Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells

Genetic and molecular heterogeneity,together with intrinsic and acquired resistance to therapy,represent the major obstacles to the successful treatment of different types of breast carcinoma.Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade,poor prognosis,and therapy resistance.Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas,and these genes are recognized as potential antitumor targets.Our aim was to evaluate the effect of retinoic acid(RA),a well-known cyto-differentiating agent,on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes.By applying various experimental approaches,we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines.We have shown that RA inhibits cell growth,reduces the number of Ki-67 positive cells,and causes cell-cycle arrest.RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression,including a higher decrease in cell viability,reduction in colony formation,and significant remodeling of cellular structure.We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines.By functional analysis,we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2,pointing to a SOX2-independent mechanism of action.The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders.Together,our study shows that the response of breast carcinoma cell lines to RA treatment may vary,highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.

Design and Optimization of a GaN GIT Based PFC Boost Converter

The advent of GaN power devices brings the possibility of pushing up frequencies of power electronics system beyond the capacity of conventional Si counterparts.To harvest the high frequency operation benefits of GaN technology,not only GaN devices should be used optimally by providing proper switching and conduction conditions to best accommodate parasitic elements inherent with the devices,other components should also be capable of facilitating high frequency operation.In this paper,PFC boost converter is used as a platform to harvest the benefits of GaN technology and,at the same time,to uncover the limitations in pushing power electronics systems up.A 600W PFC boost converter with a maximum switching frequency of 3MHz is designed and implemented,which reached an average efficiency of 98.5%.The results indicate that,when properly used,a GaN PFC boost converter could operate at a frequency that is beyond the reach of conventional Si ones.As well,with availability of GaN devices,high frequency operation of power electronics systems is no longer limited by the lack of switching devices but by practical issues e.g.high frequency magnetic materials,high frequency controllers,etc.

TG-interacting Factor(TGIF) Downregulates SOX3 Gene Expression in the NT2/D1 Cell Line

SOX3 is a member of the Sox gene family implicated in brain formation and cognitive function. It is considered to be one of the earliest neural markers in vertebrates, playing a role in specifying neuronal fate. Recently, we have established the first link between TALE （three- amino-acid loop extension） proteins, PBX1 （pre-B-cell leukemia homeobox 1） and MEIS1 （myeloid ecotropic viral integration site 1 homologue）, and the expression of the human SOX3 gene. Here we present the evidence that TGIF （TG-interacting factor） is an additional TALE superfamily member involved in the regulation of human SOX3 gene expression in NT2/D1 cells by direct interaction with the consensus binding site that is conserved in primate orthologue promoters. Functional analysis demonstrated that mutation of the TGIF binding site resulted in the activation of SOX3 promoter. TGIF overexpression downregulates SOX3 promoter activity and decreases endogenous SOX3 protein expression in both uninduced and retinoic acid （RA）-induced NT2/D1 ceils. Up to now, this is the first transcription factor identified as a negative regulator of SOX3 gene expression. The obtained results further underscore the significance of TALE proteins as important transcriptional regulators of SOX3 gene expression.

AN ADAPTIVE FAST INTERFACE TRACKING METHOD

An adaptive numerical scheme is developed for the propagation of an interface in a velocity field based on the fast interface tracking method proposed in [2]. A multiresolution stategy to represent the interface instead of point values, allows local grid refinement while controlling the approximation error on the interface. For time integration, we use an explicit Runge-Kutta scheme of second-order with a multiseale time step, which takes longer time steps for finer spatial scales. The implementation of the algorithm uses a dynamic tree data structure to represent data in the computer memory. We briefly review first the main algorithm, describe the essential data structures, highlight the adaptive scheme, and illustrate the computational efficiency by some numerical examples.