756 research outputs found

    Effects of Teaching Resourcefulness and Acceptance on Affect, Behavior, and Cognition of Chronically Ill Elders

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    This clinical trial examined changes in affect, behavior, and cognition in 176 chronically ill elders who were randomly assigned to Resourcefulness Training (RT), Acceptance Training (AT), or Diversional Activities (DA). The RT group improved on affect (t(1,42) = 4.91; p \u3c .001) and cognition (t(1,42) = 2.03; p\u3c .05) and these effects lasted 12 weeks. The AT group improved on affect (t(1,36) = 3.08; p \u3c .01), but this improvement did not persist. The RT and AT groups both showed positive behavior changes after six weeks. There were no changes in the DA group. The findings suggest that teaching elders resourcefulness and acceptance of chronic conditions may promote healthy functioning and improve their quality of life

    Dislocation and degradation from the ER are regulated by cytosolic stress

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    Akey step in ER-associated degradation (ERAD) is dislocation of the substrate protein from the ER into the cytosol to gain access to the proteasome. Very little is known about how this process is regulated, especially in the case of polytopic proteins. Using pulse-chase analysis combined with subcellular fractionation, we show that connexins, the four transmembrane structural components of gap junctions, can be chased in an intact form from the ER membrane into the cytosol of proteasome inhibitor–treated cells. Dislocation of endogenously expressed connexin from the ER was reduced 50–80% when the cytosolic heat shock response was induced by mild oxidative or thermal stress, but not by treatments that instead upregulate the ER unfolded protein response. Cytosolic but not ER stresses slowed the normally rapid degradation of connexins, and led to a striking increase in gap junction formation and function in otherwise assembly-inefficient cell types. These treatments also inhibited the dislocation and turnover of a connexin-unrelated ERAD substrate, unassembled major histocompatibility complex class I heavy chain. Our findings demonstrate that dislocation is negatively regulated by physiologically relevant, nonlethal stress. They also reveal a previously unrecognized relationship between cytosolic stress and intercellular communication

    Intracellular Transport, Assembly, and Degradation of Wild-Type and Disease-linked Mutant Gap Junction Proteins

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    More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot–Marie–Tooth disease (CMTX). How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To address these issues, we have studied the intracellular transport, assembly, and degradation of three CMTX-linked Cx32 mutants stably expressed in PC12 cells. Each mutant had a distinct fate: E208K Cx32 appeared to be retained in the endoplasmic reticulum (ER), whereas both the E186K and R142W mutants were transported to perinuclear compartments from which they trafficked either to lysosomes (R142W Cx32) or back to the ER (E186K Cx32). Despite these differences, each mutant was soluble in nonionic detergent but unable to assemble into homomeric connexons. Degradation of both mutant and wild-type connexins was rapid (t1/2 \u3c 3 h) and took place at least in part in the ER by a process sensitive to proteasome inhibitors. The mutants studied are therefore unlikely to cause disease by accumulating in degradation-resistant aggregates but instead are efficiently cleared from the cell by quality control processes that prevent abnormal connexin molecules from traversing the secretory pathway

    FEM modeling of magnetic microwire and its using for stress monitoring inside the composite beam

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    The proposed article is devoted to the stress evaluation inside the composite beam using the embedded magnetic microwire sensors. The interlaminar stresses with high values can occur inside the composite structures during the operation. It is essential to monitor the stresses and to increase the lifetime of the composite materials by prediction using the research results from the stress distribution estimation and also during the operation using the embedded magnetic microwire-based sensors. In the article the results of the mechanical stress distribution between the magnetic microwire coating and core and the discussion about the experimental application of the magnetic microwire inside the composite beam are presented

    Assembly of a polymer lab-on-chip device for impedimetric measurements of D-dimers in whole blood

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    This paper reports the development and characterisation of an assembly technology for a polymer lab-on-chip. The system consists of a 150 m deep hot embossed microfluidic channel in polycarbonate and Au electrodes fabricated separately by photolithography on polyethylenenaphthalate. The system is designed for impedimetric immunoassay detection in whole blood. Electrode layer and microfluidic substrate are joined by means of a 50 m thick double-sided medical grade adhesive tape, adjusted with an optical alignment system. The bond proved to be liquid tight at room temperature. An alignment accuracy of 34 m (+/- 19 m) evaluated over a set of 23 samples, was achieved. The effect of alignment accuracy of the intermediate adhesive film on whole blood flow properties in the device is studied. Already an alignment error of 70 m increases the flushing out time of whole blood by approximately 20 %

    Two-Functional Direct Current Sputtered Silver-Containing Titanium Dioxide Thin Films

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    The article reports on structure, mechanical, optical, photocatalytic and biocidal properties of Ti–Ag–O films. The Ti–Ag–O films were reactively sputter-deposited from a composed Ti/Ag target at different partial pressures of oxygen on unheated glass substrate held on floating potentialUfl. It was found that addition of ~2 at.% of Ag into TiO2film has no negative influence on UV-induced hydrophilicity of TiO2film. Thick (~1,500 nm) TiO2/Ag films containing (200) anatase phase exhibit the best hydrophilicity with water droplet contact angle (WDCA) lower than 10° after UV irradiation for 20 min. Thick (~1,500 nm) TiO2/Ag films exhibited a better UV-induced hydrophilicity compared to that of thinner (~700 nm) TiO2/Ag films. Further it was found that hydrophilic TiO2/Ag films exhibit a strong biocidal effect under both the visible light and the UV irradiation with 100% killing efficiency ofEscherichia coliATCC 10536 after UV irradiation for 20 min. Reported results show that single layer of TiO2with Ag distributed in its whole volume exhibits, after UV irradiation, simultaneously two functions: (1) excellent hydrophilicity with WDCA < 10° and (2) strong power to killE. colieven under visible light due to direct toxicity of Ag

    An unfolding signifier: London's Baltic Exchange in Tallinn

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    In the summer of 2007 an unusual cargo arrived at Muuga and Paldiski harbors outside Tallinn. It consisted of nearly 50 containers holding over 1,000 tons of building material ranging from marble columns, staircases and fireplaces, to sculpted allegorical figures, wooden paneling and old-fashioned telephone booths. They were once part of the Baltic Exchange in the City of London. Soon they will become facets of the landscape of Tallinn. The following article charts this remarkable story and deploys this fragmented monument to analyze three issues relating to the Estonian capital: the relocation of the ‘Bronze Soldier’, the demolition of the Sakala Culture Center, and Tallinn’s future role as European Cultural Capital in 2011

    Localization of a Breathing Crack Using Super-Harmonic Signals due to System Nonlinearity

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76712/1/AIAA-38947-457.pd

    Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17ÎČ-HSD10 modulators for Alzheimer’s disease treatment

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    This work was supported by the Ministry of Health of the Czech Republic (no. NV15-28967A), Charles University in Prague (no. GAUK B-CH/992214, SVV 260 291) and the Alzheimer’s Society (specifically The Barcopel Foundation). This research is part-funded by the MSD Scottish Life Sciences fund.Amyloid-beta peptide (AÎČ) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer’s disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17ÎČ-hydroxysteroid dehydrogenase type 10 (17ÎČ-HSD10). Altered enzyme function caused by the AÎČ-ABAD interaction, was previously shown to cause mitochondrial distress and a consequent cytotoxic effect, therefore providing a feasible target in AD drug development. Based on previous frentizole derivatives studies, we report two novel series of benzothiazolyl ureas along with novel insights into the structure and activity relationships for inhibition of ABAD. Two compounds ( 37 , 39 ) were identified as potent ABAD inhibitors, where compound 39 exhibited comparable cytotoxicity with the frentizole standard; however, one-fold higher cytotoxicity than the parent riluzole standard. The calculated and experimental physical chemical properties of the most potent compounds showed promising features for blood-brain barrier penetration.PostprintPeer reviewe
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