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- Zhukova, Nataliya, et al.
(författare)
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WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
- 2014
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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| 2. |
- Riedel, Gernot J, et al.
(författare)
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Reducing Thermal Resistance of AlGaN/GaN Electronic Devices Using Novel Nucleation Layers
- 2009
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Ingår i: IEEE Electron Device Letters. - 0741-3106 .- 1558-0563. ; 30:2, s. 103-106
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Tidskriftsartikel (refereegranskat)abstract
- Currently, up to 50% of the channel temperature in AlGaN/GaN electronic devices is due to the thermal-boundary resistance (TBR) associated with the nucleation layer (NL) needed between GaN and SiC substrates for high-quality heteroepitaxy. Using 3-D time-resolved Raman thermography, it is shown that modifying the NL used for GaN on SiC epitaxy from the metal-organic chemical vapor deposition (MOCVD)-grown standard AIN-NL to a hot-wall MOCVD-grown AIN-NL reduces NL TBR by 25%, resulting in similar to 10% reduction of the operating temperature of AlGaN/GaN HEMTs. Considering the exponential relationship between device lifetime and temperature, lower TBR NLs open new opportunities for improving the reliability of AlGaN/GaN devices.
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| 3. |
- Ali, Sharafat, 1976-, et al.
(författare)
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Issues associated with the development of transparent oxynitride glasses
- 2015
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Ingår i: Ceramics International. - : Elsevier. - 0272-8842 .- 1873-3956. ; 41:3, s. 3345-3354
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Tidskriftsartikel (refereegranskat)abstract
- Oxynitride glasses and glass ceramics are increasingly recognized as potential materials in specialist applications in modern industrial sectors. Oxynitride glasses have superior mechanical, rheological and optical properties to their oxide glass counterparts. Properties of these glasses can be tailored by changes in nitrogen content and additions of various alkaline-earth and or rare-earth elements. In contrast to oxide glasses, oxynitride glasses are difficult to prepare which adds to production costs. Furthermore, they contain impurities in the form of elemental silicon and silicides, have poor oxidation resistance in air above their glass transition temperatures and have poor transparency in the visible region. This article reviews the above issues in relation to the potential applications of these glasses.
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| 4. |
- van Hees, Vincent T, et al.
(författare)
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Estimation of Daily Energy Expenditure in Pregnant and Non-Pregnant Women Using a Wrist-Worn Tri-Axial Accelerometer
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- ackground: Few studies have compared the validity of objective measures of physical activity energy expenditure (PAEE) in pregnant and non-pregnant women. PAEE is commonly estimated with accelerometers attached to the hip or waist, but little is known about the validity and participant acceptability of wrist attachment. The objectives of the current study were to assess the validity of a simple summary measure derived from a wrist-worn accelerometer (GENEA, Unilever Discover, UK) to estimate PAEE in pregnant and non-pregnant women, and to evaluate participant acceptability. less thanbrgreater than less thanbrgreater thanMethods: Non-pregnant (N = 73) and pregnant (N = 35) Swedish women (aged 20-35 yrs) wore the accelerometer on their wrist for 10 days during which total energy expenditure (TEE) was assessed using doubly-labelled water. PAEE was calculated as 0.96TEE-REE. British participants (N = 99; aged 22-65 yrs) wore accelerometers on their non-dominant wrist and hip for seven days and were asked to score the acceptability of monitor placement (scored 1 [least] through 10 [most] acceptable). less thanbrgreater than less thanbrgreater thanResults: There was no significant correlation between body weight and PAEE. In non-pregnant women, acceleration explained 24% of the variation in PAEE, which decreased to 19% in leave-one-out cross-validation. In pregnant women, acceleration explained 11% of the variation in PAEE, which was not significant in leave-one-out cross-validation. Median (IQR) acceptability of wrist and hip placement was 9(8-10) and 9(7-10), respectively; there was a within-individual difference of 0.47 (p andlt; .001). less thanbrgreater than less thanbrgreater thanConclusions: A simple summary measure derived from a wrist-worn tri-axial accelerometer adds significantly to the prediction of energy expenditure in non-pregnant women and is scored acceptable by participants.
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