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Abstract Discrete time-translational symmetry in a periodically driven many-body system can be spontaneously broken to form a discrete time crystal, an exotic new phase of matter. We present observations characteristic of discrete time crystalline order in a driven system of paramagnetic P-donor impurities in isotopically enriched 28Si cooled below 10 K. The observations exhibit a stable subharmonic peak at half the drive frequency which remains pinned even in the presence of pulse error, a signature of discrete time crystalline order. This signal has a finite lifetime of ∼100 Floquet periods, but this effect is long-lived relative to coherent spin–spin interaction timescales, lasting ∼104 times longer. We present simulations of the system based on the paradigmatic central spin model and show good agreement with experiment. We investigate the role of dissipation and interactions within this model, and show that both are capable of giving rise to discrete time crystal-like behaviour.

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. http://purl.org/eprint/status/PeerReviewed published version Article

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. This study made use of data generated by the Wellcome Trust Case Control consortium. Functional studies were supported by the Florida Breast Cancer Foundation. A full description of funding and acknowledgments is provided in Supplementary Note 1.

Scattering amplitudes of partons in QCD contain infrared divergences which can be resummed to all orders in terms of an anomalous dimension. Independently, in the limit of high-energy forward scattering, large logarithms of the energy can be resummed using Balitsky-Fadin-Kuraev-Lipatov theory. We use the latter to analyze the infrared-singular part of amplitudes to all orders in perturbation theory and to next-to-leading-logarithm accuracy in the high-energy limit, resumming the two-Reggeon contribution. Remarkably, we find a closed form for the infrared-singular part, predicting the Regge limit of the soft anomalous dimension to any loop order. Comment: 35 pages, 8 figures

Abstract We used microPET to map the dose–response to the novel P-glycoprotein (P-gp) inhibitor tariquidar (TQD) of the initial influx of the P-gp substrate [ 18 F]-MPPF in rat brain, and to test for effects of P-gp inhibition on the subsequent binding of [ 18 F]-MPPF to serotonin 5-HT 1A receptors. Summation maps of [ 18 F]-MPPF uptake during the first 100 seconds after intravenous injection were calculated in groups of rats with vehicle (glucose 5%) pretreatment, or following pretreatment with TQD at doses of 5, 15, or 30 mg/kg. The early summation image ( K 1 -weighted), were validated as a surrogate marker for the physiological blood–brain clearance ( K 1 ; ml g − 1 min − 1 ) by linear graphic analysis of the unidirectional blood–brain clearance relative to an image-based arterial input measured in the left ventricle of the heart. In the same animals, parametric maps of the [ 18 F]-MPPF binding potential (BP ND ) were calculated from the entire 60-minute emission recordings using conventional reference tissue methods. All [ 18 F]-MPPF recordings were followed by an [ 18 F]-FDG emission recording, the summation of which was used for spatial normalization to a rat brain atlas. Test–retest variability of K 1 -weighted uptake and BP ND was 25%. TQD treatment evoked a global dose-dependent increase in K 1 -weighted summation, which increased 2.5-fold with TQD (30 mg/kg), suggesting an IC 50 of 5 mg/kg TQD. All TQD doses increased the apparent [ 18 F]-MPPF BP ND calculated by the Logan method by 30%–40%, a bias likely arising due to increased free [ 18 F]-MPPF concentrations in brain. TQD (15 mg/kg) evoked a 45% global increase in [ 18 F]-FDG uptake, suggesting perturbation of brain energy metabolism due to P-gp blockade.

Nanoparticles of plasmonic materials can sustain oscillations of their free electron density, called localized surface plasmon resonances (LSPRs), giving them a broad range of potential applications. Mg is an earth-abundant plasmonic material attracting growing attention owing to its ability to sustain LSPRs across the ultraviolet, visible, and near-infrared wavelength range. Tuning the LSPR frequency of plasmonic nanoparticles requires precise control over their size and shape; for Mg, this control has previously been achieved using top-down fabrication or gas-phase methods, but these are slow and expensive. Here, we systematically probe the effects of reaction parameters on the nucleation and growth of Mg nanoparticles using a facile and inexpensive colloidal synthesis. Small NPs of 80 nm were synthesized using a low reaction time of 1 min and ���100 nm NPs were synthesized by decreasing the overall reaction concentration, replacing the naphthalene electron carrier with biphenyl or using metal salt additives of FeCl3 or NiCl2 at longer reaction times of 17 h. Intermediate sizes up to 400 nm were further selected via the overall reaction concentration or using other metal salt additives with different reduction potentials. Significantly larger particles of over a micrometer were produced by reducing the reaction temperature and, thus, the nucleation rate. We showed that increasing the solvent coordination reduced Mg NP sizes, while scaling up the reaction reduced the mixing efficiency and produced larger NPs. Surprisingly, varying the relative amounts of Mg precursor and electron carrier had little impact on the final NP sizes. These results pave the way for the large-scale use of Mg as a low-cost and sustainable plasmonic material. Support for this project was provided by the EU Framework Programme for Research and Innovation Horizon 2020 (ERC Starting Grant SPECs 804523). E.R.H. is thankful for funding from the EPSRC NanoDTC Cambridge (EP/L015978/1). J.A. acknowledges financial support from Natural Sciences and Engineering Research Council of Canada and Fonds de Recherche du Qu��bec���Nature et Technologies postdoctoral fellowships (BP and B3X programs). C.B. is thankful for funding from the Engineering and Physical Sciences Research Council (Standard Research Studentship (DTP) EP/R513180/1). B.P. and L.T.M. acknowledge support from UK Engineering and Physical Science and Research Council (grant number EP/L020443/2). Thanks to Giulio I. Lampronti for helpful discussions and support.

Dinoflagellates are microbial eukaryotes that have exceptionally large nuclear genomes; however, their organelle genomes are small and fragmented and contain fewer genes than those of other eukaryotes. The genus Amoebophrya (Syndiniales) comprises endoparasites with high genetic diversity that can infect other dinoflagellates, such as those forming harmful algal blooms (e.g., Alexandrium). We sequenced the genome (~100 Mb) of Amoebophrya ceratii to investigate the early evolution of genomic characters in dinoflagellates. The A. ceratii genome encodes almost all essential biosynthetic pathways for self-sustaining cellular metabolism, suggesting a limited dependency on its host. Although dinoflagellates are thought to have descended from a photosynthetic ancestor, A. ceratii appears to have completely lost its plastid and nearly all genes of plastid origin. Functional mitochondria persist in all life stages of A. ceratii, but we found no evidence for the presence of a mitochondrial genome. Instead, all mitochondrial proteins appear to be lost or encoded in the A. ceratii nucleus. The parasitic marine dinoflagellate Amoebophrya is the first known eukaryote with aerobic mitochondria without a genome.

Anuran metamorphosis is characterized by profound morphological changes including remodeling of tissues and organs. This transition is initiated by thyroid hormones (THs). However, the current knowledge of changing levels of THs during metamorphosis relies on pooled samples using methods known for high variability with sparse reporting of measured variation. Moreover, establishing a clear linkage between key gene expression bioindicators and TH levels throughout the metamorphic process is needed. Using state-of-the-art ultra-high performance liquid chromatography isotope-dilution tandem mass spectrometry, we targeted 12 THs and metabolites in the serum of Rana [Lithobates] catesbeiana (n=5-10) across seven distinct postembryonic stages beginning with premetamorphic tadpoles (Gosner stage 31-33) and continuing through metamorphosis to a juvenile frog (Gosner stage 46). TH levels were related to TH-relevant gene transcripts (thra, thrb, and thibz) in back skin of the same individual animals. Significant increases from basal levels were observed for thyroxine (T4) and 3,3’,5-triiodothyronine (T3) at Gosner stage 41, reaching maximal levels at Gosner stage 44 (28 ± 10 and 2.3 ± 0.5 ng/mL, respectively), and decreasing to basal levels in juvenile frogs. In contrast, 3,5-diiodothyronine (T2) increased significantly at Gosner stage 40 and was maintained elevated until stage 44. While thra transcript levels remained constant and then decreased at the end of metamorphic climax, thrb and thibz were induced to maximal levels at Gosner stage 41, followed by a decrease to basal levels in the froglet. This exemplifies the exquisite timing of events during metamorphosis as classic early response genes are transcribed in anticipation of peak TH concentrations. The distinct T2 concentration profile suggests a biological role of this biomolecule in anuran postembryonic development and an additional aspect that may be a target of anthropogenic chemicals that can disrupt anuran metamorphosis and TH signalling. Hence, as a second aim of the study, we set out to find additional bioindicators of metamorphosis, which can aid future investigations of developmental disruption. Using a sensitive nanoLC-Orbitrap system an untargeted analysis workflow was applied. Among 6,062 endogenous metabolites, 421 showed metamorphosis-dependent concentration dynamics. These potential bioindicators included several carnitines, prostaglandins and some steroid hormones.

The Ophiuchus stream is a short arc-like stellar feature of uncertain origin located $\sim 5$ kpc North of the Galactic centre. New proper motions from the second $Gaia$ data release reconcile the direction of motion of stream members with the stream arc, resolving a puzzling mismatch reported in earlier work. We use N-body simulations to show that the stream is likely only on its second pericentric passage, and thus was formed recently. The simulations suggest that the entire disrupted progenitor is visible in the observed stream today, and that little further tidal debris lies beyond the ends of the stream. The luminosity, length, width, and velocity dispersion of the stream suggest a globular cluster (GC) progenitor substantially fainter and of lower surface brightness than estimated in previous work, and unlike any other known globulars in the Galaxy. This result suggests the existence of clusters that would extend the known GC population to fainter and more weakly bound systems than hitherto known. How such a weakly-bound cluster of old stars survived until it was disrupted so recently, however, remains a mystery. Integrating backwards in time, we find that the orbits of Sagittarius and Ophiuchus passed within $\sim 5$ kpc of each other about $\sim 100$ Myrs ago, an interaction that might help resolve this puzzle. 11 pages, 7 figures, submitted to MNRAS

We consider the problem of distributed source simulation with no communication, in which Alice and Bob observe sequences $U^{n}$ and $V^{n}$ respectively, drawn from a joint distribution $p_{UV}^ {\otimes n}$ , and wish to locally generate sequences $X^{n}$ and $Y^{n}$ respectively with a joint distribution that is close (in KL divergence) to $p_{XY}^ {\otimes n}$ . We provide a single-letter condition under which such a simulation is asymptotically possible with a vanishing KL divergence. Our condition is nontrivial only in the case where the Gacs-Korner (GK) common information between $U$ and $V$ is nonzero, and we conjecture that only scalar Markov chains $X-U-V-Y$ can be simulated otherwise. Motivated by this conjecture, we further examine the case where both $p_{UV}$ and $p_{XY}$ are doubly symmetric binary sources with parameters $p,q\leq 1/2$ respectively. While it is trivial that in this case $p\leq q$ is both necessary and sufficient, we use Fourier analytic tools to show that when $p$ is close to $q$ then any successful simulation is close to being scalar in the total variation sense.