Statistical Network Analysis for Functional MRI: Summary Networks and Group Comparisons

Comparing weighted networks in neuroscience is hard, because the topological properties of a given network are necessarily dependent on the number of edges of that network. This problem arises in the analysis of both weighted and unweighted networks. The term density is often used in this context, in order to refer to the mean edge weight of a weighted network, or to the number of edges in an unweighted one. Comparing families of networks is therefore statistically difficult because differences in topology are necessarily associated with differences in density. In this review paper, we consider this problem from two different perspectives, which include (i) the construction of summary networks, such as how to compute and visualize the mean network from a sample of network-valued data points; and (ii) how to test for topological differences, when two families of networks also exhibit significant differences in density. In the first instance, we show that the issue of summarizing a family of networks can be conducted by adopting a mass-univariate approach, which produces a statistical parametric network (SPN). In the second part of this review, we then highlight the inherent problems associated with the comparison of topological functions of families of networks that differ in density. In particular, we show that a wide range of topological summaries, such as global efficiency and network modularity are highly sensitive to differences in density. Moreover, these problems are not restricted to unweighted metrics, as we demonstrate that the same issues remain present when considering the weighted versions of these metrics. We conclude by encouraging caution, when reporting such statistical comparisons, and by emphasizing the importance of constructing summary networks.Comment: 16 pages, 5 figure

Group Analysis of Self-organizing Maps based on Functional MRI using Restricted Frechet Means

Studies of functional MRI data are increasingly concerned with the estimation of differences in spatio-temporal networks across groups of subjects or experimental conditions. Unsupervised clustering and independent component analysis (ICA) have been used to identify such spatio-temporal networks. While these approaches have been useful for estimating these networks at the subject-level, comparisons over groups or experimental conditions require further methodological development. In this paper, we tackle this problem by showing how self-organizing maps (SOMs) can be compared within a Frechean inferential framework. Here, we summarize the mean SOM in each group as a Frechet mean with respect to a metric on the space of SOMs. We consider the use of different metrics, and introduce two extensions of the classical sum of minimum distance (SMD) between two SOMs, which take into account the spatio-temporal pattern of the fMRI data. The validity of these methods is illustrated on synthetic data. Through these simulations, we show that the three metrics of interest behave as expected, in the sense that the ones capturing temporal, spatial and spatio-temporal aspects of the SOMs are more likely to reach significance under simulated scenarios characterized by temporal, spatial and spatio-temporal differences, respectively. In addition, a re-analysis of a classical experiment on visually-triggered emotions demonstrates the usefulness of this methodology. In this study, the multivariate functional patterns typical of the subjects exposed to pleasant and unpleasant stimuli are found to be more similar than the ones of the subjects exposed to emotionally neutral stimuli. Taken together, these results indicate that our proposed methods can cast new light on existing data by adopting a global analytical perspective on functional MRI paradigms.Comment: 23 pages, 5 figures, 4 tables. Submitted to Neuroimag

Optical investigation of the charge-density-wave phase transitions in NbSe3NbSe_{3}

We have measured the optical reflectivity $R(\omega)$ of the quasi one-dimensional conductor $NbSe_{3}$ from the far infrared up to the ultraviolet between 10 and 300 $K$ using light polarized along and normal to the chain axis. We find a depletion of the optical conductivity with decreasing temperature for both polarizations in the mid to far-infrared region. This leads to a redistribution of spectral weight from low to high energies due to partial gapping of the Fermi surface below the charge-density-wave transitions at 145 K and 59 K. We deduce the bulk magnitudes of the CDW gaps and discuss the scattering of ungapped free charge carriers and the role of fluctuations effects

Manufacturing and Installation of the Compound Cryogenic Distribution Line for the Large Hadron Collider

The Large Hadron Collider (LHC) [1] currently under construction at CERN will make use of superconducting magnets operating in superfluid helium below 2 K. A compound cryogenic distribution line (QRL) will feed with helium at different temperatures and pressures the local elementary cooling loops in the cryomagnet strings. Low heat inleak to all temperature levels is essential for the overall LHC cryogenic performance. Following a competitive tendering, CERN adjudicated in 2001 the contract for the series line to Air Liquide (France). This paper recalls the main features of the technical specification and shows the project status. The basic choices and achievements for the industrialization phase of the series production are also presented, as well as the installation issues and status

Temporally ordered collective creep and dynamic transition in the charge-density-wave conductor NbSe3

We have observed an unusual form of creep at low temperatures in the charge-density-wave (CDW) conductor NbSe$_3$. This creep develops when CDW motion becomes limited by thermally-activated phase advance past individual impurities, demonstrating the importance of local pinning and related short-length-scale dynamics. Unlike in vortex lattices, elastic collective dynamics on longer length scales results in temporally ordered motion and a finite threshold field. A first-order dynamic phase transition from creep to high-velocity sliding produces "switching" in the velocity-field characteristic.Comment: 4 pages, 4 eps figures; minor clarifications To be published in Phys. Rev. Let

On the origin of the A1g_{1g} and B1g_{1g} electronic Raman scattering peaks in the superconducting state of YBa2_{2}Cu3_{3}O7−δ_{7-\delta}

The electronic Raman scattering has been investigated in optimally oxygen doped YBa$_{2}$Cu$_{3}$O$_{7-\delta}$ single crystals as well as in crystals with non-magnetic, Zn, and magnetic, Ni, impurities. We found that the intensity of the A$_{1g}$ peak is impurity independent and their energy to $T_{c}$ ratio is almost constant ($2\Delta/k_{B}T_{c}\sim5$). Moreover, the signal at the B$_{1g}$ channel is completely smeared out when non-magnetic Zn impurities are present. These results are qualitatively interpreted in terms of the Zeyher and Greco's theory that relates the electronic Raman scattering in the A$_{1g}$ and B$_{1g}$ channels to \textit{d}-CDW and superconducting order parameters fluctuations, respectively.Comment: Submited to Phys. Rev. Let

The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

International audienceHeparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumorigenesis, albeit mechanisms remain mostly obscure. HS function is mainly controlled by sulfotransferases, and here we report a novel cellular and pathophysiological significance for the 3-O-sulfotransferase 3-OST3A (HS3ST3A), catalyzing the final maturation step of HS, in breast cancer. We show that 3-OST3A is epigenetically repressed in all breast cancer cell lines of a panel representative of distinct molecular subgroups, except in human epidermal growth factor receptor 2-positive (HER2+) sloan-kettering breast cancer (SKBR3) cells. Epigenetic mechanisms involved both DNA methylation and histone modifications, producing different repressive chromatin environments depending on the cell molecular signature. Gain and loss of function experiments by cDNA and siRNA transfection revealed profound effects of 3-OST3A expression on cell behavior including apoptosis, proliferation, response to trastuzumab in vitro and tumor growth in xenografted mice. 3-OST3A exerted dual activities acting as tumor-suppressor in lumA-michigan cancer foundation (MCF)-7 and triple negative-MD Anderson (MDA) metastatic breast (MB)-231 cells, or as an oncogenic factor in HER2+-SKBR3 cells. Mechanistically, fluorescence-resonance energy transfer-fluorescence-lifetime imaging microscopy experiments indicated that the effects of 3-OST3A in MCF-7 cells were mediated by altered interactions between HS and fibroblast growth factor-7 (FGF-7). Further, this interplay between HS and FGF-7 modulated downstream ERK, AKT and p38 cascades, suggesting that altering 3-O-sulfation affects FGFR2IIIb-mediated signaling. Corroborating our cellular data, a clinical study conducted in a cohort of breast cancer patients uncovered that, in HER2+ patients, high level expression of 3-OST3A in tumors was associated with reduced relapse-free survival. Our findings define 3-OST3A as a novel regulator of breast cancer pathogenicity, displaying tumor-suppressive or oncogenic activities in a cell-and tumor-dependent context, and demonstrate the clinical value of the HS-O-sulfotransferase 3-OST3A as a prognostic marker in HER2+ patients

Characterization of a Nonclassical Class I MHC Gene in a Reptile, the Galápagos Marine Iguana (Amblyrhynchus cristatus)

Squamates are a diverse order of vertebrates, representing more than 7,000 species. Yet, descriptions of full-length major histocompatibility complex (MHC) genes in this group are nearly absent from the literature, while the number of MHC studies continues to rise in other vertebrate taxa. The lack of basic information about MHC organization in squamates inhibits investigation into the relationship between MHC polymorphism and disease, and leaves a large taxonomic gap in our understanding of amniote MHC evolution. Here, we use both cDNA and genomic sequence data to characterize a class I MHC gene (Amcr-UA) from the Galápagos marine iguana, a member of the squamate subfamily Iguaninae. Amcr-UA appears to be functional since it is expressed in the blood and contains many of the conserved peptide-binding residues that are found in classical class I genes of other vertebrates. In addition, comparison of Amcr-UA to homologous sequences from other iguanine species shows that the antigen-binding portion of this gene is under purifying selection, rather than balancing selection, and therefore may have a conserved function. A striking feature of Amcr-UA is that both the cDNA and genomic sequences lack the transmembrane and cytoplasmic domains that are necessary to anchor the class I receptor molecule into the cell membrane, suggesting that the product of this gene is secreted and consequently not involved in classical class I antigen-presentation. The truncated and conserved character of Amcr-UA lead us to define it as a nonclassical gene that is related to the few available squamate class I sequences. However, phylogenetic analysis placed Amcr-UA in a basal position relative to other published classical MHC genes from squamates, suggesting that this gene diverged near the beginning of squamate diversification

Status of a European Standard for the protection of helium cryostats against excessive pressure

The overpressure protection of various types of cryogenic vessels is covered by a number of International Standards. Helium cryostats, however, include additional components such as superconducting magnets and cavities, electrical heaters and control valves with associated piping, which significantly influence the potential risk. At the European Committee for Standardization CEN, a new working group was hence founded as CEN/TC 268/WG6, dealing with ‘Specific helium technology applications’. Its aim is to develop a European Standard for the protection of helium cryostats against excessive pressure that is harmonized with the European Pressure Equipment Directive. It will cover the typical conditions in accidental scenarios in order to harmonize the risk assessment as well as design practices for the pressure relieving systems. We report about the general concept of this new Standard, its structure and content, and the actual status of the project