There are two studies in this dissertation. Both are about a program called “PICK a Partner.” The first study looked at how the program went for 682 people from the community who were taught PICK. These people ranged in age from 18 to 25. Those in attendance were given questions at the beginning of the program about their thoughts, perceptions, and knowledge regarding dating relationships. They were given these same questions at the end of the program. The scores on the questions at the end of the program were compared with scores on the questions at the beginning of the program. Peoples’ scores increased from before to after on all four questionnaires. These scores were also compared with scores from a group of students aged 18 to 25 from a university. Those that attended the program had higher scores; the scores of those from the university who did not attend the program stayed about the same. The second study examined how teachers influence scores and how individual characteristics of participants influence change in scores. The second study showed that teacher characteristics do matter somewhat in helping participants increase in knowledge. In addition, how religious a person is and whether they are a man or woman also matter, but only a little, in helping participants increase in knowledge. Future studies on PICK and the strengths and weaknesses of these studies are discussed.

<p>This study investigates a new interaction technique for collaboration on handheld computers called Pick-and-Drop. The technique is an extension of the popular Drag-and-Drop method used in many graphical interfaces today, but with Pick-and-Drop on-screen objects can be picked from one screen with a pen and dropped onto another. </p><p>The aim of the study is to answer whether Pick-and-Drop promote collaboration among children by letting them focus more on other users and the task at hand than on the computer interaction. The study also investigates in what way collaborative situations can benefit from Pick-and-Drop. </p><p>A prototype Pick-and-Drop system was implemented on four customized handheld computers equipped with wireless network communication. The prototype allowed spontaneous collaboration using ad-hoc networks and peer-to-peer communication. Radio Frequency Identification (RFID) tags were used to identify the pens when picking and dropping objects from the screen. </p><p>Ten children aged 6-7 years old participated in the study at an after- school recreational centre. They tried Pick-and-Drop by playing a collaborative game of buying and selling apples using golden coins represented as icons on the screen. The test was video filmed for later analysis. </p><p>The study showed that Pick-and-Drop offers effective collaborative interaction based on a mix of turn taking and concurrent interaction. Users do not have to switch focus when using an application or sharing data as the interaction style stays the same. There was an interesting difference in control over the interaction when users shared objects by “giving” or by “taking”. Users stayed in better control when they shared objects through giving.</p>

Niemann-Pick Type C (NPC) disease is an autosomal recessive disorder that results in accumulation of unesterified cholesterol in late endosomes/lysosomes (LE/Ls), leading to progressive neurodegeneration and premature death. Microglia are resident immune cells of the central nervous system, which upon activation can secrete potentially neurotoxic molecules such as tumor necrosis factor-alpha (TNFα). Inappropriate activation of microglia has been implicated in NPC disease. Primary microglia cultures from the cerebral cortex of Npc1-/- mice have an altered cholesterol distribution characteristic of NPC-deficient cells. Immunocytochemical analysis revealed increased TNFα staining in Npc1-/- microglia. However, Npc1-/- and Npc1+/+ microglia showed similar mRNA levels of pro-inflammatory cytokines and similar levels of TNFα secretion. To determine whether Npc1-/- microglia contribute to neuron death in NPC disease, microglia were co-cultured with cerebellar granule cells. Surprisingly, the extent of neuronal death was the same in neurons cultured with Npc1+/+ or Npc1-/- microglia. Thus, Npc1-/- microglia have an altered phenotype compared to Npc1+/+ microglia, but this does not lead to neuron death in an in vitro co-culture system. Treatment options for NPC disease remain limited. A consequence of cholesterol sequestration in the LE/Ls, is that cholesterol movement to the endoplasmic reticulum, where cholesterol metabolism is regulated, is impaired. Cyclodextrin (CD), a compound that binds cholesterol, has recently been found to delay the onset of neurological symptoms and prolong life of Npc1-/- mice. Since the brain consists of both neurons and glia, it remains unclear if CD acts directly on neurons and/or other cells in the brain. Neurons cultured from the cerebellum and astrocytes cultured from the cortex of Npc1-/- mice were treated with a low dose (0.1mM) of CD. This treatment decreased cholesterol sequestration and decreased the rate of cholesterol synthesis in Npc1-/- neurons and astrocytes. CD also decreased mRNAs encoding proteins involved in cholesterol synthesis in Npc1-/- neurons and increased genes involved in cholesterol efflux in Npc1-/- astrocytes. Moreover, CD increased cholesterol esterification in Npc1-/- astrocytes. These results suggest that cholesterol trapped in LE/Ls in Npc1-/- neurons and astrocytes was released by CD treatment and reached the ER, thereby regulating cholesterol homeostasis. / Experimental Medicine

In this thesis, a strategy to accomplish pick-and-place operations using a six degree-of-freedom (DOF) robotic arm attached to a wheeled mobile robot is presented. This research work is part of a bigger project in developing a robotic-assisted nursing to be used in medical settings. The significance of this project relies on the increasing demand for elderly and disabled skilled care assistance which nowadays has become insufficient. Strong efforts have been made to incorporate technology to fulfill these needs. Several methods were implemented to make a 6-DOF manipulator capable of performing pick-and-place operations. Some of these methods were used to achieve specific tasks such as: solving the inverse kinematics problem, or planning a collision-free path. Other methods, such as forward kinematics description, workspace evaluation, and dexterity analysis, were used to describe the manipulator and its capabilities. The manipulator was accurately described by obtaining the link transformation matrices from each joint using the Denavit-Hartenberg (DH) notations. An Iterative Inverse Kinematics method (IIK) was used to find multiple configurations for the manipulator along a given path. The IIK method was based on the specific geometric characteristic of the manipulator, in which several joints share a common plane. To find admissible solutions along the path, the workspace of the manipulator was considered. Algebraic formulations to obtain the specific workspace of the 6-DOF manipulator on the Cartesian coordinate space were derived from the singular configurations of the manipulator. Local dexterity analysis was also required to identify possible orientations of the end-effector for specific Cartesian coordinate positions. The closed-form expressions for the range of such orientations were derived by adapting an existing dexterity method. Two methods were implemented to plan the free-collision path needed to move an object from one place to another without colliding with an obstacle. Via-points were added to avoid the robot mobile platform and the zones in which the manipulator presented motion difficulties. Finally, the segments located between initial, final, and via-points positions, were connected using straight lines forming a global path. To form the collision-free path, the straight-line were modified to avoid the obstacles that intersected the path. The effectiveness of the proposed analysis was verified by comparing simulation and experimental results. Three predefined paths were used to evaluate the IIK method. Ten different scenarios with different number and pattern of obstacles were used to verify the efficiency of the entire path planning algorithm. Overall results confirmed the efficiency of the implemented methods for performing pick-and-place operations with a 6-DOF manipulator.

In this study, we consider the Air Cargo Scheduling Problem based on a real life application. The aim is to move cargo and passengers that have different priorities and delivery time window, from a number of origin airports to destination airports by means of a transportation system. The system has predefined carrier routes and a heterogeneous fleet of aircraft. The problem is formulated as a heterogeneous vehicle, multi commodity, pick-up, and delivery network flow problem with a large set of system specific constraints. The proposed model determines set of movement requirements assigned on each route leg and number and type of aircraft assigned for each route in a reasonable amount of time. The model is tested with the real and generated data and the results are compared with the current methodology under different scenarios. The model produced better results in a short amount of time compared to the current methodology.

Robotic automation has been the major driving force in modern industrial developments. High speed pick-and-place operations find their place in many manufacturing applications. The goal of this project is to develop a class of high speed robots that has a planar workspace. The presented robots are intended for pick-and-place applications that have a relatively large workspace. In order to achieve this goal, the robots must be both stiff and light. The design strategies adapted in this study were expanded from the research work by Prof Khajepour and Dr. Behzadipour. The fundamental principles are to utilize a parallel mechanism to enhance robot stiffness and cable construction to reduce moving inertia. A required condition for using cable construction is the ability to hold all cables under tension. This can only be achieved under certain conditions. The design phase of the study includes a static analysis on the robot manipulator that ensures certain mechanical components are always held under tension. This idea is extended to address dynamic situations where the manipulator velocity and acceleration are bounded. Two concept robot configurations, 2D-Deltabot, and 2D-Betabot are presented. Through a series of analyses from the robot inverse kinematic model, the dynamic properties of a robot can be computed in an effective manner. It was determined that the presented robots can achieve 4g acceleration and 4m/s maximum speed within their 700mm by 100mm workspace with a pair of 890W rotary actuators controlling two degrees of freedom. The 2D-Deltabot was chosen for prototype development. A kinematics calibration algorithm was developed to enhance the robot accuracy. Experimental test results had shown that the 2D-Deltabot was capable of running at 81 cycles per minute on a 730mm long pick-and-place path. Further experiments showed that the robot had a position accuracy of 0. 62mm and a position repeatability of 0. 15mm, despite a few manufacturing errors from the prototype fabrication.

Robotic automation has been the major driving force in modern industrial developments. High speed pick-and-place operations find their place in many manufacturing applications. The goal of this project is to develop a class of high speed robots that has a planar workspace. The presented robots are intended for pick-and-place applications that have a relatively large workspace. In order to achieve this goal, the robots must be both stiff and light. The design strategies adapted in this study were expanded from the research work by Prof Khajepour and Dr. Behzadipour. The fundamental principles are to utilize a parallel mechanism to enhance robot stiffness and cable construction to reduce moving inertia. A required condition for using cable construction is the ability to hold all cables under tension. This can only be achieved under certain conditions. The design phase of the study includes a static analysis on the robot manipulator that ensures certain mechanical components are always held under tension. This idea is extended to address dynamic situations where the manipulator velocity and acceleration are bounded. Two concept robot configurations, 2D-Deltabot, and 2D-Betabot are presented. Through a series of analyses from the robot inverse kinematic model, the dynamic properties of a robot can be computed in an effective manner. It was determined that the presented robots can achieve 4g acceleration and 4m/s maximum speed within their 700mm by 100mm workspace with a pair of 890W rotary actuators controlling two degrees of freedom. The 2D-Deltabot was chosen for prototype development. A kinematics calibration algorithm was developed to enhance the robot accuracy. Experimental test results had shown that the 2D-Deltabot was capable of running at 81 cycles per minute on a 730mm long pick-and-place path. Further experiments showed that the robot had a position accuracy of 0. 62mm and a position repeatability of 0. 15mm, despite a few manufacturing errors from the prototype fabrication.

In this study we discuss the Vehicle Routing Problem with multiple use of vehicles (VRPM). In this variant of the routing problem the vehicles may replenish at any time at the depot. We present a detailed review of existing literature and propose two mathematical models to solve the VRPM. For these two models and their several variants we provide computational results based on the test problems taken from the literature. We also discuss a case study in which we are simultaneously dealing with side constraints such as time windows, working hour limits, backhaul customers and a heterogeneous vehicle fleet.

This work analyzes human-in-the-loop robotic systems to determine where human input can be most beneficial to a collaborative task. This is accomplished by implementing a pick-and-place task using a human-in-the-loop robotic system and determining which segments of the task, when replaced by human guidance, provide the most improvement to overall task performance and require the least cognitive effort. The first experiment entails implementing a pick and place task on a commercial robotic arm. Initially, we look at a pick-and-place task that is segmented into two main areas: coarse approach towards a goal object and fine pick motion. For the fine picking phase, we look at the importance of user guidance in terms of position and orientation of the end effector. Results from this initial experiment show that the most successful strategy for our human-in-the-loop system is the one in which the human specifies a general region for grasping, and the robotic system completes the remaining elements of the task. We extend this study to include a second experiment, utilizing a more complex robotic system and pick-and-place task to further analyze human impact in a human-in-the-loop system in a more realistic setting. In this experiment, we use a robotic system that utilizes an Xbox Kinect as a vision sensor, a more cluttered environment, and a pick-and-place task that we segment in a way similar to the first experiment. Results from the second experiment indicate that allowing the user to make fine tuned adjustments to the position and orientation of the robotic hand can improve task success in high noise situations in which the autonomous robotic system might otherwise fail. The experimental setups and procedures used in this thesis can be generalized and used to guide similar analysis of human impact in other human-in-the-loop systems performing other tasks.

Ebolavirus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection and in many outbreaks, case fatality rate exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV. Here we report the properties of a benzylpiperazine adamantane diamide-derived compound identified in a screen for inhibitors of EboV infection. We found that the inhibitor is specific, reversible, and that the target(s) for inhibition are present in cells and not in virus particles. The compound is not an inhibitor of acid pH-dependent endosome protease activity, which is required for EboV infection. Treatment of cells with this compound causes accumulation of cholesterol in late endosomes and lysosomes (LE/LY), suggesting it inhibits one or more proteins involved in regulation of cholesterol uptake into cells. Using mutant cell lines and informative derivatives of the inhibitor, we found the inhibitor target is the endosomal membrane protein Niemann-Pick C1 (NPC1). NPC1 is a polytopic LE/LY membrane protein that mediates uptake of lipoprotein-derived cholesterol into cells. We find that NPC1 is essential for EboV infection, that NPC1 binds to the protease-cleaved GP1 subunit of the EboV glycoprotein, and that the anti-viral compound inhibits infection by targeting NPC1 and interfering with binding to GP1. Furthermore, analysis of viral variants resistant to the anti-viral compound revealed that the residues which confer resistance are located on the surface of the receptor binding domain of GP1. Combined with the results of previous studies of GP structure and function, our findings support a model of EboV infection in which cleavage of the GP1 subunit by endosomal cathepsin proteases removes heavily glycosylated domains to expose the N-terminal domain, which is a ligand for NPC1 and regulates membrane fusion by the GP2 subunit. Thus, NPC1 is essential for EboV entry and a target for anti-viral therapy.