A subsampling method for the computation of multivariate estimators with high breakdown point

All known robust location and scale estimators with high breakdown point for multivariate sample's are very expensive to compute. In practice, this computation has to be carried out using an approximate subsampling procedure. In this work we describe an alternative subsampling scheme, applicable to both the Stahel-Donoho estimator and the estimator based on the Minimum Volume Ellipsoid, with the property that the number of subsamples required is substantially reduced with respect to the standard subsampling procedures used in both cases. We also discuss some bias and variability properties of the estimator obtained from the proposed subsampling process

Using angles to identify concentrated multivariate outliers

This article describes a procedure for the detection of multivariate outliers based on the analysis of certain angular properties of the observations. The method is simple, exploratory in nature, and particularly well suited for the detection of concentrated contamination patterns, in which the outliers appear to form a cluster, separated from the sample. It is shown that it presents good properties for the identification of contaminations on high-dimensional sample spaces and for high contamination levels, including some cases in which methods based on robust estimators (the minimum covariance determinant and minimum volume ellipsoid estimators, the Stahel–Donoho estimator, or other recent proposals) may fail. The use of the procedure is illustrated through several examplesPublicad

Cholangiocyte anion exchange and biliary bicarbonate excretion

Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. The excretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3- exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells (hepatocytes for the former and cholangiocytes for the latter). These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels (CFTR in cholangiocytes and not yet determined in hepatocytes) and aquaporins (AQP8 in hepatocytes and AQP1 in cholangiocytes). cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis

Insulin-like growth factor I (IGF-I) and liver cirrhosis

Insulin-like growth factor I (IGF-I) is a polypeptide hormone secreted by multiple tissues in response to growth hormone (GH). It is partly responsible for GH activity, and also has glucose-lowering and anabolizing effects. Ninety percent of circulating IGF-I originates in the liver and has autocrine, paracrine, and endocrine effects, the latter on multiple tissues. Liver cirrhosis results in a progressive decline of hepatic IGF-I output, and this factor may become undetectable in advanced disease. Some cirrhosis complications, mainly those nutritional and metabolic in nature (insuline resistance, malnutrition, osteopenia, hypogonadism, intestinal disorders), may be at least partly related to this IGF-I deficiency, since some IGF-I effects represent a reverse image of cirrhosis complications. Despite this, IGF-I replacement therapy has been never suggested for cirrhosis. A number of experimental studies in cirrhotic rats showed that therapy using low-dose recombinant IGF-I exerts two types of effect on experimental cirrhosis: a) liver improvement driven by improved hepatocellular function, portal hypertension, and liver fibrosis; and b) cirrhosis-related extrahepatic disorder improvement driven by improved food efficiency, muscle mass, bone mass, gonadal function and structure, and intestinal function and structure, with a normalization of sugar and amino acid malabsorption, and improved intstinal barrier function, manifested by reduced endotoxemia and bacterial translocation. Subsequently, the first randomized, double-blind, placebo-controlled, pilot clinical trial in a small number of cirrhotic patients showed increased serum albumin and improved energy metabolism as a result of IGF-I use. Further clinical trials are needed to identify adequate IGF-I doses, administration duration and frequency, and the subgroup of cirrhotic patients who will benefit most from this replacement therapy

Relationships among main soil properties and three N availability indices.

A biological (aerobic incubation for 3 and 6 weeks) and a chemical method [successive extractions with cold 0.1 (H1-N) and 0.5 M HCl (H2-N)] were applied to 21 soils to determine: a) the potentially mineralizable-N; b) the most useful soil variables for predicting soil N availability; and c) their usefulness for predicting N uptake by a greenhouse wheat crop. At t=3, both net N mineralized (NNM) and net N mineralization rate (NNMR) were correlated: a) positively with SOM- and CEC-related variables; and b) positively with soil δ 15N and negatively with soil pH, suggesting that Nmineralization, dominated by nitrification, is associated with NO3 --N losses and soil acidification. At t=6, all previously discussed variables were important for NNM, but not for NNMR, mainly controlled by the available-P content. The importance of H1-N increased with N2-inputs and decreased with NO3 - losses and soil-N. Relationships of H1-N and H2-N with soil CEC and texture showed the strong relations among nutrients content, biological activity and N mineralization, as well as the recalcitrance of clay-bounded SOM. Soil total-N correlations with wheat-N in absolute amount (positive) and as percentage of soil-N (negative) showed an important supply of available-N by N-rich soils, despite their slow N turnover. The best regression models for wheat-N always included 1-2 main available nutrients. The percentage of soil N exported to plant biomass was negatively correlated with noncrystalline Al compounds and soil δ 15N. Mineralized-N and wheat-N pools did not share many correlations with soil properties and seemed to come from different sources; consequently, the former pool, which only explained a quarter of wheat-N variance, was not more useful than soil total-N for predicting it. Only a positive correlation with soil total-N was shared by wheat-N and hydrolysable-N, highlighting that the latter N pools are mainly unrelated. Nevertheless, half of wheat-N variation was explained by its negative relationship with the percentage of soil-N as (H1+H2)-N; a possible explanation is that chemically labile N is also biologically labile, being cumulated because of a limiting factor for microbial N mineralization or plant growth and emerging as a good predictor for wheat-N uptake.Peer reviewe

Reliability analysis for systems with large hydro resources in a deregulated electric power market

This work describes a procedure that determines the optimal allocation for the yearly energy resulting from random water inflows to the different subperiods of a year so that the expected benefits are maximized. Its main idea is to distribute the energy stored in reservoirs in each period into two parts: one is directly sold in the energy market, while the other is made available to cover any unplanned outages of thermal units. The method proposed fulfills two objectives, to distribute the hydro energy optimally according to economic criteria and to assess the impact of new market rules on the reliability of an electric system. The procedure will be illustrated by an example based on the Spanish generating system.This work was supported by the Project PB-98-0728 of the Ministerio de Educación, Cultura y Deporte, Spain.Publicad

New therapies for hepatitis C

Hepatitis C virus is an important public health threat, not only because of the high prevalence of this infection in western and third world countries, but also because of the high rate of resistance to the available antiviral therapy that consists on the use of pegylated interferon plus ribavirin. Currently, new forms of therapy are being developed based on a more precise knowledge of the structure and function of the viral proteins and of the strategies used by the virus to escape the immune and interferon systems. The new therapeutic approaches aim at different objectives: a) the inhibition of viral replication by blocking the viral protease and/or replicase; b) the use of other types of interferon with more potent antiviral effect, c) the induction of a specific anti-viral immune response by means of immunomodulatory compounds or therapeutic vaccination, d) the blockade of "de novo" infection of other cells with neutralizing antibodies, e) the induction of a antiviral state in the liver by transferring to this organ the gene of interferon and/or immunostimulating cytokines

Gene therapy of liver cancer

The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/pro-drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition, gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer

Gauge invariance in simple mechanical systems

This article discusses and explains the Hamiltonian formulation for a class of simple gauge invariant mechanical systems consisting of point masses and idealized rods. The study of these models may be helpful to advanced undergraduate or graduate students in theoretical physics to understand, in a familiar context, some concepts relevant to the study of classical and quantum field theories. We use a geometric approach to derive the Hamiltonian formulation for the model considered in the paper: four equal masses connected by six ideal rods. We obtain and discuss the meaning of several important elements, in particular, the constraints and the Hamiltonian vector fields that define the dynamics of the system, the constraint manifold, gauge symmetries, gauge orbits, gauge fixing, and the reduced phase space.The authors want to thank Juan Margalef and Mariano Santander for their useful comments. This work has been supported by the Spanish MINECO research grants FIS2012-34379, FIS2014-57387-C3-3-P and the Consolider-Ingenio 2010 Program CPAN (CSD2007-00042)

Band structure in the polymer quantization of the harmonic oscillator

We discuss the detailed structure of the spectrum of the Hamiltonian for the polymerized harmonic oscillator and compare it with the spectrum in the standard quantization. As we will see the non-separability of the Hilbert space implies that the point spectrum consists of bands similar to the ones appearing in the treatment of periodic potentials. This feature of the spectrum of the polymeric harmonic oscillator may be relevant for the discussion of the polymer quantization of the scalar field and may have interesting consequences for the statistical mechanics of these models.We would like to thank W Chojnacki, A Corichi, J Lewandowski, T Pawłowski, P Singh and M Varadarajan for their valuable comments. This work has been supported by the Spanish MICINN research grants FIS2009-11893, FIS2012-34379 and the Consolider-Ingenio 2010 Program CPAN (CSD2007-00042)