| 41. |
- Fallqvist, Mikael, et al.
(författare)
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The influence of surface topography on the formation of build-up layers and wear of CVD-Al2O3 coatings
- 2009
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Ingår i: Wear of Materials. - Las Vegas.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- During the last years it has become more and more obvious that the surface topography and surface texture strongly influences the performance of CVD and PVD coated cutting tools. As a result the interest for different types of pre- and post-surface treatments of the substrates and the deposited coatings has increased. In the present study the friction and wear characteristics of CVD a-Al2O3 coated cemented carbide exposed to different post-surface treatments, including grinding, wet and dry micro-blasting and polishing, have been investigated using modified scratch testing and pin-on-disc testing using , AISI 304 stainless steel, AISI A2 tool and steel reinforcing iron as counter materials. The influence of the coating surface topography/texture on the resulting friction characteristics, tendency to build up layer formation and prevailing wear mechanisms were identified by optical profilometry, FEG-SEM and EDX analysis. Based on the results obtained, the potential of pin-on-disc testing in the tribological characterisation of CVD coatings for cutting tool applications is discussed.
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| 42. |
- Gabrielson, Marike, et al.
(författare)
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Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 29:3, s. 574-581
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women.Methods: This study within the KARMA cohort included pre-diagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score.Results: DHEAS and percentage density were independently and positively associated with breast cancer risk (P = 0.007 and P < 0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P = 0.008) and Tyrer-Cuzick (+1.3 units, P = 0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units (P = 0.006) and 0.4 units (P = 0.007), respectively, compared with only including density.Conclusions: DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer.Impact: Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.
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| 43. |
- Gabrielson, Marike, et al.
(författare)
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Inclusion of Plasma Prolactin Levels in Current Risk Prediction Models of Premenopausal and Postmenopausal Breast Cancer
- 2018
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Ingår i: JNCI CANCER SPECTRUM. - : OXFORD UNIV PRESS. - 2515-5091. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating plasma prolactin is associated with breast cancer risk and may improve our ability to identify high-risk women. Mammographic density is a strong risk factor for breast cancer, but the association with prolactin is unclear. We studied the association between breast cancer, established breast cancer risk factors and plasma prolactin, and improvement of risk prediction by adding prolactin. Methods: We conducted a nested case-control study including 721 breast cancer patients and 1400 age-matched controls. Plasma prolactin levels were assayed using immunoassay and mammographic density measured by STRATUS. Odds ratios (ORs) were calculated by multivariable adjusted logistic regression, and improvement in the area under the curve for the risk of breast cancer by adding prolactin to established risk models. Statistical tests were two-sided. Results: In multivariable adjusted analyses, prolactin was associated with risk of premenopausal (OR, top vs bottom quintile = 1.9; 1.88 (95% confidence interval [CI] = 1.08 to 3.26) but not with postmenopausal breast cancer. In postmenopausal cases prolactin increased by 10.6% per cBIRADS category (P-trend = .03). In combined analyses of prolactin and mammographic density, ORs for women in the highest vs lowest tertile of both was 3.2 (95% CI = 1.3 to 7.7) for premenopausal women and 2.44 (95% CI = 1.44 to 4.14) for postmenopausal women. Adding prolactin to current risk models improved the area under the curve of the Gail model (+2.4 units, P = .02), Tyrer-Cuzick model (+3.8, P = .02), and the CAD2Y model (+1.7, P = .008) in premenopausal women. Conclusion: Circulating plasma prolactin and mammographic density appear independently associated with breast cancer risk among premenopausal women, and prolactin may improve risk prediction by current risk models.
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| 44. |
- Geli, Patricia, et al.
(författare)
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A multi-type branching model with varying environment for bacterial dynamics with postantibiotic effect
- 2009
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Ingår i: Journal of Theoretical Biology. - : Elsevier BV. - 0022-5193 .- 1095-8541. ; 256:1, s. 58-64
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Tidskriftsartikel (refereegranskat)abstract
- A multi-type branching process with varying environment was used to construct a pharmacokinetic/pharmacodynamic (PK/PD) model that captures the postantibiotic effect (PAE) seen in bacterial populations after exposure of antibiotics. This phenomenon of continued inhibition of bacterial growth even after removal of the antibiotic from the growth medium is of high relevance in the context of optimizing dosing regimens. The clinical implication of long PAEs lies in the interesting possibility of increasing the intervals between drug administrations. The model structure is generalizable to most types of antibiotics and is useful both as a theoretical framework for understanding the time properties of PAE and to explore optimal antibiotic dosing regimens. Data from an in vitro study with Escherichia coli exposed to different dosing regimens of cefotaxime were used to evaluate the model.
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| 45. |
- Geli Rolfhamre, Patricia, 1979-
(författare)
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From Penicillin Binding Proteins to Community Interventions : Mathematical and Statistical Models Related to Antibiotic Resistance
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance has become a major public health concern and mathematical models are important analytical tools for the understanding, evaluation and prediction of the resistance problem and related control strategies.The risk of emerging antibiotic resistance and selection has rarely been a concern in the design of antibiotic drug dosing regimens. In the first paper, a selection of antibiotic resistant subpopulations for different antibiotic dosing regimens was studied in vitro. The demonstrated complex relationship was influenced by both the rise of new mutants and a postantibiotic effect (PAE) (continued inhibition of bacterial growth after removal of the antibiotic drug). By constructing a mathematical model that incorporated biologically relevant parameters, we were able to assess the risks of resistance development under different dosing strategies.In the second paper, the model for PAEs is further developed to determine the implications for different dosing regimens. The result challenges the conventional notion that long PAEs promote extended drug dosing intervals and it allows new hypotheses to be tested experimentally based on the findings from the theoretical framework.Since PAE experiments often are time-consuming and laborious, very few studies have been reporting variation for this phenomenon. In the third paper, an extension to capture the stochastic behavior of bacterial population growth under drug exposure is made. The stochastic nature of the model is also an important complement to the existing deterministic models on drug dose drug effect relationships.The last paper describes a controlled clinical intervention study aiming at determining whether the frequency of trimethoprim resistance in E. coli can be decreased by a sudden and drastic reduction in trimethoprim use. In addition to evaluating the intervention effect, the model, given estimated parameters, is also used for predicting other interesting outcomes.
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| 46. |
- Hagey, Daniel W., et al.
(författare)
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Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells
- 2016
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 26:7, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.
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| 47. |
- Hakonen, Aron, 1970, et al.
(författare)
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Dimer-on-mirror SERS substrates with attogram sensitivity fabricated by colloidal lithography.
- 2015
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:21
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Tidskriftsartikel (refereegranskat)abstract
- Nanoplasmonic substrates with optimized field-enhancement properties are a key component in the continued development of surface-enhanced Raman scattering (SERS) molecular analysis but are challenging to produce inexpensively in large scale. We used a facile and cost-effective bottom-up technique, colloidal hole-mask lithography, to produce macroscopic dimer-on-mirror gold nanostructures. The optimized structures exhibit excellent SERS performance, as exemplified by detection of 2.5 and 50 attograms of BPE, a common SERS probe, using Raman microscopy and a simple handheld device, respectively. The corresponding Raman enhancement factor is of the order 10(11), which compares favourably to previously reported record performance values.
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| 48. |
- Hanzén, Sarah, et al.
(författare)
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Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 166:1, s. 140-151
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Tidskriftsartikel (refereegranskat)abstract
- Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.
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| 49. |
- Hedberg, P. A. Mikael, et al.
(författare)
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Measurements and Simulations of the Flow Distribution in a Down-Scaled Multiple Outlet Spillway with Complex Channel
- 2024
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Ingår i: Water. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2073-4441. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of mass flow through a three-outlet spillway modeled after a scaled-down spillway were conducted. The inlet and channel leading up to the outlets were placed to lead the water toward the outlet at an angle. With this, measurements of the water level at three locations were recorded by magnetostrictive sensors. The volumetric flow rates for each individual outlet were recorded separately to study the differences between them. Additionally, Acoustic Doppler Velocimetry was used to measure water velocities close to the outlets. The conditions changed were the inlet volume flow rate and the flow distribution was measured at 90, 100, 110, and 200 L per second. Differences between the outlets were mostly within the error margin of the instruments used in the experiments with larger differences shown for the 200 L test. The results produced together with a CAD model of the setup can be used for verification of CFD methods. A simulation with the k-epsilon turbulence model is included and compared to earlier experiments and the new experimental results. Larger differences are seen in the new experiments. Differing inlet conditions are assumed as the principal cause for the differences seen.
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| 50. |
- Hedberg, P. A. Mikael, 1989-, et al.
(författare)
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Numerical modelling of flow in parallel spillways
- 2020
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Ingår i: Proceedings of the 8th IAHR International Symposium on Hydraulic Structures ISHS2020. - : The University of Queensland.
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Konferensbidrag (refereegranskat)abstract
- Mathematical modelling of single spillways is well documented in literature. For parallel spillways however, there is a lack of documented, verified, and validated cases. Here, in this article, ANSYS-CFX is used to simulate the flow over three parallel ogee-crested spillways. For mesh size verification, a grid convergence study is performed by Richardson extrapolation. The turbulence model chosen for this simulation is the k-ε model and the volume of fluid method is used to simulate the water-air interface. This article details the models ability to accurately predict flow distribution at the spillways, and the water levels. The mesh is kept relatively coarse at the channel inlet with increased mesh density at the spillways. The results are validated against experimental data from Vattenfall AB, R&Ds laboratories. The geometry and boundary conditions of the experiment are tailored for CFD. The flow rate of each spillway is measured separately with high accuracy, and for several different inlet volumetric flows. The simulation results lie within the error estimates of the measuring tools used in the experiments, within ±1%. The volume flow rate differences between the three outlets is very small, within ±1%.
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