Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC₅₀ values of 3.4–37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC₅₀ value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (−7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.     

Associated Primes of the Example of Brenner and Monsky

Recently, Brenner and Monsky found an example of an ideal in a hypersurface ring whose tight closure does not commute with localization, thus answered the localization problem in tight closure theory in the negative. In this article, we use Monsky's calculations to analyze the set of associated primes of the Frobenius powers of this ideal and show that this set is infinite.     

Large displacement analysis of shear deformable composite beams with interlayer slips

This paper presents a novel geometric non-linear finite element formulation for the analysis of shear deformable two-layer beams with interlayer slips. We adopt the co-rotational approach where the motion of the element is decomposed into two parts: a rigid body motion which defines a local coordinate system and a small deformational motion of the element relative to this local coordinate system. The main advantage of this approach is that the transformation matrices relating local and global quantities are independent to the choice of the geometrical linear local element. The effect of transverse shear deformation of the layers is taken into account by assuming that each layer behaves as a Timoshenko beam element. The layers are assumed to be continuously connected and partial interaction is considered by considering a continuous relationship between the interface shear flow and the corresponding slip. In order to avoid curvature and shear locking phenomena, the local linear element is formulated using “exact” displacement shape functions derived from the closed-form solution of the governing equations of a two-layer beam element. Finally, three numerical applications are presented in order to assess the performance of the proposed formulation.     

Inducing anisotropy in bulk Nd-Fe-Co-Al-B nanocrystalline alloys by quenching in magnetic field

We have observed magnetic anisotropy in bulk Nd_55−xCo_xFe₃₀Al₁₀B₅ (x=10, 15 and 20) alloys prepared by copper mold suction casting method with a presence of external magnetic field (quenching field) μ₀H=0.25 T. By changing direction of the measuring field from perpendicular to parallel one in comparison with that of the quenching field, coercive force of the alloys slightly decreases while remanent magnetization and squareness of hysteresis loop increase more clearly. It is also found that the higher Co-concentration in the alloys the larger magnetic anisotropy is induced. The structure analyses manifest nanocrystalline particles embedded in residual amorphous matrix of the alloys. The size of the particles is in range of 10-30 nm and their crystalline phases consist of Nd₂(Fe,Co)₁₄B, Nd₃Co, Nd₃Al, NdAl₂ and Nd.     

Globally solving a nonlinear UAV task assignment problem by stochastic and deterministic optimization approaches

In this paper, we consider a task allocation model that consists of assigning a set of m unmanned aerial vehicles (UAVs) to a set of n tasks in an optimal way. The optimality is quantified by target scores. The mission is to maximize the target score while satisfying capacity constraints of both the UAVs and the tasks. This problem is known to be NP-hard. Existing algorithms are not suitable for the large scale setting. Scalability and robustness are recognized as two main issues. We deal with these issues by two optimization approaches. The first approach is the Cross-Entropy (CE) method, a generic and practical tool of stochastic optimization for solving NP-hard problem. The second one is Branch and Bound algorithm, an efficient classical tool of global deterministic optimization. The numerical results show the efficiency of our approaches, in particular the CE method for very large scale setting.     

Drop deposition of thin nanostructured coatings of lead telluride

The current-voltage relationships of deposited structures are measured for cluster structures consisting of nanoparticles of lead telluride. Variation in the value of the tunnel current is shown. Optimum conditions for the possible emergence of quantum-hopping conductivity due to carrier tunneling (the characteristic sizes of the nanoclusters and the distances between them) are determined.     

A Strong Law for Mixing Random Variables

A sharp almost sure bound is derived for limit points of average sum of weakly dependent random variables, which ensures strong laws of large numbers for and -mixing random variables, without assumptions on rate of tending to zero of and -mixing parameters _n and _n.