Sequential networks for cosmic ray simulations

A hybrid model of generating cosmic ray showers based on neural networks is presented. We show that the neural network learns the solution to the governing cascade equation in one dimension. We then use the neural network to generate the energy spectra at every height slice. Pitfalls of training to generate a single height slice is discussed, and we present a sequential model which can generate the entire shower from an initial table. Errors associated with the model and the potential to generate the full three dimensional distribution of the shower is discussed

POM2/CSI1 is essential for functional association of cellulose synthase and microtubules in Arabidopsis

In plants, regulation of cellulose synthesis is fundamental for morphogenesis and plant growth. Cellulose is synthesized at the plasma membrane, and the orientation of synthesis is guided by cortical microtubules; however, the guiding mechanism is currently unknown. We show that the conditional root elongation pom2 mutants are impaired in cell elongation, fertility, and microtubule-related functions. Map-based cloning of the POM-POM2 locus revealed that it is allelic to CELLULOSE SYNTHASE INTERACTING1 (CSI1). Fluorescently tagged POM2/CSI1s associated with both plasma membrane-located cellulose synthases (CESAs) and post-Golgi CESA-containing compartments. Interestingly, while CESA insertions coincided with cortical microtubules in the pom2/csi1 mutants, the microtubule-defined movement of the CESAs was significantly reduced in the mutant. We propose that POM2/CSI1 provides a scaffold between the CESAs and cortical microtubules that guide cellulose synthesis

Tropical Dominating Sets in Vertex-Coloured Graphs

Given a vertex-coloured graph, a dominating set is said to be tropical if every colour of the graph appears at least once in the set. Here, we study minimum tropical dominating sets from structural and algorithmic points of view. First, we prove that the tropical dominating set problem is NP-complete even when restricted to a simple path. Then, we establish upper bounds related to various parameters of the graph such as minimum degree and number of edges. We also give upper bounds for random graphs. Last, we give approximability and inapproximability results for general and restricted classes of graphs, and establish a FPT algorithm for interval graphs.Comment: 19 pages, 4 figure

Monitoring of Noctiluca Bloom in Mandapam and Keelakarai Coastal Waters; Southeast Coast of India

Monitoring the Harmful Algal Blooms was carried out during July to December 2008 in Mandapam and Keelakarai coastal waters of Tamil Nadu, Southeast coast of India. In the month of October several fishes and shellfishes were died due to Noctiluca blooms along these two areas. The present investigation the following species of phyto and zooplankton were found to be common; phytoplankton such as Coscinodiscus sp., Skeletonema costatum, Bacillaria paradoxa, Thallassiothrix frauenfeldii, T. longisima, Leptocylindrus sp., and  zooplankton such as Paracalanus parvus, Acrocalanus gracilis, Pseudodiaptomus serricautatus, Rhincalanus cornutus, R. nasutus, Euterpina acutifrons, Nannocalanus minor, Eucalanus attenuates, E. crassus, Fish larvae, Fish eggs, Barnacle nauplii, Bivalve larvae, Gastropod larvae, Copepod nauplii  and Mysis larvae. The hydrobiological parameters also analysed during bloom and after blooms; the dissolved oxygen (2.6 – 4.9µM L-1) nutrients varied between nitrate (0.66 – 1.01µM L-1) nitrite (0.11 – 0.21µM L-1) phosphate (0.51 – 0.86µM L-1) and silicate (0.81 – 4.2µM L-1)

Targeting Glycosylation Pathways and the Cell Cycle: Sugar-Dependent Activity of Butyrate-Carbohydrate Cancer Prodrugs

SummaryShort-chain fatty acid (SCFA)-carbohydrate hybrid molecules that target both histone deacetylation and glycosylation pathways to achieve sugar-dependent activity against cancer cells are described in this article. Specifically, n-butyrate esters of N-acetyl-d-mannosamine (But4ManNAc, 1) induced apoptosis, whereas corresponding N-acetyl-d-glucosamine (But4GlcNAc, 2), d-mannose (But5Man, 3), or glycerol (tributryin, 4) derivatives only provided transient cell cycle arrest. Western blots, reporter gene assays, and cell cycle analysis established that n-butyrate, when delivered to cells via any carbohydrate scaffold, functioned as a histone deacetylase inhibitor (HDACi), upregulated p21WAF1/Cip1 expression, and inhibited proliferation. However, only 1, a compound that primed sialic acid biosynthesis and modulated the expression of a different set of genes compared to 3, ultimately killed the cells. These results demonstrate that the biological activity of butyrate can be tuned by sugars to improve its anticancer properties

CMV infection of liver transplant recipients: comparison of antigenemia and molecular biology assays

BACKGROUND: CMV is a major clinical problem in transplant recipients. Thus, it is important to use sensitive and specific diagnostic techniques to rapidly and accurately detect CMV infection and identify patients at risk of developing CMV disease. In the present study, CMV infection after liver transplantation was monitored retrospectively by two molecular biology assays - a quantitative PCR assay and a qualitative NASBA assay. The results were compared with those obtained by prospective pp65 antigenemia determinations. MATERIALS AND METHODS: 87 consecutive samples from 10 liver transplanted patients were tested for CMV by pp65 antigenemia, and CMV monitor and NASBA pp67 mRNA assay. RESULTS: CMV infection was detected in all patients by antigenemia and CMV monitor, whereas NASBA assay identified only 8/10 patients with viremia. Furthermore, CMV infection was never detected earlier by molecular biology assays than by antigenemia. Only 5/10 patients with CMV infection developed CMV disease. Using a cut off value of 8 cells/50,000, antigenemia was found to be the assay that better identified patients at risk of developing CMV disease. However, the kinetics of the onset of infection detected by NASBA and CMV monitor seemed to have better identified patients at risk of developing CMV disease. Furthermore, before onset of disease, CMV pp67 mRNA was found to have similar or better negative and positive predictive values for the development of CMV disease. CONCLUSIONS: The present data, suggests that the concomitant use of antigenemia and pp67 mRNA assay gives the best identification of patients at risk of developing CMV disease

Visualization of cellulose synthases in Arabidopsis secondary cell walls

Cellulose biosynthesis in plant secondary cell walls forms the basis of vascular development in land plants, with xylem tissues constituting the vast majority of terrestrial biomass. We used plant lines that contained an inducible master transcription factor controlling xylem cell fate to quantitatively image fluorescently tagged cellulose synthase enzymes during cellulose deposition in living protoxylem cells. The formation of secondary cell wall thickenings was associated with a redistribution and enrichment of CESA7-containing cellulose synthase complexes (CSCs) into narrow membrane domains. The velocities of secondary cell wall–specific CSCs were faster than those of primary cell wall CSCs during abundant cellulose production. Dynamic intracellular of endomembranes, in combination with increased velocity and high density of CSCs, enables cellulose to be synthesized rapidly in secondary cell walls

Kinetics and Ligand-Binding Preferences of Mycobacterium tuberculosis Thymidylate Synthases, ThyA and ThyX

Mycobacterium tuberculosis kills approximately 2 million people each year and presents an urgent need to identify new targets and new antitubercular drugs. Thymidylate synthase (TS) enzymes from other species offer good targets for drug development and the M. tuberculosis genome contains two putative TS enzymes, a conventional ThyA and a flavin-based ThyX. In M. tuberculosis, both TS enzymes have been implicated as essential for growth, either based on drug-resistance studies or genome-wide mutagenesis screens. To facilitate future small molecule inhibitors against these proteins, a detailed enzymatic characterization was necessary.After cloning, overexpression, and purification, the thymidylate-synthesizing ability of ThyA and ThyX gene products were directly confirmed by HPLC analysis of reaction products and substrate saturation kinetics were established. 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) was a potent inhibitor of both ThyA and ThyX, offering important clues to double-targeting strategies. In contrast, the folate-based 1843U89 was a potent inhibitor of ThyA but not ThyX suggesting that it should be possible to find ThyX-specific antifolates. A turnover-dependent kinetic assay, combined with the active-site titration approach of Ackermann and Potter, revealed that both M. tuberculosis enzymes had very low k(cat) values. One possible explanation for the low catalytic activity of M. tuberculosis ThyX is that its true biological substrates remain to be identified. Alternatively, this slow-growing pathogen, with low demands for TMP, may have evolved to down-regulate TS activities by altering the turnover rate of individual enzyme molecules, perhaps to preserve total protein quantities for other purposes. In many organisms, TS is often used as a part of larger complexes of macromolecules that control replication and DNA repair.Thus, the present enzymatic characterization of ThyA and ThyX from M. tuberculosis provides a framework for future development of cell-active inhibitors and the biological roles of these TS enzymes in M. tuberculosis

Femtogram Doubly Clamped Nanomechanical Resonators Embedded in a High-Q Two-Dimensional Photonic Crystal Nanocavity

We demonstrate a new optomechanical device system which allows highly efficient transduction of femtogram nanobeam resonators. Doubly clamped nanomechanical resonators with mass as small as 25 fg are embedded in a high-finesse two-dimensional photonic crystal nanocavity. Optical transduction of the fundamental flexural mode around 1 GHz was performed at room temperature and ambient conditions, with an observed displacement sensitivity of 0.94 fm/Hz^(1/2). Comparison of measurements from symmetric and asymmetric double-beam devices reveals hybridization of the mechanical modes where the structural symmetry is shown to be the key to obtain a high mechanical quality factor. Our novel configuration opens the way for a new category of "NEMS-in-cavity" devices based on optomechanical interaction at the nanoscale.Comment: Nano Lett. 201

ModBase, a database of annotated comparative protein structure models, and associated resources

ModBase (http://salilab.org/modbase) is a database of annotated comparative protein structure models. The models are calculated by ModPipe, an automated modeling pipeline that relies primarily on Modeller for fold assignment, sequence–structure alignment, model building and model assessment (http://salilab.org/modeller/). ModBase currently contains 10 355 444 reliable models for domains in 2 421 920 unique protein sequences. ModBase allows users to update comparative models on demand, and request modeling of additional sequences through an interface to the ModWeb modeling server (http://salilab.org/modweb). ModBase models are available through the ModBase interface as well as the Protein Model Portal (http://www.proteinmodelportal.org/). Recently developed associated resources include the SALIGN server for multiple sequence and structure alignment (http://salilab.org/salign), the ModEval server for predicting the accuracy of protein structure models (http://salilab.org/modeval), the PCSS server for predicting which peptides bind to a given protein (http://salilab.org/pcss) and the FoXS server for calculating and fitting Small Angle X-ray Scattering profiles (http://salilab.org/foxs)