1,766 research outputs found
On the benefits of philosophy as a way of life in a general introductory course
Philosophy as a way of life (PWOL) places investigations of value, meaning, and the good life at the center of philosophical investigation, especially of one’s own life. I argue PWOL is compatible with general introductory philosophy courses, further arguing that PWOL-based general introductions have several philosophical and pedagogical benefits. These include the ease with which high impact practices, situated skill development, and students’ ability to ‘think like a disciplinarian’ may be incorporated into such courses, relative to more traditional introductory courses, as well as the demonstration of philosophy’s value to students by explicitly tying philosophical investigation to students own lives
Evaluating price-based demand response in practice – with application to the EcoGrid EU Experiment
Characterization of Pax3 and Sox10 Transgenic Xenopus Laevis Embryos as Tools to Study Neural Crest Development
The neural crest is a multipotent population of cells that originates a variety of cell types. Many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. A major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use as lineage tracers, or modified genes for use in functional studies. Unfortunately, no such transgenic animals currently exist for the amphibians Xenopus laevis and tropicalis, key model systems for studying neural crest development. Here we describe the generation and characterization of two transgenic Xenopus laevis lines, Pax3-GFP and Sox10-GFP, in which GFP is expressed in the pre-migratory and migratory neural crest, respectively. We show that Pax3-GFP could be a powerful tool to study neural crest induction, whereas Sox10-GFP could be used in the study of neural crest migration in living embryos
Corporate Social Responsibility and Millennial\u27s\u27 Stakeholder Approach
Corporate Social Responsibility has evolved in recent decades in professional practice and law. This was predicted in a seminal work by Howe and Strauss. This paper describes this evolution and illuminates millennials\u27 philosophy and attitudes as more aligned with stakeholder theory than stockholder theory. The predicted millennial upheaval, as posited by Howe and Strauss, is evidenced by strong belief statements as interpreted by the raters in this study
Teratozoospermia: spotlight on the main genetic actors in the human
BACKGROUND Male infertility affects >20 million men worldwide and represents a major health concern. Although multifactorial, male infertility has a strong genetic basis which has so far not been extensively studied. Recent studies of consanguineous families and of small cohorts of phenotypically homogeneous patients have however allowed the identification of a number of autosomal recessive causes of teratozoospermia. Homozygous mutations of aurora kinase C (AURKC) were first described to be responsible for most cases of macrozoospermia. Other genes defects have later been identified in spermatogenesis associated 16 (SPATA16) and dpy-19-like 2 (DPY19L2) in patients with globozoospermia and more recently in dynein, axonemal, heavy chain 1 (DNAH1) in a heterogeneous group of patients presenting with flagellar abnormalities previously described as dysplasia of the fibrous sheath or short/stump tail syndromes, which we propose to call multiple morphological abnormalities of the flagella (MMAF). METHODS A comprehensive review of the scientific literature available in PubMed/Medline was conducted for studies on human genetics, experimental models and physiopathology related to teratozoospermia in particular globozoospermia, large headed spermatozoa and flagellar abnormalities. The search included all articles with an English abstract available online before September 2014. RESULTS Molecular studies of numerous unrelated patients with globozoospermia and large-headed spermatozoa confirmed that mutations in DPY19L2 and AURKC are mainly responsible for their respective pathological phenotype. In globozoospermia, the deletion of the totality of the DPY19L2 gene represents ∼81% of the pathological alleles but point mutations affecting the protein function have also been described. In macrozoospermia only two recurrent mutations were identified in AURKC, accounting for almost all the pathological alleles, raising the possibility of a putative positive selection of heterozygous individuals. The recent identification of DNAH1 mutations in a proportion of patients with MMAF is promising but emphasizes that this phenotype is genetically heterogeneous. Moreover, the identification of mutations in a dynein strengthens the emerging point of view that MMAF may be a phenotypic variation of the classical forms of primary ciliary dyskinesia. Based on data from human and animal models, the MMAF phenotype seems to be favored by defects directly or indirectly affecting the central pair of axonemal microtubules of the sperm flagella. CONCLUSIONS The studies described here provide valuable information regarding the genetic and molecular defects causing infertility, to improve our understanding of the physiopathology of teratozoospermia while giving a detailed characterization of specific features of spermatogenesis. Furthermore, these findings have a significant influence on the diagnostic strategy for teratozoospermic patients allowing the clinician to provide the patient with informed genetic counseling, to adopt the best course of treatment and to develop personalized medicine directly targeting the defective gene product
Characterization of a junctionless diode
A diode has been realised using a silicon junctionless (JL) transistor. The device contains neither PN junction nor Schottky junction. The device is measured at different temperatures. The characteristics of the JL diode are essentially identical to those of a regular PN junction diode. The JL diode has an on/off current ratio of 10(8), an ideality factor of 1.09, and a reverse leakage current of 1 x 10(-14) A at room temperature. The mechanism of the leakage current is discussed using the activation energy (E-A). The turn-on voltage of the device can be tuned by JL transistor threshold voltage. (C) 2011 American Institute of Physics. (doi: 10.1063/1.3608150
Development of a regional GPS-based ionospheric TEC model for South Africa
Advances in South African space physics research and related disciplines require better spatial and time resolution ionospheric information than was previously possible with the existing ionosonde network. A GPS-based, variable degree adjusted spherical harmonic (ASHA) model was developed for near real-time regional ionospheric total electron content (TEC) mapping over South Africa. Slant TEC values along oblique GPS signal paths are quantified from a network of GPS receivers and converted to vertical TEC by means of the single layer mapping function. The ASHA model coefficients and GPS differential biases are estimated from vertical TEC at the ionospheric pierce points and used to interpolate TEC at any location within the region of interest. Diurnal TEC variations with one minute time resolution and time-varying 2D regional TEC maps are constructed. In order to validate the ASHA method, simulations with an IRI ionosphere were performed, while the ASHA results from actual data were compared with two independent GPS-based methodologies and measured ionosonde data
In Vivo Airway Surface Liquid Cl− Analysis with Solid-State Electrodes
The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl−] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl−] in the “thin” ASL (∼30 μm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl−] in vivo. In initial experiments, the electrode measured [Cl−] in physiologic salt solutions, small volume (7.6 μl) test solutions, and in in vitro cell culture models, with ≥93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl− measurements were made in the following airway regions and species. First, ASL [Cl−] was measured in normal human nasal cavity and averaged 117.3 ± 11.2 mM (n = 6). Second, ASL [Cl−] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 ± 1.8 mM; (n = 6) and 126.9 ± 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 ± 4.2 mM (n = 13); and monkey bronchus = 112.3 ± 10.9 mM (n = 3). Third, Cl− measurements were made in small (1–2 mm) diameter airways of the rabbit (108.3 ± 7.1 mM, n = 5) and monkey (128.5 ± 6.8 mM, n = 3). The measured [Cl−], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology
Identification et caractérisation de gènes impliqués dans l'infertilité masculine
Près de 15% des couples sont confrontés à des problèmes d'infertilité. Dans près de la moitié des cas, une composante masculine est retrouvée, avec souvent une anomalie des paramètres du spermogramme montrant une diminution de la qualité du sperme. L'étiologie de la grande majorité des infertilités masculines reste inconnue et une origine génétique est probablement responsable d'une proportion importante des troubles de la spermatogénèse. Ce travail comporte deux parties: dans la 1ère partie, l'analyse d'une large cohorte de patients (n=87), nous a permis d'identifier deux nouvelles mutations du gène AURKC. La mutation [c.36-2A>G] a été identifiée uniquement à l'état hétérozygote chez deux frères et le 2ème variant identifié [p.Y248*]: est une mutation récurrente retrouvée chez 11 patients non apparenté d'origine maghrébine et européenne. La 2ème partie de notre étude a été réalisée sur 20 patients infertiles présentant un phénotype homogène d'anomalies flagellaire de type flagelles courts, absents et de calibre irrégulier associé a une asthénozoospermie. Nous avons appliqué la stratégie d'homozygotie par filiation qui a permis de mettre en évidence deux régions d'homozygoties communes: la 1ère région, située sur le chromosome 3, est commune à 9/20 patients et la 2ème sur le chromosome 20 commune à 13/20 patients. Trois gènes candidats présents dans ces régions ont été sélectionnés : les gènes KIF9, SPAG4 et DNAH1. Le séquençage du gène DNAH1 a permis de mettre en évidence des mutations de type faux-sens [c.3877G>A], run-on [c.12796 T>C] et d'épissage [c.5094+1G>A] [c.11958-1G>A]. L'absence de la protéine DNAH1 a pu être mise en évidence par immunomarquage sur les spermatozoïdes d'un patients porteur de la mutation [c.11958-1G>A] et confirme la dégradation du transcrit muté par NMD également observé. Les analyses par microscopie électronique sur les spermatozoïdes d'un patient de la cohorte ont permis de mettre en évidence des anomalies de la structure de l'axonème. Cette étude précise le diagnostic d'infertilité masculine et élargit les connaissances sur les gènes impliquées dans la spermatogenèse.About 15% of couples are confronted with infertility problems. In half of the cases, a male factor component is found, often with abnormal semen parameters. The etiology of the large majority of male infertility remains unknown and genetic origin is probably responsible of a significant proportion of spermatogenesis disorders. This work comprises two parts: in the first part, the analysis of a large cohort of patients (n = 87), allowed us to identify two new mutations in AURKC gene. A splice site mutation [c.36-2A> G] was identified in only two brothers and the second variant identified [p.Y248*] is a recurrent mutation found in 11 unrelated patients. The second part of our study was carried out on 20 infertile patients with flagellar abnormalities associated with asthenozoospermia. We have applied the strategy of homozygosity by descent who has bring out two regions of homozygosity: the first region, located on chromosome 3, is common for 9/20 patients and the second one, located on chromosome 20, is common for 13/20 patients. Three candidate genes present in these regions were selected: KIF9, SPAG4 and DNAH1. Sequencing of DNAH1 gene has bring out three type of mutations: missense mutation [c.3877G> A], run-on mutation [c.12796 T> C] and splice site mutation [c.5094 +1 G> A] [c.11958-1G> A]. The absence of dnah1 protein has been shown by immunostaining of spermatozoa of a patient carrier the mutation [c.11958-1G> A] and confirms the degradation of the mutated transcript by NMD. An electron microscopic analysis of spermatozoa of one patient of the cohort reveals axoneme abnormalities. This study clarifies the diagnosis of male infertility and broadens the knowledge of the genes involved in spermatogenesis.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF
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