The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability

The fragile WWOX gene, encompassing the chromosomal fragile site FRA16D, is frequently altered in human cancers. While vulnerable to DNA damage itself, recent evidence has shown that the WWOX protein is essential for proper DNA damage response (DDR). Furthermore, the gene product, WWOX, has been associated with multiple protein networks, highlighting its critical functions in normal cell homeostasis. Targeted deletion of Wwox in murine models suggests its in vivo requirement for proper growth, metabolism, and survival. Recent molecular and biochemical analyses of WWOX functions highlighted its role in modulating aerobic glycolysis and genomic stability. Cumulatively, we propose that the gene product of FRA16D, WWOX, is a functionally essential protein that is required for cell homeostasis and that its deletion has important consequences that contribute to the neoplastic process. This review discusses the essential role of WWOX in tumor suppression and genomic stability and how its alteration contributes to cancer transformation.     

Robust Control of Robotic Manipulators in the Task-Space Using an Adaptive Observer Based on Chebyshev Polynomials

In this paper, an adaptive observer for robust control of robotic manipulators is proposed.The lumped uncertainty is estimated using Chebyshev polynomials. Usually, the uncertainty upper bound is required in designing observer-controller structures. However, obtaining this bound is a challenging task. To solve this problem, many uncertainty estimation techniques have been proposed in the literature based on neuro-fuzzy systems. As an alternative, in this paper, Chebyshev polynomials have been applied to uncertainty estimation due to their simpler structure and less computational load.Based on strictly-positive-real(SPR) Lyapunov theory, the stability of the closed-loop system can be verified. The Chebyshev coefficients are tuned based on the adaptation rules obtained in the stability analysis. Also, to compensate the truncation error of the Chebyshev polynomials, a continuous robust control term is designed while in previous related works, usually a discontinuous term is used. An SCARA manipulator actuated by permanent magnet DC motors is used for computer simulations.Simulation results reveal the superiority of the designed method.     

Structural basis for the selectivity of the external thioesterase of the surfactin synthetase

Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in bacteria, fungi and plants use two different types of thioesterases for the production of highly active biological compounds. Type I thioesterases (TEI) catalyse the release step from the assembly line of the final product where it is transported from one reaction centre to the next as a thioester linked to a 4'-phosphopantetheine (4'-PP) cofactor that is covalently attached to thiolation (T) domains. The second enzyme involved in the synthesis of these secondary metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the regeneration of functional 4'-PP cofactors of holo-T domains of NRPS and PKS systems. Mispriming of 4'-PP cofactors by acetyl- and short-chain acyl-residues interrupts the biosynthetic system. This repair reaction is very important, because roughly 80% of CoA, the precursor of the 4'-PP cofactor, is acetylated in bacteria. Here we report the three-dimensional structure of a type II thioesterase from Bacillus subtilis free and in complex with a T domain. Comparison with structures of TEI enzymes shows the basis for substrate selectivity and the different modes of interaction of TEII and TEI enzymes with T domains. Furthermore, we show that the TEII enzyme exists in several conformations of which only one is selected on interaction with its native substrate, a modified holo-T domain.     

静压循环膨胀挤压后超细/纳米晶粒纯铜管的织构演化与力学各向异性

采用静压循环膨胀挤压工艺(HTCEE)加工超细粒纯铜管,研究了其织构演化和力学各向异性行为。对于超细晶铜（UFG）管,在纵向和周向记录了不同的变形行为和显著的拉伸性能各向异性。研究结果表明HTCEE工艺使材料轴向的屈服强度和极限强度分别提高了3.6倍和1.67倍。同时,这一过程使周向的屈服强度和极限强度分别提高了1.15倍和1.12倍。作为力学各向异性判据的周向极限抗拉强度与轴向极限抗拉强度之比,对于退火粗晶粒和热处理后的UFG管分别为1.7和1.16。因此,结果表明HTCEE过程对力学各向异性有降低作用。此外,HTCEE工艺在两个方向上的延性损失都很低,这是HTCEE工艺的另一个优点。硬度测量显示,周向硬度值略有增加,这与拉伸试验的趋势一致。进行织构分析,以确定晶粒的分布,得到的111极点图证明了织构的演化,并证实了力学性能的各向异性。扫描电镜(SEM)显示,在两个正交方向拉伸试验后,出现了不同的断裂模式。     

Effects of intermediate Ni layer on mechanical properties of Al–Cu layered composites fabricated through cold roll bonding

Layered composites have attracted considerable interest in the recent literature on metal composites. Their mechanical properties depend on the quality of the bonding provided by the intermediate layers. In this study, we analyzed the mechanical properties and bond strengths provided by the nickel layer with respect to its thickness and nature (either powder or coating). The results suggest that bond strength decreases with an increase in the content of nickel powder. At 0.3vol% of nickel coating, we found the nature of nickel to be less efficient in terms of bond strength. A different picture arose when the content of nickel was increased and the bond strength increased in nickel coated samples. In addition, the results demonstrate that mechanical properties such as bend strength are strongly dependent on bond strength.     

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia

Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.     

A Markovian approach to determining process means with dual quality characteristics

This paper studies a production system where products are produced continuously and whose specification limits are specified for screening inspection. In this paper, we consider dual quality characteristics and different costs associated with each quality characteristic that falls below a lower specification limit or above an upper specification limit. Due to these different costs, the expected total profit will greatly depend on the process parameters, especially a process mean. This paper develops a Markovian-based model for determining the optimum process means with the consideration of dual quality characteristics in a single-stage system. The proposed model is then illustrated through a numerical example and sensitivity analysis is performed to validate the model. The results showed that the optimum process mean for both quality characteristics have a significant effect on the performance of the system. Since the literature survey shows that dealing with multi-quality characteristics is extremely limited, the proposed model, coupled with the Markovian approach, provides a unique contribution to this field.     

QUADRATIC REPRESENTATION FOR ROADWAY PROFILE THAT MINIMIZES EARTHWORK COST

Roadway design usually involves choices regarding grade selection and earthwork (transportation) that can be solved using linear programming. Previous work considered the road profile as series of interconnected linear segments. In these models, constraints are included in the linear programming formulation to insure continuity of the road, which cause sharp connectivity points at the intersection of the linear segments. This sharp connectivity needs to be smoothed out after l;he linear programming solution is found and the earth in the smoothed portion of the roadway has to be moved to the landfill. In previous research, the smoothing issue is dealt with after an optimal solution is found. This increases the work required by the design engineer and consequently increases the construction cost; furthermore, the optimal solution is violated by this smoothing operation. In this paper, the issue of sharp connectivity points is resolved by representing the road profile by a quadratic function. The continuit