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1
Chen, Shao Hsien, Chin Mou Hsu, Kuo Lin Chiu, and Chu Peng Chan. "Research on High Performance Direct-Driving Motor Applied to Swivel Spindle Head." Applied Mechanics and Materials 701-702 (December 2014): 874–78. http://dx.doi.org/10.4028/www.scientific.net/amm.701-702.874.
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Swivel spindle head is a key component used in five-axis machine tool of high performance and is of great importance in application and design. Nowadays, more and more components are manufactured by high performance multi-axis CNC machine tools, such as components of spaceflight, renewable energy and automobile, etc. Therefore, high performance machine tools of multiple axes are more and more urgently demanded, while Swivel spindle head is one of the most important components for a multi-axis machine tool. Hence, Swivel spindle head is one of the key to developers multi-axis machine tool . The study explores the highly responsive direct-driving motor able to drive the spindle head to rotate with multi-driving rotary technology. The dual-driving motor rotates via multi-driving units, generates torsion that magnifies and eliminates its clearance, and then drives the spindle head to rotate. Results of the test show that the completed machine tool can meet the standards of dual axis rotary head with high preformation in, no matter, speed, distance, positional accuracy, repeated accuracy or maximum torque, etc.
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Chen, Shao Hsien, Chin Mou Hsu, Kuo Lin Chiu, and Chu Peng Chan. "The Impact of Different Direct-Driving Motor Design on Swivel Spindle Head." Applied Mechanics and Materials 789-790 (September 2015): 791–94. http://dx.doi.org/10.4028/www.scientific.net/amm.789-790.791.
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Swivel spindle head is a key component used in gantry type five-axis machine tool of high performance and is of great importance in its application and design. Nowadays, more and more components are manufactured by high precision CNC machine tools, such as components of spaceflight, renewable energy and automobile, etc. Therefore, high precision machine tools of multiple axes are more and more urgently demanded, while dual axis rotary head is one of the most important components for a multi-axis machine tool. Hence, it will be a key to develop dual axis spindle head that meets high precision needs. The study explores the highly responsive direct-driving motor able to drive the spindle head to rotate with multi-driving rotary technology. The dual-driving motor rotates via multi-driving units, generates torsion that magnifies and eliminates its clearance, and then drives the spindle head to rotate. Results of the test show that the completed machine tool can meet the standards of dual axis rotary head with high precision in, no matter, speed, distance, positional accuracy, repeated accuracy or maximum torque, etc.
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Mikhov, Mikho, and Marin Zhilevski. "Study and Performance Improvement of the Drive Systems for a Class of Machine Tools." MATEC Web of Conferences 299 (2019): 05003. http://dx.doi.org/10.1051/matecconf/201929905003.
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This paper deals with some problems in the modernization of a type of machine tools with multi–coordinate drive systems. The basic requirements to the drives of each coordinate axis and the spindle are presented. Using the analysis carried out, a practical approach to appropriate selection of the respective drives is applied. The methodology offered is illustrated with some examples for choice of drives with direct current and alternating current motors. Some experimental research of cases with different feed and spindle drives are described and discussed. Better capabilities of the modernized machines for processing more complex workpieces are achieved, at a relatively low price. This research and the obtained results can be used in the design and tuning of electric drives for the considered type of machines with numerical program control.
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Ishizaki, Kosuke, Burak Sencer, and Eiji Shamoto. "Cross Coupling Controller for Accurate Motion Synchronization of Dual Servo Systems." International Journal of Automation Technology 7, no. 5 (September 5, 2013): 514–22. http://dx.doi.org/10.20965/ijat.2013.p0514.
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In order to attain higher manufacturing efficiency, “dual” (two) servo systems are widely used in advanced Computer Numerical Controlled (CNC) machine tools. A well-known example is the linear motor driven gantry type of micro machine tools where dual servos are employed to drive the heavier gantry axis. Recently, dual servos are also used in spindle systems. “Double sided milling” is an example where two spindles are required to cooperatively remove material on both sides of a workpiece. Synchronization of dual servo systems is crucial for achieving the desired manufacturing accuracy. This paper presents a crosscoupling controller to accurately synchronize dualmotor driven servo systems. Proposed cross coupling controller penalizes differential positioning error between dual servo drives by modifying the reference position and velocity commands. It improves motion synchronization without affecting the overall tracking bandwidth. A tuning method for the proposed controller is also presented for the control engineer’s practice.
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Rakhmanov, S. R. "Elaboration of a lubrication system for universal spindle hinges of rolling mills." Ferrous Metallurgy. Bulletin of Scientific , Technical and Economic Information 77, no. 9 (September 21, 2021): 1047–53. http://dx.doi.org/10.32339/0135-5910-2021-9-1047-1053.
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The experience of running drives of most of heavy-duty rolling mills shows that the designs of universal spindles with blade hinges under conditions of increased alternating loads are most acceptable comparing with other spindles types. Open friction surfaces are the drawbacks of these types of spindles, which complicate the matter of continuous supply of lubrication. Perfected effective system of forced lubrication of rolling mill spindles hinges proposed. The facility for their lubrication has a bearing support of balancing design, spindle, in radial holes of which spring-loaded plungers are installed in a diametrically opposite order. Besides, the facility has suction valves and force valves installed in the spindle axial holes, connecting with the radial ones. A methodology proposed to select the eccentricity of the internal cylindrical surface of the bearing support of the spindle hinge, the axis of which is located eccentrically relative the spindle rotation axis. A calculating scheme and a mathematical model of the process of lubrication supply into joints of rolling mill spindle hinge elaborated. A differential equation of lubrication motion in the conical slot of the hinge between a blade and insertions drawn up. Parameters of hydrodynamic motion of lubrication in the conical slot established. Modes of the lubrication motion in the conical slot between roller blade and hinge insertion determined. Based on experience of operation of friction couple bronze-steel, a lubrication for rolling mills universal spindles proposed. To improve the operation characteristics of hinges based on the friction couple bronze-steel, a thick lubrication having antifriction properties namely based on oils with additives ИП-10, КП-10 and ДФ-11 proposed. Dependence of pressure distribution along the length of the hinge conical slot presented for various lubrications of low viscosity (ИП-10 + ДФ-11) and high viscosity (КП-10 + ДФ-11). The quality effect of the speed of roller blade movable wall on distribution of speeds of lubrication layer motion over the height of the hinge conical slot for comparatively low and comparatively high boundary speeds demonstrated.
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Nunes, Vanessa, Margarida Dantas, Domingos Castro, Elisa Vitiello, Irène Wang, Nicolas Carpi, Martial Balland, et al. "Centrosome–nuclear axis repositioning drives the assembly of a bipolar spindle scaffold to ensure mitotic fidelity." Molecular Biology of the Cell 31, no. 16 (July 21, 2020): 1675–90. http://dx.doi.org/10.1091/mbc.e20-01-0047.
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Wilck, Ines, Andreas Wirtz, Torben Merhofe, Dirk Biermann, and Petra Wiederkehr. "Minimisation of Pose-Dependent Regenerative Vibrations for 5-Axis Milling Operations." Journal of Manufacturing and Materials Processing 5, no. 3 (September 10, 2021): 99. http://dx.doi.org/10.3390/jmmp5030099.
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The machining of free-formed surfaces, e.g., dies or moulds, is often affected by tool vibrations, which can affect the quality of the workpiece surface. Furthermore, in 5-axis milling, the dynamic properties of the system consisting of the tool, spindle and machine tool can vary depending on the tool pose. In this paper, a simulation-based methodology for optimising the tool orientation, i.e., tilt and lead angle of simultaneous 5-axis milling processes, is presented. For this purpose, a path finding algorithm was used to identify process configurations, that minimise tool vibrations based on pre-calculated simulation results, which were organised using graph theory. In addition, the acceleration behaviour of the feed drives, which limits the ability of adjusting the tool orientation with a high adaption frequency, as well as potential collisions of the tool, tool chuck and spindle with the workpiece were considered during the optimisation procedure.
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Křepela, J., and Vladislav Singule. "Simulation of the Dynamic Behaviors of the C Axis Drive by the Turning Center." Solid State Phenomena 147-149 (January 2009): 356–61. http://dx.doi.org/10.4028/www.scientific.net/ssp.147-149.356.
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The paper describes the mathematical model for C axis of the multifunction turning center with worm gear. Talks about the mathematical model with multi-body mass dynamic system. The drive works in the positional feedback and his mathematical model is specified for detection of the dynamical behaviors of the C axis. The turning center is designed for a heavy roughing forged piece from high carbon steels by the power of main motor 71kW. The C axis must be designed as accurate angle position axis and with big dynamic stability of regulation by step or pulse loading. The C axis drive is constructed with help of a hydraulic connected up the worm gearing on a spindle. The driven side of the worm gear is created two dual worms with own servomotors. Worm wheel is solved as one part with two gears. Servomotors are controlled with the mode speed/torque coupling (MASTER-SLAVE), which guarantees the constant torque prestressing between the servomotors. The difference of a torques guarantees leaning of both worm teeth on opposite tooth faces of both gears of the worm wheel. In the dynamic model are involved the friction on the worm gears, torsion stiffness located with help of the FEM and moment of inertia for all parts. 3D models of the C axis is designed in the program ProEngineer. From complete 3D model of the C axis are transfered individual parts to the FEM in surroundings Ansys as volume parts. In this paper is main output influence of the diference between the 3D and 2D for calculation of the stiffness in the contact of the worm gear on the whole dynamic system of the C axis. The value of the torsion stiffness by more situation of the load on the worm gear is used subsequently to the multi-body mass system of the C axis drive and to the eigen frequencies analyses. Results of this paper will be sensitivity check of the changing torsion stiffness on the worm gear by the loading changing on the resulted position accuracy on the C axis. Next review is, if the control modul MASTER-SLAVE is partially this problem of the difference between values of stiffness from 2D or 3D model or also stiffness non-linearity eliminated.
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Wu, Dong Xu, Guo Li, Bo Wang, Zheng Qiao, and Lei Lv. "Fabrication of Microstructured Surfaces by Five-Axis Ultra Precision Machine Tool." Key Engineering Materials 625 (August 2014): 187–91. http://dx.doi.org/10.4028/www.scientific.net/kem.625.187.
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In this paper, a five-axis ultra precision machine tool for fabrication of microstructured surfaces is presented. This machine consists of two rotary axes (C&B) and three linear axes (X&Y&Z). High precision aerostatic bearing and torque motor are adopted in C axis (main spindle) and B axis. X axis and Z axis use the hydrostatic guideway and are driven by linear motors. Y axis is driven by torque motor and precision ball screw. This machine is able to realize multiple processing methods, including ultra precision diamond turning, ultra precision milling, fly-cutting, fast tool servo and slow tool servo diamond turning.Furthermore, a large number of experiment researches are carried out. Some typical microstructure surfaces are manufactured, for sinusoidal grid surface, the surface roughness Ra is 11.9nm, which is machined by slow tool servo diamond turning. Micro pyramid array surface is fabricated by using fly-cutting, which performs well both in the profile accuracy and the repeatability. These experiment researches prove that this ultra precision machine is superior in accuracy and system reliability.
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Merk, Daniel J., Pengcheng Zhou, Samuel M. Cohen, Maria F. Pazyra-Murphy, Grace H. Hwang, Kristina J. Rehm, Jose Alfaro, et al. "The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors." Developmental Neuroscience 42, no. 5-6 (2020): 170–86. http://dx.doi.org/10.1159/000512976.
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During neural development, stem and precursor cells can divide either symmetrically or asymmetrically. The transition between symmetric and asymmetric cell divisions is a major determinant of precursor cell expansion and neural differentiation, but the underlying mechanisms that regulate this transition are not well understood. Here, we identify the Sonic hedgehog (Shh) pathway as a critical determinant regulating the mode of division of cerebellar granule cell precursors (GCPs). Using partial gain and loss of function mutations within the Shh pathway, we show that pathway activation determines spindle orientation of GCPs, and that mitotic spindle orientation correlates with the mode of division. Mechanistically, we show that the phosphatase Eya1 is essential for implementing Shh-dependent GCP spindle orientation. We identify atypical protein kinase C (aPKC) as a direct target of Eya1 activity and show that Eya1 dephosphorylates a critical threonine (T410) in the activation loop. Thus, Eya1 inactivates aPKC, resulting in reduced phosphorylation of Numb and other components that regulate the mode of division. This Eya1-dependent cascade is critical in linking spindle orientation, cell cycle exit and terminal differentiation. Together these findings demonstrate that a Shh-Eya1 regulatory axis selectively promotes symmetric cell divisions during cerebellar development by coordinating spindle orientation and cell fate determinants.
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Chen, En Ping, Shao Hui Li, Feng He Wu, and Chong Min Jiang. "Structure Design of Biaxial Rotary Milling Head with High-Torque, High-Precision and Mechanical Spindle." Key Engineering Materials 621 (August 2014): 337–45. http://dx.doi.org/10.4028/www.scientific.net/kem.621.337.
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As a key component of heavy five-axis linkage CNC machine tools, the existing mechanical biaxial rotary milling heads are usually driven by worm gear, timing belt, or multi-stage gears. Worm gear is inefficiency to transmit motion, hard to maintain the accuracy and difficult to eliminate all clearance; Timing belt can be seriously worn and cannot maintain good accuracy; and multi-stage gears transmission has defects such as long chain, low transmission stiffness. This paper aims at designing a biaxial rotary milling head with large output torque of 3000Nm, high precision and high rigidity. So a new design for biaxial rotary milling head with mechanical spindle, gear transmission and swinging fork structure is proposed. An integral supporting axis is applied to increase the rigidity of A-axis; through the closed numerical loop control based on precise encoder and the decoupling technology of feed motion of A/C axis, the contradiction between large reduction ratio and high precision transmission is solved, and then the requirement of high positioning accuracy (10") is met. Theoretical calculation and simulated analysis shown, the new design not only can guarantee transmission accuracy and dynamic characteristics of biaxial rotary milling head, but also can improve its structural stiffness and meet the high demands of large torque, high precision and high rigidity.
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Choirony, Iklil Vurqon, Mohammad Slamed Hariyanto, Miftachul Ulum, Achmad Ubaidillah, Haryanto Haryanto, and Riza Alfita. "Rancang Bangun Acrylic Engraver and Cutting Machine Menggunakan CNC Milling 3 Axis Berbasis Mikrokontroler." Elektrika 13, no. 1 (May 24, 2021): 13. http://dx.doi.org/10.26623/elektrika.v13i1.3071.
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<p><em><span lang="EN-US">The purpose of this research is to design and implement an automatic acrylic carving and cutting tool using a microcontroller-based 3-axis CNC machine. Computer Numerical Control (CNC) is a machine technology that is operated automatically to support the demand for a product that has a complex shape and high accuracy. In general, the construction of a 3-axis CNC machine and its working system is synchronization between the computer and its mechanics. This tool has a work process by utilizing the G-Code method as a command on the machine to carry out engraving and cutting automatically. The G-code was obtained from a previously designed image and then converted using the Aspire 9.0 software. Engraving and cutting is done by sending the G-code file to the microcontroller via the Universal G-code Sender software, then the microcontroller sends a signal to drive the motor driver which then drives the stepper motor so that the actuator movement is generated according to the image in the G-code file. Simultaneously the spindle motor will be active to engrave or cut acrylic. In this study, a trial scenario was carried out to determine the precision and accuracy of the tool, namely by engraving and cutting flat shapes such as squares, circles, triangles and segments. The percentage of success generated from this tool is 97,08% to 100%. Furthermore, testing is carried out to make products in the form of engraving writing, logos and calligraphy. Apart from that, we also tested cutting letters and key chains. When the test is carried out, the accuracy level is 1mm. </span></em></p>
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Sablin, Pavel, Alexander Kosmynin, and Vladimir Shchetinin. "Controlled spindle supports as a tool for ensuring machining quality." Proceedings of Irkutsk State Technical University 24, no. 5 (October 2020): 1019–29. http://dx.doi.org/10.21285/1814-3520-2020-5-1019-1029.
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The purpose of the work is to provide conditions for machined workpiece surface quality control based on the use of gas-magnetic supports in machine-tool systems (on example of the 3K227A internal grinding machine). To model the trajectory of tool and workpiece mutual movement the methods of nonlinear dynamics are used. The literature data on the problem are analyzed and experimental studies are carried out. Based on the considered issues of controlling the dynamic stability of technological systems under machining by means of contactless controlled gas-magnetic supports of spindle units, a scheme for adaptive control of the machine-tool system is proposed. It allows in many respects to eliminate external mechanical effects on the technological system, internal vibrations caused by drives and moving parts, as well as to compensate temperature deformations of the spindle unit frame and body. An adaptive control system based on gas-magnetic supports of the spindle assembly and the workpiece, as well as the control systems of the position of workpiece and tool (on example of 3K227A internal grinding machine) are demonstrated in action. The gas-magnetic support control system developed at Komsomolsk-na-Amure State Technical University makes it possible to set the position of the rotor axis with the accuracy of 0.1 microns. The study results obtained lead to the conclusion that the control of two adaptive links on the gas-magnetic supports, i.e., the spindle assembly of the tool and the spindle assembly of the workpiece, allows to achieve a rotation accuracy of up to 0.2 microns. The methods of nonlinear dynamics make it possible to construct an attractor (trajectory) of the tool tip movement in the real time, which provides a possibility to affect the input parameters of the machining process and thereby to control the output parameters. In addition to this, the control system of machine-tool system dynamic stability is applicable to other processing types as well, including edge cutting machining.
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Kondo, Kazuki, and Shin-Ichi Tooe. "Measurement of the Tangential Grinding Force Using the Slip of an Induction Motor—Construction of the Measurement System." Advanced Materials Research 76-78 (June 2009): 107–12. http://dx.doi.org/10.4028/www.scientific.net/amr.76-78.107.
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A new system for measuring a tangential grinding force using the slip of the rotational speed of an induction motor was developed. The motor slip is measured as the change in the rotational period for the induction motor. The system operates LabVIEW software on a personal computer, and a rotary encoder is connected with the motor spindle, which drives the axis of a grinding wheel. A signal of one pulse per rotation from the rotary encoder is input to the interface of the computer to measure the rotational period. LabVIEW has the flexibility of a programming language and operates within a graphic environment in compiling the signal, analyzing measurements, and displaying analysis results. Thus, the present system is simpler than previous development tools. This work conducts a grinding experiment using the developed system to verify the sensitivity and response in measuring the motor slip. As an example of application, semidry grinding is investigated by measuring tangential grinding forces. Hence, we demonstrate the effectiveness of the developed system for data processing in the analysis of grinding phenomena.
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Lázaro-Diéguez, Francisco, Iaroslav Ispolatov, and Anne Müsch. "Cell shape impacts on the positioning of the mitotic spindle with respect to the substratum." Molecular Biology of the Cell 26, no. 7 (April 2015): 1286–95. http://dx.doi.org/10.1091/mbc.e14-08-1330.
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All known mechanisms of mitotic spindle orientation rely on astral microtubules. We report that even in the absence of astral microtubules, metaphase spindles in MDCK and HeLa cells are not randomly positioned along their x-z dimension, but preferentially adopt shallow β angles between spindle pole axis and substratum. The nonrandom spindle positioning is due to constraints imposed by the cell cortex in flat cells that drive spindles that are longer and/or wider than the cell's height into a tilted, quasidiagonal x-z position. In rounder cells, which are taller, fewer cortical constraints make the x-z spindle position more random. Reestablishment of astral microtubule–mediated forces align the spindle poles with cortical cues parallel to the substratum in all cells. However, in flat cells, they frequently cause spindle deformations. Similar deformations are apparent when confined spindles rotate from tilted to parallel positions while MDCK cells progress from prometaphase to metaphase. The spindle disruptions cause the engagement of the spindle assembly checkpoint. We propose that cell rounding serves to maintain spindle integrity during its positioning.
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Gönczy, Pierre, Silke Pichler, Matthew Kirkham, and Anthony A. Hyman. "Cytoplasmic Dynein Is Required for Distinct Aspects of Mtoc Positioning, Including Centrosome Separation, in the One Cell Stage Caenorhabditis elegans Embryo." Journal of Cell Biology 147, no. 1 (October 4, 1999): 135–50. http://dx.doi.org/10.1083/jcb.147.1.135.
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We have investigated the role of cytoplasmic dynein in microtubule organizing center (MTOC) positioning using RNA-mediated interference (RNAi) in Caenorhabditis elegans to deplete the product of the dynein heavy chain gene dhc-1. Analysis with time-lapse differential interference contrast microscopy and indirect immunofluorescence revealed that pronuclear migration and centrosome separation failed in one cell stage dhc-1 (RNAi) embryos. These phenotypes were also observed when the dynactin components p50/dynamitin or p150Glued were depleted with RNAi. Moreover, in 15% of dhc-1 (RNAi) embryos, centrosomes failed to remain in proximity of the male pronucleus. When dynein heavy chain function was diminished only partially with RNAi, centrosome separation took place, but orientation of the mitotic spindle was defective. Therefore, cytoplasmic dynein is required for multiple aspects of MTOC positioning in the one cell stage C. elegans embryo. In conjunction with our observation of cytoplasmic dynein distribution at the periphery of nuclei, these results lead us to propose a mechanism in which cytoplasmic dynein anchored on the nucleus drives centrosome separation.
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Schnerch, Dominik, Julia Felthaus, Lara Mentlein, Monika Engelhardt, and Ralph M. Waesch. "Analysis of Mitosis In Acute Myeloid Leukemia Using Live-Cell Imaging." Blood 116, no. 21 (November 19, 2010): 3363. http://dx.doi.org/10.1182/blood.v116.21.3363.3363.
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Abstract Abstract 3363 Proper mitotic control is a prerequisite to guarantee the equal distribution of the genetic material onto the two developing daughter cells. A mitotic key regulator is cyclin B. High levels of cyclin B facilitate entry into mitosis whereas its controlled degradation coordinates chromosome separation and cytokinesis. The latter events are coordinated by the anaphase- promoting complex / cyclosome (APC/C), a ubiquitin ligase that couples ubiquitin chains to cyclin B, mediating its proteasomal degradation. The regulation of the APC/C-activity by complex protein networks, such as the spindle assembly checkpoint, therefore presents the basis for an accurate mitosis. Mitotic errors give rise to daughter cells with an aberrant set of chromosomes and contribute to genetic instability. Genetic instability is a hallmark of cancer cells and plays an important role in the onset and progression of acute myeloid leukemia (AML). In rare cases, de novo AMLs present with multiple cytogenetic aberrations (complex karyotype). However, a larger number of patients develop karyotype deviations in the course of the disease, sometimes even under therapy, which comes along with an adverse prognosis. Understanding the biology that drives the gain and loss of genetic material therefore bears the potential of identifying new therapeutic targets. We compared a number of lymphoblastic and myeloid cell lines and found AML cell lines to be deficient in arresting at metaphase in the presence of the microtubule-disrupting agent nocodazole. Cyclin B was expressed at much lower levels in the AML cell line Kasumi-1 and did not accumulate following spindle disruption as observed in the lymphoblastic cell line DG-75. We could show that Kasumi-1 cells, when challenged with nocodazole, were not capable of properly maintaining chromatid-cohesion and underwent premature sister chromatid separation. These findings suggest that mitotic control mechanisms do not work tightly enough in AML cells to prevent chromosome separation in the presence of spindle disruption. We applied live-cell imaging to exactly characterize mitotic timing in Kasumi-1 cells at a single cell level. The expression of a GFP-tagged derivative of histone H2 served to visualize the nuclear envelope breakdown and anaphase onset. Detection of the latter events allowed the faithful measurement of mitotic timing. We could find a significant shortening of mitosis in Kasumi-1 cells as compared to the lymphoblastic cell line DG-75. In both AML cell lines and primary AML blasts we identified the spindle assembly checkpoint components BubR1 and Bub1 to be downregulated. Interestingly, re-expression of BubR1 in Kasumi-1 cells led to a significant stabilization of cyclin B on western blots. To address the question whether an increased expression of cyclin B leads to a more pronounced mitotic delay in the presence of spindle-disruption in AML cells is subject of current experiments. It was reported that different cell types can escape from a mitotic block as a consequence of cyclin B degradation. In the literature, this phenomenon was referred to as mitotic slippage and is known to drive genetic instability. To monitor cyclin B turnover and localization at a single cell level, we generated a chimeric cyclin B-molecule, SNAP-cyclin B, which can couple to a suitable fluorochrome in a self-labeling reaction after addition to the growth medium. In this system, the fluorescence intensity reflects the amount of chimeric cyclin B and allows the monitoring of APC/C-dependent proteolysis. In our current approaches we aim at studying cyclin B-turnover at a single cell level in AML cell lines as well as primary leukemia cells by using live-cell imaging before and after BubR1- and Bub1-rescue. An aberrant cell cycle control is found in most human malignancies and might be an important driving force in leukemogenesis. We hypothesize that BubR1, in concert with different other regulators, might lead to inaccuracies in mitotic control. This hypothesis is underlined by the shortened time to anaphase in Kasumi-1 cells and a decreased expression of cyclin B, both of which are characteristics of BubR1-depletion. Mitotic regulators are already targets in AML therapy and a deeper understanding of mitotic processes in AML might lead to improved approaches. Disclosures: No relevant conflicts of interest to declare.
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O'Connell, Christopher B., and Yu-li Wang. "Mammalian Spindle Orientation and Position Respond to Changes in Cell Shape in a Dynein-dependent Fashion." Molecular Biology of the Cell 11, no. 5 (May 2000): 1765–74. http://dx.doi.org/10.1091/mbc.11.5.1765.
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In animal cells, positioning of the mitotic spindle is crucial for defining the plane of cytokinesis and the size ratio of daughter cells. We have characterized this phenomenon in a rat epithelial cell line using microscopy, micromanipulation, and microinjection. Unmanipulated cells position the mitotic spindle near their geometric center, with the spindle axis lying roughly parallel to the long axis of the cell. Spindles that were initially misoriented underwent directed rotation and caused a delay in anaphase onset. To gain further insight into this process, we gently deformed cells with a blunted glass needle to change the spatial relationship between the cortex and spindle. This manipulation induced spindle movement or rotation in metaphase and/or anaphase, until the spindle reached a proper position relative to the deformed shape. Spindle positioning was inhibited by either treatment with low doses of nocodazole or microinjection of antibodies against dynein, apparently due to the disruption of the organization of dynein and/or astral microtubules. Our results suggest that mitotic cells continuously monitor and maintain the position of the spindle relative to the cortex. This process is likely driven by interactions among astral microtubules, the motor protein dynein, and the cell cortex and may constitute part of a mitotic checkpoint mechanism.
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Liu, Bing, Chunlian Jin, Nico De Storme, Sébastien Schotte, Cédric Schindfessel, Tim De Meyer, and Danny Geelen. "A Hypomorphic Mutant of PHD Domain Protein Male Meiocytes Death 1." Genes 12, no. 4 (April 1, 2021): 516. http://dx.doi.org/10.3390/genes12040516.
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Meiosis drives reciprocal genetic exchanges and produces gametes with halved chromosome number, which is important for the genetic diversity, plant viability, and ploidy consistency of flowering plants. Alterations in chromosome dynamics and/or cytokinesis during meiosis may lead to meiotic restitution and the formation of unreduced microspores. In this study, we isolated an Arabidopsis mutant male meiotic restitution 1 (mmr1), which produces a small subpopulation of diploid or polyploid pollen grains. Cytological analysis revealed that mmr1 produces dyads, triads, and monads indicative of male meiotic restitution. Both homologous chromosomes and sister chromatids in mmr1 are separated normally, but chromosome condensation at metaphase I is slightly affected. The mmr1 mutant displayed incomplete meiotic cytokinesis. Supportively, immunostaining of the microtubular cytoskeleton showed that the spindle organization at anaphase II and mini-phragmoplast formation at telophase II are aberrant. The causative mutation in mmr1 was mapped to chromosome 1 at the chromatin regulator Male Meiocyte Death 1 (MMD1/DUET) locus. mmr1 contains a C-to-T transition at the third exon of MMD1/DUET at the genomic position 2168 bp from the start codon, which causes an amino acid change G618D that locates in the conserved PHD-finger domain of histone binding proteins. The F1 progenies of mmr1 crossing with knockout mmd1/duet mutant exhibited same meiotic defects and similar meiotic restitution rate as mmr1. Taken together, we here report a hypomorphic mmd1/duet allele that typically shows defects in microtubule organization and cytokinesis.
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Galardy, Paul J., and Ying Zhang. "USP44 Is Highly Over-Expresed In T-Cell Acute Lymphoblastic Leukemia and Leads to the Development of Chromosome Missegregation and Aneupoloidy." Blood 116, no. 21 (November 19, 2010): 29. http://dx.doi.org/10.1182/blood.v116.21.29.29.
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Abstract Abstract 29 Acute lymphoblastic leukemia (ALL) cells are frequently characterized by abnormal numbers of chromosomes, a condition known as aneuploidy. Aneuploidy in ALL is not just a curiosity, but impacts on the prognosis and risk stratification in children. Additionally, aneuploidy itself contributes to the development of cancer by dysregulating gene expression, and driving the loss of heterozygosity of mutated tumor suppressor genes. The molecular underpinnings of aneuploidy in ALL are largely unknown. The mitotic checkpoint is a complex pathway that acts in mitosis to prevent the premature onset of anaphase that leads to improper segregation of chromosomes and aneuploidy. Through the concerted action of many intermediates, the mitotic checkpoint functions to inhibit the activity of a large ubiquitin E3 ligase complex known as the anaphase promoting complex/cyclosome (APC/C) that drives the separation of paired sister chromatids by effecting the ubiquitin-dependent degradation of cyclin B1 and securin. The de-ubiquitinating enzyme USP44 was recently identified as an important regulator of mitotic progression that assists in maintaining mitotic checkpoint signaling until all chromosomes are properly attached to the mitotic spindle. Microarray studies of childhood acute leukemias have observed high levels of USP44 in T-cell ALL, but the significance of this observation is unclear. Here we show that USP44 is indeed over-expressed in T-ALL in children and that its presence may contribute to aneuploidy that is frequently observed in this disease. We compared the expression of USP44 in a series of 24 samples from patients with T-ALL to that found in ten samples of peripheral T-cells isolated from healthy donors, using quantitative real-time PCR. There was a dramatic increase in the expression of USP44 in T-ALL with 18 out of 24 cases having at least 3-fold increase, with an average of 16-fold increase, in USP44 mRNA. We next studied the consequences of USP44 over-expression in primary cells using live-cell microscopy. We find that excess USP44 leads to dramatic and significant increase in chromosome missegregation with most defects involving lagging chromosomes due to improper chromosome attachment to the mitotic spindle. We observe that these mitotic errors lead to the development of aneuploidy, through a mechanism that requires USP44 catalytic activity. These effects are accompanied by reinforced mitotic checkpoint signaling that leads to delayed progression through mitosis, and a prolonged duration of mitotic arrest in cells exposed to spindle poisons such as nocodazole or paclitaxel. At the molecular level, we observe that excess USP44 leads to enhanced binding of the mitotic checkpoint effector Mad2 to the APC/C and increased levels of cyclin B1 in early mitosis. Taken together, we conclude that USP44 is a chromosome instability gene that is frequently expressed at high levels in T-ALL cells, and that this may contribute to the pathogenesis of T-ALL by leading to chromosome shuffling and aneuploidy. These data have important implications in our understanding of the pathogenesis of this disease and may contribute to understanding the therapeutic effectiveness of novel aurora inhibitors in cancer. Disclosures: No relevant conflicts of interest to declare.
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Rose, L. S., and K. Kemphues. "The let-99 gene is required for proper spindle orientation during cleavage of the C. elegans embryo." Development 125, no. 7 (April 1, 1998): 1337–46. http://dx.doi.org/10.1242/dev.125.7.1337.
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The orientation of cell division is a critical aspect of development. In 2-cell C. elegans embryos, the spindle in the posterior cell is aligned along the long axis of the embryo and contributes to the unequal partitioning of cytoplasm, while the spindle in the anterior cell is oriented transverse to the long axis. Differing spindle alignments arise from blastomere-specific rotations of the nuclear-centrosome complex at prophase. We have found that mutations in the maternally expressed gene let-99 affect spindle orientation in all cells during the first three cleavages. During these divisions, the nuclear-centrosome complex appears unstable in position. In addition, in almost half of the mutant embryos, there are reversals of the normal pattern of spindle orientations at second cleavage: the spindle of the anterior cell is aligned with the long axis of the embryo and nuclear rotation fails in the posterior cell causing the spindle to form transverse to the long axis. In most of the remaining embryos, spindles in both cells are transverse at second cleavage. The distributions of several asymmetrically localized proteins, including P granules and PAR-3, are normal in early let-99 embryos, but are perturbed by the abnormal cell division orientations at second cleavage. The accumulation of actin and actin capping protein, which marks the site involved in nuclear rotation in 2-cell wild-type embryos, is abnormal but is not reversed in let-99 mutant embryos. Based on these data, we conclude that let-99(+) is required for the proper orientation of spindles after the establishment of polarity, and we postulate that let-99(+) plays a role in interactions between the astral microtubules and the cortical cytoskeleton.
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Labbé, Jean-Claude, Erin K. McCarthy, and Bob Goldstein. "The forces that position a mitotic spindle asymmetrically are tethered until after the time of spindle assembly." Journal of Cell Biology 167, no. 2 (October 18, 2004): 245–56. http://dx.doi.org/10.1083/jcb.200406008.
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Regulation of the mitotic spindle's position is important for cells to divide asymmetrically. Here, we use Caenorhabditis elegans embryos to provide the first analysis of the temporal regulation of forces that asymmetrically position a mitotic spindle. We find that asymmetric pulling forces, regulated by cortical PAR proteins, begin to act as early as prophase and prometaphase, even before the spindle forms and shifts to a posterior position. The spindle does not shift asymmetrically during these early phases due to a tethering force, mediated by astral microtubules that reach the anterior cell cortex. We show that this tether is normally released after spindle assembly and independently of anaphase entry. Monitoring microtubule dynamics by photobleaching segments of microtubules during anaphase revealed that spindle microtubules do not undergo significant poleward flux in C. elegans. Together with the known absence of anaphase A, these data suggest that the major forces contributing to chromosome separation during anaphase originate outside the spindle. We propose that the forces positioning the mitotic spindle asymmetrically are tethered until after the time of spindle assembly and that these same forces are used later to drive chromosome segregation at anaphase.
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Zhang, Xi, Sheng Bao, and Fang Cheng. "Measurement of Radial and Axial Error Motion in a High Precision Spindle." Advanced Materials Research 381 (November 2011): 34–37. http://dx.doi.org/10.4028/www.scientific.net/amr.381.34.
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The performance of a spindle is critical for high precision machining. In this paper, the spindle error motion in a high precision milling center was measured. The spindle is driven by air turbine with rotation speed of 120,000rpm. The radial and axial error motion of the axis of rotation was measured. The capacitive displacement sensors with nanometer resolution were mounted against the master gauge pin through the dedicated setup. Tlusty method was adopted to synchronize angular position of the spindle and data sampling. The measured radial and axial error motion of the spindle were 2.73μm and 2.59μm respectively. Despite of motion errors, the better machining accuracy still can be achieved. It seems that cutting force may improve the rotation performance of a spindle with aerostatic bearing.
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Han, Pei Cen, Zhao Hui Ye, Yong Ming Zhou, and Shi Yuan Yang. "SOPC-Based Motion Controller with NURBS Interpolator." Advanced Materials Research 898 (February 2014): 937–43. http://dx.doi.org/10.4028/www.scientific.net/amr.898.937.
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SOPC becomes popular nowadays, which combines software and hardware in a single chip. In this paper, a multi-axis motion controller is implemented based on a SOPC system with a NIOSII processor in a single FPGA chip. The motion controller includes DDA module, spindle module and NURBS calculation module realized in Verilog HDL. DDA algorithm is used to drive the motors while spindle module is to drive the spindle. Because of NURBS recursive nature, NURBS calculation module is used to accelerate the calculation which takes the advantage of parallel structure. The NIOSII processor realizes the feedrate scheduling, in which constant feedrate is adopted. The second-order interpolation algorithm is used to control the feedrate.
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Majda, Paweł, and Bartosz Powałka. "Accuracy and repeatability positioning of high-performancel athe for non-circular turning." Archives of Mechanical Technology and Materials 37, no. 1 (November 27, 2017): 85–90. http://dx.doi.org/10.1515/amtm-2017-0014.
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AbstractThis paper presents research on the accuracy and repeatability of CNC axis positioning in an innovative lathe with an additional Xsaxis. This axis is used to perform movements synchronized with the angular position of the main drive, i.e. the spindle, and with the axial feed along the Z axis. This enables the one-pass turning of non-circular surfaces, rope and trapezoidal threads, as well as the surfaces of rotary tools such as a gear cutting hob, etc. The paper presents and discusses the interpretation of results and the calibration effects of positioning errors in the lathe’s numerical control system. Finally, it shows the geometric characteristics of the rope thread turned at various spindle speeds, including before and after-correction of the positioning error of the Xsaxis.
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Guo, Yong Feng, Ze Bin Ling, Kai Zhang, and Ye Rui Feng. "Model Structure and Simulation Analysis of a Novel Magetic Suspension Spindle Apparatus for Micro EDM." Advanced Materials Research 941-944 (June 2014): 2121–26. http://dx.doi.org/10.4028/www.scientific.net/amr.941-944.2121.
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In the Micro Electronic Discharge Manufacture (The diameter of electrode is no more than 0.5mm), the response frequency of the spindle in Z axis is too low to satisfy the requirement of rapid response. Considering this problem, a novel spindle apparatus based on the Magnetic Suspension drive principle is proposed in this paper, the basic structure and principle are introduced. At the same time, the Magnetic field distribution and they are analyzed by the finite element software Ansoft Maxwell. Theory conduction and simulation results indicates that the response frequency of the spindle and the electromagnetic forces satisfy the design requirement, the novel spindle can shift in a small range around the equilibrium position, and there is no magnetic coupling effect in each other degrees of freedom of the spindle, so the independent PID algorithm can be used in the control of each degree.
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Giannikopoulos, Petros, and David M. Parham. "Rhabdomyosarcoma: How Advanced Molecular Methods Are Shaping the Diagnostic and Therapeutic Paradigm." Pediatric and Developmental Pathology 24, no. 5 (June 9, 2021): 395–404. http://dx.doi.org/10.1177/10935266211013621.
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For the past 40 years, progress in rhabdomyosarcoma (RMS) has been focused on understanding its molecular basis and characterizing the mutations that drive its tumorigenesis and progression. Genetic predisposition to RMS has allowed discovery of key genetic pathways and driver mutations. Subclassification of RMS into embryonal (ERMS) and alveolar (ARMS) subtypes has shifted from histology to PAX-FOXO1 fusion status, and new driver mutations have been found in spindle cell RMS. Comprehensive molecular profiling leveraging genome-scale next-generation sequencing (NGS) indicates that the RAS/RAF/PI3K axis is mutated in the majority of ERMS and modulated by downstream effects of PAX-FOXO1 fusions in ARMS. Because of the continued poor outcome of high-risk RMS, a variety of molecular targets have been or are now being tested in current or recent therapy trials. New techniques such as single cell sequencing, spatial multi-omics, and CRISPR/Cas9 genome editing offer potential for further discovery, but a need for clinically annotated specimens persists.
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Rankin, Kathleen E., and Linda Wordeman. "Long astral microtubules uncouple mitotic spindles from the cytokinetic furrow." Journal of Cell Biology 190, no. 1 (July 5, 2010): 35–43. http://dx.doi.org/10.1083/jcb.201004017.
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Astral microtubules (MTs) are known to be important for cleavage furrow induction and spindle positioning, and loss of astral MTs has been reported to increase cortical contractility. To investigate the effect of excess astral MT activity, we depleted the MT depolymerizer mitotic centromere-associated kinesin (MCAK) from HeLa cells to produce ultra-long, astral MTs during mitosis. MCAK depletion promoted dramatic spindle rocking in early anaphase, wherein the entire mitotic spindle oscillated along the spindle axis from one proto-daughter cell to the other, driven by oscillations of cortical nonmuscle myosin II. The effect was phenocopied by taxol treatment. Live imaging revealed that cortical actin partially vacates the polar cortex in favor of the equatorial cortex during anaphase. We propose that this renders the polar actin cortex vulnerable to rupture during normal contractile activity and that long astral MTs enlarge the blebs. Excessively large blebs displace mitotic spindle position by cytoplasmic flow, triggering the oscillations as the blebs resolve.
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Horiuchi, Osamu, Mitsuyoshi Nomura, Bo Xiao Ma, Takayuki Shibata, Yoshihiko Murakami, and Masami Masuda. "Influence of Thermal Behavior of Spindle on Machining Accuracy in Micro-Endmilling." Advanced Materials Research 418-420 (December 2011): 2040–45. http://dx.doi.org/10.4028/www.scientific.net/amr.418-420.2040.
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This paper describes on the influence of thermal behavior of spindle on machining accuracy in micro-endmilling. In order to make clear the reasons why the depth of slot varies during slotting repeated, temperatures around the spindle head and the thermal expansion of spindle axis were investigated. The machine tool used for experiment was a small type of vertical machining center. The spindle used for experiment was a ball bearing spindle which rotated at 10000-40000 min-1. The spindle head made of aluminum alloy had various cooling systems for spindle motor and ball bearings, and the temperature of spindle head changed only a few degrees C. Therefore it seems difficult to assume that the primary cause was thermal deformation of spindle head structure, even though the coefficient of thermal expansion of aluminum alloy is approximately twice of that of steel. Finally the thermal expansion of spindle axis was partly measured and relation between the thermal expansion and the variation of depth of slots was investigated. The main results obtained are as follows, (1) Slotting after a long period warming-up of spindle resulted in a small change of depth of slot, but slotting without any warming-up caused an initial rapid increase and then saturation of depth of slot, (2) Temperature rise of spindle head and adjacent structure seemed out of relation to the variation of depth of slot, (3) The partially measured thermal expansion of spindle as well as temperature of lower flange of spindle showed qualitatively similar change corresponding to depth of slot.
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Schulze, Harald, Marei Dose, Manav Korpal, Joseph E. Italiano, and Ramesh A. Shivdasani. "RanBP10 Is a Cytoplasmic GDP/GTP Exchange Factor That Modulates Microtubule Dynamics in Late Megakaryocytes." Blood 106, no. 11 (November 16, 2005): 738. http://dx.doi.org/10.1182/blood.v106.11.738.738.
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Abstract Megakaryocytes are large cells within the bone marrow that undergo complex fragmentation to release up to thousands of virtually identical blood platelets into the periphery. Each platelet contains a characterisitic microtubule (MT) marginal band that is derived from MT filaments present in long protrusion-like intermediate structures, designated proplatelets, that are immediate precursors of platelets. These MT filaments are generated in the MK periphery, where they require massive mobilization that is supposed to be different from either normal interphase MT nucleation that commonly depends on γ-tubulin in the MT-organizing center. or from MTs in the mitotic spindle that require Ran·GTP, which is generated along condensed chromosomes by the chromatin-asociated guanine nucleotide exchange factor (GEF) RCC1. We first demonstrated that γ-tubulin is absent in most of the mature or proplatelet-forming MKs, where it is therefore unlikely to attribute to the total MT nucleation. MTs are tubular cytoskeletal structures that contain polymerized α- or β-tubulin subunits. Mammalian genomes share 5–6 β-tubulin isotypes of which β1-tubulin is the most divergent, especially in its C-terminal domain. β1-tubulin expression is restricted to late MKs and platelets, where it accounts for most of the β-tubulin in MT filaments. Its ablation in the mouse results in thrombocytopenia, spherocytosis and attenuated platelet function. We therefore sought to identify proteins that bind to β1-tubulin and performed a yeast two-hybrid screen using a MK-derived cDNA library. We identified a cytoplasmic Ran-binding protein, RanBP10, as a factor that associates with cellular MTs and unexpectedly harbors GEF activity toward Ran. Loss of RanBP10 in cultured MKs disrupts MT organization and its overexpression drives accumulation of extranuclear Ran and assembly of thick and abnormally long MTs. RanBP10 thus functions as a localized β-tubulin binding protein that harbors GEF activity toward Ran in the cytoplasm, much like RCC1 in the nucleus. Our results suggest that spatiotemporally restricted generation of Ran·GTP in the cytoplasm organizes specialized MTs required for thrombopoiesis and that RanBP10 provides a molecular link between Ran and non-centrosomal MTs.
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Haase, Karen P., Jaime C. Fox, Amy E. Byrnes, Rebecca C. Adikes, Sarah K. Speed, Julian Haase, Brandon Friedman, et al. "Stu2 uses a 15-nm parallel coiled coil for kinetochore localization and concomitant regulation of the mitotic spindle." Molecular Biology of the Cell 29, no. 3 (February 2018): 285–94. http://dx.doi.org/10.1091/mbc.e17-01-0057.
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The yeast microtubule polymerase Stu2’s C-terminal domain is a 15-nm parallel, homodimeric coiled coil with two spatially distinct conserved regions. Determinants in these conserved regions optimally position Stu2 on the mitotic spindle to drive proper spindle structure and dynamics.
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Mariani, M., M. McHugh, S. Sieber, P. Fiedler, C. Ferlini, and S. Shahabi. "HGF/c-Met axis drives cancer aggressiveness in the neoadjuvant setting of ovarian cancer." Gynecologic Oncology 133 (June 2014): 96. http://dx.doi.org/10.1016/j.ygyno.2014.03.255.
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Sang, Lu Ping. "Turning-Milling Machining Center of Each Axis Movement Principle and the Headstock Structure Analysis." Advanced Materials Research 912-914 (April 2014): 878–81. http://dx.doi.org/10.4028/www.scientific.net/amr.912-914.878.
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Turning milling machining center are analyzed the structure and working principle of headstock of numerical control machine tool headstock consists of motor, drive system and components of the head of a bed, is mainly used to achieve the main movement of the machine tool. Spindle structure adopts precision double row cylindrical roller bearing and two-way thrust angular contact ball bearing group and type. The machine is the best combination of lathe and milling machine. Configuration French NUM1060 system, realize five axis control, a loading card can complete a variety of difficult machining of complex.
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Padtha, Pakornwit, and Kiatfa Tangchaichit. "Deformation of Hard Disk Drive Media Caused by Thermal Stress and Induced Air Flow." Advanced Materials Research 1061-1062 (December 2014): 866–73. http://dx.doi.org/10.4028/www.scientific.net/amr.1061-1062.866.
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The spindle motor in a hard disk drive spins at a high rotational speed. These rotations generate air flow and thermal stress. Air flow is induced by the surface roughness of the media that is moving at a high speed through air. This air passes over the surface of many parts in the drive, including the media. Thermal stress is generated by heat in the parts, e.g. voice coil motor, pre-amplifier, slider pole tips, which are heated by electric power and by the spinning of the spindle motor. The air flow and thermal stress cause a change in the media shape called deformation.Simulation results show the trend of deformation has more bending when the slider moves outward from the media axis. The pressure acted more on the underside than on the upper side which caused the media to bend up to the top cover side of hard disk drive. The maximum deformation, 15 μm, occurred at the rim of media while the distance between the media and the slider is 30 μm; thus they did not contact each other.
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Mann, Barbara J., Sai K. Balchand, and Patricia Wadsworth. "Regulation of Kif15 localization and motility by the C-terminus of TPX2 and microtubule dynamics." Molecular Biology of the Cell 28, no. 1 (January 2017): 65–75. http://dx.doi.org/10.1091/mbc.e16-06-0476.
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Mitotic motor proteins generate force to establish and maintain spindle bipolarity, but how they are temporally and spatially regulated in vivo is unclear. Prior work demonstrated that a microtubule-associated protein, TPX2, targets kinesin-5 and kinesin-12 motors to spindle microtubules. The C-terminal domain of TPX2 contributes to the localization and motility of the kinesin-5, Eg5, but it is not known whether this domain regulates kinesin-12, Kif15. We found that the C-terminal domain of TPX2 contributes to the localization of Kif15 to spindle microtubules in cells and suppresses motor walking in vitro. Kif15 and Eg5 are partially redundant motors, and overexpressed Kif15 can drive spindle formation in the absence of Eg5 activity. Kif15-dependent bipolar spindle formation in vivo requires the C-terminal domain of TPX2. In the spindle, fluorescent puncta of GFP-Kif15 move toward the equatorial region at a rate equivalent to microtubule growth. Reduction of microtubule growth with paclitaxel suppresses GFP-Kif15 motility, demonstrating that dynamic microtubules contribute to Kif15 behavior. Our results show that the C-terminal region of TPX2 regulates Kif15 in vitro, contributes to motor localization in cells, and is required for Kif15 force generation in vivo and further reveal that dynamic microtubules contribute to Kif15 behavior in vivo.
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Crowder, Marina E., Jonathan R. Flynn, Karen P. McNally, Daniel B. Cortes, Kari L. Price, Paul A. Kuehnert, Michelle T. Panzica, Armann Andaya, Julie A. Leary, and Francis J. McNally. "Dynactin-dependent cortical dynein and spherical spindle shape correlate temporally with meiotic spindle rotation in Caenorhabditis elegans." Molecular Biology of the Cell 26, no. 17 (September 2015): 3030–46. http://dx.doi.org/10.1091/mbc.e15-05-0290.
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Oocyte meiotic spindles orient with one pole juxtaposed to the cortex to facilitate extrusion of chromosomes into polar bodies. In Caenorhabditis elegans, these acentriolar spindles initially orient parallel to the cortex and then rotate to the perpendicular orientation. To understand the mechanism of spindle rotation, we characterized events that correlated temporally with rotation, including shortening of the spindle in the pole-to pole axis, which resulted in a nearly spherical spindle at rotation. By analyzing large spindles of polyploid C. elegans and a related nematode species, we found that spindle rotation initiated at a defined spherical shape rather than at a defined spindle length. In addition, dynein accumulated on the cortex just before rotation, and microtubules grew from the spindle with plus ends outward during rotation. Dynactin depletion prevented accumulation of dynein on the cortex and prevented spindle rotation independently of effects on spindle shape. These results support a cortical pulling model in which spindle shape might facilitate rotation because a sphere can rotate without deforming the adjacent elastic cytoplasm. We also present evidence that activation of spindle rotation is promoted by dephosphorylation of the basic domain of p150 dynactin.
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Al Jord, Adel, Asm Shihavuddin, Raphaël Servignat d’Aout, Marion Faucourt, Auguste Genovesio, Anthi Karaiskou, Joëlle Sobczak-Thépot, Nathalie Spassky, and Alice Meunier. "Calibrated mitotic oscillator drives motile ciliogenesis." Science 358, no. 6364 (October 5, 2017): 803–6. http://dx.doi.org/10.1126/science.aan8311.
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Cell division and differentiation depend on massive and rapid organelle remodeling. The mitotic oscillator, centered on the cyclin-dependent kinase 1–anaphase-promoting complex/cyclosome (CDK1-APC/C) axis, spatiotemporally coordinates this reorganization in dividing cells. Here we discovered that nondividing cells could also implement this mitotic clocklike regulatory circuit to orchestrate subcellular reorganization associated with differentiation. We probed centriole amplification in differentiating mouse-brain multiciliated cells. These postmitotic progenitors fine-tuned mitotic oscillator activity to drive the orderly progression of centriole production, maturation, and motile ciliation while avoiding the mitosis commitment threshold. Insufficient CDK1 activity hindered differentiation, whereas excessive activity accelerated differentiation yet drove postmitotic progenitors into mitosis. Thus, postmitotic cells can redeploy and calibrate the mitotic oscillator to uncouple cytoplasmic from nuclear dynamics for organelle remodeling associated with differentiation.
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Carmena, Ana, Aljona Makarova, and Stephan Speicher. "The Rap1–Rgl–Ral signaling network regulates neuroblast cortical polarity and spindle orientation." Journal of Cell Biology 195, no. 4 (November 14, 2011): 553–62. http://dx.doi.org/10.1083/jcb.201108112.
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A crucial first step in asymmetric cell division is to establish an axis of cell polarity along which the mitotic spindle aligns. Drosophila melanogaster neural stem cells, called neuroblasts (NBs), divide asymmetrically through intrinsic polarity cues, which regulate spindle orientation and cortical polarity. In this paper, we show that the Ras-like small guanosine triphosphatase Rap1 signals through the Ral guanine nucleotide exchange factor Rgl and the PDZ protein Canoe (Cno; AF-6/Afadin in vertebrates) to modulate the NB division axis and its apicobasal cortical polarity. Rap1 is slightly enriched at the apical pole of metaphase/anaphase NBs and was found in a complex with atypical protein kinase C and Par6 in vivo. Loss of function and gain of function of Rap1, Rgl, and Ral proteins disrupt the mitotic axis orientation, the localization of Cno and Mushroom body defect, and the localization of cell fate determinants. We propose that the Rap1–Rgl–Ral signaling network is a novel mechanism that cooperates with other intrinsic polarity cues to modulate asymmetric NB division.
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Nilsson, Monique B., Huiying Sun, Jacqulyne Robichaux, Matthias Pfeifer, Ultan McDermott, Jon Travers, Lixia Diao, et al. "A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components." Science Translational Medicine 12, no. 559 (September 2, 2020): eaaz4589. http://dx.doi.org/10.1126/scitranslmed.aaz4589.
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Acquired resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) remains a clinical challenge. Especially challenging are cases in which resistance emerges through EGFR-independent mechanisms, such as through pathways that promote epithelial-to-mesenchymal transition (EMT). Through an integrated transcriptomic, proteomic, and drug screening approach, we identified activation of the yes-associated protein (YAP) and forkhead box protein M1 (FOXM1) axis as a driver of EMT-associated EGFR TKI resistance. EGFR inhibitor resistance was associated with broad multidrug resistance that extended across multiple chemotherapeutic and targeted agents, consistent with the difficulty of effectively treating resistant disease. EGFR TKI–resistant cells displayed increased abundance of spindle assembly checkpoint (SAC) proteins, including polo-like kinase 1 (PLK1), Aurora kinases, survivin, and kinesin spindle protein (KSP). Moreover, EGFR TKI–resistant cells exhibited vulnerability to SAC inhibitors. Increased activation of the YAP/FOXM1 axis mediated an increase in the abundance of SAC components in resistant cells. The clinical relevance of these finding was indicated by evaluation of specimens from patients with EGFR mutant lung cancer, which showed that high FOXM1 expression correlated with expression of genes encoding SAC proteins and was associated with a worse clinical outcome. These data revealed the YAP/FOXM1 axis as a central regulator of EMT-associated EGFR TKI resistance and that this pathway, along with SAC components, are therapeutic vulnerabilities for targeting this multidrug-resistant phenotype.
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Mariani, Marisa, Mark McHugh, Marco Petrillo, Steven Sieber, Shiquan He, Mirko Andreoli, Zheyang Wu, et al. "HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer." Oncotarget 5, no. 13 (June 1, 2014): 4855–67. http://dx.doi.org/10.18632/oncotarget.2049.
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Yang, Xiao Jun, Bing Li, and Dong Lai Zhang. "Post-Processing Development of a New PTS-X Hybrid Kinematics Machine." Key Engineering Materials 375-376 (March 2008): 719–23. http://dx.doi.org/10.4028/www.scientific.net/kem.375-376.719.
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A new 5-degrees-of-freedom hybrid kinematic machine(HKM) consisting of a 4-degrees-of-freedom PTS-based parallel kinematics platform with center constraint branch and a serial X axis is developed. The will-be-machined workpiece is mounted on the platform and the spindle movement is driven by the X axis. This new HKM is very different from a conventional serial-type machine. Therefore, a special algorithm that can transfer the cutter location data (CL-data) into machine specific NC commands is essential for the applications of the PTS-X based HKM in real machining of the workpiece with the complicated surface. The workpiece’s location approach on the platform and the orientation transformation of the moving platform relative to the machine coordination system are investigated.
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Yao, Yan, Keisuke Nishizawa, Noriyuki Kato, Masaomi Tsutsumi, and Keiichi Nakamoto. "Identification Method of Geometric Deviations for Multi-Tasking Machine Tools Considering the Squareness of Translational Axes." Applied Sciences 10, no. 5 (March 6, 2020): 1811. http://dx.doi.org/10.3390/app10051811.
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Some methods to identify geometric deviations of five-axis machining centers have been proposed until now. However, they are not suitable for multi-tasking machine tools because of the different configuration and the mutual motion of the axes. Therefore, in this paper, an identification method for multi-tasking machine tools with a swivel tool spindle head in a horizontal position is described. Firstly, geometric deviations are illustrated and the mathematical model considering the squareness of translational axes is established according to the simultaneous three-axis control movements. The influences of mounting errors of the measuring instrument on circular trajectories are investigated and the measurements for the B axis in the Cartesian coordinate system and the measurements for the C axis in a cylindrical coordinate system are proposed. Then, based on the simulation results, formulae are derived from the eccentricities of the circular trajectories. It is found that six measurements are required to identify geometric deviations, which should be performed separately in the B axis X-direction, in B axis Y-direction, in C axis axial direction, and three times in C axis radial direction. Finally, a numerical experiment is conducted and identified results successfully match the geometric deviations. Therefore, the proposed method is proved to identify geometric deviations effectively for multi-tasking machine tools.
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Lee, Jeng Nan, Chen Hua She, Chyouh Wu Brian Huang, Hung Shyong Chen, and Huang Kuang Kung. "Toolpath Planning and Simulation for Cutting Test of Non-Orthogonal Five-Axis Machine Tool." Key Engineering Materials 625 (August 2014): 402–7. http://dx.doi.org/10.4028/www.scientific.net/kem.625.402.
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Owing to NAS 979 describes a cutting test for five-axis machine center with a universal spindle, several conditions for C-type machine tool have not been defined yet. This paper proposes a cutting test for a non-orthogonal swivel head and a rotary table type five-axis machine tool (C type) to evaluate its performance. The workpiece consists of 10 machining features. These features include the multi-axis simultaneous machining patterns and the positioning machining patterns. The flat end mill cutters are applied in each machining feature. Cutter location data for the test piece was generated using a commercial CAD/CAM system (UG) and converted to five-axis NC code using a postprocessor created in UG Post Builder. This UG postprocessor is verified through the developed postprocessor utilizing the modified D-H notation. It is also verified using VERICUT® solid cutting simulation software demonstrated the veracity of the generated five-axis NC code. The machining test is applicable for a variety of five-axis machine tool configurations.
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Chen, Xiu Mei, Qiu Shi Han, and Bao Ying Peng. "Research on Cam Contour Error of Grinding Machining." Applied Mechanics and Materials 620 (August 2014): 199–204. http://dx.doi.org/10.4028/www.scientific.net/amm.620.199.
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In order to obtain higher cam quality, the research on the cam contour error is studied. The cam is machined in the way of X-C biaxial linkage motions. The linear motor drives the grinding wheel mechanism to get the motion of X axis, and the motion of C axis is the rotating of cam driven by the torque motor. Because of the servo-system-lag of the two axes, the cam contour error is formed in the X-C biaxial linkage motions. Moreover, the following position error of X axis and C axis is not same as the cam contour error. The relationship between axis following position error and cam contour error is studied. The mathematical model of cam contour error is constructed, the relationship between the cam contour error and the following position error are obtained. At last, the conclusion which the cam contour error can be controlled is made, although the following position error exists at the same time. To design the contour error controller for higher quality cam is based on the above conclusion.
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Finley, Kenneth R., and Judith Berman. "Microtubules in Candida albicans Hyphae Drive Nuclear Dynamics and Connect Cell Cycle Progression to Morphogenesis." Eukaryotic Cell 4, no. 10 (October 2005): 1697–711. http://dx.doi.org/10.1128/ec.4.10.1697-1711.2005.
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ABSTRACT Candida albicans is an opportunistic fungal pathogen whose virulence is related to its ability to switch between yeast, pseudohyphal, and true-hyphal morphologies. To ask how long-distance nuclear migration occurs in C. albicans hyphae, we identified the fundamental properties of nuclear movements and microtubule dynamics using time-lapse microscopy. In hyphae, nuclei migrate to, and divide across, the presumptive site of septation, which forms 10 to 15 μm distal to the basal cell. The mother nucleus returns to the basal cell, while the daughter nucleus reiterates the process. We used time-lapse microscopy to identify the mechanisms by which C. albicans nuclei move over long distances and are coordinated with hyphal morphology. We followed nuclear migration and spindle dynamics, as well as the time and position of septum specification, defined it as the presumptum, and established a chronology of nuclear, spindle, and morphological events. Analysis of microtubule dynamics revealed that premitotic forward nuclear migration is due to the repetitive sliding of astral microtubules along the cell cortex but that postmitotic forward and reverse nuclear migrations are due primarily to spindle elongation. Free microtubules exhibit cell cycle regulation; they are present during interphase and disappear at the time of spindle assembly. Finally, a growth defect in strains expressing Tub2-green fluorescent protein revealed a connection between hyphal elongation and the nuclear cell cycle that is coordinated by hyphal length and/or volume.
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Lee, Il Taek, Hyun Sik Kim, Changon Park, Dong Pyo Hong, and Hee Yong Kang. "The Friction Welding Characteristic Analysis of the Al 7075-T6 According to the Spindle Speed and Upset Pressure." Advanced Materials Research 690-693 (May 2013): 2647–50. http://dx.doi.org/10.4028/www.scientific.net/amr.690-693.2647.
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The propeller shaft of rear-wheel drive vehicle is an axis which transfers power from an engine to rear-wheel through differential gear box. In this study, we studied the properties of friction welding required to produce the aluminum propeller shaft of lightweight rear-wheel-drive vehicle. We studied welding property to apply Al 7075-T6 aluminum yoke to automobile connects driving shaft and differential gear box. Here, solid phase friction welding method was used. In friction welding process, the principal parameter is spindle speed, up-set pressure and up-set time. We analyzed variable characteristics of friction welding strength according to the change of the spindle rate and up-set pressure. Friction welding strength was analyzed with ultimate tensile strength test with universal testing machine (UTM). The Al 7075-T6 was used as the round bar of the diameter of 25mm. The ultimate tensile strength was 552.3 MPa. It is 94% of ultimate tensile strength of pure Al 7075-T6 material. The main parameters of characteristics are discussed in detail based on analysis of the main effects plot and multi-vari chart. Finally, the core factors to get the maximum effect of friction welding investigated.
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Falk, Jill E., Ian W. Campbell, Kelsey Joyce, Jenna Whalen, Anupama Seshan, and Angelika Amon. "LTE1 promotes exit from mitosis by multiple mechanisms." Molecular Biology of the Cell 27, no. 25 (December 15, 2016): 3991–4001. http://dx.doi.org/10.1091/mbc.e16-08-0563.
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In budding yeast, alignment of the anaphase spindle along the mother–bud axis is crucial for maintaining genome integrity. If the anaphase spindle becomes misaligned in the mother cell compartment, cells arrest in anaphase because the mitotic exit network (MEN), an essential Ras-like GTPase signaling cascade, is inhibited by the spindle position checkpoint (SPoC). Distinct localization patterns of MEN and SPoC components mediate MEN inhibition. Most components of the MEN localize to spindle pole bodies. If the spindle becomes mispositioned in the mother cell compartment, cells arrest in anaphase due to inhibition of the MEN by the mother cell–restricted SPoC kinase Kin4. Here we show that a bud-localized activating signal is necessary for full MEN activation. We identify Lte1 as this signal and show that Lte1 activates the MEN in at least two ways. It inhibits small amounts of Kin4 that are present in the bud via its central domain. An additional MEN-activating function of Lte1 is mediated by its N- and C-terminal GEF domains, which, we propose, directly activate the MEN GTPase Tem1. We conclude that control of the MEN by spindle position is exerted by both negative and positive regulatory elements that control the pathway’s GTPase activity.
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Lei, Xiao Bao, Feng Xie, and Ji Wen Zhao. "Design of a 5-Axis CNC Machine Tool Applied to Dental Restoration." Key Engineering Materials 568 (July 2013): 75–80. http://dx.doi.org/10.4028/www.scientific.net/kem.568.75.
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In this work, a 5-axis machine tool used for dental restorations is designed. In view of the fact that its special characteristics of the applications, the mechanical structure and main part of the machine tool have been designed and chosen with careful calculation. The machine tool is equipped with a high speed electro-spindle driven by computerized velocity and can rotate at a maximum speed of 60,000 rpm, which driving unite is equipped with servomotor and optical grating for its better motion precision control. Meanwhile, by using the motion controller card, the machine is controlled with a closed-loop numerical control system. Based on the theory of multi-body system, and through analyzing the matrix of the position transformation and the displacement transformation, a model for positioning errors is put forth for error compensation in programming way. The grinding programs enable exact copies of the object to be fabricated. The satisfactory results show this machine tool has excellent performances.
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Tran, Ngoc Hai, Cung Le, and Anh Dung Ngo. "An Investigation on Speed Control of a Spindle Cluster Driven by Hydraulic Motor: Application to Metal Cutting Machines." International Journal of Rotating Machinery 2019 (February 19, 2019): 1–17. http://dx.doi.org/10.1155/2019/4359524.
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In this article, we present an experimental study on the speed stability of a spindle driven by a hydraulic motor, which is controlled by a proportional valve, through a V-belt transmission. The research includes the dynamic modeling of the transmission cluster and the transmission from the hydraulic motor to the working shaft via V-belt mechanism, together with the establishment of a mathematical model and fuzzy self-tuning PID controller model. In the model, the V-belt is assumed as an elastic module, and the friction coefficient and mass inertia moment of the hydraulic motor are considered as constant. The Matlab software is used to simulate the speed response of the hydraulic motor to the working shaft. Based on theoretical study, we resemble the experimental system and determine the parameters for the fuzzy self-tuning PID controller. We conduct experiment and investigate the speed stability of the working shaft from 300 to 1100 (rpm) based on transient response parameters such as the time delay, the setting time, the overshoot, and the rotation error at steady state. Thereby, in this study, the simulation and the experiment results are compared and evaluated regarding the speed stability of the working shaft driven by hydraulic motor transmitted through V-belt mechanism. The findings show the speed controllability by using proportional valve to manipulate the oil flow and applying a self-tuning PID controller to achieve very good results such as the error difference of 0.001 to 0.036%, the delay of 0.01 to 0.02 seconds, no overshoot, and the settling error less than 5% compared to the set values. On the other hand, we include the effect of the oil temperature of 40 to 80°C on the working shaft speed (500, 900 rpm) in this study and derive that the system works well at temperature range of 40 to 70°C. On these findings, we propose the applicability of this system on the current machinery cutters. In addition, we verify the effects of the hydraulic drive for main shaft, controlled by fuzzy PID, by comparison of the roughness of the machining work piece with respect to the one using the 3-phase motor drive.
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Singh, Deepika, and Christian Pohl. "Coupling of Rotational Cortical Flow, Asymmetric Midbody Positioning, and Spindle Rotation Mediates Dorsoventral Axis Formation in C. elegans." Developmental Cell 28, no. 3 (February 2014): 253–67. http://dx.doi.org/10.1016/j.devcel.2014.01.002.
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