or duplication of effort. A concerted effort and consolidation of resources between countries may alleviate the resource-intensity of maintaining individual national guidelines. Despite significant resource investment into the development and maintenance of clinical practice guidelines, their implementation is suboptimal. Effective strategies of guideline dissemination must be given more consideration, to ensure adequate implementation and improved patient care management in the future.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Structure-switching M₃L₂ Ir(III) coordination cages with photo-isomerising azo-aromatic linkers

Cyclotriguaiacylene has been functionalised with 3- or 4-pyridyl-azo-phenyl groups to form a series of molecular hosts with three azobenzene-type groups that exhibit reversible photo-isomerisation. Reaction of the host molecules with [Ir(C^N)₂(NCMe)₂]+ where C^N is the cyclometallating 2-phenylpyridinato, 2-(4-methylphenyl)pyridinato or 2-(4,5,6-trifluorophenyl)pyridinato results in the self-assembly of a family of five different [{Ir(C^N)₂}₃(L)₂]³+ coordination cages. Photo-irradiation of each of the cages with a high energy laser results in E → Z photo-isomerisation of the pyridyl-azo-phenyl groups with up to 40% of groups isomerising. Isomerisation can be reversed by exposure to blue light. Thus, the cages show reversible structure-switching while maintaining their compositional integrity. This represents the largest photo-induced structural change yet reported for a structurally-integral component of a coordination cage. Energy minimised molecular models indicate a switched cage has a smaller internal space than the initial all-E isomer. The [Ir(C^N)₂(NCMe)₂]+ cages are weakly emissive, each with a deep blue luminescence at ca. 450 nm