We searched for long-duration microlensing events originating from intermediate-mass black holes (BH) in the halo of the Milky Way, using archival data from the EROS-2 and MACHO photometric surveys ...towards the Large Magellanic Cloud (LMC). We combined data from these two surveys to create a common database of light curves for 14.1 million objects in the LMC, covering a total duration of 10.6 years, with flux series measured in four wide passbands. We carried out a microlensing search on these light curves, complemented by the light curves of 22.7 million objects, observed only by EROS-2 or only by MACHO, over about 7 years, with flux series measured in only two passbands. A likelihood analysis, taking into account the LMC self-lensing and Milky Way disk contributions, allows us to conclude that compact objects with masses in the range 10 − 100
M
⊙
cannot make up more than ∼15% of a standard halo total mass (at a 95% confidence level). Our analysis sensitivity weakens for heavier objects, although we still rule out the possibility of ∼50% of the halo being made of ∼1000
M
⊙
BHs. Combined with previous EROS results, an upper limit of ∼15% of the total halo mass can be obtained for the contribution of compact halo objects in the mass range 10
−6
− 10
2
M
⊙
.
Much of the Earth's biosphere has been appropriated for the production of harvestable biomass in the form of food, fuel and fibre. Here we show that the simplification and intensification of these ...systems and their growing connection to international markets has yielded a global production ecosystem that is homogenous, highly connected and characterized by weakened internal feedbacks. We argue that these features converge to yield high and predictable supplies of biomass in the short term, but create conditions for novel and pervasive risks to emerge and interact in the longer term. Steering the global production ecosystem towards a sustainable trajectory will require the redirection of finance, increased transparency and traceability in supply chains, and the participation of a multitude of players, including integrated 'keystone actors' such as multinational corporations.
We report an investigation of the Chan–Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and ...allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan–Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.
Hypoglycaemia (low plasma glucose) is a serious and potentially fatal complication of insulin-treated diabetes. In healthy individuals, hypoglycaemia triggers glucagon secretion, which restores ...normal plasma glucose levels by stimulation of hepatic glucose production. This counterregulatory mechanism is impaired in diabetes. Here we show in mice that therapeutic concentrations of insulin inhibit glucagon secretion by an indirect (paracrine) mechanism mediated by stimulation of intra-islet somatostatin release. Insulin's capacity to inhibit glucagon secretion is lost following genetic ablation of insulin receptors in the somatostatin-secreting δ-cells, when insulin-induced somatostatin secretion is suppressed by dapagliflozin (an inhibitor of sodium-glucose co-tranporter-2; SGLT2) or when the action of secreted somatostatin is prevented by somatostatin receptor (SSTR) antagonists. Administration of these compounds in vivo antagonises insulin's hypoglycaemic effect. We extend these data to isolated human islets. We propose that SSTR or SGLT2 antagonists should be considered as adjuncts to insulin in diabetes therapy.
Dothideomycetes is the largest class of kingdom Fungi and comprises an incredible diversity of lifestyles, many of which have evolved multiple times. Plant pathogens represent a major ecological ...niche of the class Dothideomycetes and they are known to infect most major food crops and feedstocks for biomass and biofuel production. Studying the ecology and evolution of Dothideomycetes has significant implications for our fundamental understanding of fungal evolution, their adaptation to stress and host specificity, and practical implications with regard to the effects of climate change and on the food, feed, and livestock elements of the agro-economy. In this study, we present the first large-scale, whole-genome comparison of 101 Dothideomycetes introducing 55 newly sequenced species. The availability of whole-genome data produced a high-confidence phylogeny leading to reclassification of 25 organisms, provided a clearer picture of the relationships among the various families, and indicated that pathogenicity evolved multiple times within this class. We also identified gene family expansions and contractions across the Dothideomycetes phylogeny linked to ecological niches providing insights into genome evolution and adaptation across this group. Using machine-learning methods we classified fungi into lifestyle classes with >95 % accuracy and identified a small number of gene families that positively correlated with these distinctions. This can become a valuable tool for genome-based prediction of species lifestyle, especially for rarely seen and poorly studied species.
ABSTRACT
The International Pulsar Timing Array 2nd data release is the combination of data sets from worldwide collaborations. In this study, we search for continuous waves: gravitational wave ...signals produced by individual supermassive black hole binaries in the local universe. We consider binaries on circular orbits and neglect the evolution of orbital frequency over the observational span. We find no evidence for such signals and set sky averaged 95 per cent upper limits on their amplitude h95. The most sensitive frequency is 10 nHz with h95 = 9.1 × 10−15. We achieved the best upper limit to date at low and high frequencies of the PTA band thanks to improved effective cadence of observations. In our analysis, we have taken into account the recently discovered common red noise process, which has an impact at low frequencies. We also find that the peculiar noise features present in some pulsars data must be taken into account to reduce the false alarm. We show that using custom noise models is essential in searching for continuous gravitational wave signals and setting the upper limit.
Upgraded electronics, improved water system dynamics, better calibration and analysis techniques allowed Super-Kamiokande-IV to clearly observe very low-energy B8 solar neutrino interactions, with ...recoil electron kinetic energies as low as ∼3.5 MeV. Super-Kamiokande-IV data-taking began in September of 2008; this paper includes data until February 2014, a total livetime of 1664 days. The measured solar neutrino flux is (2.308±0.020(stat)−0.040+0.039(syst))×106/(cm2 sec) assuming no oscillations. The observed recoil electron energy spectrum is consistent with no distortions due to neutrino oscillations. An extended maximum likelihood fit to the amplitude of the expected solar zenith angle variation of the neutrino-electron elastic scattering rate in SK-IV results in a day/night asymmetry of (−3.6±1.6(stat)±0.6(syst))%. The SK-IV solar neutrino data determine the solar mixing angle as sin2θ12=0.327−0.031+0.026, all SK solar data (SK-I, SK-II, SK III and SK-IV) measures this angle to be sin2θ12=0.334−0.023+0.027, the determined mass-squared splitting is Δm212=4.8−0.8+1.5×10−5 eV2.
The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This ...mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ̃ confidence level, using a low-background, 14.6-kilogram CsINa scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.
Abstract
Objectives
To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer ...screening.
Methods
A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review.
Results
Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud’s phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD −1189.96) or lactate dehydrogenase (WMD −336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers.
Conclusion
Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.
The Chan–Evans–Lam reaction is a valuable C–N bond forming process. However, aryl boronic acid pinacol (BPin) ester reagents can be difficult coupling partners that often deliver low yields, in ...particular in reactions with aryl amines. Herein, we report effective reaction conditions for the Chan–Evans–Lam amination of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was found to enable effective C–N bond formation using aryl amines while EtOH is not required for the coupling of alkyl amines.
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