Shannon entropy approach reveals relevant genes in Alzheimer's disease

Alzheimer's disease (AD) is the most common type of dementia and affects millions of people worldwide. Since complex diseases are often the result of combinations of gene interactions, microarray data and gene co-expression analysis can provide tools for addressing complexity. Our study aimed to find groups of interacting genes that are relevant in the development of AD. In this perspective, we implemented a method proposed in a previous work to detect gene communities linked to AD. Our strategy combined co-expression network analysis with the study of Shannon entropy of the betweenness. We analyzed the publicly available GSE1297 dataset, achieved from the GEO database in NCBI, containing hippocampal gene expression of 9 control and 22 AD human subjects. Co-expressed genes were clustered into different communities. Two communities of interest (composed by 72 and 39 genes) were found by calculating the correlation coefficient between communities and clinical features. The detected communities resulted stable, replicated on two independent datasets and mostly enriched in pathways closely associated with neuro-degenative diseases. A comparison between our findings and other module detection techniques showed that the detected communities were more related to AD phenotype. Lastly, the hub genes within the two communities of interest were identified by means of a centrality analysis and a bootstrap procedure. The communities of the hub genes presented even stronger correlation with clinical features. These findings and further explorations on the detected genes could shed light on the genetic aspects related with physiological aspects of Alzheimer's disease

Thermostable Hexameric Form of Eis (Rv2416c) Protein of M. tuberculosis Plays an Important Role for Enhanced Intracellular Survival within Macrophages

Eis protein is reported to enhance the intracellular survival of Mycobacterium tuberculosis in human macrophages. Eis protein is not only known to skew away the immunity by disturbing the protective TH1 response, but aminoglycoside acetyltransferase activity of Eis is reported to regulate autophagy, inflammation and cell death. Here we have gained insight into the structure-function properties of Eis. Eis protein is a hexameric αβ protein. Although urea and guanidinium hydrochloride (GdmCl) was found to induce one-step unfolding of Eis but size exclusion chromatography showed that GdmCl treated Eis maintained its hexameric form. SDS-PAGE assay confirmed that hexameric form of Eis is partially stable to SDS and converts into trimers and monomers. Out of these three forms, aminoglycoside acetyltransferase activity is found to be associated only with hexamers. The Tm of Eis was found to be ∼75°C. Aminoglycoside acetyltransferase Eis demonstrated remarkable heat stability retaining >80% of their activity at 70°C which falls down to ∼50% at 75°C and is completely inactive at 80°C. Further, intracellular survival assay with heated samples of M. smegmatis harboring eis gene of M. tuberculosis H37Rv demonstrated a possible role for the thermostability associated with Eis protein in the enhanced intracellular survival within macrophages. In sum, these data reveal that only hexameric form of Eis has a thermostable aminoglycoside acetyltransferase activity. This is the first report showing the thermostability associated with aminoglycoside acetyltransferase activity of Eis protein being one of the essential features for the execution of its biological role

Machine learning and DWI brain communicability networks for Alzheimer's disease detection

Signal processing and machine learning techniques are changing the clinical practice based on medical imaging from many perspectives. A major topic is related to (i) the development of computer aided diagnosis systems to provide clinicians with novel, non-invasive and low-cost support-tools, and (ii) to the development of new methodologies for the analysis of biomedical data for finding new disease biomarkers. Advancements have been recently achieved in the context of Alzheimer's disease (AD) diagnosis through the use of diffusionweighted imaging (DWI) data. When combinedwith tractography algorithms, this imaging modality enables the reconstruction of the physical connections of the brain that can be subsequently investigated through a complex network-based approach. A graph metric particularly suited to describe the disruption of the brain connectivity due to AD is communicability. In this work, we develop a machine learning framework for the classification and feature importance analysis of AD based on communicability at the whole brain level. We fairly compare the performance of three state-of-the-art classification models, namely support vector machines, random forests and artificial neural networks, on the connectivity networks of a balanced cohort of healthy control subjects and AD patients from the ADNI database. Moreover, we clinically validate the information content of the communicabilitymetric by performing a feature importance analysis. Both performance comparison and feature importance analysis provide evidence of the robustness of the method. The results obtained confirm that the whole brain structural communicability alterations due to AD are a valuable biomarker for the characterization and investigation of pathological conditions

Apparatus for synthesizing and separating synthesis products e.g. gaseous and liquid phases on bed, maintains heavier liquid phase at lower portion of first meatus due to gravity and lighter liquid phase at upper portion of meatus

NOVELTY - The apparatus has header that is set to make the heavier and lighter liquid phases flow along outer side surface of a third tube (8) as far as first closure element (13). The third tube is provided with second side openings for directly connecting the first and second meatus. The heavier liquid phase is maintained at lower portion of the first meatus due to gravity and lighter liquid phase is maintained at upper portion of the first meatus until the liquid phases fall into a fourth tube (9). The heavier liquid phase is collectible through a collection hole (12). USE - Apparatus e.g. reactor/separator for synthesizing and separating synthesis products e.g. gaseous phase and heavier and lighter liquid phases on catalytic bed, used in production of biodiesel. ADVANTAGE - Since heavier liquid phase is maintained at lower portion of the first meatus due to gravity and lighter liquid phase is maintained at upper portion of the first meatus, sedimentation separation of the liquid phases is improved. The structure of the apparatus is simplified and the apparatus is constructed easily. The efficacy and use of catalyst are maximized. DETAILED DESCRIPTION - The apparatus has synthesis module (M1) that is set with a first tube (1) which is provided with an opening at one end and closed at second end by a mesh (7). The first tube is adapted to contain a catalytic bed (6). A separation module (M2) is set to separate heavier and lighter liquid phases and gaseous phase originating from the synthesis module. A second tube (1') is arranged adjacent to second end of the first tube. A first closure element is provided with a through hole for sole passage of the second liquid and of the gaseous phase. A third tube is affixed to first end of second tube. A first meatus is set between second tube and the third tube. The fourth tube is set inside the third tube so as to define a second meatus between the third tube and the fourth tube. A separation zone is set between the heavier and lighter liquid phases. A collection hole is set in the second tube to collect the heavier liquid phase. The third tube is set with first side openings at first end, and is set with a header for collecting the liquid phases originating from the synthesis module. The first meatus is directly inserted into the third tube and subsequently into the fourth tube. A control system is set between the liquid phases, to check and maintain interface level below the upper end of the first side openings. The control system has interface level indicator that is connected to the second tube by second side holes envisaged in side surface of the second tube. One of the second side holes is arranged in proximity of the first closure element and other is positioned above the upper end of the first side openings. The protrusions are arranged along cylindrical side surface of the third tube, and are separated by spaces for passage of the liquid phases from the header to the first meatus. A redistribution module (M3) is set to redistribute the lighter liquid phase and gaseous phase originating from the fourth tube. A fifth tube (1") is arranged adjacent to second end of the second tube. The closure element is set with a central perforated area. A sixth tube (14) is set to descent and release of the gaseous phase. The central perforated area is provided with several holes for homogeneous distribution of lighter liquid phase downstream of the redistribution module. The sixth tube is affixed to a second closure element (15). The mesh is provided with a passage area. The synthesis module, separation module and redistribution module are vertically-stacked. An INDEPENDENT CLAIM is included for a method for synthesizing and separating synthesis products e.g. gaseous phase and heavier and lighter liquid phases on catalytic bed, involves synthesizing on a catalytic bed and producing the synthesis products. The liquid phases and gaseous phase are separated in the separation module

On the Optimum Long Baseline for the Next Generation Neutrino Oscillation Experiments

For high energy long baseline neutrino oscillation experiments, we propose a Figure of Merit criterion to compare the statistical quality of experiments at various oscillation distances under the condition of identical detectors and a given neutrino beam. We take into account all possible experimental errors under general consideration. In this way the Figure of Merit is closely related to the usual statistical criterion of number of sigmas. We use a realistic neutrino beam for an entry level neutrino factory and a possible superbeam from a meson source and a 100 kt detector for the calculation. We considered in detail four oscillation distances, 300 km, 700 km, 2100 km and 3000 km, in the neutrino energy range of 0.5-20 GeV for a 20 GeV entry level neutrino factory and a 50 GeV superbeam. We found that the very long baselines of 2100 km and 3000 km are preferred for the neutrino factory according to the figure of merit criterion. Our results also show that, for a neutrino factory, lower primary muon energies such as 20 GeV are preferred rather than higher ones such as 30 or 50 GeV. For the superbeam, the combination of a long baseline such as 300 km and a very long baseline like 2100 km will form a complete measurement of the oscillation parameters besides the CP phase. To measure the CP phase in a superbeam, a larger detector (a factor 3 beyond what is considered in this article) and/or a higher intensity beam will be needed to put some significant constraints on the size of the CP angle.Comment: 21 LaTeX pages, 13 PS figures, typos corrected, references adde

Neutrino Oscillations in the Framework of Three-Generation Mixings with Mass Hierarchy

We have analyzed the results of reactor and accelerator neutrino oscillation experiments in the framework of a general model with mixing of three neutrino fields and a neutrino mass hierarchy that can accommodate the results of the solar neutrino experiments. It is shown that $\nu_\mu \leftrightarrows \nu_e$ oscillations with $0.6 \le \Delta m^2 \le 100 \, \mathrm{eV}^2$ and amplitude larger than $2 \times 10^{-3}$ are not compatible with the existing limits on neutrino oscillations if the non-diagonal elements of the mixing matrix $\left| U_{e3} \right|$ and $\left| U_{\mu3} \right|$ are small. Thus, if the excess of electron events recently observed in the LSND experiment is due to $\nu_\mu \leftrightarrows \nu_e$ oscillations, the mixing in the lepton sector is basically different from the CKM mixing of quarks. If this type of mixing is realized in nature, the observation of $\nu_\mu \leftrightarrows \nu_e$ oscillations would not influence $\nu_\mu \leftrightarrows \nu_\tau$ oscillations that are being searched for in the CHORUS and NOMAD experiments.Comment: Revtex file, 13 pages + 2 figures (included). The postscript file of text and figures is available at http://www.to.infn.it/teorici/giunti/papers.html or ftp://ftp.to.infn.it/pub/giunti/1995/dftt-25-95/dftt-25-95.ps.

The CAST Time Projection Chamber

One of the three X-ray detectors of the CAST experiment searching for solar axions is a Time Projection Chamber (TPC) with a multi-wire proportional counter (MWPC) as a readout structure. Its design has been optimized to provide high sensitivity to the detection of the low intensity X-ray signal expected in the CAST experiment. A low hardware threshold of 0.8 keV is safely set during normal data taking periods, and the overall efficiency for the detection of photons coming from conversion of solar axions is 62 %. Shielding has been installed around the detector, lowering the background level to 4.10 x 10^-5 counts/cm^2/s/keV between 1 and 10 keV. During phase I of the CAST experiment the TPC has provided robust and stable operation, thus contributing with a competitive result to the overall CAST limit on axion-photon coupling and mass.Comment: 19 pages, 11 figures and images, submitted to New Journal of Physic

Search for solar Kaluza-Klein axions in theories of low-scale quantum gravity

We explore the physics potential of a terrestrial detector for observing axionic Kaluza-Klein excitations coming from the Sun within the context of higher-dimensional theories of low-scale quantum gravity. In these theories, the heavier Kaluza-Klein axions are relatively short-lived and may be detected by a coincidental triggering of their two-photon decay mode. Because of the expected high multiplicity of the solar axionic excitations, we find experimental sensitivity to a fundamental Peccei-Quinn axion mass up to $10^{-2}$ eV (corresponding to an effective axion-photon coupling $g_{a\gamma \gamma} \approx 2.\times 10^{-12}$ GeV$^{-1}$) in theories with 2 extra dimensions and a fundamental quantum-gravity scale $M_{\rm F}$ of order 100 TeV, and up to $3.\times 10^{-3}$ eV (corresponding to $g_{a\gamma \gamma} \approx 6.\times 10^{-13}$ GeV$^{-1}$) in theories with 3 extra dimensions and $M_{\rm F}=1$ TeV. For comparison, based on recent data obtained from lowest level underground experiments, we derive the experimental limits: $g_{a \gamma \gamma} \stackrel{<}{{}_\sim} 2.5\times 10^{-11}$ GeV$^{-1}$ and $g_{a \gamma \gamma} \stackrel{<}{{}_\sim} 1.2\times 10^{-11}$ GeV$^{-1}$ in the aforementioned theories with 2 and 3 large compact dimensions, respectively.Comment: 19 pages, extended version, as to appear in Physical Review

Search for solar axions using Li-7

We describe a novel approach to the search for solar, near-monochromatic hadronic axions, the latter being suggested to be created in the solar core during M1 transitions between the first excited level of Li-7, at 478 keV, and the ground state. As a result of Doppler broadening, in principle these axions can be detected via resonant absorption by the same nuclide on the Earth. Excited nuclei of Li-7 are produced in the solar interior by Be-7 electron capture and thus the axions are accompanied by emission of Be-7 solar neutrinos of energy 384 keV. An experiment was made which has yielded an upper limit on hadronic axion mass of 32 keV at the 95% confidence level.Comment: revtex, 4 pages with 2 figures, title revised, minor changes, matches version to appear in Phys. Rev.