Probing the frictional properties of soft materials at the nanoscale

The understanding of friction in soft materials is of increasing importance due to the demands of industries such as healthcare, biomedical, food and personal care, the incorporation of soft materials into technology, and in the study of interacting biological interfaces. Many of these processes occur at the nanoscale, but even at micrometer length scales there are fundamental aspects of tribology that remain poorly understood. With the advent of Friction Force Microscopy (FFM), there have been many fundamental insights into tribological phenomena, such as ‘stick-slip’ and ‘super-lubricity’ at the atomic scale. This review examines the growing field of soft tribology, the experimental aspects of FFM and its underlying theory. Moving to the nanoscale changes the contact mechanics which govern adhesive forces, which in turn play a pivotal role in friction, along with deformation of the soft interface, and dissipative phenomena. We examine recent progress and future prospects in soft nanotribology

Arsenicosis, possibly from contaminated groundwater, associated with noncirrhotic intrahepatic portal hypertension.

BACKGROUND AND AIMS: Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH), a chronic microangiopathy of the liver caused by arsenicosis from use of contaminated groundwater, was reported from Asia. This study aimed to see, if in the twenty-first century, arsenicosis was present in NCIPH patients at our hospital and, if present, to look for groundwater contamination by arsenic in their residential locality. METHODS: Twenty-seven liver biopsy proven NCIPH patients, 25 portal hypertensive controls with hepatitis B or C related cirrhosis and 25 healthy controls, matched for residential locality, were studied. Eighty-four percent to 96 % of study subjects belonged to middle or lower socioeconomic category. Arsenicosis was looked for by estimation of arsenic levels in finger/toe nails and by skin examination. Arsenic levels in nails and in ground water (in NCIPH patients with arsenicosis) was estimated by mass spectrometry. RESULTS: Nail arsenic levels were raised in five (10 %) portal hypertensive study subjects [two NCIPH patients (both had skin arsenicosis) and three portal hypertensive controls]. All of these five patients were residents of West Bengal or Bangladesh. Skin arsenicosis was noted in three NCIPH patients (11 %) compared to none of disease/healthy controls. Ground water from residential locality of one NCIPH patient with arsenicosis (from Bangladesh) showed extremely high level of arsenic (79.5 μg/L). CONCLUSIONS: Arsenicosis and microangiopathy of liver, possibly caused by environmental contamination continues in parts of Asia. Further studies are needed to understand the mechanisms of such 'poverty-linked thrombophilia'

Correlating diameter, mechanical and structural properties of poly(l-lactide) fibres from needleless electrospinning

The development and application of nanofibres requires a thorough understanding of the mechanical properties on a single fibre level including respective modelling tools for precise fibre analysis. This work presents a mechanical and morphological study of poly-l-lactide nanofibres developed by needleless electrospinning. Atomic force microscopy (AFM) and micromechanical testing (MMT) were used to characterise the mechanical response of the fibres within a diameter range of 200–1400 nm. Young’s moduli E determined by means of both methods are in sound agreement and show a strong increase for thinner fibres below a critical diameter of 800 nm. Similar increasing trends for yield stress and hardening modulus were measured by MMT. Finite element analyses show that the common practice of modelling three-point bending tests with either double supported or double clamped beams is prone to significant bias in the determined elastic properties, and that the latter is a good approximation only for small diameters. Therefore, an analytical formula based on intermediate boundary conditions is proposed that is valid for the whole tested range of fibre diameters, providing a consistently low error in axial Young’s modulus below 10%. The analysis of fibre morphology by differential scanning calorimetry and 2D wide-angle X-ray scattering revealed increasing polymer chains alignment in the amorphous phase and higher crystallinity of fibres for decreasing diameter. The combination of these observations with the mechanical characterisation suggests a linear relationship between Young’s modulus and both crystallinity and molecular orientation in the amorphous phase

Deep RNA Sequencing Reveals Novel Cardiac Transcriptomic Signatures for Physiological and Pathological Hypertrophy

Although both physiological hypertrophy (PHH) and pathological hypertrophy (PAH) of the heart have similar morphological appearances, only PAH leads to fatal heart failure. In the present study, we used RNA sequencing (RNA-Seq) to determine the transcriptomic signatures for both PHH and PAH. Approximately 13–20 million reads were obtained for both models, among which PAH showed more differentially expressed genes (DEGs) (2,041) than PHH (245). The expression of 417 genes was barely detectable in the normal heart but was suddenly activated in PAH. Among them, Foxm1 and Plk1 are of particular interest, since Ingenuity Pathway Analysis (IPA) using DEGs and upstream motif analysis showed that they are essential hub proteins that regulate the expression of downstream proteins associated with PAH. Meanwhile, 52 genes related to collagen, chemokines, and actin showed opposite expression patterns between PHH and PAH. MAZ-binding motifs were enriched in the upstream region of the participating genes. Alternative splicing (AS) of exon variants was also examined using RNA-Seq data for PAH and PHH. We found 317 and 196 exon inclusions and exon exclusions, respectively, for PAH, and 242 and 172 exon inclusions and exclusions, respectively for PHH. The AS pattern was mostly related to gains or losses of domains, changes in activity, and localization of the encoded proteins. The splicing variants of 8 genes (i.e., Fhl1, Rcan1, Ndrg2, Synpo, Ttll1, Cxxc5, Egfl7, and Tmpo) were experimentally confirmed. Multilateral pathway analysis showed that the patterns of quantitative (DEG) and qualitative (AS) changes differ depending on the type of pathway in PAH and PHH. One of the most significant changes in PHH is the severe downregulation of autoimmune pathways accompanied by significant AS. These findings revealed the unique transcriptomic signatures of PAH and PHH and also provided a more comprehensive understanding at both the quantitative and qualitative levels

Survival and development of Campoletis chlorideae on various insect and crop hosts: implications for Bt-transgenic crops

The parasitic wasp, Campoletis chlorideae is an important larval parasitoid of Helicoverpa armigera a serious pest of cotton, grain legumes and cereals. Large-scale deployment of Bt-transgenic crops with resistance to H. armigera may have potential consequences for the development and survival of C. chlorideae. Therefore, we studied the tritrophic interactions of C. chlorideae involving eight insect host species and six host crops under laboratory conditions. The recovery of H. armigera larvae following release was greater on pigeonpea and chickpea when compared with cotton, groundnut and pearl millet. The parasitism by C. chlorideae females was least with reduction in cocoon formation and adult emergence on H. armigera larvae released on chickpea. Host insects also had significant effect on the development and survival of C. chlorideae. The larval period of C. chlorideae was prolonged by 2-3 days on Spodoptera exigua, Mythimna separata and Achaea janata when compared with H. armigera, Helicoverpa assulta and Spodoptera litura. Maximum cocoon formation and adult emergence were recorded on H. armigera (82.4% and 70.5%, respectively) than on other insect hosts. These studies have important implications on development and survival of C. chlorideae on alternate insect hosts on non-transgenic crop plants, when there is paucity of H. armigera larvae on transgenic crops expressing Bt-toxins

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Controlled Crosslinking Is a Tool To Precisely Modulate the Nanomechanical and Nanotribological Properties of Polymer Brushes

Covalent crosslinking of weak polyelectrolyte brushes widens the tuning potential for their swelling, nanomechanical, and nanotribological properties, which can be simultaneously adjusted by varying the crosslinker content and the pH of the surroundings. We demonstrate that this is especially valid for poly(hydroxyethyl methacrylate) (PHEMA) brushes and brush hydrogels, and their ionizable, succinate-modified derivatives (PHEMA-SA), covalently crosslinked with different amounts of di(ethylene glycol) dimethacrylate (DEGDMA) during surface-initiated atom transfer radical polymerization (SI-ATRP). Atomic force microscopy (AFM) methods highlight how pristine PHEMA films are stiff and display high coefficients of friction in water. Their succinate derivatives swell profusely in aqueous, media. Under acidic conditions they are neutral, compliant, and lubricious, with apparent Young's moduli (E*) lying between 10 and 30 kPa. Their contact mechanical behavior can be described by either the Johnson-Kendall-Roberts (JKR) or the Derjaguin-Muller-Toporov (DMT) model, depending on crosslinker content. In contrast, under basic conditions, brushes and brush hydrogels become charged, expand, and present a rigid, electrostatic barrier toward the AFM probe. Friction is extremely low at relatively low applied loads, whereas it increases at higher loads, to an extent that is regulated by the number of crosslinks within the films

Surface-grafted assemblies of cyclic polymers: Shifting between high friction and extreme lubricity

The interfacial physicochemical properties of \u201cbrushes\u201d constituted by cyclic polymers strongly depend on their surface density, and they can be modulated within a broader range with respect to those displayed by linear brush analogues of identical composition. This is especially valid for the nanotribological characteristics of poly(2-ethyl-2-oxazoline) (PEOXA) brushes, assembled on titanium oxide surfaces by grafting-to technique. At low surface coverage, cyclic PEOXA (C-PEOXA) grafts flatten down towards the grafting surface and provide high friction when sheared against an identical countersurface. In contrast, densely grafted C-PEOXA assemblies stretch vertically forming a molecularly smooth surface that hinders interpenetration with the opposing brush, and dramatically reduces friction, greatly surpassing the lubricious properties typically attained by applying linear grafts. Differently from their nanotribological properties, C-PEOXA brushes always show improved resistance towards the adsorption of proteins if compared to their linear counterparts, irrespective of their grafting density. The enhancement in biopassivity achieved by applying cyclic PEOXAs is ascribed to their intrinsic tendency to hinder protein penetration within a brush layer