| 1. |
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| 2. |
- Choularton, T. W., et al.
(author)
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The Great Dun Fell Cloud Experiment 1993 : An overview
- 1997
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In: Atmospheric Environment. - 1352-2310. ; 31:16, s. 2393-2405
-
Journal article (peer-reviewed)abstract
- The 1993 Ground-based Cloud Experiment on Great Dun Fell used a wide range of measurements of trace gases, aerosol particles and cloud droplets at five sites to study their sources and sinks especially those in cloud. These measurements have been interpreted using a variety of models. The conclusions add to our knowledge of air pollution, acidification of the atmosphere and the ground, eutrophication and climate change. The experiment is designed to use the hill cap cloud as a flow-through reactor, and was conducted in varying levels of pollution typical of much of the rural temperate continental northern hemisphere in spring-time.
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| 3. |
- Gordon, I.E., et al.
(author)
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The HITRAN2020 molecular spectroscopic database
- 2022
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In: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier. - 0022-4073 .- 1879-1352. ; 277
-
Journal article (peer-reviewed)abstract
- The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years). All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules. The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition.
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| 4. |
- Oostrum, L. C., et al.
(author)
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Repeating fast radio bursts with WSRT/Apertif
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
-
Journal article (peer-reviewed)abstract
- Context. Repeating fast radio bursts (FRBs) present excellent opportunities to identify FRB progenitors and host environments as well as to decipher the underlying emission mechanism. Detailed studies of repeating FRBs might also hold clues as to the origin of FRBs as a population. Aims. We aim to detect bursts from the first two repeating FRBs, FRB 121102 (R1) and FRB 180814.J0422+73 (R2), and to characterise their repeat statistics. We also want to significantly improve the sky localisation of R2 and identify its host galaxy. Methods. We used the Westerbork Synthesis Radio Telescope to conduct extensive follow-up of these two repeating FRBs. The new phased-array feed system, Apertif, allows one to cover the entire sky position uncertainty of R2 with fine spatial resolution in a single pointing. The data were searched for bursts around the known dispersion measures of the two sources. We characterise the energy distribution and the clustering of detected R1 bursts. Results. We detected 30 bursts from R1. The non-Poissonian nature is clearly evident from the burst arrival times, which is consistent with earlier claims. Our measurements indicate a dispersion measure (DM) of 563.5(2) pc cm(-3), suggesting a significant increase in DM over the past few years. Assuming a constant position angle across the burst, we place an upper limit of 8% on the linear polarisation fraction for the brightest burst in our sample. We did not detect any bursts from R2. Conclusions. A single power-law might not fit the R1 burst energy distribution across the full energy range or widely separated detections. Our observations provide improved constraints on the clustering of R1 bursts. Our stringent upper limits on the linear polarisation fraction imply a significant depolarisation, either intrinsic to the emission mechanism or caused by the intervening medium at 1400 MHz, which is not observed at higher frequencies. The non-detection of any bursts from R2, despite nearly 300 h of observations, implies either a highly clustered nature of the bursts, a steep spectral index, or a combination of the two assuming that the source is still active. Another possibility is that R2 has turned off completely, either permanently or for an extended period of time.
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| 5. |
- Li, M, et al.
(author)
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Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.
- 2014
-
In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 19:4
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10−5, odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10−6). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.
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| 6. |
- Sherwood, S. C., et al.
(author)
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An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence
- 2020
-
In: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 58:4
-
Research review (peer-reviewed)abstract
- We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult-to-quantify uncertainties and different priors. The 66% range is 2.6-3.9 K for our Baseline calculation and remains within 2.3-4.5 K under the robustness tests; corresponding 5-95% ranges are 2.3-4.7 K, bounded by 2.0-5.7 K (although such high-confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing-feedback paradigm for interpreting past changes.
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| 7. |
- Tye, Andrew M., et al.
(author)
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Dissolved inorganic carbon export from rivers of Great Britain : Spatial distribution and potential catchment-scale controls
- 2022
-
In: Journal of Hydrology. - : Elsevier. - 0022-1694 .- 1879-2707. ; 615
-
Journal article (peer-reviewed)abstract
- Dissolved inorganic carbon (DIC) fluxes from the land to ocean have been quantified for many rivers globally. However, CO2 fluxes to the atmosphere from inland waters are quantitatively significant components of the global carbon cycle that are currently poorly constrained. Understanding, the relative contributions of natural and human-impacted processes on the DIC cycle within catchments may provide a basis for developing improved management strategies to mitigate free CO2 concentrations in rivers and subsequent evasion to the atmosphere. Here, a large, internally consistent dataset collected from 41 catchments across Great Britain (GB), accounting for ∼36% of land area (∼83,997 km2) and representative of national land cover, was used to investigate catchment controls on riverine dissolved inorganic carbon (DIC), bicarbonate (HCO3−) and free CO2 concentrations, fluxes to the coastal sea and annual yields per unit area of catchment. Estimated DIC flux to sea for the survey catchments was 647 kt DIC yr−1 which represented 69% of the total dissolved carbon flux from these catchments. Generally, those catchments with large proportions of carbonate and sedimentary sandstone were found to deliver greater DIC and HCO3− to the ocean. The calculated mean free CO2 yield for survey catchments (i.e. potential CO2 emission to the atmosphere) was 0.56 t C km−2 yr−1. Regression models demonstrated that whilst river DIC (R2 = 0.77) and HCO3− (R2 = 0.77) concentrations are largely explained by the geology of the landmass, along with a negative correlation to annual precipitation, free CO2 concentrations were strongly linked to catchment macronutrient status. Overall, DIC dominates dissolved C inputs to coastal waters, meaning that estuarine carbon dynamics are sensitive to underlying geology and therefore are likely to be reasonably constant. In contrast, potential losses of carbon to the atmosphere via dissolved CO2, which likely constitute a significant fraction of net terrestrial ecosystem production and hence the national carbon budget, may be amenable to greater direct management via altering patterns of land use.
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| 8. |
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| 9. |
- Eng, W., et al.
(author)
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Occupancy of human brain GABA(A) receptors by the novel alpha 5 subtype-selective benzodiazepine site inverse agonist alpha 5IA as measured using [C-11]flumazenil PET imaging
- 2010
-
In: Neuropharmacology. - : Elsevier BV. - 0028-3908 .- 1873-7064. ; 59:7-8, s. 635-639
-
Journal article (peer-reviewed)abstract
- GABA(A) receptor alpha 5-selective inverse agonists enhance cognitive performance in pre-clinical species. However, a key aspect of the clinical development of such compounds is the demonstration that in man such compounds are devoid of the anxiogenic-like activity associated with non-selective inverse agonists such as FG 7142. The triazolophthalazine alpha 5IA (3-(5-methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-yl) methyloxy]-1,2,4-triazolo[3,4-a]phthalazine) is an alpha 5-selective inverse agonist which enhances cognitive performance in rodents and encouragingly in human Phase I Safety and Tolerability studies it was devoid of the anxiogenic-like activity associated with FG 7142. However, in order to appropriately interpret this latter observation, it was considered important to demonstrate that the absence of anxiogenic-like activity occurs at significant levels of receptor occupancy. Consequently, the occupancy of human brain GABAA receptors was measured using [C-11]flumazenil positron emission tomography in three healthy normal young male volunteers following a single oral dose of 2 mg alpha 5IA. One hour after dosing, mean occupancy levels were 53% and this fell to 16% by 8 h post-dose, with the plasma alpha 5IA concentration corresponding to 50% occupancy being 10 ng/mL. These data clearly show that an alpha 5-selective inverse agonist is not associated with anxiogenic-like side effects at doses that give 50% occupancy.
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| 10. |
- Garcia-Martin, E. Elena, et al.
(author)
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Sources, Composition, and Export of Particulate Organic Matter Across British Estuaries
- 2023
-
In: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 128:4
-
Journal article (peer-reviewed)abstract
- Estuaries receive and process a large amount of particulate organic carbon (POC) prior to its export into coastal waters. Studying the origin of this POC is key to understanding the fate of POC and the role of estuaries in the global carbon cycle. Here, we evaluated the concentrations of POC, as well as particulate organic nitrogen (PON), and used stable carbon and nitrogen isotopes to assess their sources across 13 contrasting British estuaries during five different sampling campaigns over 1 year. We found a high variability in POC and PON concentrations across the salinity gradient, reflecting inputs, and losses of organic material within the estuaries. Catchment land cover appeared to influence the contribution of POC to the total organic carbon flux from the estuary to coastal waters, with POC contributions >36% in estuaries draining catchments with a high percentage of urban/suburban land, and <11% in estuaries draining catchments with a high peatland cover. There was no seasonal pattern in the isotopic composition of POC and PON, suggesting similar sources for each estuary over time. Carbon isotopic ratios were depleted (-26.7 +/- 0.42 parts per thousand, average +/- sd) at the lowest salinity waters, indicating mainly terrigenous POC (TPOC). Applying a two-source mixing model, we observed high variability in the contribution of TPOC at the highest salinity waters between estuaries, with a median value of 57%. Our results indicate a large transport of terrigenous organic carbon into coastal waters, where it may be buried, remineralized, or transported offshore. Plain Language Summary Estuaries transport and process a large amount terrigenous particulate organic matter (i.e., carbon and nitrogen) prior to its export to coastal waters. In order to understand the fate of organic carbon and the role of estuaries in the global carbon cycle it is essential to improve our knowledge on its composition, origin, and amount of carbon transported. We quantified the elemental concentrations and stable isotopes composition of carbon and nitrogen to quantify the amount of terrigenous particulate organic matter transported by 13 British estuaries, which drain catchments of diverse land cover under different hydrological conditions. We found a great variability in particulate organic carbon (POC) and particulate organic nitrogen concentrations across the salinity gradient, implying inputs, and losses of material within the estuaries. Each estuary had similar sources of particulate material throughout the year. In most of the estuaries, the POC had a terrigenous origin at the lowest salinity waters. The terrigenous organic carbon contribution decreased toward coastal waters with an average contribution of 57% at the highest salinity waters, indicating a large transport of terrigenous organic carbon into coastal waters.
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| 11. |
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| 12. |
- Kumar, Nitin, et al.
(author)
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Adaptation of host transmission cycle during Clostridium difficile speciation
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:9, s. 1315-1320
-
Journal article (peer-reviewed)abstract
- Bacterial speciation is a fundamental evolutionary process characterized by diverging genotypic and phenotypic properties. However, the selective forces that affect genetic adaptations and how they relate to the biological changes that underpin the formation of a new bacterial species remain poorly understood. Here, we show that the spore-forming, healthcare-associated enteropathogen Clostridium difficile is actively undergoing speciation. Through large-scale genomic analysis of 906 strains, we demonstrate that the ongoing speciation process is linked to positive selection on core genes in the newly forming species that are involved in sporulation and the metabolism of simple dietary sugars. Functional validation shows that the new C. difficile produces spores that are more resistant and have increased sporulation and host colonization capacity when glucose or fructose is available for metabolism. Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple dietary sugars and producing high levels of resistant spores, that is adapted for healthcare-mediated transmission.
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| 13. |
- Sofieva, V. F., et al.
(author)
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Harmonized dataset of ozone profiles from satellite limb and occultation measurements
- 2013
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In: Earth System Science Data. - : Copernicus GmbH. - 1866-3516 .- 1866-3508. ; 5:2, s. 349-363
-
Journal article (peer-reviewed)abstract
- In this paper, we present a HARMonized dataset of OZone profiles (HARMOZ) based on limb and occultation measurements from Envisat (GOMOS, MIPAS and SCIAMACHY), Odin (OSIRIS, SMR) and SCISAT (ACE-FTS) satellite instruments. These measurements provide high-vertical-resolution ozone profiles covering the altitude range from the upper troposphere up to the mesosphere in years 2001–2012. HARMOZ has been created in the framework of the European Space Agency Climate Change Initiative project.The harmonized dataset consists of original retrieved ozone profiles from each instrument, which are screened for invalid data by the instrument teams. While the original ozone profiles are presented in different units and on different vertical grids, the harmonized dataset is given on a common pressure grid in netCDF (network common data form)-4 format. The pressure grid corresponds to vertical sampling of ~ 1 km below 20 km and 2–3 km above 20 km. The vertical range of the ozone profiles is specific for each instrument, thus all information contained in the original data is preserved. Provided altitude and temperature profiles allow the representation of ozone profiles in number density or mixing ratio on a pressure or altitude vertical grid. Geolocation, uncertainty estimates and vertical resolution are provided for each profile. For each instrument, optional parameters, which are related to the data quality, are also included.For convenience of users, tables of biases between each pair of instruments for each month, as well as bias uncertainties, are provided. These tables characterize the data consistency and can be used in various bias and drift analyses, which are needed, for instance, for combining several datasets to obtain a long-term climate dataset.This user-friendly dataset can be interesting and useful for various analyses and applications, such as data merging, data validation, assimilation and scientific research.The dataset is available at http://www.esa-ozone-cci.org/?q=node/161 or at doi:10.5270/esa-ozone_cci-limb_occultation_profiles-2001_2012-v_1-201308.
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| 14. |
- Alef, Walter, et al.
(author)
-
BRAND - The next generation receiver for VLBI
- 2018
-
In: Proceedings of Science. - Trieste, Italy : Sissa Medialab. - 1824-8039. ; 344
-
Conference paper (peer-reviewed)abstract
- The aim of the BRAND EVN project is to build a very wide receiver prototype for primary focus with a frequency range from 1.5 GHz to 15.5 GHz In addition we will investigate solutions for secondary focus telescopes. The project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 730562 [RadioNet]. We present the status of the project which was started on January 1st, 2017 and is progressing smoothly: Feed, LNA, filters, major digital components, and some of the firmware are available now. © Copyright owned by the author(s) under the terms of the Creative Commons.
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| 15. |
- Ali, Hassan, et al.
(author)
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Vibrational spectroscopic characterisation of salmeterol xinafoate polymorphs and a preliminary investigation of their transformation using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry
- 2008
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In: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670 .- 1873-4324. ; 620:1-2, s. 103-12
-
Journal article (peer-reviewed)abstract
- Knowledge and control of the polymorphic phases of chemical compounds are important aspects of drug development in the pharmaceutical industry. Salmeterol xinafoate, a long acting beta-adrenergic receptor agonist, exists in two polymorphic Forms, I and II. Raman and near infrared spectra were obtained of these polymorphs at selected wavelengths in the range of 488-1064 nm; significant differences in the Raman and near-infrared spectra were apparent and key spectral marker bands have been identified for the vibrational spectroscopic characterisation of the individual polymorphs which were also characterised with X ray diffractometry. The solid-state transition of salmeterol xinafoate polymorphs was studied using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry isothermally between transitions. This method assisted in the unambiguous characterisation of the two polymorphic forms by providing a simultaneous probe of both the thermal and vibrational data. The study demonstrates the value of a rapid in situ analysis of a drug polymorph which can be of potential value for at-line in-process control
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| 16. |
- Annan, James D., et al.
(author)
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A new global surface temperature reconstruction for the Last Glacial Maximum
- 2022
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 18:8, s. 1883-1896
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Journal article (peer-reviewed)abstract
- We present a new reconstruction of surface air temperature and sea surface temperature for the Last Glacial Maximum. The method blends model fields and sparse proxy-based point estimates through a data assimilation approach. Our reconstruction updates that of Annan and Hargreaves (2013), using the full range of general circulation model (GCM) simulations which contributed to three generations of the PMIP database, three major compilations of gridded sea surface temperature (SST) and surface air temperature (SAT) estimates from proxy data, and an improved methodology based on an ensemble Kalman filter. Our reconstruction has a global annual mean surface air temperature anomaly of −4.5 ± 0.9◦C relative to the pre-industrial climate. This is slightly colder than the previous estimate of Annan and Hargreaves (2013), with an upwards revision on the uncertainty due to different methodological assumptions. It is, however, substantially less cold than the recent reconstruction of Tierney et al. (2020). We show that the main reason for this discrepancy is in the choice of prior. We recommend the use of the multi-model ensemble of opportunity as potentially offering a credible prior, but it is important that the range of models included in the PMIP ensembles represent the main sources of uncertainty as realistically and comprehensively as practicable if they are to be used in this way.
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| 17. |
- Annan, James D., et al.
(author)
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What could we learn about climate sensitivity from variability in the surface temperature record?
- 2020
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In: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 11:3, s. 709-719
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Journal article (peer-reviewed)abstract
- We examine what can be learnt about climate sensitivity from variability in the surface air temperature record over the instrumental period, from around 1880 to the present. While many previous studies have used trends in observational time series to constrain equilibrium climate sensitivity, it has also been argued that temporal variability may also be a powerful constraint. We explore this question in the context of a simple widely used energy balance model of the climate system. We consider two recently proposed summary measures of variability and also show how the full information content can be optimally used in this idealised scenario. We find that the constraint provided by variability is inherently skewed, and its power is inversely related to the sensitivity itself, discriminating most strongly between low sensitivity values and weakening substantially for higher values. It is only when the sensitivity is very low that the variability can provide a tight constraint. Our investigations take the form of perfect model experiments, in which we make the optimistic assumption that the model is structurally perfect and all uncertainties (including the true parameter values and nature of internal variability noise) are correctly characterised. Therefore the results might be interpreted as a best-case scenario for what we can learn from variability, rather than a realistic estimate of this. In these experiments, we find that for a moderate sensitivity of 2.5 degrees C, a 150-year time series of pure internal variability will typically support an estimate with a 5 %-95% range of around 5 degrees C (e.g. 1.9-6.8 degrees C). Total variability including that due to the forced response, as inferred from the detrended observational record, can provide a stronger constraint with an equivalent 5 %-95 % posterior range of around 4 degrees C (e.g. 1.8-6.0 degrees C) even when uncertainty in aerosol forcing is considered. Using a statistical summary of variability based on autocorrelation and the magnitude of residuals after detrending proves somewhat less powerful as a constraint than the full time series in both situations. Our results support the analysis of variability as a potentially useful tool in helping to constrain equilibrium climate sensitivity but suggest caution in the interpretation of precise results.
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| 18. |
- Brierley, Chris M., et al.
(author)
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Large-scale features and evaluation of the PMIP4-CMIP6 midHolocene simulations
- 2020
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:5, s. 1847-1872
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Journal article (peer-reviewed)abstract
- The mid-Holocene (6000 years ago) is a standard time period for the evaluation of the simulated response of global climate models using palaeoclimate reconstructions. The latest mid-Holocene simulations are a palaeoclimate entry card for the Palaeoclimate Model Intercomparison Project (PMIP4) component of the current phase of the Coupled Model Intercomparison Project (CMIP6) - hereafter referred to as PMIP4-CMIP6. Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the Northern Hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of -0.3 K, which is -0.2K cooler than the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe, and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of emergent constraints on the hydrological cycle, feedback strength, and potentially climate sensitivity.
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| 19. |
- Bugiardini, Enrico, et al.
(author)
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MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy
- 2019
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 28:16, s. 2711-2719
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Journal article (peer-reviewed)abstract
- Mitochondrial disorders are clinically and genetically heterogeneous and are associated with a variety of disease mechanisms. Defects of mitochondrial protein synthesis account for the largest subgroup of disorders manifesting with impaired respiratory chain capacity; yet, only a few have been linked to dysfunction in the protein components of the mitochondrial ribosomes. Here, we report a subject presenting with dyskinetic cerebral palsy and partial agenesis of the corpus callosum, while histochemical and biochemical analyses of skeletal muscle revealed signs of mitochondrial myopathy. Using exome sequencing, we identified a homozygous variant c.215C>T in MRPS25, which encodes for a structural component of the 28S small subunit of the mitochondrial ribosome (mS25). The variant segregated with the disease and substitutes a highly conserved proline residue with leucine (p.P72L) that, based on the high-resolution structure of the 28S ribosome, is predicted to compromise inter-protein contacts and destabilize the small subunit. Concordant with the in silico analysis, patient's fibroblasts showed decreased levels of MRPS25 and other components of the 28S subunit. Moreover, assembled 28S subunits were scarce in the fibroblasts with mutant mS25 leading to impaired mitochondrial translation and decreased levels of multiple respiratory chain subunits. Crucially, these abnormalities were rescued by transgenic expression of wild-type MRPS25 in the mutant fibroblasts. Collectively, our data demonstrate the pathogenicity of the p.P72L variant and identify MRPS25 mutations as a new cause of mitochondrial translation defect.
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| 20. |
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| 21. |
- Chattopadhyay, G., et al.
(author)
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Modelling and analysis of rail maintenance cost
- 2007
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In: International Journal of Production Economics. - : Elsevier BV. - 0925-5273 .- 1873-7579. ; 105:2, s. 475-482
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Journal article (peer-reviewed)abstract
- Lubrication at wheel flange and rails on sharp curves is considered as an effective solution for reducing wear loss of material from effective cross-section of rail and wheels. Rail administrations around the world have been increasing axle loads and traffic densities in rail networks. This has led to traffic initiated wear, fatigue initiated surface cracks and rail breaks. Limited research has been carried out on the overall impact of combining lubrication strategies and rail grinding. This paper presents a model for lubrication strategy and rail-grinding interval to reduce wear and rolling contact fatigue (RCF). Data from rail industry is collected and used for numerical illustration.
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| 22. |
- Chattopadhyay, G., et al.
(author)
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Rail-wheel lubrication : A conceptual decision model
- 2005
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In: International Conference on Operations Research Applications in Infrastructure Development in conjunction with the 2005 Annual Convention of Operational Research Society of India (ICORAID-2005-ORSI).
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Conference paper (peer-reviewed)
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| 23. |
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| 24. |
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| 25. |
- Erondu, Ngozi, et al.
(author)
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Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults
- 2006
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 4:4, s. 275-282
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Journal article (peer-reviewed)abstract
- Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonism of NPY Y1 and NPY Y5 receptors (NPYxR) is considered a potentially important anti-obesity drug target. We tested the hypothesis that blockade of the NPY5R will lead to weight loss in humans using MIK-0557, a potent, highly selective, orally active NPY5R antagonist. The initial series of experiments reported herein, including a multiple-dose positron-emission tomography study and a 12 week proof-of concept/dose-ranging study, suggested an optimal MK-0557 dose of 1 mg/day. The hypothesis was then tested in a 52 week, multicenter, randomized, double-blind, placebo-controlled trial involving 1661 overweight and obese patients. Although statistically significant at 52 weeks, the magnitude of induced weight loss was not clinically meaningful. These observations provide the first clinical insight into the human NPY-energy homeostatic pathway and suggest that solely targeting the NPY5R in future drug development programs is unlikely to produce therapeutic efficacy.
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| 26. |
- Fearon, Elizabeth, et al.
(author)
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Associations between friendship characteristics and HIV and HSV-2 status amongst young South African women in HPTN-068
- 2017
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In: Journal of the International AIDS Society. - : John Wiley & Sons. - 1758-2652. ; 20
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Journal article (peer-reviewed)abstract
- Introduction: Prevalence of HIV among young women in South Africa remains extremely high. Adolescent peer groups have been found to be an important influence on a range of health behaviours. The characteristics of young women's friendships might influence their sexual health and HIV risk via connections to sexual partners, norms around sexual initiation and condom use, or provision of social support. We investigated associations between young women's friendships and their Herpes Simplex Virus Type 2 (HSV-2) and HIV infection status in rural South Africa. Methods: Our study is a cross-sectional, egocentric network analysis. In 2011 to 2012, we tested 13- to 20-year-old young women for HIV and HSV-2, and collected descriptions of five friendships for each. We generated summary measures describing friend socio-demographic characteristics and the number of friends perceived to have had sex. We used logistic regression to analyse associations between friend characteristics and participant HIV and HSV-2 infection, excluding likely perinatal HIV infections. Results: There were 2326 participants included in the study sample, among whom HIV and HSV-2 prevalence were 3.3% and 4.6% respectively. Adjusted for participant and friend socio-demographic characteristics, each additional friend at least one year older than the participant was associated with raised odds of HIV (odds ratio (OR)=1.37, 95% CI 1.03 to 1.82) and HSV-2 (adjusted OR=1.41, 95% CI 1.18 to 1.69). Each additional friend perceived to have ever had sex also raised the odds of HIV (OR=1.29, 95% CI 1.03 to 1.63) and HSV-2 (OR=1.18, 95% CI 1.03 to 1.35). Discussion: We found good evidence that a greater number of older friends and friends perceived to have had sex were associated with increased risk for HSV-2 and HIV infection among young women. Conclusions: The characteristics of young women's friendships could contribute to their risk of HIV infection. The extent to which policies or programmes influence age-mixing and young women's normative environments should be considered.
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| 27. |
- Fearon, Elizabeth, et al.
(author)
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Friendships Among Young South African Women, Sexual Behaviours and Connections to Sexual Partners (HPTN 068)
- 2019
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In: Aids and Behavior. - : Springer. - 1090-7165 .- 1573-3254. ; 23:6, s. 1471-1483
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Journal article (peer-reviewed)abstract
- Friends could be influential on young women's sexual health via influences on sexual behaviours and as connections to sexual partners, but are understudied in sub-Saharan Africa. We cross-sectionally surveyed 2326 13-20year-old young women eligible for grades 8-11 in rural South Africa about their sexual behaviour and up to three sexual partners. Participants each described five specific but unidentified friends and the relationships between them in an egocentric' network analysis design. We used logistic regression to investigate associations between friendship characteristics and participants' reports of ever having had sex (n=2326) and recent condom use (n=457). We used linear regression with random effects by participant to investigate friendship characteristics and age differences with sexual partners (n=633 participants, 1051 partners). We found that it was common for friends to introduce young women to those who later became sexual partners, and having older friends was associated with having older sexual partners, (increase of 0.37years per friend at least 1year older, 95% CI 0.21-0.52, adjusted). Young women were more likely to report ever having had sex when more friends were perceived to be sexually active (adjusted OR 1.85, 95% CI 1.72-2.01 per friend) and when they discussed sex, condoms and HIV with friends. Perception of friends' condom use was not associated with participants' reported condom use. While this study is preliminary and unique in this population and further research should be conducted, social connections between friends and sexual partners and perceptions of friend sexual behaviours could be considered in the design of sexual health interventions for young women in South Africa.
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| 31. |
- Rahpoe, N., et al.
(author)
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Relative drifts and biases between six ozone limb satellite measurements from the last decade
- 2015
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In: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 8:10, s. 4369-4381
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Journal article (peer-reviewed)abstract
- As part of European Space Agency's (ESA) climate change initiative, high vertical resolution ozone profiles from three instruments all aboard ESA's Envisat (GOMOS, MIPAS, SCIAMACHY) and ESA's third party missions (OSIRIS, SMR, ACE-FTS) are to be combined in order to create an essential climate variable data record for the last decade. A prerequisite before combining data is the examination of differences and drifts between the data sets. In this paper, we present a detailed analysis of ozone profile differences based on pairwise collocated measurements, including the evolution of the differences with time. Such a diagnosis is helpful to identify strengths and weaknesses of each data set that may vary in time and introduce uncertainties in long-term trend estimates. The analysis reveals that the relative drift between the sensors is not statistically significant for most pairs of instruments. The relative drift values can be used to estimate the added uncertainty in physical trends. The added drift uncertainty is estimated at about 3 % decade-1 (1s). Larger differences and variability in the differences are found in the lowermost stratosphere (below 20 km) and in the mesosphere.
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| 32. |
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| 36. |
- Shepheard, S, et al.
(author)
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Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370
- 1999
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 19:10, s. 851-858
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Journal article (peer-reviewed)abstract
- This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10−5 M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg−1, iv) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg−1, iv) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg−1, iv), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg−1, iv. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.
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| 37. |
- Williamson, Jennifer L., et al.
(author)
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Landscape controls on riverine export of dissolved organic carbon from Great Britain
- 2021
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In: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X.
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Journal article (peer-reviewed)abstract
- The dissolved organic carbon (DOC) export from land to ocean via rivers is a significant term in the global C cycle, and has been modified in many areas by human activity. DOC exports from large global rivers are fairly well quantified, but those from smaller river systems, including those draining oceanic regions, are generally under-represented in global syntheses. Given that these regions typically have high runoff and high peat cover, they may exert a disproportionate influence on the global land–ocean DOC export. Here we describe a comprehensive new assessment of the annual riverine DOC export to estuaries across the island of Great Britain (GB), which spans the latitude range 50–60° N with strong spatial gradients of topography, soils, rainfall, land use and population density. DOC yields (export per unit area) were positively related to and best predicted by rainfall, peat extent and forest cover, but relatively insensitive to population density or agricultural development. Based on an empirical relationship with land use and rainfall we estimate that the DOC export from the GB land area to the freshwater-seawater interface was 1.15 Tg C year−1 in 2017. The average yield for GB rivers is 5.04 g C m−2 year−1, higher than most of the world’s major rivers, including those of the humid tropics and Arctic, supporting the conclusion that under-representation of smaller river systems draining peat-rich areas could lead to under-estimation of the global land–ocean DOC export. The main anthropogenic factor influencing the spatial distribution of GB DOC exports appears to be upland conifer plantation forestry, which is estimated to have raised the overall DOC export by 0.168 Tg C year−1. This is equivalent to 15% of the estimated current rate of net CO2 uptake by British forests. With the UK and many other countries seeking to expand plantation forest cover for climate change mitigation, this ‘leak in the ecosystem’ should be incorporated in future assessments of the CO2 sequestration potential of forest planting strategies.
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| 38. |
- Hargreaves, D., et al.
(author)
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- 2004
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Reports (peer-reviewed)
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