Performance Monitoring of Control Systems using Likelihood Methods

Evaluating deterioration in performance of control systems using closed loop operating data is addressed. A framework is proposed in which acceptable performance is expressed as constraints on the closed loop transfer function impulse response coefficients. Using likelihood methods, a hypothesis test is outlined to determine if control deterioration has occurred. The method is applied to a simulation example as well as data from an operational distillation column, and the results are compared to those obtained using minimum variance estimation approaches

Optimal and Robust Design of Integrated Control and Diagnostic Modules

The problem of designing an integrated control and diagnostic module is considered. The four degree of freedom controller is recast into a general framework wherein results from optimal and robust control theory can be easily implemented. For the case of an H2 objective, it is shown that the optimal control-diagnostic module involves constructing an optimal controller, closing the loop with this controller, and then designing an optimal diagnostic module for the closed loop. When uncertain plants are involved, this two-step method does not lead to reasonable diagnostics, and the control and diagnostic modules must be synthesized simultaneously. An example shows how this design can be accomplished with available methods

Avery Final Report: Identification and Cross-Directional Control of Coating Processes

Coating refers to the covering of a solid with a uniform layer of liquid. Of special industrial interest is the cross-directional control of coating processes, where the cross-direction refers to the direction perpendicular to the substrate movement. The objective of the controller is to maintain a uniform coating under unmeasured process disturbances. Assumptions that are relevant to coating processes found in industry are used to develop a model for control design. We show how to identify the model from input-output data. This model is used to derive a model predictive controller to maintain flat profiles of coating across the substrate by varying the liquid flows along the cross direction. The model predictive controller computes the control action which minimizes the predicted deviation in cross-directional uniformity. The predictor combines the estimate obtained from the model with the measurement of the cross-directional uniformity to obtain a prediction for the next time step. A filter is used to obtain robustness to model error and insensitivity to measurement noise. The tuning of the noise filter and different methods for handling actuator constraints are studied in detail. The three different constraint-handling methods studied are: the weighting of actuator movements in the objective function, explicitly adding constraints to the control algorithm, i.e. constrained model predictive control, and scaling infeasible control actions calculated from an unconstrained control law to be feasible. Actuator constraints, measurement noise, model uncertainty, and the plant condition number are investigated to determine which of these limit the achievable closed loop performance. From knowledge of how these limitations affect the performance we find how the plant could be modified to improve the process uniformity. Also, because identification of model parameters is time-consuming and costly, we study how accurate the identification must be to achieve a given level of performance. The theory developed throughout the paper is rigorously verified though simulations and experiments on a pilot plant. The effect of interactions on the closed loop performance is shown to be negligible for this pilot plant. The measurement noise and the actuator constraints are shown to have the largest effect on closed loop performance

Merlin Phosphorylation by p21-activated Kinase 2 and Effects of Phosphorylation on Merlin Localization

The Nf2 tumor suppressor gene product merlin is related to the membrane-cytoskeleton linker proteins of the band 4.1 superfamily, including ezrin, radixin, and moesin (ERMs). Merlin is regulated by phosphorylation in a Rac/cdc42-dependent fashion. We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and immunodepletion. By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization. Neurofibromatosis type 2 (NF2)1 is an inherited disorder characterized by the development of Schwann cell tumors of the eighth cranial nerve. Mutations and loss of heterozygosity of theNF2 gene have been detected in NF2 patients and in various sporadic tumors, including schwannomas, meningiomas, and ependymomas (1). In further support of a role for NF2 in tumor suppression, mice heterozygous for an Nf2 mutation are predisposed to a wide variety of tumors with high metastatic potential (2). In a separate model in which Nf2 is inactivated specifically in Schwann cells, mice develop schwannomas and Schwann cell hyperplasia (3). The longest and predominant splice form of the Nf2gene codes for a 595-amino acid protein highly similar to the band 4.1 family of proteins. It is most closely related to the ERM proteins,moesin, ezrin, and radixin. The ERM proteins are thought to function as cell membrane-cytoskeleton linkers and are localized to cortical actin structures near the plasma membrane such as microvilli, membrane ruffles, and lamellipodia (4, 5). Likewise, merlin is localized to cortical actin structures, in patterns that partially overlap with the ERMs (1). It has been proposed that intramolecular binding of the N-terminal and C-terminal domains conformationally regulates the ERM proteins by masking binding sites for interacting proteins. The ERMs can also form homodimers and heterodimers, among themselves and with merlin, adding an additional level of complexity to the regulation of these proteins (6). The recently solved crystal structure of the moesin N/C-terminal complex strengthens this model of conformational regulation (7). Given the sequence and, most likely, structural similarities of merlin to the ERM proteins, it is possible that merlin itself could be regulated in a similar fashion. Recent studies (8, 9) have implicated additional factors in the regulation of the ERMs, including phospholipids and phosphorylation. Previous work from our group and others (10, 11) has shown that merlin is differentially phosphorylated as well and that merlin protein levels are affected by growth conditions such as cell confluency, loss of adhesion, or serum deprivation. Merlin is found in an hypophosphorylated form when the combination of cellular and environmental conditions are growth-inhibitory (10). ERMs can be phosphorylated by Rho kinase, and this phosphorylation can affect intramolecular association and cellular localization. Phosphorylation and/or phospholipids may promote the transition of the proteins to an active form by “opening” intra- and intermolecular associations. These active monomers can then bind to other interacting proteins and the actin cytoskeleton and induce actin-rich membrane projections (5,8, 12, 13). The induction of merlin phosphorylation by activated alleles of the Rho family GTPases has also been examined. Interestingly, although activated Rho did not induce noticeable phosphorylation of merlin, activated forms of Rac and cdc42 did. The site of Rac-induced phosphorylation was determined to be a serine at position 518; mutation of serine 518 results in reduced basal phosphorylation and eliminated Rac-induced phosphorylation (11). Although Rac and cdc42 are implicated in the regulation of many pathways, they are most associated with regulation of cytoskeleton reorganization and gene expression (for recent reviews see Refs.14-16). In light of the data demonstrating that activated Rac/cdc42 leads to phosphorylation and possible inactivation of merlin, the elucidation of the responsible effector pathways and their effects on merlin function are of major importance. Understanding this regulation of merlin could lead to a more complete appreciation of the effects of merlin loss in tumors

Asymmetric root distributions reveal press–pulse responses in retreating coastal forests

The impacts of climate change on ecosystems are manifested in how organisms respond to episodic and continuous stressors. The conversion of coastal forests to salt marshes represents a prominent example of ecosystem state change, driven by the continuous stress of sea-level rise (press), and episodic storms (pulse). Here, we measured the rooting dimension and fall direction of 143 windthrown eastern red cedar (Juniperus virginiana) trees in a rapidly retreating coastal forest in Chesapeake Bay (USA). We found that tree roots were distributed asymmetrically away from the leading edge of soil salinization and towards freshwater sources. The length, number, and circumference of roots were consistently higher in the upslope direction than downslope direction, suggesting an active morphological adaptation to sea-level rise and salinity stress. Windthrown trees consistently fell in the upslope direction regardless of aspect and prevailing wind direction, suggesting that asymmetric rooting destabilized standing trees, and reduced their ability to withstand high winds. Together, these observations help explain curious observations of coastal forest resilience, and highlight an interesting nonadditive response to climate change, where adaptation to press stressors increases vulnerability to pulse stressors

Genetic Interactions Affect Lung Function in Patients with Systemic Sclerosis.

Scleroderma, or systemic sclerosis (SSc), is an autoimmune disease characterized by progressive fibrosis of the skin and internal organs. The most common cause of death in people with SSc is lung disease, but the pathogenesis of lung disease in SSc is insufficiently understood to devise specific treatment strategies. Developing targeted treatments requires not only the identification of molecular processes involved in SSc-associated lung disease, but also understanding of how these processes interact to drive pathology. One potentially powerful approach is to identify alleles that interact genetically to influence lung outcomes in patients with SSc. Analysis of interactions, rather than individual allele effects, has the potential to delineate molecular interactions that are important in SSc-related lung pathology. However, detecting genetic interactions, or epistasis, in human cohorts is challenging. Large numbers of variants with low minor allele frequencies, paired with heterogeneous disease presentation, reduce power to detect epistasis. Here we present an analysis that increases power to detect epistasis in human genome-wide association studies (GWAS). We tested for genetic interactions influencing lung function and autoantibody status in a cohort of 416 SSc patients. Using Matrix Epistasis to filter SNPs followed by the Combined Analysis of Pleiotropy and Epistasis (CAPE), we identified a network of interacting alleles influencing lung function in patients with SSc. In particular, we identified a three-gene network comprising WNT5A, RBMS3, and MSI2, which in combination influenced multiple pulmonary pathology measures. The associations of these genes with lung outcomes in SSc are novel and high-confidence. Furthermore, gene coexpression analysis suggested that the interactions we identified are tissue-specific, thus differentiating SSc-related pathogenic processes in lung from those in skin

Worcester’s Missing Political Voice and the Fate of the Auditorium

The political activism of the 25,000 Worcester college students has been rare given the potential power of numbers. Even on issues that directly affect them they exert no influence. This paper reports a case study of our effort to recruit students to attend a city wide charrette with a focus on Lincoln Square. Prior research indicates that the college students of Worcester want a gathering place and one proposal for the Memorial Auditorium dominating Lincoln Square is to make it a College Crossroads . The East Highland Neighborhood Association supports this proposal for the Auditorium and sponsored our effort to determine if the students will mobilize for this cause. We also assessed support for several other uses of the Auditorium that the adjacent neighborhood might support

A Spatial Stochastic Model of AMPAR Trafficking and Subunit Dynamics

In excitatory neurons, the ability of a synaptic connection to strengthen or weaken is known as synaptic plasticity and is thought to be the cellular basis for learning and memory. Understanding the mechanism of synaptic plasticity is an important step towards understanding and developing treatment methods for learning and memory disorders. A key molecular process in synaptic plasticity for mammalian glutamatergic neurons is the exocytosis (delivery to the synapse) of AMPA-type glutamate receptors (AMPARs). While the protein signaling pathways responsible for exocytosis have long been investigated with experimental methods, it remains unreasonable to study the system in its full complexity via only in vitro and in vivo studies. A large number of protein interaction states are observed, creating a system both difficult to monitor and limited in spatiotemporal resolution in an experimental setting. Thus, a computational modeling approach could be employed to help elucidate the underlying protein interaction mechanisms. Here we develop a systematic model to investigate the spatiotemporal patterning of AMPARs. We replicate in silico two distinct mechanisms of AMPAR trafficking related to variation in AMPAR subunit functionality. This model is validated against current knowledge of AMPAR trafficking and used to explore spatial localization of AMPARs to specific synaptic sites, as well as to describe the differences in the spatiotemporal dynamics between the two interacting pathways. These findings help to explain how AMPAR trafficking occurs and can serve as a step towards understanding the role it plays in synaptic plasticity

Biophysical controls of marsh soil shear strength along an estuarine salinity gradient

Sea-level rise, saltwater intrusion, and wave erosion threaten coastal marshes, but the influence of salinity on marsh erodibility remains poorly understood. We measured the shear strength of marsh soils along a salinity and biodiversity gradient in the York River estuary in Virginia to assess the direct and indirect im-pacts of salinity on potential marsh erodibility. We found that soil shear strength was higher in monospecific salt marshes (5–36 kPa) than in biodiverse freshwater marshes (4–8 kPa), likely driven by differences in below ground biomass. However, we also found that shear strength at the marsh edge was controlled by sediment characteristics, rather than vegetation or salinity, suggesting that inherent relationships may be obscured in more dynamic environments. Our results indicate that York River freshwater marsh soils are weaker than salt marsh soils, and suggest that salinization of these freshwater marshes may lead to simultaneous losses in biodiversity and erodibility

Professional decision-making in medicine: Development of a new measure and preliminary evidence of validity

INTRODUCTION: This study developed a new Professional Decision-Making in Medicine Measure that assesses the use of effective decision-making strategies: seek help, manage emotions, recognize consequences and rules, and test assumptions and motives. The aim was to develop a content valid measure and obtain initial evidence for construct validity so that the measure could be used in future research or educational assessment. METHODS: Clinical scenario-based items were developed based on a review of the literature and interviews with physicians. For each item, respondents are tasked with selecting two responses (out of six plausible options) that they would choose in that situation. Three of the six options reflect a decision-making strategy; these responses are scored as correct. Data were collected from a sample of 318 fourth-year medical students in the United States. They completed a 16-item version of the measure (Form A) and measures of social desirability, moral disengagement, and professionalism attitudes. Professionalism ratings from clerkships were also obtained. A sub-group (n = 63) completed a second 16-item measure (Form B) to pilot test the instrument, as two test forms are useful for pre-posttest designs. RESULTS: Scores on the new measure indicated that, on average, participants answered 75% of items correctly. Evidence for construct validity included the lack of correlation between scores on the measure and socially desirable responding, negative correlation with moral disengagement, and modest to low correlations with professionalism attitudes. A positive correlation was observed with a clerkship rating focused on professionalism in peer interactions. CONCLUSIONS: These findings demonstrate modest proficiency in the use of decision-making strategies among fourth-year medical students. Additional research using the Professional Decision-Making Measure should explore scores among physicians in various career stages, and the causes and correlates of scores. Educators could utilize the measure to assess courses that teach decision-making strategies