Growth kinetics of the granulosa cell population in ovarian follicles: an approach by mathematical modelling

This paper describes, from a mathematical viewpoint, the cellular changes in the granulosa of ovarian follicles during their terminal development. A dynamic model takes into account the processes of (1) cell division, (2) exit from the cell cycle towards differentiation, and (3) apoptotic cell death. Proliferative cells leave the cycle in an irreversible way. The risk of entering apoptosis applies to non-cycling cells. Changes in the cell numbers and in the growth fraction are derived from differential equations. The transitions between the different cell states are ruled by time-dependent rates. Numerical applications of the model concern ovulating and degenerating ovarian follicles in the ewe. The main feature of the ovulating case is the progressive exhaustion of the proliferating compartment for the benefit of the non-cycling cells. From an initial mainly proliferative state the granulosa progressively switches to a highly differentiated state, so that the growth fraction continuously decreases. In the atretic cases, the pattern of changes in the total viable cell number is influenced by the follicular age at the onset of the apoptotic process and by the intensity of the cell death rate. As apoptosis affects the non-cycling cells, the growth fraction is no longer strictly decreasing. The sensitivity of the model to the parameters is studied in a more general framework than the granulosa cell population.     

Multiprocessor modeling of parallel Particle Swarm Optimization applied to nuclear engineering problems

Particle Swarm Optimization (PSO) is a population-based metaheuristic (PBM), in which solution candidates evolve through simulation of a simplified social adaptation model. Putting together robustness, efficiency and simplicity, PSO has gained great popularity. Many successful applications of PSO are reported, in which PSO demonstrated to have advantages over other well-established PBM. However, computational costs are still a great constraint for PSO, as well as for all other PBMs, especially in optimization problems with time consuming objective functions. To overcome such difficulty, parallel computation has been used. The default advantage of parallel PSO (PPSO) is the reduction of computational time. Master-slave approaches, exploring this characteristic are the most investigated. However, much more should be expected. It is known that PSO may be improved by more elaborated neighborhood topologies. Hence, in this work, we develop several different PPSO algorithms exploring the advantages of enhanced neighborhood topologies implemented by communication strategies in multiprocessor architectures. The proposed PPSOs have been applied to two complex and time consuming nuclear engineering problems: i) reactor core design (CD) and ii) fuel reload (FR) optimization. After exhaustive experiments, it has been concluded that: i) PPSO still improves solutions after many thousands of iterations, making prohibitive the efficient use of serial (non-parallel) PSO in such kind of real-world problems and ii) PPSO with more elaborated communication strategies demonstrated to be more efficient and robust than the master-slave model. Advantages and peculiarities of each model are carefully discussed in this work.     

Alpha-tocopherol as a modulator of smooth muscle cell proliferation

The effects of alpha-tocopherol and beta-tocopherol have been studied in rat and human aortic smooth muscle cells. Alpha-tocopherol, but not beta-tocopherol, inhibited smooth muscle cell proliferation and protein kinase C in a dose-dependent manner, at concentrations ranging from 10 to 50 microM. Beta-tocopherol added simultaneously with alpha-tocopherol prevented both proliferation and protein kinase C inhibition. Protein kinase C inhibition was cell cycle-dependent and it was prevented by okadaic acid, a protein phosphatase inhibitor. Protein kinase C activity measured from aortas of cholesterol-fed rabbits was also inhibited by alpha-tocopherol. By using protein kinase C (PKC) isoform-specific inhibitors and immunoprecipitation reactions it was found that PKC-alpha was selectively inhibited by alpha-tocopherol. Further, an activation of protein phosphatase 2A by alpha-tocopherol was found, which caused PKC-alpha dephosphorylation and inhibition. Ultimately, this cascade of events at the level of cell signal transduction leads to the inhibition of smooth muscle cell proliferation.     

Size Effects in Thin Face-Centered Cubic Metals for Different Complex Forming Loadings

Influence of the size effects on the mechanical behavior of face-centered cubic metals was studied for complex loadings close to microforming ones. The effect of a reduction in thickness (t) over grain size (d) ratio on the mechanical behavior for high-purity nickel and copper is investigated for three different loadings by tensile and Nakazima tests (plane strain conditions and balanced biaxial expansion). Experimental results highlight a strong degradation of the mechanical properties of Cu and Ni when the t/d ratio is reduced below a critical value, independently of the strain path. However, this effect occurs if the equivalent plastic strain is larger than a critical level which is strain path dependent and related to the stress triaxiality. The current study reveals that plastic anisotropy is also affected by size effects. An excellent correlation is obtained between the t/d ratio and the thickness reduction, through the mean normal plastic anisotropy parameter which is widely used to estimate sheet formability. A size effect map based on forming limit diagrams is proposed to depict the optimal conditions of microforming.     

Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery

Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vascularization of diethylnitrosamine-induced hepatocarcinomas using a computerized tomography scanner approach. The efficacy of gene transfer was then evaluated by three routes of administration: intraportal, selective injection through the hepatic artery and direct injection into the tumor. Diethylnitrosamine-induced hepatocarcinomas had predominantly an arterial blood supply, 67% of the total liver blood supply. Compared with intraportal administration, arterial injection improved gene transfer into tumors whereas that to the non-tumor areas was diminished. In addition, this route of injection allowed the efficient transduction of dysplastic nodules. Diethylnitrosamine-induced hepatocarcinoma in rats is a relevant model for the study of human hepatocarcinoma due to its vascularization. Arterial infusion improved the ratio of transduced tumorous to nontumorous cells and allowed targeting of gene transfer to dysplastic nodules. This will be useful in the design of gene therapy for hepatocarcinoma.     

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