| 1. |
- 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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| 2. |
- Staudt, Matthias, 1977, et al.
(författare)
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Coupling of an erbium spin ensemble to a superconducting resonator
- 2012
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 1361-6455 .- 0953-4075. ; 45:12, s. Art. no. 124019-
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Tidskriftsartikel (refereegranskat)abstract
- A quantum coherent interface between optical and microwave photons can be used as a basic building block within a future quantum information network. The interface is envisioned as an ensemble of rare-earth ions coupled to a superconducting resonator, allowing for coherent transfer between optical and microwave photons. Towards this end, we have realized a hybrid device coupling a Er3+-doped Y2SiO5 crystal in a superconducting coplanar waveguide cavity. We observe a collective spin coupling of 4 MHz and a spin linewidth of down to 75 MHz.
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| 3. |
- Börve, Alexander, et al.
(författare)
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Smartphone Teledermoscopy Referrals: A Novel Process for Improved Triage of Skin Cancer Patients.
- 2015
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 95:2, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- In this open, controlled, multicentre and prospective observational study, smartphone teledermoscopy referrals were sent from 20 primary healthcare centres to 2 dermatology departments for triage of skin lesions of concern using a smartphone application and a compatible digital dermoscope. The outcome for 816 patients referred via smartphone teledermoscopy was compared with 746 patients referred via the traditional paper-based system. When surgical treatment was required, the waiting time was significantly shorter using teledermoscopy for patients with melanoma, melanoma in situ, squamous cell carcinoma, squamous cell carcinoma in situ and basal cell carcinoma. Triage decisions were also more reliable with teledermoscopy and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits. Only 4 teledermoscopy referrals (0.4%) had to be excluded due to poor image quality. Smartphone teledermoscopy referrals allow for faster and more efficient management of patients with skin cancer as compared to traditional paper referrals.
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| 4. |
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| 5. |
- Paoli, John, 1975, et al.
(författare)
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Response to the letter by Leitch et al.
- 2015
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Ingår i: Acta dermato-venereologica. - 1651-2057. ; 95:7, s. 870-1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Persson, Fredrik, 1978, et al.
(författare)
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Excess Dissipation in a Single-Electron Box: The Sisyphus Resistance
- 2010
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 10:3, s. 953-957
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the ac response of a single-electron box (SEB). We apply a radio frequency signal with a Frequency larger than the tunneling rate and drive the system out of equilibrium. We observe much more dissipation in the SEB then one would expect from a simple circuit model, We can explain this in terms of a mechanism that we call the Sisyphus resistance. The Sisyphus resistance has a strong gate dependence which can be used for electrometery applications.
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| 7. |
- Persson, Fredrik, 1978, et al.
(författare)
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Fast readout of a single Cooper-pair box using its quantum capacitance
- 2010
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 82:13, s. Article Number: 134533 -
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Tidskriftsartikel (refereegranskat)abstract
- We have fabricated a single Cooper-pair box (SCB) together with an on-chip lumped element resonator. By utilizing the quantum capacitance of the SCB, its state can be read out by detecting the phase of a radio-frequency signal reflected off the resonator. The resonator was optimized for fast readout. By studying quasiparticle tunneling events in the SCB, we have characterized the performance of the readout and found that we can perform a single-shot parity measurement, with a signal-to-noise ratio of 1, in approximately 50 ns. This is an order of magnitude faster than previously reported measurements.
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| 8. |
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| 9. |
- Sandberg, Carin, 1969, et al.
(författare)
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Fluorescence Diagnostics of Basal Cell Carcinomas Comparing Methyl-aminolaevulinate and Aminolaevulinic Acid and Correlation with Visual Clinical Tumour Size.
- 2011
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 91:4, s. 398-403
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence diagnostics based on aminolaevulinic acid (ALA) fluorescence has been suggested as an in vivo pre-surgical tool for tumour demarcation. We performed fluorescence diagnostics of 35 basal cell carcinomas (BCCs) undergoing photodynamic therapy (PDT) using methyl-aminolaevulinate (MAL). In addition, a semi-automated thresholding algorithm was implemented to detect the potential tumour region. The mean tumour fluorescence contrast was found to be 1.65±0.06 during the first MAL-PDT session, and increased to 1.84±0.07 at the second treatment (p<0.01). This could imply that disruption of the skin barrier and inflammatory responses after the first session of PDT led to higher accumulation of proto-porphyrin IX during the second session of PDT. The tumour areas detected based on fluorescence in small BCCs (<1 cm2) were in general (n=18/23) larger than the visual clinical tumour size. In addition, the fluorescence contrast using MAL (1.65±0.06) was found to be significantly higher (p<10-4) than the contrast (data from previous study) after application of ALA (1.20±0.06). Thus, MAL generally provides higher tumour contrast than ALA in BCCs, and should be preferred for use in fluore-scence diagnostics. Correlation between fluorescence, lack of treatment response and/or pain was not observed.
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| 10. |
- Sandberg, Martin, 1977, et al.
(författare)
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Exploring circuit quantum electrodynamics using a widely tunable superconducting resonator
- 2009
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Ingår i: Physica Scripta. - 1402-4896 .- 0031-8949. ; T137, s. Art. no. 014018-
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Tidskriftsartikel (refereegranskat)abstract
- We have fabricated and characterized systems consisting of superconducting quantum bits (qubits) of the transmon type, coupled to a tunable transmission line resonator. The resonator consists of a superconducting quarter wavelength coplanar waveguide (CPW) resonator that is made tunable by terminating the transmission line to ground through a superconducting quantum interference device (SQUID). Here we present measurements on two devices where we observe Rabi oscillations as we drive the qubit, and vacuum Rabi splitting both as we tune the qubits into resonance with the resonator and as we tune the resonator into resonance with the qubits. We also observe coherent interaction between two resonant qubits. In addition, we demonstrate that we can calculate the response very accurately using a multilevel Hamiltonian.
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