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Flexural mechanism design is one of the latest field for mechanism researches in these recent years. In this paper, it will address one method of normalized dimensional parameters. According to the traditionally change of the appearance of flexural hinge, the different parameters will be designed through to the differences of several combination. On the other hand, we use the Finite Element Method to analyze the kinematics behavior of different hinges. Finally, we come up with a series of complete data that provide designers a reference for designing.

Studying movement, through the design and development of a narrow residential site with access from water and land at opposing ends. Utilizing parallel planes, connect three zones of the site and maximizing directional views along its length, while formulating an architectural language of path and passage. The façade design is a layering of fixed and active colored glass planes to allow dominate parallel wall, to run through the site without the obstruction of frames. Active glass planes rotate along horizontal and vertical axis and connect the interior and exterior living spaces. Glass façade design led to development of a hinging mechanism to provide rotational movement at various opening increments and locking points, while incorporating it into the fixed glazing system. / Master of Architecture

Origami-inspired design is an emerging field capable of producing compact and efficient designs. The object of a surrogate fold is to provide a fold-like motion in a non-paper material without undergoing yielding. Compliant mechanisms provide a means to achieve these objectives as large deflections are achieved. The purpose of this thesis is to present a summary of existing compliant joints suitable for use as surrogate folds. In doing so, motions are characterized which no existing compliant joint provides. A series of compliant joints is proposed which provides many of these motions. The possibility of patterning compliant joints to form an array is discussed. Arrays capable of producing interesting motions are noted.

GPCRs, influencing myriads of cellular functions, are the members of the largest family of the membrane proteins. However, their structures and the signaling mechanisms still remain enigmatic. In case of the Glycoprotein Hormone Receptor (GpHR) family the structure-function relationship is less understood because of a large extra-cellular domain (ECD). This large ECD, consisting of Leucine Rich Repeats (LRRs) and membrane-proximal hinge region, is sufficient for specific binding to the hormone (Ascoli, Fanelli, & Segaloff, 2002), but for receptor activation, hormone binding is translated via a conformation wave starting at hinge region and relayed to the transmembrane domain. Several biochemical, immunological and molecular biological tools have been employed to elucidate the structure-function relationship of the hormones and their receptors. These studies also helped in deciphering some of the regions present in both the hormones and the receptors involved in maintaining the specificity of their interaction (Fan & Hendrickson, 2005; Fox, Dias, & Van Roey, 2001; Wu, Lustbader, Liu, Canfield, & Hendrickson, 1994). However, the complete understanding of the hormone‐receptor contact sites and mechanism of receptor activation are still an enigma. Understanding the molecular details of these phenomena can lead to the development of novel strategies of regulating hormone action or regulating receptor activation in a hormone independent manner. The crystal structure of FSHR ECD (amino acids 17-366) revealed that LRRs form a semicircular palm shaped structure with the C terminus region, designated as the hinge region, protruding out like a thumb. The hinge region, rather than being a separate functional unit, was found to be an integral part of the LRR domain, having two such repeats (LRR11 &12). LRR 11 is connected to LRR12 through a hairpin loop (amino acids 280-344) harboring the invariant sulfated tyrosine residue (sTyr) in YD/EY motif (X. Jiang et al., 2012). The heterodimeric hormones consisting of a common  subunit and a hormone specific  subunit, bind to the primary hormone binding site at LRR 4-6 as reported in the FSHR-FSH co crystal (Fan & Hendrickson, 2005). This primary binding of the hormone at LRR 4-6 creates a pocket (comprising of the residues P16α, L17α, F18α, F74α, L37β, Y39β, and P45β) in the hormone for secondary binding at sTyr residue. This interaction is proposed to initiate conformation change in the hinge region which further leads to FSHR activation (X. Jiang et al., 2012). Thus, the role of hinge region in GpHR activation got evolved from a linker to a switch, which decides the fate of the receptor activity (Agrawal & Dighe, 2009; Majumdar & Dighe, 2012). sTyr residue being conserved, presents itself as a potential player in activation mechanism of all the three receptors of the family (Bonomi, Busnelli, Persani, Vassart, & Costagliola, 2006; Kreuchwig, Kleinau, & Krause, 2013). Precise involvement of sTyr in GpHR activation is yet to be explored. The previous studies from the laboratory using the hinge region specific polyclonal and monoclonal antibodies established the unequivocal role of the hinge region in FSHR and TSHR activation (Agrawal & Dighe, 2009; Majumdar & Dighe, 2012). However, its function in LHR activation has not been conclusively established. Due to the unavailability of the structural information of LHR ECD/hinge, it is more difficult to study and explain the role of hinge region in LHR activation. The hormone independent signaling by point mutants of LHR also remains poorly understood. In the present study an attempt has been made to understand the role of the hinge region in LHR signaling and modulating role of LRRs in hinge mediated LHR activation. The present study was initiated with an overall objective of understanding the molecular details of LHR activation mechanism keeping hinge at the centre of the picture. To have clarity of this picture with a holistic view of the mechanism, multi-pronged approach was adopted. Initially, ScFvs against LHR hinge region were employed as tools to probe into the hormone‐receptor interactions. Antibodies against glycoprotein hormones and their receptors have often provided insights into the mechanism of hormone‐receptor interactions and signal transduction (Agrawal & Dighe, 2009; Dighe & Moudgal, 1983; Gadkari, Sandhya, Sowdhamini, & Dighe, 2007; Gadkari et al., 2007; Kene, Nalavadi, Dighe, Iyer, & Mahale, 2004; Majumdar, Railkar, & Dighe, 2012a, 2012b). In this study, Single chain Fragment variables (ScFvs) against the hinge region of LH receptor have been employed to understand the mechanism of receptor activation. The effects of LHR ScFvs on hCG-LHR interactions have been investigated and three of the ScFvs, JE10, JE4 and JG1 could bypass the hormone and activate the receptor directly, with JE10 being the most potent one. The effect on the signaling was specific for LHR as no increase in cAMP response was observed for TSHR/FSHR in presence of these ScFvs. JE10 surprisingly was unique and could alter the hCG-LHR interaction by decreasing hormone affinity and simultaneously increasing the Bmax for the hormone. JE10 binding was decreased to the pre-formed hormone receptor complex suggesting that hCG and the stimulatory antibody show stearic hindrance at the binding sites on hinge or hormone binding induces conformational change in the epitope of JE10. The change in affinity and Bmax of the hormone by JE10 could be due to unmasking of new binding sites for hormones or an allosteric effect on the protomer interaction like explained in case of a small TMD specific allosteric modulator of FSHR (Xuliang Jiang et al., 2014). JE10 could also potentiate hCG signaling at sub-saturating concentrations of hCG, the precise mechanism of which is not clear. Through TSHR-LHR chimeric mutants, a stretch from amino acids 313-349, within the hinge region, was identified as the site recognized by JE10. In order to study structural features of the JE10 epitope, LHR ECD was modeled on the basis of FSHRED crystal structure. With most of the motifs being structurally conserved (CF3 and YPSHCCAFF); the major portion of the hinge region was found to be unstructured. This unstructured region harbored the JE10 epitope as well as the functionally important conserved sTyr residue. The CD spectra of LHR hinge in presence of ScFv JE10 suggested a ScFv induced helical conformation and stabilization of the hinge loop region, which was constrained in the homology model into helices. As loop was now constrained in the Mode 2, so was the interaction of sTyr, which was now in contact with positively charged residues, probably stabilizing its charge. The YEY motif mutants further confirmed the indirect essential role of Y331 in activation of LHR by JE10. Another approach followed to study hCG-LHR interactions was use of a series of LHR N-terminal truncation mutants and truncation mutants along with one of the LHR CAM (S277Q/D578Y). The effect of these truncations on hormone binding and receptor activation was investigated. The deletion of Cysteine box (Cb-1) of LHR (present at N-terminus of ECD) leads to abrogation of hCG binding, indicating importance of this region in maintaining ECD conformation required for hormone binding. This is the most unexplored region of the ECD. Though Cb-1 does not bind to the hormone directly (as is evident from the crystal structure) but it is indirectly essential for hormone binding. The basal activity of these truncated mutants was as low as that of the wild type LHR, reconfirming that no region of LHR ECD acts as an inverse agonist for the TMD (Karges, Gidenne, Aumas, Kelly, & Milgrom, 2005). Truncation mutants with CAM (double mutants) also showed low basal activity, suggesting that intact ECD is prerequisite for keeping LHR in a conformation, best suited for hormone binding and binding of G protein for activation. That best conformation still needs to be explored. Truncation mutants did not get stimulated by JE10 also. This observation is opposite to the previous studies in which FSHR/TSHR truncated mutants could be stimulated by hinge specific antibodies (Agrawal & Dighe, 2009; Majumdar & Dighe, 2012). This difference points out to the variations in which LHR hinge-TMD interactions prevail and lead to the receptor activation. This variation was also confirmed with a previous report in which the binding of TSHR-ECL specific antisera to wild type LHR and TSHR-LHR 6 chimeric mutant suggested that hinge of LHR does not seem to be constraining the TMD (Majumdar et al., 2012b). Thus the LHR TMD itself possesses all the inhibitory interactions, also indicated by the presence of most of the activating mutations in LHR TMD (Piersma, Verhoef-post, Berns, & Themmen, 2007). Protomer interaction is the newest aspect of GpHR activation mechanism and has not reached any conclusive, physiologically relevant explanations yet. By co-transfection of wild type LHR and ECD truncated mutants, this study suggests the LHR protomer interaction and proposes the involvement of allosteric effect of ECD on LHR protomer interaction. The effect of JE10 on activating and inactivating mutants of LHR were quite interesting. The ScFv could bind to the activating mutant D578Y (associated with precocious puberty). This mutant exhibited higher basal cAMP production, but was activated even further by the ScFv. The inactivating mutant A593P is a completely inactive receptor associated with (associated with pseudo-hermaphroditism. It does not respond to the hormone at all. The ScFv JE10 binds to this receptor and stimulates cAMP production. This observation is rather striking, as it is possible to activate a completely inactive mutant that could not be stimulated by the hormone by a binder specific for the hinge region. It is not clear how the binder that interacts with the hinge region affects the function of the inactive TMD thus providing an interesting tool to investigate the interactions between the hinge region and TMD that are probably key to understand the activation of GpHR. which has been shown to be central to the GpHR activation mechanism, (Agrawal & Dighe, 2009; Majumdar et al., 2012b; Schaarschmidt, Huth, Meier, Paschke, & Jaeschke, 2014). As per the recently suggested model by Deupi et. al., that each mutation and agonist can take a different pathway during activation (Kobilka & Deupi, 2007). The activated state induced by JE10 in D578Y and A593P seems to be different from the wild type LHR, with each activated receptor state having different capacity to bind to the G protein. The difference in G protein capacity in itself reflects the different receptor turnover or different Gs uncouplings or different Gs binding affinities, which needs to be further investigated, opening up another avenue for exploration. There is a lacuna in understanding the signal relay from the hinge to TMD. However, JE10 seems to be activating the wild type LHR and the mutants directly or indirectly by modulating the 6th helix of the TMD, known to be important for hormone independent activation of LHR (Fanelli, 2000; Latronico & Segaloff, 2007; Majumdar et al., 2012b). As evident from the absence of any hinge mediated constrain on LHR TMD and absence of uncharged residues present in LHR LRRD-TMD interface (LHR ECD Model 1), LHR hinge does not seem to be maintaining significant interactions with the TMD in absence of a ligand or in its basal state. Hormone/ agonist binding or activating mutations act as a positive regulator (inducing conformation change in hinge), required to bridge the interactions between LHR hinge and the TMD, which is supported by various studies in the past (Karges et al., 2005; Majumdar et al., 2012b; Nishi, Nakabayashi, Kobilka, & Hsueh, 2002; Osuga et al., 1997; Ryu, Gilchrist, Tung, Ji, & Ji, 1998; Zeng, Phang, Song, Ji, & Ji, 2001). This interaction bridged by the conformational change in the hinge region, seems to isomerize the closed state of LHR into an activated state. The present study supports the conformational induction model for receptor activation in which intramolecular interactions between the two domains (hinge-TMD) lead to the receptor activation. In conclusion, this study presents a possible mechanism of activation of LHR by a partial agonist ScFv, which induces the conformation change in the disordered loop region (a.a.313-349) of the hinge and stabilizes it into helical state. This conformation change is predicted to be important for relaying the activation signal to the TMD. The study also demonstrates the activation of a completely inactive mutant A593P by JE10, suggesting a distinct possibility of its use as a therapeutic tool in treating infertility caused by inactivating mutations in LHR. On a second note, the study extends the role of LRRs, apart from direct hormone binding, to an indirect allosteric role in hormone binding, LHR activation and functional stability. This functional stability does not seem to be restricted to a single LHR but also depends on its interaction with nearby protomers. Though there are evidences for and against each of the above discussed possibilities, as yet there is no accepted model that explains the precise steps of receptor activation, hence, the molecular details of these interactions needs to be investigated in future.

A precast concrete structural system offers many advantages over in-situ casting. For example, greater control over the quality of materials and workmanship, improved health and safety (with casting carried out at ground level rather than at height) and cost efficiency (with standard forms continually re-used) are all realised through the off-site production of structural elements. As a result, a large body of research has been conducted into their performance, with many national codes of practice also devoting specific sections to design and detailing. However, contemporary design practice has been shown to not always correctly reflect the findings of published experimental studies. Concrete technology is continually evolving, as is the industry s knowledge of how to model and predict the behaviour of the resulting structural components. Using such understanding to design and justify the more efficient, cost-effective or flexible manufacture of precast components can offer a key commercial advantage to a precast manufacturer. In this context, the numerical and experimental investigations undertaken as part of this study have been specifically focussed on quantifying the advantages of utilising beneficial alternatives. Specifically the research has looked at improvements in concrete mixes, lightweight aggregates and reinforcing strategies, for precast structural elements required to transfer loads both vertically and horizontally. However, because of the non-standard solutions considered, different approaches have been used to demonstrate their suitability. Towards this goal, an alternative assessment strategy was devised for slender precast concrete panels with central reinforcement. The procedure was found to lead to design capacities that are in good agreement with actual experimental findings and should thus result in future manufacturing efficiency. The method can also be used for alternative concrete types and reinforcement layouts. Fresh and early-age material characteristics of self-compacting concrete mixes with a partial or complete replacement of traditional gravel and sand constituents with lightweight alternatives were investigated. This was done to demonstrate the feasibility of their use for the manufacture of large scale structural components, with clear benefits in terms of lifting and transportation. A computational push-down procedure was utilised to demonstrate the potential unsuitability of current tying regulations for avoiding a progressive collapse event in precast framed structures. The findings are considered to be of particular significance for these structures due to the segmental nature of the construction and the associated inherent lack of structural continuity.

This thesis presents a) a scheme for selecting the most suitable flexure hinge compliance equations, and b) a simple methodology of deriving kinetostatic models of micro-motion stages by incorporating the scheme mentioned above. There were various flexure hinge equations previously derived using different methods to predict the compliances of circular flexure hinges. However, some of the analytical/empirical compliance equations provide better accuracies than others depending on the t/R ratios of circular flexure hinges. Flexure hinge compliance equations derived previously using any particular method may not be accurate for a large range of t/R ratios. There was no proper scheme developed on how to select the most suitable and accurate hinge equation from the previously derived formulations. Therefore, the accuracies and limitations of the previously derived compliance equations of circular flexure hinges were investigated, and a scheme to guide designers for selecting the most suitable hinge equation based on the t/R ratios of circular flexure hinges is presented in this thesis. This thesis also presents the derivation of kinetostatic models of planar micromotion stages. Kinetostatic models allow the fulfillment of both the kinematics and the statics design criteria of micro-motion stages. A precise kinetostatic model of compliant micro-motion stages will benefit researchers in at least the design and optimisation phases where a good estimation of kinematics, workspace or stiffness of micro-motion stages could be realised. The kinetostatic model is also an alternative method to the finite-element approach which uses commercially available software. The modelling and meshing procedures using finite-element software could be time consuming. The kinetostatic model of micro-motion stages wasdeveloped based on the theory of the connection of serial and parallel springs. developed based on the theory of the connection of serial and parallel springs. The derivation of the kinetostatic model is simple and the model is expressed in closed-form equations. Material properties and link parameters are variables in this model. Compliances of flexure hinges are also one of the variables in the model. Therefore the most suitable flexure hinge equation can be selected based on the scheme aforementioned in order to calculate the kinetostatics of micro-motion stages accurately. Planar micro-motion stages with topologies of a four-bar linkage and a 3-RRR (revolute-revolute-revolute) structure were studied in this thesis. These micromotion stages are monolithic compliant mechanisms which consist of circular flexure hinges. Circular flexure hinges are used in most of the micro-motion stages which require high positioning accuracies. This is because circular flexure hinges provide predominantly rotational motions about one axis and they have small parasitic motions about the other axes. The 3-RRR micro-motion stage studied in this thesis has three-degrees-of-freedom (DOF). The 3-RRR stage consists of three RRR linkages and each RRR linkage has three circular flexure hinges. A Pseudo-Rigid-Body-Model (PRBM), a kinetostatic model and a two-dimensional finite-elementanalysis (FEA) model generated using ANSYS of micro-motion stages are presented and the results of these models were compared. Advantages of the kinetostatic model was highlighted through this comparison. Finally, experiments are presented to verify the accuracy of the kinetostatic model of the 3-RRR micromotion stage. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289361 / Thesis (Ph.D.) -- University of Adelaide, School of Mechanical Engineering, 2007

Current designs of bileaflet mechanical heart valves (BMHVs) and trileaflet polymeric heart valves(TPHVs) are plagued by unacceptable levels of hemolysis and thrombus formation in critical areas thereby producing mediocre clinical performance. The objective of this study is: (1) to investigate the influence of BMHV designs on hinge flow characteristics, (2) to quantify the influence of hinge gap width tolerance in a BMHV design, and (3) to investigate the influence of TPHV design on flow characteristics. St. Jude Medical (SJM) provided four transparent mitral BMHVs: one 23 mm CarboMedics (CM), one 27 mm SJM Standard and two 27 mm prototype BHMVs with altered hinge gap widths. Aortech Inc. provided three 23 mm aortic prototype TPHVs. Laser Doppler velocimetry and Particle Image velocimetry were used to measure flow velocity inside these valve prostheses. The flows through the valves were maintained within physiological limits. All valves revealed Reynolds shear stress (RSS) levels greater than 200 Pa far exceeding the threshold for platelet activation and hemolysis. MHV hinge flows in the mitral position were characterized by a strong recirculation during ventricular diastole while leakage jets over and adjacent to leaflets were prominent during ventricular systole. CM hinge flow had higher RSS than in the SJM hinge. The large gap width hinge had the largest leakage jet size and highest RSS (>400 Pa) during ventricular diastole. The Standard gap width hinge showed better washout during systole and provided optimum hemodynamic performance than the prototype designs. In aortic prototype PHVs, elevated RSS conducive to hemolysis was observed along the central jet during systole and the leakage jet at the high central region inside the valve during diastole. This study showed that hinge geometry designs and hinge gap width tolerance governed the success of the bileaflet MHV design. Also the performance of the three aortic PHVs is dependent on commissural designs and leaflet thicknesses. Owing to the critical nature flow fields on clinical outcomes studies such as the current study should be conducted in the pre-clinical evaluation phase for all new MHV or PHVs.

This study presents a novel polyimide-based self-assembly three dimensional micro blade using surface micromachining technology for the development of micro-fan chip. The high surface-tension-force of reflowed polyimide has can be used to lift the free-standing micro blade. In addition, the thesis introduces a micro hinge structure to effectively limit the maximum lifting angle of the micro blade and to accurately lock hinge-pin into the vertical position. Many parameters have been investigated its influence on the surface-tension- force of polyimide, including the thickness of polyimide and the temperature/time in reflow processing. Based on the experimental results, 18 £gm-thick polyimide can lift the micro blade at 70¢X angle under 380 ¢J/10 hrs reflow condition. On the other hand, 25 £gm-thick polyimide has demonstrated its maximum lifting angle can be achieved to 130¢X utilizing the very high surface-tension-force induced by over contraction and deformation when it was reflowed at higher temperature (400 ¢J). Finally, this dissertation has studied the relation between the position of polyimide elastic-joint and the deflection angle (£r). Furthermore, this thesis has successfully demonstrated a novel multi-joint and asymmetrical microstructure for the development of the spiral and out-of-plane 3D micro blade.

Within the cell nucleus, there are regions of highly condensed, transcriptionally silent chromatin called heterochromatin. Heterochromatin plays an important role in both chromosomal stability and gene regulation within the cell. Heterochromatin assembly is mediated by Heterochromatin Protein 1 (HP1) binding to epigenetically marked histone tails, most notably methylated H3K9. HP1 is post-translationally phosphorylated at serine and threonine residues, and this phosphorylation has been shown to increase HP1’s binding affinity for methylated H3K9 and heterochromatin formation. To study the effect of phosphorylation on heterochromatin assembly and HP1 localization within the nucleus, the unicellular protozoan Tetrahymena thermophila was used. Tetrahymena is an ideal model for this work because cells have a dynamic chromatin environment. Tetrahymena have an HP1-like protein, tHP1, which localizes to transcriptionally silent chromatin bodies within the otherwise transcriptionally active macronucleus. tHP1 is known to be phosphorylated at threonine-64 (site one) and at either serine-102 or threonine-103 (site two). Previous work shows that when phosphorylation at both sites is prevented, tHP1 exhibits decreased localization to chromatin bodies. In order to determine which site of phosphorylation accounts for tHP1’s localization to regions of heterochromatin, mutant proteins that allow phosphorylation at only one of the two sites were generated. The efforts to engineer a mutant protein that cannot be phosphorylated at site two and to visualize the protein’s localization throughout cell development are discussed. When phosphorylation is prevented at site two, tHP1 localization to regions of heterochromatin remains intact. These results suggest that phosphorylation at site one, not site two, may be responsible for tHP1 localization to macronuclear chromatin bodies. A mechanism by which site one phosphorylation influences tHP1 targeting to regions of heterochromatin is proposed. Furthermore, bioinformatics techniques are employed to identify other tHP1-like proteins within Tetrahymena. Characterization of these proteins will likely contribute to a more complete model of how heterochromatin is assembled in Tetrahymena.