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This thesis presents a technique for designing planar four-bar linkages by coupling optimization, dynamics and kinematics. This synthesis technique gives the designer the ability to design linkages having a desired resistance profiles under an assumed motion profile. The design approach presented in this thesis calculates the resistance forces by using both the static and the anticipated dynamic effects of the resistance loading. Almost all research to date has assumed that the static forces in the linkage dominate the dynamic forces; hence, the dynamic effects have been neglected. This thesis shows that this assumption is often invalid. The traditional approach for designing resistance-generating mechanisms has been based on closed-form methods that attempt to exactly match the resistance at a small number of discrete positions. This work uses a numerical optimization method that allows for the matching of the entire resistance curve by approximately matching a set of positions that define the shape of the curve. This work furthers the discipline of mechanism design by combining dynamics into existing linkage synthesis methods, resulting in an improved synthesis method that includes both static and dynamic effects. While this approach can be used in many applications, this work focuses on the design of exercise equipment. This focus is because exercise equipment designed to optimally stress a specific muscle group usually have a specific " strength curve " used to design the resistance load. The "strength curve" is the locus of all maximum loads moveable by the exerciser in all body part positions over the full range of motion. This application ideally suits the specification of the problem addressed in this thesis. / Master of Science

This thesis presents a technique for the optimal synthesis of planar four-bar linkages for specified force or torque generation. Unlike most previous research in mechanism force synthesis, this thesis targets linkage applications for which the mechanical advantage is prescribed but the position function is not. The advantage of this approach is that emphasis is placed on the force-generating properties of the linkage and not the output positions of the mechanism. Closed-form synthesis of force-generating linkages based on Burmester theory has recently been developed in detail. Unfortunately, closed-form methods can only be used to solve a limited class of problems and frequently require substantial intuition on the part of the designer in adjusting the input parameter specifications. The approach presented here uses optimization theory to search a solution space for the mechanism that most nearly meets the designer's specification. Use of optimization allows a greater number of constraints to be applied to the synthesis such that more practical solutions can be obtained. The proposed design technique seeks to minimize an objective function that depends primarily on the force generation properties of the linkage and secondarily on the other applied constraints. As a demonstration of the theoretical method, the optimal linkage synthesis technique is applied to a specific problem, namely, the design of a linkage for a weight-loaded exercise machine. Example solutions are generated and evaluated against the design constraints and mechanical advantage requirements. The design methodology presented has been implemented into a software package which is currently being used in industry for the design of similar linkages. / Master of Science

Understanding microscale biological processes as cells develop into tissues is one of the most important, yet most difficult, problems in modern biology. Cells encounter a dynamic chemical and physical environment and delineating the myriad of variables proves daunting with even the most sophisticated experiments. This dissertation focuses on the development and application of unique enabling technologies designed to sample and control biological microenvironments. By developing two approaches – one aimed at intracellular biochemistry and another for extracellular targets – based on photochemistry and optical force generation, research presented here will allow new areas of subcellular dynamics to be addressed. On the intracellular side, enzyme-immobilized polymeric microspheres or enzyme microstructures are placed into the cell cytosol via optical tweezers for sustained and localized chemical modification of the intracellular environment. This approach is complemented by the use of extracellular guidance barriers formed from photo-induced crosslinking of proteins. Through the use of minimally toxic photosensitizers and femtosecond (fs) near infrared (NIR) light, it is possible to fabricate three-dimensional protein structures in a living cell’s environment. Moreover, this work explores the ability to form protein structures with enzymatic activity as well as with high aspect-ratio features at micron resolution. Finally, the photochemical transformation of serotonin into a highly fluorescent visible photoproduct is investigated as a means to overcome problems associated with sample size in neurotransmitter detection during synaptic chemical signaling. Optimization of this multiphoton process entails understanding the mechanism by which the photoproduct is created and experiments towards this goal are presented here. Ultimately, the precision and flexibility of these technologies will allow access to new areas of the biosciences. / text

<div>Manual function is a key determinant of functional independence. It is well known that manual dexterity declines with aging and negatively impacts quality of life. Therefore, much work has focused on understanding the biomechanics and motor control of manual function in general, and the action of the fingers in particular. Previous research has revealed consistent patterns of interdependence in the action of the fingers that (1) alter with age, and (2) have consequences for manual control, and thereby manual function. Most of this previous work on finger behavior quantifies finger capacities and interactions in terms of maximal forces. However, activities of daily living likely require individuals to rapidly change forces more frequently than produce maximal forces. Therefore, the present work quantifies, for the first time, finger capacities and interactions during rapid increase and decrease in finger forces, and how these quantities change with age. </div><div><br></div><div>Young and older adults performed maximal force production tasks and also tasks that required them to rapidly increase or decrease finger forces from three initial force levels using multiple combinations of the fingers of their dominant hand. The maximal finger forces and force rates, and the interdependence of the fingers (enslaving, individuation, sharing, and deficit) during both behaviors are reported in detail. Overall, similarities in finger behavior patterns obtained from maximal force and maximal force rates were observed. However, some differences are also noted, and novel findings (especially, comparison between force increase and decrease) are reported. Finally, future work that may lead to clinical applications is discussed. </div>

Microtubules are a part of the cell cytoskeleton that performs different functions, such as providing the mechanical support for the shape of a cell, acting as tracks along which the motor protein move organelles from one part of the cell to another, or the forming mitotic spindle during the cell division. The microtubules are dynamic structures, namely they can grow and shrink. The phase of microtubule growth alternates with the phase of shrinkage that results in the dynamic microtubule network in the cell. However, to form stable and spatially well-defined structures, such as a mitotic spindle, the cell needs to control this stochastic process. This is done by microtubule-associated proteins (MAPs). One class of MAPs is the proteins of XMAP216/Dis1 family, which are microtubule polymerases. The founding member of this family is X. laevis XMAP215. XMAP215 is a processive polymerase acting on the microtubule plus end. XMAP215 binds either directly or reaches the microtubule plus end by the diffusion along the microtubule lattice. Being at the microtubule plus-end XMAP215 stays there transiently and helps to incorporate up to 25 tubulin dimers into microtubule lattice before it dissociates and, therefore, it processively tracks the growing microtubule end during polymerization. There are two hypothesis of microtubule assembly promotion: (i) XMAP215 repeatedly releases an associated tubulin dimer into the microtubule growing plus end or (ii) structurally stabilizes a polymerized tubulin intermediate at the growing plus end and, therefore, preventing depolymerization events. The first way results into the increase of on-rate of tubulin dimers at the microtubule end, whereas the second way results into the decrease of off-rate of tubulin dimers at the microtubule end. Here, I show the study of the mechanism of microtubule growth acceleration by XMAP215 and the dependence of XMAP215 polymerization activity on the applied force. To answer these questions, I investigated the addition of tubulin dimers to the plus end of the microtubule by XMAP215 and how this addition depends on the applied force. XMAP215 remains at the microtubule end for several rounds of tubulin addition surfing both growing and shrinking microtubule ends. Therefore, if one could track the position of the XMAP215 molecules at the very tip of a microtubule with sufficient resolution, it would provide the information about the dynamics of the microtubule end. The technique, which can detect the position of the object of interest with high spatial and temporal resolution in addition to being able to exert a force, is an optical trap. A calibrated optical trap not only provides a good measure of displacement but also enables force measurements. To monitor the position of the molecules of interest, the molecules of interest are usually attached to a microsphere. Hence, I tethered XMAP215 to a microsphere held by an optical trap, and used XMAP215 as a handle to interact with the microtubule tip. When the microtubule grows, the XMAP215 coated microsphere will move in the optical trap and this movement can be detected with high temporal and spatial resolution. My work demonstrates that cooperatively working XMAP215 molecules can not only polymerize microtubule but also harness the energy of microtubule polymerization or depolymerization to transport some cargo. There is an evidence that orthologues of XMAP215 in budding yeasts, fission yeasts and Drosophila localize on the kinetochores. Therefore, the ability of the bearing some load during microtubule polymerization could be potentially important for the XMAP215 functioning during cell division. I also showed the influence of external force applied to the XMAP215 molecules. Pointing toward microtubule growth, a force of 0.5 pN applied to the microtubule tip-coupled XMAP215-coated microsphere increases XMAP215 polymerization activity. However, the force of the same magnitude but applied against microtubule growth does not affect XMAP215 polymerization activity. This result can be explained by the fact, that the force acting in the direction of microtubule growth constrains XMAP215 to be at the very microtubule tip. Hence, XMAP215 can not diffuse away from plus-end and there is higher chance to incorporate tubulin dimers into the microtubule plus-end. The on- and off-rate of tubulin dimers at the microtubule end are both decreased when the external force applied either in direction of microtubule growth or opposite to it. The external force affects the off-rate slightly stronger than on-rate of tubulin dimer. Taking together, my study gives new insights into the mechanism of microtubule polymerization by XMAP215 and shows some novel properties of this protein.

In recent decades, Sweden's and most of Europe's defense budgets have fallen. It has created a greater need between countries for the cost-effective maintenance of defense capabilities. The Swedish Finnish Naval Task Group (SFNTG) is a part of this trend. It will be operational in 2023 and aims to jointly use the marine forces of the countries in a cost-effective way. In this case study, the cooperation in SFNTG between Swedish and Finnish combat boats is investigated. Based on the increased need for defense cooperation, different concepts for describing and applying collaborations in the short and long term have been created. In this work the term Joint Force Generation was used to analyze the different systems of the Swedish and Finnish combat boats. The term Pooling &amp; Sharing was used to analyze cooperation in the longer term. The purpose is to explore how the political and strategic plans will work on the tactical level of cooperation. Empiricism has been gathered through interviews by officers from both countries. Literature study of reports on the meaning of cooperation have been made. The work was limited to research &amp; development, maintenance, management and material purchases. The interviews showed that the different communicationsystems in the combat boats required extra human resources and a common communicationsystem was desirable. Conclusions are that there are shortcomings of a functioning relationship for the combat boats to meet the requirements of the year 2023. The use of each other's bases as another goal must coordinate logistics, training and warehousing to create better impact. In the longer perspective a greater political understanding must be for the importance of the joint material purchases. The major gain is in cost savings through various forms of collective research development.

Microtubules are a part of the cell cytoskeleton that performs different functions, such as providing the mechanical support for the shape of a cell, acting as tracks along which the motor protein move organelles from one part of the cell to another, or the forming mitotic spindle during the cell division. The microtubules are dynamic structures, namely they can grow and shrink. The phase of microtubule growth alternates with the phase of shrinkage that results in the dynamic microtubule network in the cell. However, to form stable and spatially well-defined structures, such as a mitotic spindle, the cell needs to control this stochastic process. This is done by microtubule-associated proteins (MAPs). One class of MAPs is the proteins of XMAP216/Dis1 family, which are microtubule polymerases. The founding member of this family is X. laevis XMAP215. XMAP215 is a processive polymerase acting on the microtubule plus end. XMAP215 binds either directly or reaches the microtubule plus end by the diffusion along the microtubule lattice. Being at the microtubule plus-end XMAP215 stays there transiently and helps to incorporate up to 25 tubulin dimers into microtubule lattice before it dissociates and, therefore, it processively tracks the growing microtubule end during polymerization. There are two hypothesis of microtubule assembly promotion: (i) XMAP215 repeatedly releases an associated tubulin dimer into the microtubule growing plus end or (ii) structurally stabilizes a polymerized tubulin intermediate at the growing plus end and, therefore, preventing depolymerization events. The first way results into the increase of on-rate of tubulin dimers at the microtubule end, whereas the second way results into the decrease of off-rate of tubulin dimers at the microtubule end. Here, I show the study of the mechanism of microtubule growth acceleration by XMAP215 and the dependence of XMAP215 polymerization activity on the applied force. To answer these questions, I investigated the addition of tubulin dimers to the plus end of the microtubule by XMAP215 and how this addition depends on the applied force. XMAP215 remains at the microtubule end for several rounds of tubulin addition surfing both growing and shrinking microtubule ends. Therefore, if one could track the position of the XMAP215 molecules at the very tip of a microtubule with sufficient resolution, it would provide the information about the dynamics of the microtubule end. The technique, which can detect the position of the object of interest with high spatial and temporal resolution in addition to being able to exert a force, is an optical trap. A calibrated optical trap not only provides a good measure of displacement but also enables force measurements. To monitor the position of the molecules of interest, the molecules of interest are usually attached to a microsphere. Hence, I tethered XMAP215 to a microsphere held by an optical trap, and used XMAP215 as a handle to interact with the microtubule tip. When the microtubule grows, the XMAP215 coated microsphere will move in the optical trap and this movement can be detected with high temporal and spatial resolution. My work demonstrates that cooperatively working XMAP215 molecules can not only polymerize microtubule but also harness the energy of microtubule polymerization or depolymerization to transport some cargo. There is an evidence that orthologues of XMAP215 in budding yeasts, fission yeasts and Drosophila localize on the kinetochores. Therefore, the ability of the bearing some load during microtubule polymerization could be potentially important for the XMAP215 functioning during cell division. I also showed the influence of external force applied to the XMAP215 molecules. Pointing toward microtubule growth, a force of 0.5 pN applied to the microtubule tip-coupled XMAP215-coated microsphere increases XMAP215 polymerization activity. However, the force of the same magnitude but applied against microtubule growth does not affect XMAP215 polymerization activity. This result can be explained by the fact, that the force acting in the direction of microtubule growth constrains XMAP215 to be at the very microtubule tip. Hence, XMAP215 can not diffuse away from plus-end and there is higher chance to incorporate tubulin dimers into the microtubule plus-end. The on- and off-rate of tubulin dimers at the microtubule end are both decreased when the external force applied either in direction of microtubule growth or opposite to it. The external force affects the off-rate slightly stronger than on-rate of tubulin dimer. Taking together, my study gives new insights into the mechanism of microtubule polymerization by XMAP215 and shows some novel properties of this protein.

No description available.

Approved for public release; distribution is unlimited. / MBA Professional Report / Over the years, the United Nations' (UN) peacekeeping operations have increased significantly. When a crisis develops, the UN is expected to respond. It examines the overall situation in order to assess the political and military goals, required composition of force, equipment, training, financial implications, circumstances of deployment and effectiveness of the peacekeeping operation required. The UN does not have any permanent force structure; it is dependent on its member States for contribution of forces, though the equipment may or may not be provided by the troops' contributing countries. The UN has a standard procedure for acquiring peacekeeping operations/services. The process is a contract between the UNDPKO and the troops' contributing countries. Though there are similarities betweeen UN-followed contract management process and the generaly accepted contract management process identified in the contract management body of knowledge, there are many differences as well. The purpose of this study is both to evaluate the existing UN contract management process being followed to acquire peacekeeping operations/services from various troops' contributing countries against the generally accepted contract management process identified in the contract management body of knowledge as well as to evaluate the effectiveness of the UN contract management process maturity so as to assess the effectiveness of the UN contract management process for obtaining peacekeeping operations/services from troops' contributing countries.