An automatic deep learning approach for coronary artery calcium segmentation

Coronary artery calcium (CAC) is a significant marker of atherosclerosis and cardiovascular events. In this work we present a system for the automatic quantification of calcium score in ECG-triggered non-contrast enhanced cardiac computed tomography (CT) images. The proposed system uses a supervised deep learning algorithm, i.e. convolutional neural network (CNN) for the segmentation and classification of candidate lesions as coronary or not, previously extracted in the region of the heart using a cardiac atlas. We trained our network with 45 CT volumes; 18 volumes were used to validate the model and 56 to test it. Individual lesions were detected with a sensitivity of 91.24%, a specificity of 95.37% and a positive predicted value (PPV) of 90.5%; comparing calcium score obtained by the system and calcium score manually evaluated by an expert operator, a Pearson coefficient of 0.983 was obtained. A high agreement (Cohen's k = 0.879) between manual and automatic risk prediction was also observed. These results demonstrated that convolutional neural networks can be effectively applied for the automatic segmentation and classification of coronary calcifications

The VITROVAC Cavity for the TERA/PIMMS Medical Synchrotron

A proton and light-ion medical synchrotron is characterised by a large frequency swing for the RF between the injection and the top energy. For this purpose, a VITROVAC®-loaded RF cavity has been developed for the Proton-Ion Medical Machine Study (PIMMS) at CERN, and for TERA, the Italian project of a proton and light-ion synchrotron for cancer therapy, based on the PIMMS study. The main features are a large frequency swing, particularly extended to the low frequency range, a very large relative permeability and a low Q factor. The total power needed is less than 100 kW, while a very small bias power is required for the frequency tuning. The main mechanical characteristics are compactness (less than 1.5 m), and simplicity of construction. As a result, the requirements of the medical synchrotron are comfortably satisfied, namely: 0.4 to 3 MHz swing, 3 kV peak voltage at a repetition rate of less than 1 s

Somatostatin binding capacity, guanylate cyclase and tyrosine phosphatase activities during pancreatic proliferation in the rat induced by gastrectomy

Gastrectomy increased pancreatic growth and this effect was associated with an increase in the number of somatostatin-14 (SS) receptors (146% of control) without altering their affinity. SS increased guanylate cyclase activity twofold in pancreatic acinar membranes from gastrectomized rats. The gastrectomy decreased pancreatic SS-like immunoreactivity (SS-LI) content (55% of control levels) and tyrosine phosphatase activity (74% of control levels). Administration of proglumide (20 mg/kg, IF), a gastrin/cholecystokinin (CCK) receptor antagonist, suppressed the inhibitory effect of gastrectomy on basal tyrosine phosphatase activity and SS-LI content, which returned to control levels. Furthermore, proglumide suppressed the increase of the number of SS receptors and of SS-stimulated guanylate cyclase activity induced by gastrectomy. All this suggests that pancreatic acinar cell growth is associated with upregulation of SS receptors, which could represent a mechanism promoted by the cell to negatively regulate the mitogenic activity of pancreatic growth factors such as CCK. In addition, the results also suggest that the negative regulation of tyrosine phosphatase activity may be important in the events involved in the pancreatic hyperplasia observed after gastrectomy

Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2α overexpression

International audienceBACKGROUND: Activator protein-2alpha (AP-2alpha) is a transcription factor that belongs to the family of AP-2 proteins that have essential roles in tumorigenesis. Indeed, AP-2alpha is considered as a tumour-suppressor gene in different tissues such as colonic, prostatic or breast epithelial cells. Moreover, AP-2alpha also participates in the control of colon and breast cancer cells sensitivity towards chemotherapeutic drugs. Despite its potential interest, very few data are available regarding the roles of AP-2alpha in pancreatic cancer. METHODS: We have developed a stable pancreatic CAPAN-1 cell line overexpressing AP-2alpha. Consequences of overexpression were studied in terms of in vivo cell growth, gene expression, migration capacity and chemosensitivity. RESULTS: In vivo tumour growth of CAPAN-1 cells overexpressing AP-2alpha was significantly decreased by comparison to control cells. An altered expression pattern of cell cycle-controlling factors (CDK-4, CDK-6, cyclin-G1, p27(kip1) and p57(kip2)) was observed in AP-2alpha-overexpressing clones by microarrays and western blot analysis. Promoter activity and ChIP analysis indicated that AP-2alpha induces p27(kip1) protein levels by direct binding to and transactivation of its promoter. Moreover, AP-2alpha overexpression increased the chemosensitivity of CAPAN-1 cells to low doses of gemcitabine and reduced their in vitro migration capacity. CONCLUSION: Our data suggested that AP-2alpha overexpression could be exploited to decrease in vivo tumour growth of pancreatic cancer cells and to increase their sensitivity to gemcitabine

Topoisomerase II alpha and TLE3 as predictive markers of response to anthracycline and taxane-containing regimens for neoadjuvant chemotherapy in breast cancer.

PURPOSE: Anthracyclines and taxanes are considered the standard for neoadjuvant chemotherapy of breast cancer, although they are often associated with serious side effects and wide variability of individual response. In this study, we analyzed the value of topoisomerase II alpha (TOP2A) and transducin-like enhancer of split 3 (TLE3) as predictive markers of response to therapy with anthracyclines and taxanes. MATERIALS AND METHODS: TOP2A and TLE3 protein expressions were evaluated using immunohistochemistry on 28 samples, obtained by core needle biopsy in patients with locally advanced breast carcinoma, subsequently subjected to epirubicin- and paclitaxel-based neoadjuvant chemotherapy. The immunohistochemical staining was correlated with the clinical response measured by the tumor size reduction evaluated by breast magnetic resonance imaging, prior and after chemotherapy, and by pathologic evaluation of the surgical specimen. RESULTS: Neoadjuvant chemotherapy achieved a size reduction in 26/28 tumors (92.9%), with an average percentage decrease of 45.6%. A downstaging was achieved in 71.4% of the cases of locally advanced carcinoma. TOP2A positivity was correlated with a greater reduction in tumor diameter (P=0.06); negative staining for TLE3 was predictive of a better response to neoadjuvant chemotherapy (P=0.07). A higher reduction in tumor diameter (P=0.03) was also found for tumors that were concurrently TLE3-negative and TOP2A-positive. CONCLUSION: TOP2A and TLE3 showed a correlation with response to neoadjuvant chemotherapy. While TOP2A is a well-known marker of response to anthracyclines-based chemotherapy, TLE3 is a new putative predictor of response to taxanes. Data from the current study suggest that TOP2A and TLE3 warrant further investigation in a larger series as predictors of response to neoadjuvant chemotherapy for locally advanced breast carcinoma

AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages

Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation

Spatially resolved X-ray excited optical luminescence

Spatially resolved luminescence distributions in semiconductor heterostructures were investigated by core level excitation using hard X-ray (sub-) microbeams. Compact and mobile XEOL instruments have been developed and well adapted on the hard X-ray beamline ID22 of the European Synchrotron Radiation Facility for different wavelength collection ranges: UV-VIS and NIR. Linked by multimode optical fibers, their special designs provide precise scanning microscopy and allow easy access for multiple detection modes. Based on the hard X-ray microprobe station of ID22, details of the equipments, spectral data and representative examples are briefly described. Data collections from InAs and InGaN quantum heterostructures support the excellent performance of the optical devices. © 2011 Elsevier B.V. All rights reserved.This work was partially supported by the NANOWIRING Marie Curie ITN (EU project No. PITN-GA-2010-265073).Peer Reviewe