Data-driven control design for neuroprotheses: a virtual reference feedback tuning (VRFT) approach

This paper deals with design of feedback controllers for knee joint movement of paraplegics using functional electrical stimulation (FES) of the paralyzed quadriceps muscle group. The controller design approach, virtual reference feedback tuning (VRFT), is directly based on open loop measured data and fits the controller in such a way that the closed-loop meets a model reference objective. The use of this strategy, avoiding the modeling step, significantly reduces the time required for controller design and considerably simplifies the rehabilitation protocols. Linear and nonlinear controllers have been designed and experimentally tested, preliminarily on a healthy subject and finally on a paraplegic patient. Linear controller is effective when applied on small range of knee joint angle. The design of a nonlinear controller allows better performances. It is also shown that the control design is effective in tracking assigned knee angle trajectories and rejecting disturbances

Online identification and nonlinear control of the electrically stimulated quadriceps muscle

A new approach for estimating nonlinear models of the electrically stimulated quadriceps muscle group under nonisometric conditions is investigated. The model can be used for designing controlled neuro-prostheses. In order to identify the muscle dynamics (stimulation pulsewidth-active knee moment relation) from discrete-time angle measurements only, a hybrid model structure is postulated for the shank-quadriceps dynamics. The model consists of a relatively well known time-invariant passive component and an uncertain time-variant active component. Rigid body dynamics, described by the Equation of Motion (EoM), and passive joint properties form the time-invariant part. The actuator, i.e. the electrically stimulated muscle group, represents the uncertain time-varying section. A recursive algorithm is outlined for identifying online the stimulated quadriceps muscle group. The algorithm requires EoM and passive joint characteristics to be known a priori. The muscle dynamics represent the product of a continuous-time nonlinear activation dynamics and a nonlinear static contraction function described by a Normalised Radial Basis Function (NRBF) network which has knee-joint angle and angular velocity as input arguments. An Extended Kalman Filter (EKF) approach is chosen to estimate muscle dynamics parameters and to obtain full state estimates of the shank-quadriceps dynamics simultaneously. The latter is important for implementing state feedback controllers. A nonlinear state feedback controller using the backstepping method is explicitly designed whereas the model was identified a priori using the developed identification procedure

Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors

Valproic acid (VPA, 2-propylpentanoic acid) is an established drug in the long-term therapy of epilepsy. Recently, VPA was demonstrated to inhibit histone deacetylases (HDACs) class I enzyme at therapeutically relevant concentrations, thereby, mimicking the prototypical histone deacetylase inhibitors, tricostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA). In the present study, we investigated the cellular effects of VPA, TSA and SAHA on four human melanoma cell lines (WM115, WM266, A375, SK-Mel28) with particular reference to the modulation of regulators of apoptosis, including Bcl-2, BclXL, Mcl-1, Apaf-1, BclXs, NOXA, TRAIL-R1, TRAIL-R2, caspase 8, and survivin). Firstly, we found that VPA induced apoptosis in two of the four human melanoma cell lines, while both TSA and SAHA exhibited an antiproliferative and apoptotic effects in all four cell lines, a different expression of Bcl-2 and BclXL/S occurred. On the other hand, SAHA and VPA modulated differently pro- and antiapoptotic factors. In particular, the treatment with VPA enhanced the level of expression of survivin only in VPAresistant cell lines, whereas down-regulation of survivin was induced by VPA and SAHA in VPA-sensitive cells. In the latter, since activation of caspase 8 was documented, a receptor-mediated apoptosis was suggested. Taken together, our results suggest that HDAC inhibitors may represent a promising therapeutic strategy to treat melanoma

Dependency of global mean precipitation on surface temperature

Copyright © 2008 American Geophysical UnionWe investigate the causes of temperature dependent changes in global precipitation in contemporary General Circulation Models (GCMs) subjected to a doubling of atmospheric CO2 concentration. By analyzing the energy budget of the troposphere, we find that changes are dominated by processes robustly simulated by GCMs. Importantly, shortwave cloud feedbacks, whose uncertainty is largely responsible for the wide range of GCM temperature climate sensitivities, are shown to have little effect. This is because these mainly arise from the scattering of shortwave radiation that has little impact on the tropospheric heating that controls precipitation. Hence, we expect that the range of simulated precipitation sensitivities to temperature will not change greatly in future GCMs, despite the recent suggestion that satellite observations indicate that GCM precipitation changes are significantly in error

Closed-loop Control of a Vibrant Duct Gravimetric Feeder

Abstract -In this work the control system for a gravimetric feeder with vibrant duct for polymer extrusion process has been designed. The plant considered in this paper is a blending machine that mixes up to six components: each component is measured by a dedicated vibrant duct. All components are mixed directly in the chambers of the extruder screw. The mass delivered by each meter is measured by a load cell. The control objectives are: accurate mass flow estimate on the basis of the weight; accurate mass flow regulation; minimum settling time; robustness of the controller parameters against the variation of material and structure of meter

How much will precipitation increase with global warming?

Copyright © 2008 American Geophysical UnionThe advent of meteorological satellites during the 1970s made possible the observation of the seasonally shifting patterns of global precipitation. It was not until recently, however, that the record could be considered long enough to investigate longer-term trends and the relationship between global precipitation and global warming. Using data from the Special Sensor Microwave Imager (SSM/I) instrument, Wentz et al. [2007] reported that global mean precipitation increased at a rate of 7.4±2.6% per °C between 1987 and 2006. Meanwhile, general circulation models (GCMs) used to predict climate change simulate twentieth- and 21st-century mean precipitation increases of about 13% per °C [Held and Soden, 2006]. This difference seems surprising because some GCMs can adequately reproduce the much longer twentieth- century surface-based land-mean precipitation record [Lambert et al., 2005]. Global precipitation changes are tied to the surface energy budget through evaporation and to the tropospheric energy budget through condensation. Thus, if GCMs do underestimate global precipitation changes, the simulation of other climate variables will be affected

The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE:The study protocol

Background: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods: IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients' demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions: IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease's awareness

Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington's Disease patients: a case series

BACKGROUND: Chorea in Huntington's Disease (HD) is usually treated with antidopaminergic neuroleptics like haloperidol, olanzapine and tiaprid or dopamine depleting drugs like tetrabenazine. Some patients with hyperkinesia, however, react to treatment with antidopaminergic drugs by developing extrapyramidal side effects. In earlier studies valproic acid showed no beneficial effect on involuntary choreatic movements. Myoclonus is rare in HD and is often overseen or misdiagnosed as chorea. METHODS: In this report, we present eight patients whose main symptom is myoclonic hyperkinesia. All patients were treated with valproic acid and scored by using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before and after treatment. In addition to this, two patients agreed to be videotaped. RESULTS: In seven patients myoclonus and, therefore the UHDRS motor score improved in a dose dependent manner. In three of these patients antidopaminergic medication could be reduced. CONCLUSION: In the rare subgroup of HD patients suffering from myoclonic hyperkinesia, valproic acid is a possible alternative treatment

Environment And Genetics in Lung cancer Etiology (EAGLE) study: An integrative population-based case-control study of lung cancer

Background: Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. Methods/Design: We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. Discussion: EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health