Learning High-dimensional Gaussian Graphical Models under Total Positivity without Adjustment of Tuning Parameters

We consider the problem of estimating an undirected Gaussian graphical model when the underlying distribution is multivariate totally positive of order 2 (MTP2), a strong form of positive dependence. Such distributions are relevant for example for portfolio selection, since assets are usually positively dependent. A large body of methods have been proposed for learning undirected graphical models without the MTP2 constraint. A major limitation of these methods is that their structure recovery guarantees in the high-dimensional setting usually require a particular choice of a tuning parameter, which is unknown a priori in real world applications. We here propose a new method to estimate the underlying undirected graphical model under MTP2 and show that it is provably consistent in structure recovery without adjusting the tuning parameters. This is achieved by a constraint-based estimator that infers the structure of the underlying graphical model by testing the signs of the empirical partial correlation coefficients. We evaluate the performance of our estimator in simulations and on financial data

DNA cleavage and antitumour activity of platinum(II) and copper(II) compounds derived from 4-methyl-2-N-(2-pyridylmethyl)aminophenol: spectroscopic, electrochemical and biological investigation

The reaction of the redox-active ligand, Hpyramol (4-methyl-2-N-(2-pyridylmethyl)aminophenol) with K2PtCl4 yields monofunctional square-planar [Pt(pyrimol)Cl], PtL-Cl, which was structurally characterised by single-crystal X-ray diffraction and NMR spectroscopy. This compound unexpectedly cleaves supercoiled double-stranded DNA stoichiometrically and oxidatively, in a non-specific manner without any external reductant added, under physiological conditions. Spectro-electrochemical investigations of PtL-Cl were carried out in comparison with the analogue CuL-Cl as a reference compound. The results support a phenolate oxidation, generating a phenoxyl radical responsible for the ligand-based DNA cleavage property of the title compounds. Time-dependent in vitro cytotoxicity assays were performed with both PtL-Cl and CuL-Cl in various cancer cell lines. The compound CuL-Cl overcomes cisplatin-resistance in ovarian carcinoma and mouse leukaemia cell lines, with additional activity in some other cells. The platinum analogue, PtL-Cl also inhibits cell-proliferation selectively. Additionally, cellular-uptake studies performed for both compounds in ovarian carcinoma cell lines showed that significant amounts of Pt and Cu were accumulated in the A2780 and A2780R cancer cells. The conformational and structural changes induced by PtL-Cl and CuL-Cl on calf thymus DNA and phi X174 supercoiled phage DNA at ambient conditions were followed by electrophoretic mobility assay and circular dichroism spectroscopy. The compounds induce extensive DNA degradation and unwinding, along with formation of a monoadduct at the DNA minor groove. Thus, hybrid effects of metal-centre variation, multiple DNA-binding modes and ligand-based redox activity towards cancer cell-growth inhibition have been demonstrated. Finally, reactions of PtL-Cl with DNA model bases (9-Ethylguanine and 5'-GMP) followed by NMR and MS showed slow binding at Guanine-N7 and for the double stranded self complimentary oligonucleotide d(GTCGAC)(2) in the minor groove

EVOLUTIONARY ANALYSIS AND DETECTION OF POSITIVE SELECTION OF HEMAGGLUTININ AND NEURAMINIDASE GENES OF H5N1 AVIAN INFLUENZA FROM CHICKEN, DUCK AND GOOSE ACROSS ASIA

Outbreaks of very high pathogenic avian influenza (H5N1) viruses are being reported in poultry in almost all countries including Asia. It has been reported that the spread is very fast and found that this virus is spreading in avian species for several years. In this study, the evidence of positive selection prominent to mutations were analyzed for the Hemagglutinin (HA) and Neuraminidase (NA) nucleotide sequences of H5N1 avian influenza from chicken, duck, and goose across Asia. H5N1 avian influenza viruses are being a severe risk to public health. Detection of positive selection sites in Hemagglutinin (HA) and Neuraminidase (NA) genes will help to trace the evolutionary path of these viruses from different poultry hosts. The positive/ diversifying selection (dN/dS (ω) >1) was found to be showing significant signals in the mutation of HA and NA genes and is evolving rapidly. The cumulative dN/dS (ω) ratio was found ranging from 0.21 to 0.23 in the HA gene and 0.16 to 0.25 in the NA gene of Avian Influenza Virus from chicken, duck, and goose. Furthermore, statistical Bayesian model methods were applied to interpret the genetic diversity of H5N1 strain, the evolutionary rates were ranging from 2.36x10-3 to 5.19x10-3 in the HA gene and 2.28x10-3 to 6.25x10-3 in the NA gene from chicken, duck, and goose respectively, which revealed a rapid evolution in these viruses with respect to their genetic ancestor. Substitution rates and selection pressure in these three different hosts indicate that their dynamics of mutation and replication remain similar among the species studied and are important for evolution

Working Group Report: Neutrino and Astroparticle Physics

This is the report of neutrino and astroparticle physics working group at WHEPP-8. We present the discussions carried out during the workshop on selected topics in the above fields and also indicate progress made subsequently. The neutrino physics subgroup studied the possibilites of constraining neutrino masses, mixing and CPT violation in lepton sector from future experiments. Neutrino mass models in the context of abelian horizontal symmetries, warped extra dimensions and in presence of triplet Higgs were studied. Effect of threshold corrections on radiative magnification of mixing angles was investigated. The astroparticle physics subgroup focused on how various particle physics inputs affect the CMBR fluctuation spectrum, and on brane cosmology. This report also contains an introduction on how to use the publicly available code CMBFAST to calculate the CMBR fluctuations.Comment: Prepared for the 8th Workshop on High-Energy Physics Phenomenology (WHEPP-8), IIT Mumbai, India, 5-16 Jan 200

Leptonic CP Violation and Neutrino Mass Models

We discuss leptonic mixing and CP violation at low and high energies, emphasizing possible connections between leptogenesis and CP violation at low energies, in the context of lepton flavour models. Furthermore we analyse weak basis invariants relevant for leptogenesis and for CP violation at low energies. These invariants have the advantage of providing a simple test of the CP properties of any lepton flavour model.Comment: 26 pages, no figures, submitted to the Focus Issue on `Neutrino Physics` edited by F. Halzen, M. Lindner and A. Suzuki, to be published in New Journal of Physic