Classical Loop Research Articles

Simple nonlinear interferometer-based all-optical thresholder and its applications for optical CDMA

We present an experimental demonstration of an ultrafast all-optical thresholder based on a nonlinear Sagnac interferometer. The proposed design is intended for operation at very small nonlinear phase shifts. Therefore, it requires an in-loop nonlinearity lower than for the classical nonlinear loop mirror scheme. Only 15 meters of conventional (non-holey) silica-based fiber is used as a nonlinear element. The proposed thresholder is polarization insensitive and is good for multi-wavelength operation, meeting all the requirements for autocorrelation detection in various optical CDMA communication systems. The observed cubic transfer function is superior to the quadratic transfer function of second harmonic generation-based thresholders.

Sustained IL-6/STAT-3 Signaling in Cholangiocarcinoma Cells Due to SOCS-3 Epigenetic Silencing

Interleukin 6 (IL-6)-mediated signal transducers and activators of transcription 3 (STAT-3) phosphorylation (activation) is aberrantly sustained in cholangiocarcinoma cells resulting in enhanced myeloid cell leukemia 1 (Mcl-1) expression and resistance to apoptosis. Because suppressor of cytokine signaling 3 (SOCS) controls the IL-6/STAT-3 signaling pathway by a classic feedback loop, the aims of this study were to examine SOCS-3 regulation in human cholangiocarcinoma. SOCS-3 expression was assessed in human cholangiocarcinoma tissue and the Mz-ChA-1 and CCLP1 human cholangiocarcinoma cell lines. An inverse correlation was observed between phospho-STAT-3 and SOCS-3 protein expression in cholangiocarcinoma. In those cancers failing to express SOCS-3, extensive methylation of the SOCS-3 promoter was demonstrated in tumor but not in paired nontumor tissue. Likewise, methylation of the socs-3 promoter was also identified in 2 cholangiocarcinoma cell lines. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine (DAC), restored IL-6 induction of SOCS-3, terminated the phospho-STAT-3 response, and reduced cellular levels of Mcl-1. Enforced expression of SOCS-3 also reduced IL-6 induction of phospho-STAT-3 and Mcl-1. Either DAC treatment or enforced SOCS-3 expression sensitized the cells to TRAIL-mediated apoptosis. SOCS-3 epigenetic silencing is responsible for sustained IL-6/STAT-3 signaling and enhanced Mcl-1 expression in cholangiocarcinoma.

Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis

The immunovariant N-ethyl-N-nitrosourea-induced mutations Pococurante (Poc) and Lackadaisical were found to alter MyD88, creating striking receptor-selective effects. Poc, in particular, prevented sensing of all MyD88-dependent Toll-like receptor (TLR) ligands except diacyl lipopeptides. Furthermore, Poc-site and classical BB loop mutations caused equivalent phenotypes when engrafted into any TLR/IL-1 receptor/resistance (TIR) domain. These observations, complemented by data from docking studies and site-directed mutagenesis, revealed that BB loops and Poc sites interact homotypically across the receptor:adapter signaling interface, whereas the C-terminal alpha(E)-helices support adapter:adapter and receptor:receptor oligomerization. We have thus defined the TIR domain surface that mediates association between TLRs and MyD88 and the surface required for MyD88 or TLR oligomerization. Moreover, MyD88 engages individual TLRs differently, suggesting the feasibility of selective pharmacologic TIR domain receptor blockade.

Mixed Slip-Deceleration Control in Automotive Braking Systems

AbstractIn road vehicles, wheel locking can be prevented by means of closed-loop anti-lock braking systems (ABS). Automatic braking is extensively used also for electronic stability control (ESC) systems. In braking control systems, two output variables are usually considered for regulation purposes: wheel deceleration and wheel longitudinal slip. Wheel deceleration is the controlled output traditionally used in ABS, since it can be easily measured with a simple wheel encoder; however, the dynamics of a classical regulation loop on the wheel deceleration critically depend on the road conditions. A regulation loop on the wheel longitudinal slip is simpler and dynamically robust; moreover, slip control is perfectly suited for both ABS and ESC applications. However, the wheel-slip measurement is critical, since it requires the estimation of the longitudinal speed of the vehicle body, which cannot be directly measured. Noise sensitivity of slip control hence is a critical issue, especially at low speed. In this work a new control strategy called mixed slip-deceleration (MSD) control is proposed: the basic idea is that the regulated variable is a convex combination of wheel deceleration and longitudinal slip. This strategy turns out to be very powerful and flexible: it inherits all the attractive dynamical features of slip control, while providing a much lower sensitivity to slip-measurement noise.

Adaptive precision positioning of smart composite panels subjected to external disturbances

This paper addresses the simultaneous precision positioning and vibration suppression of smart composite panels with piezoelectric patches. The filtered-x least mean square (LMS) adaptive feedforward control (AFC) for vibration/noise reduction is extended for this purpose, and AFCs with feedback loops are developed. The introduced feedback loops enhance the computational efficiency of the adaptive LMS algorithm and vibration suppression capability. Besides the classic PID feedback loop, the internal model configuration is introduced as well for the case in which the external disturbance is unknown. Experiments are performed on an active composite panel under a harmonic or random disturbance. The effects of the convergence factors of the adaptive algorithm on the overshoot and settling time of the position response of the smart composite panel are investigated. The vibration suppression and precision positioning capabilities of the AFC and the AFC with feedback loops are compared and discussed. The experimental results demonstrate that the overall positioning and vibration suppression performances for the AFC with feedback loops are better than those for the AFC.

10-GHz clock recovery using an optoelectronic phase-locked loop based on three-wave mixing in periodically poled lithium niobate

Clock recovery is a critical function of any digital communications system. To replace the classical electronic phase-locked loops (PLLs) at higher bit rates, several all-optical or optoelectronic clock recovery methods are being studied. This letter presents an optoelectronic PLL where three-wave mixing in a periodically poled lithium niobate (PPLN) device provides the phase comparator. Since PPLN is passive, it generates no amplified spontaneous emission noise; also, the error signal is in the visible (763 nm), therefore easily separated from infrared input signals. Clock recovery is performed on a 10-GHz sinusoidal optical signal. Being based on ultrafast nonlinear effects, this scheme should be able to reach still higher bit rates, on the order of several hundred gigahertz. Also, subclock extraction (e.g., 40-to-10 GHz) should be possible without modifications.

Variation in physical activity lies with the child, not his environment: evidence for an ‘activitystat’ in young children (EarlyBird 16)

There is currently wide interest in the physical activity of children, but little understanding of its control. Here, we use accelerometers to test the hypothesis that habitual activity in young children is centrally, rather than environmentally, regulated. By central regulation we mean a classic biological feedback loop, with a set-point individual to the child, which controls his/her activity independently of external factors. Non-intervention, observational and population-based, set in the home and at school. Girls were systematically less active than boys, and both weekday/weekend day and year-on-year activities were correlated (r=0.43-0.56). A fivefold variation in timetabled PE explained less than 1% of the total variation in physical activity. The activity cost of transport to school was only 2% of total activity, but over 90% of it was recovered elsewhere in the day. The weekly activity recorded by children in Plymouth was the same (to within <0.3%) as that recorded independently in Glasgow, 800 km away. Total daily activity was unrelated to time reportedly spent watching TV. The correlations within groups and the similarities between them suggest that physical activity in children is under central biological regulation. There are implications both for public health planners and for the potentially novel signalling pathways involved.

Viewing a Stressful Episode of ER

See related article, pages 1186–1193 How cardiac cells sense, respond, and adapt to acute and chronic changes of their metabolic and environmental milieu remain among the most enigmatic and fundamental questions in contemporary cardiovascular biology and medicine. With more than 700 000 deaths and 6 million hospital discharges annually in the U.S., ischemic heart disease remains a major public health problem. If prompt therapy is delayed, myocardial injury from depletion of high-energy phosphates from inhibition of oxidative phosphorylation is inevitable. Ischemia/reperfusion (I/R) also unleashes a cascade of cellular and molecular events whose sequalae may sustain organ function at diminished capacity but, beyond a critical balance, threatens the organism’s survival. Reactive oxygen and nitrogen species (ROS; RNS), released from the mitochondria and other sources, alter the tertiary and quaternary structures of proteins, exposing their hydrophobic residues to allow conformational tendencies toward protein misfolding and aggregation.1 Nevertheless, highly sophisticated schemes equipped with molecular sensors, rapid response pathways, and adaptor mechanisms have evolved to mitigate the accumulation of unfolded proteins in a compartment specific manner, principally the cytoplasm and endoplasmic reticulum (ER). Although the cardiovascular field has paid considerably more attention to the cytoprotective mechanisms of heat shock proteins in response to I/R, termed the “classical” heat shock response, a parallel series of events has been unfolding at a breathtaking pace in the ER, with arguably considerable excitement to warrant a sneak preview of the article published in this issue of Circulation Research . To place into perspective the current buzz being garnered by the ER requires a brief discussion of more familiar themes in the field, which were developed thanks to the pioneering efforts of cardiovascular scientists, and others, working on the complementary stress response network, best exemplified by heat shock “stress” proteins and their transcriptional regulators. First discovered by …

Long-lasting aftereffect of a single prism adaptation: shifts in vision and proprioception are independent

After a single adaptation session to prisms with gradually incremented shift magnitude, the prism adaptation aftereffect was measured by open loop mid-sagittal pointing (O) to a visual target without visual feedback. This aftereffect corresponded to the summation of the shift in proprioception, measured by straight ahead pointing without vision (S), and the visual straight ahead judgement (V), measured by verbal stopping of an LED moving from two opposite directions. However, the measurement of the aftereffects made over a period of 7 days revealed significantly different decay curves in V, O and S. Surprisingly the S shift was still present up to 7 days after the training, while V had returned to the original level by 2 h, which was the first measurement after subjects returned to a normal visual environment. O had returned to pre-test level after 1 day. After 3 days Wilkinson's (J Exp Psychol 89:250-257, 1971) additive hypothesis (O=S-V) no longer fit the data. Rather "O=Pl-V", where Pl (Pr) is the shift in proprioception measured by passive lateral arm movements from left (right), fitted better during the whole 7 days of aftereffect in our study. Therefore, the aftereffect of our strong prism adaptation revealed, firstly, that classical open loop pointing consisted of aftereffect shifts equal to the summation of the shifts in the two passively measurable aftereffect components, vision (V) and proprioception (Pl), rather than with active straight ahead pointing (S). Secondly, the decay of the shift in visual perception and in passively measurable proprioception is independent. The former decays fast, and the latter decays slowly with two separate waves. Thirdly, we suggest that the use of visual perception-dependent spatial codes for visual-manual transformation and the vision-independent internal egocentric reference frame are mutually exclusive. We proposed a model to explain these possible mechanisms.

Equivalence between transfer-matrix and observed-state feedback control

An observed-state feedback is built for a given multiple input–multiple output (MIMO) control loop, where the controller is specified in transfer-matrix form. This contribution solves for the first time, for MIMO systems, the classical problem of finding a feedback gain and an observer gain such that the observed-state feedback control loop has the same sensitivity as that provided by a one-degree-of-freedom classical control loop.

Unusual cause of respiratory distress misdiagnosed as refractory asthma

We report a young lady, who was labeled as a case of refractory asthma for a few years, based on history of shortness of breath on minimal exertion, noisy breathing and normal chest radiograph. Repeated upper airway exam by an otolaryngologist and computerized tomography scan, were normal. On presentation to our hospital, she was diagnosed to have fixed upper airway obstruction, based on classical flow-volume loop findings. Fibroptic bronchoscopy revealed a web-shaped subglottic stenosis. The histopathology of a biopsy taken from that area, showed non-specific inflammation. No cause for this stenosis could be identified. The patient was managed with rigid bronchoscopy dilatation, without recurrence. We report this case as idiopathic subglottic stenosis, that was misdiagnosed as refractory bronchial asthma, stressing the importance of performing spirometry in the clinic.

Loop shaping design for tracking performance in machine axes

A modern interpretation of classical loop shaping control design methods is presented in the context of tracking control for linear motor stages. Target applications include noncontacting machines such as laser cutters and markers, water jet cutters, and adhesive applicators. The methods are directly applicable to the common PID controller and are pertinent to many electromechanical servo actuators other than linear motors. In addition to explicit design techniques a PID tuning algorithm stressing the importance of tracking is described. While the theory behind these techniques is not new, the analysis of their application to modern systems is unique in the research literature. The techniques and results should be important to control practitioners optimizing PID controller designs for tracking and in comparing results from classical designs to modern techniques. The methods stress high-gain controller design and interpret what this means for PID. Nothing in the methods presented precludes the addition of feedforward control methods for added improvements in tracking. Laboratory results from a linear motor stage demonstrate that with large open-loop gain very good tracking performance can be achieved. The resultant tracking errors compare very favorably to results from similar motions on similar systems that utilize much more complicated controllers.

Torque-Dependent Compliance Control in the Joint Space for Robot-Mediated Motor Therapy

This paper is focused on the design of interaction control of robotic machines for rehabilitative motor therapy of the upper limb. The control approach tries to address requirements deriving from the application field and adopts a bioinspired approach for regulating robot behavior in the interaction with the patient. An inner-outer loop control scheme is proposed. In order to tune the level of force and improve robot adaptability in the interaction with the patient, a classical outer force control loop is used. For the inner loop, a novel control law for low-level tuning of robot compliance is introduced, that is borrowed from studies on the biological mechanisms for regulating the elastic properties of the human arm. A dedicated simulation tool, which models the dynamics of an operational robotic machine interacting with a human subject, has been developed. Validation of basic adaptability and safety requirements of the control scheme is carried out in simple tasks, e.g., reaching and contact/noncontact transitions, as well as in simulated situations of typical motor exercises. In particular, the simulation tests demonstrate the adaptive capabilities of the proposed control schemes, e.g., in counterbalancing patient incorrect movements related to the various levels of disability. Moreover, preliminar experimental tests carried out on a real robotic system demonstrated the possibility of using the proposed approach for guaranteeing safe interaction with the patient.

SOCS3 was induced by hypoxia and suppressed STAT3 phosphorylation in pulmonary arterial smooth muscle cells

Recently identified suppressors of cytokine signaling (SOCS) have been proposed as negative regulators of cytokine signaling, which have distinct mechanisms of inhibiting JAK-STAT pathway. In this study, using cultures of rat primary pulmonary vascular smooth muscle cells (PASMC), we found that hypoxia induced strongly STAT3 phosphorylation by up to four-fold. At the same time, mRNA for the endogenous cytokine signaling repressor SOCS3, but not SOCS1, was markedly induced in PASMC as early as 2h following hypoxic stimulation. Furthermore, forced expression of SOCS3 gene suppressed tyrosine phosphorylation of STAT3 and transcription of c-myc gene by more than 70% and 60% in PASMC under hypoxic conditions, respectively. Additionally, we showed here that hypoxia enhanced nearly two-fold increase of PASMC proliferation and overexpression of SOCS3 gene downregulated hypoxia-induced PASMC proliferation by about 50%. The finding suggest that STAT3-dependent pathway is involved in the activation and proliferation of PASMC stimulated by hypoxia, and SOCS3 is a rapidly hypoxia-inducible gene and acts to inhibit activation of cellular signaling pathway in a classical negative feedback loop.

A negative feedback mechanism involving nitric oxide and nuclear factor kappa-B modulates endothelial nitric oxide synthase transcription

Nuclear factor kappa B (NFκB), commonly a proinflammatory transcription factor, is responsible for increasing transcription of the endothelial cell nitric oxide synthase (eNOS) in response to laminar shear stress. Nitric oxide (NO) production can be stimulated by shear, and NO is known to inhibit NFκB activation. We hypothesized that this inhibitory action of NO on NFκB activation serves as a negative feedback to inhibit NFκB activity and eNOS transcription. Exposure of bovine aortic endothelial cells to laminar shear stimulated steady state eNOS mRNA expression and eNOS promoter activity as measured using an eNOS promoter/CAT construct. These effects of shear were enhanced by the NOS inhibitor l-NAME and decreased by the NO-donor DPTA-NO by 30–50%. The NFκB inhibitor panepoxydone prevented the increase in eNOS mRNA caused by shear confirming a role of NFκB in this response. Shear stress stimulated a transient (30 min) nuclear translocation of the NFκB subunit p50. Treatment with l-NAME increased binding of the NFκB subunit p50 to consensus oligonucleotide-coated microtiter plates, while having only minimal effect on binding of p65, strongly suggesting that nitric oxide mainly inhibits p50 activation. Using the biotin switch method, we found that shear stress stimulates p50 nitrosylation and this was prevented by l-NAME. Moreover, transfection of endothelial cells with a vector encoding the C62S p50, a variant with a point mutation of the nitrosylation site C62, markedly increased nuclear translocation of p50 and doubled eNOS mRNA expression under shear stress compared to that observed in cells transfected with wild-type p50. We conclude that this interaction between shear, NFκB activation, NO production and NFκB inhibition represents a classical negative feedback loop, which prevents sustained activation of NFκB. In the absence of NO, shear stimulation of NFκB and eNOS transcription are enhanced. Our findings emphasize the critical role of NO in modulation of the endothelial cell inflammatory state. Several common diseases, including hypercholesteremia, hypertension and diabetes, are associated with eNOS dysfunction. Under these conditions, decreased NO availability may result in sustained activation of NFκB in response to shear and unrestrained endothelial inflammation.

Towards a text mining methodology using association rule extraction

This paper proposes a methodology for text mining relying on the classical knowledge discovery loop, with a number of adaptations. First, texts are indexed and prepared to be processed by frequent itemset levelwise search. Association rules are then extracted and interpreted, with respect to a set of quality measures and domain knowledge, under the control of an analyst. The article includes an experimentation on a real-world text corpus holding on molecular biology.

Expression of Xenopus suppressor of cytokine signaling 3 (xSOCS3) is induced by epithelial wounding

The suppressor of cytokine signaling (SOCS) family of proteins are intracellular mediators of cytokine signaling. These proteins are induced rapidly by cytokine stimulation and act in a classic negative-feedback loop to attenuate the cellular response to the cytokine signal. In this study, we present the cloning and initial characterization of the Xenopus SOCS3 gene. We show that xSOCS3 is rapidly induced in response to epithelial wounding in the tadpole. The induction of xSOCS3 in response to trauma is transient with maximal expression being reached 1 hr after the injury and diminishing after that. Unlike other genes known to be responsive to wound-induced activation of the mitogen-activated protein (MAP) kinase pathway, such as Egr1, SOCS3 expression in response to trauma is unaffected by blockade of the MAP kinase pathway by chemical inhibitors.

A Control Strategy on Starting up of Vehicle with Automatic Manual Transmissions (AMT)*

Recently, starting control takes an important role in the automatic manual transmission systems; clutch engagement control is the key of it. In order to improve the starting performance of AMT vehicle, clutch dynamic response must be control during the slipping phase. Therefore, this paper puts forward a control strategy for the dry clutch engagement process, considered as a finite time optimal control problem. The main idea of this strategy is to obtain a linear quadratic state feedback controller by solving the optimal control problem. The performance obtained with the proposed controller are compared with those achievable by means of a classical open loop control strategy. Moreover, different starting operating conditions are used to test the controller performance. Numerical simulations shows the good performance obtained by the proposed controller, which guarantees fast engagement, minimize the slip losses, reduce the fuel consumption and improve in the shift quality.

Entorhinal cortex entrains epileptiform activity in CA1 in pilocarpine-treated rats

Layer III neurons of the medial entorhinal cortex (mEC) project to CA1 via the temporoammonic pathway and exert a powerful feed-forward inhibition of CA1 pyramidal neurons. The present study evaluates the hypothesis that disrupted inhibition of CA1 pyramidal neurons causes an eased propagation of entorhinal seizures to the hippocampus via the temporoammonic pathway. Using a method to induce a confined epileptic focus in brain slices, we investigated the spread of epileptiform activity from the disinhibited mEC to CA1 in control and pilocarpine-treated rats that had displayed status epilepticus and spontaneous recurrent seizures. In pilocarpine-treated rats, the mEC showed a moderate layer III cell loss and an enhanced susceptibility to epileptiform discharges compared to control animals. Entorhinal discharges propagated to CA1 in pilocarpine-treated rats but not in controls. Disconnecting CA3 from CA1 did not affect the spread of epileptiform activity to CA1 excluding its propagation via the trisynaptic hippocampal loop. Mimicking the invasion of epileptiform discharges by repetitive stimulation of the temporoammonic pathway caused a facilitation of field potentials in CA1 that were contaminated by population spikes and afterdischarges in pilocarpine-treated but not control rats. Single cell recordings of CA1 pyramidal neurons revealed a dramatic loss of feed-forward inhibition and the occurrence of strong postsynaptic excitatory potentials in pilocarpine-treated rats. Excitatory responses in CA1 were characterized by multiple NMDA receptor-mediated afterdischarges and a strong paired-pulse facilitation in response to activation of the temporoammonic pathway. Our results suggest that, irrespective of the enhanced seizure-susceptibility of the mEC in epileptic rats, the loss of feed-forward inhibition and the enhanced NMDA receptor-mediated excitability CA1 pyramidal cells ease the spread of epileptiform activity from the mEC to CA1 via the temporoammonic pathway bypassing the classical trisynaptic hippocampal loop.

Assessing statistical precision, power, and robustness of alternative experimental designs for two color microarray platforms based on mixed effects models

Recommendations on experimental designs for two color microarray systems have been generally conflicting as they pertain to the general choice between reference and non-reference loop designs. This conflict may currently exist because many previously published assessments may not have effectively connected design layout with the level of biological relative to technical replication. We reassess various reference and non-reference designs for statistical efficiency in terms of standard errors of mean differences, power of test, and robustness using recently developed mixed model software tools. In minimally replicated cases ( n = 2), it appears that the reference design outperforms the classical loop design whereby a sample from each animal is used for only one particular array hybridization. Alternatively, the reference design was consistently inferior to those connected loop designs in which a sample from each animal is used in two different hybridizations. Nevertheless, the gap in power between these two designs diminished as the biological to residual variance ratio increased. The statistical efficiency of a single large classical loop design for the comparison of many treatments was demonstrated to be highly sensitive to missing arrays relative to a common reference design ( n = 2). However, the use of two loops within an interwoven loop design was shown to be substantially more robust to missing arrays and statistically more efficient relative to a common reference design. Furthermore, the use of more than one loop leads to less disparity in precision and power comparisons between any two treatments.