2,158 research outputs found
An entropic approach to equity market integration and consumption-based capital asset pricing models
This study examines the degree of equity market integration and segmentation domestically and internationally. The conventional method on this literature either is subject to the joint hypothesis test problem or lacks the sampling distribution theory needed to make inferences about the integration hypothesis. To circumvent both problems, this study proposes using the nonparametric entropic approach to test for the market integration hypothesis. The proposed approach also allows us to perform an alternative test of conventional consumption-based capital asset pricing models. Both monthly and quarterly data from December, 1980 through November, 1996 are used for Taiwan and U.S. equity markets. At the industry portfolio level, we find that both equity markets are integrated domestically and internationally. The negligible value of the estimates of segmentation indices provides evidence that the two equity markets are not segmented domestically or internationally. We also find that the power felicity consumption-based capital asset pricing model cannot be rejected separately for these two equity markets
JUMPS IN DIFFERENT LEVELS OF WATER: AN OPTIMAL ENVIRONMENT TO JUMP ON LAND
The purpose of this study was to compare rate of force development (RFD) and rate of impact force (RIF) among on-land and in different levels of water jumps. Fourteen male participants were recruited in this study. Participants carried out the testing on land first and followed by testing in knee-high (LOW), trochanter major high (MID), and nasal-high (HIGH) of water. In each condition, participants performed 3 countermovement jumps (CMJ) separated by 15 sec rest. RFD and RIF were calculated. A repeated measure ANOVA was used for assessing the differences of variables among different conditions. The results showed that RFD for LOW is significantly lower than the others, and loading impact on-land is significantly higher than the others. Jumping in MID and HIGH are optimal levels of water for jumps training
Exploring AADL verification tool through model transformation
International audienceArchitecture Analysis and Design Language (AADL) is often used to model safety-critical real-time systems. Model transformation is widely used to extract a formal specification so that AADL models can be verified and analyzed by existing tools. Timed Abstract State Machine (TASM) is a formalism not only able to specify behavior and communication but also timing and resource aspects of the system. To verify functional and nonfunctional properties of AADL models, this paper presents a methodology for translating AADL to TASM. Our main contribution is to formally define the translation rules from an adequate subset of AADL (including thread component, port communication, behavior annex and mode change) into TASM. Based on these rules, a tool called AADL2TASM is implemented using Atlas Transformation Language (ATL). Finally, a case study from an actual data processing unit of a satellite is provided to validate the transformation and illustrate the practicality of the approach
Metabolic regulation of functional decline during in vitro expansion of human mesenchymal stem cells
Human mesenchymal stem cells (hMSCs) isolated from various adult tissues are primary candidates in cell therapy and being tested in clinical trials for a wide range of diseases. The pro-regenerative and therapeutic properties of hMSCs are largely attributed to their trophic effects that coordinately modulate the progression of inflammation and enhance the endogenous tissue repair by host progenitor cells. However, immediately after isolation and upon culture expansion, hMSCs lose their in vivo quiescent state and start to accumulate genetic and phenotypic changes that significantly alter their phenotypic properties with reduced clonogenic population and therapeutic potential [1]. The culture-induced changes lead to both cellular senescence and metabolic alteration, resulting in reduced therapeutic outcome in various disease models. Since clinical application requires defined cellular properties and large-scale production of hMSCs, preserving cellular homeostasis during hMSCs in vitro expansion is a major barrier for hMSCs-based therapy and production. Once viewed as a mere consequence of the state of a cell, metabolism is now known to play active roles in regulating cellular events that govern stem cell phenotype and age-related functional properties during in vitro culture. Replicative passaging of hMSCs leads to cellular senescence following with insufficient energy production, decline of stemness and functional properties. Here, we report that energy metabolism in regulating hMSC aging-related properties due to in vitro replicative culture expansion in 2D planner or spinner flask bioreactor. hMSCs under in vitro culture up to 15 passages exhibited higher senescence with significant morphological alteration. 13C-glucose-based GC-MS metabolomics analysis suggested that metabolically heterogeneity at low passage hMSCs population while metabolic shift from glycolysis towards OXPHOS at high passage hMSCs. Rapid production of energy required for maintaining cellular properties of hMSCs alters mitochondrial function and leads to breakdown of cellular homeostasis with metabolic and redox imbalance. The alteration of metabolic profile and disruption of cellular homeostasis results in the replicative senescence and decline of therapeutic potentials of hMSCs. Understanding of hMSCs aging during in vitro culture expansion provides the insight of metabolic regulation for stem cell fate and engineering aspects for preserving and rejuvenating hMSCs functions via 3D culture or restore of metabolic balance [2].
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Elevated 1- α
A uremic patient developed hypercalcemia after tuberculosis infection, and his ionized calcium levels correlated with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) levels. We performed further studies to determine whether monocytes are alternative sites of 1,25(OH)2D3 conversion beyond renal tubular cells. Using an ex vivo bioassay, in this study, we found that 1-α hydroxylase (CYP27B1) activity in monocytes is significantly higher in patients with active tuberculosis (TB) than in those with frequent TB contact. However, when monocytes from patients with active TB were restimulated with antigen derived from Mycobacterium tuberculosis, less 1,25(OH)2D3 was observed. In contrast, the level of 1,25(OH)2D3 was unchanged in those with frequent TB contact. We conclude that monocytes may be an alternative source of 1-α hydroxylase that could convert 25-hydroxyvitamin D3 to the more active 1,25(OH)2D3
Metabolism Regulation Of Phenotypic And Therapeutic Properties Of Human Mesenchymal Stem Cells
Introduction
Human mesenchymal stem cells (hMSCs) isolated from various adult tissues are primary candidates in cell therapy and tissue regeneration. The pro-regenerative properties of hMSCs are largely attributed to their trophic effects by the release of factors that coordinately modulate the progression of inflammation and enhance the endogenous tissue repair by host progenitor cells. However, immediately after isolation and upon culture expansion, hMSCs acquire and accumulate genetic and phenotypic changes that significantly alter their phenotypic properties with reduced clonogenic and therapeutic potential. The culture-induced changes are not only correlated with reduced clonogenicity and proliferation but also with reduced therapeutic outcome in various disease models. Thus, preserving hMSC therapeutic potency following in vitro expansion is an important goal in hMSC application. Once viewed as a mere consequence of the state of a cell, metabolism is now known to play active roles in regulating cellular events that govern stem cell phenotype and functional properties. Our long term objective is to understand the role of energy metabolism in regulating hMSC cell fate with ultimate goals of developing metabolic strategies to augment hMSCs therapeutic properties.
Results
Our recent studies show that hMSCs have heterogeneity at the level of primary energy metabolism [1] and possess metabolic plasticity to reconfigure their metabolic network in their reacquisition of stem cell primitive properties and immune-modulatory property [2]. First, 13C-glucose-based metabolomics analysis suggested that hMSC are metabolically heterogeneous and that clonogenic subpopulation of hMSCs enriched in low density culture (100 cells/cm2) possesses a metabolic phenotype that differs from that of hMSCs in high-density (3,000 cells/cm2) in their levels of glycolysis metabolism and pentose phosphate pathway (PPP). Metabolic inhibition studies revealed that glycolysis and PPP play active roles in maintaining hMSCs clonogenicity by regulating ATP generation, maintaining cellular redox state, and scavenging exogenous reactive oxygen species [1]. Second, we showed that hMSCs possess metabolic plasticity and effectively reconfigure their metabolism during 3D aggregation culture, and that this metabolic reconfiguration plays a central role in their reacquisition of primitive phenotypic properties [2]. Specifically, aggregate formation of hMSCs remodeled their mitochondrial network with reduced mitochondrial membrane potential, resulting in metabolic reconfiguration with reduced mitochondrial citric acid cycle (TCA cycle) activity, increased aerobic glycolysis, and anaplerotic flux. The effects of metabolic reconfiguration on stem cell gene expression and secretory function was recapitulated in the gain- and loss-of-function experiments using small molecule metabolic modulators, confirming its functional role in regulating hMSC properties. Finally, we showed that hMSC immuno-activation in response to interferon-Îł (IFN-Îł) treatment is associated with metabolic reconfiguration towards increased aerobic glycolysis, characterized by increased glucose consumption and upregulation of glycolysis-related genes and enzymes. We further demonstrated that both glucose deprivation and glycolysis inhibition were sufficient to abolish the secretion of indoleamine 2,3-dioxygenase (IDO) a critical anti-inflammatory cytokine secreted by hMSCs, suggesting the central role of aerobic glycolysis in regulating hMSC immunomodulatory properties.
Conclusions
Together, the results revealed the mechanistic connection between metabolic regulation and hMSC therapeutic phenotype, and demonstrated the regulation of metabolism as a strategy in potentiating hMSCs properties for cell therapy. In the presentation, the implication of these findings in hMSC bioprocessing and therapeutic application will be discussed.
References
[1]. Liu, Y., N. Munoz, B.A. Bunnell, T.M. Logan, and T. Ma, Density-Dependent Metabolic Heterogeneity in Human Mesenchymal Stem Cells. Stem Cells, 2015. 33(11): p. 3368-81.
[2]. Liu, Y., N. Munoz, A.C. Tsai, B.A. Bunnell, T.M. Logan, and T. Ma, Metabolic Reconfiguration Supports Reacquisition of Primitive Phenotype in Human Mesenchymal Stem Cell Aggregates. Stem Cells, 2016. August 2016, (Accepted
Clonal spread of SCCmec type IV methicillin-resistant Staphylococcus aureus between community and hospital
ABSTRACTThe staphylococcal chromosome cassette (SCC)mec types of 382 hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) isolates in Taiwan were analysed over a 7-year period (1999â2005). There was an abrupt increase in SCCmec type IV in HA-MRSA during 2005. The molecular epidemiology of a subset (n = 69) of HA-MRSA isolates with SCCmec types III, IV or V was characterised and compared with that of community-acquired MRSA (CA-MRSA) (n = 26, collected during 2005). Pulsed-field gel electrophoresis revealed three major pulsotypes (A, B and C) and 15 minor clones. Pulsotypes B and C, which contained isolates carrying SCCmec types IV and V, respectively, included both CA-MRSA and HA-MRSA isolates. Among 24 toxin genes analysed, five genes had significant differential distribution between CA-MRSA and SCCmec type III HA-MRSA. Furthermore, among SCCmec type IV isolates, the seb gene was detected more commonly in HA-MRSA. Analysis of representative members of the three major pulsotypes by multilocus sequence typing revealed two sequence types (STs), namely ST239 (SCCmec III) and ST59 (SCCmec IV or SCCmec V). This suggests that ST59:SCCmec IV, which is usually community-acquired, has become an important nosocomial pathogen in the hospital studied
Dissemination of transposon Tn6001 in carbapenem-non-susceptible and extensively drug-resistant Pseudomonas aeruginosa in Taiwan
Recycling Nonmagnetic Material from De-sulferization Slag as Coarse Aggregate through Cold-Pressing Technique
Every year there was approximately 500,000 tons of de-sulferization slag generated in Taiwan, but the recycling amount was very slightly. A new approach, the cold-pressing technique that incorporates the principles of the cement chemistry and composite material was developed to recycle innocuous resources (e.g. construction residual soil, granite and lime sludge, and sediment, etc.) as recycling coarse aggregate. Even this technique also has successfully been applied to recycle stainless steel reductive slag with low volume stability. This paper aims to show that using cold-pressing technique can recycle nonmagnetic material from de-sulferization slag as coarse aggregate. Herein the cement-based composite is regarded as concrete. Particularly, the mixture proportions with a low cement amount of 100 kg/m3 and more than 70% (by weight) of nonmagnetic material from de-sulferization were designed. The test results show that the specific gravity of recycling coarse aggregate is about 1.67 in the OD state; the absorption capacity is 27.65%; the dry loose density (i.e. unit weight) is about 1,106 kg/m3; and other characteristics conform to ASTM C33. Therefore the cold-pressing technique is a new and practicable approach to recycle nonmagnetic material from de-sulferization slag in future
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