Development of fluorocarbon evaporative cooling recirculators and controls for the ATLAS inner silicon tracker

We report on the development of evaporative fluorocarbon cooling recirculators and their control systems for the ATLAS inner silicon tracker. We have developed a prototype circulator using a dry, hermetic compressor with C/sub 3/F/sup 8/ refrigerant, and have prototyped the remote-control analog pneumatic links for the regulation of coolant mass flows and operating temperatures that will be necessary in the magnetic field and radiation environment around ATLAS. pressure and flow measurement and control use 150+ channels of standard ATLAS LMB ("Local Monitor Board") DAQ and DACs on a multi-drop CAN network administered through a BridgeVIEW user interface. A hardwired thermal interlock system has been developed to cut power to individual silicon modules should their temperatures exceed safe values. Highly satisfactory performance of the circulator under steady state, partial-load and transient conditions was seen, with proportional fluid flow tuned to varying circuit power. Future developments, including a 6 kW demonstrator with ~25 cooling circuits, are outlined

Comparative analysis of module-based versus direct methods for reverse-engineering transcriptional regulatory networks

We have compared a recently developed module-based algorithm LeMoNe for reverse-engineering transcriptional regulatory networks to a mutual information based direct algorithm CLR, using benchmark expression data and databases of known transcriptional regulatory interactions for Escherichia coli and Saccharomyces cerevisiae. A global comparison using recall versus precision curves hides the topologically distinct nature of the inferred networks and is not informative about the specific subtasks for which each method is most suited. Analysis of the degree distributions and a regulator specific comparison show that CLR is 'regulator-centric', making true predictions for a higher number of regulators, while LeMoNe is 'target-centric', recovering a higher number of known targets for fewer regulators, with limited overlap in the predicted interactions between both methods. Detailed biological examples in E. coli and S. cerevisiae are used to illustrate these differences and to prove that each method is able to infer parts of the network where the other fails. Biological validation of the inferred networks cautions against over-interpreting recall and precision values computed using incomplete reference networks.Comment: 13 pages, 1 table, 6 figures + 6 pages supplementary information (1 table, 5 figures

Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius

We report the discovery of very shallow (DF/F = 3.4 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as due to the presence of a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We use CoRoT color information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy and preliminary results from Radial Velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star are derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. We examine carefully all conceivable cases of false positives, and all tests performed support the planetary hypothesis. Blends with separation larger than 0.40 arcsec or triple systems are almost excluded with a 8 10-4 risk left. We conclude that, as far as we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 +/- 3 10-5 day and a radius of Rp = 1.68 +/- 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. CoRoT-7b is very likely the first Super-Earth with a measured radius.Comment: Accepted in Astronomy and Astrophysics; typos and language corrections; version sent to the printer w few upgrade

Functional brain defects in a mouse model of a chromosomal t(1;11) translocation that disrupts DISC1 and confers increased risk of psychiatric illness

A balanced t(1;11) translocation that directly disrupts DISC1 is linked to schizophrenia and affective disorders. We previously showed that a mutant mouse, named Der1, recapitulates the effect of the translocation upon DISC1 expression. Here, RNAseq analysis of Der1 mouse brain tissue found enrichment for dysregulation of the same genes and molecular pathways as in neuron cultures generated previously from human t(1;11) translocation carriers via the induced pluripotent stem cell route. DISC1 disruption therefore apparently accounts for a substantial proportion of the effects of the t(1;11) translocation. RNAseq and pathway analysis of the mutant mouse predicts multiple Der1-induced alterations converging upon synapse function and plasticity. Synaptosome proteomics confirmed that the Der1 mutation impacts synapse composition, and electrophysiology found reduced AMPA:NMDA ratio in hippocampal neurons, indicating changed excitatory signalling. Moreover, hippocampal parvalbumin-positive interneuron density is increased, suggesting that the Der1 mutation affects inhibitory control of neuronal circuits. These phenotypes predict that neurotransmission is impacted at many levels by DISC1 disruption in human t(1;11) translocation carriers. Notably, genes implicated in schizophrenia, depression and bipolar disorder by large-scale genetic studies are enriched among the Der1-dysregulated genes, just as we previously observed for the t(1;11) translocation carrier-derived neurons. Furthermore, RNAseq analysis predicts that the Der1 mutation primarily targets a subset of cell types, pyramidal neurons and interneurons, previously shown to be vulnerable to the effects of common schizophrenia-associated genetic variants. In conclusion, DISC1 disruption by the t(1;11) translocation may contribute to the psychiatric disorders of translocation carriers through commonly affected pathways and processes in neurotransmission

Fluorocarbon evaporative cooling developments for the ATLAS pixel and semiconductor tracking detectors

Heat transfer coefficients 2-5.103 Wm-2K-1 have been measured in a 3.6 mm I.D. heated tube dissipating 100 Watts - close to the full equivalent power (~110 W) of a barrel SCT detector "stave" - over a range of power dissipations and mass flows in the above fluids. Aspects of full-scale evaporative cooling circulator design for the ATLAS experiment are discussed, together with plans for future development

Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras.

von Willebrand factor (vWF) is essential for the induction of occlusive thrombosis in stenosed and injured pig arteries and for normal hemostasis. To separate the relative contribution of plasma and platelet vWF to arterial thrombosis, we produced chimeric normal and von Willebrand disease pigs by crossed bone marrow transplantation; von Willebrand disease (vWD) pigs were engrafted with normal pig bone marrow and normal pigs were engrafted with vWD bone marrow. Thrombosis developed in the chimeric normal pigs that showed normal levels of plasma vWF and an absence of platelet vWF; but no thrombosis occurred in the chimeric vWD pigs that demonstrated normal platelet vWF and an absence of plasma vWF. The ear bleeding times of the chimeric pigs were partially corrected by endogenous plasma vWF but not by platelet vWF. Our animal model demonstrated that vWF in the plasma compartment is essential for the development of arterial thrombosis and that it also contributes to the maintenance of bleeding time and hemostasis

Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations

International audienceINTRODUCTION: Breast carcinoma is the main malignant tumor occurring in patients with Cowden disease, a cancer-prone syndrome caused by germline mutation of the tumor suppressor gene PTEN characterized by the occurrence throughout life of hyperplastic, hamartomatous and malignant growths affecting various organs. The absence of known histological features for breast cancer arising in a PTEN-mutant background prompted us to explore them for potential new markers. METHODS: We first performed a microarray study of three tumors from patients with Cowden disease in the context of a transcriptomic study of 74 familial breast cancers. A subsequent histological and immunohistochemical study including 12 additional cases of Cowden disease breast carcinomas was performed to confirm the microarray data. RESULTS: Unsupervised clustering of the 74 familial tumors followed the intrinsic gene classification of breast cancer except for a group of five tumors that included the three Cowden tumors. The gene expression profile of the Cowden tumors shows considerable overlap with that of a breast cancer subgroup known as molecular apocrine breast carcinoma, which is suspected to have increased androgenic signaling and shows frequent ERBB2 amplification in sporadic tumors. The histological and immunohistochemical study showed that several cases had apocrine histological features and expressed GGT1, which is a potential new marker for apocrine breast carcinoma. CONCLUSIONS: These data suggest that activation of the ERBB2-PI3K-AKT pathway by loss of PTEN at early stages of tumorigenesis promotes the formation of breast tumors with apocrine features

Transiting exoplanets from the CoRoT space mission. VIII. CoRoT-7b: the first super-Earth with measured radius

Copyright © The European Southern Observatory (ESO)Aims. We report the discovery of very shallow (ΔF/F ≈ 3.4×10−4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results. We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40'' or triple systems are almost excluded with a 8 × 10−4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10−5 day and a radius of Rp = 1.68 ± 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. Conclusions. CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800–2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived