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Due to the existence of a flexible isolation layer the flow pattern of granular ore rock in the synchronous filling shrinkage method breaks through the description range of the traditional ore drawing theory,so studies on the flow pattern of granular ore rock in a single funnel under a flexible isolation layer have important significance for enriching the ore drawing theory. Based on the similarity principle,a physical test model was designed,by which the morphology of the draw ore body and the loosen ore body was delineated and drawn by marking particles. The basic data of testing were recorded with a high-definition camera. The evolution laws of the spatial morphology of the draw ore body,loosen ore body,and cavity during single funnel drawing under a flexible isolation layer were analyzed on the basis of these basic data. The draw ore body showed completely closed and quasi-ellipsoidal morphology before the highest horizon ore settled; but after this settlement the draw ore body was gyrostatic. Before settlement of the highest horizon ore occurred,the loosen ore body showed completely closed and quasi-ellipsoid morphology; but after this settlement appeared,the loose body shape was trumpet-shaped on the whole,with an exponential curve in the upper part and a quasi-ellipsoid in the lower part. The cavity began to form at the moment when the settlement of the highest horizon ore occurred. The isolation layer was tangent to the ore layer at the cavity boundary. The cutting angle increased with the increasing fall depth of the isolation layer and kept invariant after it reached to the natural repose angle. With the sinkage of the isolation layer,the position of the tangent point gradually changed from the center to both sides until the end of ore drawing.

Defective neurogenesis in the postnatal brain can lead to many neurological and psychiatric disorders, yet the mechanism behind postnatal neurogenesis remains to be investigated. Huntingtin-associated protein 1 (HAP1) participates in intracellular trafficking in neurons, and its absence leads to postnatal death in mice. Here, we used tamoxifen-induced (TM-induced) Cre recombination to deplete HAP1 in mice at different ages. We found that HAP1 reduction selectively affects survival and growth of postnatal mice, but not adults. Neurogenesis, but not gliogenesis, was affected in HAP1-null neurospheres and mouse brain. In the absence of HAP1, postnatal hypothalamic neurons exhibited reduced receptor tropomyosin-related kinase B (TRKB) levels and decreased survival. HAP1 stabilized the association of TRKB with the intracellular sorting protein sortilin, prevented TRKB degradation, and promoted its anterograde transport. Our findings indicate that intracellular sorting of neurotrophin receptors is critical for postnatal neurogenesis and could provide a therapeutic target for defective postnatal neurogenesis., Introduction Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Unlike embryonic neurogenesis, which is largely controlled by transcription factors, and adult neurogenesis, which [...]

This paper proposes a systematic methodology for dimension synthesis, kinematics, and statics of a novel 2SPS + SPR + SP parallel manipulator with 3DOF. First, a workspace is varied and analyzed by varying the orientation of a revolute joint, and an optimum orientation of revolute joint is determined. Second, the inverse displacement is analyzed, and the formulas are derived for solving general inverse/forward velocities and accelerations. Third, the geometric constraints of constrained forces are determined and the formulas are derived for solving the active/constrained forces. [DOI: 10.1115/1.2936897] Keywords: parallel manipulator, workspace, kinematics, statics

Joubert syndrome is an autosomal recessive disorder characterized by congenital malformation of the cerebellum and brainstem, with abnormal decussation in the brain. Mutations in the Abelson helper integration site 1 gene, which encodes the protein AHI1, have been shown to cause Joubert syndrome. In this study, we found that mouse Ahi1 formed a stable complex with huntingtin-associated protein 1 (Hap1), which is critical for neonatal development and involved in intracellular trafficking. Hap1-knockout mice showed significantly reduced Ahi1 levels, defective cerebellar development, and abnormal axonal decussation. Suppression of Ahi1 also decreased the level of Hap1; and truncated Ahi1, which corresponds to the mutations in Joubert syndrome, inhibited neurite outgrowth in neuronal culture. Reducing Hap1 expression suppressed the level and internalization of TrkB, a neurotrophic factor receptor that mediates neurogenesis and neuronal differentiation, which led to decreased TrkB signaling. These findings provide insight into the pathogenesis of Joubert syndrome and demonstrate the critical role of the Ahi1-Hap1 complex in early brain development., Introduction Clinical features of Joubert syndrome (JS) include neonatal hypotonia (loss of muscle tone), ataxia, developmental delay, mental retardation, and frequently abnormalities in breathing and eye movements (1-3). Various abnormalities [...]

Non-human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non-human primate models of human diseases. Huntington's disease [...]

The hypothalamus responds to circulating leptin and insulin in the control of food intake and body weight. A number of neurotransmitters in the hypothalamus, including [gamma]-aminobutyric acid (GABA), also have key roles in feeding. Huntingtin-associated protein 1 (Hap1) is expressed more abundantly in the hypothalamus than in other brain regions, and lack of Hap1 in mice leads to early postnatal death. Hap1 is also involved in intracellular trafficking of the GABA[sub.A] receptor. Here, we report that fasting upregulates the expression of Hap1 in the rodent hypothalamus, whereas intracerebroventricular administration of insulin downregulates Hap1 by increasing its degradation through ubiquitination. Decreasing the expression of mouse hypothalamic Hap1 by siRNA reduces the level and activity of hypothalamic GABA[sub.A] receptors and causes a decrease in food intake and body weight. These findings provide evidence linking hypothalamic Hap1 to GABA in the stimulation of feeding and suggest that this mechanism is involved in the feeding-inhibitory actions of insulin in the brain., Author(s): Guoqing Sheng [1]; Guo-qing Chang [2]; John Y Lin [3]; Zhao-Xue Yu [1]; Zhi-Hui Fang [1]; Juan Rong [1]; Stuart A Lipton [3, 4]; Shi-Hua Li [1]; Gang Tong [...]

Author(s): Lucia Pastorino [1, 7]; Anyang Sun [1, 6, 7]; Pei-Jung Lu [2, 7]; Xiao Zhen Zhou [1]; Martin Balastik [1]; Greg Finn [1]; Gerburg Wulf [1]; Jormay Lim [1]; [...]