123 research outputs found
Phenylalanine as a hydroxyl radical-specific probe in pyrite slurries
The abundant iron sulfide mineral pyrite has been shown to catalytically produce hydrogen peroxide (H2O2) and hydroxyl radical (.OH) in slurries of oxygenated water. Understanding the formation and fate of these reactive oxygen species is important to biological and ecological systems as exposure can lead to deleterious health effects, but also environmental engineering during the optimization of remediation approaches for possible treatment of contaminated waste streams. This study presents the use of the amino acid phenylalanine (Phe) to monitor the kinetics of pyrite-induced .OH formation through rates of hydroxylation forming three isomers of tyrosine (Tyr) - ortho-, meta-, and para-Tyr. Results indicate that about 50% of the Phe loss results in Tyr formation, and that these products further react with .OH at rates comparable to Phe. The overall loss of Phe appeared to be pseudo first-order in [Phe] as a function of time, but for the first time it is shown that initial rates were much less than first-order as a function of initial substrate concentration, [Phe]o. These results can be rationalized by considering that the effective concentration of .OH in solution is lower at a higher level of reactant and that an increasing fraction of .OH is consumed by Phe-degradation products as a function of time. A simplified first-order model was created to describe Phe loss in pyrite slurries which incorporates the [Phe]o, a first-order dependence on pyrite surface area, the assumption that all Phe degradation products compete equally for the limited supply of highly reactive .OH, and a flux that is related to the release of H2O2 from the pyrite surface (a result of the incomplete reduction of oxygen at the pyrite surface). An empirically derived rate constant, Kpyr, was introduced to describe a variable .OH-reactivity for different batches of pyrite. Both the simplified first-order kinetic model, and a more detailed numerical simulation, yielded results that compare well to the observed kinetic data describing the effects of variations in concentrations of both initial Phe and pyrite. This work supports the use of Phe as a useful probe to assess the formation of .OH in the presence of pyrite, and its possible utility for similar applications with other minerals
Identification of key parameters controlling demographically structured vegetation dynamics in a land surface model: CLM4.5(FATES)
Vegetation plays an important role in regulating global carbon cycles and is a key component of the Earth system models (ESMs) that aim to project Earth\u27s future climate. In the last decade, the vegetation component within ESMs has witnessed great progress from simple âbig-leafâ approaches to demographically structured approaches, which have a better representation of plant size, canopy structure, and disturbances. These demographically structured vegetation models typically have a large number of input parameters, and sensitivity analysis is needed to quantify the impact of each parameter on the model outputs for a better understanding of model behavior. In this study, we conducted a comprehensive sensitivity analysis to diagnose the Community Land Model coupled to the Functionally Assembled Terrestrial Simulator, or CLM4.5(FATES). Specifically, we quantified the first- and second-order sensitivities of the model parameters to outputs that represent simulated growth and mortality as well as carbon fluxes and stocks for a tropical site with an extent of 1Ă1â. While the photosynthetic capacity parameter (Vc,max25) is found to be important for simulated carbon stocks and fluxes, we also show the importance of carbon storage and allometry parameters, which determine survival and growth strategies within the model. The parameter sensitivity changes with different sizes of trees and climate conditions. The results of this study highlight the importance of understanding the dynamics of the next generation of demographically enabled vegetation models within ESMs to improve model parameterization and structure for better model fidelity
Cryptococcus gattii in North American Pacific Northwest: whole-population genome analysis provides insights into species evolution and dispersal
The emergence of distinct populations of Cryptococcus gattii in the temperate North American Pacific Northwest (PNW) was surprising, as this species was previously thought to be confined to tropical and semitropical regions. Beyond a new habitat niche, the dominant emergent population displayed increased virulence and caused primary pulmonary disease, as opposed to the predominantly neurologic disease seen previously elsewhere. Whole-genome sequencing was performed on 118 C. gattii isolates, including the PNW subtypes and the global diversity of molecular type VGII, to better ascertain the natural source and genomic adaptations leading to the emergence of infection in the PNW. Overall, the VGII population was highly diverse, demonstrating large numbers of mutational and recombinational events; however, the three dominant subtypes from the PNW were of low diversity and were completely clonal. Although strains of VGII were found on at least five continents, all genetic subpopulations were represented or were most closely related to strains from South America. The phylogenetic data are consistent with multiple dispersal events from South America to North America and elsewhere. Numerous gene content differences were identified between the emergent clones and other VGII lineages, including genes potentially related to habitat adaptation, virulence, and pathology. Evidence was also found for possible gene introgression from Cryptococcus neoformans var. grubii that is rarely seen in global C. gattii but that was present in all PNW populations. These findings provide greater understanding of C. gattii evolution in North America and support extensive evolution in, and dispersal from, South America. Importance: Cryptococcus gattii emerged in the temperate North American Pacific Northwest (PNW) in the late 1990s. Beyond a new environmental niche, these emergent populations displayed increased virulence and resulted in a different pattern of clinical disease. In particular, severe pulmonary infections predominated in contrast to presentation with neurologic disease as seen previously elsewhere. We employed population-level whole-genome sequencing and analysis to explore the genetic relationships and gene content of the PNW C. gattii populations. We provide evidence that the PNW strains originated from South America and identified numerous genes potentially related to habitat adaptation, virulence expression, and clinical presentation. Characterization of these genetic features may lead to improved diagnostics and therapies for such fungal infections. The data indicate that there were multiple recent introductions of C. gattii into the PNW. Public health vigilance is warranted for emergence in regions where C. gattii is not thought to be endemic
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
Life Beyond the Solar System: Remotely Detectable Biosignatures
For the first time in human history, we will soon be able to apply to the scientific method to the question "Are We Alone?" The rapid advance of exoplanet discovery, planetary systems science, and telescope technology will soon allow scientists to search for life beyond our Solar System through direct observation of extrasolar planets. This endeavor will occur alongside searches for habitable environments and signs of life within our Solar System. While these searches are thematically related and will inform each other, they will require separate observational techniques. The search for life on exoplanets holds potential through the great diversity of worlds to be explored beyond our Solar System. However, there are also unique challenges related to the relatively limited data this search will obtain on any individual world
Powerful Bivariate Genome-Wide Association Analyses Suggest the SOX6 Gene Influencing Both Obesity and Osteoporosis Phenotypes in Males
Current genome-wide association studies (GWAS) are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically. was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat. gene's importance in co-regulation of obesity and osteoporosis
Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study
Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating âŒ380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72Ă10â7. The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62Ă10â3 and 2.44Ă10â3, respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values<10â5 in the two samples. The PLCL1 gene's relevance to HF was also observed in a Chinese sample containing 403 females, including 266 with HF and 177 control subjects. A SNP of the PLCL1 gene, rs3771362 that is only âŒ0.6 kb apart from the most significant SNP detected in our GWAS (rs7595412), achieved a p value of 7.66Ă10â3 (odds ratioâ=â0.26) for association with HF. Additional biological support for the role of PLCL1 in BS comes from previous demonstrations that the PLCL1 protein inhibits IP3 (inositol 1,4,5-trisphosphate)-mediated calcium signaling, an important pathway regulating mechanical sensing of bone cells. Our findings suggest that PLCL1 is a novel gene associated with variation in hip BS, and provide new insights into the pathogenesis of HF
Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study
BACKGROUND
Worldwide, haemoglobin E ÎČ-thalassaemia is the most common genotype of severe ÎČ-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia.
METHODS
In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality.
FINDINGS
109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 ÎŒg/L (vs concentration â€1300 ÎŒg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration â€5 mg/g) were associated with poorer survival.
INTERPRETATION
Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival.
FUNDING
Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal
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Beyond ecosystem modeling: a roadmap to community cyberinfrastructure for ecological dataâmodel integration
In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks to informing models with observations have reduced our capacity to fully exploit the growing volume and variety of available data. Here, we take a critical look at the information infrastructure that connects ecosystem modeling and measurement efforts, and propose a roadmap to community cyberinfrastructure development that can reduce the divisions between empirical research and modeling and accelerate the pace of discovery. A new era of dataâmodel integration requires investment in accessible, scalable, transparent tools that integrate the expertise of the whole community, including both modelers and empiricists. This roadmap focuses on five key opportunities for community tools: the underlying foundationsof community cyberinfrastructure; data ingest; calibration of models to data; modelâdata benchmarking; and data assimilation and ecological forecasting. This communityâdriven approach is key to meeting the pressing needs of science and society in the 21st century
Search for dark matter produced in association with bottom or top quarks in âs = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fbâ1 of protonâproton collision data recorded by the ATLAS experiment at âs = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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