| 1. |
- Bale, S. D., et al.
(författare)
-
The FIELDS Instrument Suite for Solar Probe Plus
- 2016
-
Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 204:1-4, s. 49-82
-
Forskningsöversikt (refereegranskat)abstract
- NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.
|
|
| 2. |
|
|
| 3. |
- Kattge, Jens, et al.
(författare)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
|
|
| 4. |
- Moortgat-Pick, G., et al.
(författare)
-
Polarized positrons and electrons at the linear collider
- 2008
-
Ingår i: Physics reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 460:4-5, s. 131-243
-
Forskningsöversikt (refereegranskat)abstract
- The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization.
|
|
| 5. |
- Cavalieri, A L, et al.
(författare)
-
Clocking femtosecond X rays.
- 2005
-
Ingår i: Phys Rev Lett. - 0031-9007. ; 94:11
-
Tidskriftsartikel (refereegranskat)abstract
- Linear-accelerator-based sources will revolutionize ultrafast x-ray science due to their unprecedented brightness and short pulse duration. However, time-resolved studies at the resolution of the x-ray pulse duration are hampered by the inability to precisely synchronize an external laser to the accelerator. At the Sub-Picosecond Pulse Source at the Stanford Linear-Accelerator Center we solved this problem by measuring the arrival time of each high energy electron bunch with electro-optic sampling. This measurement indirectly determined the arrival time of each x-ray pulse relative to an external pump laser pulse with a time resolution of better than 60 fs rms.
|
|
| 6. |
- Gaffney, K J, et al.
(författare)
-
Observation of structural anisotropy and the onset of liquidlike motion during the nonthermal melting of InSb
- 2005
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 95:12
-
Tidskriftsartikel (refereegranskat)abstract
- The melting dynamics of laser excited InSb have been studied with femtosecond x-ray diffraction. These measurements observe the delayed onset of diffusive atomic motion, signaling the appearance of liquidlike dynamics. They also demonstrate that the root-mean-squared displacement in the [111] direction increases faster than in the [110] direction after the first 500 fs. This structural anisotropy indicates that the initially generated fluid differs significantly from the equilibrium liquid.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Limpens, J., et al.
(författare)
-
Climatic modifiers of the response to nitrogen deposition in peat-forming Sphagnum mosses : a meta-analysis
- 2011
-
Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 191:2, s. 496-507
-
Tidskriftsartikel (refereegranskat)abstract
- Peatlands in the northern hemisphere have accumulated more atmospheric carbon (C) during the Holocene than any other terrestrial ecosystem, making peatlands long-term C sinks of global importance. Projected increases in nitrogen (N) deposition and temperature make future accumulation rates uncertain. Here, we assessed the impact of N deposition on peatland C sequestration potential by investigating the effects of experimental N addition on Sphagnum moss. We employed meta-regressions to the results of 107 field experiments, accounting for sampling dependence in the data. We found that high N loading (comprising N application rate, experiment duration, background N deposition) depressed Sphagnum production relative to untreated controls. The interactive effects of presence of competitive vascular plants and high tissue N concentrations indicated intensified biotic interactions and altered nutrient stochiometry as mechanisms underlying the detrimental N effects. Importantly, a higher summer temperature (mean for July) and increased annual precipitation intensified the negative effects of N. The temperature effect was comparable to an experimental application of almost 4 g N m(-2) yr(-1) for each 1 degrees C increase. Our results indicate that current rates of N deposition in a warmer environment will strongly inhibit C sequestration by Sphagnum-dominated vegetation.
|
|
| 11. |
- Limpens, J., et al.
(författare)
-
Glasshouse vs field experiments : do they yield ecologically similar results for assessing N impacts on peat mosses?
- 2012
-
Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 195:2, s. 408-418
-
Tidskriftsartikel (refereegranskat)abstract
- Peat bogs have accumulated more atmospheric carbon (C) than any other terrestrial ecosystem today. Most of this C is associated with peat moss (Sphagnum) litter. Atmospheric nitrogen (N) deposition can decrease Sphagnum production, compromising the C sequestration capacity of peat bogs. The mechanisms underlying the reduced production are uncertain, necessitating multifactorial experiments. We investigated whether glasshouse experiments are reliable proxies for field experiments for assessing interactions between N deposition and environment as controls on Sphagnum N concentration and production. We performed a meta-analysis over 115 glasshouse experiments and 107 field experiments. We found that glasshouse and field experiments gave similar qualitative and quantitative estimates of changes in Sphagnum N concentration in response to N application. However, glasshouse-based estimates of changes in production even qualitative assessments diverged from field experiments owing to a stronger N effect on production response in absence of vascular plants in the glasshouse, and a weaker N effect on production response in presence of vascular plants compared to field experiments. Thus, although we need glasshouse experiments to study how interacting environmental factors affect the response of Sphagnum to increased N deposition, we need field experiments to properly quantify these effects.
|
|
| 12. |
- Lindenberg, AM, et al.
(författare)
-
Atomic-scale visualization of inertial dynamics
- 2005
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 308:5720, s. 392-395
-
Tidskriftsartikel (refereegranskat)abstract
- The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface. Our measurements point toward analogies between this nonequilibrium phase transition and the short-time dynamics intrinsic to equilibrium liquids.
|
|
| 13. |
|
|
| 14. |
- Sikkema, Lisa, et al.
(författare)
-
An integrated cell atlas of the lung in health and disease
- 2023
-
Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
-
Tidskriftsartikel (refereegranskat)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
|
|
| 15. |
- Trainer, P J, et al.
(författare)
-
Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- 2000
-
Ingår i: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
|
|
| 16. |
- Warkentin, T. E., et al.
(författare)
-
Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin
- 2005
-
Ingår i: Blood. - 0006-4971. ; 106:12, s. 3791-6
-
Tidskriftsartikel (refereegranskat)abstract
- Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti-PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low.
|
|
| 17. |
|
|
| 18. |
- Sale, Peter F., et al.
(författare)
-
Transforming management of tropical coastal seas to cope with challenges of the 21st century
- 2014
-
Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X .- 1879-3363. ; 85:1, s. 8-23
-
Tidskriftsartikel (refereegranskat)abstract
- Over 1.3 billion people live on tropical coasts, primarily in developing countries. Many depend on adjacent coastal seas for food, and livelihoods. We show how trends in demography and in several local and global anthropogenic stressors are progressively degrading capacity of coastal waters to sustain these people. Far more effective approaches to environmental management are needed if the loss in provision of ecosystem goods and services is to be stemmed. We propose expanded use of marine spatial planning as a framework for more effective, pragmatic management based on ocean zones to accommodate conflicting uses. This would force the holistic, regional-scale reconciliation of food security, livelihoods, and conservation that is needed. Transforming how countries manage coastal resources will require major change in policy and politics, implemented with sufficient flexibility to accommodate societal variations. Achieving this change is a major challenge - one that affects the lives of one fifth of humanity.
|
|
| 19. |
|
|
| 20. |
- Walsh, Roddy, et al.
(författare)
-
Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
-
Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
|
|
| 21. |
|
|
| 22. |
- Casamajo, Arnau Rué, et al.
(författare)
-
Biocatalysis in Drug Design: Engineered Reductive Aminases (RedAms) Are Used to Access Chiral Building Blocks with Multiple Stereocenters
- 2023
-
Ingår i: Journal of the American Chemical Society. - : NA. - 0002-7863 .- 1520-5126. ; 145:40, s. 22041-22046
-
Tidskriftsartikel (refereegranskat)abstract
- Novel building blocks are in constant demand during the search for innovative bioactive small molecule therapeutics by enabling the construction of structure-activity-property-toxicology relationships. Complex chiral molecules containing multiple stereocenters are an important component in compound library expansion but can be difficult to access by traditional organic synthesis. Herein, we report a biocatalytic process to access a specific diastereomer of a chiral amine building block used in drug discovery. A reductive aminase (RedAm) was engineered following a structure-guided mutagenesis strategy to produce the desired isomer. The engineered RedAm (IR-09 W204R) was able to generate the (S,S,S)-isomer 3 in 45% conversion and 95% ee from the racemic ketone 2. Subsequent palladium-catalyzed deallylation of 3 yielded the target primary amine 4 in a 73% yield. This engineered biocatalyst was used at preparative scale and represents a potential starting point for further engineering and process development.
|
|
| 23. |
- Cook, David C., et al.
(författare)
-
Plant biosecurity policy-making modelled on the human immune system: What would it look like?
- 2014
-
Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011. ; 41, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- This paper takes inspiration from the field of bio-mimicry to suggest what a plant biosecurity system might look like if it was modelled on the human immune system. We suggest structural and institutional changes to current biosecurity systems that would facilitate adaptive preparation and response policies, focusing particularly on the Australian plant biosecurity system. By improving information exchanges, interpretation and managing overlapping complementary response capabilities of this system, novel policies emerge that increase resilience to harmful weeds, pests and diseases. This is achieved by adding an element of flexibility in invasion response to cope with different circumstances and contexts, rather than a 'one size fits all' approach. While we find bio-mimicry to be a potentially useful system design tool, there are key differences between the immune and biosecurity systems that the analogy makes clear. Perhaps the most important of these stems from the inability of immune systems to imagine future threats. (C) 2014 Elsevier Ltd. All rights reserved.
|
|
| 24. |
- Lindenberg, A.M., et al.
(författare)
-
Ultrafast x-ray measurements of inertial atomic-scale motion
- 2005
-
Ingår i: Quantum Electronics and Laser Science Conference. ; , s. 742-744
-
Konferensbidrag (refereegranskat)abstract
- Using a new, accelerator-based source of femtosecond x-rays, we directly measure atomic displacements on an optically-modified potential energy surface. It is shown that the short time dynamics are predominantly inertial in character.
|
|
| 25. |
- Lindstrom, J., et al.
(författare)
-
Take Action to Prevent Diabetes : The IMAGE Toolkit for the Prevention of Type 2 Diabetes in Europe
- 2010
-
Ingår i: Hormone and Metabolic Research. - Wuppertal, Germany. : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 42:Suppl 1, s. S37-S55
-
Tidskriftsartikel (refereegranskat)abstract
- When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: Prevention is Better Than Cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18% of total healthcare expenditure in Europe. The Good News is That Diabetes is Preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50% following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play.
|
|
| 26. |
- Munoz-Ramirez, Z. Y., et al.
(författare)
-
A 500-year tale of co-evolution, adaptation, and virulence:Helicobacter pyloriin the Americas
- 2021
-
Ingår i: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 15:1, s. 78-92
-
Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pyloriis a common component of the human stomach microbiota, possibly dating back to the speciation ofHomo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinctH. pylorisubpopulations, associated with different human populations, and more recent admixture amongH. pylorisubpopulations can provide information about human migrations. However, little is known about the degree to which someH. pylorigenes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzedH. pylorigenomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723H. pyloristrains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions fromH. pyloripopulations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel AmericanH. pylorisubpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region.
|
|
| 27. |
- Solberg, E E, et al.
(författare)
-
Sudden cardiac arrest in sports - need for uniform registration : A Position Paper from the Sport Cardiology Section of the European Association for Cardiovascular Prevention and Rehabilitation.
- 2016
-
Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:6, s. 657-667
-
Tidskriftsartikel (refereegranskat)abstract
- There are large variations in the incidence, registration methods and reported causes of sudden cardiac arrest/sudden cardiac death (SCA/SCD) in competitive and recreational athletes. A crucial question is to which degree these variations are genuine or partly due to methodological incongruities. This paper discusses the uncertainties about available data and provides comprehensive suggestions for standard definitions and a guide for uniform registration parameters of SCA/SCD. The parameters include a definition of what constitutes an 'athlete', incidence calculations, enrolment of cases, the importance of gender, ethnicity and age of the athlete, as well as the type and level of sporting activity. A precise instruction for autopsy practice in the case of a SCD of athletes is given, including the role of molecular samples and evaluation of possible doping. Rational decisions about cardiac preparticipation screening and cardiac safety at sport facilities requires increased data quality concerning incidence, aetiology and management of SCA/SCD in sports. Uniform standard registration of SCA/SCD in athletes and leisure sportsmen would be a first step towards this goal.
|
|
| 28. |
- Wiseman, Frances K, et al.
(författare)
-
Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP.
- 2018
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 141:8, s. 2457-2474
-
Tidskriftsartikel (refereegranskat)abstract
- Down syndrome, caused by trisomy of chromosome 21, is the single most common risk factor for early-onset Alzheimer's disease. Worldwide approximately 6 million people have Down syndrome, and all these individuals will develop the hallmark amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of 40 and the vast majority will go on to develop dementia. Triplication of APP, a gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in the absence of Down syndrome. However, whether triplication of other chromosome 21 genes influences disease pathogenesis in the context of Down syndrome is unclear. Here we show, in a mouse model, that triplication of chromosome 21 genes other than APP increases amyloid-β aggregation, deposition of amyloid-β plaques and worsens associated cognitive deficits. This indicates that triplication of chromosome 21 genes other than APP is likely to have an important role to play in Alzheimer's disease pathogenesis in individuals who have Down syndrome. We go on to show that the effect of trisomy of chromosome 21 on amyloid-β aggregation correlates with an unexpected shift in soluble amyloid-β 40/42 ratio. This alteration in amyloid-β isoform ratio occurs independently of a change in the carboxypeptidase activity of the γ-secretase complex, which cleaves the peptide from APP, or the rate of extracellular clearance of amyloid-β. These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.
|
|
| 29. |
- Arnold, TD, et al.
(författare)
-
Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking αVβ8-TGFβ signaling in the brain
- 2014
-
Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 141:23, s. 4489-4499
-
Tidskriftsartikel (refereegranskat)abstract
- Vascular development of the central nervous system and blood-brain barrier (BBB) induction are closely linked processes. The role of factors that promote endothelial sprouting and vascular leak, such as vascular endothelial growth factor A, are well described, but the factors that suppress angiogenic sprouting and their impact on the BBB are poorly understood. Here, we show that integrin αVβ8 activates angiosuppressive TGFβ gradients in the brain, which inhibit endothelial cell sprouting. Loss of αVβ8 in the brain or downstream TGFβ1-TGFBR2-ALK5-Smad3 signaling in endothelial cells increases vascular sprouting, branching and proliferation, leading to vascular dysplasia and hemorrhage. Importantly, BBB function in Itgb8 mutants is intact during early stages of vascular dysgenesis before hemorrhage. By contrast, Pdgfbret/ret mice, which exhibit severe BBB disruption and vascular leak due to pericyte deficiency, have comparatively normal vascular morphogenesis and do not exhibit brain hemorrhage. Our data therefore suggest that abnormal vascular sprouting and patterning, not BBB dysfunction, underlie developmental cerebral hemorrhage.
|
|
| 30. |
- Carter, M. S., et al.
(författare)
-
Synthesizing greenhouse gas fluxes across nine European peatlands and shrublands - responses to climatic and environmental changes
- 2012
-
Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 9:10, s. 3739-3755
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we compare annual fluxes of methane (CH4), nitrous oxide (N2O) and soil respiratory carbon dioxide (CO2) measured at nine European peatlands (n = 4) and shrublands (n = 5). The sites range from northern Sweden to Spain, covering a span in mean annual air temperature from 0 to 16 degrees C, and in annual precipitation from 300 to 1300 mm yr(-1). The effects of climate change, including temperature increase and prolonged drought, were tested at five shrubland sites. At one peatland site, the long-term (> 30 yr) effect of drainage was assessed, while increased nitrogen deposition was investigated at three peatland sites. The shrublands were generally sinks for atmospheric CH4, whereas the peatlands were CH4 sources, with fluxes ranging from -519 to + 6890 mg CH4-Cm-2 yr(-1) across the studied ecosystems. At the peatland sites, annual CH4 emission increased with mean annual air temperature, while a negative relationship was found between net CH4 uptake and the soil carbon stock at the shrubland sites. Annual N2O fluxes were generally small ranging from -14 to 42 mg N2O-Nm(-2) yr(-1). Highest N2O emission occurred at the sites that had highest nitrate (NO3-) concentration in the soil water. Furthermore, experimentally increased NO3- deposition led to increased N2O efflux, whereas prolonged drought and long-term drainage reduced the N2O efflux. Soil CO2 emissions in control plots ranged from 310 to 732 g CO2-C m(-2) yr(-1). Drought and long-term drainage from -519 to + 6890 mg CH4-C m(-2) yr(-1) across the studied ecosystems. At the peatland sites, annual CH4 emission increased with mean annual air temperature, while a negative relationship was found between net CH4 uptake and the soil carbon stock at the shrubland sites. Annual N2O fluxes were generally small ranging from -14 to 42 mg N2O-N m(-2) yr(-1). Highest N2O emission occurred at the sites that had highest nitrate (NO3-) concentration in the soil water. Furthermore, experimentally increased NO3- deposition led to increased N2O efflux, whereas prolonged drought and long-term drainage reduced the N2O efflux. Soil CO2 emissions in control plots ranged from 310 to 732 g CO2-Cm-2 yr(-1). Drought and long-term drainage generally reduced the soil CO2 efflux, except at a hydric shrubland where drought tended to increase soil respiration. In terms of fractional importance of each greenhouse gas to the total numerical global warming response, the change in CO2 efflux dominated the response in all treatments (ranging 71-96%), except for NO3- addition where 89% was due to change in CH4 emissions. Thus, in European peatlands and shrublands the effect on global warming induced by the investigated anthropogenic disturbances will be dominated by variations in soil CO2 fluxes.
|
|
| 31. |
- Dormann, Carsten F., et al.
(författare)
-
Biotic interactions in species distribution modelling : 10 questions to guide interpretation and avoid false conclusions
- 2018
-
Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:9, s. 1004-1016
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Recent studies increasingly use statistical methods to infer biotic interactions from co‐occurrence information at a large spatial scale. However, disentangling biotic interactions from other factors that can affect co‐occurrence patterns at the macroscale is a major challenge.Approach: We present a set of questions that analysts and reviewers should ask to avoid erroneously attributing species association patterns to biotic interactions. Our questions relate to the appropriateness of data and models, the causality behind a correlative signal, and the problems associated with static data from dynamic systems. We summarize caveats reported by macroecological studies of biotic interactions and examine whether conclusions on the presence of biotic interactions are supported by the modelling approaches used.Findings: Irrespective of the method used, studies that set out to test for biotic interactions find statistical associations in species’ co‐occurrences. Yet, when compared with our list of questions, few purported interpretations of such associations as biotic interactions hold up to scrutiny. This does not dismiss the presence or importance of biotic interactions, but it highlights the risk of too lenient interpretation of the data. Combining model results with information from experiments and functional traits that are relevant for the biotic interaction of interest might strengthen conclusions.Main conclusions: Moving from species‐ to community‐level models, including biotic interactions among species, is of great importance for process‐based understanding and forecasting ecological responses. We hope that our questions will help to improve these models and facilitate the interpretation of their results. In essence, we conclude that ecologists have to recognize that a species association pattern in joint species distribution models will be driven not only by real biotic interactions, but also by shared habitat preferences, common migration history, phylogenetic history and shared response to missing environmental drivers, which specifically need to be discussed and, if possible, integrated into models.
|
|
| 32. |
- Graham, Nicholas A. J., et al.
(författare)
-
Climate Warming, Marine Protected Areas and the Ocean-Scale Integrity of Coral Reef Ecosystems
- 2008
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:8, s. e3039-
-
Tidskriftsartikel (refereegranskat)abstract
- Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change.
|
|
| 33. |
- Greinacher, A, et al.
(författare)
-
Heparin-induced thrombocytopenia : towards standardization of platelet factor 4/heparin antigen tests.
- 2010
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8:9, s. 2025-31
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is based on detection of heparin-dependent platelet-activating antibodies. Platelet factor 4 (PF4)/heparin enzyme-immunoassays (EIA) are a widely available surrogate for platelet-activating antibodies. OBJECTIVE: Defining the optical density (OD) reactivity profiles of a PF4/heparin EIA in reference subject and patient populations and the correlation of the EIA results (expressed in OD units) with the prevalence of platelet-activating antibodies. PATIENTS/METHODS: Using quantile regression we determined the 97.5th percentile of PF4/heparin-immunoglobulin G (IgG) EIA reactivities in non-heparin-treated individuals [blood donors (n = 935)] and patients before heparin therapy (n = 1207). In patients with suspected HIT, we compared the correlation of EIA-IgG reactivities (Greifswald laboratory; n = 2821) and the heparin-induced platelet activation assay (HIPA) with the correlation of reactivities of another EIA-IgG (McMaster laboratory; n = 1956) with the serotonin-release assay (SRA). RESULTS: PF4/heparin-IgG EIA OD reactivities had a lower OD 97.5th percentile in blood donors compared with patient groups before heparin treatment (P < 0.001). The percentage of sera testing positive in the functional assays strongly correlated with PF4/heparin-IgG EIA OD reactivities in both laboratories with very similar results (correlation coefficient > 0.9) when normalized OD ranges (maximum OD divided by 10) were used instead of absolute OD values. CONCLUSIONS: Results of PF4/heparin-IgG EIA should not be reported as only positive or negative as there is no single acceptable cut-off value. Instead, reporting PF4/heparin-IgG EIA OD results in ranges allows for risk-stratified prediction for presence of platelet-activating antibodies. Use of normalized OD ranges permits a standardized approach for inter-laboratory comparisons.
|
|
| 34. |
- Henderson, Neil C., et al.
(författare)
-
Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs
- 2013
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:12, s. 1617-1624
-
Tidskriftsartikel (refereegranskat)abstract
- Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding alpha(v) integrin subunit because various alpha(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of beta(3), beta(5) or beta(6) integrins or conditional loss of beta(8) integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the alpha(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of alpha(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all alpha(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
|
|
| 35. |
- Hochberg, Z., et al.
(författare)
-
Child health, developmental plasticity, and epigenetic programming
- 2011
-
Ingår i: Endocrine reviews. - : The Endocrine Society. - 0163-769X .- 1945-7189. ; 32:2, s. 159-224
-
Forskningsöversikt (refereegranskat)abstract
- Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developmental origins of health and disease and life-history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies in response to local ecological and/or social conditions. The window of developmental plasticity extends from preconception to early childhood and involves epigenetic responses to environmental changes, which exert their effects during life-history phase transitions. These epigenetic responses influence development, cell- and tissue-specific gene expression, and sexual dimorphism, and, in exceptional cases, could be transmitted transgenerationally. Translational epigenetic research in child health is a reiterative process that ranges from research in the basic sciences, preclinical research, and pediatric clinical research. Identifying the epigenetic consequences of fetal programming creates potential applications in clinical practice: the development of epigenetic biomarkers for early diagnosis of disease, the ability to identify susceptible individuals at risk for adult diseases, and the development of novel preventive and curative measures that are based on diet and/or novel epigenetic drugs.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Mageiros, Leonardos, et al.
(författare)
-
Genome evolution and the emergence of pathogenicity in avian Escherichia coli
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Chickens are the most common birds on Earth and colibacillosis is among the most common diseases affecting them. This major threat to animal welfare and safe sustainable food production is difficult to combat because the etiological agent, avian pathogenic Escherichia coli (APEC), emerges from ubiquitous commensal gut bacteria, with no single virulence gene present in all disease-causing isolates. Here, we address the underlying evolutionary mechanisms of extraintestinal spread and systemic infection in poultry. Combining population scale comparative genomics and pangenome-wide association studies, we compare E. coli from commensal carriage and systemic infections. We identify phylogroup-specific and species-wide genetic elements that are enriched in APEC, including pathogenicity-associated variation in 143 genes that have diverse functions, including genes involved in metabolism, lipopolysaccharide synthesis, heat shock response, antimicrobial resistance and toxicity. We find that horizontal gene transfer spreads pathogenicity elements, allowing divergent clones to cause infection. Finally, a Random Forest model prediction of disease status (carriage vs. disease) identifies pathogenic strains in the emergent ST-117 poultry-associated lineage with 73% accuracy, demonstrating the potential for early identification of emergent APEC in healthy flocks.
|
|
| 39. |
- Sheppard, J M H, et al.
(författare)
-
Simulations of the phonon Bragg switch in GaAs
- 2005
-
Ingår i: Solid State Communications. - : Elsevier BV. - 1879-2766 .- 0038-1098. ; 136:3, s. 181-185
-
Tidskriftsartikel (refereegranskat)abstract
- It has recently been proposed that X-rays can be switched on sub-picosecond time-scales by using laser-generated coherent optical phonons: The so called phonon Bragg switch. We present here detailed simulations of the efficiency of such a switch by solving the time-dependent generalized Takagi-Taupin equations utilizing a perturbative approach. We explore the switching efficiency in diffraction from the (004) planes of GaAs as a function of both excited phonon wave vector and amplitude.
|
|
| 40. |
- Smith, LK, et al.
(författare)
-
Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1100-
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selectively controls their transport and translation during adaptation to BRAF-targeted therapy. UHMK1 inactivation induces cell death by disrupting therapy induced metabolic reprogramming, and importantly, delays resistance to BRAF and MEK combination therapy in multiple in vivo models. We propose selective mRNA processing and translation by UHMK1 constitutes a mechanism of non-genetic resistance to targeted therapy in melanoma by controlling metabolic plasticity induced by therapy.
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Wegmann, F., et al.
(författare)
-
Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens
- 2012
-
Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 30:9
-
Tidskriftsartikel (refereegranskat)abstract
- Protection against mucosally transmitted infections probably requires immunity at the site of pathogen entry(1), yet there are no mucosal adjuvant formulations licensed for human use. Polyethyleneimine (PEI) represents a family of organic polycations used as nucleic acid transfection reagents in vitro and DNA vaccine delivery vehicles in vivo(2,3). Here we show that diverse PEI forms have potent mucosal adjuvant activity for viral subunit glycoprotein antigens. A single intranasal administration of influenza hemagglutinin or herpes simplex virus type-2 (HSV-2) glycoprotein D with PEI elicited robust antibody-mediated protection from an otherwise lethal infection, and was superior to existing experimental mucosal adjuvants. PEI formed nanoscale complexes with antigen, which were taken up by antigen-presenting cells in vitro and in vivo, promoted dendritic cell trafficking to draining lymph nodes and induced non-proinflammatory cytokine responses. PEI adjuvanticity required release of host double-stranded DNA that triggered Irf3-dependent signaling. PEI therefore merits further investigation as a mucosal adjuvant for human use.
|
|
| 44. |
- Abdelrazak Morsy, Mohammad Hamdy, et al.
(författare)
-
SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma
- 2024
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 143:19, s. 1953-1964
-
Tidskriftsartikel (refereegranskat)abstract
- Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara -C) resistance in several hematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara -C ef fi cacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMGbox containing protein 11 (SOX11) as a novel direct binding partner and fi rst known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identi fi ed SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar af fi nity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara -C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identi fi ed SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its fi rst known endogenous inhibitor with potentially important implications for clinical therapy strati fi cation.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Fennell, David A., et al.
(författare)
-
Tourism, animals & the vacant niche : a scoping review and pedagogical agenda
- 2024
-
Ingår i: Current Issues in Tourism. - : Routledge. - 1368-3500 .- 1747-7603. ; , s. 1-29
-
Tidskriftsartikel (refereegranskat)abstract
- The topic of animal ethics has advanced in tourism studies since its inception in 2000, based on a diverse range of studies on species involvement, types of uses and contexts, level of engagement, states of animals, and theoretical perspectives. While there is still considerable scope to amplify research on animal-based tourism, a gap exists in tourism pedagogy amidst the field’s emphasis on a new expanding consciousness platform. We review the depth of existing scholarship on animal ethics in tourism and develop an agenda for advancing animal ethics pedagogy for the future. Our intent is to issue a call to action for curriculum committees, programme administrators, and educators to recognise and act on this critical moral domain in tourism education.
|
|
| 48. |
- Lyon, Alexander R, et al.
(författare)
-
Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.
- 2016
-
Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 18:1, s. 8-27
-
Tidskriftsartikel (refereegranskat)abstract
- Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed.
|
|
| 49. |
- Mercer, Laina D., et al.
(författare)
-
Comparing universal kriging and land-use regression for predicting concentrations of gaseous oxides of nitrogen (NOx) for the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)
- 2011
-
Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 45:26, s. 4412-4420
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies that assess the health effects of long-term exposure to ambient air pollution are used to inform public policy. These studies rely on exposure models that use data collected from pollution monitoring sites to predict exposures at subject locations. Land-use regression (LUR) and universal kriging (UK) have been suggested as potential prediction methods. We evaluate these approaches on a dataset including measurements from three seasons in Los Angeles, CA. Methods: The measurements of gaseous oxides of nitrogen (NOx) used in this study are from a "snapshot" sampling campaign that is part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). The measurements in Los Angeles were collected during three two-week periods in the summer, autumn, and winter, each with about 150 sites. The design included clusters of monitors on either side of busy roads to capture near-field gradients of traffic-related pollution. LUR and UK prediction models were created using geographic information system (GIS)-based covariates. Selection of covariates was based on 10-fold cross-validated (CV) R-2 and root mean square error (RMSE). Since UK requires specialized software, a computationally simpler two-step procedure was also employed to approximate fitting the UK model using readily available regression and GIS software. Results: UK models consistently performed as well as or better than the analogous LUR models. The best CV R-2 values for season-specific UK models predicting log(NOx) were 0.75, 0.72, and 0.74 (CV RMSE 0.20, 0.17, and 0.15) for summer, autumn, and winter, respectively. The best CV R-2 values for season-specific LUR models predicting log(NOx) were 0.74, 0.60, and 0.67 (CV RMSE 0.20, 0.20, and 0.17). The two-stage approximation to UK also performed better than LUR and nearly as well as the full UK model with CV R-2 values 0.75, 0.70, and 0.70 (CV RMSE 0.20, 0.17, and 0.17) for summer, autumn, and winter, respectively. Conclusion: High quality LUR and UK prediction models for NOx in Los Angeles were developed for the three seasons based on data collected for MESA Air. In our study, UK consistently outperformed LUR. Similarly, the 2-step approach was more effective than the LUR models, with performance equal to or slightly worse than UK. (C) 2011 Elsevier Ltd. All rights reserved.
|
|
| 50. |
- Mourkas, Evangelos, et al.
(författare)
-
Host ecology regulates interspecies recombination in bacteria of the genus Campylobacter
- 2022
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd.. - 2050-084X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Horizontal gene transfer (HGT) can allow traits that have evolved in one bacterial species to transfer to another. This has potential to rapidly promote new adaptive trajectories such as zoonotic transfer or antimicrobial resistance. However, for this to occur requires gaps to align in barriers to recombination within a given time frame. Chief among these barriers is the physical separation of species with distinct ecologies in separate niches. Within the genus Campylobacter, there are species with divergent ecologies, from rarely isolated single-host specialists to multihost generalist species that are among the most common global causes of human bacterial gastroenteritis. Here, by characterizing these contrasting ecologies, we can quantify HGT among sympatric and allopatric species in natural populations. Analyzing recipient and donor population ancestry among genomes from 30 Campylobacter species, we show that cohabitation in the same host can lead to a six-fold increase in HGT between species. This accounts for up to 30% of all SNPs within a given species and identifies highly recombinogenic genes with functions including host adaptation and antimicrobial resistance. As described in some animal and plant species, ecological factors are a major evolutionary force for speciation in bacteria and changes to the host landscape can promote partial convergence of distinct species through HGT.
|
|
