| 1. |
- Breznau, Nate, et al.
(author)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Journal article (peer-reviewed)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 2. |
- Carrad, D J, et al.
(author)
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Hybrid Nanowire Ion-to-Electron Transducers for Integrated Bioelectronic Circuitry
- 2017
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In: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 17:2, s. 827-833
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Journal article (peer-reviewed)abstract
- A key task in the emerging field of bioelectronics is the transduction between ionic/protonic and electronic signals at high fidelity. This is a considerable challenge since the two carrier types exhibit intrinsically different physics and are best supported by very different materials types - electronic signals in inorganic semiconductors and ionic/protonic signals in organic or bio-organic polymers, gels, or electrolytes. Here we demonstrate a new class of organic-inorganic transducing interface featuring semiconducting nanowires electrostatically gated using a solid proton-transporting hygroscopic polymer. This model platform allows us to study the basic transducing mechanisms as well as deliver high fidelity signal conversion by tapping into and drawing together the best candidates from traditionally disparate realms of electronic materials research. By combining complementary n- and p-type transducers we demonstrate functional logic with significant potential for scaling toward high-density integrated bioelectronic circuitry.
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| 3. |
- Gluschke, J. G., et al.
(author)
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Integrated bioelectronic proton-gated logic elements utilizing nanoscale patterned Nafion
- 2021
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In: Materials Horizons. - : Royal Society of Chemistry (RSC). - 2051-6347 .- 2051-6355. ; 8:1, s. 224-233
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Journal article (peer-reviewed)abstract
- A central endeavour in bioelectronics is the development of logic elements to transduce and process ionic to electronic signals. Motivated by this challenge, we report fully monolithic, nanoscale logic elements featuring n- and p-type nanowires as electronic channels that are proton-gated by electron-beam patterned Nafion. We demonstrate inverter circuits with state-of-the-art ion-to-electron transduction performance giving DC gain exceeding 5 and frequency response up to 2 kHz. A key innovation facilitating the logic integration is a new electron-beam process for patterning Nafion with linewidths down to 125 nm. This process delivers feature sizes compatible with low voltage, fast switching elements. This expands the scope for Nafion as a versatile patternable high-proton-conductivity element for bioelectronics and other applications requiring nanoengineered protonic membranes and electrodes.
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| 4. |
- Nygård, K., et al.
(author)
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ForMAX – a beamline for multiscale and multimodal structural characterization of hierarchical materials
- 2024
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In: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 31:Pt 2, s. 363-377
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Journal article (peer-reviewed)abstract
- The ForMAX beamline at the MAX IV Laboratory provides multiscale and multimodal structural characterization of hierarchical materials in the nanometre to millimetre range by combining small- and wide-angle X-ray scattering with full-field microtomography. The modular design of the beamline is optimized for easy switching between different experimental modalities. The beamline has a special focus on the development of novel fibrous materials from forest resources, but it is also well suited for studies within, for example, food science and biomedical research.
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| 5. |
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| 6. |
- Price, Alison J, et al.
(author)
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Circulating Folate and Vitamin B12 and Risk of Prostate Cancer : A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls.
- 2016
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 70:6, s. 941-951
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Journal article (peer-reviewed)abstract
- BACKGROUND: Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear.OBJECTIVE: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade.DESIGN, SETTING, AND PARTICIPANTS: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incident PCa and subtype by stage and grade.RESULTS AND LIMITATIONS: Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation.CONCLUSIONS: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation.PATIENT SUMMARY: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.
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| 7. |
- Van Parys, A., et al.
(author)
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Assessment of Dietary Choline Intake, Contributing Food Items, and Associations with One-Carbon and Lipid Metabolites in Middle-Aged and Elderly Adults: The Hordaland Health Study
- 2022
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In: Journal of Nutrition. - : Elsevier BV. - 0022-3166. ; 152:2, s. 513-524
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Journal article (peer-reviewed)abstract
- Background: Choline is an essential nutrient for humans and is involved in various physiologic functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism, and the fat-soluble choline form phosphatidylcholine is essential for VLDL synthesis and secretion in the liver connecting choline to the lipid metabolism. Dietary recommendations for choline are not available in the Nordic countries primarily due to data scarcity. Objectives: The aim of this study was to investigate the dietary intake of total choline and individual choline forms, dietary sources, and the association of total choline intake with circulating one-carbon metabolites and lipids. Methods: We included 5746 participants in the Hordaland Health Study, a survey including community-dwelling adults born in 1925-1927 (mean age 72 y, 55% women) and 1950-1951 (mean age 48 y, 57% women). Dietary data were obtained using a 169-item FFQ, and choline content was calculated using the USDA Database for Choline Content of Common Foods, release 2. Metabolites of the one-carbon and lipid metabolism were measured in a nonfasting blood sample obtained at baseline, and the association with total choline intake was assessed using polynomial splines. Results: The geometric mean (95% prediction interval) energy-adjusted total choline intake was 260 (170, 389) mg/d, with phosphatidylcholine being the main form (44%). The major food items providing dietary choline were eggs, low-fat milk, potatoes, and leafy vegetables. Dietary total choline was inversely associated with circulating concentrations of total homocysteine, glycine, and serine and positively associated with choline, methionine, cystathionine, cysteine, trimethyllysine, trimethylamine-N-oxide, and dimethylglycine. A weak association was observed between choline intake and serum lipids. Conclusions: Phosphatidylcholine was the most consumed choline form in community-dwelling adults in Norway. Our findings suggest that choline intake is associated with the concentration of most metabolites involved in the one-carbon and lipid metabolism. © 2021 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition.
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| 8. |
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| 9. |
- Deng, M. T., et al.
(author)
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Majorana bound state in a coupled quantum-dot hybrid-nanowire system
- 2016
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6319, s. 1557-1562
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Journal article (peer-reviewed)abstract
- Hybrid nanowires combining semiconductor and superconductor materials appear well suited for the creation, detection, and control of Majorana bound states (MBSs). We demonstrate the emergence of MBSs from coalescing Andreev bound states (ABSs) in a hybrid InAs nanowire with epitaxial Al, using a quantum dot at the end of the nanowire as a spectrometer. Electrostatic gating tuned the nanowire density to a regime of one or a few ABSs. In an applied axial magnetic field, a topological phase emerges in which ABSs move to zero energy and remain there, forming MBSs. We observed hybridization of the MBS with the end-dot bound state, which is in agreement with a numerical model. The ABS/MBS spectra provide parameters that are useful for understanding topological superconductivity in this system.
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| 10. |
- Grijseels, S., et al.
(author)
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Identification of the decumbenone biosynthetic gene cluster in penicillium decumbens and the importance for production of calbistrin
- 2018
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In: Fungal Biology and Biotechnology. - : Springer Science and Business Media LLC. - 2054-3085. ; 5:1, s. 1-17
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Journal article (peer-reviewed)abstract
- Background: Filamentous fungi are important producers of secondary metabolites, low molecular weight molecules that often have bioactive properties. Calbistrin A is a secondary metabolite with an interesting structure that was recently found to have bioactivity against leukemia cells. It consists of two polyketides linked by an ester bond: a bicy-clic decalin containing polyketide with structural similarities to lovastatin, and a linear 12 carbon dioic acid structure. Calbistrin A is known to be produced by several uniseriate black Aspergilli, Aspergillus versicolor-related species, and Penicillia. Penicillium decumbens produces calbistrin A and B as well as several putative intermediates of the calbistrin pathway, such as decumbenone A-B and versiol. Results: A comparative genomics study focused on the polyketide synthase (PKS) sets found in three full genome sequence calbistrin producing fungal species, P. decumbens, A. aculeatus and A. versicolor, resulted in the identification of a novel, putative 13-membered calbistrin producing gene cluster (calA to calM). Implementation of the CRISPR/ Cas9 technology in P. decumbens allowed the targeted deletion of genes encoding a polyketide synthase (calA), a major facilitator pump (calB) and a binuclear zinc cluster transcription factor (calC). Detailed metabolic profiling, using UHPLC-MS, of the ∆calA (PKS) and ∆calC ( TF) strains confirmed the suspected involvement in calbistrin productions as neither strains produced calbistrin nor any of the putative intermediates in the pathway. Similarly analysis of the excreted metabolites in the ∆calB (MFC-pump) strain showed that the encoded pump was required for efficient export of calbistrin A and B. Conclusion: Here we report the discovery of a gene cluster (calA-M) involved in the biosynthesis of the polyketide calbistrin in P. decumbens. Targeted gene deletions proved the involvement of CalA (polyketide synthase) in the biosynthesis of calbistrin, CalB (major facilitator pump) for the export of calbistrin A and B and CalC for the transcriptional regulation of the cal-cluster. This study lays the foundation for further characterization of the calbistrin biosynthetic pathway in multiple species and the development of an efficient calbistrin producing cell factory.
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