| 1. |
- Gustafsson, Nina M. S., et al.
(författare)
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Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The glycolytic PFKFB3 enzyme is widely overexpressed in cancer cells and an emerging anticancer target. Here, we identify PFKFB3 as a critical factor in homologous recombination (HR) repair of DNA double-strand breaks. PFKFB3 rapidly relocates into ionizing radiation (IR)-induced nuclear foci in an MRN-ATM-gamma H2AX-MDC1-dependent manner and co-localizes with DNA damage and HR repair proteins. PFKFB3 relocalization is critical for recruitment of HR proteins, HR activity, and cell survival upon IR. We develop KAN0438757, a small molecule inhibitor that potently targets PFKFB3. Pharmacological PFKFB3 inhibition impairs recruitment of ribonucleotide reductase M2 and deoxynucleotide incorporation upon DNA repair, and reduces dNTP levels. Importantly, KAN0438757 induces radiosensitization in transformed cells while leaving non-transformed cells unaffected. In summary, we identify a key role for PFKFB3 enzymatic activity in HR repair and present KAN0438757, a selective PFKFB3 inhibitor that could potentially be used as a strategy for the treatment of cancer.
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| 2. |
- Ålöw, Tobias, et al.
(författare)
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Recensioner
- 2016
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Ingår i: Svensk Exegetisk Årsbok. - Uppsala : Svenska exegetiska sällskapet. - 1100-2298. ; 81, s. 217-284
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- Book reviews:Herbert W. Basser with Marsha B. CohenThe Gospel of Matthew and Judaic Traditions: A Relevance-based Commentary(Tobias Ålöw)Alicia J. Batten och John S. Kloppenborg (red.)James, 1 & 2 Peter, and Early Jesus Traditions(Leonhard Franke)Bible Works 10 (Bo Krister Ljungberg)Derek R. BrownThe God of This Age: Satan in the Churches and Letters of the Apostle Paul(Torsten Löfstedt)William P. Brown (ed.)The Oxford Handbook of the Psalms (David Willgren)Constantine R. CampbellAdvances in the Study of Greek: New Insights for Reading the New Testament (Jan H. Nylund)Nancy L. deClaissé-Walford (ed.) The Shape and Shaping of the Book of Psalms: The Current State of Scholarship(David Willgren)Nancy L. deClaissé-Walford, Rolf A. Jacobson and Beth Laneel Tanner The Book of Psalms(David Willgren)Thomas B. Dozeman, Konrad Schmid och Baruch J. Schwartz (red.) The Pentateuch: International Perspectives on Current Research(Stig Norin)Ole Jakob FiltvedtThe Identity of God’s People and the Paradox of Hebrews(Mikael Tellbe)David Hellholm, Tor Vegge, Øyvind Norderval and Christer Hellholm (eds.)Ablution, Initiation, and Baptism: Late Antiquity, Early Judaism, and Early Christianity(James A. Kelhoffer)Wesley Hill Paul and the Trinity: Persons, Relations, and the Pauline Letters(Mikael Tellbe)Douglas S. HuffmanVerbal Aspect Theory and the Prohibitions in the Greek New Testament(Jan H. Nylund)Thomas KazenScripture, Interpretation, or Authority? Motives and Arguments in Jesus’ Halakic Conflicts(Cecilia Wassén)Judith M. LieuMarcion and the Making of a Heretic: God and Scripture in the Second Century(James A. Kelhoffer)L. Michael Morales (ed.)Cult and Cosmos: Tilting Toward a Temple-Centered Theology(Stefan Green)Mark D. Nanos och Magnus Zetterholm (red.)Paul within Judaism: Restoring the First-Century Context to the Apostle(Martin Landgren)Carol A. Newsom och Brennan W. BreedDaniel: A Commentary(LarsOlov Eriksson)Maren Niehoff (red.)Homer and the Bible in the Eyes of Ancient Interpreters(Blazenka Scheuer)Kurt L. NollCanaan and Israel in Antiquity: A Textbook on History and Religion(Richard Pleijel)Ken Parry (ed.) The Wiley Blackwell Companion to Patristics(Carl Johan Berglund)Ralf Rothenbusch“... abgesondert zur Tora Gottes hin”: Ethnisch-religiöse Identitäten im Esra/Nehemiabuch(Lena-Sofia Tiemeyer)Michael L. SatlowHow the Bible Became Holy(Martin Wessbrandt)Birke Siggelkow-BernerDie jüdischen Feste im Bellum Judaicum des Flavius Josephus(Birger Olsson)Lena-Sofia Tiemeyer och Hans M. Barstad (red.)Continuity and Discontinuity: Chronological and Thematic Development in Isaiah 40–66(Stefan Green)W. Dennis Tucker Jr.Constructing and Deconstructing Power in Psalms 107–150(David Willgren)Helmut Utzschneider och Wolfgang OswaldExodus 1–15(LarsOlov Eriksson)Urban C. Von WahldeThe Gospel and Letters of John, vol. 1:Introduction, Analysis, and Reference The Gospel and Letters of John, vol. 2: Commentary on the Gospel of JohnThe Gospel and Letters of John, vol. 3: Commentary on the Three Johannine Letters(Birger Olsson)Benjamin L. WhiteRemembering Paul: Ancient and Modern Contests over the Image of the Apostle(Martin Wessbrandt)
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| 3. |
- Best, Jonathan G., et al.
(författare)
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Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) : Protocol for a randomized controlled trial
- 2022
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 17:5, s. 583-589
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim: Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. Methods and design: OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. Study outcomes: The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. Sample size target: A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. Discussion: OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938
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| 4. |
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| 5. |
- Garcia-Ruiz, A., et al.
(författare)
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Hermetic all-fiber phase modulators using Joule heating in carbon-coated fibers
- 2018
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Ingår i: Optics InfoBase Conference Papers. - Washington, D.C. : OSA - The Optical Society. - 9781557528209
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Konferensbidrag (refereegranskat)abstract
- Certain applications of fiber sensors (e.g. avionics, oil industry) imply extreme operating conditions spurring the development of hermetic all-fiber devices. We present a hermetic all-fiber phase modulator based on Joule heating in a carbon-coated fiber.
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| 6. |
- Garcia-Ruiz, Andres, et al.
(författare)
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Hermetic Carbon Coatings for Electro-Thermal All-Fiber Phase Modulators
- 2019
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Ingår i: Journal of Lightwave Technology. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0733-8724 .- 1558-2213. ; 37:18, s. 4567-4572
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Tidskriftsartikel (refereegranskat)abstract
- Joule effect and thermal response of several carbon-coated fibers are modeled and analyzed. An electro-thermally driven all-fiber phase modulator based on these principles is proposed and a proof of concept of it is characterized. This kind of fiber could be the basis for developing all-fiber components aimed to operate in environments where the strength increase and impermeability to hydrogen diffusion guaranteed by the carbon coating is crucial.
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| 7. |
- Havervall, Sebastian, et al.
(författare)
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Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19
- 2022
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 291:1, s. 72-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.Methods: We investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.Results: All COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).Conclusions: The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.
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| 8. |
- Lauren, Ida, et al.
(författare)
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Long-term SARS-CoV-2-specific and cross-reactive cellular immune responses correlate with humoral responses, disease severity, and symptomatology
- 2022
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Ingår i: Immunity, Inflammation and Disease. - : John Wiley & Sons. - 2050-4527. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cellular immune memory responses post coronavirus disease 2019 (COVID-19) have been difficult to assess due to the risks of contaminating the immune response readout with memory responses stemming from previous exposure to endemic coronaviruses. The work herein presents a large-scale long-term follow-up study investigating the correlation between symptomology and cellular immune responses four to five months post seroconversion based on a unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific peptide pool that contains no overlapping peptides with endemic human coronaviruses. Methods: Peptide stimulated memory T cell responses were assessed with dual interferon-gamma (IFN gamma) and interleukin (IL)-2 Fluorospot. Serological analyses were performed using a multiplex antigen bead array. Results: Our work demonstrates that long-term SARS-CoV-2-specific memory T cell responses feature dual IFN gamma and IL-2 responses, whereas cross-reactive memory T cell responses primarily generate IFN gamma in response to SARS-CoV-2 peptide stimulation. T cell responses correlated to long-term humoral immune responses. Disease severity as well as specific COVID-19 symptoms correlated with the magnitude of the SARS-CoV-2-specific memory T cell response four to five months post seroconversion. Conclusion: Using a large cohort and a SARS-CoV-2-specific peptide pool we were able to substantiate that initial disease severity and symptoms correlate with the magnitude of the SARS-CoV-2-specific memory T cell responses.
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| 9. |
- Lundström, Erik, 1964-, et al.
(författare)
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Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke Results From EFFECTS, a Randomized Controlled Trial
- 2021
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 52:10, s. 3082-3087
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The EFFECTS (Efficacy of Fluoxetine-a Randomised Controlled Trial in Stroke) recently reported that 20 mg fluoxetine once daily for 6 months after acute stroke did not improve functional outcome but reduced depression and increased fractures and hyponatremia at 6 months. The purpose of this predefined secondary analysis was to identify if any effects of fluoxetine were maintained or delayed over 12 months. METHODS: EFFECTS was an investigator-led, randomized, placebo-controlled, double-blind, parallel group trial in Sweden that enrolled adult patients with stroke. Patients were randomized to 20 mg oral fluoxetine or matching placebo for 6 months and followed for another 6 months. The primary outcome was functional outcome (modified Rankin Scale), at 6 months. Predefined secondary outcomes for these analyses included the modified Rankin Scale, health status, quality of life, fatigue, mood, and depression at 12 months. RESULTS: One thousand five hundred patients were recruited from 35 centers in Sweden between 2014 and 2019; 750 were allocated fluoxetine and 750 placebo. At 12 months, modified Rankin Scale data were available in 715 (95%) patients allocated fluoxetine and 712 (95%) placebo. The distribution of modified Rankin Scale categories was similar in the 2 groups (adjusted common odds ratio, 0.92 [95% CI, 0.76-1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (interquartile range, 75-100) versus 93 (interquartile range, 82-100); P=0.0021 and communication 93 (interquartile range, 82-100) versus 96 (interquartile range, 86-100); P=0.024 domains of the Stroke Impact Scale compared with placebo. There were no other differences in secondary outcomes. CONCLUSIONS: Fluoxetine after acute stroke had no effect on functional outcome at 12 months. Patients allocated fluoxetine scored worse on memory and communication on the Stroke Impact Scale compared with placebo, but this is likely to be due to chance.
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| 10. |
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