| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aughton, Karen, et al.
(författare)
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hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:22
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Tidskriftsartikel (refereegranskat)abstract
- Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.Simple Summary:Recent clinical trials suggest that combination therapies that include either gemcitabine or 5-fluorouracil (5-FU) both give significant survival benefits for pancreatic cancer patients. The tumor level of the nucleoside transporter hENT1 is prognostic in patients treated with adjuvant gemcitabine but not adjuvant 5-FU. This work shows for the first time that hENT1 is only predictive of benefit from gemcitabine over 5-FU in patients with low levels of CDA transcript. A choice between adjuvant 5-FU based combination therapies (such as FOLFIRINOX) and gemcitabine-based therapy (e.g., GemCap) could be made based on a combination of hENT1 protein and CDA mRNA measured in a resected tumor.
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| 3. |
- Brinson, Robert G., et al.
(författare)
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Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics
- 2019
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Ingår i: mAbs. - : Informa UK Limited. - 1942-0862 .- 1942-0870. ; 11:1, s. 94-105
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Tidskriftsartikel (refereegranskat)abstract
- The increased interest in using monoclonal antibodies (mAbs) as a platform for biopharmaceuticals has led to the need for new analytical techniques that can precisely assess physicochemical properties of these large and very complex drugs for the purpose of correctly identifying quality attributes (QA). One QA, higher order structure (HOS), is unique to biopharmaceuticals and essential for establishing consistency in biopharmaceutical manufacturing, detecting process-related variations from manufacturing changes and establishing comparability between biologic products. To address this measurement challenge, two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) methods were introduced that allow for the precise atomic-level comparison of the HOS between two proteins, including mAbs. Here, an inter-laboratory comparison involving 26 industrial, government and academic laboratories worldwide was performed as a benchmark using the NISTmAb, from the National Institute of Standards and Technology (NIST), to facilitate the translation of the 2D-NMR method into routine use for biopharmaceutical product development. Two-dimensional H-1,N-15 and H-1,C-13 NMR spectra were acquired with harmonized experimental protocols on the unlabeled Fab domain and a uniformly enriched-N-15, 20%-C-13-enriched system suitability sample derived from the NISTmAb. Chemometric analyses from over 400 spectral maps acquired on 39 different NMR spectrometers ranging from 500 MHz to 900 MHz demonstrate spectral fingerprints that are fit-for-purpose for the assessment of HOS. The 2D-NMR method is shown to provide the measurement reliability needed to move the technique from an emerging technology to a harmonized, routine measurement that can be generally applied with great confidence to high precision assessments of the HOS of mAb-based biotherapeutics.
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| 4. |
- Grini, S., et al.
(författare)
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Dynamic Impurity Redistributions in Kesterite Absorbers
- 2020
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Ingår i: Physica status solidi. B, Basic research. - : Wiley. - 0370-1972 .- 1521-3951.
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Tidskriftsartikel (refereegranskat)abstract
- Cu2ZnSn(S,Se)4 is a promising nontoxic earth-abundant solar cell absorber. To optimize the thin films for solar cell device performance, postdeposition treatments at temperatures below the crystallization temperature are normally performed, which alter the surface and bulk properties. The polycrystalline thin films contain relatively high concentrations of impurities, such as sodium, oxygen and hydrogen. During the treatments, these impurities migrate and likely agglomerate at lattice defects or interfaces. Herein, impurity redistribution after air annealing for temperatures up to 200 °C and short heavy water treatments are studied. In addition, nonuniformities of the sodium distribution on a nanometer and micrometer scale are characterized by atom probe tomography and secondary ion mass spectrometry, respectively. Sodium and oxygen correlate to a greater extent after heat treatments, supporting strong binding between the two impurities. Redistributions of these impurities occur even at room temperature over longer time periods. Heavy water treatments confirm out-diffusion of sodium with more incorporation of oxygen and hydrogen. It is observed that the increased hydrogen content does not originate from the heavy water. The existence of an “ice-like” layer on top of the Cu2ZnSnS4 layer is proposed.
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| 5. |
- Grini, Sigbjörn, et al.
(författare)
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Low temperature incorporation of selenium in Cu2ZnSnS4 : Diffusion and nucleation
- 2018
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Ingår i: Thin Solid Films. - : ELSEVIER SCIENCE SA. - 0040-6090 .- 1879-2731. ; 665, s. 159-163
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Tidskriftsartikel (refereegranskat)abstract
- Band gap grading of Cu2ZnSn(S, Se)(4) (CZTSSe) solar cells can be achieved by varying the S-r = [S]/([S]+[Se]) ratio in the absorber layer with depth. One approach is a two-step annealing process where the absorber is first sulfurized to Cu2ZnSnS4 (CZTS) followed by selenization to form CZTSSe. However, once nucleation of CZTSSe initiates, the rapid interchange of S and Se limits the control over the Sr ratio with depth. Here, we have studied incorporation of Se into CZTS and observed the behavior of Se below and up to the nucleation temperature of CZTSSe. Se diffusion at 337 and 360 degrees C is dominated by grain boundary diffusion while some increase of Se is also seen in the region from 100 to 800 nm from the surface. After selenization at 409 degrees C, recrystallization is observed and CZTSSe grains are formed. The recrystallization is more rapid for a smaller average grain size and is facilitated by diffusion of Na from the back contact. The grain boundary diffusion is identified with secondary ion mass spectrometry measurements by measuring the accumulation in the CZTS/Mo interface for three samples with different average grain size.
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| 6. |
- Grini, Sigbjörn, et al.
(författare)
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Secondary ion mass spectrometry as a tool to study selenium gradient in Cu2ZnSn(S,Se)4
- 2017
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Ingår i: Physica Status Solidi. C, Current topics in solid state physics. - : Wiley. - 1610-1634 .- 1610-1642. ; :6
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Tidskriftsartikel (refereegranskat)abstract
- Secondary ion mass spectrometry (SIMS) has been utilized to study compositional gradients in compound-sputtered and annealed Cu2ZnSn(S,Se)(4) (CZTSSe). SIMS image depth profiling shows a non-uniform spatial distribution of selenium and supports a mechanism where selenization is accompanied by grain growth rather than substitution of selenium for sulfur. Furthermore, SIMS depth profiles of S and Se using O-2(+) primary ions and detecting molecular ions of the MCs+ type using Cs+ primary ions have been compared, where a linear relationship between the sulfur and selenium concentration suitable for compositional analysis is observed for concentrations with an Se/(S+Se) ratio in the range from 0.25 to 0.65. 3D image of the spatial Se distribution in a 20 x 20 mu m(2) grid measured with SIMS image depth profiling.
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| 7. |
- Grini, Sigbjörn, et al.
(författare)
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Strong Interplay between Sodium and Oxygen in Kesterite Absorbers : Complex Formation, Incorporation, and Tailoring Depth Distributions
- 2019
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Ingår i: Advanced Energy Materials. - : WILEY-V C H VERLAG GMBH. - 1614-6832 .- 1614-6840. ; 9:27
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Tidskriftsartikel (refereegranskat)abstract
- Sodium and oxygen are prevalent impurities in kesterite solar cells. Both elements are known to strongly impact performance of the kesterite devices and can be connected to efficiency improvements seen after heat treatments. The sodium distribution in the kesterite absorber is commonly reported, whereas the oxygen distribution has received less attention. Here, a direct relationship between sodium and oxygen in kesterite absorbers is established using secondary ion mass spectrometry and explained by defect analyses within the density functional theory. The calculations reveal a binding energy of 0.76 eV between the substitutional defects Na-Cu and O-S in the nearest neighbor configuration, indicating an abundance of Na Symbol of the Klingon Empire O complexes in kesterite absorbers at relevant temperatures. Oxygen incorporation is studied by introducing isotopic O-18 at different stages of the Cu2ZnSnS4/Mo/soda-lime glass baseline processing. It is observed that oxygen from the Mo back contact and contaminations during the sulfurization are primary contributors to the oxygen distribution. Indeed, unintentional oxygen incorporation leads to immobilization of sodium. This results in a strong correlation between sodium and oxygen, in excellent agreement with the theoretical calculations. Consequently, oxygen availability should be monitored to optimize postdeposition heat treatments to control impurities in kesterite absorbers and ultimately, the solar cell efficiency.
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| 8. |
- Hansen, Lea B.S., et al.
(författare)
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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| 9. |
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| 10. |
- Larsen, Jes K, et al.
(författare)
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Surface modification through air annealing Cu2ZnSn(S,Se)4 absorbers
- 2017
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 633, s. 118-121
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies demonstrate that air annealing can have a positive effect on the device performance of Cu2ZnSn(SxSe1-x)(4)[CZTSSe] solar cells. In this work air annealing of the selenium containing CZTSSe is compared to the pure sulfide CZTS. It is discovered that the selenium containing absorbers benefit from air annealing at higher temperatures than selenium free absorbers. The highest efficiency obtained utilizing the air annealing treatment on selenium containing absorbers is 9.7%. We find that the band gap is narrowed when air annealing, which is partially explained by increased Cu-Zn disorder. Furthermore Zn enrichment of the surface after etching is identified as a possible cause of enhanced device performance. It is additionally observed that elemental selenium present on the CZTSSe surface is reduced in the air annealing treatment. Selenium removal is another possible explanation for the enhanced performance caused by the air annealing treatment.
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