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The recent development of North Sea oil has seen the construction of massive structures founded in the seabed of the North Sea. Inadequacies in existing site investigation techniques employed for the design of the foundations of these structures have shown that a need exists for a device to permit an accurate and rapid assessment of the soil conditions existing below the seabed. This thesis considers the application of the vibrohammer, a machine capable of driving piles tubes or rods rapidly into the ground under a self-adjusting combination of vibration and impact, as the driving mechanism both for a coring device and a dynamic penetrometer. In so doing it presents the historical development of the vibrohammer from its introduction in the U.S.S.R. circa 1940, together with the parallel development, also in the U.S.S.R., of theoretical treatments of vibro-impact dynamics. An experimental investigation is carried out at both model and full-scale level and confirms that a vibrohammer is capable of self-adjusting the magnitude of the impacts it generates with increasing soil resistance. The capacity of a vibrohammer to produce rapid penetration rates does not arise from a potential to produce large impacts but from the ability to produce an optimum combination of vibration and impact. Optimum machine parameters at which the self-adjustment results in maximum depths of penetration are identified and explained both from the experimental work and a computer simulation of the vibro-hammering process. A possible mechanism by which this self-adjustment occurs is proposed. The application of a vibrohammer as the driving mechanism for a dynamic penetrometer requires the selection of machine parameters different from those which result in maximum penetration depths. In order to maximise the ratio of the measured dynamic soil resistance to the corresponding static soil resistance it is necessary to operate a vibrohammer in a predominantly impact mode. The development of a mechanical adaptor unit by which existing pure vibratory coring devices may be modified to operate as a vibrohammer is presented and discussed in the light of preliminary field test results.

<p>Signal transductions are essential processes for living cells to react to environmental stimuli adequately, and they need to be tightly regulated as they can affect cell survival and cell fate determination. Since many of these signaling events rely on the presence of receptors on the cell membrane, members of endocytic proteins play critical regulatory roles in signaling via changing the localization of the receptors. In particular, endocytic adaptors are the linkers that connect membrane cargo and other members of endocytic machinery to accomplish the process. We focused on the roles of the endocytic adaptors epsins and their cargoes in signaling, as both epsins’ transmembrane and cytosolic cargoes participate in signaling pathways.</p> <p>We investigated the molecular mechanism of how epsins recognize specific ubiquitinated membrane cargoes among other ubiquitinated membrane proteins. Through genetic, biochemical, and cell biological approaches, we identified the first yeast transmembrane cargo, Ena1, a P-type ATPase sodium pump. We report that the simultaneous presence of phosphorylation and ubiquitination on the Ena1 are required for epsin-specific recognition. We also demonstrated that post-translational modifications are Yck1/2 and Art3-Rsp5 dependent, and the spatial arrangement of the modifications is essential. </p> <p>In addition to the regulation of signaling pathways through internalizing transmembrane cargoes, epsins are also involved in the regulation of Rho GTPase signaling pathways. Through direct interaction, epsins inhibit activities of their cytosolic cargoes, Rho GTPase activating proteins (RhoGAPs). Ocrl1 is one of the epsin interacting RhoGAP domain-containing proteins. The deficiency of Ocrl1 leads to a lethal developmental disease called Lowe syndrome (LS). While the patients display developmental problems affecting the brain and eyes, they also suffer from kidney dysfunction that results in death. The pathological mechanism is currently obscure and no cure, partly due to the lack of an adequate cell model from the affected tissues. We generated the first iPSC model from fibroblasts of LS patients and normal individuals and further generated kidney cells from these iPSCs. Consistent with observations obtained from LS fibroblasts, the LS iPSC derived kidney cells from patient cells also have a deficiency in ciliogenesis.</p> Further, we discovered that Six2, a crucial transcriptional factor in kidney development, is mislocalized to the Golgi-apparatus in patient iPSC-derived kidney cells as well as in an <i>OC</i><i>RL1</i> K.O. proximal tubular cell line. Disproportional cell lineage differentiation is also observed in the patient group. The iPSC model provides an opportunity to investigate the differences between normal and disease cell differentiation in all the affected tissues, generate organoids, and develop cell replacement therapies.

University of Macau / Faculty of Science and Technology. / Department of Electromechanical Engineering

by Li Chi Keung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 95-100). / Acknowledgements --- p.ii / Abstract --- p.iii / Notations --- p.vii / List of Figures --- p.viii / List of Tables --- p.x / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Serial Manipulator and Parallel Manipulator --- p.1 / Chapter 1.2 --- Literature Overview --- p.4 / Chapter 1.3 --- Objective --- p.10 / Chapter Chapter 2 --- Classification and General Approach / Chapter 2.1 --- Overview --- p.11 / Chapter 2.2 --- Classification of Stewart Platform Type Parallel Manipulators --- p.12 / Chapter 2.3 --- Sub-structures of Stewart Platform Type Mechanism --- p.14 / Chapter 2.3.1 --- Point-Line (PL) Structure --- p.14 / Chapter 2.3.2 --- Point-Body (PB) Structure --- p.16 / Chapter 2.3.3 --- Line-Line (LL) Structure --- p.17 / Chapter 2.3.4 --- Line-Body (LB) Structure --- p.21 / Chapter 2.4 --- Approach for Closed-Form Direct Position Analysis --- p.25 / Chapter 2.4.1 --- DOF of Stewart Platform Type Parallel Mechanism --- p.26 / Chapter 2.4.2 --- DOF of Stewart Platform Type Parallel Mechanism with Disconnected Legs --- p.27 / Chapter 2.4.3 --- Formation of Rotation and Translation Matrices --- p.28 / Chapter 2.4.4 --- Formation of Closure Equations --- p.32 / Chapter 2.4.5 --- Elimination of Variables --- p.33 / Chapter 2.4.6 --- Final Solution --- p.35 / Chapter 2.5 --- Summary --- p.35 / Chapter Chapter 3 --- Case Studies / Chapter 3.1 --- Overview --- p.37 / Chapter 3.2 --- Type 5-5 Case II --- p.38 / Chapter 3.3 --- Type 6-5 --- p.47 / Chapter 3.4 --- Type 6-6 with 4 Collinear Joint Centers on Both Link (type 6-6 (L4L)) --- p.51 / Chapter 3.5 --- Type 6-6 with 4 Collinear Joint Centers on Movable Link (type 6-6 (L4B)) --- p.59 / Chapter 3.6 --- Summary --- p.63 / Chapter Chapter 4 --- Singularity Analysis / Chapter 4.2 --- General Theory --- p.64 / Chapter 4.2.1 --- Multiple Root Configuration --- p.64 / Chapter 4.2.2 --- Special Configuration --- p.66 / Chapter 4.2.3 --- Multiple Root Configuration and Special Configuration --- p.66 / Chapter 4.3 --- Examples --- p.66 / Chapter 4.3.2 --- Special Planar Parallel Manipulator --- p.66 / Chapter 4.3.4 --- Special Stewart Platform Type Parallel Manipulator --- p.71 / Chapter 4.4 --- Summary --- p.74 / Chapter Chapter 5 --- Conclusions and Recommendations for Future Research / Chapter 5.1 --- Conclusions --- p.75 / Chapter 5.2 --- Recommendations for Future Research --- p.77 / Appendices / Chapter A.l --- Direct Position Analysis of P5B Structure --- p.79 / Chapter A.2 --- Analytic Expressions for Symbols of Type 5-5 Case II --- p.82 / Chapter A.3 --- Analytic Expressions for Sybmols of Type 6-6 (L4L) --- p.84 / Chapter A.4 --- Mathematica Scripts for Case Studies in Chapter 3 --- p.85 / Chapter A.4.1 --- Type 5-5 Case II --- p.85 / Chapter A.4.2 --- Type 6-6 with 4 Collinear Joint Centers on Both Link Connected Together --- p.91 / Reference --- p.95

by Ho Siu Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 105-110). / ACKNOWLEDGEMENT --- p.i / ABSTRACT --- p.ii / NOMENCLATURE --- p.iii / TABLE OF CONTENTS --- p.v / LIST OF FIGURES --- p.vii / Chapter 1 --- INTRODUCTION --- p.1 / Chapter 2 --- FORM-CLOSURE GRASP --- p.9 / Chapter 2.1 --- Condition for Form-closure Grasp --- p.9 / Chapter 2.2 --- Construction of Form-closure Grasp --- p.12 / Chapter 2.3 --- Configuration Stability of Form-closure Grasp --- p.28 / Chapter 2.4 --- Determination of Object Frame from a Form-closure Grasp --- p.33 / Chapter 3 --- DYNAMIC MODEL OF MULTI-ARM SYSTEMS HANDLING ONE OBJECT --- p.36 / Chapter 3.1 --- System Description --- p.36 / Chapter 3.2 --- Manipulator Dynamics --- p.37 / Chapter 3.3 --- Object Dynamics --- p.37 / Chapter 3.4 --- Contact Forces --- p.38 / Chapter 3.5 --- Kinematic Relations --- p.40 / Chapter 3.6 --- Overall System --- p.41 / Chapter 3.7 --- Constraint Space Matrices --- p.42 / Chapter 3.8 --- Motion Space Matrices --- p.48 / Chapter 3.9 --- General Joint Model --- p.54 / Chapter 4 --- FORWARD DYNAMICS OF MULTI-ARM SYSTEMS HANDLING ONE OBJECT --- p.65 / Chapter 4.1 --- Previous Works --- p.65 / Chapter 4.2 --- Modified Approach --- p.69 / Chapter 4.3 --- Constraint Violation Stabilization Method --- p.73 / Chapter 4.4 --- Computation Requirement of the Algorithm --- p.75 / Chapter 5 --- CONCLUSION --- p.78 / Chapter 5.1 --- Future Researches --- p.79 / APPENDICES / Chapter A --- PROOFS AND DISCUSSIONS RELATED TO CHAPTER TWO --- p.81 / Chapter B --- IMPLEMENTATION OF THE ALGORITHM FOR DETERMINING THE OBJECT FRAME FROM A FORM-CLOSURE GRASP --- p.95 / Chapter C --- EXPRESSING WRENCHES WITH ZERO-PITCH WRENCHES --- p.96 / Chapter D --- IMPLEMENTATION OF THE PROPOSED SIMULATION ALGORITHM --- p.98 / REFERENCES --- p.105