7,911 research outputs found
Extend the debt as it is not deeply out-of-the-money
In this paper, we modify the extendible debts model proposed in Longstaff (1990) to help relieve the moral hazard problem induced in the original model. In Longstaff¡¦s model, extending the maturity of the defaulted debts gives the borrower an incentive to default even if the borrower is insolvent. In this paper, we argue that the debt should not be extended if it is defaulted severely. We have shown that the extendible debt valuation can be obtained by the compound option pricing besides the PDE approach. We also have derived the fair interest rate of the extendible debts in this paper.
EFFECTS ON POSTURAL CONSTRAINTS ON OVERARM THROWING
This study explored the effects of postural constraints on overarm throwing. 10 participants were required to perform an overarm throwing movement by 3 tasks which under postural constraints. Tasks were including trunk-fixed, sitting, and standing. 10 pieces of 3D motion capture system were used to record the maximum velocity of body segments as data and one-way repeated measures ANOVA (a=.05) with HSD post-hoc tests was conducted to analysis the data. Therefore, the results indicated that the performance of overarm throwing by 3 tasks were different significantly, which proved the kinetic chain formed by links connected in series gave body segments more velocities. Moreover, it meat trunk and lower limbs played the roles to transport velocity as performing overarm throwing
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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SWITCHING THE HORIZONTAL GRF TO THE PATH OF PROGRESSION IN THE TABLE TENNIS FOREHAND DRIVE
Knowing the kinetic strategies of the lower limbs is a crucial factor to investigate the forehand drive which comprises the changes of the foot placement. It is difficult to directly evaluate the movement of feet with the data of ground reaction force (GRF) and impulse (GRI).This study tried to analyze table tennis forehand drives via the GRF and GRI data based upon the anatomical perspective. The motion and the GRF data were collected from eight right-handed Taiwanese elite table tennis players. The horizontal GRF data were transformed to a reference frame and then integrated with time to get the GRI. During the forehand drive shot, the participants performed a greater lateral impulse to cause the trunk rotation and decelerated their body from initial to mid-phase and then accelerated the body to perform a forehand drive shot
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-γ (IFN-γ) 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
Effects of subthalamic nucleus deep brain stimulation on quality of life and motor and depressive symptoms in Parkinson's disease
AbstractThe objective of this paper is to review the available literature concerning the effects of subthalamic nucleus deep brain stimulation (STN-DBS) on quality of life (QoL) and motor and depressive symptoms in patients with Parkinson's disease (PD). These studies demonstrate that STN-DBS has an effect on QoL and symptoms in patients with PD. There was a significant improvement in QoL following STN-DBS compared with no improvement after medical therapy. PD patients treated with STN-DBS had a 40–50% improvement in motor function. Nevertheless, depressive symptoms did not reveal consistent change
Fisher information analysis on quantum-enhanced parameter estimation in electromagnetically-induced-transparency spectrum with single photons
Electromagnetically-induced-transparency (EIT) spectroscopy has been used as
a sensitive sensor in quantum metrology applications. The sensitivity of a
sensor strongly depends on the measurement precision of EIT spectrum. In this
work, we present a theoretical study of the spectral lineshape measurement on a
three-level -type EIT media based on Fisher information (FI) analysis.
Using two kinds of probing source: the single-photon Fock state and the
coherent state, we calculate the FI in an EIT medium and quantify the quantum
advantage and limitations of the single-photon probe. The analysis of FI
structure also provides a clear picture to classify the spectral lineshape into
two different regimes, the EIT and Aulter-Townes splitting (ATS). This work
provides a systematic analysis of the single-photon EIT spectrum, which
provides essential knowledge of quantum sensing based on EIT and deepens our
understanding of spectral characteristics of -type media.Comment: 15 pages, 15 figure
Creating a ribonuclease T-tat that preferentially recognizes and hydrolyzes HIV-1 TAR RNA in vitro and in vivo
A ribonuclease, RNase T-tat, specifically designed to hydrolyze the TAR RNA of HIV-1 virus has been engineered. The protein was made by domain swapping the TAT peptide at the loop 3 position of ribonuclease T1. The RNase T-tat maintains a guanine-specific RNA hydrolytic activity, and characteristically displayed a specific affinity for the TAR RNA of HIV-1. In the in vitro and in vivo assays, the RNase T-tat preferentially inhibited the expression of TAR-bearing mRNA through cis-TAR targeting, suggesting that RNase T-tat may be potentially useful for the disruption of the initial stage of the transcription process of HIV-1 virus
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