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This article presents a new family of kinematically redundant parallel mechanisms (KR-PMs) with two rotations and one translation (2R1T) based on the Lie group method. Compared with the 2-UPR/RPU PM, these PMs have two main advantages, namely, larger reachable workspaces of the moving platforms and higher motion/force transmission performance, as verified by three typical cases. The inverse kinematics, velocities, singularities, and workspaces of the 2-UPR/PRPU PM are analyzed in detail. A new method for motion/force transmission performance evaluation of KR-PMs in accordance with the indices for nonredundant PMs is proposed. Moreover, the local and global motion/force transmission performances of the 2-UPR/PRPU PM are determined using the new method. [ABSTRACT FROM AUTHOR]

This article presents a new family of kinematically redundant parallel mechanisms (KR-PMs) with two rotations and one translation (2R1T) based on the Lie group method. Compared with the 2-UPR/RPU PM, these PMs have two main advantages, namely, larger reachable workspaces of the moving platforms and higher motion/force transmission performance, as verified by three typical cases. The inverse kinematics, velocities, singularities, and workspaces of the 2-UPR/PRPU PM are analyzed in detail. A new method for motion/force transmission performance evaluation of KR-PMs in accordance with the indices for nonredundant PMs is proposed. Moreover, the local and global motion/force transmission performances of the 2-UPR/PRPU PM are determined using the new method. [ABSTRACT FROM AUTHOR]

Kinematic calibration is commonly used to improve the accuracy of a parallel mechanism. This paper presents an effective method for calibrating an overconstrained three degrees-of-freedom parallel manipulator employing a direct kinematic model. An error-mapping function is formulated from the differential of its kinematic model which is established through vector chains with the geometrical errors. To simplify the measurement of the error, the positioning and orientation error of the moving platform is replaced by the positioning error of the tool center point, which can be measured by a laser tracker accurately. Three different objective functions F1, F2, and F∞, respectively, representing 1-norm, 2-norm, and inf-norm of the error vector are used to identify the geometrical parameters of the manipulator. The results of computer simulation show that parameters after kinematic calibration through minimizing the objective function F2 is highly accurate and efficient. A calibration experiment is carried out to verify the effectiveness of the method. The maximum residual of calibration points reduces greatly from 3.904 to 0.256 mm during parameter identification. The positioning errors of all points on and inside the space surrounded by the calibration points are smaller than 0.4 mm after error compensation. [ABSTRACT FROM AUTHOR]

Background: Lung cancer, predominantly non-small-cell lung cancer (NSCLC), is the leading cause of cancer deaths worldwide. There is a great need to identify critical effectors involved in metastasis of NSCLC that will facilitate the development of new therapeutic strategies. Here we evaluated the potential role of miR-125b in the metastasis of NSCLC cells. Methods: Human NSCLC cells were isolated from surgical tissues with Cancer Cell Isolation Kit. Expressions of miR- 125b and TP53INP1 were detected with real-time PCR and western blot. Human miR-125b mimics, miR-125b inhibitor, TP53INP1 expression plasmid and TP53INP1 siRNA were transfected into NSCLC cells with nucleofector transfection kit. NSCLC metastasis was determined with adhesion assay, invasive assay and lung tumor metastasis model. Results: The expression of miR-125b was significantly higher in poorly differentiated NSCLC cells that are endowed with high metastatic potentials. Up-regulation of miR-125b could enhance the metastatic potential of NSCLC cells in vitro and in vivo, while down-regulation of miR-125b resulted in decreased metastatic potentials in vitro and in vivo. Further, tumor protein 53-induced nuclear protein 1 (TP53INP1) was an important target of miR-125b involved in metastasis of NSCLC cells. TP53INP1 served as a negative regulator of NSCLC metastasis. Decreased expression of TP53INP1 in tumor tissues was inversely associated with their expression of miR-125b, significantly lower in poorly differentiated tumors and inversely correlated with the clinical stages in patients with NSCLC. Conclusions: These findings demonstrated that miR-125b promoted tumor metastasis via targeting TP53INP1 in human NSCLC cells, which uncovered a real clinical relevance of microRNAs in tumor biology, and provided novel potential candidates for NSCLC clinical practice. [ABSTRACT FROM AUTHOR]

Accumulating data suggested that functional expression of Toll-like receptors (TLRs) in tumor cells was involved in tumor progression. Our previous study demonstrated that TLR9 signaling could enhance the tumor progression of human lung cancer cells in vitro and in vivo. We further showed that miR-574-5p was the mostly up-regulated miRNA in human lung cancer cells under TLR9 signaling by miRNA array analysis. Here we characterized the potential role of miRNA-574-5p in enhanced tumor progression induced by TLR9 signaling in human lung cancer. We confirmed that TLR9 signaling effectively elevated the expression of miR-574-5p in human lung cancer cells. Notably, we found that down-regulation of miRNA-574- 5p using miR-574-5p inhibitor in vitro or miR-574-5p sponge in vivo significantly abrogated the enhanced tumor progression induced by TLR9 signaling. Further studies showed that miR-574-5p was an important player associated with enhanced tumor progression of human lung cancer cells. Notably, we identified checkpoint suppressor 1 (Ches1) as the dominant direct target for miRNA-574-5p to confer the TLR9 signaling enhanced tumor progression. We revealed that over-expression of Ches1 significantly inhibited the cell cycle entry of human lung cancer cells. Finally, we revealed that the expression of miR-574-5p was positively correlated with TLR9 and reversely correlated with Ches1 in lung cancer patients. Our findings not only facilitated the further understanding of the crosstalk between miRNAs and TLRs in tumor biology, but also provided novel potential candidates for treatment of cancer. [ABSTRACT FROM AUTHOR]

The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Here we carefully evaluated the effect of progranulin (PGRN) in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We reported that administration of PGRN maintained the body weight and survival of ALI mice. We revealed that administration of PGRN significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in bronchoalveolar lavage (BAL) fluid. Furthermore, administration of PGRN resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin, and IgM in BAL fluid. Consistently, we revealed a significant reduction of histopathology changes of lung in mice received PGRN treatment. Finally, we showed that PGRN/TNFR2 interaction was crucial for the protective effect of PGRN on the LPS-induced ALI. Our findings strongly demonstrated that PGRN could effectively ameliorate the LPS-induced ALI in mice, suggesting a potential application for PGRN-based therapy to treat clinical ARDS. [ABSTRACT FROM AUTHOR]

Type synthesis of lower mobility parallel mechanisms (PMs) has attracted extensive attention in research community of robotics over the last seven years. One important trend in this area is to synthesize PMs with prespecified motion properties. This paper focuses on the type synthesis of a special family of PMs whose moving platform can undergo a bifurcation of Schoenflies motion. First, bifurcation of Schoenflies motion in PMs is interpreted in terms of displacement group theory and the basic limb bond {X(y)} {R(N, x)} is identified. Further, the geometric condition for constructing a PM with bifurcation of Schoenflies motion is presented. The kinematic equivalence between {X(y)}{R(N, x)} and {X(y)}{X(x)} is proven. Four subcategories of irreducible representation of the product {X(y)}{X(x)} are proposed and the limb chains that produce the desired limb bond are synthesized. Finally, the partitioned mobility of PMs with bifurcation of Schoenflies motion and its effect on actuation selection are discussed. [ABSTRACT FROM AUTHOR]

One important category of parallel mechanisms is the translational parallel mechanism (TPM). This paper focuses on the structural shakiness of the nonoverconstrained TPM. Such a structural shakiness is due to the unavoidable lack of rigidity of the real bodies, which leads to uncheckable orientation changes of the moving platform of a TPM. Using algebraic properties of displacement subsets and, especially, displacement Lie subgroup theory, we show that the structural shakiness of the nonoverconstrained TPM is inherently determined by the structural type of its limb chains. A structural shakiness index (SSI) for a nonoverconstrained TPM is introduced. When the set of feasible displacements of the end body of a 5-degree-of-freedom (DOFs) limb chain contains two infinities of parallel axes of rotation, we have SSI = 2; when the displacement set of the end body of a 5-DOF limb chain contains only one infinity of parallel axes of rotation, we have SSI = 1. It is proven that nonoverconstained TPMs constructed with limb chains with SSI = 1 are much less prone to orientation changes than those constructed with limb chains with SSI = 2. Based on the SSI, we enumerate limb kinematic chains and construct 21 nonoverconstrained TPMs with less shakiness. [ABSTRACT FROM AUTHOR]

The use of lower mobility parallel manipulators with less than six degrees of freedom (DOFs) has drawn a lot of interest in the area of parallel robots. In this paper, the type synthesis of 3R2T 5-DOF parallel mechanisms (PMs) is performed systematically using the Lie group of displacements, where R denotes a rotational DOF, and T denotes a translational DOE. First, some necessary theoretical fundamentals about the displacement group are recalled. Then, a general approach is proposed for the type synthesis of 3R2T 5-DOE PMs. The limb kinematic chains, which produce the desired displacement manifolds, are synthesized and enumerated. Structural conditions, which guarantee that the intersection of the displacement manifolds generated by the limb is the desired 5-DOF manifold, are presented. An exhaustive enumeration of 3R2T 5-DOF symmetrical PMs is obtained. Finally, an input selection method is proposed. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the regulatory mechanisms underlying sepsis progression in patients with tumor necrosis factor (TNF)-α genetic variations. The GSE5760 expression profile data, which was downloaded from the Gene Expression Omnibus database, contained 30 wild-type (WT) and 28 mutation (MUT) samples. Differentially expressed genes (DEGs) between the two types of samples were identified using the Student's t-test, and the corresponding microRNAs (miRNAs) were screened using WebGestalt software. An integrated miRNA-DEG network was constructed using the Cytoscape software, based on the interactions between the DEGs, as identified using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and the correlation between miRNAs and their target genes. Furthermore, Gene Ontology and pathway enrichment analyses were conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery and the KEGG Orthology Based Annotation System, respectively. A total of 390 DEGS between the WT and MUT samples, along with 11-associated miRNAs, were identified. The integrated miRNA-DEG network consisted of 38 DEGs and 11 miRNAs. Within this network, COPS2 was found to be associated with transcriptional functions, while FUS was found to be involved in mRNA metabolic processes. Other DEGs, including FBXW7 and CUL3, were enriched in the ubiquitin-mediated proteolysis pathway. In addition, miR-15 was predicted to target COPS2 and CUL3. The results of the present study suggested that COPS2, FUS, FBXW7 and CUL3 may be associated with sepsis in patients with TNF-α genetic variations. In the progression of sepsis, FBXW7 and CUL3 may participate in the ubiquitin-mediated proteolysis pathway, whereas COPS2 may regulate the phosphorylation and ubiquitination of the FUS protein. Furthermore, COPS2 and CUL3 may be novel targets of miR.15. [ABSTRACT FROM AUTHOR]

Study Design: This is a bioinformatic study designed to investigate the time-course expression changes of microRNAs (miRNAs) after spinal cord injury (SCI).Objective: To investigate the mechanism of SCI self-repair at miRNAs level and target genes level.Summary Of Background Data: SCI results in loss of sensory and locomotor function, and SCI self-repair might provide clinical therapies; however, the mechanism of SCI self-repair remains unclear.Methods: The miRNA expression profile (GSE19890) of adult female Wistar brown rats (Rattus norvegicus) in SCI (laminectony and contusion), sham (laminectony but no contusion), and control (untreated) groups was downloaded from Gene Expression Omnibus. Totally, 35 chips were available, including five controls, five SCI-1-day, five SCI-3-day, five SCI-7-day, five sham-1-day, five sham-3-day, and five sham-7-day. Betr and limma package were used to screen time-course differentially expressed miRNAs (DEmiRNAs), followed by Bayesian hierarchical clustering (BHC), synergetic and functional enrichment analysis through BHC and cluster Profiler packages, respectively. Furthermore, STRING database and Cytoscape software were used to construct interaction networks between time-course DEmiRNAs, and GenCLip2.0 software was applied to pathway enrichment for key genes associated with nervous system.Results: Totally, 68 time-course DEmiRNAs were identified and divided into 15 BHC clusters. Then, 100 time-course DEmiRNA pairs with synergetic function were identified, and time-course DEmiRNAs and target genes interaction networks were constructed, in which 10 genes (AKT1, VEGFA, CTNNB1, IGF1, APP, PTEN, CDC42, BDNF, SOD2, and IFNG) with highest degrees were found. Furthermore, key genes were significantly enriched in neurotrophin signaling pathway.Conclusion: After SCI, miRNAs might collectively regulate target genes, facilitating or inhibiting self-repair. Modulation of these miRNAs might provide novel therapies for SCI treatment.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the expression changes of genes in colorectal cancer (CRC) and screen the potential molecular targets. Methods: The GSE37178 of mRNA expression profile including the CRC samples extracted by surgical resection and the paired normal samples was downloaded from Gene Expression Omnibus database. The genes whose expressions were changed at four different time points were screened and clustered using Mfuzz package. Then DAVID was used to perform the functional and pathway enrichment analysis for genes in different clusters. The protein-protein interaction (PPI) networks were constructed for genes in the clusters according to the STRING database. Furthermore, the related-transcription factors (TFs) and microRNAs (miRNAs) were obtained based on the resources in databases and then were combined with the PPI networks in each cluster to construct the integrated network containing genes, TFs and miRNAs. Results: As a result, 314 genes were clustered into four groups. Genes in cluster 1 and cluster 2 showed a decreasing trend, while genes in cluster 3 and cluster 4 presented an increasing trend. Then 18 TFs (e.g., TCF4, MEF2C and FOS) and 18 miRNAs (e.g., miR-382, miR-217, miR-1184, miR-326 and miR-330-5p) were identified and three integrated networks for cluster 1, 3, and 4 were constructed. Conclusions: The results implied that expression of PITX2, VSNL1, TCF4, MEF2C and FOS are time-related and associated with CRC development, accompanied by several miRNAs including miR-382, miR-217, miR-21, miR-1184, miR- 326 and miR-330-5p. All of them might be used as potential diagnostic or therapeutic target molecules for CRC. [ABSTRACT FROM AUTHOR]