A global Carleman estimate in a transmission wave equation and application to a one-measurement inverse problem

We consider a transmission wave equation in two embedded domains in $R^2$, where the speed is $a1 > 0$ in the inner domain and $a2 > 0$ in the outer domain. We prove a global Carleman inequality for this problem under the hypothesis that the inner domain is strictly convex and $a1 > a2$ . As a consequence of this inequality, uniqueness and Lip- schitz stability are obtained for the inverse problem of retrieving a stationary potential for the wave equation with Dirichlet data and discontinuous principal coefficient from a single time-dependent Neumann boundary measurement

5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells

YesMammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and enhancers at the multi-TAD EDC locus in skin epithelial cells are cell type-specific and involve extensive contacts within TADs as well as between different gene-rich TADs, forming the framework for lineage-specific transcription.This study was supported by the grants 5R01AR064580 and 1RO1AR071727 to VAB, TKS and AAS, as well as by the grants from MRC (MR/ M010015/1) and BBSRC (BB/K010050/1) to VAB

Aggressive bladder carcinoma in an HIV-positive man with tetraplegia and neurogenic bladder

Background/objective: Patients with neurogenic bladder secondary to spinal cord injury who are managed long term with an indwelling catheter are known to be at increased risk for transitional cell carcinoma of the bladder. Immunosuppression is a known risk factor for malignancies that often are more aggressive than those seen in normal populations. Method: Case report and discussion of management recommendations. Results: We summarize the case of a 44-year-old HIV-positive C5-C6 incomplete tetraplegic male (date of injury 1980), who was diagnosed with transitional cell carcinoma of the bladder and succumbed to disease within 6 months of diagnosis. The patient was a non-smoker who was never managed with an indwelling catheter. There has been no such case reported in the literature. Conclusions: HIV infection in the presence of a neurogenic bladder may carry an increased risk of aggressive bladder malignancy. More studies are warranted to determine whether routine annual screening with cystoscopy in all patients with HIV and neurogenic bladder is indicated

3D-FISH analysis of the spatial genome organization in skin cells in situ

NoSpatial genome organization in the cell nucleus plays a crucial role in the control of genome functions. Our knowledge about spatial genome organization is relying on the advances in gene imaging technologies and the biochemical approaches based on the spatial dependent ligation of the genomic regions. Fluorescent in situ hybridization using specific fluorescent DNA and RNA probes in cells and tissues with the spatially preserved nuclear and genome architecture (3D-FISH) provides a powerful tool for the further advancement of our knowledge about genome structure and functions. Here we describe the 3D-FISH protocols allowing for such an analysis in mammalian tissue in situ including in the skin. These protocols include DNA probe amplification and labeling; tissue fixation; preservation and preparation for hybridization; hybridization of the DNA probes with genomic DNA in the tissue; and post-hybridization tissue sample processing