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1.
  • Glasbey, JC, et al. (author)
  • 2021
  • swepub:Mat__t
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  • Adams, D., et al. (author)
  • Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
  • 2018
  • In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:1, s. 11-21
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters] x albumin level in grams per liter; lower values indicated worse nutritional status).RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (+/- SD) mNIS+7 at baseline was 80.9 +/- 41.5 in the patisiran group and 74.6 +/- 37.0 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.0 +/- 1.7 versus 28.0 +/- 2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (+/- SD) baseline Norfolk QOL-DN score was 59.6 +/- 28.2 in the patisiran group and 55.5 +/- 24.3 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.7 +/- 1.8 versus 14.4 +/- 2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08 +/- 0.02 m per second with patisiran versus -0.24 +/- 0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7 +/- 9.6 versus -119.4 +/- 14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups.CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis.
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  • Martin, W. P., et al. (author)
  • Obesity is common in chronic kidney disease and associates with greater antihypertensive usage and proteinuria: evidence from a cross-sectional study in atertiary nephrology centre
  • 2020
  • In: Clinical Obesity. - : Wiley. - 1758-8103 .- 1758-8111. ; 10:6
  • Journal article (peer-reviewed)abstract
    • Obesity is a treatable risk factor for chronic kidney disease progression. We audited the reporting of body-mass index in nephrology outpatient clinics to establish the characteristics of individuals with obesity in nephrology practice. Body-mass index, clinical information and biochemical measures were recorded for patients attending clinics between 3(rd)August, 2018 and 18(th)January, 2019. Inferential statistics and Pearson correlations were used to investigate relationships between body-mass index, type 2 diabetes, hypertension and proteinuria. Mean +/- SD BMI was 28.6 +/- 5.8 kg/m(2)(n = 374). Overweight and obesity class 1 were more common in males (P= .02). Amongst n = 123 individuals with obesity and chronic kidney disease, mean +/- SD age, n (%) female and median[IQR] eGFR were 64.1 +/- 14.2 years, 52 (42.3%) and 29.0[20.5] mL/min/BSA, respectively. A positive correlation between increasing body-mass index and proteinuria was observed in such patients (r= 0.21,P= .03), which was stronger in males and those with CKD stages 4 and 5. Mean body-mass index was 2.3 kg/m(2)higher in those treated with 4-5 versus 0-1 antihypertensives (P= .03). Amongst n = 59 patients with obesity, chronic kidney disease and type 2 diabetes, 2 (3.5%) and 0 (0%) were prescribed a GLP-1 receptor analogue and SGLT2-inhibitor, respectively. Our data provides a strong rationale not only for measuring body-mass index but also for acting on the information in nephrology practice, although prospective studies are required to guide treatment decisions in people with obesity and chronic kidney disease.
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  • Pöntinen, M., et al. (author)
  • Euclid: Identification of asteroid streaks in simulated images using deep learning
  • 2023
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
  • Journal article (peer-reviewed)abstract
    • The material composition of asteroids is an essential piece of knowledge in the quest to understand the formation and evolution of the Solar System. Visual to near-infrared spectra or multiband photometry is required to constrain the material composition of asteroids, but we currently have such data, especially in the near-infrared wavelengths, for only a limited number of asteroids. This is a significant limitation considering the complex orbital structures of the asteroid populations. Up to 150 000 asteroids will be visible in the images of the upcoming ESA Euclid space telescope, and the instruments of Euclid will offer multiband visual to near-infrared photometry and slitless near-infrared spectra of these objects. Most of the asteroids will appear as streaks in the images. Due to the large number of images and asteroids, automated detection methods are needed. A non-machine-learning approach based on the Streak Det software was previously tested, but the results were not optimal for short and/or faint streaks. We set out to improve the capability to detect asteroid streaks in Euclid images by using deep learning. We built, trained, and tested a three-step machine-learning pipeline with simulated Euclid images. First, a convolutional neural network (CNN) detected streaks and their coordinates in full images, aiming to maximize the completeness (recall) of detections. Then, a recurrent neural network (RNN) merged snippets of long streaks detected in several parts by the CNN. Lastly, gradient-boosted trees (XGBoost) linked detected streaks between different Euclid exposures to reduce the number of false positives and improve the purity (precision) of the sample. The deep-learning pipeline surpasses the completeness and reaches a similar level of purity of a non-machine-learning pipeline based on the StreakDet software. Additionally, the deep-learning pipeline can detect asteroids 0.25–0.5 magnitudes fainter than StreakDet. The deep-learning pipeline could result in a 50% increase in the number of detected asteroids compared to the StreakDet software. There is still scope for further refinement, particularly in improving the accuracy of streak coordinates and enhancing the completeness of the final stage of the pipeline, which involves linking detections across multiple exposures.
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  • Denoncourt, R. N., et al. (author)
  • Burden of Illness for Patients with Hereditary Attr Amyloidosis with Polyneuropathy Begins with Symptom Onset and Increases with Disease Progression
  • 2016
  • In: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 19:7, s. A436-A436
  • Journal article (peer-reviewed)abstract
    • Objectives: Hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN), also known as familial amyloidotic polyneuropathy (FAP), is an inherited, progressive disease leading to death within 5-15 years. hATTR-PN is due to a mutation in the transthyretin (TTR) gene. Patisiran is an investigational, RNA interference (RNAi) therapeutic targeting TTR. This abstract aims to further characterize hATTR-PN burden of illness.Methods: The ongoing, patisiran Phase 3 APOLLO trial was utilized to collect patient-reported EQ-5D, Norfolk-DN, Rasch-built Overall Disability Scale (R-ODS), and healthcare resource utilization from hATTR-PN patients with symptomatic disease.Results: APOLLO included 225 patients; median age of 62 years (range: 24-82), median neurological impairment score (NIS) of 6-141.6 and representative of the global patient population (19 countries) with a broad range of mutations and disease severities. At baseline, 57 patients had a Polyneuropathy Disability (PND) Score I and 168 patients had a PND Score ≥ II. By FAP Stage, 104 were FAP Stage 1 and 121 were FAP Stage 2. 41 patients (PND Score ≥ II) reported ≥1 hospitalization of ≥3 nights in duration due to hATTR-PN in the 12 months prior to enrollment. Mean EQ-5D scores were 0.76 (PND Score I) and 0.59 (PND Score ≥ II). Patients reported perceived health status on the EQ-VAS with mean scores of 66.9 (PND Score I) and 51.3 (PND Score ≥ II). Mean Norfolk-QoL-DN scores were 35.5 (PND Score I) and 66.0 (PND Score ≥ II). 145 patients (131 PND Score ≥ II) reported they cannot work because of hATTR-PN. Mean R-ODS scores were 40.9 and 25.9 for PND Score I and PND Score ≥ II, respectively.Conclusions: These data, from the largest controlled study of patients with hATTR-PN to date, further demonstrate that patients experience considerable burden of illness early in the course of disease and this burden increases with disease progression.
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11.
  • Green, Jonathan M. H., et al. (author)
  • Research priorities for managing the impacts and dependencies of business upon food, energy, water and the environment
  • 2017
  • In: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 12:2, s. 319-331
  • Journal article (peer-reviewed)abstract
    • Delivering access to sufficient food, energy and water resources to ensure human wellbeing is a major concern for governments worldwide. However, it is crucial to account for the 'nexus' of interactions between these natural resources and the consequent implications for human wellbeing. The private sector has a critical role in driving positive change towards more sustainable nexus management and could reap considerable benefits from collaboration with researchers to devise solutions to some of the foremost sustainability challenges of today. Yet opportunities are missed because the private sector is rarely involved in the formulation of deliverable research priorities. We convened senior research scientists and influential business leaders to collaboratively identify the top forty questions that, if answered, would best help companies understand and manage their food-energy-water-environment nexus dependencies and impacts. Codification of the top order nexus themes highlighted research priorities around development of pragmatic yet credible tools that allow businesses to incorporate nexus interactions into their decision-making; demonstration of the business case for more sustainable nexus management; identification of the most effective levers for behaviour change; and understanding incentives or circumstances that allow individuals and businesses to take a leadership stance. Greater investment in the complex but productive relations between the private sector and research community will create deeper and more meaningful collaboration and cooperation.
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  • Finnerty, N. J., et al. (author)
  • Brain nitric oxide: Regional characterisation of a real-time microelectrochemical sensor
  • 2012
  • In: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270. ; 209:1, s. 13-21
  • Journal article (peer-reviewed)abstract
    • A reliable method of directly measuring endogenously generated nitric oxide (NO) in real-time and in various brain regions is presented. An extensive characterisation of a previously described amperometric sensor has been carried out in the prefrontal cortex and nucleus accumbens of freely moving rats. Systemic administration of saline caused a transient increase in signal from baseline levels in both the prefrontal cortex (13 +/- 3 pA, n = 17) and nucleus accumbens (12 +/- 3 pA, n = 8). NO levels in the prefrontal cortex were significantly increased by 43 +/- 9 pA (n = 9) following administration of L-arginine. A similar trend was observed in the nucleus accumbens, where an increase of 44 +/- 9 pA (n = 8) was observed when compared against baseline levels. Systemic injections of the non-selective NOS inhibitor L-NAME produced a significant decrease in current recorded in the prefrontal cortex (24 +/- 6 pA, n = 5) and nucleus accumbens (17 +/- 3 pA, n = 6). Finally it was necessary to validate the sensors functionality in vivo by investigating the effect of the interferent ascorbate on the oxidation current. The current showed no variation in both regions over the selected time interval of 60 min, indicating no deterioration of the polymer membrane. A detailed comparison identified significantly greater affects of administrations on NO sensors implanted in the striatum than those inserted in the prefrontal cortex and the nucleus accumbens. (c) 2012 Elsevier B.V. All rights reserved.
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  • Huttunen, Roope J., et al. (author)
  • Quantitative detection of cell surface protein expression by time-resolved fluorimetry
  • 2007
  • In: Luminescence. - : Wiley. - 1522-7243 .- 1522-7235. ; 22:3, s. 163-170
  • Journal article (peer-reviewed)abstract
    • A method is introduced for quantitative detection of cell surface protein expression. The method is based on immunocytochemistry, the use of long decay time europium(III) chelate and platinum(II) porphyrin labels, and detection of photoluminescence emission from adhered cells by time-resolved fluorimetry. After immunocytochemistry, the assay wells are evaporated to dryness and measured in the dry state. This protocol allows repeated and postponed analysis and microscopy imaging. In order to investigate the performance of the method, we chose expression of intercellular adhesion molecule-1 (ICAM-1) of endothelial cell line EAhy926 as a research target. The expression of ICAM-1 on the cells was enhanced by introduction of a cytokine, tumour necrosis factor-alpha (TNF alpha). The method gave signal: background ratios (S:B) of 20 and 9 for europium and platinum labels, respectively, whereas prompt fluorescent FITC label gave a S:13 of 3. Screening window coefficients (=Z'-factor) were >0.5 for all the three labels, thus indicating a score for an excellent screening assay. In conclusion, the method appears to be an appropriate choice for protein expression analysis, both in high-throughput screening applications, and for detailed sample investigation by fluorescent microscopy imaging. Copyright (C) 2007 John Wiley & Sons, Ltd.
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  • Northington, F. J., et al. (author)
  • Failure to complete apoptosis following neonatal hypoxia-ischemia manifests as "continuum" phenotype of cell death and occurs with multiple manifestations of mitochondrial dysfunction in rodent forebrain
  • 2007
  • In: Neuroscience. - : Elsevier BV. - 0306-4522. ; 149:4, s. 822-33
  • Journal article (peer-reviewed)abstract
    • Controversy surrounds proper classification of neurodegeneration occurring acutely following neonatal hypoxia-ischemia (HI). By ultrastructural classification, in the first 24 h after neonatal hypoxia-ischemia in the 7-day-old (p7) rat, the majority of striatal cells die having both apoptotic and necrotic features. There is formation of a functional apoptosome, and activation of caspases-9 and -3 occurring simultaneously with loss of structurally intact mitochondria to 34.7+/-25% and loss of mitochondrial cytochrome c oxidase activity to 34.7+/-12.7% of control levels by 3 h after hypoxia-ischemia. There is also loss of the mitochondrial motor protein, kinesin. This combination of activation of apoptosis pathways simultaneous with significant mitochondrial dysfunction may cause incomplete packaging of nuclear and cytoplasmic contents and a hybrid of necrotic and apoptotic features. Evidence for an intermediate biochemistry of cell death including expression of the 17 kDa isoform of caspase-3 in dying neurons lacking a classic apoptotic morphology and degradation of the neuronal cytoskeletal protein spectrin by caspase-3 and calcium-activated calpains yielding 120 kDa and 145/150 kDa fragments, respectively, is also found. In summary, neonatal hypoxia-ischemia triggers apoptotic cascades, and simultaneously causes mitochondrial structural and functional failure. The presence of a "continuum" phenotype of cell death that varies on a cell-by-cell basis suggests that the phenotype of cell death is dependent on the energy available to drive the apoptotic pathways to completion.
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  • O'Riordan, C. M., et al. (author)
  • Galaxy mass profiles from strong lensing II : The elliptical power-law model
  • 2020
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 496:3, s. 3424-3435
  • Journal article (peer-reviewed)abstract
    • We present a systematic analysis of the constraints σγ on the mass profile slope γ obtainable when fitting a singular power-law ellipsoid model to a typical strong lensing observation of an extended source. These results extend our previous analysis of circular systems, Paper I. We draw our results from 676 mock observations covering a range of image configurations, each created with a fixed signal to noise ratio S = 100 in the images. We analyse the results using a combination of theory and a simplified model which identifies the contribution to the constraints of the individual fluxes and positions in each of the lensed images. The main results are: 1. For any lens ellipticity, the constraints σγ for two image systems are well described by the results of Paper I, transformed to elliptical coordinates; 2. We derive an analytical expression for σγ for systems with the source aligned with the axis of the lens; 3. For both two-image systems and aligned systems, σγ is limited by the flux uncertainties; 4. The constraints for off-axis four-image systems are a factor of two to eight better, depending on source size, than for two-image systems, and improve with increasing lens ellipticity. We show that the constraints on γ in these systems derive from the complementary positional information of the images alone, without using flux. The complementarity improves as the offset of the source from the axis increases, such that the best constraints σγ < 0.01, for S = 100, occur when the source approaches the caustic.
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  • O'Riordan, C. M., et al. (author)
  • Galaxy mass profiles from strong lensing - III. The two-dimensional broken power-law model
  • 2021
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:3, s. 3687-3694
  • Journal article (peer-reviewed)abstract
    • When modelling strong gravitational lenses, i.e. where there are multiple images of the same source, the most widely used parametrization for the mass profile in the lens galaxy is the singular power-law model rho(r)proportional to r(-gamma). This model may be insufficiently flexible for very accurate work, for example, measuring the Hubble constant based on time delays between multiple images. Here, we derive the lensing properties - deflection angle, shear, and magnification - of a more adaptable model where the projected mass surface density is parametrized as a continuous two-dimensional broken power law (2DBPL). This elliptical 2DBPL model is characterized by power-law slopes t(1) and t(2) either side of the break radius theta(B). The key to the 2DBPL model is the derivation of the lensing properties of the truncated power-law (TPL) model, where the surface density is a power law out to the truncation radius theta(T) and zero beyond. This TPL model is also useful by itself. We create mock observations of lensing by a TPL profile where the images form outside the truncation radius, so there is no mass in the annulus covered by the images. We then show that the slope of the profile interior to the images may be accurately recovered for lenses of moderate ellipticity. This demonstrates that the widely held notion that lensing measures the slope of the mass profile in the annulus of the images, and is insensitive to the mass distribution at radii interior to the images, is incorrect.
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  • Rabe, Patrick, et al. (author)
  • X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis
  • 2021
  • In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:34
  • Journal article (peer-reviewed)abstract
    • Isopenicillin N synthase (IPNS) catalyzes the unique reaction of L-delta-(alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.
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  • Finnerty, N., et al. (author)
  • Increased brain nitric oxide levels following ethanol administration
  • 2015
  • In: Nitric oxide. - : Elsevier BV. - 1089-8603 .- 1089-8611. ; 47, s. 52-57
  • Journal article (peer-reviewed)abstract
    • Nitric oxide is a ubiquitous messenger molecule, which at elevated concentrations has been implicated in the pathogenesis of several neurological disorders. Its role in oxidative stress, attributed in particular to the formation of peroxynitrite, proceeds through its high affinity for the superoxide radical. Alcoholism has recently been associated with the induction of oxidative stress, which is generally defined as a shift in equilibrium between pro-oxidant and anti-oxidant species in the direction of the former. Furthermore, its primary metabolite acetaldehyde, has been extensively associated with oxidative damage related toxic effects following alcohol ingestion. The principal objective of this study was the application of long term in vivo electrochemistry (LIVE) to investigate the effect of ethanol (0.125, 0.5 and 2.0 g kg-1) and acetaldehyde (12.5, 50 and 200 mg kg-1) on NO levels in the nucleus accumbens of freely moving rats. Systemic administrations of ethanol and acetaldehyde resulted in a dose-dependent increases in NO levels, albeit with very differing time courses. Subsequent to this the effect on accumbal NO levels, of subjecting the animal to different drug combinations, was also elucidated. The nitric oxide synthase inhibitor L-NAME (20 mg kg-1) and acetaldehyde sequestering agent D-penicillamine (50 mg kg-1) both attenuated the increase in NO levels following ethanol (1 g kg-1) administration. Conversely, the alcohol dehydrogenase inhibitor 4-methylpyrazole (25 mg kg-1) and catalase inhibitor sodium azide (10 mg kg-1) potentiated the increase in NO levels following ethanol administration. Finally, dual inhibition of aldehyde dehydrogenase and catalase by cyanamide (25 mg kg-1) caused an attenuation of ethanol effects on NO levels. Taken together these data highlight a robust increase in brain NO levels following systemic alcohol administration which is dependent on NO synthase activity and may involve both alcohol- and acetaldehyde-dependent mechanisms. © 2015 Elsevier Inc. All rights reserved.
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  • Ljungman, P., et al. (author)
  • Long-term follow-up of HCV-infected hematopoietic SCT patients and effects of antiviral therapy
  • 2012
  • In: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 47:9, s. 1217-1221
  • Journal article (peer-reviewed)abstract
    • This prospective study was initiated in 1993 with the aim to study late effects and responses to antiviral therapy in a cohort of hepatitis C virus (HCV)-infected patients. A total of 195 patients were included from 12 centers. In all, 134 patients had undergone allogeneic and 61 autologous hematopoietic SCT (HSCT). The median follow-up from HSCT is currently 16.8 years and the maximum 27.2 years. Overall 33 of 195 patients have died of which 6 died from liver complications. The survival probability was 81.6% and the cumulative incidence for death in liver complications was 6.1% at 20 years after HSCT. The cumulative incidence of severe liver complications (death from liver failure, cirrhosis and liver transplantation) was 11.7% at 20 years after HSCT. In all, 85 patients have been treated with IFN; 42 in combination with ribavirin. The sustained response rate was 40%. The rates of severe side effects were comparable to other patient populations and no patient developed significant exacerbations of GVHD. Patients receiving antiviral therapy had a trend toward a decreased risk of severe liver complications (odds ratio=0.33; P=0.058). HCV infection is associated with morbidity and mortality in long-term survivors after HSCT. Antiviral therapy can be given safely and might reduce the risk for severe complications.
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27.
  • O'Riordan, C. M., et al. (author)
  • Galaxy mass profiles from strong lensing I : the circular power-law model
  • 2019
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 487:4, s. 5143-5154
  • Journal article (peer-reviewed)abstract
    • In this series of papers, we develop a formalism for constraining mass profiles in strong gravitational lenses with extended images, using fluxes in addition to positional information. We start in this paper with a circular power-law profile and show that the slope gamma is uniquely determined by only two observables: the flux ratio f(1)/f(2) and the image position ratio theta(1)/theta(2) of the two images. We derive an analytic expression relating these two observables to the slope, a result that does not depend on the Einstein angle or the structure or brightness of the source. We then find an expression for the uncertainty on the slope sigma(gamma) that depends only on the position ratio theta(1)/theta(2) and the total signal-to-noise ratio (S/N) in the images. For example, in a system with position ratio theta(1)/theta(2)= 0.5, S/N=100, and gamma= 2 we find that gamma is constrained to a precision of +/- 0.03. We then test these results against a series of mock observations. We invert the images and fit an 11-parameter model, including ellipticity and position angle for both lens and source and measure the uncertainty on gamma. We find agreement with the theoretical estimate for all mock observations. In future papers, we will examine the radial range of the galaxy over which the constraint on the slope applies, and extend the analysis to elliptical lenses.
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  • Svensson, Carl Johan, 1976, et al. (author)
  • Models of open populations with space-limited recruitment in stochastic environments: relative importance of recruitment and survival in populations of Semibalanus balanoides
  • 2004
  • In: Marine Ecology Progress Series. ; 275, s. 185-197
  • Journal article (peer-reviewed)abstract
    • The relative importance of recruitment and post-recruitment processes in determining adult density among marine species varies considerably between species and populations. This study aimed to investigate the relative effects of variation in recruitment and survival rates on the density dynamics of 3 spatially separated natural populations of the barnacle Semibalanus balanoides (Isle of Man, SW Ireland and west Sweden). We analysed 2 different data-based stochastic matrix models of open populations with space-limited recruitment. Assumption testing supported the application of matrix-model theory for studying and comparing population variables of open populations. Recruitment was found to be partly dependent on free space, and mortality was size-specific and independent of other vital rates. Model simulations showed that the relative importance of recruitment and survival in shaping adult density depends on the existing variation of these vital rates at each location. In the Isle of Man the variation in density was primarily caused by variability in recruitment, while in SW Ireland the variability in survival induced the most variation. In west Sweden variation was high due to variability in both recruitment and survival. A life-cycle elasticity analysis across locations indicated that the population dynamics were generally more sensitive to changes in survival than to changes in recruitment. Also, locations with high variability in vital rates seemed better able to buffer sudden changes in vital rates. In addition, differences in survival and growth produced population structures that varied between populations. In the Isle of Man and west Sweden the populations consisted of mainly Size Category 1 individuals, while the population in SW Ireland had a linear relationship between size category and the proportion of individuals.
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