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The production of K∗(892)± meson resonance is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at sNN−−−√=5.02 TeV using the ALICE detector at the LHC. The resonance is reconstructed via its hadronic decay channel K∗(892)±→K0Sπ±. The transverse momentum distributions are obtained for various centrality intervals in the pT range of 0.4-16 GeV/c. The reported measurements of integrated yields, mean transverse momenta, and particle yield ratios are consistent with previous ALICE measurements for K∗(892)0. The pT-integrated yield ratio 2K∗(892)±/(K++K−) in central Pb-Pb collisions shows a significant suppression (9.3σ) relative to pp collisions. Thermal model calculations overpredict the particle yield ratio. Although both simulations consider the hadronic phase, only HRG-PCE accurately represents the measurements, whereas MUSIC+SMASH tends to overpredict them. These observations, along with the kinetic freeze-out temperatures extracted from the yields of light-flavored hadrons using the HRG-PCE model, indicate a finite hadronic phase lifetime, which increases towards central collisions. The pT-differential yield ratios 2K∗(892)±/(K++K−) and 2K∗(892)±/(π++π−) are suppressed by up to a factor of five at pT<2 GeV/c in central Pb-Pb collisions compared to pp collisions at s√= 5.02 TeV. Both particle ratios and are qualitatively consistent with expectations for rescattering effects in the hadronic phase. The nuclear modification factor shows a smooth evolution with centrality and is below unity at pT>8 GeV/c, consistent with measurements for other light-flavored hadrons. The smallest values are observed in most central collisions, indicating larger energy loss of partons traversing the dense medium.
The production of K∗(892)± meson resonance is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at sNN−−−√=5.02 TeV using the ALICE detector at the LHC. The resonance is reconstructed via its hadronic decay channel K∗(892)±→K0Sπ±. The transverse momentum distributions are obtained for various centrality intervals in the pT range of 0.4-16 GeV/c. The reported measurements of integrated yields, mean transverse momenta, and particle yield ratios are consistent with previous ALICE measurements for K∗(892)0. The pT-integrated yield ratio 2K∗(892)±/(K++K−) in central Pb-Pb collisions shows a significant suppression (9.3σ) relative to pp collisions. Thermal model calculations overpredict the particle yield ratio. Although both simulations consider the hadronic phase, only HRG-PCE accurately represents the measurements, whereas MUSIC+SMASH tends to overpredict them. These observations, along with the kinetic freeze-out temperatures extracted from the yields of light-flavored hadrons using the HRG-PCE model, indicate a finite hadronic phase lifetime, which increases towards central collisions. The pT-differential yield ratios 2K∗(892)±/(K++K−) and 2K∗(892)±/(π++π−) are suppressed by up to a factor of five at pT<2 GeV/c in central Pb-Pb collisions compared to pp collisions at s√= 5.02 TeV. Both particle ratios and are qualitatively consistent with expectations for rescattering effects in the hadronic phase. The nuclear modification factor shows a smooth evolution with centrality and is below unity at pT>8 GeV/c, consistent with measurements for other light-flavored hadrons. The smallest values are observed in most central collisions, indicating larger energy loss of partons traversing the dense medium.
The total charm-quark production cross section per unit of rapidity dσ(cc)/dy, and the fragmentation fractions of charm quarks to different charm-hadron species f(c → hc), are measured for the first time in p–Pb collisions at √sNN = 5.02 TeV at midrapidity (−0.96 < y < 0.04 in the centre-ofmass frame) using data collected by ALICE at the CERN LHC. The results are obtained based on all the available measurements of prompt production of ground-state charm-hadron species: D0, D+,D+s, and J/ψ mesons, and Λ+cand Ξ0cbaryons. The resulting cross section is dσ(cc)/dy = 219.6±6.3 (stat.)+10.5−11.8(syst.)+7.6−2.9(extr.)±5.4 (BR)±4.6 (lumi.)±19.5 (rapidity shape) +15.0 (Ω0c) mb, which is consistent with a binary scaling of pQCD calculations from pp ollisions. The measured fragmentation fractions are compatible with those measured in pp collisions at √s = 5.02 and 13 TeV, showing an increase in the relative production rates of charm baryons with respect to charm mesons in pp and p–Pb collisions compared with e+e − and e−p collisions. The pT-integrated nuclear modification factor of charm quarks, RpPb(cc) = 0.91±0.04 (stat.) +0.08 −0.09 (syst.) +0.04 −0.03 (extr.)±0.03 (lumi.), is found to be consistent with unity and with theoretical predictions including nuclear modifications of the parton distribution functions.
This work aims to differentiate strangeness produced from hard processes (jet-like) and softer processes (underlying event) by measuring the angular correlation between a high-momentum trigger hadron (h) acting as a jet-proxy and a produced strange hadron (φ(1020) meson). Measuring h–φ correlations at midrapidity in p–Pb collisions at √sNN = 5.02 TeV as a function of event multiplicity provides insight into the microscopic origin of strangeness enhancement in small collision systems. The jet-like and the underlying-event-like strangeness production are investigated as a function of event multiplicity. They are also compared between a lower and higher momentum region. The evolution of the per-trigger yields within the near-side (aligned with the trigger hadron) and away-side (in the opposite direction of the trigger hadron) jet is studied separately, allowing for the characterization of two distinct jet-like production regimes. Furthermore, the h–φ correlations within the underlying event give access to a production regime dominated by soft production processes, which can be compared directly to the in-jet production. Comparisons between h–φ and dihadron correlations show that the observed strangeness enhancement is largely driven by the underlying event, where the φ/h ratio is significantly larger than within the jet regions. As multiplicity increases, the fraction of the total φ(1020) yield coming from jets decreases compared to the underlying event production, leading to high-multiplicity events being dominated by the increased strangeness production from the underlying event
The production cross section of inclusive isolated photons has been measured by the ALICE experiment at the CERN LHC in pp collisions at centre-of-momentum energy of s√=13 TeV collected during the LHC Run 2 data-taking period. The measurement is performed by combining the measurements of the electromagnetic calorimeter EMCal and the central tracking detectors ITS and TPC, covering a pseudorapidity range of |ηγ|<0.67 and a transverse momentum range of 7<pγT<200 GeV/c. The result extends to lower pγT and xγT=2pγT/s√ ranges, the lowest xγT of any isolated photon measurements to date, extending significantly those measured by the ATLAS and CMS experiments towards lower pγT at the same collision energy with a small overlap between the measurements. The measurement is compared with next-to-leading order perturbative QCD calculations and the results from the ATLAS and CMS experiments as well as with measurements at other collision energies. The measurement and theory prediction are in agreement with each other within the experimental and theoretical uncertainties.
Solute carrier (SLC) are related to various diseases in human and promising pharmaceutical targets but more structural and functional information on SLCs is required to expand their use for drug design and therapy. The 7-transmembrane segment inverted (7-TMIR) fold was identified for the SLC families 4, 23 and 26 in the last decade thus detailed analysis of the structure function relationship of one of these families might also yield insights for the other two. SVCT1 and SVCT2 from the SLC23 family are sodium dependent ascorbic acid transporters in human but structural analysis of the SLC23 family is exclusively based on two homologs – UraA from E. coli and UapA from A. nidulans – yielding two inward-facing and one occluded conformation. In combination with outward-facing conformations from SLC4 transporters, and additional information from the SLC26 family, an elevator transport mechanism for all 7-TMIR proteins was identified but detailed mechanistic features of the transport remain elusive due to the lack of multiple conformations from individual transporters.
To increase the understanding of 7-TMIR protein structure and function in this study, the transport mechanism of SLC23 transporters was analyzed by two strategies including selection of alpaca derived nanobodies and synthetic nanobodies against UraA as prokaryotic model protein of the SLC23 family. The second strategy involved mutagenesis of UraA at functional relevant positions regarding the conformational change during transport. Therefore, available structures of 7-TMIR proteins and less related elevator transporters were analyzed and a common motif identified – the alpha helical inter-domain linkers. The proposed rigid body movement for transport in combination with the characteristic alpha helical secondary structure of the linkers connecting both rigid bodies led to the hypothesis of functional relevance of the linkers and a conformational hinge being located in close proximity to the linkers. These positions were identified and used to modulate the biophysical properties of the transporter. Mutagenesis at three relevant positions led to loss of transport functionality and these UraA variants could be recombinantly produced and purified to further examine the underlying mechanistic effects. The variants UraAG320P and UraAP330G from the periplasmic inter-domain linker showed increased dimerization and thermal stability as well as substrate binding in solution. The substrate affinity of UraAG320P was identified to be 5-fold higher compared to the wildtype. The solvent accessibility of the substrate binding site in UraAG320P and UraAP330G revealed reduced open probability that indicated an altered conformational space compared to UraAWT. This phenomenon was analyzed in more detail by differential hydrogen-deuterium exchange mass spectrometry and the results supported the hypothesis of a reduced open probability and gave further insights into the impact of the two mutations in the periplasmic inter-domain linker in UraA.
This thesis further presents strategies for phage display selection of nanobodies with epitope bias and a post selection analysis pipeline to identify nanobodies with desired binding characteristics. Thereby, whole cell transport inhibition highlighted periplasmic epitope binders and conformational selectivity. A cytoplasmic epitope could be identified by pulldown with inside-out membrane vesicles for one cytoplasmic side binder. Thermal stabilization analysis of the target protein in differential scanning fluorometry was performed in presence of two different nanobodies to identify simultaneous binding by additional thermal stabilization respectively competition by intermediate melting temperatures. Combination of epitope information with simultaneous DSF could be used to identify the stabilization of different UraA conformations by a set of binders and presents a general nanobody selection strategy for other SLCs. Synthetic nanobodies (sybodies) were also included in the analysis pipeline and Sy45 identified as promising candidate for co-crystallization that gave rise to UraAWT crystals in several conditions in presence or absence of uracil. Similar crystals could be obtained in combination with UraAG320P that were further optimized to gain structural information on this mutant. The structure was solved by molecular replacement and the model refined at 3.1 Å resolution confirming the cytoplasmic epitope of Sy45 as predicted by the selection pipeline. The stabilized conformation was inward-facing similar to the reported UapA structure but significantly different to the previously reported inward-facing structure of UraA. The structure further confirmed the structural integrity of the UraA mutant G320P. Despite the monomeric state of UraA in the structure, the gate domain aligned reasonably well with the gate domain of the previously published dimeric UraA structure in the occluded conformation and allowed detailed analysis of the conformational transition in UraA from inward-facing to occluded by a single rigid body movement. Thereby little movement in the gate domain of UraA was observed in contrast to a previously reported transport mechanism. Core domain rotation around a rotation axis parallel to the substrate barrier was found to explain the major part of conformational transition from inward-facing to occluded and experimentally supported the hypothesized mechanism by Chang et al. (2017). Additionally, the conformational hinge around position G320 in UraA could be identified as well as the impact of the backbone rigidity introduced by the highly conserved proline residue at position 330 in UraA on the conformational transition. This position was found to serve as anchoring point the inter-domain linker and determines the coordinated movement of inter-domain linker and core domain. The functional analysis further highlighted the requirement of alpha helical secondary structure within the inter-domain linker that serves as amphipathic structural entity that can adjust to changed core-gate domain distances and angles during transport by extension/compression or bending while preserving the rigid linkage.
The applied strategies to modulate the conformational space of UraA by mutagenesis at the hinge positions in the inter-domain linkers is transferrable to other transporters and might facilitate their structural and functional characterization.
Further, this study discusses the conformational thermostabilization of UraA that is based on increased melting temperatures upon restriction of its conformational freedom. The term ‘conformational thermostabilization’ introduced by Serrano-Vega et al. (2007) could be experimentally supported and the direct correlation between the conformational freedom and thermostabilization was qualitatively analyzed for UraA. The concept of conformational thermostabilization might help in characterization of other dynamic transport systems as well.