| 1. |
- Kirchhof, Paulus, et al.
(författare)
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Comprehensive risk reduction in patients with atrial fibrillation : emerging diagnostic and therapeutic options - a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference
- 2012
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:1, s. 8-27
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Forskningsöversikt (refereegranskat)abstract
- While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
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| 2. |
- Apaydin, Dogukan, 1991, et al.
(författare)
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UVC photonic crystal surface-emitting lasers with low-divergent far-fields
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Photonic crystal surface-emitting lasers (PCSEL) emitting in the ultraviolet (UV) C spectral range are exciting devices due to their low divergence and single-mode emission capable of high output powers as already demonstrated in the infrared [1] and blue spectral range [2]. This is due to their unique design, which incorporates a photonic crystal leading to a large optical gain area. PCSELs are based upon in-plane feedback from the photonic crystal and out-of-plane emission by the diffraction of the modes with zero group velocity at the photonic band edges. We recently demonstrated, to the best of our knowledge, the first UVC PCSEL with an emission at 279 nm. The device structure consists of 3 x 2 nm AlGaN quantum wells (QW) in a 60 nm Al0.70Ga0.30N waveguide and AlN cladding layers. The 140x140 μm large photonic crystal is dry etched into the top AlN cladding layer with a hexagonal lattice consisting of circular holes with a lattice constant of 140 nm and an etch depth of 65 nm, leaving 65 nm between the bottom of the photonic crystals and the first quantum well. Lasing in these PCSELs was achieved by resonant pumping of the QWs by a 266 nm pulsed laser with a spot size of 82 μm at room temperature. The devices exhibit threshold pump power densities from 25 down to 13 MW/cm2 showing a spectral narrowing down to 25 pm. Far-field patterns and band structures were investigated for a range of filling factors (fraction of the surface that is etched) between 10% to 26%, and the far-fields contain emission bands that were not yet reported in PCSELs at longer wavelengths. Changing the filling factor affects the photonic crystal band structure and thereby the optical mode at the Γ-point that will reach threshold first. This feature enables us to intentionally select the lasing mode with the desired far-field pattern. By a proper choice of filling factor, the intensity in the angular emission bands is diminished, resulting in a far-field with a narrow beam divergence of <1°.
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| 3. |
- Bruder, Lukas, et al.
(författare)
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Coherent multidimensional spectroscopy in the gas phase
- 2019
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 52:18
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Tidskriftsartikel (refereegranskat)abstract
- Recent work applying multidimentional coherent electronic spectroscopy at dilute samples in the gas phase is reviewed. The development of refined phase cycling approaches with improved sensitivity has opened up new opportunities to probe even dilute gas-phase samples. In this context, first results of two-dimensional spectroscopy performed at doped helium droplets reveal the femtosecond dynamics upon the electronic excitation of cold, weakly-bound molecules, and even the induced dynamics from the interaction with the helium environment. Such experiments, offering well-defined conditions at low temperatures, are potentially enabling the isolation of fundamental processes in the excitation and charge transfer dynamics of molecular structures which so far have been masked in complex bulk environments.
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| 4. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 5. |
- Griewahn, Laura, et al.
(författare)
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SPATA2 restricts OTULIN-dependent LUBAC activity independently of CYLD
- 2023
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 42:1
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Tidskriftsartikel (refereegranskat)abstract
- SPATA2 mediates the recruitment of CYLD to immune receptor complexes by bridging the interaction of CYLD with the linear ubiquitylation assembly complex (LUBAC) component HOIP. Whether SPATA2 exhibits functions independently of CYLD is unclear. Here, we show that, while Cyld−/− and Spata2−/− mice are viable, double mutants exhibit highly penetrant perinatal lethality, indicating independent functions of SPATA2 and CYLD. Cyld−/−Spata2−/− fibroblasts show increased M1-linked TNFR1-SC ubiquitylation and, similar to Cyld−/−Spata2−/− macrophages and intestinal epithelial cells, elevated pro-inflammatory gene expression compared with Cyld−/− or Spata2−/− cells. We show that SPATA2 competes with OTULIN for binding to HOIP via its PUB-interacting motif (PIM) and its zinc finger domain, thereby promoting autoubiquitylation of LUBAC. Consistently, increased pro-inflammatory signaling in Cyld−/−Spata2−/− cells depends on the presence of OTULIN. Our data therefore indicate that SPATA2 counteracts, independently of CYLD, the deubiquitylation of LUBAC by OTULIN and thereby attenuates LUBAC activity and pro-inflammatory signaling.
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| 6. |
- Kaltenbaek, Rainer, et al.
(författare)
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Macroscopic Quantum Resonators (MAQRO) : 2015 update
- 2016
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Ingår i: EPJ Quantum Technology. - : Springer Berlin/Heidelberg. - 2196-0763. ; 3:1
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Forskningsöversikt (refereegranskat)abstract
- Do the laws of quantum physics still hold for macroscopic objects - this is at the heart of Schrodinger's cat paradox - or do gravitation or yet unknown effects set a limit for massive particles? What is the fundamental relation between quantum physics and gravity? Ground-based experiments addressing these questions may soon face limitations due to limited free-fall times and the quality of vacuum and microgravity. The proposed mission Macroscopic Quantum Resonators (MAQRO) may overcome these limitations and allow addressing such fundamental questions. MAQRO harnesses recent developments in quantum optomechanics, high-mass matter-wave interferometry as well as state-of-the-art space technology to push macroscopic quantum experiments towards their ultimate performance limits and to open new horizons for applying quantum technology in space. The main scientific goal is to probe the vastly unexplored 'quantum-classical' transition for increasingly massive objects, testing the predictions of quantum theory for objects in a size and mass regime unachievable in ground-based experiments. The hardware will largely be based on available space technology. Here, we present the MAQRO proposal submitted in response to the 4th Cosmic Vision call for a medium-sized mission (M4) in 2014 of the European Space Agency (ESA) with a possible launch in 2025, and we review the progress with respect to the original MAQRO proposal for the 3rd Cosmic Vision call for a medium-sized mission (M3) in 2010. In particular, the updated proposal overcomes several critical issues of the original proposal by relying on established experimental techniques from high-mass matter-wave interferometry and by introducing novel ideas for particle loading and manipulation. Moreover, the mission design was improved to better fulfill the stringent environmental requirements for macroscopic quantum experiments.
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| 7. |
- Kirchhof, Paulus, et al.
(författare)
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A roadmap to improve the quality of atrial fibrillation management : proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference
- 2016
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 18:1, s. 37-50
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Tidskriftsartikel (refereegranskat)abstract
- At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.
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| 8. |
- Kirchhof, Paulus, et al.
(författare)
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Personalized management of atrial fibrillation : Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference
- 2013
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 15:11, s. 1540-1556
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Tidskriftsartikel (refereegranskat)abstract
- The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.
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| 9. |
- Kranak, Verina F., et al.
(författare)
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Hydrogenous Zintl Phase Ba3Si4Hx (x=1-2) : Transforming Si-4 Butterfly Anions into Tetrahedral Moieties
- 2015
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 54:3, s. 756-764
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Tidskriftsartikel (refereegranskat)abstract
- The hydride Ba3Si4Hx (x = 1-2) was prepared by sintering the Zintl phase Ba3Si4, which contains Si-4(6-) butterfly-shaped polyanions, in a hydrogen atmosphere at pressures of 10-20 bar and temperatures of around 300 degrees C. Initial structural analysis using powder neutron and X-ray diffraction data suggested that Ba3Si4Hx adopts the Ba3Ge4C2 type [space group I4/mcm (No. 140), a approximate to 8.44 angstrom, c approximate to 11.95 angstrom, Z = 8] where Ba atoms form a three-dimensional array of corner-condensed octahedra, which are centered by H atoms. Tetrahedron-shaped Si-4 polyanions complete a perovskite-like arrangement. Thus, hydride formation is accompanied by oxidation of the butterfly polyanion, but the model with the composition Ba3Si4H is not charge-balanced. First-principles computations revealed an alternative structural scenario for Ba3Si4Hx, which is based on filling pyramidal Ba-5 interstices in Ba3Si4. The limiting composition is x = 2 [space group P4(2)/mmm (No. 136), a approximate to 8.4066 angstrom, c approximate to 12.9186 angstrom, Z = 8], and for x > 1, Si atoms also adopt tetrahedron-shaped polyanions. Transmission electron microscopy investigations showed that Ba3Si4Hx is heavily disordered in the c direction. Most plausible is to assume that Ba3Si4Hx has a variable H content (x = 1-2) and corresponds to a random intergrowth of P- and I-type structure blocks. In either form, Ba3Si4Hx is classified as an interstitial hydride. Polyanionic hydrides in which H is covalently attached to Si remain elusive.
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| 10. |
- Lüönd, Antonia M., et al.
(författare)
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Don’t get too close to me: depressed and non-depressed survivors of child maltreatment prefer larger comfortable interpersonal distances towards strangers
- 2022
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Ingår i: European Journal of Psychotraumatology. - : Taylor & Francis. - 2000-8198 .- 2000-8066. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood maltreatment (CM) is frequently linked to interpersonal problemssuch as difficulties in social relationships, loneliness, and isolation. These difficulties mightpartly stem from troubles regulating comfortable interpersonal distance (CIPD).Objective: We experimentally investigated whether CM manifests in larger CIPD and whetherall subtypes of CM (i.e., physical, emotional, or sexual abuse and physical or emotional neglect)affect CIPD.Methods: Using the stop-distance method (i.e. a team member approached participants untilthe latter indicated discomfort), we assessed CIPD in 84 adults with a self-reported history ofCM (24 with depressive symptoms) and 57 adult controls without a history of CM (withoutdepressive symptoms).Results: Adults with CM showed a larger CIPD (Mdn = 86 cm) than controls (Mdn = 68 cm), andCIPD was largest for those with CM combined with current depressive symptoms (Mdn =145 cm) (p’s < .047). In the latter group, all subtypes of CM were associated with a largerCIPD compared to controls (p’s < .045). In the CM group without depressive symptoms, onlythose with emotional abuse (p = .040) showed a larger CIPD than controls.Conclusions: These results add to findings of differential socio-emotional long-termconsequences of CM, depending upon the subtype of CM. Future research should explorewhether a larger CIPD has a negative impact on social functioning in individuals exposed toCM, particularly in those with depressive symptoms.
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