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- Agardh, Carl-David, et al.
(author)
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Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.
- 2005
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In: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 19:4, s. 238-246
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Journal article (peer-reviewed)abstract
- The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 μg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 μg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 μg dose group. GADA log levels clearly increased (P=.0002) in response to 500 μg Diamyd. The CD4+CD25+/CD4+CD25− cell ratio increased (P=.0128) at 24 weeks in the 20 μg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.
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- Bengtsson, Ylva, et al.
(author)
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Ulriksdals slott under 350 år
- 1995
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Reports (pop. science, debate, etc.)abstract
- Studierna har utgått från Ulriksdals slott, uppfört av Jacob De la Gardie för 350 år sedan. Som kungligt slott har Ulriksdal genomgått ombyggnader under 1600 - och 1700-talet, men präglas idag mest av Karl XVs omfattande omdaning på 1850-talet och Gustav VI Adolfs lika genomgripande förändringar på 1920-talet.Slottet har bjudit på rika studiemöjligheter av stilideal, planlösning, interiörgestaltning, snickerikultur och stormtekniska system från hela 350-årsperioden. Genom noggranna uppmätningar och inventeringar på plats kopplade till arkivstudier har slottets komplicerade förändringshistoria kunnat analyseras,
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4. |
- Borenäs, Marcus, et al.
(author)
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ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition
- 2024
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In: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:1
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Journal article (peer-reviewed)abstract
- High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.
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5. |
- Borin, Lars, et al.
(author)
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Swe-Clarin : Language Resources and Technology for Digital Humanities
- 2016
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In: <em>Extended Papers of the International Symposium on Digital Humanities</em>. - : CEUR. ; , s. 29-51, s. 29-51
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Conference paper (peer-reviewed)abstract
- CLARIN is a European Research Infrastructure Consortium (ERIC), which aims at (a) making extensive language-based materials available as primary research data to the humanities and social sciences (HSS); and (b) offering state-of-the-art language technology (LT) as an eresearch tool for this purpose, positioning CLARIN centrally in what is often referred to as the digital humanities (DH). The Swedish CLARIN node Swe-Clarin was established in 2015 with funding from the Swedish Research Council.In this paper, we describe the composition and activities of Swe-Clarin, aiming at meeting the requirements of all HSS and other researchers whose research involves using text and speech as primary research data, and spreading the awareness of what Swe-Clarin can offer these research communities. We focus on one of the central means for doing this: pilot projects conducted in collaboration between HSS researchers and Swe-Clarin, together formulating a research question, the addressing of which requires working with large language-based materials. Four such pilot projects are described in more detail, illustrating research on rhetorical history, second-language acquisition, literature, and political science. A common thread to these projects is an aspiration to meet the challenge of conducting research on the basis of very large amounts of textual data in a consistent way without losing sight of the individual cases making up the mass of data, i.e., to be able to move between Moretti’s “distant” and “close reading” modes.While the pilot projects clearly make substantial contributions to DH, they also reveal some needs for more development, and in particular a need for document-level access to the text materials. As a consequence of this, work has now been initiated in Swe-Clarin to meet this need, so that Swe-Clarin together with HSS scholars investigating intricate research questions can take on the methodological challenges of big-data language-based digital humanities.
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6. |
- Borin, Lars, 1957, et al.
(author)
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Swe-Clarin: Language resources and technology for Digital Humanities
- 2017
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In: Digital Humanities 2016. Extended Papers of the International Symposium on Digital Humanities (DH 2016) Växjö, Sweden, November, 7-8, 2016. Edited by Koraljka Golub, Marcelo Milra. Vol-2021. - Aachen : M. Jeusfeld c/o Redaktion Sun SITE, Informatik V, RWTH Aachen.. - 1613-0073.
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Conference paper (peer-reviewed)abstract
- CLARIN is a European Research Infrastructure Consortium (ERIC), which aims at (a) making extensive language-based materials available as primary research data to the humanities and social sciences (HSS); and (b) offering state-of-the-art language technology (LT) as an e-research tool for this purpose, positioning CLARIN centrally in what is often referred to as the digital humanities (DH). The Swedish CLARIN node Swe-Clarin was established in 2015 with funding from the Swedish Research Council. In this paper, we describe the composition and activities of Swe-Clarin, aiming at meeting the requirements of all HSS and other researchers whose research involves using text and speech as primary research data, and spreading the awareness of what Swe-Clarin can offer these research communities. We focus on one of the central means for doing this: pilot projects conducted in collaboration between HSS researchers and Swe-Clarin, together formulating a research question, the addressing of which requires working with large language-based materials. Four such pilot projects are described in more detail, illustrating research on rhetorical history, second-language acquisition, literature, and political science. A common thread to these projects is an aspiration to meet the challenge of conducting research on the basis of very large amounts of textual data in a consistent way without losing sight of the individual cases making up the mass of data, i.e., to be able to move between Moretti’s “distant” and “close reading” modes. While the pilot projects clearly make substantial contributions to DH, they also reveal some needs for more development, and in particular a need for document-level access to the text materials. As a consequence of this, work has now been initiated in Swe-Clarin to meet this need, so that Swe-Clarin together with HSS scholars investigating intricate research questions can take on the methodological challenges of big-data language-based digital humanities.
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7. |
- Borin, Lars, 1957, et al.
(author)
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Swe-Clarin: Language resources and technology for digital humanities
- 2016
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In: CEUR Workshop Proceedings. - 1613-0073. ; 2021, s. 29-51
-
Conference paper (peer-reviewed)abstract
- CLARIN is a European Research Infrastructure Consortium (ERIC), which aims at (a) making extensive language-based materials available as primary research data to the humanities and social sciences (HSS); and (b) offering state-of-the-art language technology (LT) as an e-research tool for this purpose, positioning CLARIN centrally in what is often referred to as the digital humanities (DH). The Swedish CLARIN node Swe-Clarin was established in 2015 with funding from the Swedish Research Council. In this paper, we describe the composition and activities of Swe-Clarin, aiming at meeting the requirements of all HSS and other researchers whose research involves using text and speech as primary research data, and spreading the awareness of what Swe-Clarin can offer these research communities. We focus on one of the central means for doing this: pilot projects conducted in collaboration between HSS researchers and Swe-Clarin, together formulating a research question, the addressing of which requires working with large language-based materials. Four such pilot projects are described in more detail, illustrating research on rhetorical history, second-language acquisition, literature, and political science. A common thread to these projects is an aspiration to meet the challenge of conducting research on the basis of very large amounts of textual data in a consistent way without losing sight of the individual cases making up the mass of data, i.e., to be able to move between Moretti’s “distant” and “close reading” modes.
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8. |
- Cervantes-Madrid, Diana Lizeth, 1987, et al.
(author)
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Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells.
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- Neuroblastoma is the most commonly diagnosed extracranial tumor in the first year of life. Approximately 9% of neuroblastoma patients present germline or somatic aberrations in the gene encoding for anaplastic lymphoma kinase (ALK). This increases in high-risk neuroblastomas, which have a 14% frequency of ALK aberrations at the time of diagnosis and show increasing numbers at relapse. Abrogating ALK activity with kinase inhibitors is employed as clinical therapy in malignancies such as non-small cell lung cancer and has shown good results in pediatric inflammatory myofibroblastic tumors and anaplastic large cell lymphomas. A phase I clinical trial of the first generation ALK inhibitor, crizotinib, in neuroblastoma patients showed modest results and suggested that further investigation was needed. Continuous development of ALK inhibitors has resulted in the third generation inhibitor repotrectinib (TPX-0005), which targets the active kinase conformations of ALK, ROS1 and TRK receptors. In the present study we investigated the effects of repotrectinib in a neuroblastoma setting in vitro and in vivo. Neuroblastoma cell lines were treated with repotrectinib to investigate inhibition of ALK and to determine its effect on proliferation. PC12 cells transfected with different ALK mutant variants were used to study the efficacy of repotrectinib to block ALK activation/signaling. The in vivo effect of repotrectinib was also analyzed in a neuroblastoma xenograft model. Our results show that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma.
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