3,449 research outputs found
Ritual for the foundation of a temple (archaic), tablet concordance HT 38 - CTH 414
No full textTranscription of the ritual text for the foundation of a temple (archaic) based on the tablet concordance HT 38 (inventory no. BM 108575). Emmanuel Laroche translated this text as "Rituel de fondation d'un temple (archaïsant),” and classified the concordance in the category of Anatolian magic in ritual texts (Catalogue des textes Hittites, No. 414).Paper (1 sheet
5-HT(1B) receptor agonist enhances breakpoint for cocaine on a progressive ratio (PR) schedule during maintenance of self-administration in female rats but reduces breakpoint for sucrose
No full textBackground: Previous research showed that the 5-HT(1B) receptor agonist CP94253 enhanced cocaine reinforcement rate during maintenance of daily self-administration (SA), but inhibited reinforcement rate after 21 days of abstinence in male rats. Here we examined whether female rats show similar effects of CP94253 during maintenance as males across estrous cycle phases. Methods: Female rats trained on a fixed ratio 5 (FR5) cocaine reinforcement schedule were tested for the effects of CP94253 (5.6 mg/kg, s.c.) on cocaine reinforcement rate during each phase of the estrous cycle, with access to either low (0.075 and 0.1875) or high (0.375 and 0.75) cocaine doses available for 1 h sequentially in descending dose order. Other female and male rats trained on a progressive ratio (PR) schedule of cocaine or sucrose reinforcement were tested for CP94253 (0, 3.2, 5.6, and 10 mg/kg, s.c.) effects on reinforcement rate in 3-h sessions. CP94253 effects on responding during sucrose cue-reactivity were also examined post-abstinence. Results: Regardless of sex, CP94253 enhanced breakpoints on the PR schedule during maintenance of cocaine SA but attenuated breakpoints for sucrose reinforcement and decreased responding during sucrose cue-reactivity. FR results showed that CP94253 attenuated cocaine reinforcement rate during all estrous cycle phases except metestrus. Conclusions: Overall, we suggest that CP94253 increased incentive motivation for cocaine during maintenance of SA in female and male rats, yet decreased motivation for sucrose. We also suggest that 5-HT(1B)Rs modulate motivation similarly across sexes except when females are in metestrus
Sex Differences and the Role of the Serotonin System in Early Life Stress-Induced Ethanol-Motivated Behaviors in Adulthood
No full textAlcohol is a psychoactive substance with dependence-producing properties that has been used by many cultures in human society for millennia. Among people 20-39 years old, 13.5% of total deaths are attributed to alcohol, and harmful use is a causal factor in more than 200 diseases and injury conditions. Current pharmacological treatments of alcohol use disorder mainly target the positive reinforcing properties of alcohol or increase sensitivity to the adverse effects of alcohol. However, these medications have limited efficacy in reducing alcohol use and maintaining sobriety. The majority of these treatments stem from data conducted solely in males and fail to target the psychological distress underlying alcohol motivation in those assigned female at birth and individuals with adverse childhood experiences who are more apt to drink to relieve negative affective states. The dorsal raphe nucleus (DRN)-serotonin (5-HT) system has an important role in mood regulation, is sexually dimorphic, vulnerable to stress-induced perturbations during development, and shows an inverse relationship with ethanol (EtOH) consumption. These characteristics make the 5-HT system an ideal target to investigate the mechanisms underlying aberrant alcohol consumption and drinking despite negative consequences, especially in at-risk populations. Our guiding hypothesis was that DRN 5-HT neurotransmission would underlie the sex-dependent effects of early life stress on EtOH intake and consumption despite negative consequences. To test this hypothesis, we first investigated the effects of sex and early life stress on EtOH-motivated behaviors in rats during adulthood. Next, we examined the role of the DRN 5-HT system in sex- and stress-dependent EtOH-motivated behaviors. Adolescent social isolation stress (SIS) was used as a translational model of early life stress.
Male and female rats were group housed or isolated postweaning before undergoing voluntary EtOH consumption (i.e., homecage drinking, self-administration (SA), footshock-punished SA) paradigms in adulthood to test the effects of sex and stress on EtOH consumption and consumption despite negative consequences. Consistent with our hypothesis, behavioral results indicated that SIS increased homecage EtOH preference and consumption, as well as responding during SA, particularly in females. Females also showed more punishment-resistant responding for EtOH than males.
To complement these behavioral findings, we employed a combination of electrophysiological, functional neuroanatomy, and chemogenetic strategies to explore the role of the DRN 5-HT system in sex- and stress-dependent EtOH-motivated behaviors. Both SIS and EtOH exposure induced hypofunction of 5-HT neurons, particularly in females, paralleling SIS-induced increases in EtOH-motivated behaviors. Chemogenetic strategies expanded upon the sex- and stress-dependent nature of this relationship. Chemogenetic activation of DRN 5-HT neurons in Tph2-iCre rats reduced responding for both natural and EtOH reward and elevated punished responding for EtOH, indicating a causal connection between DRN 5-HT signaling and acute responding to rewards and punishment.
Collectively, our findings reveal an inverse relationship between EtOH intake and 5-HT neurotransmission, further implicating EtOH consumption as an important negative reinforcer to “normalize” SIS-induced hypofunction of the DRN 5-HT system, particularly in stress-sensitive females. Furthermore, our conclusions highlight the DRN 5-HT system as a potential pharmacotherapeutic target to treat aberrant alcohol consumption as a means to “self-medicate” hypofunction of the 5-HT system in at-risk populations.Biomedical Neuroscienc
The serotonergic dorsal raphe nucleus in opiate dependence and stress-induced relapse
No full textOpioids are used for the clinical treatment of pain, but can lead to tolerance and addiction. In this project we examined the role of the serotonin (5-HT) system originating from the dorsal raphe nucleus (DRN) during morphine exposure, withdrawal, abstinence and following an acute stressor capable of initiating behavioral relapse. Following four days of morphine exposure rats showed a preference for the morphine paired side of the conditioned place preference (CPP) chamber. After four days of morphine abstinence, rats showed no net preference for the morphine paired side. The next day rats were exposed to forced swim stress and returned to the CPP chamber where they demonstrated stress-induced reinstatement. Utilizing whole-cell patch-clamp we demonstrated an increase in the amplitude of inhibitory post-synaptic currents (IPSCs) in 5-HT DRN neurons, but not non 5-HT DRN neurons of morphine-conditioned subjects. Next the stress neurohormone corticotrophin releasing factor (CRF) was administered in vitro instead of forced swim. We found an increase in CRF-R2-mediated inward current of 5-HT DRN neurons in animals with a morphine history. From this experiment we concluded that morphine history sensitizes 5-HT DRN neurons to the GABAergic inhibitory effects of stress and to some of the effects of CRF. In the next series of experiments we surgically implanted either morphine or placebo pellets in rats for 72 hours to create physical dependence. The pellets were subsequently removed, and animals experienced up to seven days of abstinence with and without forced swim stress exposure. Real time quantitative PCR was used to measure the mRNA levels of genes at multiple points across this timeline. We examined genes involved in trophic support, stress responses and 5-HT regulation. We determined that mRNA levels for brain-derived neurotrophic factor (BDNF) and the BDNF receptor TrkB were downregulated after opiate exposure, and again following seven days of abstinence. Following seven days of abstinence there was a decrease in mRNA levels of the CRF-R1 receptor and an increase in mRNA levels of the CRF-R2 receptor. During acute opiate exposure there was a decrease in mRNA levels for the autoregulatory 5-HT1A receptor. Finally following forced swim, there was an increase in mRNA levels of the 5-HT synthesis enzyme TPH2. Collectively these results indicate that a morphine history in abstinent subjects may produce hypofunctioning of the 5-HT DRN system induced by multiple neurochemical mechanisms and this dysregulation may enhance vulnerability to stress-induced relapse.Cell Biolog
Risk analysis of High-Temperature Aquifer Thermal Energy Storage (HT-ATES)
No full textThe storage of heat in aquifers, also referred to as Aquifer Thermal Energy Storage (ATES), bears a high potential to bridge the seasonal gap between periods of highest thermal energy demand and supply. With storage temperatures higher than 50 °C, High-Temperature (HT) ATES is capable to facilitate the integration of (non-)renewable heat sources into complex energy systems. While the complexity of ATES technology is positively correlated to the required storage temperature, HT-ATES faces multidisciplinary challenges and risks impeding a rapid market uptake worldwide. Therefore, the aim of this study is to provide an overview and analysis of these risks of HT-ATES to facilitate global technology adoption. Risk are identified considering experiences of past HT-ATES projects and analyzed by ATES and geothermal energy experts. An online survey among 38 international experts revealed that technical risks are expected to be less critical than legal, social and organizational risks. This is confirmed by the lessons learned from past HT-ATES projects, where high heat recovery values were achieved, and technical feasibility was demonstrated. Although HT-ATES is less flexible than competing technologies such as pits or buffer tanks, the main problems encountered are attributed to a loss of the heat source and fluctuating or decreasing heating demands. Considering that a HT-ATES system has a lifetime of more than 30 years, it is crucial to develop energy concepts which take into account the conditions both for heat sources and heat sinks. Finally, a site-specific risk analysis for HT-ATES in the city of Hamburg revealed that some risks strongly depend on local boundary conditions. A project-specific risk management is therefore indispensable and should be addressed in future research and project developments.Accepted Author ManuscriptWater Resource
Failure mode of segmental endoprostheses for tumour surgery: retrospective review of five Institutions
No full textFailure mode of segmental endoprostheses for tumour surgery: retrospective review of five Institution
Le ricostruzioni di femore distale con megaprotesi modulari: sopravvivenza degli impianti e complicazioni in uno studio multicentrico di 951 casi
No full textLe ricostruzioni di femore distale con megaprotesi modulari: sopravvivenza degli impianti e complicazioni in uno studio multicentrico di 951 cas
Cause di fallimento degli impianti in 2174 megaprotesi modulari: analisi dela casisitica di 5 centri di Oncologia Muscoloscheletrica
No full textCause di fallimento degli impianti in 2174 megaprotesi modulari: analisi dela casisitica di 5 centri di Oncologia Muscoloscheletric
Improving identification of HT-ATES performance drivers and -barriers
No full textHigh temperature aquifer thermal energy storage (HT-ATES) can potentially solve the mismatch between heat supply and demand. It can provide a large scale seasonal heat storage solution. Thereby it enables an increase in full load hours of the base heat source, which can benefit project performance on both costs and emissions. However, the limited number of successful pilot projects indicates the technology has not escaped its state of infancy. There is a gap from concept to implementation, which is signified by the disagreement of experts on performance drivers and barriers of HT-ATES. This research aims to narrow the described knowledge gap, by improving identification of HT-ATES performance drivers and barriers. Thereby it strives to improve decision making of HT-ATES implementation, and further enhance future HT-ATES application in heating projects. The broad scope of research demands both a diagnostic and design-orientated approach, and fits seamlessly with a multi-criteria decision analysis. The analysis entails the stages of creating, evaluating, comparing and ranking of case-specific scenarios. Parametric variation changes the conditions for HT-ATES implementation across the scenarios. A simulation model is developed and connected to a groundwater model to apply the parametric variation, to create the different scenarios, and consequently to produce the quantitative information for further evaluation. During the stages of creating, evaluating, comparing and ranking, the methodology systematically produces new results on the opportunities and risks introduced by HT-ATES, and additionally on the HT-ATES performance drivers and barriers. The results show that HT-ATES enables the opportunity of improving project performance with respect to the internal rate of return and emissions. Groundwater impact remains the greatest risk, but it can be minimised with smart decision making. To support the decision maker and to overcome the risk of groundwater impact, the research proposes several performance-enhancing, non-explicit guidelines. The guidelines focus on realising an HT-ATES implementation, where project performance with respect to internal rate of return, emissions and groundwater impact are balanced. Thereby they explain the major HT-ATES performance drivers and barriers. The guidelines are summarised below. The decision maker is recommended to .. 1. .. minimise the uncertainty, through thorough subsurface characterization before implementation. Secondly, to focus on aquifers with a minimum depth of 200 [m] and a minimum hydraulic conductivity of 5 [m/d] 2. .. assure network return temperatures during peak demand are below expected storage temperatures 3. .. not consider project life-times exceeding 20 years 4. .. assure yearly maximum base source heat production is always lower than yearly consumer heat demand 5. .. to strive for a flat demand curve and apply peak-shaving, by means of, for example, variable heat prices Currently, the guidelines have the purpose of giving direction to the decision maker, but they will become more explicit once the methodology is improved, and the uncertainty and number of assumptions in the model is decreased.Electrical Engineering | Sustainable Energy Technolog
Youth work, racist behaviour and young people Education or blame?
No full textThis paper explores the issue of racist behaviour by young people, particularly
White young people and the response of youth workers and other educators to
that racism. In particular, it argues that anti-racism is simply not working with the
young people it really needs to work with. The paper provides evidence that
youth workers have been disempowered by understandings of anti-racist policy
and practice, and that the same policies may well, unintentionally, be having a
negative affect on the most marginalised white young people. The paper argues
that this may well be due to ‘deficit’ understandings of such white young people,
understandings close to ‘underclass’ pathology.
The paper was conceived before the events of summer 2001, which saw violent
clashes involving white and Asian young people, and the Police, in several
towns in the North of England, and violent incidents directed at Asylum Seekers
across the UK, culminating in a racist murder in Sighthill, Glasgow. However,
these events can be viewed as all too predictable. They pose fundamental
questions of theory and practice for Youth Workers and other educators already
working with young people who may support, or even perpetrate, such acts of
racist violence.
This paper aims to debate these questions by focussing in particular on the
findings and lessons of an action research project carried out by the University
of Huddersfield, material from which has since been published by the
Commission for Racial Equality as ‘Open Talk, Open Minds’ (CRE, 1999). The
methodology and findings of this research are discussed below
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