Identification of partial loss of function p53 gene mutations utilizing a yeast-based functional assay

Missense mutations within the central DNA binding region of p53 are the most prevalent mutations found in human cancer. Numerous studies indicate that ‘hot-spot’ p53 mutants (which comprise ∼30% of human p53 gene mutations) are largely devoid of transcriptional activity. However, a growing body of evidence indicates that some non-hot-spot p53 mutants retain some degree of transcriptional activity in vivo, particularly against strong p53 binding sites. We have modified a previously described yeast-based p53 functional assay to readily identify such partial loss of function p53 mutants. We demonstrate the utility of this modified p53 functional assay using a diverse panel of p53 mutants.

Mathematical programming model for heat exchanger design through optimization of partial objectives

Mathematical programming can be used for the optimal design of shell-and-tube heat exchangers (STHEs). This paper proposes a mixed integer non-linear programming (MINLP) model for the design of STHEs, following rigorously the standards of the Tubular Exchanger Manufacturers Association (TEMA). Bell–Delaware Method is used for the shell-side calculations. This approach produces a large and non-convex model that cannot be solved to global optimality with the current state of the art solvers. Notwithstanding, it is proposed to perform a sequential optimization approach of partial objective targets through the division of the problem into sets of related equations that are easier to solve. For each one of these problems a heuristic objective function is selected based on the physical behavior of the problem. The global optimal solution of the original problem cannot be ensured even in the case in which each of the sub-problems is solved to global optimality, but at least a very good solution is always guaranteed. Three cases extracted from the literature were studied. The results showed that in all cases the values obtained using the proposed MINLP model containing multiple objective functions improved the values presented in the literature.

A note on the real projection of the zeros of partial sums of Riemann zeta function

This paper proves that the real projection of each simple zero of any partial sum of the Riemann zeta function ζn(s):=∑nk=11ks,n>2 , is an accumulation point of the set {Res : ζ n (s) = 0}.

The impact of the withdrawal from Afghanistan on Russia’s security. Egmont Security Policy Brief No. 54, March 2014

ISAF’s withdrawal from Afghanistan in 2014 will directly impact the wider region. Not only is there a risk of instability spilling over to Central Asia, but the drawdown will also accelerate the ongoing shift in the balance of power in Central Asia towards China. Should a spillover occur, the burden will mainly fall on Russia and China. Russia will, however, only continue playing the dominant role in the security of the former Soviet Central Asia (FSCA) until China takes on responsibility for the security of its direct sphere of influence or “dingwei”. Russia’s Near Abroad, however, overlaps both with the EU’s Eastern Neighbourhood in Europe and China’s dingwei in Central Asia and the Far East. It is, therefore, necessary to approach Russian reactions to these encroachments on its historical spheres of influence in a single context, taking into account the interrelationship between these three.