A dusty compact object bridging galaxies and quasars at cosmic dawn.

Understanding how super-massive black holes form and grow in the early Universe has become a major challenge1,2 since it was discovered that luminous quasars existed only 700 million years after the Big Bang3,4. Simulations indicate an evolutionary sequence of dust-reddened quasars emerging from heavily dust-obscured starbursts that then transition to unobscured luminous quasars by expelling gas and dust5. Although the last phase has been identified out to a redshift of 7.6 (ref. 6), a transitioning quasar has not been found at similar redshifts owing to their faintness at optical and near-infrared wavelengths. Here we report observations of an ultraviolet compact object, GNz7q, associated with a dust-enshrouded starburst at a redshift of 7.1899 ± 0.0005. The host galaxy is more luminous in dust emission than any other known object at this epoch, forming 1,600 solar masses of stars per year within a central radius of 480 parsec. A red point source in the far-ultraviolet is identified in deep, high-resolution imaging and slitless spectroscopy. GNz7q is extremely faint in X-rays, which indicates the emergence of a uniquely ultraviolet compact star-forming region or a Compton-thick super-Eddington black-hole accretion disk at the dusty starburst core. In the latter case, the observed properties are consistent with predictions from cosmological simulations7 and suggest that GNz7q is an antecedent to unobscured luminous quasars at later epochs.

Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin.

BACKGROUND: Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. OBJECTIVES: To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. METHODS: Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. RESULTS: Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. CONCLUSIONS: Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.

Analysis of the Robertsonian (1;29) fusion in Bovinae reveals a common mechanism: insights into its clinical occurrence and chromosomal evolution.

The interest in Robertsonian fusion chromosomes (Rb fusions), sometimes referred to as Robertsonian translocations, derives from their impact on mammalian karyotype evolution, as well from their influence on fertility and disease. The formation of a Rb chromosome necessitates the occurrence of double strand breaks in the pericentromeric regions of two chromosomes in the satellite DNA (satDNA) sequences. Here, we report on the fine-scale molecular analysis of the centromeric satDNA families in the Rb(1;29) translocation of domestic cattle and six antelope species of the subfamily Bovinae. We do so from two perspectives: its occurrence as a chromosomal abnormality in cattle and, secondly, as a fixed evolutionarily rearrangement in spiral-horned antelope (Tragelaphini). By analysing the reorganization of satDNAs in the centromeric regions of translocated chromosomes, we show that Rb fusions are multistep, complex rearrangements which entail the precise elimination and reorganization of specific (peri)centromeric satDNA sequences. Importantly, these structural changes do not influence the centromeric activity of the satellite DNAs that provide segregation stability to the translocated chromosome. Our results suggest a common mechanism for Rb fusions in these bovids and, more widely, for mammals in general.

Efficacy and safety of administering oral misoprostol by titration compared to vaginal misoprostol and dinoprostone for cervical ripening and induction of labour: study protocol for a randomised clinical trial.

BACKGROUND: Among the various methods available, the administration of prostaglandins is the most effective for inducing labour in women with an unfavourable cervix. Recent studies have compared treatment with various titrated doses of oral misoprostol with vaginal misoprostol or dinoprostone, indicating that the use of an escalating dose of an oral misoprostol solution is associated with a lower rate of caesarean sections and a better safety profile. The objective of this study is to assess which of these three therapeutic options (oral or vaginal misoprostol or vaginal dinoprostone) achieves the highest rate of vaginal delivery within the first 24 h of drug administration. METHODS: An open-label randomised controlled trial will be conducted in Araba University Hospital (Spain). Women at ≥41 weeks of pregnancy requiring elective induction of labour who meet the selection criteria will be randomly allocated to one of three groups: 1) vaginal dinoprostone (delivered via a controlled-release vaginal insert containing 10 mg of dinoprostone, for up to 24 h); 2) vaginal misoprostol (25 µg of vaginal misoprostol every 4 h up to a maximum of 24 h); and 3) oral misoprostol (titrated doses of 20 to 60 µg of misoprostol following a 3 h on + 1 h off regimen up to a maximum of 24 h). Both intention-to-treat analysis and per-protocol analysis will be performed. DISCUSSION: The proposed study seeks to gather evidence on which of these three therapeutic options achieves the highest rate of vaginal delivery with the best safety profile, to enable obstetricians to use the most effective and safe option for their patients. TRIAL REGISTRATION: NCT02902653 Available at: https://clinicaltrials.gov/show/NCT02902653 (7th September 2016).

Quantum Steering Beyond Instrumental Causal Networks.

We theoretically predict, and experimentally verify with entangled photons, that outcome communication is not enough for hidden-state models to reproduce quantum steering. Hidden-state models with outcome communication correspond, in turn, to the well-known instrumental processes of causal inference but in the one-sided device-independent scenario of one black-box measurement device and one well-characterized quantum apparatus. We introduce one-sided device-independent instrumental inequalities to test against these models, with the appealing feature of detecting entanglement even when communication of the black box's measurement outcome is allowed. We find that, remarkably, these inequalities can also be violated solely with steering, i.e., without outcome communication. In fact, an efficiently computable formal quantifier-the robustness of noninstrumentality-naturally arises, and we prove that steering alone is enough to maximize it. Our findings imply that quantum theory admits a stronger form of steering than known until now, with fundamental as well as practical potential implications.

Search for γ-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28} cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

Resemblance in physical activity levels: The Portuguese sibling study on growth, fitness, lifestyle, and health.

OBJECTIVES: To investigate the relationships of biological, behavioral, familial, and environmental characteristics with siblings´ physical activity (PA) levels as well as the intrapair resemblance in PA. METHODS: The sample comprises 834 (390 females) biological siblings [brother-brother (BB), sister-sister (SS), brother-sister (BS)] aged 9 to 20 years. Total PA index (TPAI) was estimated by questionnaire. Information on potential behavioral, familial, and environmental correlates was obtained by self-report; body mass index (BMI), biological maturation, and physical fitness were measured. Multilevel models were used to analyze siblings´ clustered data, and sibling resemblance was estimated with the intraclass correlation (ρ). RESULTS: On average, younger sibs, those more physically fit, and those with more parental support had greater TPAI. Further, BB pairs had higher TPAI levels than SS or BS pairs, but also had greater within-pair variance. When adjusted for all covariates, SS pairs demonstrated greater resemblance in TPAI (ρ = 0.53, 95%CI = 0.38-0.68) than BS (ρ = 0.26, 95%CI = 0.14-0.43) or BB pairs (ρ = 0.18, 95%CI = 0.06-0.44). CONCLUSIONS: Age, physical fitness, and parental support were the best predictors of TPAI levels. A moderate level of resemblance in TPAI was observed in SS pairs, while lower resemblance was found for BS and BB pairs. These findings may be due to differences in the roles of shared genetic factors, familial, and environmental characteristics across different sibling types.

Correlates of children's compliance with moderate-to-vigorous physical activity recommendations: a multilevel analysis.

This study aimed to investigate the association between individual and school characteristics associated with the number of school days children comply with moderate-to-vigorous physical activity (MVPA) recommendations. Sample comprises 612 Portuguese children, aged 9-11 years, from 23 schools. Time spent in MVPA was measured by accelerometry, while individual-level correlates were obtained by anthropometry and questionnaires. School-level variables were collected by questionnaire, and accelerometer wear time and season were also considered. Maximum likelihood estimates of model parameters were obtained via a multilevel analysis with children as level-1, and school as level-2. Children who spent more time in sedentary activities and girls were less likely to comply with MVPA/daily. More mature children and those who use active transportation to school were more likely to attain the PA recommendation. Furthermore, greater accelerometer wear time and spring season increased the chance to achieve the recommended MVPA. In terms of school-level correlates, a greater number of available facilities was negatively associated with children MVPA compliance. Given the set of variables, our results showed that individual characteristics seem to be more relevant for children's compliance rates with PA/day than school context variables, which should be taken into account in the implementation of school policies and practices.

H.E.S.S. Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center.

A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l=-1.5°, b=0° and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. RESULTS: No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.

Search for Dark Matter Annihilations towards the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using γ-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant γ-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section ⟨σv⟩. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach ⟨σv⟩ values of 6×10^{-26} cm^{3} s^{-1} in the W^{+}W^{-} channel for a DM particle mass of 1.5 TeV, and 2×10^{-26} cm^{3} s^{-1} in the τ^{+}τ^{-} channel for a 1 TeV mass. For the first time, ground-based γ-ray observations have reached sufficient sensitivity to probe ⟨σv⟩ values expected from the thermal relic density for TeV DM particles.

Immunolocalization of the Anti-Müllerian Hormone (AMH) in Caprine Follicles and the Effects of AMH on In Vitro Culture of Caprine Pre-antral Follicles Enclosed in Ovarian Tissue.

The aims of this study were to evaluate the localization, by immunohistochemistry, of the anti-Müllerian hormone (AMH) in goat ovaries and to investigate its effects on the in vitro survival and development of caprine pre-antral follicles enclosed in fragments of ovarian tissue. Pre-antral follicles were cultured in vitro for 1 or 7 days in α-MEM(+) in the absence or presence of kit ligand (KL; 50 ng/ml, positive control) or AMH (50 or 150 ng/ml). The results showed that AMH was localized in oocytes and granulosa cells from the primordial follicle to antral follicle stages. Addition of AMH maintained the percentage of developing follicles, similar to that in the uncultured control; however, the percentage of developing follicles was significantly lower than that in the cultured control and KL. Nonetheless, addition of AMH to the culture medium did not affect survival rates and follicular growth. In conclusion, this study demonstrated that the expression of AMH varies according to the compartment and stage of follicular development. Furthermore, AMH inhibits the activation of caprine primordial follicles.

Modeling the dynamics of BMI changes during adolescence. The Oporto Growth, Health and Performance Study.

OBJECTIVES: The aims of this study were twofold: (i) to model changes in body mass index (BMI) of 10-18-year-old adolescents, and (ii) to investigate the effects of total physical activity (TPA), physical fitness (PF), sleep duration and fruit/vegetable consumption in BMI trajectories across time. METHODS: Data were obtained from the Oporto Growth, Health and Performance Study and comprised 6894 adolescents (3418 girls) divided into four age cohorts (10, 12, 14 and 16 years) measured annually for 3 years. BMI was computed using the standard formula (kg m(-2)); TPA was estimated with the Baecke questionnaire; PF measures included 1-mile run/walk, 50 yard dash (50YD), standing long jump (SLJ), handgrip strength (HGr) and agility shuttle run. Longitudinal changes in BMI were analyzed using the multilevel modeling approach. RESULTS: The average BMI at age of peak of height velocity was 20.7±0.07 kg m(-2) for girls (P<0.001) and 20.58±0.06 kg m(-2) for boys (P<0.001). The annual increment in BMI was 1.36±0.04 kg m(-2), P<0.001 and 1.23±0.03 kg m(-2), P<0.001 for girls and boys, respectively. PF were related to BMI trajectories in both sexes (Girls: ß1mile=0.12±0.02, P<0.001; ßSLJ=-0.01±0.00, P<0.001; ß50YD=0.28±0.05, P<0.001; ßHGr=-8.91±0.54, P<0.001; Boys: ß1mile=0.18±0.02, P<0.001; ßSLJ=-0.01±0.00, P<0.001; ß50YD=0.26±0.04, P<0.001; and ßHGr=-8.15±0.45, P<0.001). TPA only showed significant, but positive, association with girls' BMI trajectories (ß=0.10±0.03, P=0.001). After adjusting for the covariates, sleep duration and fruit/vegetable intake did not show any significant association with BMI trajectories either sex. CONCLUSIONS: BMI increased linearly with age in both gender. PF levels are negatively associated with BMI across time in both boys and girls. Therefore, promotion of PF in the adolescent years seems to be effective in the early prevention of obesity.

Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.

Gaucher's disease (GD) is caused by a ß-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation.

Unifying framework for relaxations of the causal assumptions in Bell's theorem.

Bell's theorem shows that quantum mechanical correlations can violate the constraints that the causal structure of certain experiments impose on any classical explanation. It is thus natural to ask to which degree the causal assumptions-e.g., locality or measurement independence-have to be relaxed in order to allow for a classical description of such experiments. Here we develop a conceptual and computational framework for treating this problem. We employ the language of Bayesian networks to systematically construct alternative causal structures and bound the degree of relaxation using quantitative measures that originate from the mathematical theory of causality. The main technical insight is that the resulting problems can often be expressed as computationally tractable linear programs. We demonstrate the versatility of the framework by applying it to a variety of scenarios, ranging from relaxations of the measurement independence, locality, and bilocality assumptions, to a novel causal interpretation of Clauser-Horne-Shimony-Holt inequality violations.

Constraints on an annihilation signal from a core of constant dark matter density around the milky way center with H.E.S.S.

An annihilation signal of dark matter is searched for from the central region of the Milky Way. Data acquired in dedicated on-off observations of the Galactic center region with H.E.S.S. are analyzed for this purpose. No significant signal is found in a total of ∼9 h of on-off observations. Upper limits on the velocity averaged cross section, ⟨σv⟩, for the annihilation of dark matter particles with masses in the range of ∼300 GeV to ∼10 TeV are derived. In contrast to previous constraints derived from observations of the Galactic center region, the constraints that are derived here apply also under the assumption of a central core of constant dark matter density around the center of the Galaxy. Values of ⟨σv⟩ that are larger than 3×10^{-24} cm^{3}/s are excluded for dark matter particles with masses between ∼1 and ∼4 TeV at 95% C.L. if the radius of the central dark matter density core does not exceed 500 pc. This is the strongest constraint that is derived on ⟨σv⟩ for annihilating TeV mass dark matter without the assumption of a centrally cusped dark matter density distribution in the search region.

In vitro development of secondary follicles from pre-pubertal and adult goats cultured in two-dimensional or three-dimensional systems.

The aim of this study was to evaluate the influence of two-dimensional (2D) and three-dimensional (3D) alginate culture systems on in vitro development of pre-antral caprine follicles. In addition, the influence of the reproductive age of the ovary donor on the in vitro culture success was investigated. Pre-antral follicles from pre-pubertal or adult goats were isolated and cultured directly on a plastic surface (2D) or encapsulated in an alginate-based matrix (3D). After 18 days, the oocytes underwent in vitro maturation (IVM) and in vitro fertilization (IVF) to produce embryos. The 3D system showed higher rates of follicle survival, lower rates of oocyte extrusion, and a greater number of recovered oocytes for IVM and IVF (P < 0.05). Only pre-antral follicles from adult animals produced MII oocytes and embryos. The estradiol concentrations increased from day 2 to day 12 of culture in all groups tested (P < 0.05). Conversely, progesterone concentrations were lower in 3D-cultured follicles than in 2D-cultured follicles, with differences on days 2 and 6 of culture (P < 0.05). We provide compelling evidence that a 2D or 3D alginate in vitro culture system offers a promising approach to achieving full in vitro development of caprine pre-antral follicles to produce mature oocytes that are capable of fertilization and viable embryos.

Linear-optical simulation of the cooling of a cluster-state Hamiltonian system.

A measurement-based quantum computer could consist of a local-gapped Hamiltonian system, whose thermal states-at sufficiently low temperature-are universal resources for the computation. Initialization of the computer would correspond to cooling the system. We perform an experimental quantum simulation of such a cooling process with entangled photons. We prepare three-qubit thermal cluster states exploiting the equivalence between local dephasing and thermalization for these states. This allows us to tune the system's temperature by changing the dephasing strength. We monitor the entanglement as the system cools down and observe the transitions from separability to bound entanglement, and then to free entanglement. We also analyze the performance of the system for measurement-based single-qubit state preparation. These studies constitute a basic characterization of experimental cluster-state computation under imperfect conditions.

Inferred cosmic-ray spectrum from Fermi large area telescope γ-ray observations of Earth's limb.

Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the γ-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range ∼90 GeV-6 TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68±0.04 and 2.61±0.08 above ∼200 GeV, respectively.

Noisy metrology beyond the standard quantum limit.

Parameter estimation is of fundamental importance in areas from atomic spectroscopy and atomic clocks to gravitational wave detection. Entangled probes provide a significant precision gain over classical strategies in the absence of noise. However, recent results seem to indicate that any small amount of realistic noise restricts the advantage of quantum strategies to an improvement by at most a multiplicative constant. Here, we identify a relevant scenario in which one can overcome this restriction and attain superclassical precision scaling even in the presence of uncorrelated noise. We show that precision can be significantly enhanced when the noise is concentrated along some spatial direction, while the Hamiltonian governing the evolution which depends on the parameter to be estimated can be engineered to point along a different direction. In the case of perpendicular orientation, we find superclassical scaling and identify a state which achieves the optimum.

Search for photon-linelike signatures from dark matter annihilations with H.E.S.S.

Gamma-ray line signatures can be expected in the very-high-energy (E(γ)>100 GeV) domain due to self-annihilation or decay of dark matter (DM) particles in space. Such a signal would be readily distinguishable from astrophysical γ-ray sources that in most cases produce continuous spectra that span over several orders of magnitude in energy. Using data collected with the H.E.S.S. γ-ray instrument, upper limits on linelike emission are obtained in the energy range between ∼ 500 GeV and ∼ 25 TeV for the central part of the Milky Way halo and for extragalactic observations, complementing recent limits obtained with the Fermi-LAT instrument at lower energies. No statistically significant signal could be found. For monochromatic γ-ray line emission, flux limits of (2 × 10(-7) -2 × 10(-5)) m(-2) s(-1) sr(-1) and (1 × 10(-8) -2 × 10(-6)) m(-2) s(-1)sr(-1) are obtained for the central part of the Milky Way halo and extragalactic observations, respectively. For a DM particle mass of 1 TeV, limits on the velocity-averaged DM annihilation cross section ⟨σv⟩(χχ → γγ) reach ∼ 10(-27) cm(3)s(-1), based on the Einasto parametrization of the Galactic DM halo density profile.