2,279 research outputs found

    Cuts and flows of cell complexes

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    We study the vector spaces and integer lattices of cuts and flows associated with an arbitrary finite CW complex, and their relationships to group invariants including the critical group of a complex. Our results extend to higher dimension the theory of cuts and flows in graphs, most notably the work of Bacher, de la Harpe and Nagnibeda. We construct explicit bases for the cut and flow spaces, interpret their coefficients topologically, and give sufficient conditions for them to be integral bases of the cut and flow lattices. Second, we determine the precise relationships between the discriminant groups of the cut and flow lattices and the higher critical and cocritical groups with error terms corresponding to torsion (co)homology. As an application, we generalize a result of Kotani and Sunada to give bounds for the complexity, girth, and connectivity of a complex in terms of Hermite's constant.Comment: 30 pages. Final version, to appear in Journal of Algebraic Combinatoric

    Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

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    The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

    Field-testing of the rapid assessment of disability questionnaire

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    The Rapid Assessment of Disability (RAD) questionnaire measures the magnitude and impact of disability and aims to inform the design of disability inclusive development programs. This paper reports the psychometric evaluation of the RAD

    Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity

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    Aquaglyceroporins (AQPs) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM), octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO) can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited

    The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

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    Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

    Pentamidine Is Not a Permeant but a Nanomolar Inhibitor of the Trypanosoma brucei Aquaglyceroporin-2

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    The chemotherapeutic arsenal against human African trypanosomiasis, sleeping sickness, is limited and can cause severe, often fatal, side effects. One of the classic and most widely used drugs is pentamidine, an aromatic diamidine compound introduced in the 1940s. Recently, a genome-wide loss-of-function screen and a subsequently generated trypanosome knockout strain revealed a specific aquaglyceroporin, TbAQP2, to be required for high-affinity uptake of pentamidine. Yet, the underlying mechanism remained unclear. Here, we show that TbAQP2 is not a direct transporter for the di-basic, positively charged pentamidine. Even though one of the two common cation filters of aquaglyceroporins, i.e. the aromatic/arginine selectivity filter, is unconventional in TbAQP2, positively charged compounds are still excluded from passing the channel. We found, instead, that the unique selectivity filter layout renders pentamidine a nanomolar inhibitor of TbAQP2 glycerol permeability. Full, non-covalent inhibition of an aqua(glycero)porin in the nanomolar range has not been achieved before. The remarkable affinity derives from an electrostatic interaction with Asp265 and shielding from water as shown by structure-function evaluation and point mutation of Asp265. Exchange of the preceding Leu264 to arginine abolished pentamidine-binding and parasites expressing this mutant were pentamidine-resistant. Our results indicate that TbAQP2 is a high-affinity receptor for pentamidine. Taken together with localization of TbAQP2 in the flagellar pocket of bloodstream trypanosomes, we propose that pentamidine uptake is by endocytosis

    Geohazards analysis of Pisa tunnel in a fractured incompetent rocks in Zagros Mountains, Iran.

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    The Pisa 2 tunnel with 740 m in length and 20° N trend is located along the Kazerun fault zone in Simply Folded Belt of Zagros, Iran. This tunnel has been excavated in the fractured incompetent marl layers with high expansive pressure of up to 2 kg/cm2. In this study, the geological hazards along the tunnel have been recognized and categorized. This study revealed that, in the long-term usage of the tunnel, the lining did not endure against the loading and the secondary leakages. It is mainly attributed due to the non-efficiencies of drainage and isolation systems in the tunnel site. Therefore, it caused asphalt damage, drainage damage, and wall distortion. FLAC3D software has been used in this research. We conducted various analyses for pre-excavation stress states, syn-excavation, and post-excavation strain states. The results showed no indication of instability and critical deformations during the excavation time. It also revealed that due to the non-efficiencies of drainage and isolation systems against secondary leakages and consequently marl expansion, the volumetric and shear strains (i.e., expansions and displacements) have exceeded from the critical states of strain along the tunnel. For various remedy purpose, this paper attempted several measures that can be taken in order to modify the drainage and isolation systems along the tunnel area. The reconstruction of drainage systems with suitable reinforced concrete and adequate slope has been proposed. The width of channel and isolation of backside of lining and implementation of multi-order outlets (i.e., backside of lining) for draining of groundwater into where the main drainage systems are located in the tunnel gallery were suggested

    Habitat structure: a fundamental concept and framework for urban soil ecology

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    Habitat structure is defined as the composition and arrangement of physical matter at a location. Although habitat structure is the physical template underlying ecological patterns and processes, the concept is relatively unappreciated and underdeveloped in ecology. However, it provides a fundamental concept for urban ecology because human activities in urban ecosystems are often targeted toward management of habitat structure. In addition, the concept emphasizes the fine-scale, on-the-ground perspective needed in the study of urban soil ecology. To illustrate this, urban soil ecology research is summarized from the perspective of habitat structure effects. Among the key conclusions emerging from the literature review are: (1) habitat structure provides a unifying theme for multivariate research about urban soil ecology; (2) heterogeneous urban habitat structures influence soil ecological variables in different ways; (3) more research is needed to understand relationships among sociological variables, habitat structure patterns and urban soil ecology. To stimulate urban soil ecology research, a conceptual framework is presented to show the direct and indirect relationships among habitat structure and ecological variables. Because habitat structure serves as a physical link between sociocultural and ecological systems, it can be used as a focus for interdisciplinary and applied research (e.g., pest management) about the multiple, interactive effects of urbanization on the ecology of soils

    TRY plant trait database - enhanced coverage and open access

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    Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
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