Non-Parametric Approximations for Anisotropy Estimation in Two-dimensional Differentiable Gaussian Random Fields

Spatially referenced data often have autocovariance functions with elliptical isolevel contours, a property known as geometric anisotropy. The anisotropy parameters include the tilt of the ellipse (orientation angle) with respect to a reference axis and the aspect ratio of the principal correlation lengths. Since these parameters are unknown a priori, sample estimates are needed to define suitable spatial models for the interpolation of incomplete data. The distribution of the anisotropy statistics is determined by a non-Gaussian sampling joint probability density. By means of analytical calculations, we derive an explicit expression for the joint probability density function of the anisotropy statistics for Gaussian, stationary and differentiable random fields. Based on this expression, we obtain an approximate joint density which we use to formulate a statistical test for isotropy. The approximate joint density is independent of the autocovariance function and provides conservative probability and confidence regions for the anisotropy parameters. We validate the theoretical analysis by means of simulations using synthetic data, and we illustrate the detection of anisotropy changes with a case study involving background radiation exposure data. The approximate joint density provides (i) a stand-alone approximate estimate of the anisotropy statistics distribution (ii) informed initial values for maximum likelihood estimation, and (iii) a useful prior for Bayesian anisotropy inference.Comment: 39 pages; 8 figure

Protection against Divergent Influenza H1N1 Virus by a Centralized Influenza Hemagglutinin

Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 107 virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses

NMR of liquid 3He in clay pores at 1.5 K

In the present work a new method for studying porous media by nuclear magnetic resonance of liquid 3He has been proposed. This method has been demonstrated in an example of a clay mineral sample. For the first time the integral porosity of clay sample has been measured. For investigated samples the value of integral porosity is in the range of 10-30%. Inverse Laplace transform of 3He longitudinal magnetization recovery curve has been carried out, thus distribution of relaxation times T1 has been obtained.Comment: 9 pages, 5 figure

Paclitaxel resistance in untransformed human mammary epithelial cells is associated with an aneuploidy-prone phenotype

Despite its increasing clinical use, almost no data are currently available about paclitaxel effects on non-cancerous mammary epithelial cells. We have previously established paclitaxel-resistant sub-cell lines (paclitaxel-surviving populations, PSPs; n=20), and sensitive controls (control clones, CCs; n=10), from the untransformed human mammary epithelial cell line HME1. In this study, we aimed to establish whether paclitaxel resistance was associated with a modified sensitivity to paclitaxel-induced aneuploidy. For this purpose, we analysed basal and paclitaxel-induced chromosome missegregation, apoptosis and aberrant spindle multipolarisation as well as microtubular network composition for each subline. PSP sublines showed higher basal and paclitaxel-induced chromosome missegregation than the CC sublines. This phenomenon was associated with resistance to paclitaxel-induced apoptosis. No significant difference in paclitaxel-induced spindle pole abnormalities between CC and PSP sublines was found. Besides, we showed that a majority of PSPs display a constitutively disrupted microtubular network composition due to aberrant tubulin expression and post-translational modifications. These results clearly indicate that paclitaxel resistance in untransformed human mammary epithelial cells is related to an increased susceptibility to acquire aneuploidy in response to this agent. The consequences of these paclitaxel-associated alterations could be deleterious as they can potentially trigger tumorigenesis

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Arboviral Etiologies of Acute Febrile Illnesses in Western South America, 2000–2007

Over recent decades, the variety and quantity of diseases caused by viruses transmitted to humans by mosquitoes and other arthropods (also known as arboviruses) have increased around the world. One difficulty in studying these diseases is the fact that the symptoms are often non-descript, with patients reporting such symptoms as low-grade fever and headache. Our goal in this study was to use laboratory tests to determine the causes of such non-descript illnesses in sites in four countries in South America, focusing on arboviruses. We established a surveillance network in 13 locations in Ecuador, Peru, Bolivia, and Paraguay, where patient samples were collected and then sent to a central laboratory for testing. Between May 2000 and December 2007, blood serum samples were collected from more than 20,000 participants with fever, and recent arbovirus infection was detected for nearly one third of them. The most common viruses were dengue viruses (genera Flavivirus). We also detected infection by viruses from other genera, including Alphavirus and Orthobunyavirus. This data is important for understanding how such viruses might emerge as significant human pathogens

The search for transient astrophysical neutrino emission with IceCube-DeepCore

We present the results of a search for astrophysical sources of brief transient neutrino emission using IceCube and DeepCore data acquired between 2012 May 15 and 2013 April 30. While the search methods employed in this analysis are similar to those used in previous IceCube point source searches, the data set being examined consists of a sample of predominantly sub-TeV muon-neutrinos from the Northern Sky (-5 degrees < delta < 90 degrees) obtained through a novel event selection method. This search represents a first attempt by IceCube to identify astrophysical neutrino sources in this relatively unexplored energy range. The reconstructed direction and time of arrival of neutrino events are used to search for any significant self-correlation in the data set. The data revealed no significant source of transient neutrino emission. This result has been used to construct limits at timescales ranging from roughly 1 s to 10 days for generic soft-spectra transients. We also present limits on a specific model of neutrino emission from soft jets in core-collapse supernovae

Synthesis and Biological Evaluation of 2-Methyl-4,5-Disubstituted Oxazoles as a Novel Class of Highly Potent Antitubulin Agents

Antimitotic agents that interfere with microtubule formation are one of the major classes of cytotoxic drugs for cancer treatment. Multiple 2-methyl-4-(3′,4′,5′-trimethoxyphenyl)-5-substituted oxazoles and their related 4-substituted-5-(3′,4′,5′-trimethoxyphenyl) regioisomeric derivatives designed as cis-constrained combretastatin A-4 (CA-4) analogues were synthesized and evaluated for their antiproliferative activity in vitro against a panel of cancer cell lines and, for selected highly active compounds, interaction with tubulin, cell cycle effects and in vivo potency. Both these series of compounds were characterized by the presence of a common 3′,4′,5′-trimethoxyphenyl ring at either the C-4 or C-5 position of the 2-methyloxazole ring. Compounds 4g and 4i, bearing a m-fluoro-p-methoxyphenyl or p-ethoxyphenyl moiety at the 5-position of 2-methyloxazole nucleus, respectively, exhibited the greatest antiproliferative activity, with IC50 values of 0.35-4.6 nM (4g) and 0.5–20.2 nM (4i), which are similar to those obtained with CA-4. These compounds bound to the colchicine site of tubulin and inhibited tubulin polymerization at submicromolar concentrations. Furthermore, 4i strongly induced apoptosis that follows the mitochondrial pathway. In vivo, 4i in a mouse syngeneic model demonstrated high antitumor activity which significantly reduced the tumor mass at doses ten times lower than that required for CA-4P, suggesting that 4i warrants further evaluation as a potential anticancer drug

Contribution of Pollinator-Mediated Crops to Nutrients in the Human Food Supply

The contribution of nutrients from animal pollinated world crops has not previously been evaluated as a biophysical measure for the value of pollination services. This study evaluates the nutritional composition of animal-pollinated world crops. We calculated pollinator dependent and independent proportions of different nutrients of world crops, employing FAO data for crop production, USDA data for nutritional composition, and pollinator dependency data according to Klein et al. (2007). Crop plants that depend fully or partially on animal pollinators contain more than 90% of vitamin C, the whole quantity of Lycopene and almost the full quantity of the antioxidants β-cryptoxanthin and β-tocopherol, the majority of the lipid, vitamin A and related carotenoids, calcium and fluoride, and a large portion of folic acid. Ongoing pollinator decline may thus exacerbate current difficulties of providing a nutritionally adequate diet for the global human population