Origami has been extensively studied by engineers for its unique motions and ability to collapse to small volumes. Techniques have been studied for replicating origami-like folding motion in thick materials, but limited practical applications of these techniques have been demonstrated. Developable mechanisms are a new mechanism type that has a similar ability to collapse to a low profile. The cylindrical developable mechanism has the ability to emerge from and conform to a cylindrical surface. In this work, a few practical applications of devices with novel expanding motions are presented. The design and testing of an origami-inspired deployable ballistic barrier, which was designed by combining and modifying existing thickness accommodation techniques, is discussed. The properties of cylindrical developable mechanisms are examined and two devices designed for use with minimally invasive surgical tooling are presented. Various hinge options for small-scale cylindrical developable mechanisms are then reviewed and discussed. A planar modeling assumption for curved lamina emergent torsional joints in thin-walled cylinders is then analytically and empirically validated. Conclusions are drawn and recommendations for future work are given.

This work develops models and tools to help designers address the challenges associated with designing origami-based and developable mechanisms. These models utilize strain energy, kinematics, compliant mechanisms, and graphical techniques to make the design of origami-based and developable mechanisms approachable and intuitive. Origami-based design tools are expanded through two methods. First presented is a generalized approach for identifying single-output mechanical advantage for a multiple-input compliant mechanism, such as many origami-based mechanisms. The model is used to predict the force-deflection behavior of an origami-based mechanism (Oriceps) and is verified with experimental data from magnetic actuation of the mechanism. Second is a folding technique for thick-origami, called the regional-sandwiching of compliant sheets (ReCS), which creates flat-foldable, rigid-foldable, and self-deploying thick origami-based mechanisms. The technique is used to create mountain/valley assignments for each fold about a vertex, constraining motion to a single branch of folding. Strain energy in deflected flexible members is used to enable self-deployment. Three physical models, a simple single-fold mechanism, a degree-four vertex mechanism, and a full tessellation, are presented to demonstrate the ReCS technique. Developable mechanism design is further enabled through an exploration of their feasible design space. Terminology is introduced to define the motion of developable mechanisms while interior and exterior to a developable surface. The limits of this motion are identified using defined conditions. It is shown that the more difficult of these conditions may be treated as a non-factor during the design of cylindrical developable mechanisms given certain assumptions. These limits are then applied to create a resource for designing bistable developable mechanisms (BDMs) that reach their second stable positions while exterior or interior to a cylindrical surface. A novel graphical method for identifying stable positions of linkages using a single dominant torsional spring, called the Principle of Reflection, is introduced and implemented. The results are compared with a numerical simulation of 30,000+ mechanisms to identify possible incongruencies. Two tables summarize the results as the guide for designing extramobile and intramobile BDMs. In fulfilling the research objectives, this dissertation contributes to the scientific community of origami-based and developable mechanism design approaches. As a result of this work, practitioners will be better able to approach and design complex origami-based and developable mechanisms.

The purpose of this research is to investigate the use of compliant mechanisms in space applications and design, analyze, and test a compliant space mechanism. Current space mechanisms are already highly refined and it is unclear if significant improvements in performance can be made by continuing to refine current designs. Compliant mechanisms offer a promising opportunity to change the fundamental approach to achieving controlled motion in space systems and have potential for dramatic increases in mechanism performance given the constraints of the space environment. A compliant deployment hinge was selected for development after industry input was gathered. Concepts for large-displacement compliant hinges are investigated. A design process was developed that links the performance requirements of deployment to the design parameters of a deployment hinge. A large-displacement monolithic compliant rotational hinge, the Flex-16, is designed, analyzed, and tested. It was developed for possible application as a spacecraft deployment hinge and designs were developed using three different materials (polypropylene, titanium, and carbon nanotubes) and manufacturing processes (CNC milling, electron beam manufacturing metal rapid prototyping, and a carbon nanotube framework) on two size scales (macro and micro). A parametric finite element model allowed for prediction of prototype behavior before fabrication. The Flex-16 hinge is capable of 90 degrees of deflection without failure or contact and can be designed to meet industry requirements for space.

This thesis addresses a number of challenges designers face when designing deployable origami-based arrays, specifically joint selection, design, and placement within an array. In deployable systems, the selection and arrangement of joint types is key to how the system functions. The kinematics and performance of an array is directly affected by joint performance. This work develops joint metrics which are then used to compare joint performances, constructing a tool designers can use when selecting joints for an origami array. While often a single type of joint is used throughout an array, this work shows how using multiple types of joints within the same array can offer benefits for motion deployment, and array stiffening. Origami arrays are often used for their unique solutions for stowing and deploying large planar shapes. Folds, enabled through joints, within these patterns allow the arrays to fold compactly. However, it can be difficult to fully deploy arrays, particularly array designs with a high number of joints. In addition, it is a challenge to stabilize a fully deployed array from undesired re-folding. This work introduces a strain-energy storing joint that is used to deploy and stiffen foldable origami arrays, the Lenticular Lock (LentLock). Geometry of the LentLock is introduced and the deploying and stiffening performance of the joint is shown. Folds within an origami array create the constraints that link motion between panels, and can be used to create kinematic benefits, such as creating mechanisms with a single degree-of-freedom. While many fold-constraints are required to define motion, this work shows that origami-based system contain many redundant constraints. The removal of redundant joints does not affect the motion of the array nor the observed mobility, but may decrease the likelihood of binding, simplify the overall system and decrease actuation force. This work introduces a visual and iterative approach designers can use to identify redundant constraints in origami patterns, and techniques that can be used to remove the identified redundant constraints. The presented techniques are demonstrated by removing redundant constraints from prototyped origami mechanisms. As a result of this work, designers will be better able to approach and design deployable origami-based mechanisms.

There are different phases in any design activity, one of them being concept generation. Research in automating the conceptual design process in planar mechanisms is always challenging due to the existence of many different elements and their endless combinations. There may be instances where designers arrive at a concept without considering all the alternatives. Computational synthesis aims to arrive at a design by considering the entire space of valid designs. Different researchers have adopted various methods to automate the design process that includes existence of similar graph grammar approaches. But few methods replicate the way humans’ design. An attempt is being made in the thesis in this direction and as a first step, we focus on representing and evaluating planar mechanisms designed using graph grammars. Graph grammars have been used to represent planar mechanisms but there are disadvantages in the methods currently available. This is due to the lack of information in understanding the details of a mechanism represented by the graph since the graphs do not include information about the type of joints and components such as revolute links, prismatic blocks, gears and cams. In order to overcome drawbacks in the existing methods, a novel representation scheme has been developed. In this method, labels and x, y position information in the nodes are used to represent the different mechanism types. A set of sixteen grammar rules that construct different mechanisms from the basic seed is developed, which implicitly represents a tree of candidate solutions. The scheme is tested to determine its capability in capturing the entire set of feasible planar mechanisms of one degree of freedom including Stephenson and double butterfly linkages. In addition to the representation, another important consideration is the need for an accurate and generalized evaluator for kinematic analysis of mechanisms which, given the lack of information, may not be possible with current design automation schemes. The approach employed for analysis is purely kinematic and hence the instantaneous center of rotation method is employed in this research. The velocities of pivots and links are obtained using the instant center method. Once velocities are determined, the vector polygon approach is used to obtain accelerations and geometrical intersection to determine positions of pivots. The graph grammar based analysis module is implemented in an existing object-oriented grammar framework and the results have found this to be superior to or equivalent to existing commercial packages such as Working Model and SAM for topologies consisting of four-bar loop chain with single degree of freedom. / text

Call number: LD2668 .T4 1966 M848 / Master of Science

Cloudman S91 melanoma cells respond to a variety of endocrine factors, including melanotropins and steroid hormones. The murine S91 melanoma cell line, CCL 53.1, responded to α-melanocyte-stimulating hormone (α-MSH) in a dose- and a time-dependent manner, by increased tyrosinase activity. The minimal effective dose of α-MSH required to stimulate tyrosinase activity was 10⁻⁹M. By prolonging the exposure period of the cells to the hormone from 24 to 48, to 72 hours, the magnitude of tyrosinase stimulation was increased, but the minimal effective dose was not changed. α-MSH action involved elevation of intracellular cyclic AMP levels, and did not require the influx of extracellular calcium. Three melanotropin analogues, [Nle⁴, D-Phe⁷]-α-MSH, Ac-[Nle⁴, D-Phe⁷]-α-MSH₄₋₁₁-NH₂, and Ac-[Nle⁴, D-Phe⁷]- α-MSH₄₋₁₀-NH₂, have been shown to be more active than (alpha)-MSH in dispersing melanosomes within amphibian and reptilian integumental melanophores. These analogues also demonstrate prolonged activities and resistance to enzymatic degradation. The unique properties of these melanotropin analogues led to investigate their effects on the phenotypic expression and on the proliferation of S91 melanoma cells. The relative potency and the possible prolonged actions of the three [Nle⁴, D-Phe⁷] -substituted analogues were investigated and compared to those of α-MSH. The melanotropin analogues proved to be 100-1000 fold more active than α-MSH in stimulating tyrosinase activity. These analogues elicited significant tyrosinase activation following brief contact times with the cells, and maintained their stimulatory effects for days after removal from the culture flasks, and after the α-MSH effect had totally dissipated. Contrary to previous reports that melanotropins inhibit the proliferation of melanoma cells, α-MSH and [Nle⁴, D-Phe⁷] -α-MSH stimulated, rather than inhibited, the proliferation of CCL cells under culture conditions that allowed optimal phenotypic expression. Also, the effects of the steroids, β-estradiol, progesterone, and dexamethasone, on CCL cells were studied. Dexamethasone had the most remarkable effects, which involved stimulation of tyrosinase activity and inhibition of proliferation in monolayer culture and in soft agar. Furthermore, this study defined some of the factors that influence the endocrine responsiveness of melanoma cells. The results of this study have important implications for the regulation of phenotypic expression and of proliferation in S91 melanoma cells, and for the properties of the melanoma melanotropin receptor.

This thesis takes a step beyond the current discussion on hybrid competitive strategies (HS) by identifying the underlying mechanisms and common elements of successful hybrid strategies. Reviewing empirical and theoretical literature revealed a significant gap in this respect. Therefore, the activity-based view of strategy is introduced to the discussion on HS. In a first step, four consistent and sustainable HS concepts are developed providing the basis for deriving specific HS models. A second step identifies commonalities among these HS types and theoretically derives a synthesized, common HS model. Thirdly, the critical realist stance was selected for answering this thesis’ research questions addressing consistent HS concepts, implementations, common activities achieving external and internal fit, as well as common capabilities and resources supporting these activities. In a case study approach, semi-structured, open ended interviews combining appreciative and laddering methods are conducted with twelve interviewees from five firms. The separate analysis of ladder elements and ladders allowed distinguishing constitutional from relational elements. Based on this, fourth, an empirically revised research construct is substantiated. This research finds HS firms applying intended and consistent, but mixed strategy concepts based on generating high customer benefits through combining competitive weapons of differentiation and price or total customer cost. Moreover, HS concepts centre on three strategic building blocks: customer centricity, fulfilment of customer needs and employee orientation. Additionally, the research indicates that firms apply activities primarily for achieving fit. While all firms combine both views, no activities are directed to both fit types simultaneously. Activities deploy capabilities and resources in general on two adaptive and two absorptive mechanisms. Several practical implications derive from this thesis. First, firms can apply the synthesized model as a kind of ‘blueprint’ providing orientation for how to combine competitive advantages. Second, policy makers can apply the outcomes as principles steering firms or industries to ‘higher’ levels of performance. Last, firm managers can adapt their own as well as their firm’s behaviour accordingly.

Cancer is a major cause of morbidity and mortality affecting populations in all countries and all regions. Breast cancer (BC) is the second leading cause of cancer death among women in the UK. Although the overall survival of BC has been significantly improved due to systemic therapy in early BC, the treatment of advanced/metastatic BC remains a major challenge. The main limitation of therapeutic failure is the de novo and acquired resistance of BC cells to conventional anticancer drugs. Cancer stem cells (CSCs) have been thought to be responsible for the chemoresistance. My study demonstrated that mammospheres manifested CSC characteristics and are highly resistant to several first line anti-BC drugs. This may be due to the hypoxia in the centre of the spheres. Transfection of BC cells with NFκB p65 induces CSC characters and chemoresistance. Therefore hypoxia-induced activation of NFκB could lead to escape of CSCs from apoptosis and regenerate the tumour after conventional chemotherapy. In clinic, the relapsed cancer is commonly pan-resistant to various drugs. Development of CSCs-targeting drug will be significantly important in clinic for cancer patients. Disulfiram (DS) is a commercially available anti-alcoholism drug with strong cytotoxicity in a wide range of cancer types and has a reversing II effect on chemoresistance. In this study, the anticancer efficacy of DS on cancer cell lines and CSCs was investigated. DS was highly cytotoxic to BC cell lines in vitro in a copper (Cu)-dependent manner. CI-isobologram analysis demonstrated a synergistic effect between DS/Cu and paclitaxel (PAC) in BC cell lines. DS/Cu induces reactive oxygen species (ROS), activates JNK and p38 pathways and simultaneously inhibits NFκB activity in BC cell lines. DS/Cu may trigger intrinsic apoptotic pathway via modulation of the Bcl2 family. The in vitro clonogenicity and sphere-forming ability of BC cell lines were inhibited by DS/Cu. The common stem cell markers such as aldehyde dehydrogenase (ALDH) and CD24-/CD44+ as well as Nanog, Sox2, and Oct4 were also suppressed. In PAC resistant cell line, DS abolished CSC characters and completely reversed PAC resistance. Lipo-DS blocked NFκB activation and specifically targeted CSCs in vitro. Lipo-DS also targeted CSC population in vivo and showed very strong anticancer efficacy. This study elucidated the role of NFB in bridging hypoxia with CSC-related chemoresistance. It also investigated the fundamental anticancer mechanisms of DS. The results derived from this study indicate that further study may be able to translate DS into cancer therapeutics in the future.

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