A comparison of the L2 minimum distance estimator and the EM-algorithm when fitting k-component univariate normal mixtures

The method of maximum likelihood using the EM-algorithm for fitting finite mixtures of normal distributions is the accepted method of estimation ever since it has been shown to be superior to the method of moments. Recent books testify to this. There has however been criticism of the method of maximum likelihood for this problem, the main criticism being when the variances of component distributions are unequal the likelihood is in fact unbounded and there can be multiple local maxima. Another major criticism is that the maximum likelihood estimator is not robust. Several alternative minimum distance estimators have since been proposed as a way of dealing with the first problem. This paper deals with one of these estimators which is not only superior due to its robustness, but in fact can have an advantage in numerical studies even at the model distribution. Importantly, robust alternatives of the EM-algorithm, ostensibly fitting t distributions when in fact the data are mixtures of normals, are also not competitive at the normal mixture model when compared to the chosen minimum distance estimator. It is argued for instance that natural processes should lead to mixtures whose component distributions are normal as a result of the Central Limit Theorem. On the other hand data can be contaminated because of extraneous sources as are typically assumed in robustness studies. This calls for a robust estimato

11β-hydroxysteroid dehydrogenase type I inhibition in solid tumours

Glucocorticoids, key hormonal regulators of the stress response, powerfully influence inflammation and metabolism. Reducing excessive glucocorticoid exposure is beneficial in treating metabolic and cognitive disorders, but manipulating systemic endogenous glucocorticoids risks compromising their beneficial effects. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates glucocorticoids in target tissues and thus inhibition of this enzyme presents a clinical opportunity to reduce tissue-specific glucocorticoid action. Active glucocorticoids also exert potent angiostatic effects by binding the glucocorticoid receptor (GR), and 11β-HSD1 inhibitors have proven beneficial in models of myocardial infarction by promoting angiogenesis. The possibility that 11β-HSD1 inhibitors may increase pathological angiogenesis, such as that seen in solid tumours, remains unaddressed. This project tested the hypothesis that 11β-HSD1 inhibition promotes tumour growth as a result of increased angiogenesis, using murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC). Murine SCC or PDAC cells were injected (1x106 cells/flank) into WT female mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316 (175 mg/kg, N=6/group), or into 11β-HSD1 knockout (Del1) mice fed standard diet. Developing tumours were measured by callipers over several weeks, before animals were culled and tissues collected. SCC tumours grew more rapidly in UE2316-treated mice to reach a significantly (P<0.01) larger final volume (0.158 ± 0.037 cm3) than in control mice (0.051 ± 0.007 cm3). PDA tumours were unaffected by 11β-HSD1 inhibition or deletion. Immunofluorescent co-staining of tumour sections for CD31/α-smooth muscle actin revealed no differences in vessel density, and RT-qPCR showed no difference in angiogenic factor expression, after 11β-HSD1 inhibition/deletion in either tumour type. GR and 11β-HSD1 RNA expression were greater in SCC vs PDAC tumours (P<0.001), as was 11β-HSD1 activity (P<0.0001). In studies using the aortic ring assay of ex vivo angiogenesis, 11β-HSD1 deletion, but not inhibition with UE2316, was shown to prevent glucocorticoid-mediated angiostasis. The growth/viability of tumour cell lines was not affected by UE2316 or corticosterone, as assessed by live cell imaging using the Incucyte imaging system. RNA-sequencing of SCC tumours revealed that multiple factors involved in the innate immune/inflammatory response were reduced in UE2316-treated tumours, and that extracellular matrix regulation was also altered by UE2316. Imaging of tumour sections using Second Harmonic Generation microscopy confirmed that UE2316 altered Type I collagen deposition in SCC (P<0.001) but not PDAC. 11β-HSD1 inhibition can increase tumour growth, possibly via suppression of inflammatory/immune cell signalling and alteration of the extracellular matrix, and tumours with higher GR and 11β-HSD1 content, such as SCC, may be more at risk. Interestingly this investigation found no evidence of increased angiogenesis in vivo or ex vivo after UE2316 treatment, suggesting that 11β-HSD1 inhibition does not promote angiogenesis in all ischaemic environments. Future work must focus on the effects of 11β-HSD1 inhibition on the immune and extracellular matrix component of the tumour microenvironment. While promotion of pathological angiogenesis does not appear to pose a major threat, 11β-HSD1 inhibitors may still interact with the immune and inflammatory environment in tumours to the detriment of health

NN,N\Delta Couplings and the Quark Model

We examine mass-corrected SU(6) symmetry predictions in the quark model relating vector, axial-vector and strong NN and N\Delta couplings, and demonstrate that the experimental N\Delta value is significantly higher than predicted in each case. Nevertheless the Goldberger-Treiman relation is satisfied in both sectors. Possible origins of the discrepancy of the quark model predictions with experiment are discussed.Comment: 22 pg. Latex file, figures available by reques

Pion and Sigma Polarizabilities and Radiative Transitions

Fermilab E781 plans measurements of gamma-Sigma and $\gamma$-pion interactions using a 600 GeV beam of Sigmas and pions, and a virtual photon target. Pion polarizabilities and radiative transitions will be measured in this experiment. The former can test a precise prediction of chiral symmetry; the latter for a_1(1260) ----> pi + gamma is important for understanding the polarizability. The experiment also measures polarizabilities and radiative transitions for Sigma hyperons. The polarizabilities can test predictions of baryon chiral perturbation theory. The radiative transitions to the Sigma*(1385) provide a measure of the magnetic moment of the s-quark. Previous experimental and theoretical results for gamma-pi and gamma-Sigma interactions are given. The E781 experiment is described.Comment: 13 pages text (tex), Tel Aviv U. Preprint TAUP 2204-94, uses Springer-Verlag TEX macro package lecproc.cmm (appended at end of tex file, following \byebye), which requires extracting lecproc.cmm and putting this file in your directory in addition to the tex file (mmcd.tex) before tex processing. lecproc.cmm should be used following instructions and guidelines available from Springer-Verlag. Submitted to the Proceedings of Workshop on Chiral Dynamics, Massachusetts Institute of Technology, July 1994, Eds. A. Bernstein, B. Holstein. Replaced Oct. 4 to add TAUP preprint number. Replaced Oct. 12 to correct Pb target thickness from 1.3% interaction to 0.3

Protecting the primordial baryon asymmetry in the seesaw model compatible with WMAP and KamLAND

We require that the primordial baryon asymmetry is not washed out in the seesaw model compatible with the recent results of WMAP and the neutrino oscillation experiments including the first results of KamLAND. We find that only the case of the normal neutrino mass hierarchy with an approximate $L_{e}$-symmetry satisfies the requirement. We further derive, depending on the signs of neutrino mass eigenvalues, three types of neutrino mass matrixes, where the values of each element are rather precisely fixed.Comment: 21pages; added reference

Leptogenesis in Neutrino Textures with Two Zeros

The leptogenesis is studied in the neutrino textures with two zeros, which reduce the number of independent phases of the CP violation. The phenomenological favored neutrino textures with two zeros are decomposed into the Dirac neutrino mass matrix and the right-handed Majorana one in the see-saw mechanism. Putting the condition to suppress the $\mu \to e\gamma$ decay enough, the texture zeros of the Dirac neutrino mass matrix are fixed in the framework of the MSSM with right-handed neutrinos. These textures have only one CP violatig phase. The magnitude of each entry of the Dirac mass matrix is determined in order to explain the baryon asymmetry of the universe by solving the Boltzman equations. The relation between the leptogenesis and the low energy CP violation is presented in these textures.Comment: Latex file with 20 pages, 6 eps figure

A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses

We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants

Human liver memory CD8(+) T cells use autophagy for tissue residence

Tissue-resident memory T cells have critical roles in long-term pathogen and tumor immune surveillance in the liver. We investigate the role of autophagy in equipping human memory T cells to acquire tissue residence and maintain functionality in the immunosuppressive liver environment. By performing ex vivo staining of freshly isolated cells from human liver tissue, we find that an increased rate of basal autophagy is a hallmark of intrahepatic lymphocytes, particularly liver-resident CD8(+) T cells. CD8(+) T cells with increased autophagy are those best able to proliferate and mediate cytotoxicity and cytokine production. Conversely, blocking autophagy induction results in the accumulation of depolarized mitochondria, a feature of exhausted T cells. Primary hepatic stellate cells or the prototypic hepatic cytokine interleukin (IL)-15 induce autophagy in parallel with tissue-homing/retention markers. Inhibition of T cell autophagy abrogates tissue-residence programming. Thus, upregulation of autophagy adapts CD8(+) T cells to combat mitochondrial depolarization, optimize functionality, and acquire tissue residence

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio