Singularity analysis and avoidance for an SSRMS-type reconfigurable space manipulator with a non-spherical wrist and two lockable passive telescopic links

This study focuses on addressing kinematic singularity analysis and avoidance issues for a space station remote manipulator system(SSRMS)-type reconfigurable space manipulator.The manipulator is equipped with a non-spherical wrist and two lockable passive telescopic links(LPTLs),which enable it to have both active revolute and passive prismatic joints and operate in two distinct modes.To begin with the kinematic singularity analysis,the study derives the differential kinematic equations for the manipulator and identifies the dominant Jacobian matrix that causes singularities.Subsequently,an in-depth analysis of singularities from multiple perspectives is conducted.Firstly,a kinematic singularity map method is proposed to capture the distribution of singularities within the reachable workspace.Then,the influence of the two LPTLs on singularities is thoroughly examined.Finally,a new method based on the matrix rank equivalence principle is introduced to determine singularity conditions,enabling the identification of all the singular configurations for the SSRMS-type reconfigurable manipulator.Notably,this method significantly reduces computational complexity,and the singularity conditions obtained have more concise equations.For the singularity avoidance problem,a novel method is developed,which simultaneously addresses the requirements of real-time performance,high precision,and the avoidance of both kinematic singularities and joint limit constraints.Benefiting from these excellent properties,the proposed method can effectively resolve the singularity issues encountered separately by the SSRMS-type reconfigurable manipulator in its two operational modes.Several typical simulations validate the utility of all the proposed methods.

骨细胞方向对负荷诱导的骨内液体流动和营养物质运输的影响

与年龄或某些骨骼疾病相关的骨细胞空间排列方向的变化引起了研究者们的广泛关注.本研究的目的是通过建立骨细胞相对于骨内流体流动轴偏转0°、30°、45°、60°和90°的骨单元多孔弹性力学模型,证明骨细胞方向对骨内流体流动的影响.我们假设骨陷窝-小管网络规则排列且均匀分布,且将骨单元定义为由微观尺度水平上的代表性立方周期单元(CPUC)组成.通过计算骨细胞周围骨小管的数量和3D分布来估算骨单元的微观结构参数(渗透率、孔隙率等),并建立骨单元孔隙弹性有限元模型,研究不同边界条件和载荷形式下负载诱导的骨内间质流体流动和骨内营养物质运输.结果表明,在接近正常生理活动的载荷条件下,骨细胞方向对骨单元最大流体压力(p)、最大流体速度(v)和最大流体剪切应力(τ)都有显著的影响.p值和τ值在骨单元壁内呈现不均匀分布,这说明骨细胞方向和骨小管三维分布是预测骨陷窝-小管系统渗透性各向异性程度的重要参数,但骨细胞方向对骨内营养物质运输影响很小.此外,载荷形式和骨陷窝-小管弯曲度对骨单元的液体流动行为的影响大于骨细胞方向对其的影响.这项研究的结果将有助于人们准确量化骨内液体流动行为,并增强对骨的力传导机制的理解.

Impaired dNKAP function drives genome instability and tumorigenic growth in Drosophila epithelia

Mutations or dysregulated expression of NF-kappaB-activating protein(NKAP)family genes have been found in human cancers.How NKAP family gene mutations promote tumor initiation and progression remains to be determined.Here,we characterized dNKAP,the Drosophila homolog of NKAP,and showed that impaired dNKAP function causes genome instability and tumorigenic growth in a Drosophila epithelial tumor model.dNKAP-knockdown wing imaginal discs exhibit tumorigenic characteristics,including tissue overgrowth,cell-invasive behavior,abnormal cell polarity,and cell adhesion defects.dNKAP knockdown causes both R-loop accumulation and DNA damage,indicating the disruption of genome integrity.Further analysis showed that dNKAP knockdown induces c-Jun N-terminal kinase(JNK)-dependent apoptosis and causes aberrant cell proliferation in distinct cell populations.Activation of the Notch and JAK/STAT signaling pathways contributes to the tumorigenic growth of dNKAP-knockdown tissues.Furthermore,JNK signaling is essential for dNKAP depletion-mediated cell invasion.Transcriptome analysis of dNKAP-knockdown tissues confirmed the misregulation of signaling pathways involved in promoting tumorigenesis and revealed abnormal regulation of metabolic pathways.dNKAP knockdown and oncogenic Ras,Notch,or Yki mutations show synergies in driving tumorigenesis,further supporting the tumor-suppressive role of dNKAP.In summary,this study demonstrates that dNKAP plays a tumor-suppressive role by preventing genome instability in Drosophila epithelia and thus provides novel insights into the roles of human NKAP family genes in tumor initiation and progression.

Fluorescent visualization and evaluation of NPC1L1- mediated vesicular endocytosis during intestinal cholesterol absorption in mice

Excessive cholesterol absorption from intestinal lumen contributes to the pathogenesis of hypercholesterolemia,which is an independent risk factor for atherosclerotic cardiovascular disease.Niemann-Pick C1-like 1(NPC1L1)is a major membrane protein responsible for cholesterol absorption,in which the physiological role of vesicular endocytosis is still controversial,and it lacks a feasible tool to visualize and evaluate the endocytosis of NPC1L1 vesicles in vivo.Here,we genetically labeled endogenous NPC1L1 protein with EGFP in a knock-in mouse model,and demonstrated fluorescent visualization and evaluation of the endocytic vesicles of NPC1L1-cago during intestinal cholesterol absorption.The homozygous NPC1L1-EGFP mice have normal NPC1L1 expression pattern as well as cholesterol homeostasis on chow or high-cholesterol diets.The fluorescence of NPC1L1-EGFP fusion protein localizes at the brush border membrane of small intestine,and EGFP-positive vesicles is visualized beneath the membrane as early as 5 min post oral gavage of cholesterol.Of note,the vesicles colocalize with the early endosomal marker early endosome antigen 1(EEA1)and the filipin-stained free cholesterol.Pretreatment with NPC1L1 inhibitor ezetimibe inhibits the formation of these cholesterol-induced endocytic vesicles.Our data support the notion that NPC1L1-mediated cholesterol absorption is a vesicular endocytic process.NPC1L1-EGFP mice are a useful model for visualizing cellular NPC1L1-cargo vesicle itineraries and for evaluating NPC1L1 activity in vivo in response to diverse pharmacological agents and nutrients.

Effects of combined acupuncture and eugenol on learning-memory ability and antioxidation system of hippocampus in Alzheimer disease rats via olfactory system stimulation

OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on learning-memory ability and the antioxidation system of the hippocampus in Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300±10) g, were randomly divided with 10 rats per group into a normal control group, AD model group, AD with cut olfactory nerve group, Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group. The AD model was established by injection of amyloid β1-40 (Aβ 1-40). Morris maze tests were conducted for evaluating the learning-memory ability. Content of malo- ndialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency and the mean swimming distance in the normal control group, the Xiu three-needle group, the eugenol group, and the combined acupuncture and euge-nol group were significantly shorter than those in the AD model group (all P<0.01). The combined acupuncture and eugenol group had shorter escape latency and mean swimming distance than those in the Xiu three-needle group and the eugenol group. There were no significant differences between the Xiu three-needle group and the eugenol group and between the AD group and the AD with cut olfactory nerve group (P>0.05). Compared with the normal control group, the MDA content in the hippocampus significantly increased (P<0.05) and GSH-Px and SOD activities significantly decreased in the AD model group (P<0.01). Compared with the AD model group, significantly decreased (P< 0.01) and SOD and GSH-Px activities significantly increased in the Xiu three-needle group, eugenol group, and combined acupuncture and eugenol group (P<0.05). Compared with the Xiu three-needle group and eugenol group, the MDA content significantly decreased (P<0.05) and SOD and GSH-Px activities increased (P<0.05) in the combined acupuncture and eugenol group. There were no significant differences among the three indices between the Xiu three-needle group and the eugenol group and between the AD model group and the AD with cut olfactory nerve group (P>0.05). CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus in AD rats. The combination of acupuncture with eugenol has stronger effects, and the effects depend on the olfactory pathway.

Inscuteable maintains type I neuroblast lineage identity via Numb/Notch signaling in the Drosophila larval brain

In the Drosophila larval brain, type I and type Ⅱ neuroblasts（NBs） undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors（INPs） exist only in type Ⅱ NB lineages. In this study, we reveal a novel function of Inscuteable（Insc） that acts to maintain type I NB lineage identity. In insc type I NB clones of mosaic analyses with a repressible cell marker（MARCM）, the formation of extra Deadpan（Dpn）tNB-like and GMC-like cells is observed. The lack of Insc leads to the defective localization and segregation of Numb during asymmetric cell division. By the end of cytokinesis, this results in insufficient Numb in ganglion mother cells（GMCs）. The formation of extra Deadpan（Dpn）tcells in insc clones is prevented by the attenuation of Notch activity. This suggests that Insc functions through the Numb/Notch signaling pathway. We also show that in the absence of Insc in type I NB lineages, the cellular identity of GMCs is altered where they adopt an INP-like cell fate as indicated by the initiation of Dpn expression accompanied by a transient presence of Earmuff（Erm）.These INP-like cells have the capacity to divide multiple times. We conclude that Insc is necessary for the maintenance of type I NB lineage identity. Genetic manipulations to eliminate most type I NBs with overproliferating type Ⅱ NBs in the larval brain lead to altered circadian rhythms and defective phototaxis in adult flies. This indicates that the homeogenesis of NB lineages is important for the adult＇s brain function.