A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease: Modelling Therapies for Multiple Myeloma Induced Bone Disease

Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma-induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF-β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti-tumour effect. On the other hand, the analyses indicate that treatments designed to inhibit TGF-β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells, which again contributes to the current controversy regarding the efficacy of TGF-β inhibition in multiple myeloma-induced bone disease

Nonlinear Analysis and Control of Interleaved Boost Converter Using Real-Time Cycle to Cycle Variable Slope Compensation

Switched-mode power converters are inherently nonlinear and piecewise smooth systems that may exhibit a series of undesirable operations that can greatly reduce the converter's efficiency and lifetime. This paper presents a nonlinear analysis technique to investigate the influence of system parameters on the stability of interleaved boost converters. In this approach, Monodromy matrix that contains all the comprehensive information of converter parameters and control loop can be employed to fully reveal and understand the inherent nonlinear dynamics of interleaved boost converters, including the interaction effect of switching operation. Thereby not only the boundary conditions but also the relationship between stability margin and the parameters given can be intuitively studied by the eigenvalues of this matrix. Furthermore, by employing the knowledge gained from this analysis, a real-Time cycle to cycle variable slope compensation method is proposed to guarantee a satisfactory performance of the converter with an extended range of stable operation. Outcomes show that systems can regain stability by applying the proposed method within a few time periods of switching cycles. The numerical and analytical results validate the theoretical analysis, and experimental results verify the effectiveness of the proposed approach

Quantum discord amplification induced by quantum phase transition via a cavity-Bose-Einstein-condensate system

We propose a theoretical scheme to realize a sensitive amplification of quantum discord (QD) between two atomic qubits via a cavity-Bose-Einstein condensate (BEC) system which was used to firstly realize the Dicke quantum phase transition (QPT) [Nature 464, 1301 (2010)]. It is shown that the influence of the cavity-BEC system upon the two qubits is equivalent to a phase decoherence environment. It is found that QPT in the cavity-BEC system is the physical mechanism of the sensitive QD amplification.Comment: 5 pages, 3 figure

Mathematical modelling of bone remodelling at the cellular level and the interaction between myeloma cells and the bone microenvironment

After an initial phase of growth and development, bone undergoes a continuous cycle of repair, renewal and optimization, by a process termed remodelling. Bone remodelling is the coordinated processes of resorption by osteoclasts and formation by osteoblasts, where old bone is replaced by new bone. Disorder of bone remodelling cycle can result in metabolic bone diseases, such as postmenopausal osteoporosis, hypothyroidism and primary hyperparathyroidism. Due to the large number of bone cell types, stages of differentiation, and the numerous growth factors and cell to cell interactions involved, our current understanding of bone remodelling and the coupling between osteoblasts and osteoclasts is still fragmentary.In the first part of this research, a novel predator-prey based mathematical model is developed to simulate bone remodelling cycles in trabecular bone at the basic multicelluar unit level, through integrating bone removal by osteoclasts and formation by osteoblasts. The model is able to replicate the curves of bone remodelling cycles obtained from standard bone histomorphometric analysis. The application of the model is firstly demonstrated by using experimental data recorded for normal (healthy) bone remodelling, to simulate the temporal variation in the number of osteoblasts and osteoclasts, and resultant effect on bone thickness. The reconstructed histomorphometric data and remodelling cycle characteristics compared well with the specified input data. Two sample pathological conditions, hypothyroidism and primary hyperparathyroidism, were then examined to demonstrate how the model could be applied more broadly. The model was validated by comparing model predictions (maximum populations of osteoclasts and osteoblasts) in the normal condition with experimental data. Further data is required to fully validate the model’s predictive capability.A second mathematical model is then developed to simulate how the interaction between multiple myeloma (MM) cells and the bone microenvironment leads to a ‘vicious cycle’ between tumour development and bone destruction. The model includes the roles of inhibited osteoblast activity and stimulated osteoclast activity, and is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after invasion and then removal of the tumour cells. The model explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The model’s predictions agree with published experimental and clinical observations. The model is also used to simulate therapies for MM-induced bone disease, including bisphosphonates, bortezomib and the inhibition of TGF-β. The simulation confirms that treatments with bisphosphonates and bortezomib can reduce the tumour burden and bone destruction, which is consistent with clinical observations. However, the inhibition of TGF-β does not appear to suppress bone destruction, although it does decrease the MM cell concentration