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This paper introduces and applies a structured phantom with target objects for the comparison of detection performance of digital breast tomosynthesis (DBT) against full field digital mammography (FFDM). The phantom consists of a 48 mm thick breast-shaped polymethyl methacrylate (PMMA) container filled with water and PMMA spheres of different diameters. Three-dimensionally (3D) printed spiculated masses (diameter range: 3.8-9.7 mm) and non-spiculated masses (1.6-6.2 mm) along with microcalcifications (90-250 µm) were inserted as targets. Reproducibility of the phantom application was studied on a single system using 30 acquisitions. Next, the phantom was evaluated on five different combined FFDM & DBT systems and target detection was compared for FFDM and DBT modes. Ten phantom images in both FFDM and DBT modes were acquired on these 5 systems using automatic exposure control (AEC). Five readers evaluated target detectability. Images were read with the four-alternative forced-choice (4-AFC) paradigm, with always one segment including a target and 3 normal background segments. The percentage of correct responses (PC) was assessed based on 10 trials of each reader for each object type, size and modality. Additionally, detection threshold diameters at 62.5 PC were assessed via non-linear regression fitting of the psychometric curve. The reproducibility study showed no significant differences in PC values. Evaluation of target detection in FFDM showed that microcalcification detection thresholds ranged between 110 and 118 µm and were similar compared to the detection in DBT (range of 106-158 µm). In DBT, detection of both mass types increased significantly (p=0.0001 and p=0.0002 for non-spiculated and spiculated masses respectively) compared to FFDM, achieving almost 100% detection for all spiculated mass diameters. In conclusion, a structured phantom with inserted targets was able to show evidence for detectability differences between FFDM and DBT modes for five commercial systems. This phantom has potential for application in task-based assessment at acceptance and commissioning testing of DBT systems.

Matrix metalloproteinases (MMPs) are a large family of proteases involved in many cell-matrix and cell-cell signalling processes through activation, inactivation or release of extracellular matrix (ECM) and non-ECM molecules, such as growth factors and receptors. Uncontrolled MMP activities underlie the pathophysiology of many disorders. Also matrix metalloproteinase-3 (MMP-3) or stromelysin-1 contributes to several pathologies, such as cancer, asthma and rheumatoid arthritis, and has also been associated with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and multiple sclerosis. However, based on defined MMP spatiotemporal expression patterns, the identification of novel candidate molecular targets and in vitro and in vivo studies, a beneficial role for MMPs in CNS physiology and recovery is emerging. The main purpose of this review is to shed light on the recently identified roles of MMP-3 in normal brain development and in plasticity and regeneration after CNS injury and disease. As such, MMP-3 is correlated with neuronal migration and neurite outgrowth and guidance in the developing CNS and contributes to synaptic plasticity and learning in the adult CNS. Moreover, a strict spatiotemporal MMP-3 up-regulation in the injured or diseased CNS might support remyelination and neuroprotection, as well as genesis and migration of stem cells in the damaged brain. Keywords: central nervous system, development, matrix metalloproteinase-3, plasticity, regeneration, repair. Matrix metalloproteinases: an overviewMatrix metalloproteinases (MMPs) are proteolytic enzymes that remodel the pericellular environment by degrading all protein constituents of the extracellular matrix (ECM). Besides, they also regulate many cell signalling pathways and homeostatic systems by cleavage and release of various guidance and adhesion molecules, receptors, growth factors, cytokines, etc., through either activation or inactivation. The MMP family, a subgroup of the metzincins, constitutes more than 20 mammalian members, which are all Zn 2+ -dependent endopeptidases. Based on their substrate specificity and domain organization, MMPs are classified into collagenases, gelatinases, stromelysins, membrane-type MMPs, matrilysins and 'other MMPs' (Nagase et al. 2006).MMP activities are kept under tight control. First of all, MMP expression can be regulated at the transcriptional level by growth factors, cytokines, chemokines, hormones, epigenetic processes and cell-cell/cell-ECM interactions. Membrane-trafficking and subsequent release of MMPs at the cell surface can be regulated by SNARE proteins (Kean et al. 2009). MMPs are synthesized as proenzymes with a 'cysteine switch', the disruption of the interaction between the cysteine residue in the propeptide and the Zn 2+ ion in the catalytic site, as a pre-requisite for activation. This disruption can be achieved by organomercurial compounds, heavy metals, denaturating agents or oxidants, as well as through removal of the propeptide by proteases (Van Wart and Birk...

We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity.