Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization

Comparative genomic in situ hybridization (CGH) provides a new possibility for searching genomes for imbalanced genetic material. Labeled genomic test DNA, prepared from clinical or tumor specimens, is mixed with differently labeled control DNA prepared from cells with normal chromosome complements. The mixed probe is used for chromosomal in situ suppression (CISS) hybridization to normal metaphase spreads (CGH-metaphase spreads). Hybridized test and control DNA sequences are detected via different fluorochromes, e.g., fluorescein isothiocyanate (FITC) and tetraethylrhodamine isothiocyanate (TRITC). The ratios of FITC/TRITC fluorescence intensities for each chromosome or chromosome segment should then reflect its relative copy number in the test genome compared with the control genome, e.g., 0.5 for monosomies, 1 for disomies, 1.5 for trisomies, etc. Initially, model experiments were designed to test the accuracy of fluorescence ratio measurements on single chromosomes. DNAs from up to five human chromosome-specific plasmid libraries were labeled with biotin and digoxigenin in different hapten proportions. Probe mixtures were used for CISS hybridization to normal human metaphase spreads and detected with FITC and TRITC. An epifluorescence microscope equipped with a cooled charge coupled device (CCD) camera was used for image acquisition. Procedures for fluorescence ratio measurements were developed on the basis of commercial image analysis software. For hapten ratios 4/1, 1/1 and 1/4, fluorescence ratio values measured for individual chromosomes could be used as a single reliable parameter for chromosome identification. Our findings indicate (1) a tight correlation of fluorescence ratio values with hapten ratios, and (2) the potential of fluorescence ratio measurements for multiple color chromosome painting. Subsequently, genomic test DNAs, prepared from a patient with Down syndrome, from blood of a patient with Tcell prolymphocytic leukemia, and from cultured cells of a renal papillary carcinoma cell line, were applied in CGH experiments. As expected, significant differences in the fluorescence ratios could be measured for chromosome types present in different copy numbers in these test genomes, including a trisomy of chromosome 21, the smallest autosome of the human complement. In addition, chromosome material involved in partial gains and losses of the different tumors could be mapped to their normal chromosome counterparts in CGH-metaphase spreads. An alternative and simpler evaluation procedure based on visual inspection of CCD images of CGH-metaphase spreads also yielded consistent results from several independent observers. Pitfalls, methodological improvements, and potential applications of CGH analyses are discussed

Accurate,robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.Junta de Andalucía (FISEVI, reference project CTS 2482)European Regional Development Fund (FEDER

Drip Paintings and Fractal Analysis

It has been claimed [1-6] that fractal analysis can be applied to unambiguously characterize works of art such as the drip paintings of Jackson Pollock. This academic issue has become of more general interest following the recent discovery of a cache of disputed Pollock paintings. We definitively demonstrate here, by analyzing paintings by Pollock and others, that fractal criteria provide no information about artistic authenticity. This work has also led to two new results in fractal analysis of more general scientific significance. First, the composite of two fractals is not generally scale invariant and exhibits complex multifractal scaling in the small distance asymptotic limit. Second the statistics of box-counting and related staircases provide a new way to characterize geometry and distinguish fractals from Euclidean objects

A perspective illusion or a view from the clouds? Detail of an Early 16th-Century miniature painting produced in Tabriz (Iran)

A Persian painting (910H/1505) from a manuscript of Nizami’s Khamsa preserved in the Keir Collection portrays the mi'raj of Muḥammad among many angels in a blue sky; the Ka'ba is depicted in the lower foreground while the desert surrounds almost the entire image. In the upper part of the sky ten half-bust angels look out from an oculus among the clouds. This image clearly recalls coeval European painting, and in particular the oculus painted by Andrea Mantegna on the vault of the Camera Picta or “Camera degli Sposi” in the Palazzo Ducale in Mantua. Nevertheless, the unusual and contextual introduction of a parallel and inverse perspective enables the oculus of the Keir Collection miniature to take on an appearance and consequent meaning different from the Western ones

Ulysses in the bathroom

I make paintings where imaginary characters function as possible cyphers made in reaction to my life experience. I’ve provided in this paper a concise introduction to the circumstances that motivated me to become an artist and how they continue to shape my work today. I have described to the degree possible several key features of my work, including the cultural and disciplinary influences in my work, my process, and what I understand to be the implications for my work.Studio Ar