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In 2010, the Municipality of Cuenca, through its environmental management commission (EMC), and the World Bank, through the environment and natural resources department, started a collaboration targeted towards strengthening EMC’s capacity to better manage Cuenca’s environmental assets and to provide EMC with hard evidence and data that will serve as departing point for decision-makers towards the formulation of public policy. Two main areas of focus were chosen: (i) costs of environmental degradation for Cuenca; and (ii) climate change impacts and resilience measures for Cuenca. This report describes the findings of the first area of focus. This report tries to capture the main results and to describe the assumptions and input data utilized, through a detailed step-by-step description of an internationally-accepted and validated methodology, an explanation of input data needs, equations used, assumptions made, and alternative calculation streams; and through the demonstration of this methodology as it is applied to the real case of air pollution in Cuenca. Analyses about the cost of environmental degradation are often used as an environmental priority-setting tool, because it gives the estimated socio-economic costs of environmental degradation (air pollution, inadequate water supply, sanitation, hygiene, and others). In this report, the methodology was used only for air pollution; similar studies can be replicated for other areas in order to have a full description of the different sources of pollution and the subsequent costs that Cuenca is subject to. Economic analysis (cost-benefit analysis) can be applied as a useful tool to prioritize among these interventions options with respect to their efficiency and cost effectiveness. Some policy reforms may also require to understand the political economy of reforms, for example, when taxi technology or bus technology of private firms is to be changed.

The arcuate nucleus of the hypothalamus (ARC) is a critical nexus of neuron populations that interpret peripheral signals of energy status and deliver diverse efferent outputs to metabolically active tissues. These neurons are critical to maintaining energy homeostasis, and disruption of their complex neurocircuitry results in metabolic disease phenotypes. The goals of this dissertation were to investigate the novel role for the circulating [alpha]-klotho protein to regulate neurons within the ARC to modulate peripheral metabolism. Intracerebroventricular administration of a recombinant [alpha]-klotho in lean, obese, and type I diabetic mice for 1-12 days revealed a novel role for [alpha]-klotho to regulate whole body energy and glucose metabolism. [alpha]-Klotho-treated mice experienced suppressed food intake, increased energy expenditure, and improved glucose clearance. Central [alpha]-klotho-mediated regulation of peripheral glucose metabolism was determined to be independent from body weight and insulin sensitivity but may be due to reduced hepatic gluconeogenic gene expression and improved insulin secretion. Furthermore, cerebrospinal fluid collected from humans demonstrated body weight is strongly and negatively correlated to [alpha]-klotho concentrations, suggesting central [alpha]-klotho is also important to energy homeostasis in humans. Experiments utilizing ex vivo patch clamp electrophysiology, immunohistochemical detection of the neuronal activation marker cFOS, and the immortal GT1-7 hypothalamic cell line demonstrated a novel role for [alpha]-klotho to regulate neurons in the ARC. [alpha]-Klotho decreased activity of the orexigenic neuropeptide Y/agouti-related peptide neuron population and increased activity of a subset of the anorexigenic proopiomelanocortin neuron population. [alpha]-Klotho was also shown to regulate the non-neuronal ARC astrocytes, which are involved in hormonal transport, nutrient-sensing, and neuronal health. Mechanistically, ICV pretreatment with inhibitors of fibroblast ...

The global clean and improved cooking solutions sector has evolved significantly in recent years. Clean and improved cooking solutions are also beginning to generate attractive market opportunities for local and international private enterprises in the provision of cooking appliances, fuels, and financing. This report covers all clean and improved cooking solutions that can improve on the fuel efficiency and emissions performance of traditional cooking technologies such as the three stone fire, open U-shaped clay or mud stoves, metal bucket charcoal stoves, and unvented coal stoves. Under the definition of improved cooking solutions the report includes all cook stoves that improve fuel efficiency without reducing particulate matter emissions to the low levels necessary for optimal health and environmental outcomes as defined by World Health Organization (WHO) household air pollution guidelines and the International Standards Organization International Workshop Agreement (ISO IWA) guidelines for improved cook stoves. The objectives of this report are threefold: (1) establish a common fact base for sector analysis; (2) build a case for increased sector focus and investment; and (3) inform intervention strategies. The information provided in this report constitutes a best-effort attempt to harmonize definitions and data sources to give a comprehensive picture of the overall sector landscape, with the caveat that this is likely to be somewhat imprecise in various instances because of these definitional and data quality challenges. This report is divided into the following chapters: chapter one gives introduction. Chapter two presents the case for clean and improved cooking; chapter three presents the demand for clean and improved cooking energy; chapter four deals with the supply landscape; chapter five deals with the cooking appliance supply chain; chapter six presents the sector ecosystem; and chapter seven presents’ recommendations.

Health is a direct source of human welfare and also an instrument for raising income levels. The authors discuss a number of mechanisms through which health can affect income, focusing on worker productivity, children's education, savings and investment, and demographic structure. As well as the impact of current illness, health may have large effects on prospective life spans and life cycle behavior. Studies suggest there may be a large effect of health and nutrition in uteri, and in the first few years of life, on physical and cognitive development and economic success as an adult. Macroeconomic evidence for an effect on growth is mixed, with evidence of a large effect in some studies. However, there is a possibility that gains from health may be outweighed by the effect of increased survival on population growth, until a fertility transition occurs. The low cost of some health interventions that have large-scale effects on population health makes health investments a promising policy tool for growth in developing countries. In addition, higher priority could be given to tackling widespread 'neglected' diseases that is, diseases with low mortality burdens that are not priorities from a pure health perspective, but that do have substantial effects on productivity.

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life. The research included in this thesis utilizes a C57BL/6J (B6) mouse model to examine the changes to gene expression and behaviour following a binge-like exposure to ethanol during synaptogenesis, a period of neurodevelopment characterized by the rapid formation and pruning of synaptic connectivity that correlates to brain development during the human third trimester. B6 pups were treated with a high dose (5 g/kg over 2 hours) of ethanol at postnatal day 4 (P4), P7, or on both days (P4+7). Mice were evaluated using a battery of behavioural tests designed to assess FASD-relevant phenotypes, and showed delayed achievement of neuromuscular coordination, hyperactivity, increased anxiety-related traits, and impaired spatial learning and memory. Gene expression analysis identified 315 transcripts that were altered acutely (4 hours) following ethanol exposure. Up-regulated transcripts were associated with cellular stress response, including both pro- and anti-apoptotic molecules, as well as maintenance of cell structural integrity. Down-regulated transcripts were associated with energetically costly processes such as ribosome biogenesis and cell cycle progression. Genes critical to synapse formation were also affected, as well as genes important for the appropriate development of the hypothalamic-pituitary-adrenal axis. Additionally, gene expression changes within the adult brain of mice treated with ...

Low back pain (LBP) remains the most prevalent and costly work-related disability worldwide and is directly associated with "physical" risk factors prevalent in manual material handling (MMH) tasks. Back-support exoskeletons (BSEs) are a promising ergonomic intervention to mitigate LBP risk, by reducing muscular exertion and spine loading. The purpose of this work was to help better understand both the "intended" and "unintended" consequences of BSE use on physical risk factors for LBP, as an essential prerequisite for the safe and effective implementation of this technology in actual workplaces. The first study assessed the effects of using two BSEs on objective and subjective responses during repetitive lifting involving symmetric and asymmetric postures. Wearing both BSEs significantly reduced peak levels of trunk extensor muscle activity and reduced energy expenditure. Such reductions, though, were more pronounced in the symmetric conditions and differed between the two BSEs tested. The second study quantified the assistive torque profiles of two passive BSEs using a computerized dynamometer, with both human subjects and a mannequin. Clear differences in torque magnitudes were evident between the BSEs, though both generated more assistive torques during flexion than extension. The third study estimated the effects of BSE use on lumbosacral compressive and shear forces during repetitive lifting using an optimization-based model. Using both BSEs reduced peak compression and anteroposterior shear forces, but these effects differed between tasks and BSE designs. Reductions in composite measures of trunk muscle activity did not correspond consistently with changes in spine forces when using a BSE. The fourth study quantified the effects of two passive BSEs on trunk stability and movement coordination during repetitive lifting. Some adverse effects on stability were evident for pelvis and thorax movements and coupling of these body segments, suggesting that caution is needed in selecting a BSE for a given MMH task. Overall, we found that the efficacy of BSEs is design- and task-specific. Important safety features of the exoskeletons were also identified, providing insights on their performance boundaries. Overall, the BSEs tested were more effective and safer in tasks closer to the mid-sagittal plane and with moderate degrees of trunk flexion. Doctor of Philosophy Low back pain (LBP) remains the most prevalent and costly work-related disability worldwide, and the risk of LBP is related to "physical" risk factors common in manual material handling (MMH) tasks. Back-support exoskeletons (BSEs) are a new ergonomic intervention that may reduce the risk of occupational LBP, by reducing muscular efforts and loads on the spine. For the safe use of BSEs, though, it is critical to better understand both the "intended" and "unintended" consequences of this emerging technology. In this dissertation, such consequences of BSE use were evaluated in the context of repetitive lifting tasks. The first study assessed the efficacy of two BSEs in terms of physical demands during repetitive lifting tasks involving a range of torso bending and twisting. Wearing both BSEs reduced the physical demands on back muscles and decreased energy consumption. Larger reductions, though, were observed in forward bending and such reductions differed between the two BSEs tested. The second study measured the amount of support provided by two BSEs using a new measurement method, which was examined for both human subjects and a mannequin. Clear differences in the BSE support were evident between the BSEs, and both devices generated more support during torso forward bending than returning upright. The third study estimated the effects of BSE use on low back loadings during repetitive lifting using a computational model. Using both BSEs reduced loads on the low back region, though such reductions were task-specific and depended on the BSE design. The fourth study quantified the effects of the BSE use on torso stability and movement patterns during repetitive lifting. Some adverse effects on stability were evident for lower and upper torso, suggesting that caution is needed in selecting a BSE for a given MMH task. Findings from this work show the potential benefits of BSEs for use in MMH tasks, yet such benefits can depend on the BSE design and the MMH task they are used for. Further, BSE use can lead to adverse effects, especially with tasks involving extreme working postures.

Includes bibliographical references. ; 2015 Summer. ; It is well documented that hypothalamic proopiomelanocortin (POMC) neurons are a critical component in the maintenance of energy balance. POMC neurons release peptide transmitters that modulate pathways involved in food intake, energy expenditure, and reward pathways. POMC peptide release can result in the inhibition of food intake and increased activation of these cells is thought to precipitate the development of anorexia in the activity-based anorexia (ABA) rodent model. Currently, the physiological underpinnings that drive the development of anorexia are not fully understood, but evidence suggests that POMC neurons are a likely contributor. The work presented in Chapter 2 of this dissertation provide further evidence that POMC neurons are activated during the early development of ABA and addresses whether this increase in POMC neuron activation is necessary for decreased food intake and body weight during ABA. POMC neurons were selectively inhibited during the onset of ABA. The results presented here indicate that POMC neuron activation facilitates suppression of food intake during the early stages of ABA. To determine if increased activation of POMC neurons is sufficient to induce lasting anorexia, in Chapter 3 POMC neurons were activated acutely and long-term to determine if activation of these cells alone is sufficient to initiate the development of anorexia. The data in Chapter 3 show that acute activation of POMC neurons decreases daily food intake. Prolonged activation of POMC neurons was able to give rise to long-term decreases in food intake under the proper conditions; but, the data from these experiments provide insight regarding methodological considerations that are important for long-term behavioral work in rodents. Activation or inhibition of POMC neurons through the approach used here could lead not only to altered release of peptides from these neurons, but also altered amino acid (AA) transmitter release. Unlike, the heavily studied ...

text ; Addiction is thought to arise, in part, from a maladaptive learning process in which enduring memories of drug-related experiences are formed, resulting in persistent and uncontrollable drug-seeking behavior. However, it is well known that both acute and chronic alcohol (ethanol) exposures impair various types of learning and memory in both humans and animals. Consistent with these observations, both acute and chronic exposures to ethanol suppress synaptic plasticity, the major neural substrate for learning and memory, in multiple brain areas. Therefore, it remains unclear how powerful memories associated with alcohol experience are formed during the development of alcoholism. The mesolimbic dopaminergic system is critically involved in the learning of information related to rewards, including drugs of abuse. Both natural and drug rewards, such as ethanol, cause release of dopamine in the nucleus accumbens and other limbic structures, which is thought to drive learning by enhancing synaptic plasticity. Accumulating evidence indicates that plasticity of glutamatergic transmission onto dopamine neurons may play an important role in the development of addiction. Plasticity of NMDA receptor (NMDAR)-mediated transmission may be of particular interest, as NMDAR activation is necessary for dopamine neuron burst firing and phasic dopamine release in projection areas that occurs in response to rewards or reward-predicting stimuli. NMDAR plasticity may, therefore, drive the learning of stimuli associated with rewards, including drugs of abuse. This dissertation finds that repeated in vivo ethanol exposure induces a metaplasticity of NMDAR-mediated transmission in mesolimbic dopamine neurons, expressed as an increased susceptibility to the induction of NMDAR LTP. Enhancement of NMDAR plasticity results from an increase in the potency of inositol 1,4,5- trisphosphate (IP3) in producing the facilitation of action potential-evoked Ca2+ signals critical for LTP induction. Interestingly, amphetamine exposure produces a similar enhancement of IP3R function, suggesting this neuroadaptation may be a common response to exposure to multiple drugs of abuse. Additionally, ethanol-treated mice display enhanced learning of cues associated with cocaine exposure. These findings suggest that metaplasticity of NMDAR LTP may contribute to the formation of powerful memories related to drug experiences and provide an important insight into the learning component of addiction. ; Neuroscience

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).