T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele.

Limited regions of amino acid sequence similarity frequently occur between microbial antigens and host proteins. It has been widely anticipated that during infection such sequence similarities could induce cross-reactive T cell responses, thereby initiating T cell-mediated autoimmune disease. However, the nature of major histocompatibility complex (MHC)-restricted antigen presentation confers a number of constraints that should make this type of T cell cross-reactivity a rare, MHC allele-dependent event. We tested this prediction using two insulin-dependent diabetes mellitus (IDDM)-associated antigens, coxsackievirus P2-C (Cox P2-C) protein and glutamate decarboxylase (GAD65), which share a prototypic sequence similarity of six consecutive amino acids within otherwise unrelated proteins. We surveyed a panel of 10 murine MHC class II alleles that encompass the spectrum of standard alleles for the ability to cross-reactively present Cox P2-C and GAD65. Out of the 10 restriction elements tested, the sequence similarity regions were both dominant determinants and were cross-reactively displayed after the natural processing of whole antigens, only in the context of I-Anod. These data show that cross-reactive T cell recognition of sequence similarity regions in unrelated proteins is confined to certain MHC alleles, which may explain MHC association with autoimmune disease. It is striking that these two diabetes-associated antigens were cross-reactively recognized only in the context of a diabetes susceptibility allele. Since the human and the murine class II alleles associated with IDDM share conserved features, cross-reactive T cell recognition of GAD65 and Cox P2-C may contribute to the pathogenesis of human IDDM and account for the epidemiological association of coxsackievirus with IDDM

Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes.

We previously demonstrated that a spontaneous Th1 response against glutamate decarboxylase (GAD65) arises in NOD mice at four weeks in age and subsequently T cell autoimmunity spreads both intramolecularly and intermolecularly. Induction of passive tolerance to GAD65, through inactivation of reactive T cells before the onset of autoimmunity, prevented determinant spreading and the development of insulin-dependent diabetes mellitus (IDDM). Here, we examined whether an alternative strategy, designed to induce active tolerance via the engagement of Th2 immune responses to GAD65, before the spontaneous onset of autoimmunity, could inhibit the cascade of Th1 responses that lead to IDDM. We observed that a single intranasal administration of GAD65 peptides to 2-3-wk-old NOD mice induced high levels of IgG1 antibodies to GAD65. GAD65 peptide treated mice displayed greatly reduced IFN gamma responses and increased IL-5 responses to GAD65, confirming the diversion of the spontaneous GAD65 Th1 response toward a Th2 phenotype. Consistent with the induction of an active tolerance mechanism, splenic CD4+ (but not CD8+) T cells from GAD65 peptide-treated mice, inhibited the adoptive transfer of IDDM to NOD-scid/scid mice. This active mechanism not only inhibited the development of proliferative T cell responses to GAD65, it also limited the expansion of autoreactive T cell responses to other beta cell antigens (i.e., determinant spreading). Finally, GAD65 peptide treatment reduced insulitis and long-term IDDM incidence. Collectively, these data suggest that the nasal administration of GAD65 peptides induces a Th2 cell response that inhibits the spontaneous development of autoreactive Th1 responses and the progression of beta cell autoimmunity in NOD mice

Modified Volterra model-based non-linear model predictive control of IC engines with real-time simulations

Modelling of non-linear dynamics of an air manifold and fuel injection in an internal combustion (IC) engine is investigated in this paper using the Volterra series model. Volterra model-based non-linear model predictive control (NMPC) is then developed to regulate the air–fuel ratio (AFR) at the stoichiometric value. Due to the significant difference between the time constants of the air manifold dynamics and fuel injection dynamics, the traditional Volterra model is unable to achieve a proper compromise between model accuracy and complexity. A novel method is therefore developed in this paper by using different sampling periods, to reduce the input terms significantly while maintaining the accuracy of the model. The developed NMPC system is applied to a widely used IC engine benchmark, the mean value engine model. The performance of the controlled engine under real-time simulation in the environment of dSPACE was evaluated. The simulation results show a significant improvement of the controlled performance compared with a feed-forward plus PI feedback control

Fault tolerant control for nonlinear systems using sliding mode and adaptive neural network estimator

This paper proposes a new fault tolerant control scheme for a class of nonlinear systems including robotic systems and aeronautical systems. In this method, a sliding mode control is applied to maintain system stability under the post-fault dynamics. A neural network is used as on-line estimator to reconstruct the change rate of the fault and compensate for the impact of the fault on the system performance. The control law and the neural network learning algorithms are derived using the Lyapunov method, so that the neural estimator is guaranteed to converge to the fault change rate, while the entire closed-loop system stability and tracking control is guaranteed. Compared with the existing methods, the proposed method achieved fault tolerant control for time-varying fault, rather than just constant fault. This greatly expands the industrial applications of the developed method to enhance system reliability. The main contribution and novelty of the developed method is that the system stability is guaranteed and the fault estimation is also guaranteed for convergence when the system subject to a time-varying fault. A simulation example is used to demonstrate the design procedure and the effectiveness of the method. The simulation results demonstrated that the post-fault is stable and the performance is maintained

Clinical characteristics of bloodstream infections due to ampicillin-sulbactam-resistant, non-extended-spectrum-β-lactamase-producing Escherichia coli and the role of TEM-1 hyperproduction

Ampicillin-sulbactam is commonly used as an empirical therapy for invasive infections where Escherichia coli is a potential pathogen. We evaluated the clinical and microbiologic characteristics of bloodstream infection due to E. coli, with focus on cases that were nonsusceptible to ampicillin-sulbactam and not producing extended-spectrum beta-lactamase (ESBL). Of a total of 357 unique bacteremic cases identified between 2005 and 2008, 111 (31.1%) were intermediate or resistant to ampicillin-sulbactam by disk testing. In multivariate analysis, a history of liver disease, organ transplant, peptic ulcer disease, and prior use of ampicillin-sulbactam were independent risk factors for bloodstream infection with ampicillin-sulbactam-nonsusceptible E. coli. Among cases that received ampicillin-sulbactam as an empirical therapy, an early clinical response was observed in 65% (22/34) of susceptible cases but in only 20% (1/5) of nonsusceptible cases. Among 50 ampicillin-sulbactam-resistant isolates examined, there was no clonal relatedness and no evidence of production of inhibitor-resistant TEM (IRT). Instead, the resistance was attributed to hyperproduction of TEM-1 beta-lactamase in the majority of isolates. However, promoter sequences of bla(TEM-1) did not predict resistance to ampicillin-sulbactam. While the plasmid copy number did not differ between representative resistant and susceptible isolates, the relative expression of bla(TEM-1) was significantly higher in two of three resistant isolates than in three susceptible isolates. These results suggest high-level bla(TEM-1) expression as the predominant cause of ampicillin-sulbactam resistance and also the presence of yet-unidentified factors promoting overexpression of bla(TEM-1) in these isolates

Factorized f-step radial basis function model for model predictive control

This paper proposes a new factorized f-step radial basis function network (FS-RBF) model for model predictive control (MPC). The strategy is to develop a f-step predictor for nonlinear dynamic systems and implement it with a RBF network. In contrast to the popular NARX-RBF model, the developed FS-RBF model is capable of making a designated sequence of future output prediction without requiring the unknown future process measurements. Furthermore, the developed FS-RBF model is factorized into two parts, with one part including past plant input/output and the other part including the future input/output. When this model is used as the internal model in the MPC, the factorization enables an explicit objective function for the on-line optimization in the MPC. Thus, the computing load in solving the optimization problem is greatly reduced. The developed model is used in MPC and applied to a continuous-stirred tank reactor (CSTR). The simulation results are compared with that of MPCs with other two models. The comparison confirms that the developed model make more accurate prediction so that the MPC performance is better, it also uses much less computing time than the other two models based MPC

Pitch angle control with fault diagnosis and tolerance for wind turbine generation systems

To enhance the reliability of wind turbine generation systems that are generally located in the remote area and subjected to harsh environment, we design the pitch angle control for variable speed wind turbines with the function of fault diagnosis and fault tolerance. The main fault targeted in this research is the mechanical wear and possible break of the blade, pitch gear set or shaft, which cause shaft rotary friction change. The proposed method uses a disturbance observer to diagnose the fault. The estimated fault is used for component assessment and later maintenance. The fault-tolerant control is achieved using a full-order terminal sliding mode control combined with an adaptive neural network estimator. With the compensation of the adaptive estimator, the post-fault states can be driven onto the sliding surface and converge to a small area around the origin. The full-order terminal sliding mode control ensures the state convergence in finite time. The Lyapunov method is used to derive the control law, so that the closed-loop post-fault stability and the convergence of the adaptive estimator adaptation are both guaranteed. The computer simulations of the pitch angle control based on a 5-MW variable-speed variable-pitch angle wind turbine model are conducted with different types of fault simulated. A third-order nonlinear state space model with fault term is derived, and real physical parameters are applied in the simulations. The simulation results demonstrate the feasibility and effectiveness of the proposed scheme and the potential of real-world applications. © IMechE 2021

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201