TRPV6 Determines the Effect of Vitamin D3 on Prostate Cancer Cell Growth

Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enchances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies

Social Aspects of CSCL Environments: A Research Framework

Although there are research findings supporting the positive effects of computer-supported col- laborative learning (CSCL), problems have been reported regarding the learning process itself, group formation, and group dynamics. These problems can be traced back to impeded social interaction between group members. Social interaction is necessary (a) for group members to learn from each other in a CSCL environment and (b) for socioemotional processes to help cre- ate a social space where trust, sense of community, and strong interpersonal relationships exist. This article introduces a theoretical framework consisting of three core elements: sociability, social space, and social presence, along with their relationships with group members’ mental models, social affordances and learning outcomes. It postulates that the three core elements influence the social interaction needed for both learning and the emergence of a social space. This framework serves as a basis for a research agenda for systematic social CSCL research

Physico-Chemical Modelling and Numerical Simulation of an Inductive Plasmatron

This contribution report on the development of numerical models of the inductive plasmas at sub-atmospheric pressures in the 1.2 MW Plasmatron wind tunnel constructed at the von Karman Institute. This facility will serve as an experimental means of testing thermal protection systems installed on space vehicles to protect them during the atmospheric (re-)entry phase of their flight. Numerical models are being developed to cover design and fundamental theoretical issues. As a first step in the development, the flow inside the plasma wind tunnel is assumed to be in a state of local thermodynamic equilibrium (LTE). This assumption is valid only at near the atmospheric pressure. The thermodynamic properties of a chemically reacting mixture of gases under LTE are determined by means of statistical mechanics. The transport coefficients of an ionised mixture of gases in the collision-dominated regime are computed through the Chapman-Enskog spectral Sonine solution of the Boltzmann equation. Mixture rules suited for inductive plasma conditions are referred to. Results are shown for the thermodynamic and transport properties of air and other gases; comparisons are made with numerical and experimental results of other researchers. An LTE model of the inductive plasmas inside the plasma torch of the VKI Plasmatron wind tunnel is presented. The governing MHD equations for the specific case of inductive plasmas are given. The discretisation method and the iterative solution procedure used in the model are described. Numerical results are given for an argon inductive plasma at 1 at

Numerical Simulation of Inductively Coupled Plasma Flows under Chemical Nonequilibrium

This paper presents a detailed review of the numerical modeling of inductively coupled plasma flows under local thermodynamic equilibrium and under chemical non-equilibrium. First, the physico-chemical models are described, i.e. the thermodynamics, transport phenomena and chemical kinetics models. Particular attention is given to the correct modelling of ambipolar diffusion in multi-component chemical non-equilibrium plasmas. Then, the numerical aspects are discussed, i.e. the space discretization and iterative solution strategies. Finally, computed results are presented for the flow, temperature and chemical concentration fields in an air inductively coupled plasma torch. Calculations are performed assuming local thermodynamic equilibrium and under chemical non-equilibrium, where two different finite-rate chemistry models are used. Besides important non-equilibrium effects, we observe significant demixing of oxygen and nitrogen nuclei, which occurs due to diffusion regardless of the degree of non-equilibrium in the plasma