Role of the Subthalamic Nucleus in the Circuitry Mediating Food- and Cocaine-Seeking Behavior

Thesis (PhD) - Indiana University, Psychology, 2007The subthalamic nucleus (STN) is part of the basal ganglia, which play a crucial role in motor control and in processing information from motor cortical areas. Although the STN is classically considered a motor structure, recent studies suggest that it may also be involved in the motivation for natural and drug reward. The STN may differentially modulate natural and drug reward via circuitry that includes the nucleus accumbens (NAcc), a structure belonging to the mesocorticolimbic circuit which has been identified as the neural substrate of the reinforcing effects of reward. Here, we assess the effects of bilateral STN lesions on the self-administration (SA) and subsequent reinstatement of sucrose- and cocaine-seeking behavior. Bilateral STN lesions block reinstatement of cocaine-seeking behavior, but not the reinstatement of food-seeking behavior. Neuronal correlates in the NAcc are also investigated. NAcc neurons respond to cocaine or sucrose and the conditioned stimulus (CS) during SA and the CS during reinstatement. Moreover, STN lesions have profound effects on these responses. Additionally, we assess the effects of STN lesions on operant responding for reward under a progressive ratio (PR) schedule of reinforcement, a schedule thought to measure the reinforcing efficacy of rewards. Bilateral STN lesions enhance responding for sucrose reward, but attenuate responding for cocaine reward. Furthermore, STN lesions differentially modulate NAcc neuronal activity associated with operant responding for either sucrose or cocaine reward under a PR schedule of reinforcement. Collectively, these results provide additional evidence for the role of the STN in food- and cocaine-seeking behavior and further support the NAcc in food- and cocaine-seeking behavior. In conclusion, these experiments demonstrate that the STN, classically considered a motor nucleus, differentially modulates the motivation, or craving, for natural and drug reward

Effects of external stream flow and afterbody variations on the performance of a plug nozzle

The off-design operation of an isentropic plug nozzle designed for a jet pressure ratio of 15 was investigated experimentally at subsonic Mach numbers up to 0.9 and jet pressure ratios up to 5. When installed in a cylindrical nacelle with a sharp turn at the nozzle lip, the interaction of the jet and the external stream produced low pressures on the base formed by the high lip angle. These low pressures increased the nacelle drag and caused an overexpansion of the jet, which resulted in lower pressures on the plug and, hence, reduced thrust. With a boattail ahead of the plug nozzle, the base pressures were increased and the jet overexpansion significantly reduced

The role of culture, consumtion and community in cluster development: the case of Portland's athletics and outdoor industry, Oregon (USA)

No abstract available

The Digital Life of Walkable Streets

Walkability has many health, environmental, and economic benefits. That is why web and mobile services have been offering ways of computing walkability scores of individual street segments. Those scores are generally computed from survey data and manual counting (of even trees). However, that is costly, owing to the high time, effort, and financial costs. To partly automate the computation of those scores, we explore the possibility of using the social media data of Flickr and Foursquare to automatically identify safe and walkable streets. We find that unsafe streets tend to be photographed during the day, while walkable streets are tagged with walkability-related keywords. These results open up practical opportunities (for, e.g., room booking services, urban route recommenders, and real-estate sites) and have theoretical implications for researchers who might resort to the use social media data to tackle previously unanswered questions in the area of walkability.Comment: 10 pages, 7 figures, Proceedings of International World Wide Web Conference (WWW 2015

Local Nodes in Global Networks: The Geography of Knowledge Flows in Biotechnology Innovation

The literature on innovation and interactive learning has tended to emphasize the importance of local networks, inter-firm collaboration and knowledge flows as the principal source of technological dynamism. More recently, however, this view has come to be challenged by other perspectives that argue for the importance of non-local knowledge flows. According to this alternative approach, truly dynamic economic regions are characterized both by dense local social interaction and knowledge circulation, as well as strong inter-regional and international connections to outside knowledge sources and partners. This paper offers an empirical examination of these issues by examining the geography of knowledge flows associated with innovation in biotechnology. We begin by reviewing the growing literature on the nature and geography of innovation in biotechnology research and the commercialization process. Then, focusing on the Canadian biotech industry, we examine the determinants of innovation (measured through patenting activity), paying particular attention to internal resources and capabilities of the firm, as well as local and global flows of knowledge and capital. Our study is based on the analysis of Statistics Canada’s 1999 Survey of Biotechnology Use and Development, which covers 358 core biotechnology firms. Our findings highlight the importance of in-house technological capability and absorptive capacity as determinants of successful innovation in biotechnology firms. Furthermore, our results document the precise ways in which knowledge circulates, in both embodied and disembodied forms, both locally and globally. We also highlight the role of formal intellectual property transactions (domestic and international) in promoting knowledge flows. Although we document the importance of global networks in our findings, our results also reveal the value of local networks and specific forms of embedding. Local relational linkages are especially important when raising capital—and the expertise that comes with it—to support innovation. Nevertheless, our empirical results raise some troubling questions about the alleged pre-eminence of the local in fostering innovation

NASA's Understanding of Risk in Apollo and Shuttle

Mathematical risk analysis was used in Apollo, but it gave unacceptably pessimistic resultsand was discontinued. Shuttle was designed without using risk analysis, under the assumptionthat good engineering would make it very safe. This approach led to an unnecessarily riskydesign, which directly led to the Shuttle tragedies. Although the Challenger disaster wasdirectly due to a mistaken launch decision, it might have been avoided by a safer design. Theultimate cause of the Shuttle tragedies was the Apollo era decision to abandon risk analysis

Metformin Improves Insulin Signaling in Obese Rats via Reduced IKK Action in a Fiber-Type Specific Manner

Metformin is a widely used insulin-sensitizing drug, though its mechanisms are not fully understood. Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of κB kinaseβ (IKKβ) in this same tissue are unknown. The aim of this study was to (1) determine the ability of metformin to attenuate IKKβ action, (2) determine whether changes in AMPK activity are associated with changes in IKKβ action in skeletal muscle, and (3) examine whether changes in AMPK and IKKβ function are consistent with improved insulin signaling. Lean and obese male Zuckers received either vehicle or metformin by oral gavage daily for four weeks (four groups of eight). Proteins were measured in white gastrocnemius (WG), red gastrocnemius (RG), and soleus. AMPK phosphorylation increased (P < .05) in WG in both lean (57%) and obese (106%), and this was supported by an increase in phospho-ACC in WG. Further, metformin increased IκBα levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKβ activity (P < .05), and was associated with reduced IRS1-pSer307 (30%) in the WG of obese rats (P < .02). From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKβ activity, as evidenced by elevated IκBα levels and reduced IRS1-Ser307 phosphorylation in a fiber-type specific manner

Poverty and trade liberalization: empirical evidence from 21 African countries

The study investigated the possible nexus between trade liberalization and poverty in 21 African countries covering the period 2005–2014. The study deployed the following econometric tests: descriptive statistics; the correlation matrix and variance inflator; the panel unit root test; the pooled OLS technique; and the panel co-integration test (Johansen co-integration test). In order to confirm the robustness and validity of the regression model result, Ramsey RESET, cross dependence, autocorrelation and heteroscedasticity tests were conducted. The findings reveal that foreign direct investment and inflation rate had a positive relationship with the human development index while exchange rates and trade openness were negatively related to poverty level at the 5 percent level. The study recommended urgent policy measures aimed at revamping the poverty alleviation programmes. The study recommended that in a bid to diversify export market, developing countries should target other developing countries in the spirit of South–South cooperation. Such countries should also consider the joining or strengthening of regional economic integration. Incentives for production and human capacity building in the export-oriented sector should be emplaced. Social and economic policies are required to protect any country against the adverse effects of lowered trade barriers

Mitochondrial Hâ‚‚Oâ‚‚ emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans

High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease. Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the Hâ‚‚Oâ‚‚-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial Hâ‚‚Oâ‚‚ emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves insulin sensitivity despite a high-fat diet. These findings place the etiology of insulin resistance in the context of mitochondrial bioenergetics by demonstrating that mitochondrial Hâ‚‚Oâ‚‚ emission serves as both a gauge of energy balance and a regulator of cellular redox environment, linking intracellular metabolic balance to the control of insulin sensitivity. Original version available at http://www.jci.org/articles/view/3704

A Mi\u27kmaq First Nation cosmology: investigating the practice of contemporary Aboriginal Traditional Medicine in dialogue with counselling – toward an Indigenous therapeutics

This paper explores from a Mi’kmaq and Aboriginal standpoint foundational knowledge in Indigenous therapeutics. Based on an eco-social-psycho-spiritual way of working, the article proposes Indigenous cultural models that open a window to a rich cultural repository of meanings associated with Indigenous cosmology, ontology and epistemology. The three layers of meaning, theory and practice within the symbolic ‘Medicine Lodge’ or ‘Place of The Dreaming’ give rise to ways of working that are deeply integrative and wholistic. These forms of Indigenous theory and practice have much to offer the counselling and complimentary health professions