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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Lestinsky, M., et al.
(author)
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Physics book: CRYRING@ESR
- 2016
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In: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 225:5, s. 797-882
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Research review (peer-reviewed)abstract
- The exploration of the unique properties of stored and cooled beams of highly-charged ions as provided by heavy-ion storage rings has opened novel and fascinating research opportunities in the realm of atomic and nuclear physics research. Since the late 1980s, pioneering work has been performed at the CRYRING at Stockholm (Abrahamsson et al. 1993) and at the Test Storage Ring (TSR) at Heidelberg (Baumann et al. 1988). For the heaviest ions in the highest charge-states, a real quantum jump was achieved in the early 1990s by the commissioning of the Experimental Storage Ring (ESR) at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt (Franzke 1987) where challenging experiments on the electron dynamics in the strong field regime as well as nuclear physics studies on exotic nuclei and at the borderline to atomic physics were performed. Meanwhile also at Lanzhou a heavy-ion storage ring has been taken in operation, exploiting the unique research opportunities in particular for medium-heavy ions and exotic nuclei (Xia et al. 2002).
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| 3. |
- Muller, C., et al.
(author)
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Combination of Proton Therapy and Radionuclide Therapy in Mice: Preclinical Pilot Study at the Paul Scherrer Institute
- 2019
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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 11:9
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Journal article (peer-reviewed)abstract
- Proton therapy (PT) is a treatment with high dose conformality that delivers a highly-focused radiation dose to solid tumors. Targeted radionuclide therapy (TRT), on the other hand, is a systemic radiation therapy, which makes use of intravenously-applied radioconjugates. In this project, it was aimed to perform an initial dose-searching study for the combination of these treatment modalities in a preclinical setting. Therapy studies were performed with xenograft mouse models of folate receptor (FR)-positive KB and prostate-specific membrane antigen (PSMA)-positive PC-3 PIP tumors, respectively. PT and TRT using Lu-177-folate and Lu-177-PSMA-617, respectively, were applied either as single treatments or in combination. Monitoring of the mice over nine weeks revealed a similar tumor growth delay after PT and TRT, respectively, when equal tumor doses were delivered either by protons or by beta over bar -particles, respectively. Combining the methodologies to provide half-dose by either therapy approach resulted in equal (PC-3 PIP tumor model) or even slightly better therapy outcomes (KB tumor model). In separate experiments, preclinical positron emission tomography (PET) was performed to investigate tissue activation after proton irradiation of the tumor. The high-precision radiation delivery of PT was confirmed by the resulting PET images that accurately visualized the irradiated tumor tissue. In this study, the combination of PT and TRT resulted in an additive effect or a trend of synergistic effects, depending on the type of tumor xenograft. This study laid the foundation for future research regarding therapy options in the situation of metastasized solid tumors, where surgery or PT alone are not a solution but may profit from combination with systemic radiation therapy.
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| 4. |
- Bernhardt, H., et al.
(author)
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Debris flow recurrence periods and multi-temporal observations of colluvial fan evolution in central Spitsbergen (Svalbard)
- 2017
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In: Geomorphology. - : Elsevier BV. - 0169-555X. ; 296, s. 132-141
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Journal article (peer-reviewed)abstract
- Fan-shaped accumulations of debris flow deposits are common landforms in polar regions such as Svalbard. Although depositional processes in these environments are of high interest to climate as well as Mars-analog research, several parameters, e.g., debris flow recurrence periods, remain poorly constrained. Here, we present an investigation based on remote sensing as well as in situ data of a similar to 0.4 km(2) large colluvial fan in Hanaskogdalen, central Spitsbergen. We analyzed high resolution satellite and aerial images covering five decades from 1961 to 2014 and correlated them with lichenometric dating as well as meteorological data. Image analyses and lichenometry deliver consistent results and show that the recurrence period of large debris flows (>= 400 m(3)) is about 5 to 10 years, with smaller flows averaging at two per year in the period from 2008 to 2013. While this is up to two orders of magnitude shorter than previous estimates for Svalbard (80 to 500 years), we found the average volume of -220 m(3) per individual flow to be similar to previous estimates for the region. Image data also reveal that an avulsion took place between 1961 and 1976, when the active part of the fan moved from its eastern to its western portion. A case study of the effects of a light rain event (similar to 5 mm/day) in the rainy summer of 2013, which triggered a large debris flow, further shows that even light precipitation can trigger major flows. This is made possible by multiple light rain events or gradual snow melt pre-saturating the permafrost ground and has to be taken into account when predicting the likelihood of potentially hazardous mass wasting in polar regions. Furthermore, our findings imply a current net deposition rate on the colluvial fan of similar to 480 m(3)/year, which is slightly less than the integrated net deposition rate of 576 to 720 m(3)/year resulting from the current fan volume divided by the 12,500 to 10,000 years since the onset of fan build-up after the area's deglaciation. However, the actual deposition rate, which should increase in a warmer climate including more rain, cannot be constrained due to effects like ongoing toe-cutting of the debris fan and some flows only causing internal redistributions.
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| 5. |
- Bernhardt, J, et al.
(author)
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CASE Needs Analysis. Summary. Findings on Competencies for Sustainability-driven Entrepreneurship. Based on interviews with partners from sustainability-driven enterprises and universities.
- 2016
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Reports (other academic/artistic)abstract
- The report represents the main outputs of the needs analysis of work package 1 (WP1) within the CASE project. The specific aim of the report and WP1 is to summarize concrete needs and necessary competencies for sustainability-driven entrepreneurship. For this purpose a qualitative research approach was chosen to bring together perspectives of enterprises and universities concerning a future collaboration as a possible starting-point for a long-lasting multistakeholder network. Furthermore an analysis of best practice examples was necessary in order to create synergies and use existing knowledge and good experiences of teaching towards sustainability-driven entrepreneurship. As the results show, both, companies and universities, are highly aware of the huge challenges for society, economy and natural environment on a global and regional level. That calls for integrated, holistic approaches and for comprehensive socio-economic transformation processes, involving various stakeholders from entrepreneurial, societal and educational contexts. As disciplinary analysis quickly reach their limits, research and practice for sustainability-driven entrepreneurship require comprehensive and integrated approaches. Multistakeholder networks could provide the right learning environments for complex sustainability issues.
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| 6. |
- Cumming, T. B., et al.
(author)
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Early Mobilization After Stroke Is Not Associated With Cognitive Outcome Findings From AVERT
- 2018
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In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 49:9, s. 2147-2154
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Journal article (peer-reviewed)abstract
- Background and Purpose We aimed to determine whether early mobilization after stroke affects subsequent cognitive function. Methods-AVERT (A Very Early Rehabilitation Trial) was an international, 56-site, phase 3 randomized controlled trial, conducted from 2006 to 2015. Participants were included if they were aged 18+, presented within 24 hours of stroke, and satisfied physiological limits for blood pressure, heart rate, and temperature. Participants were randomized to receive either usual stroke unit care or very early and more frequent mobilization in addition to usual stroke unit care. The Montreal Cognitive Assessment, scored 0 to 30, was introduced as a 3-month outcome during 2008. Results-Of the 2104 patients included in AVERT, 317 were assessed before the Montreal Cognitive Assessment's introduction. Of the remaining 1787, 1189 (66.5%) had complete Montreal Cognitive Assessment data, 456 (25.5%) had partially or completely missing data, 136 (7.6%) had died, and 6 (0.3%) were lost to follow-up. In surviving participants with complete data, adjusting for age and stroke severity, total Montreal Cognitive Assessment score was no different in the intervention (n=595; median, 23; interquartile range, 19-26; mean, 21.9; SD, 5.9) and usual care (n=594; median, 23; interquartile range, 19-26; mean, 21.8; SD, 5.9) groups (P=0.68). Conclusions-Exposure to earlier and more frequent mobilization in the acute stage of stroke does not influence cognitive outcome at 3 months. This stands in contrast to the primary outcome from AVERT (modified Rankin Scale), where the intervention group had less favorable outcomes than controls.
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| 7. |
- Hattermann, D., et al.
(author)
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Geese are overlooked dispersal vectors for vascular plants in archipelago environments
- 2019
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In: Journal of Vegetation Science. - : Wiley-Blackwell. - 1100-9233 .- 1654-1103. ; 30:3, s. 533-541
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Journal article (peer-reviewed)abstract
- Question: We addressed the importance of gut-mediated dispersal by greylag geese for vascular plants in archipelago environments and asked: (a) What proportion of the local species pool is dispersed by geese? (b) Which plant traits characterize species dispersed by geese? (c) Which plant communities are likely to benefit from endozoochory by geese?. Location: Three Swedish Baltic archipelagos. Methods: Goose droppings were collected on 45 islands. Plants germinating from the droppings represent the endozoochorous species pool (ESP). On 108 islands, the presence of vascular plants was recorded in each habitat. These species represent the island species pool (ISP). Differences in functional traits between ESP and ISP were expressed as effect sizes and tested using meta-regressions. Using indicator species analyses and indicator species for managed semi-natural grasslands, we identified the primary habitats of the ESP. Results: Geese dispersed viable diaspores of 97 plant species, which represents 22% of the ISP. Most ESP species were typical for small islands. Geese dispersed a higher proportion of graminoids and less woody plants, higher proportions of chamaephytes and therophytes and less phanerophytes; annuals and bi-annuals were significantly overrepresented. On average, seed volume of the ESP was 95% smaller than that of the ISP. About 51% of all ESP species were dispersed in at least two archipelagos. Geese showed a bias towards species of rocky shore habitats. Conclusion: Geese potentially disperse large amounts of diaspores of many terrestrial island plant species. Through their feeding behaviour, geese select species with certain suites of traits from the regional species pool. Plant dispersal by geese may benefit plants species of rocky shores, but species of formerly managed semi-natural grasslands may also find refuge sites on epilittoral shores after goose-mediated dispersal. The relative importance of geese as dispersal vectors may increase under on-going land-use changes and cessation of grazing networks.
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| 8. |
- Schramm, Frederic D., et al.
(author)
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An essential regulatory function of the DnaK chaperone dictates the decision between proliferation and maintenance in Caulobacter crescentus
- 2017
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 13:12
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Journal article (peer-reviewed)abstract
- Hsp70 chaperones are well known for their important functions in maintaining protein homeostasis during thermal stress conditions. In many bacteria the Hsp70 homolog DnaK is also required for growth in the absence of stress. The molecular reasons underlying Hsp70 essentiality remain in most cases unclear. Here, we demonstrate that DnaK is essential in the alpha-proteobacterium Caulobacter crescentus due to its regulatory function in gene expression. Using a suppressor screen we identified mutations that allow growth in the absence of DnaK. All mutations reduced the activity of the heat shock sigma factor sigma(32) , demonstrating that the DnaK-dependent inactivation of sigma(32) is a growth requirement. While most mutations occurred in the rpoH gene encoding sigma(32) , we also identified mutations affecting sigma(32) activity or stability in trans, providing important new insight into the regulatory mechanisms controlling sigma(32) activity. Most notably, we describe a mutation in the ATP dependent protease HslUV that induces rapid degradation of sigma(32) , and a mutation leading to increased levels of the house keeping sigma(70) that outcompete sigma(32) for binding to the RNA polymerase. We demonstrate that sigma(32) inhibits growth and that its unrestrained activity leads to an extensive reprogramming of global gene expression, resulting in upregulation of repair and maintenance functions and downregulation of the growth-promoting functions of protein translation, DNA replication and certain metabolic processes. While this re-allocation from proliferative to maintenance functions could provide an advantage during heat stress, it leads to growth defects under favorable conditions. We conclude that Caulobacter has coopted the DnaK chaperone system as an essential regulator of gene expression under conditions when its folding activity is dispensable.
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| 9. |
- Tedesco-Silva, Helio, et al.
(author)
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Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants : An Analysis From the Randomized TRANSFORM Study
- 2019
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 103:9, s. 1953-1963
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Journal article (peer-reviewed)abstract
- BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail.METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids.RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA.CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.
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