1D vs. 2D shape selectivity in the crystallization-driven self-assembly of polylactide block copolymers

yes2D materials such as graphene, LAPONITE® clays or molybdenum disulfide nanosheets are of extremely high interest to the materials community as a result of their high surface area and controllable surface properties. While several methods to access 2D inorganic materials are known, the investigation of 2D organic nanomaterials is less well developed on account of the lack of ready synthetic accessibility. Crystallization-driven self-assembly (CDSA) has become a powerful method to access a wide range of complex but precisely-defined nanostructures. The preparation of 2D structures, however, particularly those aimed towards biomedical applications, is limited, with few offering biocompatible and biodegradable characteristics as well as control over self-assembly in two dimensions. Herein, in contrast to conventional self-assembly rules, we show that the solubility of polylactide (PLLA)-based amphiphiles in alcohols results in unprecedented shape selectivity based on unimer solubility. We use log Poct analysis to drive solvent selection for the formation of large uniform 2D diamond-shaped platelets, up to several microns in size, using long, soluble coronal blocks. By contrast, less soluble PLLA-containing block copolymers yield cylindrical micelles and mixed morphologies. The methods developed in this work provide a simple and consistently reproducible protocol for the preparation of well-defined 2D organic nanomaterials, whose size and morphology are expected to facilitate potential applications in drug delivery, tissue engineering and in nanocomposites.University of Warwick, Materials GRP, EPSRC, The Royal Society, ER

Spatial expression of DNA topoisomerase I genes during cell proliferation in Daucus carota

The spatial expression of carrot (Daucus carota L.) top1 genes encoding the two isoforms of the enzyme DNA topoisomerase I (EC 5.99.1.2) was investigated. In situ hybridization analysis performed with a probe recognizing both top1 transcripts provided evidence that in explanted hypocotyls induced to proliferate in vitro by the addition of the growth regulator 2,4-dichlorophenoxyacetic acid (2,4-D), the mRNA accumulation parallels the proliferation of provascular cells of the stelar cylinder. During somatic embryogenesis, the histological distribution of top1 transcripts was strongly evident at the stage of torpedo-shaped embryos, but gene expression was not only restricted to meristematic regions. When the spatial localization was extended to carrot vegetative apices and the investigation was carried out with specific probes for top1a and top1b, both transcripts preferentially accumulated in tissues having mitotic activity

Interobserver reproducibility in pathologist interpretation of columnar-lined esophagus

Confirmation of endoscopically suspected esophageal metaplasia (ESEM) requires histology, but confusion in the histological definition of columnar-lined esophagus (CLE) is a longstanding problem. The aim of this study is to evaluate interpathologist variability in the interpretation of CLE. Thirty pathologists were invited to review three ten-case sets of CLE biopsies. In the first set, the cases were provided with descriptive endoscopy only; in the second and the third sets, ESEM extent using Prague criteria was provided. Moreover, participants were required to refer to a diagnostic chart for evaluation of the third set. Agreement was statistically assessed using Randolph’s free-marginal multirater kappa. While substantial agreement in recognizing columnar epithelium (K = 0.76) was recorded, the overall concordance in clinico-pathological diagnosis was low (K = 0.38). The overall concordance rate improved from the first (K = 0.27) to the second (K = 0.40) and third step (K = 0.46). Agreement was substantial when diagnosing Barrett’s esophagus (BE) with intestinal metaplasia or inlet patch (K = 0.65 and K = 0.89), respectively, in the third step, while major problems in interpretation of CLE were observed when only cardia/cardia-oxyntic atrophic-type epithelium was present (K = 0.05–0.29). In conclusion, precise endoscopic description and the use of a diagnostic chart increased consistency in CLE interpretation of esophageal biopsies. Agreement was substantial for some diagnostic categories (BE with intestinal metaplasia and inlet patch) with a well-defined clinical profile. Interpretation of cases with cardia/cardia-oxyntic atrophic-type epithelium, with or without ESEM, was least consistent, which reflects lack of clarity of definition and results in variable management of this entity

Retaining individualities: the photodynamics of self-ordering porphyrin assemblies

The retention of photochemical properties of individual chromophores is a key feature of biological light harvesting complexes. This is achieved despite extensive aggregation of the chromophores, which in synthetic chromophore assemblies often yields a change in spectral characteristics. As an alternative approach towards mimicking biological light harvesting complexes, we report the synthesis of porphyrin assemblies which retained the photochemical properties of the individual chromophore units despite their substantial aggregation. These new materials highlight a new bottom-up approach towards the design and understanding of more complex biomimetic and naturally occurring biological systems

Online security assessment with load and renewable generation uncertainty: The iTesla project approach

The secure integration of renewable generation into modern power systems requires an appropriate assessment of the security of the system in real-time. The uncertainty associated with renewable power makes it impossible to tackle this problem via a brute-force approach, i.e. it is not possible to run detailed online static or dynamic simulations for all possible security problems and realizations of load and renewable power. Intelligent approaches for online security assessment with forecast uncertainty modeling are being sought to better handle contingency events. This paper reports the platform developed within the iTesla project for online static and dynamic security assessment. This innovative and open-source computational platform is composed of several modules such as detailed static and dynamic simulation, machine learning, forecast uncertainty representation and optimization tools to not only filter contingencies but also to provide the best control actions to avoid possible unsecure situations. Based on High Performance Computing (HPC), the iTesla platform was tested in the French network for a specific security problem: overload of transmission circuits. The results obtained show that forecast uncertainty representation is of the utmost importance, since from apparently secure forecast network states, it is possible to obtain unsecure situations that need to be tackled in advance by the system operator

The landscape of BRAF transcript and protein variants in human cancer

Background: The BRAF protein kinase is widely studied as a cancer driver and therapeutic target. However, the regulation of its expression is not completely understood. Results: Taking advantage of the RNA-seq data of more than 4800 patients belonging to 9 different cancer types, we show that BRAF mRNA exists as a pool of 3 isoforms (reference BRAF, BRAF-X1, and BRAF-X2) that differ in the last part of their coding sequences, as well as in the length (BRAF-ref: 76 nt; BRAF-X1 and BRAF-X2: up to 7 kb) and in the sequence of their 3'UTRs. The expression levels of BRAF-ref and BRAF-X1/X2 are inversely correlated, while the most prevalent among the three isoforms varies from cancer type to cancer type. In melanoma cells, the X1 isoform is expressed at the highest level in both therapy-naïve cells and cells with acquired resistance to vemurafenib driven by BRAF gene amplification or expression of the Δ[3-10] splicing variant. In addition to the BRAF-ref protein, the BRAF-X1 protein (the full length as well as the Δ[3-10] variant) is also translated. The expression levels of the BRAF-ref and BRAF-X1 proteins are similar, and together they account for BRAF functional activities. In contrast, the endogenous BRAF-X2 protein is hard to detect because the C-terminal domain is selectively recognized by the ubiquitin-proteasome pathway and targeted for degradation. Conclusions: By shedding light on the repertoire of BRAF mRNA and protein variants, and on the complex regulation of their expression, our work paves the way to a deeper understanding of a crucially important player in human cancer and to a more informed development of new therapeutic strategies

Open access simulation toolbox for the grid connection of offshore wind farms using multi-terminal HVDC networks

Decarbonisation of the European electricity system can become dauntingly costly due to transmission and distribution network issues arising from the integration of intermittent renewable generation sources. It is expected that wind energy will be the principal renewable source by 2050 and, as such, a number of initiatives in the academia and in the industry are being carried out to propose solutions to best accommodate the wind resource. This paper presents work carried out by DEMO 1 partners within the EU FP7 project BEST PATHS. A MATLAB/Simulink toolbox consisting of the necessary building blocks for the simulation and integration of offshore wind farms using enabling technologies such as multiterminal high-voltage direct-current grids is presented. To illustrate the toolbox capabilities, a number of system topologies is studied. System performance is assessed and measured against a set of key performance indicators. To ensure knowledge dissemination, the toolbox has been made available as open access in the BEST PATHS project website

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority