446 research outputs found

    The Effects of Kinesio Tape on Postural Control in Female Athletes With Chronic Ankle Instability

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    Please refer to the pdf version of the abstract located adjacent to the title

    Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans

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    Inappropriate activation of innate immune responses in intestinal epithelial cells underlies the pathophysiology of inflammatory disorders of the intestine. Here we examine the physiological effects of immune hyperactivation in the intestine of the nematode Caenorhabditis elegans. We previously identified an immunostimulatory xenobiotic that protects C. elegans from bacterial infection by inducing immune effector expression via the conserved p38 MAP kinase pathway, but was toxic to nematodes developing in the absence of pathogen. To investigate a possible connection between the toxicity and immunostimulatory properties of this xenobiotic, we conducted a forward genetic screen for C. elegans mutants that are resistant to the deleterious effects of the compound, and identified five toxicity suppressors. These strains contained hypomorphic mutations in each of the known components of the p38 MAP kinase cassette (tir-1, nsy-1, sek-1, and pmk-1), demonstrating that hyperstimulation of the p38 MAPK pathway is toxic to animals. To explore mechanisms of immune pathway regulation in C. elegans, we conducted another genetic screen for dominant activators of the p38 MAPK pathway, and identified a single allele that had a gain-of-function (gf) mutation in nsy-1, the MAP kinase kinase kinase that acts upstream of p38 MAPK pmk-1. The nsy-1(gf) allele caused hyperinduction of p38 MAPK PMK-1-dependent immune effectors, had greater levels of phosphorylated p38 MAPK, and was more resistant to killing by the bacterial pathogen Pseudomonas aeruginosa compared to wild-type controls. In addition, the nsy-1(gf) mutation was toxic to developing animals. Together, these data suggest that the activity of the MAPKKK NSY-1 is tightly regulated as part of a physiological mechanism to control p38 MAPK-mediated innate immune hyperactivation, and ensure cellular homeostasis in C. elegans

    Innate Immunity in the C. elegans Intestine Is Programmed by a Neuronal Regulator of AWC Olfactory Neuron Development

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    Olfactory neurons allow animals to discriminate nutritious food sources from potential pathogens. From a forward genetic screen, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity in Caenorhabditis elegans. During nematode development, olrn-1 is required to program the expression of odorant receptors in the AWC olfactory neuron pair. Here, we show that olrn-1 also functions in AWC neurons in the cell non-autonomous suppression of the canonical p38 MAPK PMK-1 immune pathway in the intestine. Low activity of OLRN-1, which activates the p38 MAPK signaling cassette in AWC neurons during larval development, also de-represses the p38 MAPK PMK-1 pathway in the intestine to promote immune effector transcription, increased clearance of an intestinal pathogen, and resistance to bacterial infection. These data reveal an unexpected connection between olfactory receptor development and innate immunity and show that anti-pathogen defenses in the intestine are developmentally programmed

    Probing a Complex of Cytochromecand Cardiolipin by Magnetic Circular Dichroism Spectroscopy: Implications for the Initial Events in Apoptosis

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    Oxidation of cardiolipin (CL) by its complex with cytochrome c (cyt c) plays a crucial role in triggering apoptosis. Through a combination of magnetic circular dichroism spectroscopy and potentiometric titrations, we show that both the ferric and ferrous forms of the heme group of a CL:cyt c complex exist as multiple conformers at a physiologically relevant pH of 7.4. For the ferric state, these conformers are His/Lys- and His/OH–-ligated. The ferrous state is predominantly high-spin and, most likely, His/–. Interconversion of the ferric and ferrous conformers is described by a single midpoint potential of -80 ± 9 mV vs SHE. These results suggest that CL oxidation in mitochondria could occur by the reaction of molecular oxygen with the ferrous CL:cyt c complex in addition to the well-described reaction of peroxides with the ferric form

    Similar patterns of leaf temperatures and thermal acclimation to warming in temperate and tropical tree canopies

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    As the global climate warms, a key question is how increased leaf temperatures will affect tree physiology and the coupling between leaf and air temperatures in forests. To explore the impact of increasing temperatures on plant performance in open air, we warmed leaves in the canopy of two mature evergreen forests, a temperate Eucalyptus woodland and a tropical rainforest. The leaf heaters consistently maintained leaves at a target of 4 °C above ambient leaf temperatures. Ambient leaf temperatures (Tleaf) were mostly coupled to air temperatures (Tair), but at times, leaves could be 8–10 °C warmer than ambient air temperatures, especially in full sun. At both sites, Tleaf was warmer at higher air temperatures (Tair > 25 °C), but was cooler at lower Tair, contrary to the ‘leaf homeothermy hypothesis’. Warmed leaves showed significantly lower stomatal conductance (−0.05 mol m−2 s−1 or −43% across species) and net photosynthesis (−3.91 μmol m−2 s−1 or −39%), with similar rates in leaf respiration rates at a common temperature (no acclimation). Increased canopy leaf temperatures due to future warming could reduce carbon assimilation via reduced photosynthesis in these forests, potentially weakening the land carbon sink in tropical and temperate forests

    The sweet spot in sustainability: a framework for corporate assessment in sugar manufacturing

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    The assessment of corporate sustainability has become an increasingly important topic, both within academia and in industry. For manufacturing companies to conform to their commitments to sustainable development, a standard and reliable measurement framework is required. There is, however, a lack of sector-specific and empirical research in many areas, including the sugar industry. This paper presents an empirically developed framework for the assessment of corporate sustainability within the Thai sugar industry. Multiple case studies were conducted, and a survey using questionnaires was also employed to enhance the power of generalisation. The developed framework is an accurate and reliable measurement instrument of corporate sustainability, and guidelines to assess qualitative criteria are put forward. The proposed framework can be used for a company’s self-assessment and for guiding practitioners in performance improvement and policy decision-maki

    Contract Aware Components, 10 years after

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    The notion of contract aware components has been published roughly ten years ago and is now becoming mainstream in several fields where the usage of software components is seen as critical. The goal of this paper is to survey domains such as Embedded Systems or Service Oriented Architecture where the notion of contract aware components has been influential. For each of these domains we briefly describe what has been done with this idea and we discuss the remaining challenges.Comment: In Proceedings WCSI 2010, arXiv:1010.233

    Characterization of the S = 9 excited state in Fe8Br8 by Electron Paramagnetic Resonance

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    High Frequency electron paramagnetic resonance has been used to observe the magnetic dipole, Δ\Delta Ms_s = ±\pm 1, transitions in the S=9S = 9 excited state of the single molecule magnet Fe8_8Br8_8. A Boltzmann analysis of the measured intensities locates it at 24 ±\pm 2 K above the S=10S = 10 ground state, while the line positions yield its magnetic parameters D = -0.27 K, E = ±\pm0.05 K, and B40_4^0 = -1.3×\times 106^{-6} K. D is thus smaller by 8% and E larger by 7% than for S=10S = 10. The anisotropy barrier for S=9S = 9 is estimated as 22 K,which is 25% smaller than that for S=10S = 10 (29 K). These data also help assign the spin exchange constants(J's) and thus provide a basis for improved electronic structure calculations of Fe8_8Br8_8.Comment: 7 pages, Figs included in text, submitted to PR

    Effect of local Coulomb interactions on the electronic structure and exchange interactions in Mn12 magnetic molecules

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    We have studied the effect of local Coulomb interactions on the electronic structure of the molecular magnet Mn12-acetate within the LDA+U approach. The account of the on-site repulsion results in a finite energy gap and an integer value of the molecule's magnetic moment, both quantities being in a good agreement with the experimental results. The resulting magnetic moments and charge states of non-equivalent manganese ions agree very well with experiments. The calculated values of the intramolecular exchange parameters depend on the molecule's spin configuration, differing by 25-30% between the ferrimagnetic ground state and the completely ferromagnetic configurations. The values of the ground-state exchange coupling parameters are in reasonable agreement with the recent data on the magnetization jumps in megagauss magnetic fields. Simple estimates show that the obtained exchange parameters can be applied, at least qualitatively, to the description of the spin excitations in Mn12-acetate.Comment: RevTeX, LaTeX2e, 4 EPS figure

    DT‐PACE/ESHAP chemotherapy regimens as salvage therapy for multiple myeloma prior to autologous stem cell transplantation

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    Routine use of novel agents to treat newly diagnosed and relapsed multiple myeloma (MM) produces high response rates and improved survival. However, 15–20% of patients have suboptimal responses and their management remains challenging.1 Traditional regimens, such as DT‐PACE (dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide) and ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) are employed in patients with relapsed/refractory (RR) disease, and may bridge patients to autologous stem cell transplantation (ASCT).2-4 Originally developed to improve responses to traditional chemotherapy regimens, and enable stem cell mobilization,5-7 the role of infusional regimens in the context of novel agents is unclear, especially as recently reported series indicate relatively poor outcomes.8, 9 These regimens can be associated with significant toxicity,2 placing a burden on healthcare resources.10 We undertook a single‐centre retrospective analysis to assess the role of infusional regimens in RR MM patients to explore and identify features associated with clinical benefit. Relevant clinical information was obtained from electronic records. Overall response rate (ORR) and cytogenetic risk were assessed as per International Myeloma Working Group (IMWG) criteria (Table I).11 [Progression‐free (PFS) and overall survival (OS) were estimated using Kaplan–Meier and Cox regression methods (time‐dependent where appropriate)]
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