Nociceptin Is a Chemorepellent in \u3ci\u3eTetrahymena thermophila\u3c/i\u3e

Tetrahymena thermophila are free-living, ciliated, eukaryotic organisms that respond to stimuli by moving toward chemoattractants and avoiding chemorepellents. Chemoattractant responses involve faster ciliary beating, which propels the organisms forward more rapidly. Chemorepellent signaling involves ciliary reversal, which disrupts forward swimming, and causes the organism to jerk back and forth, swim in small circles, or spin in an attempt to get away from the repellent. Many food sources, such as proteins, are chemoattractants for Tetrahymena, while a variety of compounds are repellents. Repellents in nature are thought to come from the secretions of predators, or from ruptured organisms, which may serve as “danger” signals. Several hormones involved in human pain signaling have been shown to be chemorepellents in Tetrahymena, including substance P, ACTH, PACAP, VIP, and nociceptin. We have been studying the response of Tetrahymena to nociceptin, using pharmacological inhibitors in order to elucidate components of the nociceptin signaling pathway. We have found that G-protein inhibitors and a number of mammalian tyrosine kinase inhibitors have no effect on nociceptin avoidance. However, the tyrosine kinase inhibitor, genistein, inhibits avoidance to nociceptin, likely by an unrelated mechanism. Nociceptin avoidance is also inhibited by the calcium chelator, EGTA, and partially inhibited by the ER calcium ATPase inhibitor, thapsigargin. Whole cell electrophysiology experiments in a calcium-containing buffer show that addition of 50 μM nociceptin to the buffer causes a sustained depolarization of approximately 30 mV. This depolarization is nearly eliminated in the presence of EGTA, further supporting the hypothesis that calcium is involved in nociceptin signaling. J-113397, an inhibitor of the human nociceptin receptor, also inhibits nociceptin avoidance in Tetrahymena, though other nociceptin antagonists we tested had no effect on avoidance. Further experimentation on this organism will give a more complete picture of the signaling pathway, as well as allowing greater comparison between nociceptin avoidance in Tetrahymena and nociceptin signaling in vertebrates

Nociceptin Signaling Involves a Calcium-Based Depolarization in Tetrahymena thermophila

Tetrahymena thermophila are free-living, ciliated eukaryotes. Their behavioral response to stimuli is well characterized and easily observable, since cells swim toward chemoattractants and avoid chemorepellents. Chemoattractant responses involve increased swim speed or a decreased change in swim direction, while chemorepellent signaling involves ciliary reversal, which causes the organism to jerk back and forth, swim in small circles, or spin in an attempt to get away from the repellent. Many food sources, such as proteins, are chemoattractants for these organisms, while a variety of compounds are repellents. Repellents in nature are thought to come from the secretions of predators or from ruptured organisms, which may serve as “danger” signals. Interestingly, several peptides involved in vertebrate pain signaling are chemorepellents in Tetrahymena, including substances P, ACTH, PACAP, VIP, and nociceptin. Here, we characterize the response of Tetrahymena thermophila to three different isoforms of nociceptin. We find that G-protein inhibitors and tyrosine kinase inhibitors do not affect nociceptin avoidance. However, the calcium chelator, EGTA, and the SERCA calcium ATPase inhibitor, thapsigargin, both inhibit nociceptin avoidance, implicating calcium in avoidance. This result is confirmed by electrophysiology studies which show that 50µM nociceptin-NH2 causes a sustained depolarization of approximately 40 mV, which is eliminated by the addition of extracellular EGTA

Nociceptin Signals Through Calcium in \u3ci\u3eTetrahymena thermophila\u3c/i\u3e

Tetrahymena thermophila are free-living, ciliated, eukaryotic organisms that respond to stimuli by moving toward chemoattractants and avoiding chemorepellents. Chemoattractant responses involve faster ciliary beating, which propels the organisms forward more rapidly. Chemorepellents signaling involves ciliary reversal, which disrupts forward swimming, and causes the organisms to jerk back and forth, swim in small circles, or spin in an attempt to get away from the repellent. Many food sources, such as proteins, are chemoattractants for these organisms, while a variety of compounds are repellents. Repellents in nature are thought to come from the secretions of predators, or from ruptured organisms, which may serve as danger signals. Interestingly, several hormones involved in human pain signaling have been shown to be chemorepellents in Tetrahymena, including substance P, ACTH, PACAP, VIP, and nociceptin. Recently, we have been studying Tetrahymena response to nociceptin, using pharmacological inhibitors in order to elucidate components of the nociceptin signaling pathway. We have found that G-protein inhibitors and a number of mammalian tyrosine kinase inhibitors have no effect on nociceptin avoidance. However, the tyrosine kinase inhibitor, genistein, inhibits avoidance to nociceptin. Nociceptin avoidance is also inhibited by the calcium chelator, EGTA, which implicates calcium in the avoidance response. Electrophysiology studies done in a calcium-containing buffer show that 50 μM nociceptin causes a sustained depolarization of approximately 30 mV, further supporting the hypothesis that calcium is involved in nociceptin signaling. J-113397, an inhibitor of the human nociceptin receptor, also inhibits nociceptin avoidance in Tetrahymena. We are currently working to determine whether other inhibitors of the human nociceptin receptor have any effect on Tetrahymena, in order to get a more complete picture of the signaling pathway

Roadmap für strombasierte Kraftstoffe 03EIV116A-G

Synthetische Kraftstoffe können die Defossilisierung des Verkehrssektors mit vorantreiben. Besonders bei hohen Transportvolumina oder für große Entfernungen sind diese Kraftstoffe eine vielversprechende Option, etwa in der Luft- und Schifffahrt oder zu Teilen im Schwerlastverkehr. Auf Basis von Strom aus erneuerbaren Energien hergestellte Kraftstoffe sollen in Zukunft entscheidend dazu beitragen, die CO2-Bilanz zu verbessern und Klimaneutralität im Verkehrssektor zu erreichen. Die Forschung dockt damit an die Schnittstelle zwischen Energie- und Verkehrssektor an. Im Rahmen der BMWK-Forschungsinitiative Energiewende im Verkehr (EiV) haben von 2018 bis 2023 insgesamt 16 industriegeführte F&E-Projekte die Entwicklung synthetischer Kraftstoffe für den Luft-, See- und Straßenverkehr deutlich vorangebracht. In den Projekten wurde eine Vielzahl verschiedener Kraftstoffe, Herstellverfahren und Anwendungen betrachtet. Dabei war es die Aufgabe der „Begleitforschung Energiewende im Verkehr“ (BEniVer), als einer der 16 EiV-Projektverbünde, die Projektergebnisse der technischen Forschungsvorhaben der Förderinitiative auf Basis eigenständiger wissenschaftlicher Analysen vergleichbar zu machen. Dazu wurden einheitliche Rahmenannahmen und Methodikleitfäden entwickelt. Die Ergebnisse der Forschungsprojekte wurden in einer Gesamtbetrachtung zusammengeführt und dienten als Grundlage für technische, ökonomische und ökologische Bewertungen. Dabei beruhten die technologie-orientierten Bottom-Up-Analysen auf den neuesten Forschungsarbeiten. Diese wurden mit systemorientierten Top-Down-Analysen des Energie- und Verkehrssystems sowie möglichen Transformationspfaden auf dem Weg zur Klimaneutralität kombiniert. Weitere Analysen zur Akzeptanz und zur Markteinführung adressieren zudem gesellschaftliche Dimensionen und Auswirkungen der Einführung von strombasierten Kraftstoffen. Auf Basis der ganzheitlichen Analysen wurden Schlussfolgerungen abgeleitet. Als Ergebnis der langjährigen und fachübergreifende Begleitung der EiV-Forschungsvorhaben ist mit der Roadmap für strombasierte Kraftstoffe ein Leitfaden entstanden mit Handlungsoptionen für die Erforschung, Entwicklung, Produktion und Markteinführung dieser Kraftstoffe

Forschungsinitiative Energiewende im Verkehr, Kurzbericht zur „Roadmap für strombasierte Kraftstoffe“ 03EIV116A-G

Synthetische Kraftstoffe können die Defossilisierung des Verkehrssektors mit vorantreiben. Besonders bei hohen Transportvolumina oder für große Entfernungen sind diese Kraftstoffe eine vielversprechende Option, etwa in der Luft- und Schifffahrt oder zu Teilen im Schwerlastverkehr. Auf Basis von Strom aus erneuerbaren Energien hergestellte Kraftstoffe sollen in Zukunft entscheidend dazu beitragen, die CO2-Bilanz zu verbessern und Klimaneutralität im Verkehrssektor zu erreichen. Die Forschung dockt damit an die Schnittstelle zwischen Energie- und Verkehrssektor an. Im Rahmen der BMWK-Forschungsinitiative Energiewende im Verkehr (EiV) haben von 2018 bis 2023 insgesamt 16 industriegeführte F&E-Projekte die Entwicklung synthetischer Kraftstoffe für den Luft-, See- und Straßenverkehr deutlich vorangebracht. In den Projekten wurde eine Vielzahl verschiedener Kraftstoffe, Herstellverfahren und Anwendungen betrachtet. Dabei war es die Aufgabe der „Begleitforschung Energiewende im Verkehr“ (BEniVer), als einer der 16 EiV-Projektverbünde, die Projektergebnisse der technischen Forschungsvorhaben der Förderinitiative auf Basis eigenständiger wissenschaftlicher Analysen vergleichbar zu machen. Dazu wurden einheitliche Rahmenannahmen und Methodikleitfäden entwickelt. Die Ergebnisse der Forschungsprojekte wurden in einer Gesamtbetrachtung zusammengeführt und dienten als Grundlage für technische, ökonomische und ökologische Bewertungen. Dabei beruhten die technologie-orientierten Bottom-Up-Analysen auf den neuesten Forschungsarbeiten. Diese wurden mit systemorientierten Top-Down-Analysen des Energie- und Verkehrssystems sowie möglichen Transformationspfaden auf dem Weg zur Klimaneutralität kombiniert. Weitere Analysen zur Akzeptanz und zur Markteinführung adressieren zudem gesellschaftliche Dimensionen und Auswirkungen der Einführung von strombasierten Kraftstoffen. Auf Basis der ganzheitlichen Analysen wurden Schlussfolgerungen abgeleitet. Als Ergebnis der langjährigen und fachübergreifende Begleitung der EiV-Forschungsvorhaben ist mit der Roadmap für strombasierte Kraftstoffe ein Leitfaden entstanden mit Handlungsoptionen für die Erforschung, Entwicklung, Produktion und Markteinführung dieser Kraftstoffe

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → μ+μ−)/B(Bs → μ+μ−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier

LHCb upgrade software and computing : technical design report

This document reports the Research and Development activities that are carried out in the software and computing domains in view of the upgrade of the LHCb experiment. The implementation of a full software trigger implies major changes in the core software framework, in the event data model, and in the reconstruction algorithms. The increase of the data volumes for both real and simulated datasets requires a corresponding scaling of the distributed computing infrastructure. An implementation plan in both domains is presented, together with a risk assessment analysis

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages