The influence of parameters of consecutive speed control humps ...

This paper is aimed at analyzing the chaotic vibration of a vehicle passing the consecutive speed control humps (SCHs) on a highway. A consecutive SCHs-speed coupling excitation function is presented. The chaotic vibration of nonlinear vehicle is studied by numerical simulation under a 2-DOF nonlinear vehicle suspension model. The chaotic vibration excited by the consecutive SCHs with different parameters is analyzed. Simulation results demonstrate that the chaotic motion may occur as the vehicle moves over a series of the consecutive SCHs. Furthermore, chaotic motion can be inhibited reasonably and effectively by proper adjustment of parameters of the consecutive SCHs

Artificial bee colony algorithm with time-varying strategy

Artificial bee colony (ABC) is one of the newest additions to the class of swarm intelligence. ABC algorithm has been shown to be competitive with some other population-based algorithms. However, there is still an insufficiency that ABC is good at exploration but poor at exploitation. To make a proper balance between these two conflictive factors, this paper proposed a novel ABC variant with a time-varying strategy where the ratio between the number of employed bees and the number of onlooker bees varies with time. The linear and nonlinear time-varying strategies can be incorporated into the basic ABC algorithm, yielding ABC-LTVS and ABC-NTVS algorithms, respectively. The effects of the added parameters in the two new ABC algorithms are also studied through solving some representative benchmark functions. The proposed ABC algorithm is a simple and easy modification to the structure of the basic ABC algorithm. Moreover, the proposed approach is general and can be incorporated in other ABC variants. A set of 21 benchmark functions in 30 and 50 dimensions are utilized in the experimental studies. The experimental results show the effectiveness of the proposed time-varying strategy

A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein

Polyglutamine diseases are inherited neurodegenerative diseases caused by the expanded polyglutamine proteins (polyQs). We have identified a novel guanosine triphosphatase (GTPase) named CRAG that contains a nuclear localization signal (NLS) sequence and forms nuclear inclusions in response to stress. After ultraviolet irradiation, CRAG interacted with and induced an enlarged ring-like structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent manner. Reactive oxygen species (ROS) generated by polyQ accumulation triggered the association of CRAG with polyQ and the nuclear translocation of the CRAG–polyQ complex. Furthermore, CRAG promoted the degradation of polyQ at PML/CRAG bodies through the ubiquitin–proteasome pathway. CRAG knockdown by small interfering RNA in neuronal cells consistently blocked the nuclear translocation of polyQ and enhanced polyQ-mediated cell death. We propose that CRAG is a modulator of PML function and dynamics in ROS signaling and is protectively involved in the pathogenesis of polyglutamine diseases

Cholesterol Perturbation in Mice Results in p53 Degradation and Axonal Pathology through p38 MAPK and Mdm2 Activation

Perturbation of lipid metabolism, especially of cholesterol homeostasis, can be catastrophic to mammalian brain, as it has the highest level of cholesterol in the body. This notion is best illustrated by the severe progressive neurodegeneration in Niemann-Pick Type C (NPC) disease, one of the lysosomal storage diseases, caused by mutations in the NPC1 or NPC2 gene. In this study, we found that growth cone collapse induced by genetic or pharmacological disruption of cholesterol egress from late endosomes/lysosomes was directly related to a decrease in axonal and growth cone levels of the phosphorylated form of the tumor suppressor factor p53. Cholesterol perturbation-induced growth cone collapse and decrease in phosphorylated p53 were reduced by inhibition of p38 mitogen-activated protein kinase (MAPK) and murine double minute (Mdm2) E3 ligase. Growth cone collapse induced by genetic (npc1−/−) or pharmacological modification of cholesterol metabolism was Rho kinase (ROCK)-dependent and associated with increased RhoA protein synthesis; both processes were significantly reduced by P38 MAPK or Mdm2 inhibition. Finally, in vivo ROCK inhibition significantly increased phosphorylated p53 levels and neurofilaments in axons, and axonal bundle size in npc1−/− mice. These results indicate that NPC-related and cholesterol perturbation-induced axonal pathology is associated with an abnormal signaling pathway consisting in p38 MAPK activation leading to Mdm2-mediated p53 degradation, followed by ROCK activation. These results also suggest new targets for pharmacological treatment of NPC disease and other diseases associated with disruption of cholesterol metabolism

Rationally Improving Doramectin Production in Industrial <i>Streptomyces avermitilis</i> Strains

Avermectins (AVMs), a family of 16-membered macrocyclic macrolides produced by Streptomyces avermitilis, have been the most successful microbial natural antiparasitic agents in recent decades. Doramectin, an AVM derivative produced by S. avermitilis bkd− mutants through cyclohexanecarboxylic acid (CHC) feeding, was commercialized as a veterinary antiparasitic drug by Pfizer Inc. Our previous results show that the production of avermectin and actinorhodin was affected by several other polyketide biosynthetic gene clusters in S. avermitilis and Streptomyces coelicolor, respectively. Thus, here, we propose a rational strategy to improve doramectin production via the termination of competing polyketide biosynthetic pathways combined with the overexpression of CoA ligase, providing precursors for polyketide biosynthesis. fadD17, an annotated putative cyclohex-1-ene-1-carboxylate:CoA ligase-encoding gene, was proven to be involved in the biosynthesis of doramectin. By sequentially removing three PKS (polyketide synthase) gene clusters and overexpressing FadD17 in the strain DM203, the resulting strain DM223 produced approximately 723 mg/L of doramectin in flasks, which was approximately 260% that of the original strain DM203 (approximately 280 mg/L). To summarize, our work demonstrates a novel viable approach to engineer doramectin overproducers, which might contribute to the reduction in the cost of this valuable compound in the future

FE analysis of a novel roller form : a deep end-cavity roller for roller-type bearings

A novel roller form, a deep end-cavity roller, is proposed for roller-type bearings, with a view to reducing the weight of the structure and the centrifugal forces acting on the outer race of the bearing, and reducing the sensitivity of the bearing performance to the manufacturing precision. FE simulation results suggest that the new design would enable a straight-profile-roller bearing to have a similar performance to that for a logarithmic-profile roller bearing, as the deep end-cavity roller eliminates the sharp edge-stresses at the two apexes of the roller. Compared with the manufacture of a logarithmic-profile roller, the manufacture of a straight-profile deep end-cavity roller is simpler, and less strict on manufacturing precision. The deep end-cavity roller also enables an “in-process” correction of the contact-stress distribution between the roller and the raceway