2,260 research outputs found

    A new functional role for lateral inhibition in the striatum: Pavlovian conditioning

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    The striatum has long been implicated in reinforcement learning and has been suggested by several neurophysiological studies as the substrate for encoding the reward value of stimuli. Reward prediction error (RPE) has been used in several basal ganglia models as the underlying learning signal, which leads to Pavlovian conditioning abilities that can be simulated by the Rescorla-Wagner model.

Lateral inhibition between striatal projection neurons was once thought to have a winner-take-all function, useful in selecting between possible actions. However, it has been noted that the necessary reciprocal connections for this interpretation are too few, and the relative strength of these synaptic connections is weak. Still, modeling studies show that lateral inhibition does have an overall suppression effect on striatal activity and may play an important role in striatal processing. 

Neurophysiological recordings show task-relevant ensembles of responsive neurons at specific points in a behavioral paradigm (Barnes et al., 2005), which appear to be induced by lateral inhibition (see Ponzi and Wickens, 2010). We have developed a similarly responding, RPE-based model of the striatum by incorporating lateral inhibition. Model neurons are assigned to either the direct or the indirect pathway but lateral connections occur within and between these groups, leading to competition between both the individual neurons and their pathways. We successfully applied this model to the simulation of Pavlovian phenomena beyond those of the Rescorla-Wagner model, including negative patterning, unovershadowing, and external inhibition

    Nitrogen Cycle Chemistry with Metal-Pincer Complexes Relevant to Electrochemical Nitrogen Fixation

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    The large-scale industrial fixation of N2 to NH3 through the Haber-Bosch process has cemented itself as the primary means to provide N for fertilizer and commodity chemicals globally. However, our dependence on this process is unsustainable in the long term due to its reliance on fossil fuels to generate H2 and to provide the substantial energy input for the reaction, paired with high infrastructure requirements that necessitate centralized synthesis plants and sophisticated transportation networks. As an alternative, electrochemical fixation of N2, coupling water oxidation to provide proton (H+) and electron (e–) equivalents with the N2 reduction reaction (NRR) to achieve the 6H+/6e– reduction of N2 to 2 NH3, could operate on a smaller, localized scale while utilizing renewable sources to generate electrical energy to drive the reaction. A key challenge in achieving electrochemical N2 fixation is the development of catalysts for electrochemical NRR. Existing heterogeneous catalysts for NRR suffer from poor activity, selectivity, and robustness. Insights that aid the development of better NRR catalysts may be found by studying molecular systems that can reduce N2. This thesis probes potential N2 functionalization pathways that could be involved in electrochemical NRR by studying molecular model systems in which N2 binds to, or is cleaved by, reduced metal-pincer complexes. Chapter 1 describes electrochemical N2 fixation as an alternative to the Haber-Bosch process. A molecular approach towards understanding electrochemical NRR is proposed, especially through bimetallic N2 cleavage to form metal nitrides. Strategies for the subsequent functionalization of the metal nitride are discussed, primarily via proton-coupled electron transfer (PCET) reduction of the nitride into NH3. Challenges involved in PCET nitride reduction, as well as opportunities inspired by molecular N2 reduction catalysts and recent discoveries of potent PCET reagents, are identified and applied to a hypothetical system for electrochemical NRR. Chapter 2 describes the protonation and electrochemical reduction of Ir- and Rh-pincer complexes that can strongly bind N2. The potential utility of these complexes in an electrochemical NRR system are assessed by complimentary electrochemical and spectroscopic studies exploring their stepwise protonation and electrochemical reduction. Protonation was found to be a prerequisite for electrochemical reduction of the N2 complexes, with protonation occurring at the metal center to form metal hydrides. Protonation triggers release of the N2 ligand, preventing reductive N2 functionalization with these complexes. Chapter 3 investigates the possibility of oxidative functionalization of an N2-derived Re nitride in order to form NOx species. Although no N–O bond formation was achieved at the nitride, a series of Re nitrides was synthesized and characterized in which the metal center is oxidized by 1e– and/or the supporting pincer ligand is oxidized to a nitroxide. The Re-nitride interaction was monitored over the series using NMR and IR spectroscopies, X-ray crystallography, and computational methods. Cooperative oxidation of both the metal center and the supporting ligand results in the weakest Re-nitride interaction, more localization of the LUMO at the nitride ligand, and an umpolung in nitride reactivity. Chapter 4 applies PCET methods to N2-derived Re nitrides in an attempt to reduce the nitride to NH3, thus closing the cycle of N2 to NH3. Stepwise PCET mechanisms were prohibited by high-energy intermediates in both systems; however, the combination of SmI2 and H2O to generate a strong concerted PCET reagent resulted in formation of 74% yield of NH4+ in one system, but exclusive production of H2 in the other. Other PCET methods, such as pairing organic H-atom transfer reagents with SmI2, are also assessed for PCET nitride reduction. Chapter 5 studies the conversion of NH3 to a nitride in a Re system that can also cleave N2. Re-ammine and Re-amide intermediates were isolated, and the mechanisms of H atom removal from these to form the nitride were identified. Experimental determination of the N–H bond enthalpies in the Re-amide were used to benchmark computational studies elucidating the thermodynamics of N–H bond cleavage (and formation, the microscopic reverse). The putative Re-imide intermediate in the PCET reduction pathway was found to feature a particularly weak N–H bond, representing a thermodynamic bottleneck to PCET nitride reduction in this system

    Prison wardens\u27 perceptions of sex offenders, sex offender registration, community notification, and residency restrictions.

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    There is relatively little known about how criminal justice system actors perceive sex offenders and the fairness, efficacy, and scope of policies aimed at sex offenders. Similarly, there is sparse research that specifically examines the attitudes, beliefs, and experiences of prison wardens. Following in the footsteps of earlier research (Tewksbury & Mustaine, 2011; Tewksbury, Mustaine, & Payne, 2011, in press), the present study addresses these gaps by considering the attitudes and beliefs toward sex offenders held by wardens. This examination includes perceptions about sex offenders as prison inmates, sex offender registration, community notification, and residency restrictions. Further, this research assesses the utility of the 18-item Community Attitudes Toward Sex Offenders (CATSO) scale (Church, Wakeman, Miller, Clements, & Sun, 2008), which was advocated for use with criminal justice system actors, to determine whether or not the instrument can be effectively utilized with wardens. Findings and policy implications are discussed

    Support partners of registered sex offenders : exploring their experiences, identities, and perceptions.

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    Although it is widely recognized that many convicted criminal offenders experience considerable setbacks in communities that make their lives more arduous, registered sex offenders (RSOs) who live in American society arguably face more challenging impediments. As a result, ensuring their access to social support is especially salient. The notion that social support is particularly relevant to RSOs is perhaps best manifested through a common feature of community-based sex offender treatment programs, where participating RSOs are obligated to forge social relationships with primary support partners. These individuals are an important population to examine, as they purportedly play important roles with respect to helping a particularly stigmatized group of criminal offenders – RSOs – successfully reintegrate into society as productive, law-abiding citizens. And yet, relatively little is known about individuals who have a social link with and provide social support to publicly identified sex offenders, and no previously identified study has specifically examined support partners of RSOs. Thus, in order to provide critical, informative, and rich knowledge about individuals presumably closest to RSOs, the present study utilizes in-depth qualitative interviews with 38 support partners across two sex offender treatment programs in the South. Analyses focus on their motivations for serving as support partners, costs associated with such roles, stigma management techniques, and attitudes and beliefs toward sex offender registration and notification (SORN). Contributions to knowledge, limitations, and corresponding policy implications are discussed

    The Harrowing of Hell, a Paschal Oratorio

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    The Harrowing of Hell is an event defined in early Christian doctrine, which states that between his death on Good Friday and his triumphant resurrection at Easter, Christ descended to Hell to claim the souls languishing in Satan\u27s thralldom by dint of Original Sin, having ransomed them by his passion and death. This oratorio is a treatment of that ancient story using the vibrant colors of early instrumental sound and drawing on a variety of forms and archetypes, most importantly those of the extant operas of Claudio Monteverdi (1567-1643) and the Easter Vigil of the Roman Catholic Church

    Clinical vignette: VIPoma as a cause of persistent diarrhea

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    A 48-year-old man originally presented with a 5-day history of watery, nonbloody diarrhea without recent travel or contact with ill people. His medical history was significant for a prolonged course of Clostridium difficile diarrhea 1 year earlier. On physical exam, he had orthostatic hypotension, dry mucous membranes, mild right lower quadrant tenderness to palpation, and hyperactive bowel sounds. Laboratory testing revealed a sodium level of 130 mEq/L, a potassium level of 1.7 mEq/L, a chloride level of 102 mEq/L, a bicarbonate level of 13 mEq/L, a blood urea nitrogen level of 43 mg/dL, a creatinine level of 1.6 mg/dL, and a calcium level of 11.4 mg/dL. Despite several liters of IV hydration and aggressive potassium repletion, he remained severely hypokalemic with a potassium level of 1.5 mEq/L. He was admitted to the medical ICU for further resuscitation. Stool testing was negative for C. difficile and other infectious organisms. The patient\u27s symptoms resolved before additional evaluation, and he was discharged with a presumed diagnosis of severe viral gastroenteritis. The patient returned 1 week later with recurrence of profuse diarrhea. His physical examination was notable for a blood pressure of 104/59 mm Hg (nonorthostatic) and a pulse of 106 beats/min, again with dry mucous membranes and mild tenderness to palpation of the right lower quadrant. Serum chemistry panel revealed a sodium level of 137 mEq/L, a potassium level of 2.3 mEq/L, a chloride level of 111 mEq/L, a bicarbonate level of 10 mEq/L, a blood urea nitrogen level of 38 mg/dL, a creatinine level of 2.3 mg/dL, and a calcium level of 10.4 mg/dL. Testing was again negative for an infectious source of diarrhea, and colonoscopy was not suggestive of inflammatory bowel disease. An abdominal CT revealed a 5-cm pancreatic tail mass. The patient was later found to have an elevated vasoactive intestinal peptide (VIP) level of 1,765 pg/mL (reference range, 0 to 60 pg/mL). Fecal osmolality was not obtained. The tumor was resected, and histology confirmed a neuroendocrine tumor
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