Scaling of transverse nuclear magnetic relaxation due to magnetic nanoparticle aggregation

The aggregation of superparamagnetic iron oxide (SPIO) nanoparticles decreases the transverse nuclear magnetic resonance (NMR) relaxation time T2 of adjacent water molecules measured by a Carr-Purcell-Meiboom-Gill (CPMG) pulse-echo sequence. This effect is commonly used to measure the concentrations of a variety of small molecules. We perform extensive Monte Carlo simulations of water diffusing around SPIO nanoparticle aggregates to determine the relationship between T2 and details of the aggregate. We find that in the motional averaging regime T2 scales as a power law with the number N of nanoparticles in an aggregate. The specific scaling is dependent on the fractal dimension d of the aggregates. We find T2 N^{-0.44} for aggregates with d=2.2, a value typical of diffusion limited aggregation. We also find that in two-nanoparticle systems, T2 is strongly dependent on the orientation of the two nanoparticles relative to the external magnetic field, which implies that it may be possible to sense the orientation of a two-nanoparticle aggregate. To optimize the sensitivity of SPIO nanoparticle sensors, we propose that it is best to have aggregates with few nanoparticles, close together, measured with long pulse-echo times.Comment: 20 pages, 3 figures, submitted to Journal of Magnetism and Magnetic Material

`Third' Quantization of Vacuum Einstein Gravity and Free Yang-Mills Theories

Based on the algebraico-categorical (:sheaf-theoretic and sheaf cohomological) conceptual and technical machinery of Abstract Differential Geometry, a new, genuinely background spacetime manifold independent, field quantization scenario for vacuum Einstein gravity and free Yang-Mills theories is introduced. The scheme is coined `third quantization' and, although it formally appears to follow a canonical route, it is fully covariant, because it is an expressly functorial `procedure'. Various current and future Quantum Gravity research issues are discussed under the light of 3rd-quantization. A postscript gives a brief account of this author's personal encounters with Rafael Sorkin and his work.Comment: 43 pages; latest version contributed to a fest-volume celebrating Rafael Sorkin's 60th birthday (Erratum: in earlier versions I had wrongly written that the Editor for this volume is Daniele Oriti, with CUP as publisher. I apologize for the mistake.

meCLICK-Seq, a Substrate-Hijacking and RNA Degradation Strategy for the Study of RNA Methylation.

The fates of RNA species in a cell are controlled by ribonucleases, which degrade them by exploiting the universal structural 2'-OH group. This phenomenon plays a key role in numerous transformative technologies, for example, RNA interference and CRISPR/Cas13-based RNA editing systems. These approaches, however, are genetic or oligomer-based and so have inherent limitations. This has led to interest in the development of small molecules capable of degrading nucleic acids in a targeted manner. Here we describe click-degraders, small molecules that can be covalently attached to RNA species through click-chemistry and can degrade them, that are akin to ribonucleases. By using these molecules, we have developed the meCLICK-Seq (methylation CLICK-degradation Sequencing) a method to identify RNA modification substrates with high resolution at intronic and intergenic regions. The method hijacks RNA methyltransferase activity to introduce an alkyne, instead of a methyl, moiety on RNA. Subsequent copper(I)-catalyzed azide-alkyne cycloaddition reaction with the click-degrader leads to RNA cleavage and degradation exploiting a mechanism used by endogenous ribonucleases. Focusing on N6-methyladenosine (m6A), meCLICK-Seq identifies methylated transcripts, determines RNA methylase specificity, and reliably maps modification sites in intronic and intergenic regions. Importantly, we show that METTL16 deposits m6A to intronic polyadenylation (IPA) sites, which suggests a potential role for METTL16 in IPA and, in turn, splicing. Unlike other methods, the readout of meCLICK-Seq is depletion, not enrichment, of modified RNA species, which allows a comprehensive and dynamic study of RNA modifications throughout the transcriptome, including regions of low abundance. The click-degraders are highly modular and so may be exploited to study any RNA modification and design new technologies that rely on RNA degradation.UKRI (BBSRC DTP scholarships to S.M. and H.K.C) and the Jardine Foundation and Cambridge Trust (PhD scholarship to M.E.H.)

Energy dependence of kaon-to-proton ratio fluctuations in central Pb+Pb collisions from sNN\sqrt{s_{NN}} = 6.3 to 17.3 GeV

Kaons and protons carry large parts of two conserved quantities, strangeness and baryon number. It is argued that their correlation and thus also fluctuations are sensitive to conditions prevailing at the anticipated parton-hadron phase boundary. Fluctuations of the $(\mathrm{K}^+ + \mathrm{K}^-)/(\mathrm{p}+\bar{\mathrm{p}})$ and $\mathrm{K}^+/\mathrm{p}$ ratios have been measured for the first time by NA49 in central Pb+Pb collisions at 5 SPS energies between $\sqrt{s_{NN}}$= 6.3 GeV and 17.3 GeV. Both ratios exhibit a change of sign in $\sigma_{\mathrm{dyn}}$, a measure of non-statistical fluctuations, around $\sqrt{s_{NN}}$ = 8 GeV. Below this energy, $\sigma_{\mathrm{dyn}}$ is positive, indicating higher fluctuation compared to a mixed event background sample, while for higher energies, $\sigma_{\mathrm{dyn}}$ is negative, indicating correlated emission of kaons and protons. The results are compared to UrQMD calculations which which give a good description at the higher SPS energies, but fail to reproduce the transition to positive values.Comment: 5 pages, 4 figure

System-size and centrality dependence of charged kaon and pion production in nucleus-nucleus collisions at 40A GeV and158A GeV beam energy

Measurements of charged pion and kaon production are presented in centrality selected Pb+Pb collisions at 40A GeV and 158A GeV beam energy as well as in semi-central C+C and Si+Si interactions at 40A GeV. Transverse mass spectra, rapidity spectra and total yields are determined as a function of centrality. The system-size and centrality dependence of relative strangeness production in nucleus-nucleus collisions at 40A GeV and 158A GeV beam energy are derived from the data presented here and published data for C+C and Si+Si collisions at 158A GeV beam energy. At both energies a steep increase with centrality is observed for small systems followed by a weak rise or even saturation for higher centralities. This behavior is compared to calculations using transport models (UrQMD and HSD), a percolation model and the core-corona approach.Comment: 32 pages, 14 figures, 4 tables, typo table II correcte

Clonal haematopoiesis is not prevalent in survivors of childhood cancer

This project was funded by the Wellcome Trust Sanger Institute (grant number WT098051). G.S.V. is funded by a Wellcome Trust Senior Fellowship in Clinical Science (WT095663MA). F.F. is funded by Compagnia di San Paolo Grant: “Le cellule staminali del sangue nei guariti di leucemia” Codice SIME 2013-0958 (codice ROL 4201). I.V is funded by the Spanish Ministerio de Economía y Competitividad, Programa Ramón y Cajal

Proton -- Lambda Correlations in Central Pb+Pb Collisions at sqrt(s_{NN}) = 17.3 GeV

The momentum correlation between protons and lambda particles emitted from central Pb+Pb collisions at sqrt(s_{NN}) = 17.3 GeV was studied by the NA49 experiment at the CERN SPS. A clear enhancement is observed for small relative momenta (q_{inv} < 0.2 GeV). By fitting a theoretical model, which uses the strong interaction between the proton and the lambda in a given pair, to the measured data a value for the effective source size is deduced. Assuming a static Gaussian source distribution we derive an effective radius parameter of R_G = 3.02 \pm 0.20$(stat.)^{+0.44}_{-0.16}(syst.) fm.Comment: 14 pages, 9 figures, submitted to Phys. Rev.

Centrality dependence of proton and antiproton spectra in Pb+Pb collisions at 40A GeV and 158A GeV measured at the CERN SPS

The yields of (anti-)protons were measured by the NA49 Collaboration in centrality selected Pb+Pb collisions at 40A GeV and 158A GeV. Particle identification was obtained in the laboratory momentum range from 5 to 63 GeV/c by the measurement of the energy loss dE/dx in the TPC detector gas. The corresponding rapidity coverage extends 1.6 units from mid-rapidity into the forward hemisphere. Transverse mass spectra, the rapidity dependences of the average transverse mass, and rapidity density distributions were studied as a function of collision centrality. The values of the average transverse mass as well as the midrapidity yields of protons when normalized to the number of wounded nucleons show only modest centrality dependences. In contrast, the shape of the rapidity distribution changes significantly with collision centrality, especially at 40A GeV. The experimental results are compared to calculations of the HSD and UrQMD transport models.Comment: 25 pages, 12 figures, submitted to PR

Phase-space dependence of particle-ratio fluctuations in Pb+Pb collisions from 20A to 158A GeV beam energy

A novel approach, the identity method, was used for particle identification and the study of fluctuations of particle yield ratios in Pb+Pb collisions at the CERN Super Proton Synchrotron (SPS). This procedure allows to unfold the moments of the unknown multiplicity distributions of protons (p), kaons (K), pions ($\pi$) and electrons (e). Using these moments the excitation function of the fluctuation measure $\nu_{\text{\text{dyn}}}$[A,B] was measured, with A and B denoting different particle types. The obtained energy dependence of $\nu_{\text{dyn}}$ agrees with previously published NA49 results on the related measure $\sigma_{\text{dyn}}$. Moreover, $\nu_{\text{dyn}}$ was found to depend on the phase space coverage for [K,p] and [K,$\pi$] pairs. This feature most likely explains the reported differences between measurements of NA49 and those of STAR in central Au+Au collisions