RESUMO
The field of pulmonology saw significant advances in 2023. The publications highlighted in this article address advances and changes in practice related to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, pleural disorders, and sleep-disordered breathing. One article reviews data examining the efficacy of vaccination against respiratory syncytial virus, a respiratory viral illness that has had devastating effects globally. Four studies evaluate the role of various therapies in COPD, including dupilumab, ensifentrine, pulmonary rehabilitation programs, and lung volume reduction versus endobronchial valves. Another study explores the effect on vascular events of positive-pressure ventilation in patients with sleep-disordered breathing and recent stroke. The use of combination therapy with rituximab and mycophenolate mofetil on progression-free survival in patients with nonspecific interstitial pneumonia is the topic of another study. We also highlight an update of clinical recommendations for the evaluation of patients with pleural disorders and a systematic review analyzing the effectiveness of inhaled corticosteroids as a supplement to dual therapy for COPD.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Pneumologia , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Doenças Pulmonares Intersticiais/terapia , Asma/tratamento farmacológico , Doenças Pleurais/terapia , Síndromes da Apneia do Sono/terapiaRESUMO
BACKGROUND: The first aim of this study was to examine trends in the risk of ipsilateral invasive breast cancer (iIBC) after breast-conserving surgery (BCS) of ductal carcinoma in situ (DCIS). A second aim was to analyse the association between DCIS grade and the risk of iIBC following BCS. PATIENTS AND METHODS: In this population-based, retrospective cohort study, the Netherlands Cancer Registry collected information on 25,719 women with DCIS diagnosed in the period 1989-2021 who underwent BCS. Of these 19,034 received adjuvant radiotherapy (RT). Kaplan-Meier analyses and Cox regression models were used. RESULTS: A total of 1135 patients experienced iIBC. Ten-year cumulative incidence rates of iIBC for patients diagnosed in the periods 1989-1998, 1999-2008 and 2009-2021 undergoing BCS without RT, were 12.6%, 9.0% and 5.0% (P < 0.001), respectively. For those undergoing BCS with RT these figures were 5.7%, 3.7% and 2.2%, respectively (P < 0.001). In the multivariable analyses, DCIS grade was not associated with the risk of iIBC. CONCLUSION: Since 1989 the risk of iIBC has decreased substantially and has become even lower than the risk of invasive contralateral breast cancer. No significant association of DCIS grade with iIBC was found, stressing the need for more powerful prognostic factors to guide the treatment of DCIS.
RESUMO
Biodiesel, which can be made from a variety of natural oils, is currently promoted as a sustainable, healthier replacement for commercial mineral diesel despite little experimental data supporting this. The aim of our research was to investigate the health impacts of exposure to exhaust generated by the combustion of diesel and two different biodiesels. Male BALB/c mice (n = 24 per group) were exposed for 2 h/day for 8 days to diluted exhaust from a diesel engine running on ultra-low sulfur diesel (ULSD) or Tallow or Canola biodiesel, with room air exposures used as control. A variety of respiratory-related end-point measurements were assessed, including lung function, responsiveness to methacholine, airway inflammation and cytokine response, and airway morphometry. Exposure to Tallow biodiesel exhaust resulted in the most significant health impacts compared to Air controls, including increased airway hyperresponsiveness and airway inflammation. In contrast, exposure to Canola biodiesel exhaust resulted in fewer negative health effects. Exposure to ULSD resulted in health impacts between those of the two biodiesels. The health effects of biodiesel exhaust exposure vary depending on the feedstock used to make the fuel.
Assuntos
Poluentes Atmosféricos , Masculino , Camundongos , Animais , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Biocombustíveis/toxicidade , Biocombustíveis/análise , Material Particulado/toxicidade , Material Particulado/análise , Emissões de Veículos/toxicidade , Emissões de Veículos/análise , Enxofre , InflamaçãoRESUMO
As global biodiesel production increases, there are concerns over the potential health impact of exposure to the exhaust, particularly in regard to young children who are at high risk because of their continuing lung development. Using human airway epithelial cells obtained from young children, we compared the effects of exposure to exhaust generated by a diesel engine with Euro V/VI emission controls running on conventional diesel (ultra-low-sulfur mineral diesel, ULSD), soy biodiesel (B100), or a 20% blend of soy biodiesel with diesel (B20). The exhaust output of biodiesel was found to contain significantly more respiratory irritants, including NOx, CO, and CO2, and a larger overall particle mass. Exposure to biodiesel exhaust resulted in significantly greater cell death and a greater release of immune mediators compared to both air controls and ULSD exhaust. These results have concerning implications for potential global health impacts, particularly for the pediatric population.
Assuntos
Poluentes Atmosféricos , Emissões de Veículos , Biocombustíveis , Criança , Pré-Escolar , Células Epiteliais , Gasolina , Humanos , Minerais , Material ParticuladoRESUMO
BACKGROUND: Biodiesel, a renewable diesel fuel that can be created from almost any natural fat or oil, is promoted as a greener and healthier alternative to commercial mineral diesel without the supporting experimental data to back these claims. The aim of this research was to assess the health effects of acute exposure to two types of biodiesel exhaust, or mineral diesel exhaust or air as a control in mice. Male BALB/c mice were exposed for 2-hrs to diluted exhaust obtained from a diesel engine running on mineral diesel, Tallow biodiesel or Canola biodiesel. A room air exposure group was used as a control. Twenty-four hours after exposure, a variety of respiratory related end point measurements were assessed, including lung function, responsiveness to methacholine and airway and systemic immune responses. RESULTS: Tallow biodiesel exhaust exposure resulted in the greatest number of significant effects compared to Air controls, including increased airway hyperresponsiveness (178.1 ± 31.3% increase from saline for Tallow biodiesel exhaust exposed mice compared to 155.8 ± 19.1 for Air control), increased airway inflammation (63463 ± 13497 cells/mL in the bronchoalveolar lavage of Tallow biodiesel exhaust exposed mice compared to 40561 ± 11800 for Air exposed controls) and indications of immune dysregulation. In contrast, exposure to Canola biodiesel exhaust resulted in fewer significant effects compared to Air controls with a slight increase in airway resistance at functional residual capacity and indications of immune dysregulation. Exposure to mineral diesel exhaust resulted in significant effects between that of the two biodiesels with increased airway hyperresponsiveness and indications of immune dysregulation. CONCLUSION: These data show that a single, brief exposure to biodiesel exhaust can result in negative health impacts in a mouse model, and that the biological effects of exposure change depending on the feedstock used to make the biodiesel.
Assuntos
Biocombustíveis , Camundongos Endogâmicos BALB C , Emissões de Veículos , Animais , Emissões de Veículos/toxicidade , Biocombustíveis/toxicidade , Camundongos , Masculino , Gasolina/toxicidade , Poluentes Atmosféricos/toxicidade , Pulmão/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Exposição por InalaçãoRESUMO
To address climate change concerns, and reduce the carbon footprint caused by fossil fuel use, it is likely that blend ratios of renewable biodiesel with commercial mineral diesel fuel will steadily increase, resulting in biodiesel use becoming more widespread. Exhaust toxicity of unblended biodiesels changes depending on feedstock type, however the effect of feedstock on blended fuels is less well known. The aim of this study was to assess the impact of biodiesel feedstock on exhaust toxicity of 20% blended biodiesel fuels (B20). Primary human airway epithelial cells were exposed to exhaust diluted 1/15 with air from an engine running on conventional ultra-low sulfur diesel (ULSD) or 20% blends of soy, canola, waste cooking oil (WCO), tallow, palm or cottonseed biodiesel in diesel. Physico-chemical exhaust properties were compared between fuels and the post-exposure effect of exhaust on cellular viability and media release was assessed 24 h later. Exhaust properties changed significantly between all fuels with cottonseed B20 being the most different to both ULSD and its respective unblended biodiesel. Exposure to palm B20 resulted in significantly decreased cellular viability (96.3 ± 1.7%; p < 0.01) whereas exposure to soy B20 generated the greatest number of changes in mediator release (including IL-6, IL-8 and TNF-α, p < 0.05) when compared to air exposed controls, with palm B20 and tallow B20 closely following. In contrast, canola B20 and WCO B20 were the least toxic with only mediators G-CSF and TNF-α being significantly increased. Therefore, exposure to palm B20, soy B20 and tallow B20 were found to be the most toxic and exposure to canola B20 and WCO B20 the least. The top three most toxic and the bottom three least toxic B20 fuels are consistent with their unblended counterparts, suggesting that feedstock type greatly impacts exhaust toxicity, even when biodiesel only comprises 20% of the fuel.
Assuntos
Biocombustíveis , Material Particulado , Humanos , Biocombustíveis/toxicidade , Biocombustíveis/análise , Material Particulado/análise , Fator de Necrose Tumoral alfa , Óleo de Sementes de Algodão , Emissões de Veículos/toxicidade , Emissões de Veículos/análise , Gasolina/toxicidade , MineraisRESUMO
Phobic droplet-fiber systems possess complex geometries, which have made full characterization of such systems difficult. This work has used atomic force microscopy (AFM) to measure droplet-fiber forces for oil droplets on oleophobic fibers over a range of fiber diameters. The work adapted a previous method and a theoretical model developed by the authors for philic droplet-fiber systems. A Bayesian statistical model was also used to account for the influence of surface roughness on the droplet-fiber force. In general, it has been found that the force required to move a liquid droplet along an oleophobic filter fiber will be less than that required to move a droplet along an oleophilic fiber. However, because of the effects of pinning and/or wetting behavior, this difference may be less than would otherwise be expected. Droplets with a greater contact angle (~110°) were observed to roll along the fiber, whereas droplets with a lesser contact angle (<90°) would slide.
RESUMO
The concept of professional judgement underpins the way in which an occupational hygienist assesses an exposure problem. Despite the importance placed on professional judgement in the discipline, a method of assessment to characterise accuracy has not been available. In this paper, we assess the professional judgement of four occupational hygienists ('experts') when completing exposure assessments on a range of airborne contaminants across a number of job roles within a surface mining environment in the Pilbara region of Western Australia. The job roles assessed were project driller, mobile equipment operator, fixed plant maintainer, and drill and blast operator. The contaminants of interest were respirable crystalline silica, respirable dust, and inhalable dust. The novel approach of eliciting exposure estimates focusing on contaminant concentration and attribution of an exposure standard estimate was used. The majority of the elicited values were highly skewed; therefore, a scaled Beta distribution were fitted. These elicited fitted distributions were then compared to measured data distributions, the results of which had been collected as part of an occupational hygiene program assessing full-shift exposures to the same contaminants and job roles assessed by the experts. Our findings suggest that the participating experts within this study tended to overestimate exposures. In addition, the participating experts were more accurate at estimating percentage of an exposure standard than contaminant concentration. We demonstrate that this elicitation approach and the encoding methodology contained within can be applied to assess accuracy of exposure judgements which will impact on worker protection and occupational health outcomes.
Assuntos
Poluentes Ocupacionais do Ar , Exposição Ocupacional , Poluentes Ocupacionais do Ar/análise , Poeira/análise , Higiene , Mineração , Exposição Ocupacional/análise , Dióxido de Silício/análiseRESUMO
Biodiesel is created through the transesterification of fats/oils and its usage is increasing worldwide as global warming concerns increase. Biodiesel fuel properties change depending on the feedstock used to create it. The aim of this study was to assess the different toxicological properties of biodiesel exhausts created from different feedstocks using a complex 3D air-liquid interface (ALI) model that mimics the human airway. Primary human airway epithelial cells were grown at ALI until full differentiation was achieved. Cells were then exposed to 1/20 diluted exhaust from an engine running on Diesel (ULSD), pure or 20% blended Canola biodiesel and pure or 20% blended Tallow biodiesel, or Air for control. Exhaust was analysed for various physio-chemical properties and 24-h after exposure, ALI cultures were assessed for permeability, protein release and mediator response. All measured exhaust components were within industry safety standards. ULSD contained the highest concentrations of various combustion gases. We found no differences in terms of particle characteristics for any of the tested exhausts, likely due to the high dilution used. Exposure to Tallow B100 and B20 induced increased permeability in the ALI culture and the greatest increase in mediator response in both the apical and basal compartments. In contrast, Canola B100 and B20 did not impact permeability and induced the smallest mediator response. All exhausts but Canola B20 induced increased protein release, indicating epithelial damage. Despite the concentrations of all exhausts used in this study meeting industry safety regulations, we found significant toxic effects. Tallow biodiesel was found to be the most toxic of the tested fuels and Canola the least, both for blended and pure biodiesel fuels. This suggests that the feedstock biodiesel is made from is crucial for the resulting health effects of exhaust exposure, even when not comprising the majority of fuel composition.
Assuntos
Poluentes Atmosféricos , Biocombustíveis , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Biocombustíveis/análise , Biocombustíveis/toxicidade , Células Epiteliais , Gasolina/análise , Humanos , Material Particulado/análise , Emissões de Veículos/análise , Emissões de Veículos/toxicidadeRESUMO
The photobiology of two reef corals and the distribution of associated symbiont types were investigated over a depth gradient of 0-60 m at Scott Reef, Western Australia. Pachyseris speciosa hosted mainly the same Symbiodinium C type similar to C3 irrespective of sampling depth. By contrast, Seriatopora hystrix hosted predominantly Symbiodinium type D1a or D1a-like at shallow depths while those in deeper water were dominated by a Symbiodinium C type closely related to C1. The photosynthesis/respiration (P/R) ratio increased consistently with depth at the two sampling times (November 2008 and April 2009) for P. speciosa and in November 2008 only for S. hystrix, suggesting a reduction in metabolic energy expended for every unit of energy obtained from photosynthesis. However, in April 2009, shallow colonies of S. hystrix exhibited decreased P/R ratios down to depths of approximately 23 m, below which the ratio increased towards the maximum depth sampled. This pattern was mirrored by changes in tissue biomass determined as total protein content. The depth of change in the direction of the P/R ratio correlated with a shift from Symbiodinium D to C-dominated colonies. We conclude that while photobiological flexibility is vital for persistence in contrasting light regimes, a shift in Symbiodinium type may also confer a functional advantage albeit at a metabolic cost with increased depth.
Assuntos
Antozoários/metabolismo , Dinoflagellida/metabolismo , Ecossistema , Simbiose , Animais , Biodiversidade , Clonagem Molecular , Recifes de Corais , Dados de Sequência Molecular , Fotossíntese , Análise de Sequência de DNA , Especificidade da Espécie , Austrália OcidentalRESUMO
UNLABELLED: Iron and cholesterol are both essential metabolites in mammalian systems, and too much or too little of either can have serious clinical consequences. In addition, both have been associated with steatosis and its progression, contributing, inter alia, to an increase in hepatic oxidative stress. The interaction between iron and cholesterol is unclear, with no consistent evidence emerging with respect to changes in plasma cholesterol on the basis of iron status. We sought to clarify the role of iron in lipid metabolism by studying the effects of iron status on hepatic cholesterol synthesis in mice with differing iron status. Transcripts of seven enzymes in the cholesterol biosynthesis pathway were significantly up-regulated with increasing hepatic iron (R(2) between 0.602 and 0.164), including those of the rate-limiting enzyme, 3-hydroxy-3-methylglutarate-coenzyme A reductase (Hmgcr; R(2) = 0.362, P < 0.002). Hepatic cholesterol content correlated positively with hepatic iron (R(2) = 0.255, P < 0.007). There was no significant relationship between plasma cholesterol and either hepatic cholesterol or iron (R(2) = 0.101 and 0.014, respectively). Hepatic iron did not correlate with a number of known regulators of cholesterol synthesis, including sterol-regulatory element binding factor 2 (Srebf2; R(2) = 0.015), suggesting that the increases seen in the cholesterol biosynthesis pathway are independent of Srebf2. Transcripts of genes involved in bile acid synthesis, transport, or regulation did not increase with increasing hepatic iron. CONCLUSION: This study suggests that hepatic iron loading increases liver cholesterol synthesis and provides a new and potentially important additional mechanism by which iron could contribute to the development of fatty liver disease or lipotoxicity.
Assuntos
Colesterol/biossíntese , Ferro/administração & dosagem , Ferro/fisiologia , Animais , Fígado Gorduroso/etiologia , Masculino , Camundongos , Camundongos Endogâmicos AKRRESUMO
BACKGROUND: Biodiesel is promoted as a sustainable replacement for commercial diesel. Biodiesel fuel and exhaust properties change depending on the base feedstock oil/fat used during creation. The aims of this study were, for the first time, to compare the exhaust exposure health impacts of a wide range of biodiesels made from different feedstocks and relate these effects with the corresponding exhaust characteristics. METHOD: Primary airway epithelial cells were exposed to diluted exhaust from an engine running on conventional diesel and biodiesel made from Soy, Canola, Waste Cooking Oil, Tallow, Palm and Cottonseed. Exhaust properties and cellular viability and mediator release were analysed post exposure. RESULTS: The exhaust physico-chemistry of Tallow biodiesel was the most different to diesel as well as the most toxic, with exposure resulting in significantly decreased cellular viability (95.8 ± 6.5%) and increased release of several immune mediators including IL-6 (+223.11 ± 368.83 pg/mL) and IL-8 (+1516.17 ± 2908.79 pg/mL) above Air controls. In contrast Canola biodiesel was the least toxic with exposure only increasing TNF-α (4.91 ± 8.61). CONCLUSION: This study, which investigated the toxic effects for the largest range of biodiesels, shows that exposure to different exhausts results in a spectrum of toxic effects in vitro when combusted under identical conditions.
Assuntos
Poluentes Atmosféricos , Biocombustíveis , Células Epiteliais/efeitos dos fármacos , Emissões de Veículos/toxicidade , Poluentes Atmosféricos/análise , Biocombustíveis/toxicidade , Células Cultivadas , Culinária , Gasolina , HumanosRESUMO
The method outlined in this article is a customization of the whole exhaust exposure method generated by Mullins et al. (2016) using reprogrammed primary human airway epithelial cells as described by Martinovich et al. (2017). It has been used successfully to generate recently published data (Landwehr et al. 2021). The goal was to generate an exhaust exposure model where exhaust is collected from a modern engine, real-world exhaust concentrations are used and relevant tissues exposed to assess the effects of multiple biodiesel exposures. Exhaust was generated, gently vacuumed into a dilution chamber where it was diluted 1/15 with air and then vacuumed into an incubator containing the primary cell cultures for exposure. Exhaust physico-chemical properties including combustion gas concentrations and particle spectra were then analyzed using a combustion gas analyzer and a Universal Scanning Mobility Particle Sizer. 24 h after exposure, cellular viability and mediator release were measured using Annexin-V/PI staining and meditator multiplexing kits respectively. This method was generated to test biodiesel exhaust exposures but can be easily adapted for any type of engine exhaust exposure or even potentially other respirable environmental exposures such as woodsmoke. The main customization points for this method are:â¢Exhaust generated by a diesel engine equipped with EURO VI exhaust after treatment devices including diesel particulate filter and diesel oxidation catalyst.â¢The generated exhaust was diluted 1/15 with air to replicate real world exposure concentrations.â¢Used primary human airway epithelial cells obtained from bronchoscope brushings from multiple volunteers and reprogrammed to allow multiple, comparative exposures from the same individual.
RESUMO
BACKGROUND: Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive chemotherapy protocols but patients that relapse continue to have a poor prognosis. Such patients could benefit from augmented therapy if their clinical outcome could be more accurately predicted at the time of diagnosis. Gene expression profiling offers the potential to identify additional prognostic markers but has had limited success in generating robust signatures that predict outcome across multiple patient cohorts. This study aimed to identify robust gene classifiers that could be used for the accurate prediction of relapse in independent cohorts and across different experimental platforms. RESULTS: Using HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor (IL-7R), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low IL-7R expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-kappaB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort. CONCLUSIONS: We have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.
Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Algoritmos , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Árvores de Decisões , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , NF-kappa B/genética , Análise de Sequência com Séries de Oligonucleotídeos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Prognóstico , Receptores de Interleucina-7/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento , Proteínas Wnt/genéticaRESUMO
Challenges for wheat doubled haploid (DH) production using anther culture include genotype variability in green plant regeneration and spontaneous chromosome doubling. The frequency of chromosome doubling in our program can vary from 14% to 80%. Caffeine or trifluralin was applied at the start of the induction phase to improve early genome doubling. Caffeine treatment at 0.5 mM for 24 h significantly improved green plant production in two of the six spring wheat crosses but had no effect on the other crosses. The improvements were observed in Trojan/Havoc and Lancer/LPB14-0392, where green plant numbers increased by 14% and 27% to 161 and 42 green plants per 30 anthers, respectively. Caffeine had no significant effect on chromosome doubling, despite a higher frequency of doubling in several caffeine treatments in the first experiment (67-68%) compared to the control (56%). In contrast, trifluralin significantly improved doubling following a 48 h treatment, from 38% in the control to 51% and 53% in the 1 µM and 3 µM trifluralin treatments, respectively. However, trifluralin had a significant negative effect on green plant regeneration, declining from 31.8 green plants per 20 anthers (control) to 9-25 green plants per 20 anthers in the trifluralin treatments. Further work is required to identify a treatment regime with caffeine and/or anti-mitotic herbicides that consistently increases chromosome doubling in wheat without reducing green plant regeneration.
RESUMO
Bayesian statistical modeling has several benefits within an ecological context. In particular, when observed data are limited in sample size or representativeness, then the Bayesian framework provides a mechanism to combine observed data with other "prior" information. Prior information may be obtained from earlier studies, or in their absence, from expert knowledge. This use of the Bayesian framework reflects the scientific "learning cycle," where prior or initial estimates are updated when new data become available. In this paper we outline a framework for statistical design of expert elicitation processes for quantifying such expert knowledge, in a form suitable for input as prior information into Bayesian models. We identify six key elements: determining the purpose and motivation for using prior information; specifying the relevant expert knowledge available; formulating the statistical model; designing effective and efficient numerical encoding; managing uncertainty; and designing a practical elicitation protocol. We demonstrate this framework applies to a variety of situations, with two examples from the ecological literature and three from our experience. Analysis of these examples reveals several recurring important issues affecting practical design of elicitation in ecological problems.
Assuntos
Teorema de Bayes , Ecologia/métodos , Modelos Biológicos , Modelos Estatísticos , Animais , Demografia , Monitoramento Ambiental , Macropodidae/fisiologiaRESUMO
Although drug development typically focuses on binding thermodynamics, recent studies suggest that kinetic properties can strongly impact a drug candidate's efficacy. Robust techniques for measuring inhibitor association and dissociation rates are therefore essential. To address this need, we have developed a pair of complementary isothermal titration calorimetry (ITC) techniques for measuring the kinetics of enzyme inhibition. The advantages of ITC over standard techniques include speed, generality, and versatility; ITC also measures the rate of catalysis directly, making it ideal for quantifying rapid, inhibitor-dependent changes in enzyme activity. We used our methods to study the reversible covalent and non-covalent inhibitors of prolyl oligopeptidase (POP). We extracted kinetics spanning three orders of magnitude, including those too rapid for standard methods, and measured sub-nM binding affinities below the typical ITC limit. These results shed light on the inhibition of POP and demonstrate the general utility of ITC-based enzyme inhibition kinetic measurements.
Assuntos
Calorimetria/métodos , Serina Endopeptidases/química , Biocatálise , Inibidores Enzimáticos/química , Cinética , Prolil OligopeptidasesRESUMO
Few studies describe the primary drivers influencing soil organic carbon (SOC) stocks and the distribution of carbon (C) fractions in agricultural systems from semi-arid regions; yet these soils comprise one fifth of the global land area. Here we identified the primary drivers for changes in total SOC and associated particulate (POC), humus (HOC) and resistant (ROC) organic C fractions for 1347 sample points in the semi-arid agricultural region of Western Australia. Total SOC stock (0-0.3 m) varied from 4 to 209 t C ha(-1) with 79% of variation explained by measured variables. The proportion of C in POC, HOC and ROC fractions averaged 28%, 45% and 27% respectively. Climate (43%) and land management practices (32%) had the largest relative influence on variation in total SOC. Carbon accumulation was constrained where average daily temperature was above 17.2 °C and annual rainfall below 450 mm, representing approximately 42% of the 197,300 km(2) agricultural region. As such large proportions of this region are not suited to C sequestration strategies. For the remainder of the region a strong influence of management practices on SOC indicate opportunities for C sequestration strategies associated with incorporation of longer pasture phases and adequate fertilisation.
RESUMO
Extensive experimental investigation of the wetting processes of fibre-liquid systems during air filtration (when drag and gravitational forces are acting) has shown many important features, including droplet extension, oscillatory motion, and detachment of drops from fibres as airflow velocity increases, and also movement or flow of droplets along fibres. A detailed experimental study of the processes was conducted using stainless steel filter fibres and H2O aerosol, which coalesce on the fibre to form clamshell droplets. The droplets were predominantly observed in the Reynolds transition flow region, since this is the region where most of the above features occur. The droplet oscillation is believed to be induced by the onset of the transition from laminar to turbulent flow as the increasing droplet size increases Reynolds number for the flow around the droplet. Two-dimensional flow in this region is usually modelled using the classical Karman vortex street, however there exist no 3D equivalents. Therefore to model such oscillation it was necessary to create a new conceptual model to account for the forces both inducing and preventing such oscillation. The agreement between the model and experimental results is very good for both the radial and transverse oscillations.
RESUMO
When limited or no observed data are available, it is often useful to obtain expert knowledge about parameters of interest, including point estimates and the uncertainty around these values. However, it is vital to elicit this information appropriately in order to obtain valid estimates. This is particularly important when the experts' uncertainty about these estimates is strongly skewed, for instance when their best estimate is the same as the lowest value they consider possible. Also this is important when interest is in the aggregation of elicited values. In this paper, we compare alternative distributions for describing such estimates. The distributions considered include the lognormal, mirror lognormal, Normal and scaled Beta. The case study presented here involves estimation of the number of species in coral reefs, which requires eliciting counts within broader taxonomic groups, with highly skewed uncertainty estimates. This paper shows substantial gain in using the scaled Beta distribution, compared with Normal or lognormal distributions. We demonstrate that, for this case study on counting species, applying the novel encoding methodology developed in this paper can facilitate the acquisition of more rigorous estimates of (hierarchical) count data and credible bounds. The approach can also be applied to the more general case of enumerating a sampling frame via elicitation.