In vivo skin characterization by confocal Raman microspectroscopy

__Abstract__ Various areas of skin research depend on detailed knowledge of the molecular composition of skin and molecular structure of skin constituents. On a microscopic scale the skin is a highly heterogeneous tissue. Molecular composition and structure vary tremendously, depending on depth and location on the body, and may be affected by skin disorders and environmental factors such as sun exposure, seasonal variation, and cosmetic or medical treatments can influence the molecular properties of the skin. For many aspects of skin research or skin characterization, noninvasive methods are particularly welcome. This is partly because they cause less discomfort for the patient or volunteer, as the skin is not damaged, but more importantly because noninvasive methods enable investigation of the skin in its natural state, without affecting its integrity, morphology or molecular composition. Only noninvasive measurements can be performed repeatedly on the same skin area, and can thus be used to monitor skin changes. The aim of the work presented in this thesis was to develop confocal Raman microspectroscopy as a noninvasive technique for qualitative and quantitative analysis of the molecular composition of the human skin in vivo

Raman spectroscopy of human teeth using integrated optical spectrometers

We have designed an arrayed-waveguide grating in silicon oxynitride technology for the detection of Raman signals from tooth enamel in the spectral region between 890 nm and 912 nm. The detected signals for both parallel and cross polarizations are used to distinguish between healthy and carious regions on the tooth surface of extracted human teeth. Our experimental results are in very good agreement with those achieved using conventional Raman spectrometers. Our results represent a step toward the realization of compact, hand-held, integrated spectrometers

Franz cell diffusion testing and quantitative confocal raman spectroscopy: In vitro-in vivo correlation

Previously, we reported the use of Confocal Raman Spectroscopy (CRS) to investigate the topical delivery of actives and excipients. We have also correlated the results from CRS with findings from in vitro diffusion studies in human skin. However, until now CRS has only been used as a semi-quantitative method of determining the skin uptake of molecules, with results expressed as arbitrary units of signal intensity. Clearly, this posed challenges for using CRS to determine skin delivery and to assess the drug bioavailability and bioequivalence of topical formulations. In the present work, the permeation of niacinamide (NIA) from various formulations in human skin was studied in vitro using conventional Franz cells and in vivo using a quantitative CRS m

Arrayed waveguide grating for polarized Raman spectroscopy of human teeth

We designed an arrayed-waveguide grating spectrometer for the detection of early dental caries in teeth through polarized Raman spectroscopy. Measurement results on extracted human teeth demonstrate the feasibility of the approach

Improving clinical diagnosis of early-stage cutaneous melanoma based on Raman spectroscopy

Dermatology-oncolog

Intuitionistic quantum logic of an n-level system

A decade ago, Isham and Butterfield proposed a topos-theoretic approach to quantum mechanics, which meanwhile has been extended by Doering and Isham so as to provide a new mathematical foundation for all of physics. Last year, three of the present authors redeveloped and refined these ideas by combining the C*-algebraic approach to quantum theory with the so-called internal language of topos theory (see arXiv:0709.4364). The goal of the present paper is to illustrate our abstract setup through the concrete example of the C*-algebra of complex n by n matrices. This leads to an explicit expression for the pointfree quantum phase space and the associated logical structure and Gelfand transform of an n-level system. We also determine the pertinent non-probabilisitic state-proposition pairing (or valuation) and give a very natural topos-theoretic reformulation of the Kochen--Specker Theorem. The essential point is that the logical structure of a quantum n-level system turns out to be intuitionistic, which means that it is distributive but fails to satisfy the law of the excluded middle (both in opposition to the usual quantum logic).Comment: 26 page

Conceptual design of the International Axion Observatory (IAXO)

The International Axion Observatory (IAXO) will be a forth generation axion helioscope. As its primary physics goal, IAXO will look for axions or axion-like particles (ALPs) originating in the Sun via the Primakoff conversion of the solar plasma photons. In terms of signal-to-noise ratio, IAXO will be about 4-5 orders of magnitude more sensitive than CAST, currently the most powerful axion helioscope, reaching sensitivity to axion-photon couplings down to a few $\times 10^{-12}$ GeV$^{-1}$ and thus probing a large fraction of the currently unexplored axion and ALP parameter space. IAXO will also be sensitive to solar axions produced by mechanisms mediated by the axion-electron coupling $g_{ae}$ with sensitivity $-$for the first time$-$ to values of $g_{ae}$ not previously excluded by astrophysics. With several other possible physics cases, IAXO has the potential to serve as a multi-purpose facility for generic axion and ALP research in the next decade. In this paper we present the conceptual design of IAXO, which follows the layout of an enhanced axion helioscope, based on a purpose-built 20m-long 8-coils toroidal superconducting magnet. All the eight 60cm-diameter magnet bores are equipped with focusing x-ray optics, able to focus the signal photons into $\sim 0.2$ cm$^2$ spots that are imaged by ultra-low-background Micromegas x-ray detectors. The magnet is built into a structure with elevation and azimuth drives that will allow for solar tracking for $\sim$12 h each day.Comment: 47 pages, submitted to JINS

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function