Psoriasis is a multifactorial disease of uncertain etiology that affects approximately 2% of the population (1). Psoriatic lesions are characterized by a clinical triad consisting of skin induration, scaling, and erythema. The histologic correlates of these clinical findings include inflammation, abnormal keratinocyte proliferation/terminal differentiation, and dermal angiogenesis. The inflammatory infiltrate, particularly pronounced at the dermal-epidermal junction, consists largely of activated T cells and antigen-presenting cells (APCs) and precedes the development of epidermal hyperproliferation (2). Increased levels of inflammatory cytokines have been detected in lesional psoriatic epidermis, which may result in the potentiation of T-cell activation (3) as well as hyperproliferation and accelerated differentiation of keratinocytes (4, 5). These and other data derived from T cell-based therapeutics (6-8) suggest that activated T cells play an important role in triggering and perpetuating the disease. Engagement of the B7 family of molecules on antigen-presenting cells with their T cell-associated ligands, CD28 and CD152 (cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell-dependent neoantigens, bacteriophage φX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell-dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell-mediated diseases.

The paper describes the design and control of a transfemoral prosthesis with powered knee and ankle joints. The initial prototype is a pneumatically actuated powered-tethered device, which is intended to serve as a laboratory test bed for a subsequent self-powered version. The prosthesis design is described, including its kinematic optimization and the design of a three-axis socket load cell that measures the forces and moments of interaction between the socket and prosthesis. A gait controller is proposed based on the use of passive impedance functions that coordinates the motion of the prosthesis with the user during level walking. The control approach is implemented on the prosthesis prototype and experimental results are shown that demonstrate the promise of the active prosthesis and control approach in restoring fully powered level walking to the user.

This paper describes a control architecture and intent recognition approach for the real-time supervisory control of a powered lower limb prosthesis. The approach infers user intent to stand, sit, or walk, by recognizing patterns in prosthesis sensor data in real-time, without the need for instrumentation of the sound-side leg. Specifically, the intent recognizer utilizes time-based features extracted from frames of prosthesis signals, which are subsequently reduced to a lower dimensionality (for computational efficiency). These data are initially used to train intent models, which classify the patterns as standing, sitting, or walking. The trained models are subsequently used to infer the user's intent in real-time. In addition to describing the generalized control approach, this paper describes the implementation of this approach on a single unilateral transfemoral amputee subject, and demonstrates via experiments the effectiveness of the approach. In the real-time supervisory control experiments, the intent recognizer identified all 90 activity mode transitions, switching the underlying middle level controllers without any perceivable delay by the user. The intent recognizer also identified six activity mode transitions, which were not intended by the user. Due to the intentional overlapping functionality of the middle level controllers, the incorrect classifications neither caused problems in functionality, nor were perceived by the user.

This paper presents a self-contained powered knee and ankle prosthesis, intended to enhance the mobility of transfemoral amputees. A finite-state based impedance control approach, previously developed by the authors, is used for the control of the prosthesis during walking and standing. Experiments on an amputee subject for level treadmill and overground walking are described. Knee and ankle joint angle, torque, and power data taken during walking experiments at various speeds demonstrate the ability of the prosthesis to provide a functional gait that is representative of normal gait biomechanics. Measurements from the battery during level overground walking indicate that the self-contained device can provide more than 4500 strides, or 9 km, of walking at a speed of 5.1 km/ h between battery charges.

This paper extends a previously developed level- ground walking control methodology to enable an above knee amputee to walk up slopes using a powered knee and ankle prosthesis. Experimental results corresponding to walking on level ground and two different slope angles (5 (°) and 10 (°)) with the powered prosthesis using the control method are compared to walking under the same conditions with a passive prosthesis. The data indicate that the powered prosthesis with the upslope walking controller is able to reproduce several kinematic characteristics of healthy upslope walking that the passive prosthesis does not (such as knee flexion after heel strike and a powered ankle plantarflexion during push-off). Finally, results are shown that demonstrate the ability of the prosthesis to generate a slope estimate, which is in turn utilized to adapt the underlying control parameters to the corresponding slope.