Explore the vast range of titles available.

Collision-free path planning is a crucial capability for industrial robot in its application. In this paper, a collision avoidance strategy based on virtual body deformation (VBDCAS) is proposed to improve the planning efficiency. The main idea of VBD-CAS is to realize the obstacle avoidance according to the allowable deformation space of the robotic arm relative to the obstacle. The obstacle avoidance evaluation model with spherical obstacle is established through the limit motion analysis of robotic arms. Then, a particle swarm optimization with VBDCAS (PSO-VBD-CAS) algorithm is developed for the collision-free path planning by integrating VBD-CAS into PSO algorithm. PSO-VBD-CAS algorithm uses obstacle avoidance evaluation model to judge weather the collision is happened between robotic arm and obstacles. When the joint angles of robot is located in the allowable deformation space of robotic arm, the robotic arm does not collide with obstacles. The proposed algorithm can directly perform the collision judgment without repeatedly performing forward kinematics solution of robot and shortest distance calculation from robotic arm to obstacles. Two simulations and an experiment are used to verify the validity of the proposed method. The validation results demostrate that the proposed VBD-CAS can effectively realize the collision detection, meanwhile the PSO-VBD-CAS algorithm has a better efficiency compared to distance-based obstacle avoidance path planning methods.

Robots are main elements in Industry 4.0. Research on the design optimization of robots has a great significance in manufacturing industries. There inevitably exist various uncertainties in robot design that have an important influence on the reliability of robots. At present, the design optimization of robots considering the uncertainties is mainly focused on joints design and trajectory optimization. However, for the structural design of robots, deterministic design optimization still plays a leading role. In this paper, a simulation-based reliability design optimization method is proposed to improve the reliability of robots’ structural design. In the proposed method, the Latin hypercube sampling (LHS), computer simulation, response surface method (RSM) and SORA (Sequential Optimization and Reliability Assessment) algorithm are integrated to complete the structural design of the robot. Firstly, samples of the uncertainty design variables were obtained by LHS, and then, the reliability performance constraint functions were firstly constructed through the RSM in which the joint simulation of MTLAB and ANSYS was adopted. Afterwards, the reliability design optimization model was established on the basis of the probabilistic reliability theory. At last, the SORA algorithm was employed to realize the optimization. The design optimization problems of the big arm and the small arm of a 6 Kg industrial robot were considered to verify the proposed method. The results showed that the weights of the big arm and the small arm were, respectively, reduced by 7.73% and 25.70% compared with those of the original design, and the design was more effective in ensuring the reliability requirements compared with the deterministic optimization. Moreover, the results also demonstrated that the proposed method has a better computational efficiency compared with the reliability design optimization of the double-loop method.

BackgroundThe role of laparoscopic-assisted natural orifice specimen extraction (LA-NOSE) colectomy in the treatment of left-sided colon cancer has not been well defined, and there remains confusion about how to conveniently exteriorize specimens through natural orifices. Therefore, we introduced a homemade invention, the Cai tube, to facilitate the extraction of specimens and compared the clinical outcomes of LA-NOSE with conventional laparoscopic (CL) colectomy for left-sided colon cancer.MethodsFrom March 2015 to August 2017, patients with left-sided colon cancer were randomly divided into LA-NOSE and CL groups. Specimens were extracted through the anus with the help of a Cai tube (Patent Number: ZL201410168748.2) in the LA-NOSE group. The primary outcome measure was postoperative pain. Secondary outcomes were the duration of operation, postoperative recovery, surgical morbidity, pathological quality of the specimen, and long-term outcomes, including 3-year overall survival, disease-free survival, local recurrence, and overall recurrence.ResultsA total of 60 patients (30 per group) were recruited for this study. None of the patients required emergency conversion to conventional laparoscopic or open surgery during the operation. The postoperative maximum pain score was significantly lower in the LA-NOSE group (mean 2.5 vs. 5.1, P = 0.001), as was the additional analgesia requirement (mean 2/30 vs. 10/30, P = 0.021). Patients in the LA-NOSE group experienced a shorter first time to passage of flatus (mean 2.2 vs. 3.1 days, P = 0.026). All patients could control their defecation at 6 months after surgery. The comparison between the two groups showed no significant differences in the operative time, bleeding volume, postoperative hospital stay, surgical morbidity rates, number of lymph nodes harvested, or resection margin status. The mean follow-up was 48 months (range 7–59) and was similar in both groups. The results showed no differences in long-term outcomes between the two groups.ConclusionIn the treatment of left-sided colon cancer, compared with conventional laparoscopic colectomy, LA-NOSE colectomy using the Cai tube exhibited lower postoperative pain, shorter recovery of gastrointestinal function, and similar long-term outcomes.Registration numberChiCTR-OOR-15007060 (http://www.chictr.org.cn/).

A UPLC-PDA-QTOFMS-guided isolation strategy was employed to screen and track potentially new compounds from Garcinia oblongifolia . As a result, two new prenylated xanthones, oblongixanthones D and E ( 1 – 2 ), six new prenylated benzoylphloroglucinol derivatives, oblongifolins V–Z ( 3 – 7 ) and oblongifolin AA ( 8 ), as well as a known compound oblongifolin L ( 9 ), were isolated from the EtOAc-soluble fraction of an acetone extract of the leaves of Garcinia oblongifolia guided by UPLC-PDA-QTOFMS analysis. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analysis and mass spectrometry. Experimental and calculated ECD spectra were used to determine the absolute configurations. The results of wound healing and transwell migration assay showed that oblongixanthones D ( 1 ), E ( 2 ), and oblongifolin L ( 9 ) have the ability to inhibit cancer cell migration in lower cytotoxic concentrations. Western blotting results showed that these compounds exhibited an anti-metastasis effect mainly through downregulating RAF protein levels. In addition, 2 and 9 could inhibit phospho-MEK and phospho-ERK at downstream. Moreover, 1 , 2 , and 9 could inhibit snail protein level, suggesting that they could regulate the EMT pathway.

Scientific Reports 6: Article number: 35789; published online: 21 October 2016; updated: 23 December 2016

Objective Increasing evidence shows that microRNA (miR) is related to drug resistance in hepatocellular carcinoma (HCC). miR-34b-5p could retard tumor development, but its function in HCC is still unclear. Methods miR-34b-5p expression was determined in HCC tissues and cell lines. Analysis and verification of the binding between miR-34b-5p and metadherin (MTDH) was carried out. The actual action of miR-34b-5p and MTDH in the area of proliferation, apoptosis, invasion, and migration of cisplatin (DDP)-resistant HCC cells was monitored. Results miR-34b-5p was downregulated in HCC. Overexpression of miR-34b-5p enhanced the sensitivity of HCC cells to DDP, inhibiting proliferation, migration, and invasion and promoting apoptosis. MTDH was the direct target of miR-34b-5p. MTDH was upregulated in HCC tissues, which was negatively correlated with miR-34b-5p expression. Enhancement of MTDH can reverse the effect of upregulated miR-34b-5p on the chemosensitivity of HCC cells. Conclusion miR-34b-5p targets MTDH and enhances the chemosensitivity of HCC cells.

Sighting and binding of double-stranded DNA （ds- DNA） by a sensor in the cytoplasm trigger the activation of the immune-surveillance pathways [1]. The crystal structure of absent in melanoma 2 （AIM2） bound with DNA conclusively defines the role of AIM2 as a sensor in the innate immune system [2]. AIM2 belongs to the PYHIN family of proteins and contains a pyrin domain （PYD） followed by a hematopoietic interferon-inducible nuclear protein （HIN） domain （Figure 1A）. AIM2 binds DNA via the HIN domain and recruits the adaptor pro- tein apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） via the PYD. ASC in turn recruits caspase-1 via CARD-CARD interaction, resulting in the formation of inflammasomes comprised of AIM2, ASC and caspase-1. The molecular crowding of the AIM2 inflammasome ensures the proteolysis and transactivation of caspase-1. Activated caspase-1 cleaves pro-IL-1 ]3 and pro-IL-18 into their mature proinflamma- tory forms [3, 4]. The termination of inflammatory responses originated from inflammasomes can be accomplished by employing naturally occurring dominant-negative antagonists [4]. Dominant-negative proteins are similar to their canoni- cal counterparts except for a missing effector domain, so that they cannot relay the signals any further. They out- compete their canonical counterparts for ligands or bind- ing sites and thus block the downstream signal transduc- tion. Such regulation is essential for maintaining cellular homeostasis. To regulate inflammasome activation, mice have evolved a strategy that has so far not been discov- ered in humans. Mice use the H1N-only protein, p202, to sequester cytoplasmic dsDNA and render it unavailable for its canonical sensor, AIM2 [4]. p202 contains two HIN domains （HINa and H1Nb）, but lacks the PYD （Fig- ure 1A）. Therefore, p202 is unable to recruit the adaptor ASC, and its binding to DNA results in the termination of inflammasome signaling. The significance of p202 in the regulation of the innate immune responses is exem- plified by the fact that dysregulation of p202 function hasbeen linked to increased susceptibility to systemic lupus erythematosus [5]. To more clearly understand the mechanism of inhibi- tion of AIM2-mediated signaling by p202, it is essential to solve the structure of p202 in complex with DNA and compare it with that of AIM2 complexed with DNA. p202 has so far only been detected in mice. To compare the structure of AIM2 and p202 from the same species, we first solved the structure of the H1N domain of mu- rine AIM2 （mAIM2） in complex with dsDNA to 2.23 A resolution （Supplementary information, Table S1）. Although a 12-base pair （bp） long dsDNA was used for the crystallization, the HIN domain of mAIM2 seems to have lined up the DNA oligonucleotides end to end, gen- erating an appearance of a long and contiguous stretch of B-form DNA with putative major and minor grooves. As expected, the overall structure of the H1N domain of mAIM2 （Figure 1B） closely mirrors the structure of its human counterpart [2] （Supplementary information, Fig- ure S 1）. Minor deviations are observed at the N-terminus and in the loop regions. The surface electrostatic poten- tial distribution is similar, implying that the mechanism of tethering dsDNA is similar between human and mouse AIM2. The HIN domain of AIM2 consists of two oligonucle- otide/oligosaccharide （OB） folds [6] linked via a flexible linker （Figure 1B）. The proximal and distal OB folds are referred to as OB1 and OB2, respectively. Similar to the human ortholog, mAIM2 uses the helix-loop-helix motif located in the linker to engage DNA （Figure 1C）. Specifically, a short helix containing two turns is inserted horizontally to the vertical axis of the DNA spiral （Figure 1C）. Amino acids from the loop connecting helices ul and a2, and from helix ct2 interact with the major groove （Figure 1C）. A couple of interactions between OB2 and the DNA backbone are also observed. Residues N244, N245, K248, R249, R251, R255, K258, 0262 K273,

Asparaginyl endopeptidase （AEP） is an endo/lysosomal cysteine endopeptidase with a preference for an asparagine residue at the P1 site and plays an important role in the maturation of toll-like receptors 3/7/9. AEP is known to undergo autoproteolytic maturation at acidic pH for catalytic activation. Here, we describe crystal structures of the AEP proenzyme and the mature forms of AEP. Structural comparisons between AEP and caspases revealed similarities in the composition of key residues and in the catalytic mechanism. Mutagenesis studies identified N44, R46, H150, E189, C191, S217/S218 and D233 as residues that are essential for the cleavage of the peptide substrate. During maturation, autoproteolytic cleavage of AEP＇s cap domain opens up access to the active site on the core domain. Unexpectedly, an intermediate autoproteolytic maturation stage was discovered at approximately pH 4.5 in which the partially activated AEP could be reversed back to its proenzyme form. This unique feature was confirmed by the crystal structure of AEPpH4.s （AEP was matured at pH 4.5 and crystallized at pH 8.5）, in which the broken peptide bonds were religated and the structure was transformed back to its proenzyme form. Additionally, the AEP inhibitor cystatin C could be digested by the fully activated AEP, but could not be digested by activated cathepsins. Thus, we demonstrate for the first time that cystatins may regulate the activity of AEP through substrate competition for the active site.

The p-center problem consists of choosing a subset of vertices in an undirected graph as facilities in order to minimize the maximum distance between a client and its closest facility. This paper presents a greedy randomized adaptive search procedure with path-relinking (GRASP/PR) algorithm for the p-center problem, which combines both GRASP and path-relinking. Each iteration of GRASP/PR consists of the construction of a randomized greedy solution, followed by a tabu search procedure. The resulting solution is combined with one of the elite solutions by path-relinking, which consists in exploring trajectories that connect high-quality solutions. Experiments show that GRASP/PR is competitive with the state-of-the-art algorithms in the literature in terms of both solution quality and computational efficiency. Specifically, it virtually improves the previous best known results for 10 out of 40 large instances while matching the best known results for others.