| 1. |
- Blom, Elisabeth, et al.
(författare)
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68Ga-Labeling of RGD peptides and biodistribution
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- Several peptides comprising Arg-Gly-Asp (RGD) domain and macrocyclic chelator were labeled with 68Ga for the imaging of angiogenesis. The analogues varied in peptide constitution, linker and chelator type. The labeling efficiency did not vary with the peptide constitution and linker type, but depended on the chelator type. Four of the compounds containing 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator were labeled at 90 ± 5°C using conventional or microwave heating reaching 90% of 68Ga incorporation after 5 and 2 min respectively, when the concentration of the precursor was 2.5 μM. The compound having 2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA) as the chelator could be labeled at room temperature within 5 min using 2.5 μM peptide precursor. Two of the compounds contained a poly (ethylene glycol) (PEG) linker to the chelator. The biodistribution of the analogues was studied in male rats.
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| 2. |
- Blom, Elisabeth, et al.
(författare)
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Ga-68-Labeling of RGD peptides and biodistribution
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- Several peptides comprising Arg-Gly-Asp (RGD) domain and macrocyclic chelator were labeled with Ga-68 for the imaging of angiogenesis. The analogues varied in peptide constitution, linker and chelator type. The labeling efficiency did not vary with the peptide constitution and linker type, but depended on the chelator type. Four of the compounds containing 2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) chelator were labeled at 90 +/- 5 degrees C using conventional or microwave heating reaching 90% of Ga-68 incorporation after 5 and 2 min respectively, when the concentration of the precursor was 2.5 mu M. The compound having 2,2', 2 ''-(1,4,7-triazonane1,4,7-triyl)triacetic acid (NOTA) as the chelator could be labeled at room temperature within 5 min using 2.5 mu M peptide precursor. Two of the compounds contained a poly (ethylene glycol) (PEG) linker to the chelator. The biodistribution of the analogues was studied in male rats.
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| 3. |
- Blom, Elisabeth, et al.
(författare)
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Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers
- 2011
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 54:11, s. 685-692
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR-2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti-angiogenic drugs target VEGF/VEGFR-2 signaling and induce changes in VEGFR-2 prevalence. To monitor VEGFR-2 prevalence in the course of treatment, we are evaluating (68)Ga positron emission tomography imaging agents based on macrocyclic chelators, site-specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR-2 ligand, single-chain (sc) VEGF. The (68)Ga-labeling was performed at room temperature with NOTA (2,2', 2 ''-(1,4,7-triazonane-1,4,7-triyl) triacetic acid) conjugates or at 90 degrees C by using either conventional or microwave heating with NOTA and DOTA (2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid) conjugates. The fastest (similar to 2min) and the highest incorporation (>90%) of (68)Ga into conjugate that resulted in the highest specific radioactivity (similar to 400MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA-and DOTA-containing tracers was validated in 3-D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR-2. The NOTA-containing tracer also displayed a rapid accumulation (similar to 20s after intravenous injection) to steady-state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF-PEG-[(68)Ga] NOTA and scVEGF-PEG-[(68)Ga] DOTA might be promising tracers for monitoring VEGFR-2 prevalence and should be further explored.
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| 4. |
- Budhavant, Krishnakant, et al.
(författare)
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Changing optical properties of Black Carbon and Brown Carbon aerosols during long-range transport from the Indo-Gangetic Plain to the equatorial Indian Ocean
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Atmospheric aerosols strongly influence the global climate by their light absorption (e.g., black carbon, BC, brown carbon, BrC) and scattering (e.g., sulfate) properties. This study presents simultaneous measurements of ambient aerosol light absorption properties and chemical composition from three large-footprint South Asian receptor sites during the South Asian Pollution Experiment (SAPOEX) in December 2017 - March 2018. The BC mass absorption cross-section (BC-MAC678) values increased from 3.5 ± 1.3 at the Bhola Climate Observatory-Bangladesh (i.e., located at exit outflow of Indo-Gangetic Plain) to 6.4 ± 1.3 at the two regional receptor observatories at Maldives Climate Observatory-Hanimaadhoo (MCOH) and Maldives Climate Observatory-Gan (MCOG), an increase of 80%. This likely reflects a scavenging fractionation resulting in a population of finer BC with higher MAC678 having higher longevity. At the same time, the BrC-MAC365 decreased by a factor of three from the IGP exit to the equatorial Indian Ocean, likely due to photochemical bleaching of organic chromophores. The high chlorine-to-sodium ratio at the near-source-region BCOB suggests a significant contribution of chlorine from anthropogenic activities. This particulate Cl- has the potential to convert into Cl-radicals that can affect the oxidation capacity of the polluted air. Moreover, Cl- is shown to be near-fully consumed during the long-range transport. The results of this synoptic study over the large South Asian scale contribute rare observational constraints on optical properties of ambient BC (and BrC) aerosols over regional scales away from emission sources. It also contributes significantly to understanding the ageing effect of the optical and chemical properties of aerosols as the pollution from the Indo-Gangetic Plain disperses over the tropical ocean.
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| 5. |
- Chandrika Ranjendra Nair, Hari Ram, 1989-, et al.
(författare)
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Aerosol demasking enhances climate warming over South Asia
- 2023
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Ingår i: npj Climate and Atmospheric Science. - 2397-3722. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic aerosols mask the climate warming caused by greenhouse gases (GHGs). In the absence of observational constraints, large uncertainties plague the estimates of this masking effect. Here we used the abrupt reduction in anthropogenic emissions observed during the COVID-19 societal slow-down to characterize the aerosol masking effect over South Asia. During this period, the aerosol loading decreased substantially and our observations reveal that the magnitude of this aerosol demasking corresponds to nearly three-fourths of the CO2-induced radiative forcing over South Asia. Concurrent measurements over the northern Indian Ocean unveiled a ~7% increase in the earth’s surface-reaching solar radiation (surface brightening). Aerosol-induced atmospheric solar heating decreased by ~0.4 K d−1. Our results reveal that under clear sky conditions, anthropogenic emissions over South Asia lead to nearly 1.4 W m−2 heating at the top of the atmosphere during the period March–May. A complete phase-out of today’s fossil fuel combustion to zero-emission renewables would result in rapid aerosol demasking, while the GHGs linger on.
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| 6. |
- Chandrika Ranjendra Nair, Hari Ram, 1989-, et al.
(författare)
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Aerosol demasking enhances climate warming over South Asia
- 2023
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Ingår i: npj Climate and Atmospheric Science. - 2397-3722. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic aerosols mask the climate warming caused by greenhouse gases (GHGs). In the absence of observational constraints, large uncertainties plague the estimates of this masking effect. Here we used the abrupt reduction in anthropogenic emissions observed during the COVID-19 societal slow-down to characterize the aerosol masking effect over South Asia. During this period, the aerosol loading decreased substantially and our observations reveal that the magnitude of this aerosol demasking corresponds to nearly three-fourths of the CO2-induced radiative forcing over South Asia. Concurrent measurements over the northern Indian Ocean unveiled a ~7% increase in the earth’s surface-reaching solar radiation (surface brightening). Aerosol-induced atmospheric solar heating decreased by ~0.4 K d−1. Our results reveal that under clear sky conditions, anthropogenic emissions over South Asia lead to nearly 1.4 W m−2 heating at the top of the atmosphere during the period March–May. A complete phase-out of today’s fossil fuel combustion to zero-emission renewables would result in rapid aerosol demasking, while the GHGs linger on.
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| 7. |
- Kim, Min Seo, et al.
(författare)
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Global burden of peripheral artery disease and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2023
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:10, s. E1553-E1565
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures.Methods: Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed.Findings: In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99 center dot 2-128 center dot 4), with a global prevalence of 1 center dot 52% (95% UI 1 center dot 33-1 center dot 72), of which 42 center dot 6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14 center dot 91% [12 center dot 41-17 center dot 87] in those aged 80-84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69 center dot 4% (64 center dot 2-74 center dot 3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles.Interpretation: The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors.
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| 8. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 9. |
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| 10. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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