Resolving Photon Numbers Using Ultra-High-Resolution Timing of a Single Low-Jitter Superconducting Nanowire Detector

Photon-number-resolving (PNR) detectors are a key enabling technology in photonic quantum information processing. Here, we demonstrate the PNR capacity of conventional superconducting nanowire single-photon detectors by performing ultra-high-resolution time-tagging of the detector-generated electrical pulses. This method provides a viable approach for PNR with high detection efficiency and a high operational repetition rate. We present the implementation of such a PNR detector in the telecom C-band and its characterization by measuring the photon-number statistics of coherent light with tunable intensity. Additionally, we demonstrate the capabilities of the detection method by measuring photon-number correlations of non-classical states.Comment: 6 pages, 8 figure

Longitudinal transcriptome-wide gene expression analysis of sleep deprivation treatment shows involvement of circadian genes and immune pathways

Therapeutic sleep deprivation (SD) rapidly induces robust, transient antidepressant effects in a large proportion of major mood disorder patients suffering from a depressive episode, but underlying biological factors remain poorly understood. Research suggests that these patients may have altered circadian molecular genetic 'clocks' and that SD functions through 'resetting' dysregulated genes; additional factors may be involved, warranting further investigation. Leveraging advances in microarray technology enabling the transcriptome-wide assessment of gene expression, this study aimed to examine gene expression changes accompanying SD and recovery sleep in patients suffering from an episode of depression. Patients (N = 78) and controls (N = 15) underwent SD, with blood taken at the same time of day before SD, after one night of SD and after recovery sleep. A transcriptome-wide gene-by-gene approach was used, with a targeted look also taken at circadian genes. Furthermore, gene set enrichment, and longitudinal gene set analyses including the time point after recovery sleep, were conducted. Circadian genes were significantly affected by SD, with patterns suggesting that molecular clocks of responders and non-responders, as well as patients and controls respond differently to chronobiologic stimuli. Notably, gene set analyses revealed a strong widespread effect of SD on pathways involved in immune function and inflammatory response, such as those involved in cytokine and especially in interleukin signalling. Longitudinal gene set analyses showed that in responders these pathways were upregulated after SD; in non-responders, little response was observed. Our findings emphasize the close relationship between circadian, immune and sleep systems and their link to etiology of depression at the transcriptomic level

Sibiriline, a new small chemical inhibitor of receptor-interacting protein kinase 1, prevents immune-dependent hepatitis

Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-interacting protein kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a noncommercial, kinase-focused chemical library which allowed us to identify Sibiriline as a new inhibitor of necroptosis induced by tumor necrosis factor (TNF) in Fas-associated protein with death domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis. By using competition binding assay and recombinant kinase assays, we demonstrated that Sib is a rather specific competitive RIPK1 inhibitor. Molecular docking analysis shows that Sib is trapped closed to human RIPK1 adenosine triphosphate-binding site in a relatively hydrophobic pocket locking RIPK1 in an inactive conformation. In agreement with its RIPK1 inhibitory property, Sib inhibits both TNF-induced RIPK1-dependent necroptosis and RIPK1-dependent apoptosis. Finally, Sib protects mice from concanavalin A-induced hepatitis. These results reveal the small-molecule Sib as a new RIPK1 inhibitor potentially of interest for the treatment of immune-dependent hepatitis

Moray eels are more common on coral reefs subject to higher human pressure in the greater Caribbean

Proximity and size of the nearest market (‘market gravity’) have been shown to have strong negative effects on coral reef fish communities that can be mitigated by the establishment of closed areas. However, moray eels are functionally unique predators that are generally not subject to targeted fishing and should therefore not directly be affected by these factors. We used baited remote underwater video systems to investigate associations between morays and anthropogenic, habitat, and ecological factors in the Caribbean region. Market gravity had a positive effect on morays, while the opposite pattern was observed in a predator group subject to exploitation (sharks). Environmental DNA analyses corroborated the positive effect of market gravity on morays. We hypothesize that the observed pattern could be the indirect result of the depletion of moray competitors and predators near humans. Environmental science; ecology; biological sciences; zoology; animals; etholog

Probing the biogenesis pathway and dynamics of thylakoid membranes

How thylakoid membranes are generated to form a metabolically active membrane network and how thylakoid membranes orchestrate the insertion and localization of protein complexes for efficient electron flux remain elusive. Here, we develop a method to modulate thylakoid biogenesis in the rod-shaped cyanobacterium Synechococcus elongatus PCC 7942 by modulating light intensity during cell growth, and probe the spatial-temporal stepwise biogenesis process of thylakoid membranes in cells. Our results reveal that the plasma membrane and regularly arranged concentric thylakoid layers have no physical connections. The newly synthesized thylakoid membrane fragments emerge between the plasma membrane and pre-existing thylakoids. Photosystem I monomers appear in the thylakoid membranes earlier than other mature photosystem assemblies, followed by generation of Photosystem I trimers and Photosystem II complexes. Redistribution of photosynthetic complexes during thylakoid biogenesis ensures establishment of the spatial organization of the functional thylakoid network. This study provides insights into the dynamic biogenesis process and maturation of the functional photosynthetic machinery. Cyanobacterial thylakoid membranes host the molecular machinery for the light-dependent reactions of photosynthesis and respiratory electron flow. Here, the authors show that newly synthesized thylakoids emerge between the plasma membrane and pre-existing thylakoids and describe the time-dependent assembly process of photosynthetic complexes

Fermi Discovery of Gamma-Ray Emission from NGC 1275

We report the discovery of high-energy (E>100 MeV) gamma-ray emission from NGC 1275, a giant elliptical galaxy lying at the center of the Perseus cluster of galaxies, based on observations made with the Large Area Telescope (LAT) of the Fermi Gamma ray Space Telescope. The positional center of the gamma-ray source is only ~3' away from the NGC 1275 nucleus, well within the 95% LAT error circle of ~5'.The spatial distribution of gamma-ray photons is consistent with a point source. The average flux and power-law photon index measured with the LAT from 2008 August 4 to 2008 December 5 are F_gamma = (2.10+-0.23)x 10^{-7} ph (>100 MeV) cm^{-2} s^{-1} and Gamma = 2.17+-0.05, respectively. The measurements are statistically consistent with constant flux during the four-month LAT observing period.Previous EGRET observations gave an upper limit of F_gamma 100 MeV) cm^{-2} s^{-1} to the gamma-ray flux from NGC 1275. This indicates that the source is variable on timescales of years to decades, and therefore restricts the fraction of emission that can be produced in extended regions of the galaxy cluster. Contemporaneous and historical radio observations are also reported. The broadband spectrum of NGC 1275 is modeled with a simple one-zone synchrotron/synchrotron self-Compton model and a model with a decelerating jet flow.Comment: 27 pages, 7 figures, Accepted for publication in the Astrophysical Journa

Successful Reach and Adoption of a workplace health promotion RCT targeting a group of high-risk workers

<p>Abstract</p> <p>Background</p> <p>Cleaners are rarely introduced to workplace health promotion programs. The study's objective was to evaluate the reach and adoption of a workplace randomized controlled trial (RCT) among cleaners in Denmark.</p> <p>Methods</p> <p>Cleaning businesses with at least 30 employees, that could offer a weekly 1-hour intervention during working hours, were invited to participate. Employees working at least 20 hours/week were invited to answer a screening questionnaire and consent to participate. Analyses determined the differences in health variables between responders and non-responders, consenters and non-consenters, participants and non-participants and between participants of the RCT's three groups: physical coordination training, cognitive-behavioural theory-based training and reference group.</p> <p>Results</p> <p>From 16 eligible workplaces, a representative sample of 50% adopted the trial. Of 758 eligible employees, 78% responded to the screening questionnaire and 49% consented to participate. Consenters and participants differed from non-consenters and non-participants by having higher BMI, more chronic diseases and poorer musculoskeletal health.</p> <p>Conclusions</p> <p>This study indicates that workplace health promotion programs directed at health risk factors among cleaners enable significant adoption and reach to a high-risk subgroup of the Danish workforce.</p> <p>Trial registration</p> <p>Trial registration ISRCTN96241850</p

Worldwide Distribution of the MYH9 Kidney Disease Susceptibility Alleles and Haplotypes: Evidence of Historical Selection in Africa

MYH9 was recently identified as renal susceptibility gene (OR 3–8, p<10−8) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (≥60%) than in European Americans (<4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs) spanning introns 12–23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP). The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50–80%), less frequent in populations from the Middle East (9–27%) and Europe (0–9%), and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (FST) for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; FST ranged from 0.27–0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C) compared to the alternative allele (T) at the same locus (rs4821481, iHs = 2.67), as well as high population differentiation (FST(CEU vs. YRI) = 0.51) in HapMap Phase II data, also observable only in the Yoruba population from HGDP (FST = 0.49), pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations

Response to Therapeutic Sleep Deprivation: A Naturalistic Study of Clinical and Genetic Factors and Post-treatment Depressive Symptom Trajectory

Research has shown that therapeutic sleep deprivation (SD) has rapid antidepressant effects in the majority of depressed patients. Investigation of factors preceding and accompanying these effects may facilitate the identification of the underlying biological mechanisms. This exploratory study aimed to examine clinical and genetic factors predicting response to SD and determine the impact of SD on illness course. Mood during SD was also assessed via visual analogue scale. Depressed inpatients (n = 78) and healthy controls (n = 15) underwent ~36 h of SD. Response to SD was defined as a score of ≤ 2 on the Clinical Global Impression Scale for Global Improvement. Depressive symptom trajectories were evaluated for up to a month using self/expert ratings. Impact of genetic burden was calculated using polygenic risk scores for major depressive disorder. In total, 72% of patients responded to SD. Responders and non-responders did not differ in baseline self/expert depression symptom ratings, but mood differed. Response was associated with lower age (p = 0.007) and later age at life-time disease onset (p = 0.003). Higher genetic burden of depression was observed in non-responders than healthy controls. Up to a month post SD, depressive symptoms decreased in both patients groups, but more in responders, in whom effects were sustained. The present findings suggest that re-examining SD with a greater focus on biological mechanisms will lead to better understanding of mechanisms of depression