Faster and Space Efficient Exact Exponential Algorithms: Combinatorial and Algebraic Approaches

Abstract. Exponential algorithms, whose time complexity is O(c n) for some constant c> 1, are inevitable when exactly solving NP-complete problems unless P = NP. This chapter presents recently emerged combinatorial and algebraic techniques for designing exact exponential time algorithms. The discussed techniques can be used either to derive faster exact exponential algorithms, or to significantly reduce the space requirements while without increasing the running time. For illustration, exact algorithms arising from the use of these techniques for some optimization and counting problems are given.

Involvement of Akt/NF-κB pathway in antitumor effects of parthenolide on glioblastoma cells in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most common and most aggressive form of malignant glioma and is very difficult to treat. Controlling tumour cell invasion and angiogenesis is essential to improve the prognosis of glioblastoma patients. Since constitutive activation of nuclear factor-κB (NF-κB) is necessary for tumour progression, NF-κB may be an important pharmacological target for this disease. Our study aimed to evaluate the antitumour effects of parthenolide, a NF-κB inhibitor, in two human glioblastoma cell lines (U87MG and U373) and in glioblastoma xenografts. Furthermore, we aimed to investigate the molecular mechanisms underlying these effects.</p> <p>Methods</p> <p>The anti-invasive and anti-angiogenic effects of parthenolide were analysed using in vitro invasion and angiogenesis assays. Parthenolide-induced growth inhibition of glioblastoma cells in vitro was determined using the MTT (methyl thiazolyl tetrazolium) assay. In addition, the effect of parthenolide on orthotropic implantation in vivo was evaluated using an intracerebral human glioblastoma xenograft model.</p> <p>Results</p> <p>We found that parthenolide suppresses proliferation, invasion, and tumour- induced angiogenesis of glioblastoma cells. Molecular studies demonstrated that parthenolide suppresses gene and protein expression of angiogenic factors. Furthermore, parthenolide reduced Akt phosphorylation and activated mitochondrial signalling, suggesting that the antitumour function of parthenolide may be mediated not only by the inhibition of NF-κB but also by the inhibition of Akt signalling and the activation of apoptotic proteins. Parthenolide suppressed neovascularity and tumour growth in glioblastoma xenografts.</p> <p>Conclusion</p> <p>The present study identified parthenolide as a new therapeutic agent for glioblastomas.</p

Decoupling of differentiation between traits and their underlying genes in response to divergent selection

We dissected the relationship between genetic differentiation (Q(ST)) for a trait and its underlying genes (G(STq), differentiation for a quantitative locus) in an evolutionary context, with the aim of identifying the conditions in which these two measurements are decoupled. We used two parameters (theta(B) and theta(W)) scaling the contributions of inter- and intrapopulation allelic covariation between genes controlling the trait of interest. We monitored the changes in theta(B) and theta(W), Q(ST) and G(STq) over successive generations of divergent and stabilizing selection, in simulations for an outcrossing species with extensive gene flow. The dynamics of these parameters are characterized by two phases. Initially, during the earliest generations, differentiation of the trait increases very rapidly and the principal and immediate driver of Q(ST) is theta(B). During subsequent generations, G(STq) increases steadily and makes an equal contribution to Q(ST). These results show that selection first captures beneficial allelic associations at different loci at different populations, and then targets changes in allelic frequencies. The same patterns are observed when environmental change modifies divergent selection, as shown by the very rapid response of theta(B) to the changes of selection regimes. We compare our results with previous experimental findings and consider their relevance to the detection of molecular signatures of natural selectio