A roof plate-dependent enhancer controls the expression of Homeodomain only protein in the developing cerebral cortex

AbstractThe smallest known homeodomain protein, Homeodomain only protein (Hop), was identified and described here as a temporally and spatially restricted gene in the neurogenic regions of the developing murine CNS including the cerebral cortex. Furthermore, an evolutionarily conserved 418 base pair upstream cis-regulatory DNA sequence was found to confine the Hop expression to the CNS of transgenic mice, but not to the heart which is the second major Hop expressing organ Chen, F., Kook, H., Milewski, R., Gitler, A.D., Lu, M.M., Li, J., Nazarian, R., Schnepp, R., Jen, K., Biben, C., Runke, G., Mackay, J.P., Novotny, J., Schwartz, R.J., Harvey, R.P., Mullins, M.C., Epstein, J.A., 2002. Hop is an unusual homeobox gene that modulates cardiac development. Cell 110, 713–723; Shin, C.H., Liu, Z.P., Passier, R., Zhang, C.L., Wang, D.Z., Harris, T.M., Yamagishi, H., Richardson, J.A., Childs, G., Olson, E.N., 2002. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell 110, 725–735. The forebrain enhancer activity was successfully reproduced in vitro utilizing a combination of the electroporation and the organotypic brain culture method. Using this approach, the minimal requirement for the forebrain-specific enhancer sequence was delineated down to 200 base pairs. We further demonstrate that the Hop enhancer activity is inducible ectopically in a transgenic tissue by wild-type roof plate transplantation in vitro. Thus Hop is regulated in the forebrain by a so far unidentified paracrine signaling factor from the roof plate. Furthermore, the identified enhancer sequence provides an important tool for the targeted expression of transgenes in the medial cortex and the cortical hem

Industrial experiences with resource management under software randomization in ARINC653 avionics environments

Injecting randomization in different layers of the computing platform has been shown beneficial for security, resilience to software bugs and timing analysis. In this paper, with focus on the latter, we show our experience regarding memory and timing resource management when software randomization techniques are applied to one of the most stringent industrial environments, ARINC653-based avionics. We describe the challenges in this task, we propose a set of solutions and present the results obtained for two commercial avionics applications, executed on COTS hardware and RTOS.The work leading to these results has been funded by the European Community’s Seventh Framework Programme (FP7/2007-2013) un- der the PROXIMA Project (grant agreement 611085). Moreover, it has been partially supported by the Spanish Ministry of Science and Innovation under grant TIN2015-65316-P and the HiPEAC Network of Excellence.Peer ReviewedPostprint (published version

S-antigen and rod-opsin immunoreactions in midline brain neoplasms of transgenic mice: Similarities to pineal cell tumors and certain medulloblastomas in man.

Transgenic mice expressing the large T-antigen of the simian virus 40 (SV 40) under the control of 1) the enhancer of Moloney murine sarcoma virus (MSV) and 2) the SV 40 promoter develop undifferentiated neuroectodermal tumors located in the midline of the dorsal brain surface, abnormalities in lens fiber differentiation and retinal dysplasia. In this study the brain neoplasms of six adult animals and the brain of one 11-day old mouse were examined by conventional histology and immunocytochemical demonstration of S-antigen, rod-opsin, neuron-specific enolase, neurofilaments (160 and 200 kDa) and glial fibrillary acidic protein. According to histologic criteria the neoplasms were characterized as "primitive" neuroectodermal tumors composed mainly of small cells with scanty and ill-defined cytoplasm. Neoplastic cells displaying immunoreactive S-antigen were found in five brain tumors; three of these tumors also contained a limited number of rod-opsin immunoreactive neoplastic cells. Some tumor cells had neurite-like processes containing immunoreactive neurofilament (200 kDa). No pathologic lesions were found in the brain of the 11-day old animal. Tumors in transgenic mice may resemble pineal cell tumors and a special subtype of medulloblastoma in man. These neoplasms contain S-antigen immunoreactive and also rod-opsin immunoreactive tumors cells in certain cases. The findings suggest that transgenic mice expressing the large T-antigen of SV 40 may become a valuable animal model for analysing the origin, histogenesis and development of primitive neuroectodermal tumors with photoreceptor-like features (pineal cell tumors and certain medulloblastomas)