Locomotion is paramount in enabling human beings to effectively respond in space and time to meet different needs. There are 2 million Americans living with an amputation and the majority of those amputations are of the lower limbs. Although current powered prostheses can accommodate walking, and in some cases running, basic functions like hiking or walking on various non-rigid or dynamic terrains are requirements that have yet to be met. This paper focuses on the mechanisms involved during human locomotion, while transitioning from rigid to compliant surfaces such as from pavement to sand, grass or granular media. Utilizing a unique tool, the Variable Stiffness Treadmill (VST), as the platform for human locomotion, rigid to compliant surface transitions are simulated. The analysis of muscular activation during the transition from rigid to compliant surfaces reveals specific anticipatory muscle activation that precedes stepping on the compliant surface. These results are novel and important since the evoked activation changes can be used for altering the powered prosthesis control parameters to adapt to the new surface, and therefore result in significantly increased robustness for smart powered lower limb prostheses.

It is an exciting time in wearable robotics with new devices for spinal cord injury, gait assistance, rehabilitation, strength enhancement, manufacturing, construction, and recreation. This review will focus on lower limb wearable robotic systems that include orthoses, prostheses, and exoskeletons. The promises and challenges of these systems will be described. A review of some of the exciting systems will be presented.

A practical pilot plant convergent synthesis of MR antagonist LY2623091 was established. For synthesis convergence, a vinyl bromide geometric isomer and chiral alaninol derivative were required building blocks. Key to the synthesis route development is a stereoselective synthesis of the E-vinyl bromide via a sequential double Heck reaction, Suzuki–Miyaura cross-coupling of the vinyl bromide, a selective nitro reduction, and a highly sensitive cyanamide hydrolysis to the urea. Improvements in yield and processing were accomplished by two sets of telescoping methods which decreased the manufacturing time and provided purity enhancements.

Passive prosthetic feet are not able to provide non-amputee kinematics and kinetics for the ankle joint. Persons with amputations show reduced interlimb symmetry, slower walking speeds, and increased walking effort. To improve ankle range of motion and push off, various powered prosthetic feet were introduced. This feasibility study analyzed if predefined motor reference trajectories can be used to achieve non-amputee ankle biomechanics during walking with the powered prosthetic foot, Walk-Run Ankle. Trajectories were calculated using the desired ankle angle and ankle moment based spring deflection at a given spring stiffness. Model assumptions of the motor-spring interaction were well reflected in the experiment. The powered foot was able to improve range of motion, peak ankle power, average positive ankle power, peak ankle moment, and positive moment onset compared to a passive usage of the foot. Furthermore, symmetry improvements were identified for step length and duty factor. Further studies with an increased number of subjects are needed to show if the approach is also valid for other amputees. Using this method as a base, trajectories can be further individualized using human in the loop optimization targeting a reduction of user effort, improved stability, or gait symmetry.

Background: Current prosthetic ankle joints are designed either for walking or for running. In order to mimic the capabilities of an able-bodied, a powered prosthetic ankle for walking and running was designed. A powered system has the potential to reduce the limitations in range of motion and positive work output of passive walking and running feet.Methods: To perform the experiments a controller capable of transitions between standing, walking, and running with speed adaptations was developed. In the first case study the system was mounted on an ankle bypass in parallel with the foot of a non-amputee subject. By this method the functionality of hardware and controller was proven.Results: The Walk-Run ankle was capable of mimicking desired torque and angle trajectories in walking and running up to 2.6 m/s. At 4 m/s running, ankle angle could be matched while ankle torque could not. Limited ankle output power resulting from a suboptimal spring stiffness value was identified as a main reason.Conclusions: Further studies have to show to what extent the findings can be transferred to amputees.

An efficient synthesis of LY2886721 (1) in five steps and 46% overall yield from the chiral nitrone cycloadduct 2 is presented. Minimizing formation of a des-fluoro impurity during hydrogenolysis to cleave the isoxazolidine ring and remove the benzyl chiral auxiliary was a key challenge. Installation of the aminothiazine moiety required careful stoichiometry control of the reagents BzNCS and CDI, including in situ conversion monitoring, to minimize byproduct formation. A remarkably regioselective peptide coupling afforded 1 without competing acylation at the aminothiazine nitrogen or bis-acylation. Consideration of the combined chemistry and crystallization process identified an optimal solvent system for the peptide coupling and a reactive crystallization that afforded 1 in high purity and with physical property control. A slurry milling operation near the end of the crystallization, followed by "pH cycles" to digest fines formed during milling, significantly reduced the crystal aspect ratio and provided desirable API bulk density and powder flow properties.

A scalable, asymmetric synthesis of (3aS,6aS)-6a-(5-bromo-2-fluorophenyl)-1-((R)-1-phenylpropyl)tetrahydro-1H,3H-furo[3,4-c]isoxazole, a key intermediate in the synthesis of LY2886721, is reported. Highlights of the synthesis include the development of an asymmetric [3 + 2] intramolecular cycloaddition facilitated by trifluoroethanol, and the development of a new synthesis of (R)-N-(1-phenylpropyl)hydroxylamine tosylate which proceeds through a p-anisaldehyde imine and avoids the formation of toxic hydrogen cyanide gas as a byproduct. The synthesis proceeds over four steps and provides the product in 36% overall yield.

A Joint Torque Augmentation Robot (JTAR) was developed to aid walking in an unconstrained outdoor environment. JTAR is a unidirectional, compliant actuator based wearable robot that is designed to power an ankle joint. Since the robot is used to navigate uneven terrain, nearly full ankle range of motion is required to accomplish this goal. The device powers the forward locomotion while permitting out of plane kinematic motion to occur. Metabolic savings of 9% to 20% have been observed while using the JTAR device, when compared to an unpowered/uncoupled state.

Spring-based actuators are important in the design of wearable robotic systems. These actuators can store and release energy, and reduce the peak power requirements. Reducing these requirements allows the system to function with smaller and lighter-weight motors. Three actuators are compared: a lead screw actuator, a robotic tendon actuator, and a JackSpring™ actuator. The robotic tendon actuator adds a spring in series to the traditional actuator. The JackSpring actuator is a lead screw with a finite stiffness. A formal set of equations for the three actuators is added to Table 1 which summarizes the torque, angular speed, and power for each one. The traditional lead screw actuator cannot store and release energy and the power into the actuator must equal the power out of the actuator. The robotic tendon actuator stores and releases energy, and if a tuned spring is chosen, the power requirements can be greatly reduced. For example, if the desired external motion matches the natural frequency of the system, the motor does not need to rotate. The JackSpring actuator is a unique actuator because the stiffness and motion are coupled. It is shown that if the spring is tuned properly, the power requirements can be greatly reduced, as well.

To fuel clinical development of the experimental CNS medicine LY2140023, we developed a scalable route for the multistep synthesis of a pivotal synthetic intermediate. The core of the conformationally restricted glutamic acid-based amino acid analogue was built via a Rh-catalyzed cyclopropanation of thiophene. Regioselective functionalization of the remaining double bond was achieved by a hydroboration/oxidation sequence followed by a Bucherer-Bergs reaction to give a hydantoin with the targeted L-glutamic acid configuration. Subsequent resolution, oxidation state, and protecting group manipulations gave the key intermediate in an overall nine-step scalable streamlined route starting from thiophene.

A robotic tendon is modeled and the stiffness of the spring is tuned so that the spring power reduces the peak motor power and energy required for ankle gait. When determining stiffness from gait literature, it is usually assumed that one side of the spring is fixed. We assume that the spring is translating to derive a second method to calculate stiffness. By choosing a tuned spring based on a “dynamic stiffness”, the motor velocity was shown to be constant during the loading phase of ankle gait. We simulated this system and showed that energy was reduced and peak power was dramatically reduced. The constant velocity controller was implemented on a powered ankle foot orthosis and test data was correlated with the simulation.

Stroke is the leading cause of long-term disability in the US, and for many it causes loss of gait function. The purpose of this research is to examine stroke survivors' gait adaptations to training on the powered ankle-foot orthosis (PAFO). Of particular interest is the stroke survivors' ability to learn how to store and release energy properly while using the device. The PAFO utilizes robotic tendon technology and supports motion with a single degree of freedom - ankle rotation in the sagittal plane. This actuator comprises a motor and series spring. The user interacts with the output side of the spring while the robot controls the input side of the spring such that typical able-body ankle moments would be generated, assuming able-body ankle kinematics are seen at the output side of the spring. Three individuals post-stroke participated in a 3-week training protocol. Outcome measures (temporal, kinematic and kinetic) were derived from robot sensors and recorded for every step. These data are used to evaluate each stroke survivor's adaptations to robotic gait assistance. The robot was worn only on the paretic ankle. For validation of the kinematic results, motion capture data were collected on the third subject. All subjects showed increased cadence, ankle range of motion and power generation capabilities. Additionally, all subjects were able to achieve a larger power output than power input from the robot. Motion capture data collected from Subject 3 validated the robot sensor kinematic data on the affected side, but also demonstrated an unexpected gait adaptation on the unaffected ankle. Sensors on the gait-assisting robot provide large volumes of valuable information on how gait parameters change over time. We have developed key gait evaluation metrics based on the available robot sensor information that may be useful to future researchers. All subjects adapted their gait to the robotic assistance and many of their key metrics moved closer to typical able-body values. This suggests that each subject learned to utilize the assistive moments generated by the robot, despite having no predefined ankle trajectory input from the robot. The security of being harnessed on the treadmill led to more dramatic and favorable results. (C) Koninklijke Brill NV, Leiden, 2011

With over 600 thousand people each year surviving a stroke, it has become the leading cause of serious long-term disability in the United States [1], [2]. The adverse financial and social conditions attributed to stroke have prompted researchers and entrepreneurs to explore the viability of rehabilitation robots. The Powered Ankle Foot Orthosis (PAFO) utilizes robotic tendon technology and supports motion with a single degree of freedom, ankle rotation in the Sagittal plane. Motion capture data, robot sensor data, and functional 6 minute walk data were collected on three stroke subjects. All subjects had some positive changes in their key gait variables while using the PAFO. These changes were more dramatic while harnessed and using a treadmill as opposed to walking over ground. Robot sensor data showed significant improvements on key variables for the three subjects. Motion capture data showed improvements in knee range of motion for subject 1, and the 6 minute walk data showed an increase in distance walked for subjects 1 and 3. Comfort, stability, and robustness proved to be critical design parameters for developing a gait therapy robot capable of collecting repeatable data with low variability.

Examples of the 1,4-migration of a palladium moiety in aryl- and alkylpalladium intermediates to the acyl position of an aldehyde or formamide have been observed. The resulting acylpalladium intermediate can undergo ester or carbamate formation by reaction with an alcohol; decarbonylation, followed by beta hydride elimination to an alkene; reaction with an organomercurial to form an ester; or alkene insertion. Deuterium-labeling studies have been used to confirm the palladium migration mechanism.

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