Soluble melanin precursors are present in serum and may act as skin chromophores contributing to UVR-induced oxidative damage. Our study aimed to determine whether the soluble eumelanin precursor 5,6-dihydroxy-indole-2-carboxylic acid (DHICA) photosensitizes DNA damage in human keratinocytes exposed to UVA irradiation. The HaCaT keratinocytes were incubated with and without DHICA, before irradiation with broadband UVA (320-400 nm). The DNA photodamage was assessed using the comet assay that detects frank single-strand breaks (SSB) and specific oxidative lesions with the addition of endonuclease III. Without DHICA incubation, there was no significant increase in SSB, compared to unirradiated cells, for doses up to 48.5 J/cm2 (< 1 minimum erythemal dose). Preincubation with 0.5 microM DHICA caused an increase in SSB at every UVA dose (significant from 12.1 to 48.5 J/cm2), while varying the DHICA concentration (0.125-2 microM) showed this effect to be concentration dependent such that SSB increased and endonuclease III-sensitive sites decreased with increasing DHICA concentration. The irradiation of cells in the presence of antioxidants (catalase, mannitol and histidine) suggests that DHICA-induced photosensitization is mediated via singlet oxygen and, to a lesser extent, hydroxyl radicals. These results indicate that DHICA can induce strand breaks with UVA at clinically relevant doses via a mechanism involving reactive oxygen species.
An indirect boundary element method is developed to predict sound fields in acoustical cavities. An isoparametric quadratic boundary element is utilized. The formulations of pressure, velocity and/or impedance boundary conditions are developed and incorporated into the method. The capability to include acoustic point sources within the cavity is also implemented. The method is applied to the prediction of sound fields in spherical and rectangular cavities. All three boundary condition types are verified. Cases having a point source within the cavity domain are also studied. Numerically determined cavity pressure distributions and responses are presented. The numerical results correlate well with available analytical results.
Topical 6,4,4'-trimethylangelicin (TMA) plus UVA was used to induce intense epidermal pigmentation in inbred HRA.HRII-c/+/Skh hairless pigmented mice over a 13 day period. Subsequent UVB/UVA exposure was used to assess the photoprotective properties of this tan using skin tumors as an endpoint. Comparisons were always made with sibling albino mice. The TMA/UVA treatment was shown to be not carcinogenic when treated mice were compared with untreated control mice over 25 weeks. The tan faded despite daily exposure to UVB/UVA and did not afford any protection when TMA/UVA-treated mice with subsequent UVB/UVA were compared with pigmented mice treated with UVB/UVA only. In one group, the TMA-induced tan was maintained by application of TMA three times a week prior to UVB/UVA for the duration of the experiment. This treatment was associated with a significant increase in tumor risk in both pigmented and albino mice compared to groups treated with UVB/UVA alone. Although pigmented mice had a significant photoprotective advantage, it was shown to be outweighed by the carcinogenic risks of the TMA maintenance treatment when they were compared with mice that did not have this treatment. Nonpretanned pigmented mice developed mild pigmentation during UVB/UVA treatment that was shown to have no protective effect when those mice were compared with albinos. We conclude that induced epidermal tanning with or without furocoumarin enhancement is not an effective way to prevent skin cancer in the HRA.HRII-c/+/Skh mouse model.
Large-scale systemic mouse phenotyping, as performed by mouse clinics for more than a decade, requires thousands of mice from a multitude of different mutant lines to be bred, individually tracked and subjected to phenotyping procedures according to a standardised schedule. All these efforts are typically organised in overlapping projects, running in parallel. In terms of logistics, data capture, data analysis, result visualisation and reporting, new challenges have emerged from such projects. These challenges could hardly be met with traditional methods such as pen & paper colony management, spreadsheet-based data management and manual data analysis. Hence, different Laboratory Information Management Systems (LIMS) have been developed in mouse clinics to facilitate or even enable mouse and data management in the described order of magnitude. This review shows that general principles of LIMS can be empirically deduced from LIMS used by different mouse clinics, although these have evolved differently. Supported by LIMS descriptions and lessons learned from seven mouse clinics, this review also shows that the unique LIMS environment in a particular facility strongly influences strategic LIMS decisions and LIMS development. As a major conclusion, this review states that there is no universal LIMS for the mouse research domain that fits all requirements. Still, empirically deduced general LIMS principles can serve as a master decision support template, which is provided as a hands-on tool for mouse research facilities looking for a LIMS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-015-9586-7) contains supplementary material, which is available to authorized users.
Two boundary element formulations of acoustical behavior exist; the Direct Boundary Element Methods (DBEM) based on the Helmholtz Integral Equations and the Indirect Boundary Element Methods (IBEM) based on Hiiyqen's Principle. In this investiqat,ion, both methods are implement.ed utilizing a simple linear superparamet.ric element. In addition the IBEM is studied using a quadratic isoparametric element. The accuracy and relative efficiency of the various techniques are examined. In order to properly model aircraft interior cavities the additional capability to model. wall treatments and internal point sources is added to the methods. The procedures are verified for several well-understood cavity problems. The relative merits of each boundary element method and the finite element method is examined.
Duplex stainless steel is common in thick-walled components such as longitudinal welded pipes in the oil and gas industries and as parts of various machines in the chemical and food industries. Electron beam welding is a very suitable method for welding such components. Due to the high power density of the electron beam combined with the decreased evaporation temperature in a vacuum atmosphere, steel with a sheet thickness of up to 150 mm can be welded in one pass. In the case of the electron beam welding of duplex stainless steels, vacuum atmosphere in the working chamber causes a nitrogen effusion from the weld pool. The microstructure of the resulting weld is characterized by an unacceptable high ferrite content, which is the main reason for both low impact toughness and low pitting corrosion resistance. This work focuses on the influence of nitrided weld edge surfaces on metallurgical properties of the resulting welded joint. The aim here is to investigate the effect of increased nitrogen content at the weld edges on nitrogen loss during EB-welding. The welds produced within the experimental work were characterized by means of microstructural analysis and the use of optical and energy dispersive X-ray spectroscopy. It was shown that nitrided weld edge surfaces can compensate nitrogen loss from the weld pool and decrease the ferrite content in the resulting weld.
This work performs a non-asymptotic analysis of the generalized Lasso under the assumption of sub-exponential data. Our main results continue recent research on the benchmark case of (sub-)Gaussian sample distributions and thereby explore what conclusions are still valid when going beyond. While many statistical features remain unaffected (e.g., consistency and error decay rates), the key difference becomes manifested in how the complexity of the hypothesis set is measured. It turns out that the estimation error can be controlled by means of two complexity parameters that arise naturally from a generic-chaining-based proof strategy. The output model can be non-realizable, while the only requirement for the input vector is a generic concentration inequality of Bernstein-type, which can be implemented for a variety of sub-exponential distributions. This abstract approach allows us to reproduce, unify, and extend previously known guarantees for the generalized Lasso. In particular, we present applications to semi-parametric output models and phase retrieval via the lifted Lasso. Moreover, our findings are discussed in the context of sparse recovery and high-dimensional estimation problems.
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