Revealing Hidden Potentials of the q-Space Signal in Breast Cancer

Mammography screening for early detection of breast lesions currently suffers from high amounts of false positive findings, which result in unnecessary invasive biopsies. Diffusion-weighted MR images (DWI) can help to reduce many of these false-positive findings prior to biopsy. Current approaches estimate tissue properties by means of quantitative parameters taken from generative, biophysical models fit to the q-space encoded signal under certain assumptions regarding noise and spatial homogeneity. This process is prone to fitting instability and partial information loss due to model simplicity. We reveal unexplored potentials of the signal by integrating all data processing components into a convolutional neural network (CNN) architecture that is designed to propagate clinical target information down to the raw input images. This approach enables simultaneous and target-specific optimization of image normalization, signal exploitation, global representation learning and classification. Using a multicentric data set of 222 patients, we demonstrate that our approach significantly improves clinical decision making with respect to the current state of the art.Comment: Accepted conference paper at MICCAI 201

Aging (Albany NY)

The combination of functional genomics with next generation sequencing facilitates new experimental strategies for addressing complex biological phenomena. Here, we report the identification of a gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1p) via whole-genome re-sequencing of a dominantSaccharomyces cerevisiae mutant obtained by chemical mutagenesis. Yeast strain K6001, a screening system for lifespan phenotypes, was treated with ethyl methanesulfonate (EMS). We isolated an oxidative stress-resistant mutant (B7) which transmitted this phenotype in a background-independent, monogenic and dominant way. By massive parallel pyrosequencing, we generated an 38.8 fold whole-genome coverage of the strains, which differed in 12,482 positions from the reference (S288c) genome. Via a subtraction strategy, we could narrow this number to 13 total and 4 missense nucleotide variations that were specific for the mutant. Via expression in wild type backgrounds, we show that one of these mutations, exchanging a residue in the peroxiredoxin Tsa1p, was responsible for the mutant phenotype causing background-independent dominant oxidative stress-resistance. These effects were not provoked by altered Tsa1p levels, nor could they be simulated by deletion, haploinsufficiency or over-expression of the wild-type allele. Furthermore, via both a mother-enrichment technique and a micromanipulation assay, we found a robust premature aging phenotype of this oxidant-resistant strain. Thus, TSA1-B7 encodes for a novel dominant form of peroxiredoxin, and establishes a new connection between oxidative stress and aging. In addition, this study shows that the re-sequencing of entire genomes is becoming a promising alternative for the identification of functional alleles in approaches of classic molecular genetics

PANIC: the new panoramic NIR camera for Calar Alto

PANIC is a wide-field NIR camera, which is currently under development for the Calar Alto observatory (CAHA) in Spain. It uses a mosaic of four Hawaii-2RG detectors and covers the spectral range from 0.8-2.5 micron(z to K-band). The field-of-view is 30x30 arcmin. This instrument can be used at the 2.2m telescope (0.45arcsec/pixel, 0.5x0.5 degree FOV) and at the 3.5m telescope (0.23arcsec/pixel, 0.25x0.25 degree FOV). The operating temperature is about 77K, achieved by liquid Nitrogen cooling. The cryogenic optics has three flat folding mirrors with diameters up to 282 mm and nine lenses with diameters between 130 mm and 255 mm. A compact filter unit can carry up to 19 filters distributed over four filter wheels. Narrow band (1%) filters can be used. The instrument has a diameter of 1.1 m and it is about 1 m long. The weight limit of 400 kg at the 2.2m telescope requires a light-weight cryostat design. The aluminium vacuum vessel and radiation shield have wall thicknesses of only 6 mm and 3 mm respectively.Comment: This paper has been presented in the SPIE of Astronomical Telescopes and Instrumentation 2008 in Marseille (France

The Turkey Ig-like receptor family: identification, expression and function.

The chicken leukocyte receptor complex located on microchromosome 31 encodes the chicken Ig-like receptors (CHIR), a vastly expanded gene family which can be further divided into three subgroups: activating CHIR-A, bifunctional CHIR-AB and inhibitory CHIR-B. Here, we investigated the presence of CHIR homologues in other bird species. The available genome databases of turkey, duck and zebra finch were screened with different strategies including BLAST searches employing various CHIR sequences, and keyword searches. We could not identify CHIR homologues in the distantly related zebra finch and duck, however, several partial and complete sequences of CHIR homologues were identified on chromosome 3 of the turkey genome. They were designated as turkey Ig-like receptors (TILR). Using cDNA derived from turkey blood and spleen RNA, six full length TILR could be amplified and further divided according to the typical sequence features into one activating TILR-A, one inhibitory TILR-B and four bifunctional TILR-AB. Since the TILR-AB sequences all displayed the critical residues shown to be involved in binding to IgY, we next confirmed the IgY binding using a soluble TILR-AB1-huIg fusion protein. This fusion protein reacted with IgY derived from various gallinaceous birds, but not with IgY from other bird species. Finally, we tested various mab directed against CHIR for their crossreactivity with either turkey or duck leukocytes. Whereas no staining was detectable with duck cells, the CHIR-AB1 specific mab 8D12 and the CHIR-A2 specific mab 13E2 both reacted with a leukocyte subpopulation that was further identified as thrombocytes by double immunofluorescence employing B-cell, T-cell and thrombocyte specific reagents. In summary, although the turkey harbors similar LRC genes as the chicken, their distribution seems to be distinct with predominance on thrombocytes rather than lymphocytes

GRAVITY: getting to the event horizon of Sgr A*

We present the second-generation VLTI instrument GRAVITY, which currently is in the preliminary design phase. GRAVITY is specifically designed to observe highly relativistic motions of matter close to the event horizon of Sgr A*, the massive black hole at center of the Milky Way. We have identified the key design features needed to achieve this goal and present the resulting instrument concept. It includes an integrated optics, 4-telescope, dual feed beam combiner operated in a cryogenic vessel; near infrared wavefront sensing adaptive optics; fringe tracking on secondary sources within the field of view of the VLTI and a novel metrology concept. Simulations show that the planned design matches the scientific needs; in particular that 10 microarcsecond astrometry is feasible for a source with a magnitude of K=15 like Sgr A*, given the availability of suitable phase reference sources.Comment: 13 pages, 11 figures, to appear in the conference proceedings of SPIE Astronomical Instrumentation, 23-28 June 2008, Marseille, Franc

An Intermetallic CaFe6Ge6 Approach to Unprecedented Ca Fe O Electrocatalyst for Efficient Alkaline Oxygen Evolution Reaction

Based on the low cost and relatively high catalytic activity, considerable efforts have been devoted towards developing redox active transition metal TM oxygen electrocatalysts for the alkaline oxygen evolution reaction OER while the role of redox inactive alkaline earth metals has often been neglected in OER. Herein, for the first time, we developed a novel ternary intermetallic CaFe6Ge6 precatalyst, whose surface rapidly transforms into a porous ultrathin Ca amp; 8722;Fe amp; 8722;O heteroshell structure during alkaline OER through the oxidative leaching of surficial Ge. Benefiting from synergistic effects, this highly efficient OER active material with distinct Ca amp; 8722;Fe amp; 8722;O layers has a large electrochemical surface area and more exposed active Fe sites than a Ca free FeOx phase. Also, the presence of Ca in Ca amp; 8722;Fe amp; 8722;O is responsible for the enhanced transport and activation of hydroxyls and related OER reaction intermediate as unequivocally illustrated by a combination of quasi in situ Raman spectroscopy and various ex situ method

Methodological considerations on tract-based spatial statistics (TBSS)

Having gained a tremendous amount of popularity since its introduction in 2006, tract-based spatial statistics (TBSS) can now be considered as the standard approach for voxel-based analysis (VBA) of diffusion tensor imaging (DTI) data. Aiming to improve the sensitivity, objectivity, and interpretability of multi-subject DTI studies, TBSS includes a skeletonization step that alleviates residual image misalignment and obviates the need for data smoothing. Although TBSS represents an elegant and user-friendly framework that tackles numerous concerns existing in conventional VBA methods, it has limitations of its own, some of which have already been detailed in recent literature. In this work, we present general methodological considerations on TBSS and report on pitfalls that have not been described previously. In particular, we have identified specific assumptions of TBSS that may not be satisfied under typical conditions. Moreover, we demonstrate that the existence of such violations can severely affect the reliability of TBSS results. With TBSS being used increasingly, it is of paramount importance to acquaint TBSS users with these concerns, such that a well-informed decision can be made as to whether and how to pursue a TBSS analysis. Finally, in addition to raising awareness by providing our new insights, we provide constructive suggestions that could improve the validity and increase the impact of TBSS drastically

Black Hole Mass Estimates Based on CIV are Consistent with Those Based on the Balmer Lines

Using a sample of high-redshift lensed quasars from the CASTLES project with observed-frame ultraviolet or optical and near-infrared spectra, we have searched for possible biases between supermassive black hole (BH) mass estimates based on the CIV, Halpha and Hbeta broad emission lines. Our sample is based upon that of Greene, Peng & Ludwig, expanded with new near-IR spectroscopic observations, consistently analyzed high S/N optical spectra, and consistent continuum luminosity estimates at 5100A. We find that BH mass estimates based on the FWHM of CIV show a systematic offset with respect to those obtained from the line dispersion, sigma_l, of the same emission line, but not with those obtained from the FWHM of Halpha and Hbeta. The magnitude of the offset depends on the treatment of the HeII and FeII emission blended with CIV, but there is little scatter for any fixed measurement prescription. While we otherwise find no systematic offsets between CIV and Balmer line mass estimates, we do find that the residuals between them are strongly correlated with the ratio of the UV and optical continuum luminosities. Removing this dependency reduces the scatter between the UV- and optical-based BH mass estimates by a factor of approximately 2, from roughly 0.35 to 0.18 dex. The dispersion is smallest when comparing the CIV sigma_l mass estimate, after removing the offset from the FWHM estimates, and either Balmer line mass estimate. The correlation with the continuum slope is likely due to a combination of reddening, host contamination and object-dependent SED shapes. When we add additional heterogeneous measurements from the literature, the results are unchanged.Comment: Accepted for publication in The Astrophysical Journal. 37 text pages + 8 tables + 23 figures. Updated with comments by the referee and with a expanded discussion on literature data including new observation

An overview of the mid-infrared spectro-interferometer MATISSE: science, concept, and current status

MATISSE is the second-generation mid-infrared spectrograph and imager for the Very Large Telescope Interferometer (VLTI) at Paranal. This new interferometric instrument will allow significant advances by opening new avenues in various fundamental research fields: studying the planet-forming region of disks around young stellar objects, understanding the surface structures and mass loss phenomena affecting evolved stars, and probing the environments of black holes in active galactic nuclei. As a first breakthrough, MATISSE will enlarge the spectral domain of current optical interferometers by offering the L and M bands in addition to the N band. This will open a wide wavelength domain, ranging from 2.8 to 13 um, exploring angular scales as small as 3 mas (L band) / 10 mas (N band). As a second breakthrough, MATISSE will allow mid-infrared imaging - closure-phase aperture-synthesis imaging - with up to four Unit Telescopes (UT) or Auxiliary Telescopes (AT) of the VLTI. Moreover, MATISSE will offer a spectral resolution range from R ~ 30 to R ~ 5000. Here, we present one of the main science objectives, the study of protoplanetary disks, that has driven the instrument design and motivated several VLTI upgrades (GRA4MAT and NAOMI). We introduce the physical concept of MATISSE including a description of the signal on the detectors and an evaluation of the expected performances. We also discuss the current status of the MATISSE instrument, which is entering its testing phase, and the foreseen schedule for the next two years that will lead to the first light at Paranal.Comment: SPIE Astronomical Telescopes and Instrumentation conference, June 2016, 11 pages, 6 Figure