In mental health policy, a central ethical dilemma concerns involuntary outpatient commitment (OPC), which aims to treat vulnerable individuals with serious mental illness who decline services. The first concern regards whether coercive services undermine the quality of clinical interactions within treatment, particularly as it relates to psychiatric medication use. The second concern is the unexamined role that OPC, and coercive psychiatric programs more broadly, plays in the broader landscape of social welfare policy. To examine these concerns, the purpose of this dissertation is to analyze how the management of psychiatric medications in involuntary outpatient services is undergirded by (a) provider and client interpretations of psychiatric medications effects and (b) moral discourses related to coercion and client autonomy. To achieve this aim, I examined data from a team-based ethnography that consisted of 1000 hours of participant-observations and 56 semi-structured interviews with 20 clients, 21 providers, and 12 client family members with diverse backgrounds. I analyzed how medication compliance was discussed, monitored, and enforced in an involuntary outpatient program. My analysis demonstrates that medications were interpreted as a technology to control clinical symptoms (clinical control) though, particularly among clients, were also viewed as a method to control client mental experiences, behavioral expression, and autonomy (social control). Providers believed that medications were a necessary component of services (compulsory compliance) and could reduce client vulnerability to violence victimization and perpetration related to clinical symptoms (medicating vulnerability). To address client noncompliance, providers employed several strategies that I categorized as client manipulation. These strategies included providers, family members, and court officials strategizing ways to undermine client autonomy without clients’ knowledge (concealed collusion), deceiving clients into believing that medications were mandated when they were not (performing coercion), and minimizing the role of client consent and preferences in decision-making processes (circumventing consent). These findings demonstrate the pervasive role of manipulation to gain client medication compliance in OPC, which I named institutional coercion. They also highlight that the broader moral justifications for manipulating clients relate to their status as structurally vulnerable in their community settings and a growing relationship between the erosion of the welfare state and psychiatric coercion.

This dissertation presents a novel extremum seeking control method which combines a time-varying Kalman filter with a Newton Raphson algorithm. The Kalman filter is used to estimate the gradient and Hessian of a performance function. The resulting estimates are used in the Newton Raphson algorithm to guide the system to a local extremum of the performance function.

Convergence of the method to a local extremum is proven when the system is subject to noisy measurements. This is accomplished by showing that the output of the algorithm is a supermartingale. It is shown that the system will converge to an area around the extremum with a radius defined, in part, by the error covariance of the Kalman filter estimates.

The method is applied to two examples. The first utilizes a single independent parameter performance function. The second applies the method to the problem of formation flight for drag reduction. In the first example, two implementations of the method are examined. The first uses only gradient estimates. The second uses both gradient and Hessian estimates. Both implementations show good convergence in the presence of noisy measurements.

The second example is of formation flight for drag reduction. The problem is described in some detail and includes an aerodynamic development of the drag-reduction phenomenon. The problem is explored with two simulations. The first uses coefficient of induced drag as its performance function and estimates the gradient and Hessian of the performance function. It shows good convergence of the method. The second simulation first uses pitch angle and then aileron deflection as its performance function. It estimates the gradient but not the Hessian of the performance function. It also shows good convergence.

Proteins of the cellular membranes provide crucial functions in the body; they are the passageways into and out of the cell, the pumps that generate and maintain chemical and electrical gradients, the receptors that transduce chemical messages and the scaffolding that gives the cell its shape. In order to function, proteins have a very specific shape which forms domains for interaction; the domains of a protein may interact with small molecules and make a structural rearrangement, or they may mediate protein-protein interactions or be assembled with other protein subunits to form a protein complex. Proteins with complicated function often are arranged into protein complexes which provide modular subunits that can be switched in or out of the complex over time or across cells. This modularity allows for combinatorial regulation of the output of the protein. In the case of ion channels--proteins that allow the passage of ions from one side of the membrane to another--the particular number of subunits and the combination with which different types of subunits may be assembled determine biophysical properties, such as the opening cooperativity or the current amplitude of the channel.

Ionotropic glutamate receptors are an important class of ion channels that open in response to glutamate. Glutamate receptors are the primary excitatory receptors of the mammalian central nervous system and they receive chemical signals which they convert to an electrical signal. The glutamate receptors are ion channels composed of various glutamate receptor subunits, which determine the functional output. For example, some subunits only allow permeation of certain ions, like sodium or potassium, but others allow for calcium influx. Similarly, some subunits have faster or slower gating kinetics, which determines the current amplitude in response to glutamate. In principle, glutamate receptor subunits may be similar enough that any combinatorial assembly of the subunits would be possible; however, it is known that glutamate receptors have a highly regulated assembly process that limits the possible combinations available to the cell. Using a single-molecule technique called subunit counting, we determined the rules of assembly for a kainite-type glutamate receptor. We discovered that that GluK2 homotetramers and 2:2 GluK2/GluK5 heterotetramers are possible receptor combinations, but not 1:3 or 3:1 GluK2/GluK5 assemblies. This suggests that there are specific regulation steps in the assembly of the quaternary structure that control the number and types of subunits assembled into a finished glutamate receptor.

Once a functional glutamate receptor has been properly assembled and delivered to the membrane, they are subject to various regulatory processes. One regulatory mechanism relies upon a protein family called the transmembrane AMPA-R regulatory protein (TARP) family. TARPs traffic AMPA-type glutamate receptors to the plasma membrane of cells and can functionally regulate the receptors by slowing receptor deactivation and desensitization. The molecular details of this process were previously unknown, but we have determined that TARPs bind to AMPA receptors in an expression-dependent manner. For low expression densities of the TARP, zero or one TARP will bind to the glutamate receptor. Alternatively, higher expression will yield more TARPs bound, and in the case of stargazin, the canonical member of the TARP family, it can bind up to four to a single glutamate receptor. This suggests that the mechanism of AMPA receptor regulation by TARPs is controlled at the level of plasma membrane expression of the TARPs.

Other ion channels, instead of responding to chemical signals, are activated by the voltage across the membrane. For example, the voltage-gated calcium channel is an important source of calcium entry into the cell and is therefore a key molecule in intracellular signaling. Calcium entry is tightly regulated by processes of calcium-dependent inactivation and calcium-dependent facilitation. These processes are regulated at the C-terminus of the voltage-gated calcium channel where calmodulin, a calcium-binding protein, is bound. To study the structural details of the calcium regulation process, the molecular structure of the voltage-sensitive calcium channel C-terminus was determined by protein crystallography and individual C-termini were seen to associate with a partner C-terminus. These data suggest that, contrary to popular belief, voltage-gated calcium channels may multimerize to form channel dimers, which may have additional calcium entry regulation. However, using subunit counting, we determined that voltage-gated calcium channels are, in fact, protein monomers and overexpression of calmodulin does not mediate dimerization.

Membrane proteins are also capable of signaling between the different membrane compartments of the cell. STIM1, a calcium-sensing protein of the endoplasmic reticulum (ER), signals from the ER membrane to proteins of the plasma membrane. These protein targets include the Orai1 calcium channel, for the restocking of ER calcium, and adenylyl cyclase to stimulate the production of cAMP. Using total internal reflection fluorescence (TIRF) microscopy and electrophysiology, we elucidate the pathway by which the innate immune system of airway epithelial cells responds to a bacterial lactone. Specifically, IP3 receptors become activated which releases calcium from the ER. Next, STIM1 activates adenylyl cyclase which signals to the cystic fibrosis transmembrane conductance regulator (CFTR) via cAMP and PKA. The activation of CFTR produces a transepithelial current to cleanse the epithelial cells of any bacteria that may be present.

This study explores the cycling of phosphorus (P) in the euphotic zone following upwelling in northeastern Monterey Bay (the Red Tide Incubator region) of coastal California, with particular emphasis on how bacteria and phytoplankton that form harmful algal blooms mediate and respond to changes in P availability. In situ measurements of nutrient concentrations, phytoplankton community composition, and cell-specific alkaline phosphatase (AP) activity (determined via enzyme-labeled fluorescence assay) were measured during three cruises. Upwelling led to a 10-fold increase in dissolved inorganic (DIP) in surface waters, reaching ∼0.5 μmol L⁻¹. This DIP was drawn down rapidly as upwelling relaxed over a period of 1 week. Ratios of nitrate to DIP drawdown (∼5:1, calculated as the change in nitrate divided by the change in DIP) were lower than the Redfield ratio of 16:1, suggesting that luxury P uptake was occurring as phytoplankton bloomed. Dissolved organic (DOP) remained relatively constant (∼0.3 μmol L⁻¹) before and immediately following upwelling, but doubled as upwelling relaxed, likely due to phytoplankton excretion and release during grazing. This transition from a relatively high DIP:DOP ratio to lower DIP:DOP ratio was accompanied by a decline in the abundance of diatoms, which had low AP activity, toward localized, spatially heterogeneous blooms of dinoflagellates in the genera Prorocentrum, Ceratium, Dinophysis, Alexandrium, andScrippsiella that showed high AP activity regardless of ambient DIP levels. A nutrient addition incubation experiment showed that phytoplankton growth was primarily limited by nitrate, followed by DIP and DOP, suggesting that P regulates phytoplankton physiology and competition, but is not a limiting nutrient in this region. AP activity was observed in bacteria associated with lysed cell debris and aggregates of particulate organic material, where it may serve to facilitate P regeneration, as well as affixed to the surfaces of intact phytoplankton cells, possibly indicative of close, beneficial phytoplankton–bacteria interactions.