541 research outputs found

    Electrical and infrared properties of thin niobium microbolometers near T(sub c)

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    Niobium microbolometers approximately 1 micron wide x 2 micron long x 10 nm thick have been integrated at the feeds of equiangular spiral antennas made of 200 nm thick Nb. The device's current-voltage characteristics and infrared responsivity as a function of DC bias voltage were measured over a range of temperature spanning approximately plus or minus 2 percent around T(sub c). The greatest voltage responsivity occurs well below T(sub c), in a regime where the I-V curve is significantly hysteretic due to self-heating and resembles the I-V curve of a superconducting microbridge

    A role for GPx3 in activity of normal and leukemia stem cells

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    The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs

    Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells

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    Determination of defined roles for endogenous homeobox (Hox) genes in adult hematopoietic stem and progenitor cell (HSPC) activity has been hampered by a combination of embryonic defects and functional redundancy. Here we show that conditional homozygous deletion of the Hoxa cluster (Hoxa−/−) results in a marked reduction of adult HSPC activity, both in vitro and in vivo. Specifically, proliferation of Hoxa−/− HSPCs is reduced compared with wild-type (WT) cells in vitro and they are less competitive in vivo. Notably, the loss of Hoxa genes had little impact on HSPC differentiation. Comparative RNA sequencing analyses of Hoxa−/− and WT hematopoietic stem cells (CD150+/CD48−/Lineage−/c-kit+/Sca-1+) identified a large number of differentially expressed genes, three of which (Nr4a3, Col1a1, and Hnf4a) showed >10-fold reduced levels. Engineered overexpression of Hoxa9 in Hoxa−/− HSPCs resulted in partial phenotypic rescue in vivo with associated recovery in expression of a large proportion of deregulated genes. Together, these results provide definitive evidence linking Hoxa gene expression to proliferation of adult HSPCs

    Addressing the ethical issues associated with fieldwork education in occupational therapy: Results of an empirical study conducted in Quebec

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    Occupational therapists who contribute to fieldwork education are exposed to ethical issues when supervising trainees. Both the ethical issues and the solutions to address these ethical issues are undocumented in the literature. A qualitative study was conducted to document these issues and their solutions. Twenty-three occupational therapists with supervising experience participated in this study. All the participants reported experiencing ethical issues while supervising trainees. This article aims to present the solutions proposed by the participants in order to address the ethical issues of fieldwork education. Intrinsic solutions are linked to supervisors’ ethical, pedagogical or occupational therapy competences. The extrinsic solutions deal with the appropriate measures which can and should be implemented so as to better support the supervisors’ work and better recognize the important contribution of occupational therapists who train the next generation of occupational therapists in clinical settings. This study is likely to have implications on clinical practice, teaching, research and governance

    Analyse philosophique des ressemblances entre l’Approche du rétablissement et le Modèle du Développement Humain et du Processus de Production du Handicap = Philosophical analysis of the similarities between the recovery approach and the Human Development Model-Disability Creation Process

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    Résumé Reconnue comme la référence en matière de bonnes pratiques en santé mentale, l’approche du rétablissement (AR) implique une considération pour le processus de rétablissement personnel de l’individu et l’adoption de pratiques axées vers le rétablissement (Commission de la santé mentale du Canada, 2015; Shepherd et al., 2008, 2010). Le modèle de développement humain et du processus de production du handicap (MDH-PPH) conçoit que la participation sociale des personnes résulte de l’interaction entre les facteurs personnels et les caractéristiques de l’environnement, ces domaines étant d’égale importance dans la compréhension des situations de handicap vécues par une personne, ou par un groupe ou une communauté partageant des caractéristiques personnelles communes dans un même contexte (Fougeyrollas, 2010). Nous présentons dans cet article une analyse des ressemblances philosophiques entre l’AR et le MDH-PPH et amorçons une réflexion sur l’apport mutuel de ces approches dans la lutte contre les obstacles sociaux qui nuisent à la participation sociale des personnes en situation de vulnérabilité/handicap. Pour ce faire, une analyse philosophique de nature herméneutique a été réalisée. Cinq angles d’analyse ont été choisis : 1) anthropologique; 2) environnemental; 3) axiologique; 4) éthique; 5) politique. Quatorze éléments de ressemblances ont été décelés entre les deux approches pour l’ensemble des angles analysés justifiant un apport mutuel dans la compréhension des situations de ces personnes. Abstract Now recognized as the gold standard for promoting good mental health practice, the recovery approach (RA) involves considering the individual's recovery process and adopting recovery-oriented practices by stakeholders, organizations, and society. (Mental Health Commission of Canada, 2015; Shepherd et al., 2010; Shepherd et al., 2008). The Human Development Model – Disability Creation Process (HDM-DCP) considers that social participation results from the interaction between personal and environmental factors. According to this model, these factors have equal importance in understanding disability situations experienced by a person or by a group, or a community sharing common personal characteristics in a same context (Fougeyrollas, 2010). This paper aims to analyze the philosophical similarities between the RA and the HDM-DCP. Besides, it intends to discuss the mutual contribution of these approaches in the fight against social obstacles that limit the social participation of people who are marginalized or in vulnerability/disability situations. For this purpose, we undertook a philosophical analysis of an hermeneutic nature. Five angles of analysis were chosen to identify the philosophical similarities between RA and HDM-DCP: 1) Anthropological; 2) Environmental; 3) Axiological; 4) Ethical; 5) Political. Fourteen elements (sub-themes) of similarities were identified between the two approaches from all the philosophical angles analyzed that justify a mutual contribution to understanding marginalized and vulnerable people's situations

    Analysis of Blood Stem Cell Activity and Cystatin Gene Expression in a Mouse Model Presenting a Chromosomal Deletion Encompassing Csta and Stfa2l1

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    The cystatin protein superfamily is characterized by the presence of conserved sequences that display cysteine protease inhibitory activity (e.g., towards cathepsins). Type 1 and 2 cystatins are encoded by 25 genes of which 23 are grouped in 2 clusters localized on mouse chromosomes 16 and 2. The expression and essential roles of most of these genes in mouse development and hematopoiesis remain poorly characterized. In this study, we describe a set of quantitative real-time PCR assays and a global expression profile of cystatin genes in normal mouse tissues. Benefiting from our collection of DelES embryonic stem cell clones harboring large chromosomal deletions (to be reported elsewhere), we selected a clone in which a 95-kb region of chromosome 16 is missing (Del16qB3Δ/+). In this particular clone, 2 cystatin genes, namely Csta and Stfa2l1 are absent along with 2 other genes (Fam162a, Ccdc58) and associated intergenic regions. From this line, we established a new homozygous mutant mouse model (Del16qB3Δ/16qB3Δ) to assess the in vivo biological functions of the 2 deleted cystatins. Stfa2l1 gene expression is high in wild-type fetal liver, bone marrow, and spleen, while Csta is ubiquitously expressed. Homozygous Del16qB3Δ/16qB3Δ animals are phenotypically normal, fertile, and not overtly susceptible to spontaneous or irradiation-induced tumor formation. The hematopoietic stem and progenitor cell activity in these mutant mice are also normal. Interestingly, quantitative real-time PCR expression profiling reveals a marked increase in the expression levels of Stfa2l1/Csta phylogenetically-related genes (Stfa1, Stfa2, and Stfa3) in Del16qB3Δ/16qB3Δ hematopoietic tissues, suggesting that these candidate genes might be contributing to compensatory mechanisms. Overall, this study presents an optimized approach to globally monitor cystatin gene expression as well as a new mouse model deficient in Stfa2l1/Csta genes, expanding the available tools to dissect cystatin roles under normal and pathological conditions

    A new method to quantify and compare the multiple components of fitness-A study case with kelp niche partition by divergent microstage adaptations to Temperature

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    Point 1 Management of crops, commercialized or protected species, plagues or life-cycle evolution are subjects requiring comparisons among different demographic strategies. The simpler methods fail in relating changes in vital rates with changes in population viability whereas more complex methods lack accuracy by neglecting interactions among vital rates. Point 2 The difference between the fitness (evaluated by the population growth rate.) of two alternative demographies is decomposed into the contributions of the differences between the pair-wised vital rates and their interactions. This is achieved through a full Taylor expansion (i.e. remainder = 0) of the demographic model. The significance of each term is determined by permutation tests under the null hypothesis that all demographies come from the same pool. Point 3 An example is given with periodic demographic matrices of the microscopic haploid phase of two kelp cryptic species observed to partition their niche occupation along the Chilean coast. The method provided clear and synthetic results showing conditional differentiation of reproduction is an important driver for their differences in fitness along the latitudinal temperature gradient. But it also demonstrated that interactions among vital rates cannot be neglected as they compose a significant part of the differences between demographies. Point 4 This method allows researchers to access the effects of multiple effective changes in a life-cycle from only two experiments. Evolutionists can determine with confidence the effective causes for changes in fitness whereas population managers can determine best strategies from simpler experimental designs.CONICYT-FRENCH EMBASSADY Ph.D. gran

    Archaeal glycolipid adjuvanted vaccines induce strong influenza-specific immune responses through direct immunization in young and aged mice or through passive maternal immunization.

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    Vaccine induced responses are often weaker in those individuals most susceptible to infection, namely the very young and the elderly, highlighting the need for safe and effective vaccine adjuvants. Herein we evaluated different archaeosome formulations as an adjuvant to the H1N1 influenza hemagglutinin protein and compared immune responses (anti-HA IgG and hemagglutination inhibition assay titers) as well as protection to an influenza A virus (strain A/Puerto Rico/8/1934 H1N1) homologous challenge to those generated using a squalene-based oil-in-water nano-emulsion, AddaVax™ in a murine model. The impact of age (young adult vs aged) on vaccine induced immune responses as well as the protection in pups due to the transfer of maternal antibodies was measured. Overall, we show that archaeal lipid based adjuvants can induce potent anti-HA responses in young and aged mice that can also be passed from vaccinated mothers to pups. Furthermore, young and aged mice immunized with archaeal lipid adjuvants as well as pups from immunized mothers were protected from challenge with influenza. In addition, we show that a simple admixed archaeosome formulation composed of a single sulfated glycolipid namely sulfated lactosylarchaeol (SLA; 6′-sulfate-β-D-Galp-(1,4)-β-D-Glcp-(1,1)-archaeol) can give equal or better protection compared to AddaVax™ or the traditional antigen-encapsulated archaeosome formulations
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