517 research outputs found

    Consideration for Scaffolding Open-Ended Engineering Problems: Instructor Reflections After Three Years

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    This full research-to-practice paper is a collaboration between researchers and instructors to examine the scaffolding of open-ended problems. Most assigned homework problems are closed-ended with one correct answer and are unlike the ill-defined problems practicing engineers solve in the workplace. To begin bridging this gap, our research team of engineering education researchers and instructors have been designing and implementing ill-defined, open-ended homework problems for the past three years. This study presents instructor reflections on considerations for scaffolding open-ended problems, made after examining survey data from their own students. We present the results in six practices of scaffolding that better support students in their solving of the problems

    Vibrational Enhancement of the Effective Donor - Acceptor Coupling

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    The paper deals with a simple three sites model for charge transfer phenomena in an one-dimensional donor (D) - bridge (B) - acceptor (A) system coupled with vibrational dynamics of the B site. It is found that in a certain range of parameters the vibrational coupling leads to an enhancement of the effective donor - acceptor electronic coupling as a result of the formation of the polaron on the B site. This enhancement of the charge transfer efficiency is maximum at the resonance, where the effective energy of the fluctuating B site coincides with the donor (acceptor) energy.Comment: 5 pages, 3 figure

    The Role of <i>Roles</i> in Risk Management Change:The Case of an Italian Bank

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    This paper explores the role of roles (i.e. groups of actors characterised by the same functional tasks within an organisation), and of their interactions, within processes of change in risk management (RM). By combining insights from the literature on RM and from institutional studies, this paper suggests that change in RM can be interpreted as a process that involves both enabling and precipitating dynamics [Greenwood, R., &amp; Hinings, C. R. (1996). Understanding radical organizational change: Bringing together the old and the new institutionalism. The Academy of Management Review, 21, 1022\ue2\u80\u931054. doi:10.5465/AMR.1996.9704071862] between different roles. Aiming to address these dynamics empirically, we rely on a longitudinal case study of an Italian bank. The study shows that the interactions between roles were dependent on their respective specific interests, the different institutional templates they supported, and the shifts in power for control over relevant information. These dynamics both affected and were affected by the change in the template-in-use within the bank and allowed a sort of RM ideal (i.e. the search for more RM) to persist over evolving templates

    Quantum transport through a DNA wire in a dissipative environment

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    Electronic transport through DNA wires in the presence of a strong dissipative environment is investigated. We show that new bath-induced electronic states are formed within the bandgap. These states show up in the linear conductance spectrum as a temperature dependent background and lead to a crossover from tunneling to thermal activated behavior with increasing temperature. Depending on the strength of the electron-bath coupling, the conductance at the Fermi level can show a weak exponential or even an algebraic length dependence. Our results suggest a new environmental-induced transport mechanism. This might be relevant for the understanding of molecular conduction experiments in liquid solution, like those recently performed on poly(GC) oligomers in a water buffer (B. Xu et al., Nano Lett 4, 1105 (2004)).Comment: 5 pages, 3 figure

    Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms

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    Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans

    Human liver glycogen phosphorylase inhibitors bind at a new allosteric site

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    AbstractBackground: Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target.Results: The binding site in human liver glycogen phosphorylase (HLGP) for a class of promising antidiabetic agents was identified crystallographically. The site is novel and functions allosterically by stabilizing the inactive conformation of HLGP. The initial view of the complex revealed key structural information and inspired the design of a new class of inhibitors which bind with nanomolar affinity and whose crystal structure is also described.Conclusions: We have identified the binding site of a new class of allosteric HLGP inhibitors. The crystal structure revealed the details of inhibitor binding, led to the design of a new class of compounds, and should accelerate efforts to develop therapeutically relevant molecules for the treatment of diabetes

    Green function techniques in the treatment of quantum transport at the molecular scale

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    The theoretical investigation of charge (and spin) transport at nanometer length scales requires the use of advanced and powerful techniques able to deal with the dynamical properties of the relevant physical systems, to explicitly include out-of-equilibrium situations typical for electrical/heat transport as well as to take into account interaction effects in a systematic way. Equilibrium Green function techniques and their extension to non-equilibrium situations via the Keldysh formalism build one of the pillars of current state-of-the-art approaches to quantum transport which have been implemented in both model Hamiltonian formulations and first-principle methodologies. We offer a tutorial overview of the applications of Green functions to deal with some fundamental aspects of charge transport at the nanoscale, mainly focusing on applications to model Hamiltonian formulations.Comment: Tutorial review, LaTeX, 129 pages, 41 figures, 300 references, submitted to Springer series "Lecture Notes in Physics

    Modeling the Mechanism of Action of a DGAT1 Inhibitor Using a Causal Reasoning Platform

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    Triglyceride accumulation is associated with obesity and type 2 diabetes. Genetic disruption of diacylglycerol acyltransferase 1 (DGAT1), which catalyzes the final reaction of triglyceride synthesis, confers dramatic resistance to high-fat diet induced obesity. Hence, DGAT1 is considered a potential therapeutic target for treating obesity and related metabolic disorders. However, the molecular events shaping the mechanism of action of DGAT1 pharmacological inhibition have not been fully explored yet. Here, we investigate the metabolic molecular mechanisms induced in response to pharmacological inhibition of DGAT1 using a recently developed computational systems biology approach, the Causal Reasoning Engine (CRE). The CRE algorithm utilizes microarray transcriptomic data and causal statements derived from the biomedical literature to infer upstream molecular events driving these transcriptional changes. The inferred upstream events (also called hypotheses) are aggregated into biological models using a set of analytical tools that allow for evaluation and integration of the hypotheses in context of their supporting evidence. In comparison to gene ontology enrichment analysis which pointed to high-level changes in metabolic processes, the CRE results provide detailed molecular hypotheses to explain the measured transcriptional changes. CRE analysis of gene expression changes in high fat habituated rats treated with a potent and selective DGAT1 inhibitor demonstrate that the majority of transcriptomic changes support a metabolic network indicative of reversal of high fat diet effects that includes a number of molecular hypotheses such as PPARG, HNF4A and SREBPs. Finally, the CRE-generated molecular hypotheses from DGAT1 inhibitor treated rats were found to capture the major molecular characteristics of DGAT1 deficient mice, supporting a phenotype of decreased lipid and increased insulin sensitivity

    Step-Scan Fourier Transform Infrared Absorption Difference Time-Resolved Spectroscopy Studies of Excited State Decay Kinetics and Electronic Structure of Low-Spin d6 Transition Metal Polypyridine Complexes With 10 Nanosecond Time Resolution

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    Step-scan Fourier transform absorption difference time-resolved spectroscopy (S2FTIR ∆A TRS) has been used to collect mid-IR time-resolved infrared spectra of the transient electronic excited states of polypyridine transition metal complexes with 10 ns time resolution. The time-resolved data can be used for kinetic analysis or to generate “snapshots” of the lowest lying excited state. Shifts of vibrational bands in the excited state relative to the ground state can be used to infer significant details of the electronic structure of the excited state. The multiplex advantage of the FTIR technique allows a wide variety of vibrational bands to be analyzed for this purpose. In the example illustrated, the shift of the ester ν(CO) band in {Ru(bpy)[4,4′-(COOEt)2bpy]2}

    Dopaminergic modulation of affective and social deficits induced by prenatal glucocorticoid exposure

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    Prenatal stress or exposure to elevated levels of glucocorticoids (GCs) can impair specific neurobehavioral circuits leading to alterations in emotional processes later in life. In turn, emotional deficits may interfere with the quality and degree of social interaction. Here, by using a comprehensive behavioral approach in combination with the measurement of ultrasonic vocalizations, we show that in utero GC (iuGC)-exposed animals present increased immobility in the forced swimming test, pronounced anhedonic behavior (both anticipatory and consummatory), and an impairment in social interaction at different life stages. Importantly, we also found that social behavioral expression is highly dependent on the affective status of the partner. A profound reduction in mesolimbic dopaminergic transmission was found in iuGC animals, suggesting a key role for dopamine (DA) in the etiology of the observed behavioral deficits. Confirming this idea, we present evidence that a simple pharmacological approach—acute L-3,4-dihydroxyphenylacetic acid (L-DOPA) oral administration, is able to normalize DA levels in iuGC animals, with a concomitant amelioration of several dimensions of the emotional and social behaviors. Interestingly, L-DOPA effects in control individuals were not so straightforward; suggesting that both hypo- and hyperdopaminergia are detrimental in the context of such complex behaviors.This work was supported by a grant of Institute for the Study of Affective Neuroscience (ISAN) and Janssen Neurosciences Prize. SB and AJR have Fundacao para a Ciencia e Tecnologia (FCT) fellowships (SFRH/BD/89936/2012; SFRH/BPD/33611/2009)
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