Several million people are exposed to dioxin and dioxin-like compounds, primarily through food consumption. Skin lesions historically called "chloracne" are the most specific sign of abnormal dioxin exposure and classically used as a key marker in humans. We followed for 5 years a man who had been exposed to the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), at a single oral dose of 5 million-fold more than the accepted daily exposure in the general population. We adopted a molecular medicine approach, aimed at identifying appropriate therapy. Skin lesions, which progressively covered up to 40% of the body surface, were found to be hamartomas, which developed parallel to a complete and sustained involution of sebaceous glands, with concurrent transcriptomic alterations pointing to the inhibition of lipid metabolism and the involvement of bone morphogenetic proteins signaling. Hamartomas created a new compartment that concentrated TCDD up to 10-fold compared with serum and strongly expressed the TCDD-metabolizing enzyme cytochrome P450 1A1, thus representing a potentially significant source of enzymatic activity, which may add to the xenobiotic metabolism potential of the classical organs such as the liver. This historical case provides a unique set of data on the human tissue response to dioxin for the identification of new markers of exposure in human populations. The herein discovered adaptive cutaneous response to TCDD also points to the potential role of the skin in the metabolism of food xenobiotics.
The purpose of the paper is to give the theoretical basis for the design and optimization of X-UV interference mirrors. To achieve this original results are presented and the « state of the art » methods are reviewed. A new formulation of the Bragg conditions is obtained on the basis of the « Hill method » to solve the wave propagation equation in a periodically stratified medium. A large part of the paper is devoted to matricial formalism. The major role played by invariant quantities is emphasized. Recursive procedures to compute the reflectance are summarized. The problems of imperfections are also considered. Concerning the thickness errors, statistical universes are defined to give a coherent treatment of their effects. The matricial formalism is adopted to treat the influence of the interfacial roughness using the homogeneous transition layer model. Finally the perspective of a distributed X-UV amplifier in a periodic multilayered structure is proposed as an alternative to the Fabry-Perot resonator
The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,440 suspected HBOC families from 22 labs from 13 countries from several continents. Whereas the c.156_157insAluBRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all having in common the fact that they are relatively recent immigrants of Portuguese origin in those countries. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation has occurred 558±215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript with exon 3 skipping in c.156_157insAlu BRCA2 mutation carriers and in controls, indicating that disruption of alternative transcript ratios is the mechanism causing hereditary breast/ovarian cancer associated with this BRCA2 rearrangement. We further show that the cumulative incidence of breast cancer in c.156_157insAlu BRCA2 mutation carriers does not differ from that of other BRCA2 and BRCA1 pathogenic mutations, further strengthening its role as the major contributor to hereditary predisposition to breast cancer in Portugal. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement, ideally prior to screening of the entire coding regions of BRCA1 and BRCA2.3
2014 Les performances des multicouches dans le domaine X-UV sont tributaires des défauts structurels et géométriques des matériaux déposés. Ces défauts sont difficiles à différencier par l'analyse d'un seul pic de Bragg tel qu'observé en X mous. Dès lors, la prédiction des performances pour d'autres longueurs d'onde, devient délicate. Nous montrons comment la réflectométrie de rayons X rasants (Cu K03B11) permet de déterminer à la fois les rugosités interfaciales et les écarts d'épaisseur, ainsi que leur évolution au sein de l'empilement. Trois multicouches (W/C), de périodes comprises entre 3 et 6 nm et comportant de 20 à 40 couches élémentaires, sont analysées à titre d'exemples. Abstract. 2014 The performance of multilayers at the X-UV wavelengths depends upon the structural and geometrical imperfections of the deposited materials. These two respective contributions are not easily separated when only one Bragg peak is recorded, as is usually the case in the X-UV range, so a prediction of the performance at other wavelengths appears rather doubtful. We show how grazing incidence X-ray reflectometry (using Cu K03B11 radiation) allows the precise evaluation of both interfacial roughnesses and thickness errors, as well as their variations through the stacks. As examples, we analyse three (W/C) multilayers with periods between 3 to 6 nm and up to 40 layers.
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