2,313 research outputs found
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
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
Characterization of the 5-HT(7) receptor as a new therapeutic target for the treatment of pain
No full text[eng] The work showed in this Thesis has been part of the “5-HT7 and neuropathic pain” project in the pharmaceutical company Esteve. Thus, the aim of this Thesis was in line with the goal of the 5-HT7 project at Esteve, focused on drug discovery of 5-HT7 receptor ligands for the treatment of neuropathic pain.
Taking the advantage of a genetic approach (5-HT7 receptor knockout mice) and pharmacological tools (5-HT7 receptor ligands) we investigated at the preclinical level the role of 5-HT7 receptors in nociception and the therapeutic interest of 5-HT7 receptor ligands on pain treatment. The 5-HT7 receptor ligands used were SB-258719 and SB-269970 as 5- HT7 receptor antagonists, and AS-19, MSD-5a, E-55888 and E-57431 as 5-HT7 receptor agonists. E-55888 and E-57431 developed by Esteve were described for the first time and their binding profile and functionality (cAMP formation) were examined. In vivo behavioural studies were performed in mice and rats subjected to nociceptive, inflammatory, neurogenic or neuropathic pain conditions.
Our results showed that 5-HT7 receptors per se were not involved in the nociceptive response to a normally noxius stimulus, although when co-activated together with opioid receptors potentiated the opioidergic analgesic response in nociceptive pain conditions. Indeed, 5-HT7 receptor knockout and wild-type mice showed similar sensitivity to a noxious heat stimulus, and systemic administration of the 5-HT7 receptor agonist E-55888 or the 5-HT7 receptor antagonist SB-258719 showed no effects on acute nociceptive pain using the tail flick test in mice. However, the 5-HT7 receptor agonist E-55888 enhanced the morphine-induced analgesia in this test and this potentiation was significantly reversed by the 5-HT7 receptor antagonist SB-258719.
On the other hand, we studied the role of 5-HT7 receptors in pain conditions involving central sensitization. We showed that the 5-HT7 receptor agonists AS-19, E-55888 and E-57431 inhibited capsaicin-induced mechanical hypersensitivity, nerve injury-induced mechanical and thermal hypersensitivity and reduced the phase II formalin-induced nociception. In contrast, a promotion of mechanical hypersensitivity after administration of the 5-HT7 receptor antagonists SB-258719 and SB-269970 was observed. This reduction of hypersensitivity by agonists and promotion of hypersensitivity by antagonists was reversed by antagonists and agonists, respectively. It is important to note that effectiveness of the treatment with 5-HT7 receptor agonists was not masked by non-specific motor effects, as no motor incoordination was found in the rota-rod test at the doses used and no tolerance to the effect was evidenced following repeated systemic administrations.
The antinociceptive effects exerted by systemic 5-HT7 receptor agonists seemed to be mediated by 5-HT7 receptors localized in the spinal cord. We found that intrathecal administration of the 5-HT7 receptor agonist E-57431 inhibited mechanical hypersensitivity secondary to capsaicin injection and nerve injury-induced mechanical hypersensitivity. In contrast, a pronociceptive effect was observed after local intraplantar injection of the selective 5-HT7 receptor agonist E-57431 in the capsaicin model. Thus, the antinociceptive role mediated by central 5-HT7 receptors seems to predominate over their pronociceptive role at the periphery, resulting in an overall analgesic effect when 5-HT7 receptor agonists are administered by a systemic route. In line with these spinal antinociceptive effects, we found an increased immunoreactivity of 5-HT7 receptors in the ipsilateral dorsal horn of the spinal cord in sciatic nerve-injured mice. This increased 5-HT7 receptor expression in the dorsal horn induced by nerve injury could represent a physiological, compensatory, protective spinal mechanism relevant to the control of nociception in neuropathic pain conditions.
We observed that 5-HT7 receptors co-localized with GABAergic neurons in the ipsilateral dorsal horn of the spinal cord. Therefore, we suggested that an indirect action through activation of 5-HT7 receptors localized on inhibitory interneurons may be responsible of the antinociceptive effects observed after administration of 5-HT7 receptor agonists.
Finally, using 5-HT7 receptor knockout mice, we demonstrated that the 5-HT7 receptor agonists AS-19, E-55888 and E-57431 exerted in vivo target specific effects on pain control. We observed that systemic administration of these 5-HT7 receptor agonists reduced phase II formalin-induced nociception in wild-type but not in 5-HT7 receptor knockout mice. Taken together, these data add a piece of knowledge to the role played by 5-HT7 receptors in the control of pain and point to a new potential use of 5-HT7 receptor agonists as promising drugs for the treatment of neuropathic pain.[cat] El treball mostrat en aquesta Tesi ha format part del projecte “5-HT7 i dolor neuropàtic” de l’empresa farmacèutica Esteve. Per tant, els objectius d’aquesta Tesi estan en línea amb l’objectiu del projecte 5-HT7 d’Esteve focalitzat en el descobriment de compostos amb afinitat pel receptor 5-HT7 pel tractament del dolor neuropàtic.
A partir de l’aproximació genètica amb l’ús de ratolins genoanul•lats pel receptor 5-HT7 i d’eines farmacològiques com compostos amb afinitat pel receptor 5-HT7, vàrem investigar a nivell preclínic el paper dels receptors 5-HT7 en el dolor i l’interès terapèutic dels lligands del receptor 5-HT7 en dolor. Entre els compostos utilitzats hi trobem el SB-258719 i el SB- 269970 com antagonistes pel receptor 5-HT7, i el AS-19, MSD-5a, E-55888 i el E-57431 com agonistes pel receptor 5-HT7. E-55888 i E-57431 van ser descrits per primera vegada i es va estudiar el seu perfil d’afinitat, selectivitat i funcionalitat. Es van realitzar estudis de comportament in vivo en ratolí i rata sotmesos a unes condicions de dolor nociceptiu, inflamatori, neurogènic i neuropàtic.
Els nostres resultats van mostrar que els receptors 5-HT7 per si mateixos no estaven implicats en la resposta a un estímul nociu, mentre que sí interaccionen amb el sistema opiodèrgic en condicions de dolor nociceptiu. Ratolins genoanul•lats pel receptor 5-HT7 van mostrar la mateixa sensibilitat enfront un estímul tèrmic nociu. L’administració sistèmica de l’agonista del receptor 5-HT7 E-55888 o l’antagonista del receptor 5-HT7 SB-258719 no van mostrar efecte en el dolor agut nociceptiu. En canvi, vàrem observar que els efectes antinociceptius de la morfina per via oral obtinguts en resposta a l’estímul tèrmic nociu del tail-flick, eren potenciats amb l’administració sistèmica conjunta de l’agonista del receptor 5-HT7 E-55888. Aquesta potenciació va ser revertida al mateix temps amb la coadministració de l’antagonista del receptor 5-HT7 SB-258719.
També vàrem estudiar el paper dels receptors 5-HT7 en condicions de dolor i sensibilització central. L’administració sistèmica d’agonistes selectius pel receptor 5-HT7 inhibia la hipersensibilitat mecànica induïda per capsaicina, la hipersensibilitat mecànica i tèrmica induïda per la lesió del nervi ciàtic, i el dolor induït per la fase II del model de la formalina. Això suggeria la implicació dels receptors 5-HT7 en condicions de sensibilització central. En canvi, es va observar una promoció de la hipersensibilitat mecànica amb els antagonistes del receptor 5-HT7. Tant els efectes dels agonistes i antagonistes del receptor 5-HT7 es van revertir amb la coadministració d’antagonistes i agonistes del receptor 5-HT7, respectivament. És important senyalar que les dosis amb eficàcia analgèsica dels agonistes del receptor 5-HT7 eren inferior a les dosis que produïen efectes adversos amb el test del rota-rod. A més, no es va observar tolerància de l’efecte analgèsic amb l’administració de dosis repetides de l’agonista del receptor 5-HT7 E-57431.
L’efecte analgèsic obtingut amb l’administració sistèmica dels agonistes pel receptor 5-HT7 semblava ser degut a l’activació de receptors 5-HT7 localitzats a nivell espinal. Vàrem trobar que l’administració intratecal de l’agonista del receptor 5-HT7 E-57431 inhibia la hipersensibilitat mecànica secundària a la injecció de capsaicina i la induïda per la lesió del nervi ciàtic. En canvi, es va observar un increment de la hipersensibilitat mecànica induïda per capsaicina amb la injecció local intraplantar de l’agonista del receptor 5-HT7 E-57431. En resum, l’efecte antinociceptiu obtingut a través de l’activació dels receptors 5-HT7 a nivell espinal sembla predominar respecte l’efecte pronociceptiu de la perifèria quan s’administra sistèmicament un agonista pel receptor 5-HT7. En línea amb l’efecte antinociceptiu observat a nivell espinal, vàrem trobar un increment de la immunoreactivitat dels receptors 5-HT7 de l’asta dorsal de la medul•la espinal en ratolins amb lesió del nervi ciàtic. Aquest increment en l’expressió del receptor 5-HT7 en l’asta dorsal induït per la lesió del nervi podria representar un mecanisme espinal fisiològic, compensatori i protector rellevant pel control de dolor en condicions de dolor neuropàtic.
Vàrem observar una col•localització dels receptors 5-HT7 en cèl•lules GABAèrgiques. En aquest sentit, l’activació dels receptors 5-HT7 col•localitzats en interneurones inhibitòries de l’asta dorsal de la medul•la espinal podria ser el mecanisme d’acció implicat en els efectes antinociceptius observats amb els agonistes del receptor 5-HT7.
Finalment, utilitzant ratolins genoanul•lats pel receptor 5-HT7, vàrem demostrar que els agonistes pel receptor 5-HT7 AS-19, E-55888 i E-57431 exercien efectes diana específics em el control de dolor. L’administració subcutània d’aquests agonistes pel receptor 5-HT7 reduïren la nocicepció induïda per formalina de la fase II en ratolins salvatges però no en ratolins genoanul•lats, suggerint una especificitat dels efectes obtinguts in vivo a través del receptor 5-HT7.
Aquest treball aporta un millor coneixement del paper del receptor 5-HT7 en el control del dolor i suggereix un nou potencial ús terapèutic dels agonistes pel receptor 5-HT7 com a fàrmacs prometedors pel tractament del dolor neuropàtic
Transforming Ates To Ht-Ates, Insights From Dutch Pilot Project
No full textAquifer Thermal Energy Storage (ATES) systems combined with a heat pump save energy for space heating and cooling of buildings. In most countries the temperature of the stored heat is allowed up to 25-30°C. However, when heat is available at higher temperatures (e.g. waste heat, solar heat), it is more efficient to store higher temperatures because that improves heat pump performance or makes it unnecessary. Therefore, interest in HT-ATES development is growing. Next to developing new HT-ATES projects, there is also a large potential for additional energy savings by transforming ‘regular’ low-temperature LT-ATES systems to a HT-ATES. Such a transformation is tested for a greenhouse system in the Netherlands. This greenhouse has a LT-ATES system operational since 2012, and from 2015 onwards heat is stored in the warm well at temperatures up to 45°C. In this HT-ATES transformation pilot, water quality parameters are closely monitored as well as temperature distribution in the subsurface (using DTS). Together with the operators, the results from the ATES monitoring are used to continuously improve system performance. Numerical groundwater and heat flow simulations of actual and expected well pumping data are used to evaluate how well operation can be optimized. In this paper, the optimization using monitoring results and simulations is discussed as well as general and site specific lessons/conclusions for such transformations.Water Resource
The etiology of esophageal cancer in high- and low- risk areas of Jiangsu province, China
No full text [Background]Esophageal cancer (EC) remains one of the most common and fatal malignancies worldwide. The geographic variation in EC occurrence is striking, and China is an area with one of the highest incidences of EC. A number of epidemiological studies have been conducted toward EC in the past decades, results suggested that tobacco smoking, alcohol drinking, unhealthy dietary factors and chronic injuries of the esophageal mucosa are important in the development of this disease. Genetic polymorphisms in enzymes involved in metabolism of carcinogens may also influence individual susceptibility. However, the effects of major lifestyle and hereditary risk factors on the development of EC remain poorly understood in China. Moreover, little attention has been paid to the etiological heterogeneity between similar areas with great risk gradient. [Methods]From 2003 to 2007, a large population-based case-control study of EC has been conducted in a selected high-risk area and a selected low-risk area of Jiangsu Province, one of the highest cancer incidence areas in China. In total, 1,520 cases and 3,879 controls were recruited. In this thesis, we evaluated the role of major lifestyle factors such as tobacco smoking, alcohol drinking and dietary factors, as well as inherited determinants including family history of cancer and genetic polymorphisms of alcohol-metabolizing related genes on the risk of EC. In addition, we investigated how much of the risk gradient between two areas could be explained by variation in the distributions of major risk factors. [Results] Tobacco smoking and alcohol drinking moderately increased the risk of EC, while the positive associations were only found among men but not among women. Dietary factors were observed to play important roles in the development of EC. Specific dietary habits i.e., fast eating speed, and hot eating and/or drinking substantially elevated EC risk and could explain more than 20% of EC cases each. High intake of salty foods and fried foods, low consumption of raw garlic were also observed to increase the risk of EC. In addition to environmental and lifestyle factors, we confirmed that a positive family history can significantly increase EC risk, and found the inheritance may modify the effect of some unhealthy lifestyles. Moreover, we further explored the relationship between EC and single nucleotide polymorphismsof ADH1B, ADH1C and ALDH2 genes. Results showed that the slow metabolizing ADH1B G allele, ADH1C G allele and ALDH2 A allele significantly increased EC risk among moderate-to-heavy alcohol drinkers, and a significant interaction was observed between ALDH2 gene and alcohol consumption. Lastly, we found that more than 60% of EC cases could be attributable to major lifestyle risk factors in the study population; furthermore, dissimilar distribution of several lifestyle factors, together with variations of hereditary factors may be largely responsible for the incidence difference between two study areas. [Conclusion]The findings in this thesis confirm that unhealthy lifestyles including smoking, alcohol drinking and some dietary factors are the predominant risk factors of EC in China, and a large proportion of incidence difference between regions at varying risk could be attributed to the different prevalence of lifestyle factors. As most of the identified risk factors are modifiable, these could be translated into risk reduction prevention programs in China, and a substantial proportion of new EC cases are expected to be prevented by eliminating or avoiding these risk factors in the population. </p
"Put your own house in order first": local perceptions of EU influence on Romani integration policies in the Czech Republic
No full textThis article examines the influence of the European Union (EU) on the development and implementation of Romani integration policy in the Czech Republic from the perspective of those responsible for policy delivery. Based on analysis of key policy documents and research conducted in the Czech Republic, this article first examines how Romani integration became a more important issue during membership negotiations and then discusses how the criticism of the European Commission's Regular Reports was received by those responsible for implementing pro-Romani policies. Finally, the paper assesses how the status of full EU membership has impacted on integration policy. The article concludes that while funding for Romani integration projects has benefitted some groups, the overall impression of the EU is of a remote institution, quick to criticise and unwilling to practise what it preaches
Silence of TRIF facilitated EV71 infection in HT-29 cells.
No full textA. Knockdown of TRIF in HT-29 cells. Total RNA was extracted from HT-29-CTL and HT-29-TRIF cells. TRIF mRNA transcripts were measured by realtime RT-PCR with primers for TRIF (top). Cell lysates from HT-29-CTL and HT-29-TRIF were prepared for SDS-PAGE and western blot analysis with anti-TRIF antibody (bottom). B. Cell viability of lentivirus-infected HT-29 cells as measured by the MTT assay. C. Increased viral VP1 gene expression in TRIF-silenced HT-29. HT-29-CTL and HT-29-TRIF cells were infected with EV71 with an m.o.i. of 2, and total RNA were prepared at 12, 24, and 36 hrs p.i. for RT-PCR with specific primers for viral VP1 gene. D. EV71 viral replication decreased in TRIF-silenced HT-29 cells. HT-29-CTL and HT-29-TRIF cells were infected with EV71 and the supernatants were collected at 12, 24, and 36 hrs for infectious viral titration at Vero cells in a standard TCID50 assay.</p
Insect resistance to Nilaparvata lugens and Cnaphalocrocis medinalis in transgenic indica rice and the inheritance of gna plus sbti transgenes
No full textHydrogen sulfide activates TRPA1 and releases 5-HT from epithelioid cells of the chicken thoracic aorta
No full textEpithelioid cells in the chicken thoracic aorta are chemoreceptor cells that release 5-HT in response to hypoxia. It is likely that these cells play a role in chemoreception similar to that of glomus cells in the carotid bodies of mammals. Recently, H2S was reported to be a key mediator of carotid glomus cell responses to hypoxia. The aim of the present study was to reveal the mechanism of action of H2S on 5-HT outflow from chemoreceptor cells in the chicken thoracic aorta. The 5-HT outflow induced by NaHS, an H2S donor, and Na2S3, a polysulfide, was measured by using a HPLC equipped with an electrochemical detector. NaHS (0.3-3 mM) caused a concentration-dependent increase in 5-HT outflow, which was significantly inhibited by the removal of extracellular Ca2+. outflow induced by NaHS (0.3 mM) was also significantly inhibited by voltage-dependent L- and N-type Ca2+ channel blockers and a selective TRPA1 channel blocker. Cinnamaldehyde, a TRPA1 agonist, mimicked the secretory response to H2S. 5-HT outflow induced by Na2S3 (10 M) was also inhibited by the TRPA1 channel blocker. Furthermore, the expression of TRPA1 was localized to 5-HT-containing chemoreceptor cells in the aortic wall. These findings suggest that the activation of TRPA1 and voltage-dependent Ca2+ channels is involved in H2S-evoked 5-HT release from chemoreceptor cells in the chicken aorta. (C) 2016 Elsevier Inc. All rights reserved
High-Temperature Aquifer Thermal Energy Storage (HT-ATES) system for research development and demonstration on the TU Delft campus
No full textAt present, over half of all primary energy used in Europe is used for heating and cooling. Therefore, decarbonizing the heating supply is essential to achieve climate targets. Underground thermal energy storage is a key enabling technology for the energy transition to buffer the large seasonal mismatch between thermal energy demand and sustainable thermal energy production capabilities. In Delft, a High-Temperature Aquifer Thermal Energy Storage (HT-ATES) system will be installed at the campus of Delft University of Technology (TU Delft). It will be integrated in the wider heating system on and around the TU Delft campus, which itself is undergoing a transformation to optimally supply sustainable thermal energy. The district heating network will be extended and utilize the thermal energy from a geothermal doublet producing heat at around 75-80°C with a flow rate of ~350m3/hr. Excess energy produced by the geothermal well in summer will be stored in the HT-ATES system, and will be utilised when demand exceeds production throughout the winter. The HT-ATES system will comprise of 7 wells (3 hot wells of 80°C and 4 warm wells of 50°C) to a depth of approximately 200m, with storage in an unconsolidated sedimentary aquifer between 160-200m depth. It is designed so that the instantaneous excess power from the geothermal project can be stored and demand from the district heating network be extracted from the system.The HT-ATES system at TU Delft is partially funded by local stakeholders and the European commission within the PUSH-IT project and has two primary goals: (i) to reduce carbon emissions on TU Delft campus , and (ii) to create a unique demonstration, education and research infrastructure. The complexity of a HT-ATES requires innovative solutions during the entire system life cycle. The scientific programme that is initially planned within the project is therefore focusing on various research fields and includes:- Characterisation of the subsurface formations including mechanical, hydraulic, thermal, and chemical properties.- Evaluation and monitoring of the biological conditions and microbial diversity, and potential impact on water quality.- Innovations in drilling and completion, monitoring and performance.- Quantification of the system performance and system impact during multiple storage cycles and the full lifecycle of the HT-ATES. This will include extensively monitoring temperature distribution and water quality in the subsurface to characterise behaviour and improve models.- Demonstrate and develop the implementation of HT-ATES in an urban setting, including control of the system in the built-environment and transforming the conventional heat network to a future-proof heat network.- To allow access to other universities or institutions with active programmes in the field of Geothermal Science and Engineering to jointly carry out research and perform experiments.-Societal engagement and legal evaluation for improving the just energy transition.Geo-engineeringWater Resource
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