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| 2. |
- Lembrechts, Jonas J., et al.
(author)
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Global maps of soil temperature
- 2022
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
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Journal article (peer-reviewed)abstract
- Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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| 3. |
- Fadavi Roudsari, Anita, 1978, et al.
(author)
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Three-wave mixing traveling-wave parametric amplifier with periodic variation of the circuit parameters
- 2023
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 122:5
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Journal article (peer-reviewed)abstract
- We report on the implementation of a near-quantum-limited, traveling-wave parametric amplifier that uses three-wave mixing (3WM). To favor amplification by 3WM, we use superconducting nonlinear asymmetric inductive element (SNAIL) loops, biased with a dc magnetic flux. In addition, we equip the device with dispersion engineering features to create a stopband at the second harmonic of the pump and suppress the propagation of the higher harmonics that otherwise degrade the amplification. With a chain of 440 SNAILs, the amplifier provides up to 20 dB gain and a 3-dB bandwidth of 1 GHz. The added noise by the amplifier is found to be less than one photon.
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| 4. |
- Forsberg, Elin, et al.
(author)
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Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs
- 2023
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In: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
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Journal article (peer-reviewed)abstract
- Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.
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| 5. |
- Kamb, Anneli, et al.
(author)
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Potentials for reducing climate impacts from tourism transport behavior
- 2021
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In: Journal of Sustainable Tourism. - : Informa UK Limited. - 0966-9582 .- 1747-7646. ; 29:8, s. 1365-1382
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Journal article (peer-reviewed)abstract
- Emissions of greenhouse gases from tourism transport are rising globally, with air transport accounting for the largest share. Although travel is not likely to decrease drastically, people could travel differently, and still have similar experiences. This study aims to map the emissions from air travel and analyse the theoretical potential for emissions reduction by changing transport mode and destinations, and the readiness potential for emissions reduction based on tourists’ stated readiness to change their travel behaviour. The theoretical potential was assessed by analysing alternative trips to closer destinations and using transport modes with lower emissions or through virtual meetings. The readiness potential was assessed by a survey designed to capture people’s stated readiness to change their behaviour. The results show a theoretical potential for an emissions reduction of 67%, while the readiness potential is 26%. About half of the readiness potential for reductions is from changing destination, while only a small share is from changing transport mode. This shows that, when accounting for people’s readiness to change behaviour, destination choice has a greater potential to reduce emissions compared to transport mode choice. This finding has implications for policy makers in designing policy measures to reduce emissions.
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| 6. |
- Karlsson, Joakim, et al.
(author)
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Molecular profiling of driver events in metastatic uveal melanoma
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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| 7. |
- Ny, Lars, 1967, et al.
(author)
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Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models
- 2020
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:2, s. 266-273
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Journal article (peer-reviewed)abstract
- Background: The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients. Patients and methods: Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools. Results: Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice. Conclusions: Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.
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| 8. |
- Ny, Lars, 1967, et al.
(author)
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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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| 9. |
- Sah, Vasu R., et al.
(author)
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Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
- 2023
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In: Cancer Research Communications. ; 3:5, s. 884-895
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Journal article (peer-reviewed)abstract
- Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomark-ers needing validation and become hypothesis generating for experimental research.
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| 10. |
- Winell, Erik, 1993, et al.
(author)
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Customer engagement behaviors on physical and virtual engagement platforms
- 2023
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In: Journal of Services Marketing. - 0887-6045. ; 37:10, s. 35-50
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Journal article (peer-reviewed)abstract
- Purpose: This study aims to examine and compare the influence of the disposition to engage in engagement behaviors on physical and virtual engagement platforms, as well as the influence of these engagement behaviors on brand loyalty, value-in-use and word-of-mouth. Design/methodology/approach: Data were collected using a survey distributed to a random sample of 10,000 fans of five teams in the Swedish top-division of elite football. An exploratory factor analysis was performed to derive a distinction between prevalent platforms, scales were validated through a confirmatory factor analysis and structural equation modeling was used to test the research model. Findings: Customer disposition to engage with the sports team had a significant influence on customer engagement behaviors on both physical and virtual engagement platforms. However, engagement behaviors on virtual platforms were found to be more important than engagement behaviors on physical platforms for fostering brand loyalty and value-in-use. Practical implications: The results highlight the importance of engagement behaviors with a brand on virtual engagement platforms. Thus, brand managers should prioritize their presence on social media to generate the positive outcomes of customer engagement behaviors. Originality/value: By examining the effects of customer engagement behaviors on both physical and virtual engagement platforms, this study provides new insights to the emerging customer engagement literature.
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