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We describe the development of a very large-scale causal, computable model of biology and its specific application in the identification of molecular cause and effect hypotheses of mechanisms underlying the effects of androgen stimulation in the LNCaP prostate carcinoma cell line. In contrast to previous LNCaP studies in which genes have been hierarchically clustered by their pattern of response to...
We describe the development of a very large-scale causal, computable model of biology and its specific application in the identification of molecular cause and effect hypotheses of mechanisms underlying the effects of androgen stimulation in the LNCaP prostate carcinoma cell line. In contrast to previous LNCaP studies in which genes have been hierarchically clustered by their pattern of response to...
In breast cancer treatment for many cases intrinsic or acquired resistance against available therapeutics leads to death. According to the present biological understanding, drug resistance is caused by molecular mechanisms in the complex network of proteins that regulate cell proliferation by activation of the estrogen receptor (ER), hereby allowing the cell to bypass the classical estrogen receptor...
In breast cancer treatment for many cases intrinsic or acquired resistance against available therapeutics leads to death. According to the present biological understanding, drug resistance is caused by molecular mechanisms in the complex network of proteins that regulate cell proliferation by activation of the estrogen receptor (ER), hereby allowing the cell to bypass the classical estrogen receptor...
Signal transduction networks are often described by qualitative models that incorporate experimental findings from different cell types. However, a large body of evidence suggests that cell signaling differs substantially from one cell type to the next. Even in cases in which the topology of signaling networks is conserved, different cell types respond differently under the same experimental conditions...
Signal transduction networks are often described by qualitative models that incorporate experimental findings from different cell types. However, a large body of evidence suggests that cell signaling differs substantially from one cell type to the next. Even in cases in which the topology of signaling networks is conserved, different cell types respond differently under the same experimental conditions...
The molecular circadian clock which is present in almost all cells of animal organisms exerts a control on the cell division cycle in proliferating tissues by modulating the activity of cyclins and cyclin dependent kinases (CDKs), the proteins which determine transitions from one phase of the cell cycle to the following one, until effective division. Each peripheral cell circadian clock is under the...
The molecular circadian clock which is present in almost all cells of animal organisms exerts a control on the cell division cycle in proliferating tissues by modulating the activity of cyclins and cyclin dependent kinases (CDKs), the proteins which determine transitions from one phase of the cell cycle to the following one, until effective division. Each peripheral cell circadian clock is under the...
We report about two-photon activation of a photoactivatable derivative of the Aequorea Victoria green fluorescent protein (paGFP). This special form of the molecule increases its fluorescence intensity when excited by 488 nm after irradiation with high intensity light at 413 nm. The aim in this work was to evaluate the use of two-photon interactions for confining the molecular switching of pa-GFP...
We report about two-photon activation of a photoactivatable derivative of the Aequorea Victoria green fluorescent protein (paGFP). This special form of the molecule increases its fluorescence intensity when excited by 488 nm after irradiation with high intensity light at 413 nm. The aim in this work was to evaluate the use of two-photon interactions for confining the molecular switching of pa-GFP...
Adult-derived stem cells have recently been found to respond in vivo to inductive signals from the microenvironment and to differentiate into a phenotype that is characteristic of cells in that microenvironment. We examined the differentiation potential of an adult liver stem cell line (WBF344) in a cardiac microenvironment in vitro. WBF344 cells were established from a single cloned non-parenchymal...
Adult-derived stem cells have recently been found to respond in vivo to inductive signals from the microenvironment and to differentiate into a phenotype that is characteristic of cells in that microenvironment. We examined the differentiation potential of an adult liver stem cell line (WBF344) in a cardiac microenvironment in vitro. WBF344 cells were established from a single cloned non-parenchymal...
The present study was designed to explore an ex vivo culturing protocol for fibroblastic differentiation of human mesenchymal stem cells (hMSCs) using connective tissue growth factor (CTGF). Fibroblastic differentiation from stem cells is of widespread significance in the engineering of virtually all tissues including tendons, ligaments, periodontal ligament, cranial sutures and as interstitial filler...
The present study was designed to explore an ex vivo culturing protocol for fibroblastic differentiation of human mesenchymal stem cells (hMSCs) using connective tissue growth factor (CTGF). Fibroblastic differentiation from stem cells is of widespread significance in the engineering of virtually all tissues including tendons, ligaments, periodontal ligament, cranial sutures and as interstitial filler...
Soft tissues such as the anterior cruciate ligament (ACL) connect to bone tissue through a characteristic fibrocartilagenous interface. This interface is essential for load transfer between soft and hard tissues, and its absence is the primary cause of graft failure post ACL reconstruction surgeries. Currently, the mechanism of interface regeneration is not known. Based on in vivo observations that...
Soft tissues such as the anterior cruciate ligament (ACL) connect to bone tissue through a characteristic fibrocartilagenous interface. This interface is essential for load transfer between soft and hard tissues, and its absence is the primary cause of graft failure post ACL reconstruction surgeries. Currently, the mechanism of interface regeneration is not known. Based on in vivo observations that...
Using layer-by-layer technology in drug delivery systems is advantageous because of its high precision, mild assembly conditions, and ease of use. In this study, we investigate the use of such a system using a micronized dexamethasone core as the building template. Dexamethasone was chosen because of its hydrophobic structure and role as a cellular differentiation factor. Structural characterization...
Using layer-by-layer technology in drug delivery systems is advantageous because of its high precision, mild assembly conditions, and ease of use. In this study, we investigate the use of such a system using a micronized dexamethasone core as the building template. Dexamethasone was chosen because of its hydrophobic structure and role as a cellular differentiation factor. Structural characterization...
Several stochastic simulation tools have been developed recently for cell signaling. A comparative evaluation of the stochastic simulation tools is needed to highlight the current state of the development. In our study, we have chosen to evaluate three stochastic simulation tools: Dizzy, Systems Biology Toolbox, and Copasi, using our own MATLABreg implementation as a benchmark. The Gillespie stochastic...
Several stochastic simulation tools have been developed recently for cell signaling. A comparative evaluation of the stochastic simulation tools is needed to highlight the current state of the development. In our study, we have chosen to evaluate three stochastic simulation tools: Dizzy, Systems Biology Toolbox, and Copasi, using our own MATLABreg implementation as a benchmark. The Gillespie stochastic...
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