Mid-Infrared diagnostics of metal-rich HII regions from VLT and Spitzer Spectroscopy of Young Massive Stars in W31

We present near-IR VLT/ISAAC and mid-IR Spitzer/IRS spectroscopy of the young massive cluster in the W31 star-forming region. H-band spectroscopy provides refined classifications for four cluster members O stars with respect to Blum et al. In addition, photospheric features are detected in the massive Young Stellar Object (mYSO) #26. Spectroscopy permits estimates of stellar temperatures and masses, from which a cluster age of ~0.6 Myr and distance of 3.3 kpc are obtained, in excellent agreement with Blum et al. IRS spectroscopy reveals mid-infrared fine structure line fluxes of [Ne II-III] and [S III-IV] for four O stars and five mYSOs. In common with previous studies, stellar temperatures of individual stars are severely underestimated from the observed ratios of fine-structure lines, despite the use of contemporary stellar atmosphere and photoionization models. We construct empirical temperature calibrations based upon the W31 cluster stars of known spectral type, supplemented by two inner Milky Way ultracompact (UC) HII regions whose ionizing star properties are established. Calibrations involving [NeIII] 15.5um/[NeII] 12.8um, [SIV] 10.5um/[NeII] 12.8um or [ArIII] 9.0um/[NeII] 12.8um have application in deducing the spectral types of early- to mid- O stars for other inner Milky Way compact and UCHII regions. Finally, evolutionary phases and timescales for the massive stellar content in W31 are discussed, due to the presence of numerous young massive stars at different formation phases in a `coeval' cluster.Comment: 16 pages, 13 figures, accepted for MNRA

Biophysical characterization of the inactivation of E. coli transketolase by aqueous co-solvents

Transketolase (TK) has been previously engineered, using semi-rational directed evolution and substrate walking, to accept increasingly aliphatic, cyclic, and then aromatic substrates. This has ultimately led to the poor water solubility of new substrates, as a potential bottleneck to further exploitation of this enzyme in biocatalysis. Here we used a range of biophysical studies to characterise the response of both E. coli apo- and holo-TK activity and structure to a range of polar organic co-solvents: acetonitrile (AcCN), n-butanol (nBuOH), ethyl acetate (EtOAc), isopropanol (iPrOH), and tetrahydrofuran (THF). The mechanism of enzyme deactivation was found to be predominantly via solvent-induced local unfolding. Holo-TK is thermodynamically more stable than apo-TK and yet for four of the five co-solvents it retained less activity than apo-TK after exposure to organic solvents, indicating that solvent tolerance was not simply correlated to global conformational stability. The co-solvent concentrations required for complete enzyme inactivation was inversely proportional to co-solvent log(P), while the unfolding rate was directly proportional, indicating that the solvents interact with and partially unfold the enzyme through hydrophobic contacts. Small amounts of aggregate formed in some cases, but this was not sufficient to explain the enzyme inactivation. TK was found to be tolerant to 15% (v/v) iPrOH, 10% (v/v) AcCN, or 6% (v/v) nBuOH over 3 h. This work indicates that future attempts to engineer the enzyme to better tolerate co-solvents should focus on increasing the stability of the protein to local unfolding, particularly in and around the cofactor-binding loops

Report of the Irish RN4CAST Studey 2009-2011: a nursing workforce under strain.

Foreword: The RN4CAST consortium research study, funded by the European Commission, has provided a unique opportunity to gain insight into both organisational and nurse staffing issues across the acute hospital sector in Ireland. As part of the RN4CAST (Ireland) study, for the first time, both hospitals and medical and surgical units within thirty out of a possible thirty-one acute hospitals (with over one hundred beds) have been surveyed. Data were collected in 2009-2010. The work of the international consortium also enables comparisons of Irish findings with key findings internationally. For example it has proved possible to compare such issues as patient – to - nurse ratios and patient - to health care-staff ratios across the 12 partner countries of the consortium. This is also the case, for example, for nurse burnout levels, job satisfaction and nurse perceptions of safety and quality of care. RN4CAST (Ireland) provides a portrayal of the Irish acute hospital sector as operating in a context of dynamic challenge and change from both internal and external drivers. There is considerable evidence of significant strain on the nursing staff working in the sector. Nursing staff indicate concern regarding aspects of the quality and safety of patient care and the availability of sufficient staff and resources to do their job properly. We are of the view that unless these and a number of other issues raised in this report are managed effectively, there will be detrimental impacts on patient care, patient safety and retention and recruitment of high quality nursing staff for our health service

Decision Making for Inconsistent Expert Judgments Using Negative Probabilities

In this paper we provide a simple random-variable example of inconsistent information, and analyze it using three different approaches: Bayesian, quantum-like, and negative probabilities. We then show that, at least for this particular example, both the Bayesian and the quantum-like approaches have less normative power than the negative probabilities one.Comment: 14 pages, revised version to appear in the Proceedings of the QI2013 (Quantum Interactions) conferenc

Association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth.

OBJECTIVE: To determine the association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth. DESIGN: Multicentre prospective cohort study. SETTING: Ten European centres offering prenatal screening for toxoplasmosis. POPULATION: Deliveries after 23 weeks of gestation in 386 women with singleton pregnancies who seroconverted to toxoplasma infection before 20 weeks of gestation. Deliveries after 36 weeks in 234 women who seroconverted at 20 weeks or later, and tested positive before 37 weeks. METHODS: Comparison of infected and uninfected births, adjusted for parity and country of birth. MAIN OUTCOME MEASURES: Differences in gestational age at birth, birthweight and birthweight centile. RESULTS: Infected babies were born or delivered earlier than uninfected babies: the mean difference for seroconverters before 20 weeks was -5.4 days (95% CI: -1.4, -9.4), and at 20 weeks or more, -2.6 days (95% CI: -0.5, -4.7). Congenital infection was associated with an increased risk of preterm delivery when seroconversion occurred before 20 weeks (OR 4.71; 95% CI: 2.03, 10.9). No significant differences were detected for birthweight or birthweight centile. CONCLUSION: Babies with congenital toxoplasmosis were born earlier than uninfected babies but the mechanism leading to shorter length of gestation is unknown. Congenital infection could precipitate early delivery or prompt caesarean section or induction of delivery. We found no evidence for a significant association between congenital toxoplasmosis and reduced birthweight or small for gestational age birth

Modelling and optimisation of the one-pot, multi-enzymatic synthesis of chiral amino-alcohols based on microscale kinetic parameter determination

Advances in synthetic biology are facilitating the de novo design of complex, multi-step enzymatic conversions for industrial organic synthesis. This work describes the integration of multi-step enzymatic pathway construction with enzyme kinetics and bioreactor modelling, in order to optimise the synthesis of chiral amino-alcohols using engineered Escherichia coli transketolases (TK) and the Chromobacterium violaceum transaminase (TAm). The specific target products were (2S,3S)-2-aminopentane-1,3-diol (APD) and (2S,3R)-2-amino-1,3,4-butanetriol (ABT). Kinetic models and parameters for each of the enzymatic steps were first obtained using automated microwell experiments. These identified the TK-catalysed conversions as being up to 25 times faster than the subsequent TAm conversions and inhibition of TAm by the amino-donor used, (S)-(−)-α-methylbenzylamine (MBA), as limiting the overall conversion yields. In order to better ‘match’ the relative rates of the two enzymes an E. coli expression system, based on two compatible plasmids, was constructed to produce both enzymes in a single host. By control of induction time and temperature it was possible to produce six times more recombinant TAm than TK to help balance the reaction rates. To overcome MBA inhibition and an unfavourable reaction equilibrium, fed-batch addition of the amino-donor was introduced as well as the use of isopropylamine as an alternate amino-donor. Adopting these strategies, and using the kinetic models to optimise feeding strategies, the one pot syntheses of APD and ABT were successfully scaled-up to preparative scales. Excellent agreement was found between the kinetic profiles and yields predicted and those achieved experimentally at the larger scale. In this case the integration of these multi-disciplinary approaches enabled us to achieve up to a 6 fold greater yield using concentrations an order of magnitude higher than in previous preparative scale batch bioconversions carried out sequentially

Controls on Near‐Surface Hydraulic Conductivity in a Raised Bog

Shallow water tables protect northern peatlands and their important carbon stocks from aerobic decomposition. Hydraulic conductivity, K, is a key control on water tables. The controls on K, particularly in degraded and restored peatlands, remain a subject of ongoing research. We took 29 shallow (~50 cm) peat cores from an estuarine raised bog in Wales, UK. Parts of the bog are in close‐to‐natural condition, while other areas have undergone shallow peat cutting for fuel and drainage, followed by restoration through ditch blocking. In the laboratory we measured horizontal (Kh) and vertical (Kv) hydraulic conductivity. We fitted linear multiple regression models to describe log10‐transformed Kh and Kv on the basis of simple, easy‐to‐measure predictors. Dry bulk density and degree of decomposition were the strongest predictors of Kh and Kv. Perhaps surprisingly, the independent effect of hummocks was to produce higher‐Kv peat than in lawns; while the independent effect of restored diggings was to produce higher‐K peat than in uncut locations. Our models offer high explanatory power for Kh (adjusted r2 = 0.740) and Kv (adjusted r2 = 0.787). Our findings indicate that generalizable predictive models of peat K, similar to pedotransfer functions for mineral soils, may be attainable. Kh and Kv possess subtly different controls that are consistent with the contrasting roles of these two properties in peatland water budgets. Our near‐surface samples show no evidence for the low‐K marginal peat previously observed in deeper layers at the same site, indicating that such structures may be less important than previously believed

Amazonian chemical weathering rate derived from stony meteorite finds at Meridiani Planum on Mars

© The Author(s) 2016.Spacecraft exploring Mars such as the Mars Exploration Rovers Spirit and Opportunity, as well as the Mars Science Laboratory or Curiosity rover, have accumulated evidence for wet and habitable conditions on early Mars more than 3 billion years ago. Current conditions, by contrast, are cold, extremely arid and seemingly inhospitable. To evaluate exactly how dry today's environment is, it is important to understand the ongoing current weathering processes. Here we present chemical weathering rates determined for Mars. We use the oxidation of iron in stony meteorites investigated by the Mars Exploration Rover Opportunity at Meridiani Planum. Their maximum exposure age is constrained by the formation of Victoria crater and their minimum age by erosion of the meteorites. The chemical weathering rates thus derived are ~1 to 4 orders of magnitude slower than that of similar meteorites found in Antarctica where the slowest rates are observed on Earth

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking