321034 research outputs found
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Biophysikalische Untersuchung von an Biotransformationbeteiligten Flavinmonooxygenasen
No full textThis work deals with the expression, purification, characterization, and crystallization of ΔhFMO5,a variant of the human flavin-dependent monooxygenase 5 (hFMO5) without transmembraneregion. This modification enables the expression and purification of soluble protein withoutaddition of detergent, resulting in the isolation of active protein saturated with FAD. Theaggregation prone ΔhFMO5 was successfully expressed in a fermenter using the strain E. coliRosetta 2 (DE3) pLysS, lysed by enzymatic cell disruption and purified through affinity and sizeexclusion chromatography. Characterization of ΔhFMO5 via mass photometry reveals that insolution there is present a mixture of different oligomeric states, with the tetrameric form beingpredominant. The catalytic cycle of ΔhFMO5 includes an uncoupled metabolic pathway, in whichNADPH is consumed to regenerate the FAD cofactor without substrate turnover, leading to theformation of hydrogen peroxide. Iterative modeling of the reaction kinetics of ΔhFMO5demonstrates that substrate metabolism as a second-order reaction proceeds more slowlycompared to the uncoupled reaction. Activity measurements show that the conversion ofphenylacetone to benzyl acetate is catalyzed by ΔhFMO5 with a turnover rate of 5.1 %. N-acetylserotonin was identified as a potential endogenous substrate playing a role in the productionof melatonin and serotonin
Development of an RXR Agonist Scaffold with Pronounced Homodimer Preference
No full textThe activation of retinoid X receptors (RXRs) presents promising therapeutic potential in diverse conditions, such as cancer, inflammation, metabolic dysfunction, and neurodegeneration. However, RXRs play a central role in nuclear receptor signaling and act in various dimeric forms with multiple other ligand-activated transcription factors giving rise to promiscuous effects of RXR agonists. Here we identified a new RXR ligand chemotype addressing only part of RXR’s molecular activities. Optimization provided a new RXR modulator scaffold fully activating the RXR homodimer with nanomolar potency but displaying markedly reduced RXR heterodimer activation compared to bexarotene. Co-crystal structure analysis revealed different molecular effects on the RXR LBD conformation than bexarotene possibly mediating the selective activity. The new RXR modulator type enables studies on selective RXR homodimer activation effects and suggests that different molecular mechanisms of RXR activity can be selectively addressed with ligands
Search for heavy neutral resonances decaying to tau lepton pairs in proton-proton collisions at = 13 TeV
No full textA search for heavy neutral gauge bosons (Z') decaying into a pair of tau leptons is performed in proton-proton collisions at = 13 TeV at the CERN LHC. The data were collected with the CMS detector and correspond to an integrated luminosity of 138 fb. The observations are found to be in agreement with the expectation from standard model processes. Limits at 95% confidence level are set on the product of the Z' production cross section and its branching fraction to tau lepton pairs for a range of Z' boson masses. For a narrow resonance in the sequential standard model scenario, a Z' boson with a mass below 3.5 TeV is excluded. This is the most stringent limit to date from this type of search
Tensor network and quantum simulations of 1+1-dimensional quantum electrodynamics
No full textWe consider the Schwinger model with a single fermion flavor in the presence of a topologicalθ-term as a benchmark model to develop quantum computing (QC) and tensor network (TN)techniques, as well as to probe its physics, which shares many similarities with quantumchromodynamics (QCD). The techniques developed aim to eventually enhance our capabilitiesin simulating strongly coupled non-perturbative regimes of the Standard Model, particularlyin unexplored regions of its phase diagram where the conventionally used techniques are notapplicable.Discretizing fermions on a lattice is a crucial step in simulating lattice gauge theory (LGT)models such as the Schwinger model. Using the two common discretization schemes of Wilsonand staggered fermions, we first explore the additive mass renormalization induced by theseschemes within the Hamiltonian formalism relevant for QC and TNs. By formulating a methodto measure this mass renormalization, we demonstrate its dependence on various systemparameters. This, in turn, allows for more reliable and precise continuum extrapolations ofrelevant observables, for which we achieve excellent agreement with results from continuummass perturbation theory. This work introduces, for the first time, a method to measure themass renormalization in the Hamiltonian formalism, enabling QC and TNs to require fewerresources to achieve higher precision in continuum extrapolations. These extrapolations areessential for LGTs computations in higher dimensions to match experimental results, such asthose from the large hadron collider (LHC) experiment.Secondly, we demonstrate the capabilities of quantum hardware in simulating the first-orderphase transition of the model, utilizing a composite set of state-of-the-art error mitigationtechniques. While we classically simulate the variational quantum eigensolver (VQE) algorithmto acquire the ground states at the relevant points of the phase diagram as parameterizedquantum circuits (PQCs), we perform inference runs by preparing these states on IBM’snoisy intermediate-scale quantum (NISQ) devices and measure observables that signal thephase transition. Our results show that these quantum devices are able to reproduce thetransition with reasonable accuracy, showcasing the potential of NISQ devices in probing thephase diagram of LGTs. Additionally, we perform continuum extrapolations of the electricfield observable using TNs, providing an estimate of the resources required for continuumextrapolations in QC.Finally, the Schwinger model is studied in the context of open quantum system (OQS) in the presence of a hot environment. We prepare mesonic states of the model, such as the Schwingerboson or the electric field flux state, and evolve them under the influence of this environment,following the dynamics governed by a Lindblad master equation in the Markovian quantumBrownian motion (QBM) limit. The evolution is carried out using TNs and the adaptivetime-dependent density matrix renormalization group (DMRG) (ATD-DMRG) algorithm.Specifically, we probe the thermalization time of these mesonic states as a function of variousrelevant parameters. Additionally, we explore the connection between the thermalization timeand mutual information within the states. Finally, we demonstrate how our method can scaleto larger system sizes, achieving excellent preservation of the expected parity symmetry ofthe electric field observable. The relevance of this work to quarkonia within the quark gluonplasma (QGP) produced at the LHC and relativistic heavy ion collider (RHIC) is discussedthroughout
DNA Mimic Foldamer Recognition of a Chromosomal Protein
No full textHelical aromatic oligoamide foldamers bearing anionic side chains that mimic the overall shape and charge surface distribution of DNA were synthesized. Their interactions with chromosomal protein Sac7d, a non-sequence-selective DNA-binder that kinks DNA, were investigated by Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC), Circular Dichroism spectroscopy (CD), melting curve analysis, Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR), as well as by single crystal X-ray crystallography. The foldamers were shown to bind to Sac7d better than a DNA duplex of comparable length. The interaction is diastereoselective and takes place at the DNA binding site. Crystallography revealed that the DNA mimic foldamers have a binding mode of their own and that they can bind to Sac7d without being kinked
Unlocking the Higgs Potential: from Colliders to the Cosmos
No full textThe upcoming decades in particle physics will offer an unprecedented amount of data, opening new avenues to deepen our understanding of the fundamental laws of nature. On one hand, the High-Luminosity Large Hadron Collider (HL-LHC) will significantly enhance our experimental reach at the energy frontier. On the other hand, the Laser Interferometer Space Antenna (LISA) will inaugurate the era of the early Universe gravitational wave astronomy. The data they will collect may shed light on some of the most profound open questions in physics. At the centre of many unresolved questions in the Standard Model (SM), which include the origin of electroweak symmetry breaking, the matter-antimatter asymmetry, and the nature of dark matter, lies the scalar potential. In particular, the trilinear Higgs self-coupling offers a unique window to determine the shape of this potential. While collider experiments probe it as realised today, cosmological observations can provide insights into its evolution in the early Universe. Together, they offer complementary perspectives on one of the most fundamental ingredients of particle physics.This thesis investigates the phenomenological implications of deviations in the Higgs trilinear self-coupling within well-motivated Beyond the Standard Model (BSM) scenarios featuring extended scalar sectors, with a particular focus on the Two Higgs Doublet Model (2HDM). We perform a detailed study of Higgs pair production at the HL-LHC, the process most directly sensitive to trilinear scalar couplings, examining the effects of additional scalar states both through direct resonant production channels and through radiative corrections to the trilinear Higgs coupling. Our results show that interference effects between resonant and non-resonant contributions, affected by loop-induced modifications to scalar self-interactions, can significantly alter both the total production cross section and the invariant mass distribution, while remaining consistent with all current experimental and theoretical constraints. To account for these effects, we develop and apply dedicated computational frameworks that enable precision BSM analyses incorporating these significant loop effects.Turning to the early Universe, we examine the thermal evolution predicted by BSM scenarios and identify conditions required for a strong first-order electroweak phase transition, which is a necessary ingredient for electroweak baryogenesis. We analyse the characteristic mass hierarchies that favour such transitions and identify the most important collider signatures capable of probing the relevant parameter space. At the same time, we explore the complementary reach of cosmological observables, focusing on stochastic gravitational wave (GW) backgrounds that may be sourced by such strong transitions. We find that space-based GW astronomy could become a complementary tool for exploring fundamental questions of particle physics
High-Z sensors at MHz repetition rate FELs: first AGIPD results
No full textTo address new applications in the 20–30 keV photon energy range at the European XFEL, where silicon sensors lose quantum efficiency, the AGIPD consortia has developed anAGIPD detector prototype with high-Z sensor materials. An electron-collecting version of the chip (ecAGIPD) was designed to leverage from the higher mobility and longer lifetime of electrons with respect to holes in the candidate materials: chromium-doped gallium arsenide (GaAs:Cr) and high-flux cadmium zinc telluride (CdZnTe). This work reports on the characterization of GaAs and high-flux CdZnTe ecAGIPD prototypes at the HED instrument at the European XFEL. Their time response, linearity and performance at 2.2 and 4.5 MHz frame rates were evaluated. Preliminary results demonstrate good linearity of both materials up to 1.6e+03 15 keV photons/mm2/pulse, and a residual after-pulse signal corresponding to less than one photon on CdZnTe, up to an estimated flux of 1.2e+05 24 keV photons/mm2/pulse
Operando Characterization of Fe in Doped Ni(Fe)OH Catalysts for Electrochemical Oxygen Evolution
No full textIron-doped nickel oxyhydroxides, Ni(Fe–)OH, are among the most promising oxygen evolution reaction (OER) electrocatalysts in alkaline environments. Although iron (Fe) significantly enhances the catalytic activity, there is still no clear consensus on whether Fe directly participates in the reaction or merely acts as a promoter. To elucidate the Fe’s role, we performed operando X-ray spectroscopy studies supported by DFT on Ni(Fe–)OH electrocatalysts. We probed the reversible changes in the structure and electronic character of Ni(Fe–)OH as the electrode potential is cycled between the resting (here at 1.10 V) and operational states (1.66 V). DFT calculations and XAS simulations on a library of Fe structures in various NiOH environments are in favor of a distorted local octahedral Fe(III)O(OH) configuration at the resting state with the NiOH scaffold going from α-Ni(OH) to γ-NiOOH as the potential is increased. Under catalytic conditions, EXAFS and HERFD spectra reveal changes in p-d mixing (covalency) relative to the resting state between O/OH ligands and Fe leading to a shift from octahedral to square pyramidal coordination at the Fe site. XES measurements and theoretical simulations further support that the Fe equilibrium structure remains in a formal Fe(III) state under both resting and operational conditions. These spectral changes are attributed to potential dependent structural rearrangements around Fe. The results suggest that ligand dissociation leads to the C symmetry as the most stable intermediate of the Fe during OER. This implies that Fe has a weakly coordinated or easily dissociable ligand that could serve to coordinate the O–O bond formation and, tentatively, play an active role in the Ni(Fe–)OH electrocatalyst
In-situ synchrotron imaging of powder consolidation and melt pool dynamics in electron beam powder bed fusion
No full textElectron beam powder bed fusion (PBF-EB) is an additive manufacturing (AM) technology that enables the fabrication of metallic parts with arbitrary geometric complexity within a vacuum environment. Due to its ability to process materials at high temperatures (> 1000 °C), processing of crack and oxidation sensitive materials, as well as refractory alloys is possible. However, due to limited fundamental understanding of the intricate dynamics during powder consolidation and melt pool formation, the development of advanced processing strategies has mainly been limited to experimentally time-consuming parameter studies, as numerical models have mostly been unable to accurately predict processing conditions at the part or even layer scale. In this study, we perform high-speed in-situ X-ray imaging during multi-layer single track powder melting experiments on MiniMelt, a recently developed, custom-built PBF-EB machine for in-situ X-ray investigations. Our experiments reveal several key melt pool formation dynamics, some of which are being identified for the first time. They show how melt pool formation involves the coalescence of molten powder particles into larger droplets and how these droplets either fuse with the melt pool or solidify as balling particles. They also elucidate the origins of melt pool oscillations and spatter formation and demonstrate how the superposition of these mechanisms can lead to chaotic and escalating movement within the melt. We expect our results to improve and extend the phenomenological understanding of the powder consolidation mechanisms during PBF-EB and to aid in the development of new scanning strategies as well as the validation of numerical models
Liquid-like versus stress-driven dynamics in a metallic glass former observed by temperature scanning X-ray photon correlation spectroscopy
No full textSince several decades, the dynamics and vitrification kinetics of supercooled liquids are the subject of active research in science and engineering. Profiting from modern detector technology and highly brilliant fourth-generation synchrotron radiation, we apply temperature scanning X-ray photon correlation spectroscopy (XPCS) to probe the dynamics of a Pt-based metallic glass former in the glass, glass transition region, and supercooled liquid, covering up to six orders of magnitude in timescales. Our data demonstrates that the structural α-relaxation process is still observable in the glass, although it is partially masked by a faster source of decorrelation observed at atomic scale. We present an approach that interprets these findings as the superposition of heterogeneous liquid-like and stress-driven ballistic-like atomic motions. This work not only extends the dynamical range probed by standard isothermal XPCS but also adds a different view on the α-relaxation across the glass transition and provides insights into the anomalous, compressed temporal decay of the density-density correlation functions observed in metallic glasses and many out-of-equilibrium soft materials