Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging

Recently CMOS Active Pixels Sensors (APSs) have become a valuable alternative to amorphous Silicon and Selenium Flat Panel Imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ≤ 1.9%. The uniformity of the image quality performance has been further investigated in a typical X-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practise. Finally, in order to compare the detection capability of this novel APS with the currently used technology (i.e. FPIs), theoretical evaluation of the Detection Quantum Efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this detector compared to FPIs. Optical characterization, X-ray contrast measurements and theoretical DQE evaluation suggest that a trade off can be found between the need of a large imaging area and the requirement of a uniform imaging performance, making the DynAMITe large area CMOS APS suitable for a range of bio-medical applications

RIEDWEG (Eugène), La Libération de l’Alsace, Septembre 1944-Mars 1945

Pour le soixante-dixième anniversaire, les éditions Tallandier ont confié l’ouvrage sur la Libération de l’Alsace à un spécialiste, c’est heureux. Son récit d’ensemble est réparti en huit chapitres, deux consacrés aux opérations de la 7e Armée US face au groupe d’armées allemandes G, les suivants aux batailles de novembre, de décembre, à la réaction allemande de décembre-janvier 1944-1945, enfin à la victoire. Par rapport à ses prédécesseurs, ou devrait-on dire « son prédécesseur », F. L’Huil..

Combinatorial single-cell profiling of major chromatin types with MAbID

Gene expression programs result from the collective activity of numerous regulatory factors. Studying their cooperative mode of action is imperative to understand gene regulation, but simultaneously measuring these factors within one sample has been challenging. Here we introduce Multiplexing Antibodies by barcode Identification (MAbID), a method for combinatorial genomic profiling of histone modifications and chromatin-binding proteins. MAbID employs antibody–DNA conjugates to integrate barcodes at the genomic location of the epitope, enabling combined incubation of multiple antibodies to reveal the distributions of many epigenetic markers simultaneously. We used MAbID to profile major chromatin types and multiplexed measurements without loss of individual data quality. Moreover, we obtained joint measurements of six epitopes in single cells of mouse bone marrow and during mouse in vitro differentiation, capturing associated changes in multifactorial chromatin states. Thus, MAbID holds the potential to gain unique insights into the interplay between gene regulatory mechanisms, especially for low-input samples and in single cells

The retinoblastoma-related gene regulates stem cell maintenance in Arabidopsis roots

SummaryThe maintenance of stem cells in defined locations is crucial for all multicellular organisms. Although intrinsic factors and signals for stem cell fate have been identified in several species, it has remained unclear how these connect to the ability to reenter the cell cycle that is one of the defining properties of stem cells. We show that local reduction of expression of the RETINOBLASTOMA-RELATED (RBR) gene in Arabidopsis roots increases the amount of stem cells without affecting cell cycle duration in mitotically active cells. Conversely, induced RBR overexpression dissipates stem cells prior to arresting other mitotic cells. Overexpression of D cyclins, KIP-related proteins, and E2F factors also affects root stem cell pool size, and genetic interactions suggest that these factors function in a canonical RBR pathway to regulate somatic stem cells. Expression analysis and genetic interactions position RBR-mediated regulation of the stem cell state downstream of the patterning gene SCARECROW

Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism

The histone methyltransferase Dot1 is conserved from yeast to human and methylates lysine 79 of histone H3 (H3K79) on the core of the nucleosome. H3K79 methylation by Dot1 affects gene expression and the response to DNA damage, and is enhanced by monoubiquitination of the C-terminus of histone H2B (H2Bub1). To gain more insight into the functions of Dot1, we generated genetic interaction maps of increased-dosage alleles of DOT1. We identified a functional relationship between increased Dot1 dosage and loss of the DUB module of the SAGA co-activator complex, which deubiquitinates H2Bub1 and thereby negatively regulates H3K79 methylation. Increased Dot1 dosage was found to promote H2Bub1 in a dose-dependent manner and this was exacerbated by the loss of SAGA-DUB activity, which also caused a negative genetic interaction. The stimulatory effect on H2B ubiquitination was mediated by the N-terminus of Dot1, independent of methyltransferase activity. Our findings show that Dot1 and H2Bub1 are subject to bi-directional crosstalk and that Dot1 possesses chromatin regulatory functions that are independent of its methyltransferase activity