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- Malmström, Johan, et al.
(author)
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Proteome annotations and identifications of the human pulmonary fibroblast.
- 2004
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 3:3, s. 525-537
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Journal article (peer-reviewed)abstract
- We hereby report on a three year project initiative undertaken by our research team encompassing large-scale protein expression profiling and annotations of human primary lung fibroblast cells. An overview is given of proteomic studies of the fibroblast target cell involved in several diseases such as asthma, idiopatic pulmonary disease, and COPD. It has been the objective within our research team to map and identify the protein expressions occurring in both activated-, as well as resting cell states. The JGGL database www.2DDB.org has been built around these data, allowing advanced hypothesis building using the interactive query bioinformatic tools developed. Gene ontology has been applied to these annotations, classifying and correlating protein expressions to function. The localization as well as the biological processes involved for the annotations are being presented including an annotation-, and sequence-identification strategy, resulting in close to 2000 protein identities. Both gel based, high resolution 2D-gels, and liquid-phase separation (three-dimensional HPLC), as well as the combination of gel- and LC-based approaches (1D-gels and nano-capillary LC, reversed-phase) were utilized. Protein sequencing and structure identities were acquired by a combination of MALDI-, and electrospray-mass spectrometry techniques. Phenotypical and morphological characterizations were also made for this human disease target cell in both stimulated- and resting-cell states. The use of functional assays that demonstrate the key regulating role of growth factors and cytokine stimuli such as PDGF, TGF-, and EGF and the effect of ECM molecules such as Biglycan, are also presented and discussed.
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- Dahlke, Helen E., et al.
(author)
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Using concurrent DNA tracer injections to infer glacial flow pathways
- 2015
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In: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 29:25, s. 5257-5274
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Journal article (peer-reviewed)abstract
- Catchment hydrology has become replete with flow pathway characterizations obtained via combinations of physical hydrologic measurements (e.g. streamflow hydrographs) and natural tracer signals (e.g. stable water isotopes and geochemistry). In this study, we explored how our understanding of hydrologic flow pathways can be improved and expanded in both space and time by the simultaneous application of engineered synthetic DNA tracers. In this study, we compared the advective-dispersive transport properties and mass recovery rates of two types of synthetic DNA tracers, one consisting of synthetic DNA strands encapsulated into biodegradable microspheres and another consisting of `free' DNA, i.e. not encapsulated. The DNA tracers were also compared with a conservative fluorescent dye. All tracers were injected into a small (3.2-km(2)) valley glacier, Storglaciaren, in northern Sweden. Seven of the nine DNA tracers showed clear recovery during the sampling period and similar peak arrival times and dispersion coefficients as the conservative fluorescent dye. However, recovered DNA tracer mass ranged only from 1% to 66%, while recovered fluorescent dye mass was 99%. Resulting from the cold and opaque subglacial environment provided by the glacier, mass loss associated with microbial activity and photochemical degradation of the DNA is likely negligible, leaving sorption of DNA tracers onto suspended particles and loss of microtracer particles to sediment storage as probable explanations. Despite the difference in mass recovery, the advection and dispersion information derived from the DNA tracer breakthrough curves provided spatially explicit information that allowed inferring a theoretical model of the flow pathways that water takes through the glacier.
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- Malmström, Johan, et al.
(author)
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Nanocapillary liquid chromatography interfaced to tandem matrix-assisted laser desorption/ionization and electrospray ionization-mass spectrometry: Mapping the nuclear proteome of human fibroblasts.
- 2003
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In: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 24:21, s. 3806-3814
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Journal article (peer-reviewed)abstract
- Miniaturized liquid chromatography nanoseparation in combination with minigel fractionation of human primary cell nuclei is presented. We obtained high-sensitivity and high-throughput identification of expressed proteins by subcellular fractionation and nanocapillary liquid chromatography interfaced to both electrospray ionization (ESI)- and matrix-assisted laser desorption/ionisation (MALDI) tandem mass spectrometry. The reversed-phase nanocapillary eluents were applied directly onto the MALDI target plate as discrete crystal spots using in-line matrix infusion. When working with primary cells, only a limited amount of sample is available. To maximize the number of identified proteins from a restricted amount of sample, miniaturized sample preparation protocols and nanoflow separation is a necessity, especially when working with low-abundant proteins. From the same isolated nuclear sample, complementary separation of intact proteins by two-dimensional (2-D) gel electrophoresis was made. In total 594 gene products from the nuclear preparations were identified out of which 261 were unique. Several proteins involved in transcriptional events were identified such as TATA-binding protein, EBNA-co-activator, and interleukin enhancer binding proteins, indicating that sufficient proteomic depth is obtained to study transcriptional controlling events. Our results suggest that by sample prefractionation and downscaled nanoflow separation along with a combined mass spectrometry strategy, it is possible to identify a large number of nuclear proteins from human primary cells. These findings are of particular importance due to the disease link of these targets cells.
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- Pilla, Rachel M., et al.
(author)
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Global data set of long-term summertime vertical temperature profiles in 153 lakes
- 2021
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In: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
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- Sullivan, Richard, et al.
(author)
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Delivering affordable cancer care in high-income countries
- 2011
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In: The Lancet Oncology. - London : Lancet Oncology. - 1470-2045 .- 1474-5488. ; 12:10, s. 933-980
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Journal article (peer-reviewed)abstract
- The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
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