Activity of different desoximetasone preparations compared to other topical corticosteroids in the vasoconstriction assay

Introduction: We report on a double-blind, vehicle-controlled, single-center confirmatory study with random assignment. The purpose of the study was to investigate the topical bioavailability of different topical corticosteroid formulations in healthy human beings focussing on desoximetasone (DM). Materials and Methods: Two DM 0.25% formulations {[}ointment (DM-o) and fatty ointment (DM-fo, water-free); class III corticosteroids], the corresponding active ingredient-free vehicles and three comparators of different strength {[}clobetasol propionate 0.05% (CP 0.05%), fatty ointment, class IV; hydrocortisone (HC) 1%, fatty ointment, class I, and betamethasone (BM) 0.05%, fatty ointment, class III] were tested using the vasoconstriction assay. The degree of vasoconstriction (blanching) in the treatment field was compared to the one found in untreated control fields using chromametric measurements and clinical assessment. Results/Conclusion: DM-o 0.25%, DM-fo 0.25% and BM 0.05% showed similar vasoconstrictive potential, i.e., clear blanching. In fact, both DM preparations were proven to be non-inferior to BM 0.05%, while CP 0.05% was found a little less active. HC 1.0% and the DM vehicles showed no clear-cut vasoconstrictive effect. No adverse events related to the study medications were observed. Good topical bioavailability of both DM formulations was detected by chromametric measurement and clinical assessment. Copyright (C) 2008 S. Karger AG, Basel

Teleparallel Gravity and Dimensional Reductions of Noncommutative Gauge Theory

We study dimensional reductions of noncommutative electrodynamics on flat space which lead to gauge theories of gravitation. For a general class of such reductions, we show that the noncommutative gauge fields naturally yield a Weitzenbock geometry on spacetime and that the induced diffeomorphism invariant field theory can be made equivalent to a teleparallel formulation of gravity which macroscopically describes general relativity. The Planck length is determined in this setting by the Yang-Mills coupling constant and the noncommutativity scale. The effective field theory can also contain higher-curvature and non-local terms which are characteristic of string theory. Some applications to D-brane dynamics and generalizations to include the coupling of ordinary Yang-Mills theory to gravity are also described.Comment: 31 pages LaTeX; References adde

On species delimitation: Yet another lemur species or just genetic variation?

<p>Abstract</p> <p>Background</p> <p>Although most taxonomists agree that species are independently evolving metapopulation lineages that should be delimited with several kinds of data, the taxonomic practice in Malagasy primates (Lemuriformes) looks quite different. Several recently described lemur species are based solely on evidence of genetic distance and diagnostic characters of mitochondrial DNA sequences sampled from a few individuals per location. Here we explore the validity of this procedure for species delimitation in lemurs using published sequence data.</p> <p>Results</p> <p>We show that genetic distance estimates and <it>Population Aggregation Analysis </it>(PAA) are inappropriate for species delimitation in this group of primates. Intra- and interspecific genetic distances overlapped in 14 of 17 cases independent of the genetic marker used. A simulation of a fictive taxonomic study indicated that for the mitochondrial D-loop the minimum required number of individuals sampled per location is 10 in order to avoid false positives via PAA.</p> <p>Conclusions</p> <p>Genetic distances estimates and PAA alone should not be used for species delimitation in lemurs. Instead, several nuclear and sex-specific loci should be considered and combined with other data sets from morphology, ecology or behavior. Independent of the data source, sampling should be done in a way to ensure a quantitative comparison of intra- and interspecific variation of the taxa in question. The results of our study also indicate that several of the recently described lemur species should be reevaluated with additional data and that the number of good species among the currently known taxa is probably lower than currently assumed.</p

Energy metabolites as biomarkers in ischemic and dilated cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10(-6)). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets

Checkerboard Patterns, Interspecific Competition, and Extinction: Lessons from Distribution Patterns of Tarsiers (Tarsius) and Slow Lorises (Nycticebus) in Insular Southeast Asia

Tarsiers (Tarsius) and slow lorises (Nycticebus) are the only extant nocturnal primates occurring in Southeast Asia. Harcourt (1999) hypothesized that in insular Southeast Asia, slow lorises and tarsiers showed a checkerboard distribution on 12 small (<12,000 km2) islands, i.e., only one or the other occurs, and attributed this to extreme levels of competition between these 2 largely faunivorous primates. Further, he predicted slow lorises were able to persist on smaller islands than tarsiers. We re-evaluated these findings using an expanded dataset including 49 islands where tarsiers or slow lorises occur. Tarsiers and slow lorises live on islands of similar size (median size of ca. 300–900 km2), and both taxa inhabit an equal proportion of small, medium, and large islands. On small islands within their area of sympatry tarsiers occur on 1 island, slow lorises on 8, both genera on 3, and we can assume they have become extinct from 11 small islands since the Last Glacial Maximum. Sizes of islands where tarsiers or slow lorises have become extinct do not differ from islands where they are still extant. We show that slow lorises occur on more islands in insular Southeast Asia than perhaps previously assumed, but these islands are not smaller on average than islands where tarsiers occur. A checkerboard distribution between these taxa is not evident. More studies are needed at the macroecological level to assess the importance of biogeographic history in explaining their present-day distribution patterns

Cisgenesis and intragenesis as new strategies for crop improvement

Cisgenesis and intragenesis are emerging plant breeding technologies which offer great promise for future acceptance of genetically engineered crops. The techniques employ traditional genetic engineering methods but are confined to transferring of genes and genetic elements between sexually compatible species that can breed naturally. One of the main requirements is the absence of selectable marker genes (such as antibiotic resistance genes) in the genome. Hence the sensitive issues with regard to transfer of foreign genes and antibiotic resistance are overcome. It is a targeted technique involving specific locus; therefore, linkage drag that prolongs the time for crop improvement in traditional breeding does not occur. It has great potential for crop improvement using superior alleles that exist in the untapped germplasm or wild species. Cisgenic and intragenic plants may not face the same stringent regulatory assessment for field release as transgenic plants which is a clear added advantage that would save time. In this chapter, the concepts of cis/intragenesis and the prerequisites for the development of cis/intragenesis plants are elaborated. Strategies for marker gene removal after selection of transformants are discussed based on the few recent reports from various plant species

Atlas of the clinical genetics of human dilated cardiomyopathy

AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. CONCLUSIONS: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM

Market orientated design studies for SOFC based systems

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