Inhibition of Aβ42 Peptide Aggregation by a Binuclear Ruthenium(II)−Platinum(II) Complex: Potential for Multimetal Organometallics as Anti-amyloid Agents

[Image: see text] Design of inhibitors for amyloid-β (Aβ) peptide aggregation has been widely investigated over the years toward developing viable therapeutic agents for Alzheimer’s disease (AD). The biggest challenge seems to be inhibiting Aβ aggregation at the early stages possibly at the monomeric level, because oligomers are known to be neurotoxic. In this regard, exploiting the metal-chelating property of Aβ to generate molecules that can overcome this impediment presents some promise. Recently, one such metal complex containing Pt(II) ([Pt(BPS)Cl(2)]) was reported to effectively inhibit Aβ42 aggregation and toxicity (Barnham, et al. (2008) Proc. Natl. Acad. Sci. U.S.A.1, 6813). This complex was able bind to Aβ42 at the N-terminal part of the peptide and triggered a conformational change resulting in effective inhibition. In the current report, we have generated a mixed-binuclear metal complex containing Pt(II) and Ru(II) metal centers that inhibited Aβ42 aggregation at an early stage and seemed to have different modes of interaction than the previously reported Pt(II) complex, suggesting an important role of the second metal center. This ‘proof-of-concept’ compound will help in developing more effective molecules against Aβ aggregation by modifying the two metal centers as well as their bridging ligands, which will open doors to new rationale for Aβ inhibition

Measurement of the production cross section of prompt Ξ0c baryons in p–Pb collisions at √sNN = 5.02 TeV

The transverse momentum (pT) differential production cross section of the promptly-produced charm-strange baryon Ξ0c (and its charge conjugate Ξ0c¯¯¯¯¯¯) is measured at midrapidity via its hadronic decay into π+Ξ− in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. The Ξ0c nuclear modification factor (RpPb), calculated from the cross sections in pp and p−Pb collisions, is presented and compared with the RpPb of Λ+c baryons. The ratios between the pT-differential production cross section of Ξ0c baryons and those of D0 mesons and Λ+c baryons are also reported and compared with results at forward and backward rapidity from the LHCb Collaboration. The measurements of the production cross section of prompt Ξ0c baryons are compared with a model based on perturbative QCD calculations of charm-quark production cross sections, which includes only cold nuclear matter effects in p−Pb collisions, and underestimates the measurement by a factor of about 50. This discrepancy is reduced when the data is compared with a model in which hadronisation is implemented via quark coalescence. The pT-integrated cross section of prompt Ξ0c-baryon production at midrapidity extrapolated down to pT = 0 is also reported. These measurements offer insights and constraints for theoretical calculations of the hadronisation process. Additionally, they provide inputs for the calculation of the charm production cross section in p−Pb collisions at midrapidity

Measurement of the low-energy antitriton inelastic cross section

In this Letter, the first measurement of the inelastic cross section for antitriton−nucleus interactions is reported, covering the momentum range of 0.8≤p<2.4 GeV/c. The measurement is carried out using data recorded with the ALICE detector in pp and Pb−Pb collisions at a centre-of-mass energy per nucleon of 13 TeV and 5.02 TeV, respectively. The detector material serves as an absorber for antitriton nuclei. The raw yield of (anti)triton nuclei measured with the ALICE apparatus is compared to the results from detailed ALICE simulations based on the GEANT4 toolkit for the propagation of (anti)particles through matter, allowing one to quantify the inelastic interaction probability in the detector material. This analysis complements the measurement of the inelastic cross section of antinuclei up to A=3 carried out by the ALICE Collaboration, and demonstrates the feasibility of the study of the isospin dependence of inelastic interaction cross section with the analysis techniques presented in this Letter

Accessing the strong interaction between Λ baryons and charged kaons with the femtoscopy technique at the LHC

The interaction between Λ baryons and kaons/antikaons is a crucial ingredient for the strangeness S=0 and S=−2 sector of the meson--baryon interaction at low energies. In particular, the ΛK¯¯¯¯ might help in understanding the origin of states such as the Ξ(1620), whose nature and properties are still under debate. Experimental data on Λ−K and Λ−K¯¯¯¯ systems are scarce, leading to large uncertainties and tension between the available theoretical predictions constrained by such data. In this Letter we present the measurements of Λ−K+⊕Λ¯¯¯¯−K− and Λ−K−⊕Λ¯¯¯¯−K+ correlations obtained in the high-multiplicity triggered data sample in pp collisions at s√=13 TeV recorded by ALICE at the LHC. The correlation function for both pairs is modeled using the Lednicky−Lyuboshits analytical formula and the corresponding scattering parameters are extracted. The Λ−K−⊕Λ¯¯¯¯−K+ correlations show the presence of several structures at relative momenta k∗ above 200 MeV/c, compatible with the Ω baryon, the Ξ(1690), and Ξ(1820) resonances decaying into Λ−K− pairs. The low k∗ region in the Λ−K−⊕Λ¯¯¯¯−K+ also exhibits the presence of the Ξ(1620) state, expected to strongly couple to the measured pair. The presented data allow to access the ΛK+ and ΛK− strong interaction with an unprecedented precision and deliver the first experimental observation of the Ξ(1620) decaying into ΛK−

Measurement of Ω0c baryon production and branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) in pp collisions at √s = 13 TeV

The inclusive production of the charm-strange baryon Ω0c is measured for the first time via its semileptonic decay into Ω−e+νe at midrapidity (|y| < 0.8) in proton–proton (pp) collisions at the centre-of-mass energy √s = 13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c. The branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) is measured to be 1.12 ± 0.22 (stat.) ± 0.27 (syst.). Comparisons with other experimental measurements, as well as with theoretical calculations, are presented

Measurements of long-range two-particle correlation over a wide pseudorapidity range in p–Pb collisions at √sNN = 5.02 TeV

Correlations in azimuthal angle extending over a long range in pseudorapidity between particles, usually called the "ridge" phenomenon, were discovered in heavy-ion collisions, and later found in pp and p−Pb collisions. In large systems, they are thought to arise from the expansion (collective flow) of the produced particles. Extending these measurements over a wider range in pseudorapidity and final-state particle multiplicity is important to understand better the origin of these long-range correlations in small-collision systems. In this Letter, measurements of the long-range correlations in p−Pb collisions at sNN−−−√=5.02 TeV are extended to a pseudorapidity gap of Δη∼8 between particles using the ALICE, forward multiplicity detectors. After suppressing non-flow correlations, e.g., from jet and resonance decays, the ridge structure is observed to persist up to a very large gap of Δη∼8 for the first time in p−Pb collisions. This shows that the collective flow-like correlations extend over an extensive pseudorapidity range also in small-collision systems such as p−Pb collisions. The pseudorapidity dependence of the second-order anisotropic flow coefficient, v2({\eta}), is extracted from the long-range correlations. The v2(η) results are presented for a wide pseudorapidity range of −3.1<η<4.8 in various centrality classes in p−Pb collisions. To gain a comprehensive understanding of the source of anisotropic flow in small-collision systems, the v2(η) measurements are compared to hydrodynamic and transport model calculations. The comparison suggests that the final-state interactions play a dominant role in developing the anisotropic flow in small-collision systems

First measurement of the |t|-dependence of incoherent J/ψ photonuclear production

The first measurement of the cross section for incoherent photonuclear production of J/ψ vector meson as a function of the Mandelstam |t| variable is presented. The measurement was carried out with the ALICE detector at midrapidity, |y|<0.8, using ultra-peripheral collisions of Pb nuclei at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV. This rapidity interval corresponds to a Bjorken-x range (0.3−1.4)×10−3. Cross sections are reported in five |t| intervals in the range 0.04<|t|<1~GeV2 and compared to the predictions of different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a |t|-dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data

Multiplicity dependence of charged-particle intra-jet properties in pp collisions at √s = 13 TeV

The first measurement of the multiplicity dependence of intra-jet properties of leading charged-particle jets in proton-proton (pp) collisions is reported. The mean charged-particle multiplicity and jet fragmentation distributions are measured in minimum-bias and high-multiplicity pp collisions at s√ = 13 TeV using the ALICE detector. Jets are reconstructed from charged particles produced in the midrapidity region (|η|<0.9) using the sequential recombination anti-kT algorithm with jet resolution parameters R = 0.2, 0.3, and 0.4 for the transverse momentum (pT) interval 5−110 GeV/c. High-multiplicity events are selected by the forward V0 scintillator detectors. The mean charged-particle multiplicity inside the leading jet cone rises monotonically with increasing jet pT in qualitative agreement with previous measurements at lower energies. The distributions of jet fragmentation functions zch and ξch are measured for different jet-pT intervals. Jet-pT independent fragmentation of leading jets is observed for wider jets except at high- and low-zch. The observed "hump-backed plateau" structure in the ξch distribution indicates suppression of low-pT particles. In high-multiplicity events, an enhancement of the fragmentation probability of low-zch particles accompanied by a suppression of high-zch particles is observed compared to minimum-bias events. This behavior becomes more prominent for low-pT jets with larger jet radius. The results are compared with predictions of QCD-inspired event generators, PYTHIA 8 with Monash 2013 tune and EPOS LHC. It is found that PYTHIA 8 qualitatively reproduces the jet modification in high-multiplicity events except at high jet pT. These measurements provide important constraints to models of jet fragmentation