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11.
First Nation (Indigenous) on-reserve housing in Canada is in crisis due to severe shortages, high reported instances of mould contamination, overcrowding and structural deficiencies. The Kitamaat reserve of the Haisla First Nation provides one example. The intent of the study reported here was to engage with the Haisla to develop a culturally appropriate, environmentally responsive and energy-efficient housing type that the Haisla could implement in the future. This work was undertaken by Marceau-Evans-Johnson Architects in collaboration with researchers at the University of Victoria. In this article, the circumstances leading to the present housing crisis are reviewed, the consultative design process with the Haisla and its outcomes are described, and the concept design solution which was co-developed for future housing is presented.  相似文献   
12.
The complete molecular mechanisms underlying the pathophysiology of Alzheimer’s disease (AD) remain to be elucidated. Recently, microRNA-455-3p has been identified as a circulating biomarker of early AD, with increased expression in post-mortem brain tissue of AD patients. MicroRNA-455-3p also directly targets and down-regulates APP, with the overexpression of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression decreases with age in the brains of wild-type mice. We generated a miR-455 null mouse utilising CRISPR-Cas9 to explore its function further. Loss of miR-455 resulted in increased weight gain, potentially indicative of metabolic disturbances. Furthermore, performance on the novel object recognition task diminished significantly in miR-455 null mice (p = 0.004), indicating deficits in recognition memory. A slight increase in anxiety was also captured on the open field test. BACE1 and TAU were identified as new direct targets for miR-455-3p, with overexpression of miR-455-3p leading to a reduction in the expression of APP, BACE1 and TAU in neuroblastoma cells. In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.  相似文献   
13.
The activity for O2 reduction of iron polyphthalocyanine deposited on a range of ground graphite supports has been examined using the ultra thin electrode technique in 6N KOH. Annealing with regraphitization of ground materials of variable initial BET areas enhances activity of the catalyst film in both activation and diffusion controlled regions. At the same time the intrinsic activity of the support for O2 reduction is reduced. These results are interpreted in terms of a reduction mechanism involving activated absorption of O2 in the polyphthalocyanine film. Reaction order evidence to support this mechanism is discussed.  相似文献   
14.
Objective: Peptide YY3–36 [PYY(3–36)] has shown efficacy in appetite suppression when dosed by injection modalities (intraperitoneal (IP)/subcutaneous). Transitioning to needle-free delivery, towards inhalation, often utilizes systemic pharmacokinetics as a key endpoint to compare different delivery methods and doses. Systemic pharmacokinetics were evaluated for PYY3–36 when delivered by IP, subcutaneous, and inhalation, the systemic pharmacokinetics were then used to select doses in an appetite suppression pharmacodynamic study.

Methods: Dry-powder formulations were manufactured by spray drying and delivered to mice via nose only inhalation. The systemic plasma, lung tissue, and bronchoalveolar lavage fluid pharmacokinetics of different inhalation doses of PYY(3–36) were compared to IP and subcutaneous efficacious doses. Based on these pharmacokinetic data, inhalation doses of 70:30 PYY(3–36):Dextran T10 were evaluated in a mouse model of appetite suppression and compared to IP and subcutaneous data.

Results: Inhalation pharmacokinetic studies showed that plasma exposure was similar for a 2?×?higher inhalation dose when compared to subcutaneous and IP delivery. Inhalation doses of 0.22 and 0.65?mg/kg were for efficacy studies. The results showed a dose-dependent (not dose proportional) decrease in food consumption over 4?h, which is similar to IP and subcutaneous delivery routes.

Conclusions: The pharmacokinetic and pharmacodynamics results substantiate the ability of pharmacokinetic data to inform pharmacodynamics dose selection for inhalation delivery of the peptide PYY(3–36). Additionally, engineered PYY(3–36):Dextran T10 particles delivered to the respiratory tract show promise as a non-invasive therapeutic for appetite suppression.  相似文献   
15.
16.
Activated sludge is one of the most abundant and effective wastewater treatment process used to treat wastewater, and has been used in developed countries for nearly a century. In all that time, several hundreds of studies have explored the bacterial communities responsible for treatment, but most studies were based on a handful of samples and did not consider temporal dynamics. In this study, we used the DNA fingerprinting technique called automated ribosomal intergenic spacer region analysis (ARISA) to study bacterial community dynamics over a two-year period in two different treatment trains. We also used quantitative PCR to measure the variation of five phylogenetically-defined clades within the Accumulibacter lineage, which is a model polyphosphate accumulating organism. The total bacterial community exhibited seasonal patterns of change reminiscent of those observed in lakes and oceans. Surprisingly, all five Accumulibacter clades were present throughout the study, and the total Accumulibacter community was relatively stable. However, the abundance of each clade did fluctuate through time. Clade IIA dynamics correlated positively with temperature (ρ = 0.65, p < 0.05) while Clade IA dynamics correlated negatively with temperature (ρ = −0.35, p < 0.05). This relationship with temperature hints at the mechanisms that may be driving the seasonal patterns in overall bacterial community dynamics and provides further evidence for ecological differentiation among clades within the Accumulibacter lineage. This work provides a valuable baseline for activated sludge bacterial community variation.  相似文献   
17.
This study followed the introduction of the Arthritis Source website into the existing teaching practices of Arthritis Foundation Helpline volunteers. The goal was to examine what factors may affect a particular group of educators adopt a potentially valuable Internet tool into an existing instructional environment. Defining the possible uses of the website in reference to the volunteers' actual job duties helped provide a clearer understanding of how the volunteers might use this new technology. The researchers used qualitative techniques to focus on three volunteers who experienced different physical, environmental and cognitive means that impacted their use of the new tool. Each volunteer experienced varying levels of motivation in areas of learning, satisfaction and responses to outside influences. Each volunteer also had varying amounts of opportunity prompts in which to interact or refer the website. Consequently, Helpline volunteers experienced different rates of adopting the information-intensive website into their traditional work system.  相似文献   
18.
Retraction: The following article from the Journal of the Science of Food and Agriculture , ‘Temperature affects flavour intensity and quality of aroma in fresh basil (Ocimum basilicum L.) leaves’ by Xianmin Chang, Peter G Alderson, Tracey A Hollowood, Louise Hewson, and Charles J Wright, published online on 19 October 2005 in Wiley InterScience (www.interscience.wiley.com), has been retracted by agreement between the authors, the journal Editor in Chief, David S. Reid and John Wiley & Sons, Ltd. The retraction has been agreed due to overlap between this article and the following article published in the The Journal of Horticultural Science & Biotechnology ; ‘Effect of temperature integration on the growth and volatile oil content of Basil (Ocimum basilicum L.)’ by Xianmin Chang, Peter G Alderson and Charles J Wright. Volume 80 Issue 5, 2005, pages 593 – 598  相似文献   
19.
Two studies were conducted with samples of elementary school, middle school, and college students, who were given the Inventory of Children's Activities, which was designed to assess J. L. Holland's (1973, 1985a) RIASEC (Realistic, Investigative, Artistic, Social, Enterprising, and Conventional) types on interests and competence perceptions. The structure was examined at the scale and item levels using the randomization test of hypothesized order relations and principal-components analysis. Results indicated that (a) there were few differences in structure between interests and competence perceptions, (b) the structure of interests and competence perceptions varied across age, (c) the fit of the circular model was positively related to age, (d) elementary and middle school students evaluated their interests and competencies using different dimensions than did college students, and (e) there were scale score mean differences across gender and age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
20.
CheY serves as a structural prototype for the response regulator proteins of two-component regulatory systems. Functional roles have previously been defined for four of the five highly conserved residues that form the response regulator active site, the exception being the hydroxy amino acid which corresponds to Thr87 in CheY. To investigate the contribution of Thr87 to signaling, we characterized, genetically and biochemically, several cheY mutants with amino acid substitutions at this position. The hydroxyl group appears to be necessary for effective chemotaxis, as a Thr-->Ser substitution was the only one of six tested which retained a Che+ swarm phenotype. Although nonchemotactic, cheY mutants with amino acid substitutions T87A and T87C could generate clockwise flagellar rotation either in the absence of CheZ, a protein that stimulates dephosphorylation of CheY, or when paired with a second site-activating mutation, Asp13-->Lys, demonstrating that a hydroxy amino acid at position 87 is not essential for activation of the flagellar switch. All purified mutant proteins examined phosphorylated efficiently from the CheA kinase in vitro but were impaired in autodephosphorylation. Thus, the mutant CheY proteins are phosphorylated to a greater degree than wild-type CheY yet support less clockwise flagellar rotation. The data imply that Thr87 is important for generating and/or stabilizing the phosphorylation-induced conformational change in CheY. Furthermore, the various position 87 substitutions differentially affected several properties of the mutant proteins. The chemotaxis and autodephosphorylation defects were tightly linked, suggesting common structural elements, whereas the effects on self-catalyzed and CheZ-mediated dephosphorylation of CheY were uncorrelated, suggesting different structural requirements for the two dephosphorylation reactions.  相似文献   
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