| 1. |
- Bengtsson, Anders, 1988, et al.
(författare)
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Counterterms in gravity in the light-front formulation and a D=2 conformal-like symmetry in gravity
- 2013
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Ingår i: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479 .- 1126-6708. ; 58:5-6, s. 485-501
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we discuss gravity in the light-front formulation (light-cone gauge) and show how possible counterterms arise. We find that Poincare invariance is not enough to find the three-point counterterms uniquely. Higher-spin fields can intrude and mimic three-point higher derivative gravity terms. To select the correct term we have to use the remaining reparametrization invariance that exists after the gauge choice. We finally sketch how the corresponding programme for N = 8 Supergravity should work.
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| 2. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 3. |
- Gustavsson, Johan, 1974, et al.
(författare)
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Silicon integrated 850-nm hybrid vertical-cavity laser for life science applications
- 2017
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Ingår i: VCSEL Day 2017.
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Konferensbidrag (refereegranskat)abstract
- The integration of efficient laser sources on silicon would enable fully integrated silicon photonic circuits with a high degree of functionality and performance complexity for many applications [1]. Different integration concepts have therefore been suggested, where one such technique is the heterogeneous integration of a vertical-cavity laser (VCL), referred to as a hybrid VCL. It is promising as it has potential to offer low drive currents, high modulation bandwidths, and small footprint [2-4]. In-plane emission with waveguide-coupling can be achieved by an intra-cavity waveguide embossed with a weak diffraction grating, as an example [5]. Integration of such short-wavelength laser sources on a silicon-nitride (SiN) waveguide platform on silicon may enable fully integrated silicon photonic circuits for applications not only in short-reach optical interconnects but also in life science and bio-photonics. As a first step in realizing short-wavelength hybrid VCLs with in-plane emission coupled to a SiN waveguide, we have developed a technique to produce high performance 850-nm hybrid VCLs with out-of-plane emission. It is based on adhesive bonding of epitaxial AlGaAs-material onto a dielectric distributed Bragg reflector (DBR) on silicon [6-8]. We have fabricated devices with surface emission having sub-mA threshold current, >2 mW output power, and 25 Gbit/s modulation speed [8]. To be able to demonstrate in-plane emission with SiN waveguide coupling from our hybrid 850-nm VCLs, our next step is to add a SiN waveguide structure with embossed grating on top of the dielectric DBR, before adhesively bonding the AlGaAs-material. So far, based on numerical simulations, we have designed a device that is predicted to yield a slope efficiency of ~0.3 W/A at 25 °C for the light coupled to a single-mode waveguide, while maintaining a sub-mA threshold current for the lasing [9]. This work is supported by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 688519 (PIX4life), the Swedish Foundation for Strategic Research (SSF), and the European FP7-ERC-InSpectra Advanced Grant. References [1] Z. Zhou et al., Light Sci. Appl., vol. 4, no. 11, p. e358, 2015. [2] Y. Tsunemi et al., Opt. Express, vol. 21, no. 23, p. 28685, 2013. [3] J. Ferrara et al., Opt. Express, vol. 23, no. 3, p. 2512, 2015. [4] G.C. Park et al., Laser Photon. Rev., vol. 9, no. 3, p. L11, 2015. [5] D. A. Louderback et al., Electron. Lett., vol. 40, no. 17, p. 1064, 2004. [6] E.P. Haglund et al., Opt. Express, vol. 23, no. 26, p. 33634, 2015. [7] E.P. Haglund et al., IEEE Photon. Technol. Lett., vol. 28, no. 8, p. 856, 2016. [8] E.P. Haglund et al., IEEE J. Sel. Top. Quantum Electron., vol. 23, no. 6, p. 1700109, 2017. [9] S. Kumari et al., Submitted to IEEE Photon. J.,2017.
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| 4. |
- Gustavsson, Johan, 1974, et al.
(författare)
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Silicon-Integrated Hybrid-Vertical-Cavity Lasers for Life Science Applications
- 2017
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Ingår i: 2017 IEEE Photonics Conference. - 9781509065783 ; 2017-January
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Konferensbidrag (refereegranskat)abstract
- Hybrid 850-nm-wavelength vertical-cavity lasers formed by adhesively bonding AlGaAs-material to a dielectric distributed Bragg reflector on Silicon has experimentally enabled sub-mA threshold current and 25 Gb/s modulation speed. Numerical calculations estimate >0.3 mW/mA slope efficiency for in-plane SiN waveguide coupled light using an intra-cavity grating.
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| 5. |
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| 6. |
- Krajnovic, Sinisa, 1970, et al.
(författare)
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Large Eddy Simulation Investigation of the Hysteresis Effects in the Flow Around an Oscillating Ground Vehicle
- 2011
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Ingår i: Journal of Fluids Engineering, Transactions of the ASME. - : ASME International. - 1528-901X .- 0098-2202. ; 133:12, s. 121103-
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents large eddy simulations (LES) of flow around a simplified vehicle model oscillating around its vertical axis. The frequency of the Strouhal number St = 0.068 and a relatively small amplitude of the oscillation are chosen to be representative for the crosswind conditions of vehicles on the road. The results were found to agree well with data from previous experimental investigations. Furthermore, the differences in LES flows between quasi-steady and dynamic flow conditions are presented and underlying flow mechanisms are explored. The cause of the phenomena of hysteresis and phase shift was found in the inertia of the flow to adjust to sudden changes in the direction of the oscillation of the body.
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| 7. |
- Krajnovic, Sinisa, 1970, et al.
(författare)
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Numerical Study of Crosswind Stability of a Simplified Car in Gusty Wind
- 2010
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Ingår i: 8th MIRA International Vehicle Aerodynamics Conference.
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Konferensbidrag (refereegranskat)abstract
- This paper present large eddy simulations of flow around a simplified vehicle model oscillating around its vertical axis. The frequency of St=0.068 and relatively small amplitude of the oscillation are chosen to be representative for the crosswind conditions of vehicles on the road. The results were found to agree well with data from previous experimental investigation. Furthermore, the differences in LES flows between quasi-steady and dynamic flow conditions are presented and underlying flow mechanisms are explored. The cause for phenomena of hysteresis and phase shift was found in the inertia of the flow to adjust to sudden changes in direction of the oscillation of the body.
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| 8. |
- Kumari, Sulakshna, et al.
(författare)
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Design of an 845-nm GaAs Vertical-Cavity Silicon-Integrated Laser with an Intracavity Grating for Coupling to a SiN Waveguide Circuit
- 2017
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Ingår i: IEEE Photonics Journal. - 1943-0655. ; 9:4, s. 1504109-
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Tidskriftsartikel (refereegranskat)abstract
- A short-wavelength hybrid GaAs vertical-cavity silicon-integrated laser (VCSIL) with in-plane waveguide coupling has been designed and optimized using numerical simulations. A shallow etched silicon nitride (SiN) grating is placed inside the cavity of the hybrid vertical-cavity silicon-integrated laser to both set the polarization state of the resonant optical field and to enable output coupling to a SiN waveguide with high efficiency. The numerical simulations predict that for apertures of 4 and 6-μm oxide-confined VCSILs operating at 845-nm wavelength, a slope efficiency for the light coupled to the waveguide of 0.18 and 0.22 mW/mA is achievable, respectively, while maintaining a low threshold gain of 583 and 589 cm−1, respectively, for the lasing.
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| 9. |
- Kumari, Sulakshna, et al.
(författare)
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Integration of GaAs-based VCSEL array on SiN platform with HCG reflectors for WDM applications
- 2015
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781628414622 ; 9372, s. Art. no. 93720U-
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Konferensbidrag (refereegranskat)abstract
- We present a GaAs-based VCSEL structure, BCB bonded to a Si3N4 waveguide circuit, where one DBR is substituted by a free-standing Si3N4 high-contrast-grating (HCG) reflector realized in the Si3N4 waveguide layer. This design enables solutions for on-chip spectroscopic sensing, and the dense integration of 850-nm WDM data communication transmitters where individual channel wavelengths are set by varying the HCG parameters. RCWA shows that a 300nm-thick Si3N4 HCG with 800nm period and 40% duty cycle reflects strongly (
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| 10. |
- Mohammad, Majd, et al.
(författare)
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Staphylococcus aureus lipoproteins promote abscess formation in mice, shielding bacteria from immune killing.
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite being a major bacterial factor in alerting the human immune system, the role of Staphylococcus aureus (S. aureus) lipoproteins (Lpp) in skin infections remains largely unknown. Here, we demonstrated that subcutaneous injection of S. aureus Lpp led to infiltration of neutrophils and monocytes/macrophages and induced skin lesions in mice. Lipid-moiety of S. aureus Lpp and host TLR2 was responsible for such effect. Lpp-deficient S. aureus strains exhibited smaller lesion size and reduced bacterial loads than their parental strains; the altered phenotype in bacterial loads was TLR2-independent. Lpp expression in skin infections contributed to imbalanced local hemostasis toward hypercoagulable state. Depletion of leukocytes or fibrinogen abrogated the effects induced by Lpp in terms of skin lesions and bacterial burden. Our data suggest that S. aureus Lpp induce skin inflammation and promote abscess formation that protects bacteria from innate immune killing. This suggests an intriguing bacterial immune evasion mechanism.
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