Supramolecular gating of guest release from cucurbit[7]uril using de novo design

Herein we computationally explore the modulation of the release kinetics of an encapsulated guest molecule from the cucurbit[7]uril (CB7) cavity by ligands binding to the host portal. We uncovered a correlation between the ligand-binding affinity with CB7 and the guest residence time, allowing us to rapidly predict the release kinetics through straightforward energy minimization calculations. These high-throughput predictions in turn enable a Monte-Carlo Tree Search (MCTS) to de novo design a series of cap-shaped ligand molecules with large binding affinities and boosting guest residence times by up to 7 orders of magnitude. Notably, halogenated aromatic compounds emerge as top-ranking ligands. Detailed modeling suggests the presence of halogen-bonding between the ligands and the CB7 portal. Meanwhile, the binding of top-ranked ligands is supported by 1H NMR and 2D DOSY-NMR. Our findings open up possibilities in gating of molecular transport through a nanoscale cavity with potential applications in nanopore technology and controlled drug release

High content image analysis for human H4 neuroglioma cells exposed to CuO nanoparticles

<p>Abstract</p> <p>Background</p> <p>High content screening (HCS)-based image analysis is becoming an important and widely used research tool. Capitalizing this technology, ample cellular information can be extracted from the high content cellular images. In this study, an automated, reliable and quantitative cellular image analysis system developed in house has been employed to quantify the toxic responses of human H4 neuroglioma cells exposed to metal oxide nanoparticles. This system has been proved to be an essential tool in our study.</p> <p>Results</p> <p>The cellular images of H4 neuroglioma cells exposed to different concentrations of CuO nanoparticles were sampled using IN Cell Analyzer 1000. A fully automated cellular image analysis system has been developed to perform the image analysis for cell viability. A multiple adaptive thresholding method was used to classify the pixels of the nuclei image into three classes: bright nuclei, dark nuclei, and background. During the development of our image analysis methodology, we have achieved the followings: (1) The Gaussian filtering with proper scale has been applied to the cellular images for generation of a local intensity maximum inside each nucleus; (2) a novel local intensity maxima detection method based on the gradient vector field has been established; and (3) a statistical model based splitting method was proposed to overcome the under segmentation problem. Computational results indicate that 95.9% nuclei can be detected and segmented correctly by the proposed image analysis system.</p> <p>Conclusion</p> <p>The proposed automated image analysis system can effectively segment the images of human H4 neuroglioma cells exposed to CuO nanoparticles. The computational results confirmed our biological finding that human H4 neuroglioma cells had a dose-dependent toxic response to the insult of CuO nanoparticles.</p

Hexagonal Boron Nitride-Enhanced Optically Transparent Polymer Dielectric Inks for Printable Electronics.

Solution-processable thin-film dielectrics represent an important material family for large-area, fully-printed electronics. Yet, in recent years, it has seen only limited development, and has mostly remained confined to pure polymers. Although it is possible to achieve excellent printability, these polymers have low (≈2-5) dielectric constants (ε r ). There have been recent attempts to use solution-processed 2D hexagonal boron nitride (h-BN) as an alternative. However, the deposited h-BN flakes create porous thin-films, compromising their mechanical integrity, substrate adhesion, and susceptibility to moisture. These challenges are addressed by developing a "one-pot" formulation of polyurethane (PU)-based inks with h-BN nano-fillers. The approach enables coating of pinhole-free, flexible PU+h-BN dielectric thin-films. The h-BN dispersion concentration is optimized with respect to exfoliation yield, optical transparency, and thin-film uniformity. A maximum ε r ≈ 7.57 is achieved, a two-fold increase over pure PU, with only 0.7 vol% h-BN in the dielectric thin-film. A high optical transparency of ≈78.0% (≈0.65% variation) is measured across a 25 cm2 area for a 10 μm thick dielectric. The dielectric property of the composite is also consistent, with a measured areal capacitance variation of <8% across 64 printed capacitors. The formulation represents an optically transparent, flexible thin-film, with enhanced dielectric constant for printed electronics.EPSRC funding acknowledged (EP/L016087/1

Conformal Printing of Graphene for Single- and Multilayered Devices onto Arbitrarily Shaped 3D Surfaces

Printing has drawn a lot of attention as a means of low per-unit cost and high throughput patterning of graphene inks for scaled-up thin-form factor device manufacturing. However, traditional printing processes require a flat surface and are incapable of achieving patterning on to 3D objects. Here, we present a conformal printing method to achieve functional graphene-based patterns on to arbitrarily-shaped surfaces. Using experimental design, we formulate a water-insoluble graphene ink with optimum conductivity. We then print single and multi-layered electrically functional structures on to a sacrificial layer using conventional screen printing. The print is then floated on water, allowing the dissolution of the sacrificial layer, while retaining the functional patterns. The single and multilayer patterns can then be directly transferred on to arbitrarily-shaped 3D objects without requiring any post deposition processing. Using this technique, we demonstrate conformal printing of single and multilayer functional devices that include joule heaters, resistive deformation sensors and proximity sensors on hard, flexible and soft substrates, such as glass, latex, thermoplastics, textiles, and even candies and marshmallows. Our simple strategy offers great promises to add new device and sensing functionalities to previously inert 3D surfaces.EPSRC (EP/L016087/1) Graphene Flagshi

Conformal Printing of Graphene for Single- and Multilayered Devices onto Arbitrarily Shaped 3D Surfaces

Printing has drawn a lot of attention as a means of low per-unit cost and high throughput patterning of graphene inks for scaled-up thin-form factor device manufacturing. However, traditional printing processes require a flat surface and are incapable of achieving patterning on to 3D objects. Here, we present a conformal printing method to achieve functional graphene-based patterns on to arbitrarily-shaped surfaces. Using experimental design, we formulate a water-insoluble graphene ink with optimum conductivity. We then print single and multi-layered electrically functional structures on to a sacrificial layer using conventional screen printing. The print is then floated on water, allowing the dissolution of the sacrificial layer, while retaining the functional patterns. The single and multilayer patterns can then be directly transferred on to arbitrarily-shaped 3D objects without requiring any post deposition processing. Using this technique, we demonstrate conformal printing of single and multilayer functional devices that include joule heaters, resistive strain sensors and proximity sensors on hard, flexible and soft substrates, such as glass, latex, thermoplastics, textiles, and even candies and marshmallows. Our simple strategy offers great promises to add new device and sensing functionalities to previously inert 3D surfaces.EPSRC (EP/L016087/1) Graphene Flagshi

Bioluminescence imaging reveals inhibition of tumor cell proliferation by Alzheimer's amyloid β protein

Background: Cancer and Alzheimer's disease (AD) are two seemingly distinct diseases and rarely occur simultaneously in patients. To explore molecular determinants differentiating pathogenic routes towards AD or cancer, we investigate the role of amyloid β protein (Aβ) on multiple tumor cell lines that are stably expressing luciferase (human glioblastoma U87; human breast adenocarcinoma MDA-MB231; and mouse melanoma B16F). Results: Quantification of the photons emitted from the MDA-MB231 or B16F cells revealed a significant inhibition of cell proliferation by the conditioning media (CM) derived from amyloid precursor protein (APP) over-expressing cells. The inhibition of U87 cells was observed only after the media was conditioned for longer than 2 days with APP over-expressing cells. Conclusion: Our results suggest that Aβ plays an inhibitory role in tumor cell proliferation; this effect could depend on the type of tumor cells and amount of Aβ

What a difference a term makes:the effect of educational attainment on marital outcomes in the UK

Abstract In the past, students in England and Wales born within the first 5 monthsof the academic year could leave school one term earlier than those born later inthe year. Focusing on women, those who were required to stay on an extra termmore frequently hold some academic qualification. Using having been required tostay on as an exogenous factor affecting academic attainment, we find that holding alow-level academic qualification has no effect on the probability of being currentlymarried for women aged 25 or above, but increases the probability of the husbandholding some academic qualification and being economically active.33 Halama

The difference between registered natural head position and estimated natural head position in three dimensions

This study determined the intra-rater and inter-rater reliability of re-orientating three-dimensional (3D) facial images into the estimated natural head position. Three-dimensional facial images of 15 pre-surgical class III orthognathic patients were obtained and automatically re-orientated into natural head position (RNHP) using a 3D stereophotogrammetry system and in-house software. Six clinicians were asked to estimate the NHP of these patients (ENHP); they re-estimated five randomly selected 3D images after a 2-week interval. The differences in yaw, roll, pitch, and chin position between RNHP and ENHP were measured. For intra-rater reliability, the intra-class correlation coefficient (ICC) values ranged from 0.55 to 0.77, representing moderate reliability for roll, yaw, pitch, and chin position, while for inter-rater reliability, the ICC values ranged from 0.38 to 0.58, indicating poor to moderate reliability. The median difference between ENHP and RNHP was small for roll and yaw, but larger for pitch. There was a tendency for the clinicians to estimate NHP with the chin tipped more posteriorly (6.3 ± 5.2 mm) compared to RNHP, reducing the severity of the skeletal deformity in the anterior–posterior direction

Refinement of the GINGF3 locus for hereditary gingival fibromatosis

Hereditary gingival fibromatosis (HGF) is a rare, clinically variable disorder characterized by slowly progressive fibrous overgrowth of the gingiva. Four gene loci have been mapped for autosomal dominant non-syndromic HGF (adHGF). The molecular basis of adHGF remains largely unknown, with only a single SOS1 gene mutation identified so far at the gingival fibromatosis 1 (GINGF1) locus in one family. We identified an adHGF family with ten affected individuals in whom onset of gingival fibromatosis concurred with the eruption of the primary teeth. In order to identify the molecular basis in this family, we tested for linkage of the disease to known adHGF loci. A maximal multipoint logarithm of the odds score of 3.91 was obtained with marker D2S390 (θ = 0) at the GINGF3 locus on chromosome 2p23.3–p22.3, and linkage to other known loci was excluded. Sequencing two candidate genes, ALK and C2orf18, and a single nucleotide polymorphisms array analysis did not reveal a mutation or copy number variation in a patient from the family. We refined the GINGF3 locus to a 6.56-cM, 8.27-Mb region containing 112 known and hypothetical genes, and our data and a search of the literature suggest that GINGF3 is a major adHGF locus

CDH1 mutation distribution and type suggests genetic differences between the etiology of orofacial clefting and gastric cancer

Pathogenic variants in CDH1, encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available CDH1 variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least ‘likely pathogenic’, and correlates their molecular and structural characteristics to phenotype. We demonstrate that CDH1 variant type and location differ between HDGC and CL/P, and that there is clustering of CL/P variants within linker regions between the extracellular domains of the cadherin protein. While these differences do not provide for exact prediction of the phenotype for a given mutation, they may contribute to more accurate assessments of risk for HDGC or CL/P for individuals with specific CDH1 variants