Making optical atomic clocks more stable with 10−1610^{-16} level laser stabilization

The superb precision of an atomic clock is derived from its stability. Atomic clocks based on optical (rather than microwave) frequencies are attractive because of their potential for high stability, which scales with operational frequency. Nevertheless, optical clocks have not yet realized this vast potential, due in large part to limitations of the laser used to excite the atomic resonance. To address this problem, we demonstrate a cavity-stabilized laser system with a reduced thermal noise floor, exhibiting a fractional frequency instability of $2 \times 10^{-16}$. We use this laser as a stable optical source in a Yb optical lattice clock to resolve an ultranarrow 1 Hz transition linewidth. With the stable laser source and the signal to noise ratio (S/N) afforded by the Yb optical clock, we dramatically reduce key stability limitations of the clock, and make measurements consistent with a clock instability of $5 \times 10^{-16} / \sqrt{\tau}$

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

Demographic, criminal and psychiatric factors related to inmate suicide

A review of 19 studies suggests that it may be feasible to identify prisoners with suicide risk on the basis of demographic, psychiatric, and criminal characteristics. The present study aimed to identify combinations of characteristics that are capable of identifying potential suicide victims. Characteristics of 95 suicide victims in the Dutch prison system were compared with those of a random sample of 247 inmates in ten jails. Combinations of indicators for suicide risk were also tested for their capability of identifying 209 suicides in U.S. jails and 279 prison suicides in England and Wales. A combination of six characteristics (age 40+, homelessness, history of psychiatric care, history of drug abuse, one prior incarceration, violent offence) was capable of correctly classifying 82% of the Dutch suicide victims (82% specificity). Less powerful combinations correctly classified 53% of the U.S. suicides and 47% of the U.K. suicides. It is concluded that a set of demographic and criminal characteristics and indicators of psychiatric problems is useful for the identification of suicide risk in jails and prisons

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

The critical role of second-order normative beliefs in predicting energy conservation

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordSustaining large-scale public goods requires individuals to make environmentally friendly decisions today to benefit future generations. Recent research suggests that second-order normative beliefs are more powerful predictors of behaviour than first-order personal beliefs. We explored the role that second-order normative beliefs—the belief that community members think that saving energy helps the environment—play in curbing energy use. We first analysed a data set of 211 independent, randomized controlled trials conducted in 27 US states by Opower, a company that uses comparative information about energy consumption to reduce household energy usage (pooled N = 16,198,595). Building off the finding that the energy savings varied between 0.81% and 2.55% across states, we matched this energy use data with a survey that we conducted of over 2,000 individuals in those same states on their first-order personal and second-order normative beliefs. We found that second-order normative beliefs predicted energy savings but first-order personal beliefs did not. A subsequent pre-registered experiment provides causal evidence for the role of second-order normative beliefs in predicting energy conservation above first-order personal beliefs. Our results suggest that second-order normative beliefs play a critical role in promoting energy conservation and have important implications for policymakers concerned with curbing the detrimental consequences of climate change

The value of CCTV surveillance cameras as an investigative tool: an empirical analysis

There has been extensive research on the value of closed-circuit television (CCTV) for preventing crime, but little on its value as an investigative tool. This study sought to establish how often CCTV provides useful evidence and how this is affected by circumstances, analysing 251,195 crimes recorded by British Transport Police that occurred on the British railway network between 2011 and 2015. CCTV was available to investigators in 45% of cases and judged to be useful in 29% (65% of cases in which it was available). Useful CCTV was associated with significantly increased chances of crimes being solved for all crime types except drugs/weapons possession and fraud. Images were more likely to be available for more-serious crimes, and less likely to be available for cases occurring at unknown times or in certain types of locations. Although this research was limited to offences on railways, it appears that CCTV is a powerful investigative tool for many types of crime. The usefulness of CCTV is limited by several factors, most notably the number of public areas not covered. Several recommendations for increasing the usefulness of CCTV are discussed

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Expression and trans-specific polymorphism of self-incompatibility RNases in Coffea (Rubiaceae)

Self-incompatibility (SI) is widespread in the angiosperms, but identifying the biochemical components of SI mechanisms has proven to be difficult in most lineages. Coffea (coffee; Rubiaceae) is a genus of old-world tropical understory trees in which the vast majority of diploid species utilize a mechanism of gametophytic self-incompatibility (GSI). The S-RNase GSI system was one of the first SI mechanisms to be biochemically characterized, and likely represents the ancestral Eudicot condition as evidenced by its functional characterization in both asterid (Solanaceae, Plantaginaceae) and rosid (Rosaceae) lineages. The S-RNase GSI mechanism employs the activity of class III RNase T2 proteins to terminate the growth of "self" pollen tubes. Here, we investigate the mechanism of Coffea GSI and specifically examine the potential for homology to S-RNase GSI by sequencing class III RNase T2 genes in populations of 14 African and Madagascan Coffea species and the closely related self-compatible species Psilanthus ebracteolatus. Phylogenetic analyses of these sequences aligned to a diverse sample of plant RNase T2 genes show that the Coffea genome contains at least three class III RNase T2 genes. Patterns of tissue-specific gene expression identify one of these RNase T2 genes as the putative Coffea S-RNase gene. We show that populations of SI Coffea are remarkably polymorphic for putative S-RNase alleles, and exhibit a persistent pattern of trans-specific polymorphism characteristic of all S-RNase genes previously isolated from GSI Eudicot lineages. We thus conclude that Coffea GSI is most likely homologous to the classic Eudicot S-RNase system, which was retained since the divergence of the Rubiaceae lineage from an ancient SI Eudicot ancestor, nearly 90 million years ago.United States National Science Foundation [0849186]; Society of Systematic Biologists; American Society of Plant Taxonomists; Duke University Graduate Schoolinfo:eu-repo/semantics/publishedVersio