4,523 research outputs found
Development and application of test cases for comparing vertical ground heat exchanger models
The main objective of this paper is to establish a set of test cases for analytical verifications and intermodel comparisons of ground heat exchanger (GHX) models used in building simulation programs. Several test cases are suggested. They range from steady-state heat rejection in a single borehole to varying hourly loads with large yearly thermal imbalance in multiple borehole configurations. The usefulness of the proposed test cases is illustrated by running them with different GHX models. This comparison exercise has shown that 1-D models compare favourably well with the more elaborate 3-D models for relatively small simulation periods. The cyclic heat rejection/collection test has revealed some small deficiency in the load aggregation scheme of a particular model. Finally, the use of the asymmetric (cooling-dominated) load profile test case for a bore field composed of 100 boreholes revealed that the borehole wall temperature predicted by two GHX models can differ by as much as 10oC after a 30 year simulation
Tumor necrosis factor alpha and epidermal growth factor act additively to inhibit matrix gene expression by chondrocyte
The failure of chondrocytes to replace the lost extracellular matrix contributes to the progression of degenerative disorders of cartilage. Inflammatory mediators present in the joint regulate the breakdown of the established matrix and the synthesis of new extracellular matrix molecules. In the present study, we investigated the effects of tumor necrosis factor alpha (TNF-α) and epidermal growth factor (EGF) on chondrocyte morphology and matrix gene expression. Chondrocytes were isolated from distal femoral condyles of neonatal rats. Cells in primary culture displayed a cobblestone appearance. EGF, but not TNF-α, increased the number of cells exhibiting an elongated morphology. TNF-α potentiated the effect of EGF on chondrocyte morphology. Individually, TNF-α and EGF diminished levels of aggrecan and type II collagen mRNA. In combination, the effects of TNF-α and EGF were additive, indicating the involvement of discrete signaling pathways. Cell viability was not compromised by TNF-α or by EGF, alone or in combination. EGF alone did not activate NF-κB or alter NF-κB activation by TNF-α. Pharmacologic studies indicated that the effects of TNF-α and EGF alone or in combination were independent of protein kinase C signaling, but were dependent on MEK1/2 activity. Finally, we analyzed the involvement of Sox-9 using a reporter construct of the 48 base pair minimal enhancer of type II collagen. TNF-α attenuated enhancer activity as expected; in contrast, EGF did not alter either the effect of TNF-α or basal activity. TNF-α and EGF, acting through distinct signaling pathways, thus have additive adverse effects on chondrocyte function. These findings provide critical insights into the control of chondrocytes through the integration of multiple extracellular signals
Public biological databases and the sui generis database right
The sui generis database right is an intellectual property right created in the European Union to stimulate investment in the curation of databases. Since its inception, communities engaged in research and development efforts have questioned its potential to incentivise database production, and posit that it stifles productive downstream uses of existing datasets. European courts have restricted the right’s ambit through a restrictive interpretation of the circumstances in which it applies, which we argue, enables downstream use of biological databases. Nonetheless, residual ambiguities about potential infringement of the right exist. The prospect of unintentional infringement can frustrate downstream innovation. These ambiguities are compounded because the criteria that determine whether or not the right applies are reliant on information that is not available to the prospective downstream users of public datasets. Repealing the sui generis database right is recommended. Legislatures are advised to refrain from the implementation of broad novel intellectual property rights in the future, without first adopting safeguards that mitigate the potential for such rights to frustrate the reuse of available intangibles to the detriment of pro-social innovation
Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFα-induced MEK/ERK signalling
Introduction TNFα is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNFα activates mitogen-activated kinase kinase (MEK)/extracellular regulated kinase (ERK) in chondrocytes; however, the overall functional relevance of MEK/ERK to TNFα-regulated gene expression in chondrocytes is unknown.
Methods Chondrocytes were treated with TNFα with or without the MEK1/2 inhibitor U0126 for 24 hours. Microarray analysis and real-time PCR analyses were used to identify genes regulated by TNFα in a MEK1/2-dependent fashion. Promoter/ reporter, immunoblot, and electrophoretic mobility shift assays were used to identify transcription factors whose activity in response to TNFα was MEK1/2 dependent. Decoy oligodeoxynucleotides bearing consensus transcription factor binding sites were introduced into chondrocytes to determine the functionality of our results.
Results Approximately 20% of the genes regulated by TNFα in chondrocytes were sensitive to U0126. Transcript regulation of the cartilage-selective matrix genes Col2a1, Agc1 and Hapln1, and of the matrix metalloproteinase genes Mmp-12 and Mmp-9, were U0126 sensitive – whereas regulation of the inflammatory gene macrophage Csf-1 was U0126 insensitive. TNFα-induced regulation of Sox9 and NFKB activity was also U0126 insensitive. Conversely, TNFα-increased early growth response 1 (Egr-1) DNA binding was U0126 sensitive. Transfection of chondrocytes with cognate Egr-1 oligodeoxynucleotides attenuated the ability of TNFα to suppress Col2a1, Agc1 or Hapln1 mRNA expression.
Conclusions Our results suggest that MEK/ERK and Egr1 are required for TNFα-regulated catabolic and anabolic genes of the cartilage extracellular matrix, and hence may represent potential targets for drug intervention in osteoarthritis or rheumatoid arthritis
Modélisation de l'évolution du couvert nival, sur le sous-bassin LG4 de la rivière La Grande dans le nord du Québec, à l'aide du modèle français CROCUS
Au Québec, l'accumulation de la neige au sol prend une grande importance dans bon nombre d'activités humaines comme la production d'hydroélectricité. Face à cette importance de la neige, il devient fort intéressant de faire appel à des outils de modélisation dans le but de faire le suivi complet du manteau neigeux par la simulation des différents processus physiques agissant sur le couvert nival. En ce sens, la présente recherche vise à évaluer la capacité d'adaptation aux conditions environnementales du Québec, du modèle français multicouches CROCUS de suivi et de fonte du couvert nival, en vue de son utilisation ultérieure. Le choix du site d'étude s'accorde avec la présence de stations d'acquisition de données sur le couvert nival et la disponibilité d'un large éventail de données météorologiques essentielles aux modélisations.Suite au prétraitement des données d'entrée, le modèle CROCUS a pu être étalonné dans le but d'évaluer ses aptitudes à simuler l'évolution de l'épaisseur et de l'équivalent en eau du couvert nival, de même que les profils de densité et de température de ce couvert. Compte tenu des données disponibles, les résultats des périodes d'étalonnage et de vérification peuvent être considérés comme très bons et très encourageants pour des applications ultérieures de CROCUS au Québec.In Québec, snow accumulation on the ground is important for a large number of activities, including hydroelectric production. Snow being an important environmental aspect to look at for operations in cold regions, making use of adequate models able to simulate the various physical processes affecting the characteristics of the snowpack throughout the entire snow season becomes also quite important. So, the present project aims to evaluate the ability of the CROCUS French multilayer snow model to be adapted to Northern Quebec environmental conditions. The choice of the study area has been done on the basis of data availability on both the temporal evolution the snowpack at three automatic stations and the meteorological variables necessary as input to the model. Following preprocessing of input data, the CROCUS model has been calibrated in order to evaluate his capability to simulate the temporal evolution not only of the thickness and water equivalent of the snowpack, but also of the density and temperature profiles within the pack. Given the available data, the results for both the calibration and verification periods can be considered as good and very encouraging for future applications of the CROCUS model in Québec
Identification of compounds from Etonia rosemary \u3ci\u3e(Conradina etonia)\u3c/i\u3e
Mosquitoes transmit pathogens that result in diseases harmful to human, livestock, and wildlife hosts. Numerous measures can be used to reduce insect-borne disease risk to humans, and one approach is the use of topical repellents to prevent host-seeking arthropods from taking a blood meal. A current emphasis in the development of new repellents is that they be safe. Therefore, natural products sources are increasingly being explored. Compounds from plants of the mint family (Lamiaceae) have been demonstrated to be insect repellents. This study examines compounds from Etonia rosemary (Conradina etonia) to identify compounds for examination as insect repellents. Samples of Etonia rosemary were passively extracted with hexane, dichloromethane, and methanol and analyzed by GC/MS. This extraction method was chosen to eliminate thermal degradation of plant components that can occur during the distillation procedure. Additional headspace volatile compounds from this plant were identified using microscale purge-and-trap GC/MS. A variety of terpenes, terpenic alcohols, ketones, and aldehydes were identified in the extracts with terpenes and short-chained aldehydes detected in greatest abundance
A secure base from which to regulate: Attachment security in toddlerhood as a predictor of executive functioning at school entry
In light of emerging evidence suggesting that the affective quality of
parent-child relationships may relate to individual differences in young
children's executive functioning (EF) skills, the aim of this study was to
investigate the prospective associations between attachment security in
toddlerhood and children's EF skills in kindergarten. Mother-child dyads (N =
105) participated in 2 toddlerhood visits in their homes, when children were 15
months and 2 years of age. Mother-child attachment security was assessed with the
Attachment Q-Sort during both these visits. When children were in kindergarten
(ages 5-6), they were administered a battery of EF tasks, and their teachers
completed the Behavior Rating Inventory of Executive Function to assess
children's EF problems. The results indicated that kindergarteners who were more
securely attached to their mothers in toddlerhood showed better performance on
all EF tasks, and were considered by their teachers to present fewer EF problems
in everyday school situations. These results held above family socioeconomic
status (SES) and child age, sex, and general cognitive functioning. The fact that
early attachment security uniquely predicted both teacher reports and children's
objective EF task performance suggests that parent-child attachment may be a
promising factor to consider in the continuing search for the social antecedents
of young children's EF
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