Certified Quantum Random Numbers from Untrusted Light

A remarkable aspect of quantum theory is that certain measurement outcomes are entirely unpredictable to all possible observers. Such quantum events can be harnessed to generate numbers whose randomness is asserted based upon the underlying physical processes. We formally introduce, design and experimentally demonstrate an ultrafast optical quantum random number generator that uses a totally untrusted photonic source. While considering completely general quantum attacks, we certify and generate in real-time random numbers at a rate of 8.05 Gb/s with a rigorous security parameter of 10^(−10). Our security proof is entirely composable, thereby allowing the generated randomness to be utilised for arbitrary applications in cryptography and beyond. To our knowledge, this represents the fastest composably secure source of quantum random numbers ever reported

Entanglement quantification from incomplete measurements: Applications using photon-number-resolving weak homodyne detectors

The certificate of success for a number of important quantum information processing protocols, such as entanglement distillation, is based on the difference in the entanglement content of the quantum states before and after the protocol. In such cases, effective bounds need to be placed on the entanglement of non-local states consistent with statistics obtained from local measurements. In this work, we study numerically the ability of a novel type of homodyne detector which combines phase sensitivity and photon-number resolution to set accurate bounds on the entanglement content of two-mode quadrature squeezed states without the need for full state tomography. We show that it is possible to set tight lower bounds on the entanglement of a family of two-mode degaussified states using only a few measurements. This presents a significant improvement over the resource requirements for the experimental demonstration of continuous-variable entanglement distillation, which traditionally relies on full quantum state tomography.Comment: 18 pages, 6 figure

Demonstrating the reliability of in vivo metabolomics based chemical grouping:towards best practice

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography–mass spectrometry (LC–MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is not detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice

Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study

Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking. In this large multicentre prospective cohort study of 196 patients with dominant and autosomal recessive CMT2A, we present an in-depth genotype-phenotype study of the baseline characteristics of patients with CMT2A and longitudinal data (1-2 years) to describe the natural history. A childhood onset of autosomal dominant CMT2A is the most predictive marker of significant disease severity and is independent of the disease duration. When compared to adult onset autosomal dominant CMT2A, it is associated with significantly higher rates of use of ankle-foot orthoses, full-time use of wheelchair, dexterity difficulties and also has significantly higher CMT Examination Score (CMTESv2) and CMT Neuropathy Score (CMTNSv2) at initial assessment. Analysis of longitudinal data using the CMTESv2 and its Rasch-weighted counterpart, CMTESv2-R, show that over 1 year, the CMTESv2 increases significantly in autosomal dominant CMT2A (mean change 0.84 ± 2.42; two-tailed paired t-test P = 0.039). Furthermore, over 2 years both the CMTESv2 (mean change 0.97 ± 1.77; two-tailed paired t-test P = 0.003) and the CMTESv2-R (mean change 1.21 ± 2.52; two-tailed paired t-test P = 0.009) increase significantly with respective standardized response means of 0.55 and 0.48. In the paediatric CMT2A population (autosomal dominant and autosomal recessive CMT2A grouped together), the CMT Pediatric Scale increases significantly both over 1 year (mean change 2.24 ± 3.09; two-tailed paired t-test P = 0.009) and over 2 years (mean change 4.00 ± 3.79; two-tailed paired t-test P = 0.031) with respective standardized response means of 0.72 and 1.06. This cross-sectional and longitudinal study of the largest CMT2A cohort reported to date provides guidance for variant interpretation, informs prognosis and also provides natural history data that will guide clinical trial design

The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases

MetaCyc (MetaCyc.org) is a universal database of metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are curated from the primary scientific literature, and are experimentally determined small-molecule metabolic pathways. Each reaction in a MetaCyc pathway is annotated with one or more well-characterized enzymes. Because MetaCyc contains only experimentally elucidated knowledge, it provides a uniquely high-quality resource for metabolic pathways and enzymes. BioCyc (BioCyc.org) is a collection of more than 350 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the predicted metabolic network of one organism, including metabolic pathways, enzymes, metabolites and reactions predicted by the Pathway Tools software using MetaCyc as a reference database. BioCyc PGDBs also contain predicted operons and predicted pathway hole fillers—predictions of which enzymes may catalyze pathway reactions that have not been assigned to an enzyme. The BioCyc website offers many tools for computational analysis of PGDBs, including comparative analysis and analysis of omics data in a pathway context. The BioCyc PGDBs generated by SRI are offered for adoption by any interested party for the ongoing integration of metabolic and genome-related information about an organism

Obscured phylogeny and possible recombinational dormancy in Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>is one of the best studied organisms in all of biology, but its phylogenetic structure has been difficult to resolve with current data and analytical techniques. We analyzed single nucleotide polymorphisms in chromosomes of representative strains to reconstruct the topology of its emergence.</p> <p>Results</p> <p>The phylogeny of <it>E. coli </it>varies according to the segment of chromosome analyzed. Recombination between extant <it>E. coli </it>groups is largely limited to only three intergroup pairings.</p> <p>Conclusions</p> <p>Segment-dependent phylogenies most likely are legacies of a complex recombination history. However, <it>E. coli </it>are now in an epoch in which they no longer broadly share DNA. Using the definition of species as organisms that freely exchange genetic material, this recombinational dormancy could reflect either the end of <it>E. coli </it>as a species, or herald the coalescence of <it>E. coli </it>groups into new species.</p

Retinal Morphometric Markers of Crystallized and Fluid Intelligence Among Adults With Overweight and Obesity

Objective: To investigate the relationship between retinal morphometric measures and intellectual abilities among adults with overweight and obesity.Methods: Adults between 25 and 45 years (N = 55, 38 females) with overweight or obesity (BMI ≥ 25.0 kg/m2) underwent an optical coherence tomography (OCT) scan to assess retinal nerve fiber layer (RNFL) volume, ganglion cell layer (GCL) volume, macular volume, and central foveal thickness. Dual-Energy X-ray absorptiometry was used to assess whole-body adiposity (% Fat). The Kaufman Brief Intelligence Test-2 was used to assess general intelligence (IQ), fluid, and crystallized intelligence. Hierarchical linear regression analyses were performed to examine relationships between adiposity and intelligence measures following adjustment of relevant demographic characteristics and degree of adiposity (i.e., % Fat).Results: Although initial bivariate correlations indicated that % Fat was inversely related to fluid intelligence, this relationship was mitigated by inclusion of other demographic factors, including age, sex, and education level. Regression analyses for primary outcomes revealed that RNFL was positively related to IQ and fluid intelligence. However, only GCL was positively related to crystallized intelligence.Conclusion: This work provides novel data linking specific retinal morphometric measures – assessed using OCT – to intellectual abilities among adults with overweight and obesity.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT02740439

A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores

Objective: To evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). Methods: Patients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models. Results: Baseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4–87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99–1.97, p < 0.0001, for baseline CMTES-R score 0–9). Conclusion: The CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A. ClinicalTrials.gov identifier NCT01193075

Search For Exotic Tau-decays

The Crystal Ball detector at the Doris II storage ring at DESY was used to search for the exotic decay processes tau -&gt; e gamma, tau -&gt; e pi0, tau -&gt; e eta. No signal was observed. We obtained the following 90% CL upper limits on the branching fractions:B(tau -&gt; e gamma)&lt; 2.0x10^(-4),B(tau -&gt; e pi0) &lt; 1.4x10^(-4),B(tau -&gt; e eta) &lt; 2.4x10^(-4)