Progress in the use of adeno-associated viral vectors for gene therapy

The development of safe and efficient gene transfer vectors is crucial for the success of gene therapy trials. A viral vector system promising to meet these requirements is based on the apathogenic adeno-associated virus (AAV-2), a member of the parvovirus family. The advantages of this vector system is the stability of the viral capsid, the low immunogenicity, the ability to transduce both dividing and non-dividing cells, the potential to integrate site specifically and to achieve long-term gene expression even in vivo, and its broad tropism allowing the efficient transduction of diverse organs including the skin. All this makes AAV-2 attractive and efficient for in vitro gene transfer and local injection in vivo. This review covers the progress made in AAV vector technology including the development of AAV vectors based on other serotypes, summarizes the results obtained by AAV targeting vectors and outlines potential applications in the field of cutaneous gene therapy. Copyright (C) 2004 S. Karger AG, Basel

Prognostic significance of DNA cytometry in cutaneous malignant lymphomas.

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML

Multiscale Modeling and Simulation of Organic Solar Cells

In this article, we continue our mathematical study of organic solar cells (OSCs) and propose a two-scale (micro- and macro-scale) model of heterojunction OSCs with interface geometries characterized by an arbitrarily complex morphology. The microscale model consists of a system of partial and ordinary differential equations in an heterogeneous domain, that provides a full description of excitation/transport phenomena occurring in the bulk regions and dissociation/recombination processes occurring in a thin material slab across the interface. The macroscale model is obtained by a micro-to-macro scale transition that consists of averaging the mass balance equations in the normal direction across the interface thickness, giving rise to nonlinear transmission conditions that are parametrized by the interfacial width. These conditions account in a lumped manner for the volumetric dissociation/recombination phenomena occurring in the thin slab and depend locally on the electric field magnitude and orientation. Using the macroscale model in two spatial dimensions, device structures with complex interface morphologies, for which existing data are available, are numerically investigated showing that, if the electric field orientation relative to the interface is taken into due account, the device performance is determined not only by the total interface length but also by its shape

High-Definition Optical Coherence Tomography for the in vivo Detection of Demodex Mites

Background: Demodex mites are involved in different skin diseases and are commonly detected by skin scrape tests or superficial biopsies. A new high-definition optical coherence tomography (HD-OCT) with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode might offer the possibility of noninvasive and fast in vivo examination of demodex mites. Methods: Twenty patients with demodex-related skin diseases and 20 age- and gender-matched healthy controls were examined by HD-OCT. Mites per follicle and follicles per field of view were counted and compared to skin scrape tests. Results: HD-OCT images depicted mites in the en-face mode as bright round dots in groups of 3-5 mites per hair follicle. In the patients with demodex-related disease, a mean number of 3.4 mites per follicle were detected with a mean number of 2.9 infested follicles per area of view compared to a mean of 0.6 mites in 0.4 infested follicles in the controls. The skin scrape tests were negative in 21% of the patients. Conclusion: The innovative HD-OCT enables fast and noninvasive in vivo recognition of demodex mites and might become a useful tool in the diagnosis and treatment monitoring of demodex-related skin diseases. Copyright (C) 2012 S. Karger AG, Base

Transit Detection in the MEarth Survey of Nearby M Dwarfs: Bridging the Clean-First, Search-Later Divide

In the effort to characterize the masses, radii, and atmospheres of potentially habitable exoplanets, there is an urgent need to find examples of such planets transiting nearby M dwarfs. The MEarth Project is an ongoing effort to do so, as a ground-based photometric survey designed to detect exoplanets as small as 2 Earth radii transiting mid-to-late M dwarfs within 33 pc of the Sun. Unfortunately, identifying transits of such planets in photometric monitoring is complicated both by the intrinsic stellar variability that is common among these stars and by the nocturnal cadence, atmospheric variations, and instrumental systematics that often plague Earth-bound observatories. Here we summarize the properties of MEarth data gathered so far, and we present a new framework to detect shallow exoplanet transits in wiggly and irregularly-spaced light curves. In contrast to previous methods that clean trends from light curves before searching for transits, this framework assesses the significance of individual transits simultaneously while modeling variability, systematics, and the photometric quality of individual nights. Our Method for Including Starspots and Systematics in the Marginalized Probability of a Lone Eclipse (MISS MarPLE) uses a computationally efficient semi-Bayesian approach to explore the vast probability space spanned by the many parameters of this model, naturally incorporating the uncertainties in these parameters into its evaluation of candidate events. We show how to combine individual transits processed by MISS MarPLE into periodic transiting planet candidates and compare our results to the popular Box-fitting Least Squares (BLS) method with simulations. By applying MISS MarPLE to observations from the MEarth Project, we demonstrate the utility of this framework for robustly assessing the false alarm probability of transit signals in real data. [slightly abridged]Comment: accepted to the Astronomical Journal, 21 pages, 12 figure

The Westerbork HI Survey of spiral and irregular galaxies III: HI observations of early-type disk galaxies

We present HI observations of 68 early-type disk galaxies from the WHISP survey. They have morphological types between S0 and Sab and absolute B-band magnitudes between -14 and -22. These galaxies form the massive, high surface-brightness extreme of the disk galaxy population, few of which have been imaged in HI before. The HI properties of the galaxies in our sample span a large range; the average values of M_HI/L_B and D_HI/D_25 are comparable to the ones found in later-type spirals, but the dispersions around the mean are larger. No significant differences are found between the S0/S0a and the Sa/Sab galaxies. Our early-type disk galaxies follow the same HI mass-diameter relation as later-type spiral galaxies, but their effective HI surface densities are slightly lower than those found in later-type systems. In some galaxies, distinct rings of HI emission coincide with regions of enhanced star formation, even though the average gas densities are far below the threshold of star formation derived by Kennicutt (1989). Apparently, additional mechanisms, as yet unknown, regulate star formation at low surface densities. Many of the galaxies in our sample have lopsided gas morphologies; in most cases this can be linked to recent or ongoing interactions or merger events. Asymmetries are rare in quiescent galaxies. Kinematic lopsidedness is rare, both in interacting and isolated systems. In the appendix, we present an atlas of the HI observations: for all galaxies we show HI surface density maps, global profiles, velocity fields and radial surface density profiles.Comment: 24 pages, 11 figures. Accepted for publication in A&A. A version with the full atlas can be downloaded from http://www.astro.rug.nl/~edo/WHISPIII.ps.gz (gzipped postscript, 9.3Mb

Long-Term Maintenance of Psoriatic Human Skin on Congenitally Athymic (Nude) Mice

Transplantation of involved psoriatic and nonpsoriatic human skin onto congenitally athymie (nude) mice has been performed successfully. Although biopsies at selected intervals demonstrate that the excess glycogen deposition normally seen in psoriasis is no longer consistently present, the psoriatic grafts did retain the usual characteristic histologic differences throughout the life of the animal, up to 11 weeks. This grafting procedure potentially represents a useful method whereby the study of psoriasis can be made in a nonhuman, living system

Aquagenic wrinkling of the palms: Morphological changes in reflectance confocal microscopy and high-definition optical coherence tomography

Aquagenic wrinkling of the palms (AWP) is a rare condition, which is characterized by appearance of whitish papules and plaques, and an excessive wrinkling and swelling of the palmar skin after exposure to water. In most cases, young women are affected, and an association of AWP with cystic fibrosis (CF) has been surmised. We report on two cases of AWP, which were not related to CF, in whom we used two innovative imaging techniques, namely high-definition optical coherence tomography and reflectance confocal microscopy, to show in vivo skin changes occurring after exposure of the skin to tap water in comparison to the findings in a healthy control person

Impact of Age and Body Site on Adult Female Skin Surface pH

Background: pH is known as an important parameter in epidermal barrier function and homeostasis. Aim: The impact of age and body site on skin surface pH (pH(SS)) of women was evaluated in vivo. Methods: Time domain dual lifetime referencing with luminescent sensor foils was used for pH(SS) measurements. pH(SS) was measured on the forehead, the temple, and the volar forearm of adult females (n = 97, 52.87 +/- 18.58 years, 20-97 years). Every single measurement contained 2,500 pH values due to the luminescence imaging technique used. Results: pH(SS) slightly increases with age on all three investigated body sites. There are no significant differences in pH(SS) between the three investigated body sites. Conclusion: Adult pH(SS) on the forehead, the temple and the volar forearm increases slightly with age. This knowledge is crucial for adapting medical skin care products. Copyright (C) 2012 S. Karger AG, Base

Successful treatment of nail lichen planus with alitretinoin: Report of 2 cases and review of the literature

BACKGROUND Treatment of nail lichen planus (LP) is difficult and an optimal therapy is lacking. OBJECTIVE To report additional cases to the scant existing literature to learn more about therapeutic options for nail LP. METHODS A regimen of 30 mg alitretinoin daily in 2 cases of nail LP over a period of 9 and 8 months, respectively. RESULTS In either case, nail changes showed marked improvement under oral alitretinoin therapy within 2 and 4 months, respectively. In both patients, affected nails with end-stage destructive pterygium were resistant to any previously applied therapy. CONCLUSION Alitretinoin is an effective treatment option for nail LP. We recommend early diagnosis of nail LP and early initiation of systemic therapy with alitretinoin to prevent the development of pterygium and permanent nail damage. However, further clinical studies are needed to establish reliable guidelines for nail LP therapy