Diversity-oriented synthesis of a library of substituted tetrahydropyrones using oxidative carbon-hydrogen bond activation and click chemistry

Eighteen (2RS,6RS)-2-(4-methoxyphenyl)-6-(substituted ethyl)dihydro- 2Hpyran-4(3H)ones were synthesized via a DDQ-mediated oxidative carbon-hydrogen bond activation reaction. Fourteen of these tetrahydropyrans were substituted with triazoles readily assembled via azide-alkyne click-chemistry reactions. Examples of a linked benzotriazole and pyrazole motif were also prepared. To complement the structural diversity, the alcohol substrates were obtained from stereoselective reductions of the tetrahydropyrone. This library provides rapid access to structurally diverse non-natural compounds to be screened against a variety of biological targets. © 2011 by the authors

New Methods for Identifying Lyman Continuum Leakers and Reionization-Epoch Analogues

Identifying low-redshift galaxies that emit Lyman continuum radiation (LyC leakers) is one of the primary, indirect methods of studying galaxy formation in the epoch of reionization. However, not only has it proved challenging to identify such systems, it also remains uncertain whether the low-redshift LyC leakers are truly ‘analogues’ of the sources that reionized the Universe. Here, we use high-resolution cosmological radiation hydrodynamics simulations to examine whether simulated galaxies in the epoch of reionization share similar emission line properties to observed LyC leakers at z ∼ 3 and z ∼ 0. We find that the simulated galaxies with high LyC escape fractions (fesc) often exhibit high O32 and populate the same regions of the R23–O32 plane as z ∼ 3 LyC leakers. However, we show that viewing angle, metallicity, and ionization parameter can all impact where a galaxy resides on the O32–fesc plane. Based on emission line diagnostics and how they correlate with fesc, lower metallicity LyC leakers at z ∼ 3 appear to be good analogues of reionization-era galaxies. In contrast, local [S II]-deficient galaxies do not overlap with the simulated high-redshift LyC leakers on the S II Baldwin–Phillips–Terlevich (BPT) diagram; however, this diagnostic may still be useful for identifying leakers. We use our simulated galaxies to develop multiple new diagnostics to identify LyC leakers using infrared and nebular emission lines. We show that our model using only [C II]158 μm and [O III]88 μm can identify potential leakers from non-leakers from the local Dwarf Galaxy Survey. Finally, we apply this diagnostic to known high-redshift galaxies and find that MACS 1149_JD1 at z = 9.1 is the most likely galaxy to be actively contributing to the reionization of the Universe

Probing cosmic dawn with emission lines: predicting infrared and nebular line emission for ALMA and JWST

Infrared and nebular lines provide some of our best probes of the physics regulating the properties of the interstellar medium (ISM) at high-redshift. However, interpreting the physical conditions of high-redshift galaxies directly from emission lines remains complicated due to inhomogeneities in temperature, density, metallicity, ionisation parameter, and spectral hardness. We present a new suite of cosmological, radiation-hydrodynamics simulations, each centred on a massive Lyman-break galaxy that resolves such properties in an inhomogeneous ISM. Many of the simulated systems exhibit transient but well defined gaseous disks that appear as velocity gradients in [CII]~158.6$\mu$m emission. Spatial and spectral offsets between [CII]~158.6$\mu$m and [OIII]~88.33$\mu$m are common, but not ubiquitous, as each line probes a different phase of the ISM. These systems fall on the local [CII]-SFR relation, consistent with newer observations that question previously observed [CII]~158.6$\mu$m deficits. Our galaxies are consistent with the nebular line properties of observed $z\sim2-3$ galaxies and reproduce offsets on the BPT and mass-excitation diagrams compared to local galaxies due to higher star formation rate (SFR), excitation, and specific-SFR, as well as harder spectra from young, metal-poor binaries. We predict that local calibrations between H$\alpha$ and [OII]~3727$\AA$ luminosity and galaxy SFR apply up to $z>10$, as do the local relations between certain strong line diagnostics (R23 and [OIII]~5007$\AA$/H$\beta$) and galaxy metallicity. Our new simulations are well suited to interpret the observations of line emission from current (ALMA and HST) and upcoming facilities (JWST and ngVLA)

New methods for identifying Lyman continuum leakers and reionization-epoch analogues

Identifying low-redshift galaxies that emit Lyman Continuum radiation (LyC leakers) is one of the primary, indirect methods of studying galaxy formation in the epoch of reionization. However, not only has it proved challenging to identify such systems, it also remains uncertain whether the low-redshift LyC leakers are truly "analogues" of the sources that reionized the Universe. Here, we use high-resolution cosmological radiation hydrodynamics simulations to examine whether simulated galaxies in the epoch of reionization share similar emission line properties to observed LyC leakers at $z\sim3$ and $z\sim0$. We find that the simulated galaxies with high LyC escape fractions ($f_{\rm esc}$) often exhibit high O32 and populate the same regions of the R23-O32 plane as $z\sim3$ LyC leakers. However, we show that viewing angle, metallicity, and ionisation parameter can all impact where a galaxy resides on the O32-$f_{\rm esc}$ plane. Based on emission line diagnostics and how they correlate with $f_{\rm esc}$, lower-metallicity LyC leakers at $z\sim3$ appear to be good analogues of reionization-era galaxies. In contrast, local [SII]-deficient galaxies do not overlap with the simulated high-redshift LyC leakers on the SII-BPT diagram; however, this diagnostic may still be useful for identifying leakers. We use our simulated galaxies to develop multiple new diagnostics to identify LyC leakers using IR and nebular emission lines. We show that our model using only [CII]$_{\rm 158\mu m}$ and [OIII]$_{\rm 88\mu m}$ can identify potential leakers from non-leakers from the local Dwarf Galaxy Survey. Finally, we apply this diagnostic to known high-redshift galaxies and find that MACS1149_JD1 at $z=9.1$ is the most likely galaxy to be actively contributing to the reionization of the Universe

The nature of high [O III]88 μ m/[C II]158 μm galaxies in the epoch of reionization: Low carbon abundance and a top-heavy IMF?

ALMA observations of z > 6 galaxies have revealed abnormally high [O III]88 μm/[C II]158 μm ratios and [C II]158 μm deficits compared to local galaxies. The origin of this behaviour is unknown. Numerous solutions have been proposed including differences in C and O abundance ratios, observational bias, and differences in ISM properties, including ionization parameter, gas density, or photodissociation region (PDR) covering fraction. In order to elucidate the underlying physics that drives this high-redshift phenomenon, we employ SPHINX20, a state-of-the-art, cosmological radiation–hydrodynamics simulation, that resolves detailed ISM properties of thousands of galaxies in the epoch of reionization which has been post-processed with CLOUDY to predict emission lines. We find that the observed z > 6 [O III]88 μm–SFR and [C II]158 μm–SFR relations can only be reproduced when the C/O abundance ratio is ∼8 × lower than Solar and the total metal production is ∼4 × higher than that of a Kroupa IMF. This implies that high-redshift galaxies are potentially primarily enriched by low-metallicity core–collapse supernovae with a more top-heavy IMF. As AGB stars and type-Ia supernova begin to contribute to the galaxy metallicity, both the [C II]158 μm–SFR and [C II]158 μm luminosity functions are predicted to converge to observed values at z ∼ 4.5. While we demonstrate that ionization parameter, LyC escape fraction, ISM gas density, and CMB attenuation all drive galaxies towards higher [O III]88 μm/[C II]158 μm, observed values at z > 6 can only be reproduced with substantially lower C/O abundances compared to Solar. The combination of [C II]158 μm and [O III]88 μm can be used to predict the values of ionization parameter, ISM gas density, and LyC escape fraction and we provide estimates of these quantities for nine observed z > 6 galaxies. Finally, we demonstrate that [O I]63 μm can be used as a replacement for [C II]158 μ m in high-redshift galaxies where [C II]158 μ m is unobserved and argue that more observation time should be used to target [O I]63 μm at z > 6. Future simulations will be needed to self-consistently address the numerous uncertainties surrounding a varying IMF at high redshift and the associated metal returns

Factors related to the incorrect use of inhalers by asthma patients

PereiraResumoObjetivo: Avaliar a técnica inalatória em pacientes com asma atendidos ambulatorialmente, estabelecendo associações dessa com o grau de controle da doença. Métodos: Estudo transversal envolvendo pacientes com idade ≥ 14 anos e diagnóstico médico de asma, recrutados no Ambulatório de Asma do Hospital de Clínicas de Porto Alegre, na cidade de Porto Alegre (RS). Os pacientes completaram dois questionários (um geral e um questionário de controle da asma baseado nas diretrizes da Global Initiative for Asthma de 2011). Os pacientes demonstraram a técnica inalatória e realizaram testes de função pulmonar. A técnica inalatória incorreta foi definida como a execução incorreta de pelo menos duas etapas da avaliação. Resultados: Foram incluídos 268 pacientes. Desses, 81 (30,2%) apresentaram técnica inalatória incorreta, que foi associada com falta de controle da asma (p = 0,002). A regressão logística identificou os seguintes fatores associados com a técnica inalatória incorreta: ser viúvo (OR = 5,01; IC95%, 1,74-14,41; p = 0,003); utilizar inalador pressurizado (OR = 1,58; IC95%, 1,35-1,85; p < 0,001); ter renda familiar mensal < 3 salários mínimos (OR = 2,67; IC95%, 1,35-1,85; p = 0,008); e ter ≥ 2 comorbidades (OR = 3,80; IC95%, 1,03-14,02; p = 0,045). Conclusões: Na amostra estudada, a técnica inalatória incorreta se associou com a falta de controle da asma. Viuvez, uso de inalador pressurizado, baixo nível socioeconômico e presença de ≥ 2 comorbidades se associaram à técnica inalatória incorreta.AbstractObjective: To evaluate inhaler technique in outpatients with asthma and to determine associations between the correctness of that technique and the level of asthma control. Methods: This was a cross-sectional study involving patients ≥ 14 years of age with physician-diagnosed asthma. The patients were recruited from the Asthma Outpatient Clinic of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, Brazil. The patients completed two questionnaires (a general questionnaire and an asthma control questionnaire based on the 2011 Global Initiative for Asthma guidelines), demonstrated their inhaler technique, and performed pulmonary function tests. Incorrect inhaler technique was defined as the incorrect execution of at least two of the predefined steps. Results: We included 268 patients. Of those, 81 (30.2%) showed incorrect inhaler technique, which was associated with poor asthma control (p = 0.002). Logistic regression analysis identified the following factors associated with incorrect inhaler technique: being widowed (OR = 5.01; 95% CI, 1.74-14.41; p = 0.003); using metered dose inhalers (OR = 1.58; 95% CI, 1.35-1.85; p < 0.001); having a monthly family income < 3 times the minimum wage (OR = 2.67; 95% CI, 1.35-1.85; p = 0.008), and having ≥ 2 comorbidities (OR = 3.80; 95% CI, 1.03-14.02; p = 0.045). Conclusions: In the sample studied, incorrect inhaler technique was associated with poor asthma control. Widowhood, use of metered dose inhalers, low socioeconomic level, and the presence of ≥ 2 comorbidities were associated with incorrect inhaler technique

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

A discrete firefly algorithm to solve a rich vehicle routing problem modelling a newspaper distribution system with recycling policy

A real-world newspaper distribution problem with recycling policy is tackled in this work. In order to meet all the complex restrictions contained in such a problem, it has been modeled as a rich vehicle routing problem, which can be more specifically considered as an asymmetric and clustered vehicle routing problem with simultaneous pickup and deliveries, variable costs and forbidden paths (AC-VRP-SPDVCFP). This is the first study of such a problem in the literature. For this reason, a benchmark composed by 15 instances has been also proposed. In the design of this benchmark, real geographical positions have been used, located in the province of Bizkaia, Spain. For the proper treatment of this AC-VRP-SPDVCFP, a discrete firefly algorithm (DFA) has been developed. This application is the first application of the firefly algorithm to any rich vehicle routing problem. To prove that the proposed DFA is a promising technique, its performance has been compared with two other well-known techniques: an evolutionary algorithm and an evolutionary simulated annealing. Our results have shown that the DFA has outperformed these two classic meta-heuristics

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration