403 research outputs found
Microfluidic multipoles: theory and applications
Microfluidic multipoles (MFMs) have been realized experimentally and hold
promise for "open-space" biological and chemical surface processing. Whereas
convective flow can readily be predicted using hydraulic-electrical analogies,
the design of advanced MFMs is constrained by the lack of simple, accurate
models to predict mass transport within them. In this work, we introduce the
first exact solutions to mass transport in multipolar microfluidics based on
the iterative conformal mapping of 2D advection-diffusion around a simple edge
into dipoles and multipolar geometries, revealing a rich landscape of transport
modes. The models were validated experimentally with a library of 3D printed
MFM devices and found in excellent agreement. Following a theory-guided design
approach, we further ideated and fabricated two new classes of spatiotemporally
reconfigurable MFM devices that are used for processing surfaces with
time-varying reagent streams, and to realize a multistep automated immunoassay.
Overall, the results set the foundations for exploring, developing, and
applying open-space MFMs.Comment: 16 pages, 5 figure
Le veau de boucherie : situation actuelle et perspectives dans le cadre de la nouvelle réglementation bien-être
La filière veau de boucherie a longtemps pâti d'une mauvaise image : emploi d'anabolisants, élevage concentrationnaire, alimentation strictement lactée. Aujourd'hui de nombreux efforts ont été réalisés et la viande de veau a redoré son image : non seulement sa consommation ne semble plus diminuer mais en plus sa production est déficitaire en France. Ces aspects sont abordés dans la première partie. La mise aux normes bien-être, dictée par l'arrêté du 20 janvier 1994 et la Directive européenne 97/02, constitue l'occasion d'améliorer encore l'image de la filière mais aussi de mettre à niveau les élevages sur le plan zootechnique. La deuxième partie aborde justement les raisons ayant abouti à cette directive, les travaux menés sur le bien-être du veau et enfin les conséquences technico-économiques qu'elles impliquent. La troisième partie présente quant à elle une enquête menée auprès des vétérinaires intervenants dans la filière. Ces derniers précisent l'impact en terme sanitaire des nouvelles normes et donnent leur sentiment quant à l'avenir de la filière et le rôle du vétérinaire en son sein
Contribution des Espaces Verts A l’Atténuation De l’Effet De Serre Additionnel dans la Ville de Cotonou
Les espaces verts jouent un rôle primordial dans la réduction des gaz à effet de serre dans la ville de Cotonou. L’objectif de cette recherche est d’étudier la contribution des espaces verts à l’atténuation de l’effet de serre additionnel dans la ville de Cotonou. L’approche méthodologique utilisée a consisté premièrement à la collecte des données, ensuite à leur traitement et en fin à l’analyse des résultats. En effet, lors des enquêtes de terrain, l’échantillonnage a permis d’interroger 160 personnes.Les résultats obtenus montrent que 27 artères végétalisées ont répertoriées dans la ville de Cotonou, 15 Ronds-points végétalisés et 17 places publiques ont été reverdies. En outre, les espaces verts sont plus localisés dans les 1er, 2ème, 3ème, 4ème, 5ème, 6ème et 7ème 8ème et 12ème Arrondissements de Cotonou. Le 2ème, 9ème et le 13ème Arrondissement de Cotonou disposent très peu d’espaces verts. De plus, les espaces verts de la ville de Cotonou comptent 66 espèces végétales réparties en 48 familles. Cependant, la classe de diamètre compris entre 30 et 40 cm ont un taux élevé de carbone stocké. La capacité de stockage des artères est de 98,61 et 11,83 pour les ronds-points. De même, le stock moyen de carbone varie de 2,49 à 3,25 selon les types d’espace vert avec une différence significative au seuil de 95 %. De plus, le carbone varie de3681,17 à 2260 dans les autres espaces et de 372,50 à 210,91 dans la zone tampon. Ainsi, les espaces verts contribuent positivement la variation de carbone dans la ville de Cotonou. Des mesures ont été proposées. Il s’agit de la mise en place du Plan Climat Energie Territorial, la promotion des îlots de fraîcheur en ville et le reboisement des arbres pour stocker le CO2 et filtrer les polluants
Simulation-assisted design of microfluidic sample traps for optimal trapping and culture of non-adherent single cells, tissues, and spheroids
This work focuses on modelling design and operation of "microfluidic sample traps" (MSTs). MSTs regroup a widely used class of microdevices that incorporate wells, recesses or chambers adjacent to a channel to individually trap, culture and/or release submicroliter 3D tissue samples ranging from simple cell aggregates and spheroids, to ex vivo tissue samples and other submillimetre-scale tissue models. Numerous MST designs employing various trapping mechanisms have been proposed in the literature, spurring the development of 3D tissue models for drug discovery and personalized medicine. Yet, there lacks a general framework to optimize trapping stability, trapping time, shear stress, and sample metabolism. Herein, the effects of hydrodynamics and diffusion-reaction on tissue viability and device operation are investigated using analytical and finite element methods with systematic parametric sweeps over independent design variables chosen to correspond to the four design degrees of freedom. Combining different results, we show that, for a spherical tissue of diameter d < 500 mu m, the simplest, closest to optimal trap shape is a cube of dimensions w equal to twice the tissue diameter: w = 2d. Furthermore, to sustain tissues without perfusion, available medium volume per trap needs to be 100x the tissue volume to ensure optimal metabolism for at least 24 hours
Knockout of Vdac1 activates hypoxia-inducible factor through reactive oxygen species generation and induces tumor growth by promoting metabolic reprogramming and inflammation
BACKGROUND:
Mitochondria are more than just the powerhouse of cells; they dictate if a cell dies or survives. Mitochondria are dynamic organelles that constantly undergo fusion and fission in response to environmental conditions. We showed previously that mitochondria of cells in a low oxygen environment (hypoxia) hyperfuse to form enlarged or highly interconnected networks with enhanced metabolic efficacy and resistance to apoptosis. Modifications to the appearance and metabolic capacity of mitochondria have been reported in cancer. However, the precise mechanisms regulating mitochondrial dynamics and metabolism in cancer are unknown. Since hypoxia plays a role in the generation of these abnormal mitochondria, we questioned if it modulates mitochondrial function. The mitochondrial outer-membrane voltage-dependent anion channel 1 (VDAC1) is at center stage in regulating metabolism and apoptosis. We demonstrated previously that VDAC1 was post-translationally C-terminal cleaved not only in various hypoxic cancer cells but also in tumor tissues of patients with lung adenocarcinomas. Cells with enlarged mitochondria and cleaved VDAC1 were also more resistant to chemotherapy-stimulated cell death than normoxic cancer cells.
RESULTS:
Transcriptome analysis of mouse embryonic fibroblasts (MEF) knocked out for Vdac1 highlighted alterations in not only cancer and inflammatory pathways but also in the activation of the hypoxia-inducible factor-1 (HIF-1) signaling pathway in normoxia. HIF-1α was stable in normoxia due to accumulation of reactive oxygen species (ROS), which decreased respiration and glycolysis and maintained basal apoptosis. However, in hypoxia, activation of extracellular signal-regulated kinase (ERK) in combination with maintenance of respiration and increased glycolysis counterbalanced the deleterious effects of enhanced ROS, thereby allowing Vdac1 (-/-) MEF to proliferate better than wild-type MEF in hypoxia. Allografts of RAS-transformed Vdac1 (-/-) MEF exhibited stabilization of both HIF-1α and HIF-2α, blood vessel destabilization, and a strong inflammatory response. Moreover, expression of Cdkn2a, a HIF-1-target and tumor suppressor gene, was markedly decreased. Consequently, RAS-transformed Vdac1 (-/-) MEF tumors grew faster than wild-type MEF tumors.
CONCLUSIONS:
Metabolic reprogramming in cancer cells may be regulated by VDAC1 through vascular destabilization and inflammation. These findings provide new perspectives into the understanding of VDAC1 in the function of mitochondria not only in cancer but also in inflammatory diseases
Neuroligin-1 Is Altered in the Hippocampus of Alzheimer\u27s Disease Patients and Mouse Models, and Modulates the Toxicity of Amyloid-Beta Oligomers
Synapse loss occurs early and correlates with cognitive decline in Alzheimer’s disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by Aβo, and that it can modulate Aβo toxicity. We found that hippocampal NLGN1 was decreased in patients with AD in comparison to patients with mild cognitive impairment and control subjects. Female 3xTg-AD mice also showed a decreased NLGN1 level in the hippocampus at an early age (i.e., 4 months). We observed that chronic hippocampal Aβo injections initially increased the expression of one specific Nlgn1 transcript, which was followed by a clear decrease. Lastly, the absence of NLGN1 decreased neuronal counts in the dentate gyrus, which was not the case in wild-type animals, and worsens impairment in spatial learning following chronic hippocampal Aβo injections. Our findings support that NLGN1 is impacted early during neurodegenerative processes, and that Aβo contributes to this effect. Moreover, our results suggest that the presence of NLGN1 favors the cognitive prognosis during Aβo-driven neurodegeneration
Young children's understanding of disabilities: the influence of development, context and cognition
Throughout Europe, educational support for children with disabilities has moved towards a model of inclusive education. Such policy changes mean that for all children there will be an increased likelihood of working with and encountering children with differing disabilities and difficulties. Previous research had indicated that children had poorly differentiated views of developmental differences. The present study investigated children?s representations of different disabilities. Seventy-nine 8-9 and 10-11 year old Greek children from an urban school and a rural school completed an attitudes toward school inclusion rating scale and a semi-structured interview. Responses to the attitude scale provided generally positive views of educational inclusion. However, children were less positive about activities that might directly reflect upon themselves. Children?s responses in the interviews indicated that they were developing rich representations of differences and diversities. Children had the greatest understanding of sensory and physical disabilities, followed by learning disabilities. There was limited knowledge of dyslexia and hyperactivity and no child was familiar with the term autism. Both groups of children identified a range of developmental difficulties, with older children being more aware of specific learning disabilities, their origin and impact. Results are discussed in terms of children?s developing knowledge systems and the implications for educational practices
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