Degenerate Stability of the Caffarelli-Kohn-Nirenberg Inequality along the Felli-Schneider Curve

We show that the Caffarelli-Kohn-Nirenberg (CKN) inequality holds with a remainder term that is quartic in the distance to the set of optimizers for the full parameter range of the Felli-Schneider (FS) curve. The fourth power is best possible. This is due to the presence of non-trivial zero modes of the Hessian of the deficit functional along the FS-curve. Following an iterated Bianchi-Egnell strategy, the heart of our proof is verifying a `secondary non-degeneracy condition'. Our result completes the stability analysis for the CKN-inequality to leading order started by Wei and Wu. Moreover, it is the first instance of degenerate stability for non-constant optimizers and for a non-compact domain

Dopamine signaling in wake-promoting clock neurons is not required for the normal regulation of sleep in drosophila

Dopamine is a wake-promoting neuromodulator in mammals and fruit flies. In Drosophila melanogaster, the network of clock neurons that drives sleep/activity cycles comprises both wake-promoting and sleep-promoting cell types. The large ventrolateral neurons (l-LNvs) and small ventrolateral neurons (s-LNvs) have been identified as wake-promoting neurons within the clock neuron network. The l-LNvs are innervated by dopaminergic neurons, and earlier work proposed that dopamine signaling raises cAMP levels in the l-LNvs and thus induces excitatory electrical activity (action potential firing), which results in wakefulness and inhibits sleep. Here, we test this hypothesis by combining cAMP imaging and patch-clamp recordings in isolated brains. We find that dopamine application indeed increases cAMP levels and depolarizes the l-LNvs, but, surprisingly, it does not result in increased firing rates. Downregulation of the excitatory D1-like dopamine receptor (Dop1R1) in the l-LNvs and s-LNvs, but not of Dop1R2, abolished the depolarization of l-LNvs in response to dopamine. This indicates that dopamine signals via Dop1R1 to the l-LNvs. Downregulation of Dop1R1 or Dop1R2 in the l-LNvs and s-LNvs does not affect sleep in males. Unexpectedly, we find a moderate decrease of daytime sleep with downregulation of Dop1R1 and of nighttime sleep with downregulation of Dop1R2. Since the l-LNvs do not use Dop1R2 receptors and the s-LNvs also respond to dopamine, we conclude that the s-LNvs are responsible for the observed decrease in nighttime sleep. In summary, dopamine signaling in the wake-promoting LNvs is not required for daytime arousal, but likely promotes nighttime sleep via the s-LNvs.Fil: Fernández, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Hermann Luibl, Christiane. University Of Würzburg; AlemaniaFil: Peteranderl, Alina. University Of Wuerzburg; AlemaniaFil: Reinhard, Nils. University Of Wuerzburg; AlemaniaFil: Senthilan, Pingkalai R.. University Of Wuerzburg; AlemaniaFil: Hieke, Marie. University Of Wuerzburg; AlemaniaFil: Selcho, Mareike. University Of Wuerzburg; AlemaniaFil: Yoshii, Taishi. Okayama University; JapónFil: Shafer, Orie T.. City University of New York; Estados UnidosFil: Muraro, Nara Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Helfrich Förster, Charlotte. University Of Wuerzburg; Alemani

Mechanisms of Hsp90 regulation

Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated

Experimentation skills of primary school children

This project encompasses data and analysing scripts of the doctoral thesis of Sonja Peterander

Heating and air conditioning of battery electric city buses by reversible R744 heat pump modules

Stadtbusse weisen einen relativ hohen Energiebedarf zum Heizen und Klimatisieren des Fahrgastraums gegenüber anderen Fahrzeugarten wie Pkws oder Lkws auf, wofür die vergleichsweise große Außenfläche und die häufigen Türöffnungen ursächlich sind. Bei aktuellen batterieelektrischen Stadtbussen mit einem elektrischen Heizer reduziert sich an kalten Tagen mit Umgebungstemperaturen unter 0 °C die Fahrreichweite um etwa 50 %. Eine Wärmepumpe kann die Fahrreichweite in diesen Fällen deutlich erhöhen, wobei die derzeit eingesetzten Kältemittel R134a und R1234yf eine eingeschränkte Heizeffizienz aufweisen und darüber hinaus aus ökologischen Gründen umstritten sind. Mit dem natürlichen Kältemittel R744 (Kohlenstoffdioxid, CO2) werden diese Defizite aufgehoben. Ein modulares Wärmepumpen- und Klimaanlagensystem ermöglicht in einem Stadtbus die Verwendung von Pkw-Komponenten. Die Anzahl der Module kann bei den lokal begrenzten Einsatzgebieten von Stadtbussen an die jeweiligen Kundenbedürfnisse und klimatischen Bedingungen angepasst werden. Durch Skaleneffekte der Komponenten aus der Pkw-Produktion ist zudem von einer Erhöhung der Wirtschaftlichkeit auszugehen. Im Rahmen der vorliegenden Arbeit werden autarke, umschaltbare R744-Wärmepumpenmodule für Stadtbusse auf Basis von Pkw-Komponenten hinsichtlich der optimalen Modulanzahl und der Energieeffizienz wissenschaftlich untersucht. Bisher liegen keine wissenschaftlichen Untersuchungen zu modularen Konzepten in der Fahrzeugklimatisierung vor. Darüber hinaus werden die Heiz- und Kühlbedarfe des Innenraums bei realitätsnahen Einsatzszenarien analysiert und daraus Minimalanforderungen für batterieelektrische Stadtbusse abgeleitet. Diese Ergebnisse werden zur Bewertung der R744-Module herangezogen. Mit dem konzipierten Prototypen eines R744-Moduls wird die Funktionsfähigkeit nachgewiesen und Messungen zur Validierung eines Simulationsmodells durchgeführt. Das Simulationsmodell des R744-Prototypenmoduls liefert eine gute Übereinstimmung mit den Messdaten. Im Modell werden anschließend weitere Optimierungsmaßnahmen umgesetzt und darauf aufbauend die Maximalleistungen ermittelt sowie eine energieeffiziente Regelungsstrategie hergeleitet. Die Simulationsuntersuchungen haben gezeigt, dass im Heizfall bei geringen Lasten die aktive Anzahl an Modulen zugunsten eines energieeffizienteren Betriebs zu reduzieren sind, während im Kühlfall alle Module zu betreiben sind. In den Referenzstädten München, Stockholm, Ankara und Dubai sind drei Module zum Heizen und Kühlen eines charakteristischen Stadtbus-Innenraums für ein typisches Betriebsjahr erforderlich. Für Granada werden zwei Module und für Moskau vier Module benötigt. Die Fahrreichweite eines batterieelektrischen Stadtbusses kann im Heizfall bei -15 °C Umgebungstemperatur mit drei R744-Modulen um bis zu 52 % gegenüber einer R134a-Wärmepumpe mit elektrischem Heizer erhöht werden. Im Jahresenergievergleich dieser Technologien werden in den genannten gemäßigten bis kalten Referenzstädten 25 % des elektrischen Stroms zum Heizen und Klimatisieren und somit entsprechend Treibhausgas-Emissionen eingespart. Die vorgestellten R744-Wärmepumpenmodule auf Basis von Pkw-Komponenten stellen eine mögliche Schlüsseltechnologie zur Effizienzsteigerung und Verbreitung von batterieelektrischen Stadtbussen für einen Großteil der weltweiten urbanen Klimaregionen dar.City buses exhibit relatively high energy demands for heating and air conditioning the passenger cabin compared to other types of vehicles such as cars or trucks. This is due to the large external area and the frequent door openings. Heating a current battery electric city bus on cold days with ambient temperatures below 0 °C will reduce the driving range by approximately 50%. For this application a heat pump can increase the driving range significantly. The currently used refrigerants R134a and R1234yf have limited heating efficiency and are also topics of controversy due to their negative environmental impact. With the natural refrigerant R744 (carbon dioxide, CO2) these issues are resolved. A modular heat pump and air conditioning system makes it possible to use passenger car components in a city bus. The number of modules can be adapted to customer requirements and the climatic conditions determined for the locally limited areas where city buses are operational. Economies of scale will be achieved by using components from the passenger car industry. In the present work independent reversible R744 heat pump modules for city buses based on passenger car components are scientifically investigated with regard to the ideal number of modules and energy efficiency. So far, no scientific studies on modular concepts in vehicle HVAC systems are known. In addition, the heating and cooling demands of the cabin in realistic use cases are analysed and their minimum is deduced for battery electric city buses. This is used to evaluate the R744 modules. With the designed prototype of a R744 module the functionality is verified and measurements are taken to validate a simulation model. The simulation model of the R744 prototype module shows good correlation to the measurement data. Further optimisation steps are implemented in the model and, based on this, the maximum performance is determined and an energy-efficient control strategy is derived. The simulation studies have shown that in heating mode the active number of modules is reduced at low energy demands to ensure energy-efficient operation, while in cooling mode all modules should be activated. In the reference cities of Munich, Stockholm, Ankara and Dubai, three modules for heating and cooling a characteristic city bus cabin are required for a typical year of operation. Two modules are needed in Granada and four modules in Moscow. The driving range of a battery electric city bus can be improved in heating mode at -15 °C ambient temperature by up to 52% with three R744 modules compared to an R134a heat pump with electric heater. The comparison of annual energy consumption in the abovementioned moderately cold to cold reference cities shows that 25% of the electricity for heating and air conditioning as well as corresponding ratios of greenhouse gas emissions are saved. The presented R744 heat pump modules based on passenger car components represent a potential key technology for increasing the efficiency and market share of battery electric city buses for a large part of the world’s urban climate regions