Accelerated epigenetic aging in Werner syndrome.

Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown

Resistance-welded thermoset composites: A Bayesian approach to process optimisation for improved fracture toughness

Joining thermoset composites via resistance welding offers a novel highly efficient assembly method for next-generation aerospace structures. Resistance-welded joints combine the benefits of bonding with the capacity for high-volume manufacturing rates and eliminate the need for complex surface preparation. The influence of key welding parameters on the joint performance is investigated by assessing the Mode I fracture toughness. Double Cantilever Beam specimens with different welding parameter combinations are manufactured, tested and compared with each other. Thermoset laminates are made weldable by co-curing a chemically compatible thermoplastic film with an uncured thermoset laminate. A Bayesian approach is used to study the correlation between processing parameters and to select parameters yielding high performance by training a Gaussian process emulator. Observed Mode I fracture toughness values are comparable to high-performance thermoplastic composites. This is equivalent to an improvement of approximately 290% in Mode I fracture toughness when compared to a co-cured thermoset joint

Fullerene-based Biocomponents : New Concepts For Functionalising Membranes

Lipophilic hexakisadducts of fullerene C60 form unprecedented rod-like nanoaggregates in phospholipid-membrane bilayers, resulting in modification of the micromechanic properties and stabilisation of the membrane. Lipofullerenes with amphiphilic side chains enable additionally derivatisation and molecular recognition at the membrane surface. The amphiphilic spacer acts as a transmembrane anchor and provides the terminal functionality outside of the membrane. New systems derived from parent compound 3 carry two functional groups each and can be easily modified due to the modular synthesis. Terminal functionalities to be investigated include D(+)-biotin and IDA (iminodiacetic acid) ligands, as used in nickel-histidine tags. Modification of the lipophilic region, for instance with unsaturated addends is also possible. These addends should allow polymerisation inside the membrane and potentially lead to a tremendous increase of the membrane rigidity. Furthermore, mono- and bilayer-forming fullerene derivatives without the membrane-forming support of lecithins are investigated and exhibit interesting features

Discrete Stiffness Tailoring: Optimised design and testing of minimum mass stiffened panels

Discrete Stiffness Tailoring (DST) is a novel manufacturing concept where stiffness tailoring is achieved using discrete changes in ply angle to favourably redistribute stresses. Resulting performance increases can be exploited to potentially achieve lightweight rapidly manufacturable structures, uninhibited by the minimum tow-turning radii which limit continuous fibre steering approaches. An efficient two-stage optimisation routine is implemented to design a DST minimum-mass stiffened aircraft wing panel subject to buckling and manufacturing feasibility constraints. The panel is manufactured and compression tested to failure, extending the DST design concept to component level for the first time. A weight reduction of 14.4% is achieved compared to a constant stiffness optimum, through redistribution of load to the stiffener region. The optimum design removes material from the skin, between stiffeners. Experimentally, the optimised tailored panel achieved a buckling load, without failure, within 5% of that predicted, validating both the methodology and modelling

Feature-assisted interactive geometry reconstruction in 3D point clouds using incremental region growing

Reconstructing geometric shapes from point clouds is a common task that is often accomplished by experts manually modeling geometries in CAD-capable software. State-of-the-art workflows based on fully automatic geometry extraction are limited by point cloud density and memory constraints, and require pre- and post-processing by the user. In this work, we present a framework for interactive, user-driven, feature-assisted geometry reconstruction from arbitrarily sized point clouds. Based on seeded region-growing point cloud segmentation, the user interactively extracts planar pieces of geometry and utilizes contextual suggestions to point out plane surfaces, normal and tangential directions, and edges and corners. We implement a set of feature-assisted tools for high-precision modeling tasks in architecture and urban surveying scenarios, enabling instant-feedback interactive point cloud manipulation on large-scale data collected from real-world building interiors and facades. We evaluate our results through systematic measurement of the reconstruction accuracy, and interviews with domain experts who deploy our framework in a commercial setting and give both structured and subjective feedback.Comment: 13 pages, submitted to Computers & Graphics Journa

The growth of cubic CdS on InP(110) studied in situ by Raman spectroscopy

CdS was deposited onto clean cleaved InP(110) by molecular beam epitaxy (MBE) using a growth rate of 0.2 monolayers/min and a substrate temperature of 440 K (510 K). Raman spectra were taken in situ of the clean InP surface and after each evaporation step using an Ar+ ion laser as a light source. Due to this resonant excitation scattering signals originating from the CdS deposition are observed at coverages as low as 2 monolayers (ML). The number of phonon peaks observed and their selection rules reveal that the cubic modification is present. The spectra are dominated at all coverages by the longitudinal optical (LO) and 2LO phonon scattering intensities and the variation of the 2LO/LO intensity ratio with CdS deposition indicates changes in the electronic structure of the growing CdS. Another spectral feature in the Raman spectra is attributed to a chemically reacted layer at the interface most likely consisting of an In–S compound. The intensity of this feature is found to depend critically on the growth parameters, in particular the substrate temperature, but also on the operating time of the MBE cell. The amount of reaction at the interface also influences the critical CdS film thickness and the development of the 2LO/LO ratio. The results are discussed taking complementary photoluminescence, x‐ray diffraction, and photoemission data into account

An interleukin-1 polymorphism additionally intensified by atopy as prognostic factor for aseptic non-mechanical complications in metal knee and hip arthroplasty

Background: In contrast to infection or mechanical issues joint replacement failure following inflammatory adverse reactions is poorly understood. Objective: To assess the association of IL-1β polymorphisms and history of allergy with aseptic non-mechanical complications following arthroplasty. Methods: In 102 patients with aseptic non-mechanically caused symptomatic knee or hip arthroplasty (SA) and 93 patients with asymptomatic arthroplasty (AA) questionnaire-based history, patch test with at least standard series, lymphocyte transformation test (LTT) with nickel, cobalt and chromium and interleukin-1 polymorphism analysis were done. Three polymorphisms of the IL1B gene [IL-1b -3954 (rs1143634), IL-1b -511 (rs16944) and IL-1b -31 (rs1143627)] and one polymorphism of the IL1RN gene [IL1RN intron 2, variable number of tandem repeats, VNTR (rs2234663)] were assessed by PCR and gel electrophoresis. Results: We found no significant difference in smoking history and atopy but 25% versus 10% of self-reported metal allergy in SA versus AA; the patch test (respective, LTT) for metal sensitivity was more often positive in SA patients. The allele 498 bp of the IL1RN polymorphism occurred significantly more often in the SA group (37% versus 11%; p < 0.0001). Upon additional presence of atopy, the difference was even greater (60% vs 10%) (p < 0.000001). There was no association of IL-1 polymorphisms with metal allergy. Conclusion: The IL1RN VNTR allele 498 bp was strongly associated with SA. In patients with a history of atopy, presence of the IL1RN VNTR allele 498 bp led to a four-fold higher SA prevalence compared to patients without this allele