Adhesion as an interplay between particle size and surface roughness

Abstract Surface roughness plays an important role in the adhesion of small particles. In this paper we have investigated adhesion as a geometrical effect taking into account both the particle size and the size of the surface features. Adhesion is studied using blunt model particles on surfaces up to 10 nm root-mean-square (RMS) roughness. Measurements with particles both smaller and larger than surface features are presented. Results indicate different behavior in these areas. Adhesion of particles smaller than or similar in size to the asperities depend mainly on the size and shape of the asperities and only weakly on the size of the particle. For large particles also the particle size has a significant effect on the adhesion. A new model, which takes the relative size of particles and asperities into account, is also derived and compared to the experimental data. The proposed model predicts adhesion well over a wide range of particle/asperity length scales

Exome sequencing reveals candidate mutations implicated in sinonasal carcinoma and malignant transformation of sinonasal inverted papilloma

We explored somatic mutations in dysplastic sinonasal inverted papilloma (SNIP), SNIP with concomitant sinonasal squamous cell carcinoma (SNSCC), and SNSCC without preceding SNIP. Ten SNIP and SNSCC samples were analyzed with exome sequencing and tested for human papillomavirus. The identified mutations were compared to the most frequently mutated genes in head and neck squamous cell carcinoma (HNSCC) in the COSMIC database. Exome sequencing data were also analyzed for mutations not previously linked to SNSCC. Seven of the most commonly mutated genes in HNSCC and SNSCC in COSMIC harbored mutations in our data. In addition, we identified mutations in 23 genes that are likely to contribute to SNIP and SNSCC oncogenesis.Peer reviewe

Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer

Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs. The MutSigCV ranking identified several well-established MSI CRC driver genes and provided additional evidence for previously proposed CRC candidate genes as well as shortlisted genes that have to our knowledge not been linked to CRC before. Two genes, SMARCB1 and STK38L, were also functionally scrutinized, providing evidence of a tumorigenic role, for SMARCB1 mutations in particular. © 2018 The Authors. Published under the terms of the CC BY 4.0 licensePeer reviewe

When TADs go bad: chromatin structure and nuclear organisation in human disease

Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains. Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs. Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers. Further insights into chromatin organisation, in parallel with accumulating whole genome sequence data for disease cohorts, are likely to yield additional valuable insights into the roles of noncoding sequence variation in human disease

Adhesion of perfume-filled microcapsules to model fabric surfaces

The retention and adhesion of melamine formaldehyde (MF) microcapsules on a model fabric surface in aqueous solution were investigated using a customised flow chamber technique and atomic force microscopy (AFM). A cellulose film was employed as a model fabric surface. Modification of the cellulose with chitosan was found to increase the retention and adhesion of microcapsules on the model fabric surface. The AFM force–displacement data reveal that bridging forces resulting from the extension of cellulose chains dominate the adhesion between the microcapsule and the unmodified cellulose film, whereas electrostatic attraction helps the microcapsules adhere to the chitosan-modified cellulose film. The correlation between results obtained using these two complementary techniques suggests that the flow chamber device can be potentially used for rapid screening of the effect of chemical modification on the adhesion of microparticles to surfaces, reducing the time required to achieve an optimal formulation

Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer

Peer reviewe

Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline

Abstract Background Chromatin loops form a basic unit of interphase nuclear organization, with chromatin loop anchor points providing contacts between regulatory regions and promoters. However, the mutational landscape at these anchor points remains under-studied. Here, we describe the unusual patterns of somatic mutations and germline variation associated with loop anchor points and explore the underlying features influencing these patterns. Results Analyses of whole genome sequencing datasets reveal that anchor points are strongly depleted for single nucleotide variants (SNVs) in tumours. Despite low SNV rates in their genomic neighbourhood, anchor points emerge as sites of evolutionary innovation, showing enrichment for structural variant (SV) breakpoints and a peak of SNVs at focal CTCF sites within the anchor points. Both CTCF-bound and non-CTCF anchor points harbour an excess of SV breakpoints in multiple tumour types and are prone to double-strand breaks in cell lines. Common fragile sites, which are hotspots for genome instability, also show elevated numbers of intersecting loop anchor points. Recurrently disrupted anchor points are enriched for genes with functions in cell cycle transitions and regions associated with predisposition to cancer. We also discover a novel class of CTCF-bound anchor points which overlap meiotic recombination hotspots and are enriched for the core PRDM9 binding motif, suggesting that the anchor points have been foci for diversity generated during recent human evolution. Conclusions We suggest that the unusual chromatin environment at loop anchor points underlies the elevated rates of variation observed, marking them as sites of regulatory importance but also genomic fragility