741 research outputs found

    Sense of Community on Integrated Wilderness Trips: A Pilot Study

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    The purpose of this study was to examine sense of community on integrated wilderness trips. First, differences in perceived sense of community and perceived sense of group cohesion were analyzed from the viewpoint of the group as a whole to determine if there was any significant change over the course of a wilderness trip. Second, differences, if any, in perceived sense of community and perceived sense of group cohesion between people with disabilities and people without disabilities were determined

    Palladium(ii) complexes with chiral organoantimony(iii) ligands. Solution behaviour and solid state structures

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    The chiral compound (2-Me2NCH2C6H 4)PhSbCl (1) was obtained from (2-Me2NCH2C 6H4)Li and PhSbCl2 in 1:1 molar ratio, while (2-Me2NCH2C6H4)Mes2Sb (2) was prepared from (2-Me2NCH2C6H 4)SbCl2 and MesMgBr in 1:2 molar ratio. The compounds 1 and 2 were used to obtain the Pd(ii)/stibine complexes: [Me2NHCH 2C6H5]+[PdCl3SbCl(Ph) (C6H4CH2NMe2-2)-Sb]- (3) and [PdCl2SbMes2(C6H4CH 2NMe2-2)-N,Sb] (4). All the compounds were characterized by multinuclear NMR spectroscopy in solution, elemental analysis, mass spectrometry and single-crystal X-ray diffraction studies. In compounds 1-3 the coordination geometry around the antimony atom is pseudo-trigonal bipyramidal, while in compound 4 a tetrahedral geometry around the antimony atom is observed. Theoretical calculations at the DFT level on compounds 1-4 were used in order to gain insight into the nature of the coordinative bonds

    Cyclophilin D links programmed cell death and organismal aging in Podospora anserina

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    This is the final version of the article. Available from Wiley via the DOI in this record.Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl-cis,trans-isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wild-type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild-type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging.The research was supported by grants of the Deutsche Forschungsgemeinschaft (Os75/12-1) and by the European Commission via the Integrated Project with the acronym MiMage; (LSHM-CT-2004-512020)

    β-Glucuronidase triggers extracellular MMAE release from an integrin-targeted conjugate

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    A non-internalizing \u3b1v\u3b23 integrin ligand was conjugated to the anticancer drug MMAE through a \u3b2-glucuronidase-responsive linker. In the presence of \u3b2-glucuronidase, only the conjugate bearing a PEG4 spacer inhibited the proliferation of integrin-expressing cancer cells at low nanomolar concentrations, indicating important structural requirements for the efficacy of these therapeutics

    Architecture of the yeast elongator complex

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    The highly conserved eukaryotic Elongator complex performs specific chemical modifications on wobble base uridines of tRNAs, which are essential for proteome stability and homeostasis. The complex is formed by six individual subunits (Elp1-6) that are all equally important for its tRNA modification activity. However, its overall architecture and the detailed reaction mechanism remain elusive. Here, we report the structures of the fully assembled yeast Elongator and the Elp123 sub-complex solved by an integrative structure determination approach showing that two copies of the Elp1, Elp2, and Elp3 subunits form a two-lobed scaffold, which binds Elp456 asymmetrically. Our topological models are consistent with previous studies on individual subunits and further validated by complementary biochemical analyses. Our study provides a structural framework on how the tRNA modification activity is carried out by Elongator

    BETULA: Numerically Stable CF-Trees for BIRCH Clustering

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    BIRCH clustering is a widely known approach for clustering, that has influenced much subsequent research and commercial products. The key contribution of BIRCH is the Clustering Feature tree (CF-Tree), which is a compressed representation of the input data. As new data arrives, the tree is eventually rebuilt to increase the compression. Afterward, the leaves of the tree are used for clustering. Because of the data compression, this method is very scalable. The idea has been adopted for example for k-means, data stream, and density-based clustering. Clustering features used by BIRCH are simple summary statistics that can easily be updated with new data: the number of points, the linear sums, and the sum of squared values. Unfortunately, how the sum of squares is then used in BIRCH is prone to catastrophic cancellation. We introduce a replacement cluster feature that does not have this numeric problem, that is not much more expensive to maintain, and which makes many computations simpler and hence more efficient. These cluster features can also easily be used in other work derived from BIRCH, such as algorithms for streaming data. In the experiments, we demonstrate the numerical problem and compare the performance of the original algorithm compared to the improved cluster features

    Application of ultrafast gold luminescence to measuring the instrument response function for multispectral multiphoton fluorescence lifetime imaging

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    When performing multiphoton fluorescence lifetime imaging in multiple spectral emission channels, an instrument response function must be acquired in each channel if accurate measurements of complex fluorescence decays are to be performed. Although this can be achieved using the reference reconvolution technique, it is difficult to identify suitable fluorophores with a mono-exponential fluorescence decay across a broad emission spectrum. We present a solution to this problem by measuring the IRF using the ultrafast luminescence from gold nanorods. We show that ultrafast gold nanorod luminescence allows the IRF to be directly obtained in multiple spectral channels simultaneously across a wide spectral range. We validate this approach by presenting an analysis of multispectral autofluorescence FLIM data obtained from human skin ex vivo
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