| 1. |
- Alfredsson, K. Svante, et al.
(författare)
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Flexural analysis of discontinuous tile core sandwich structure
- 2012
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Ingår i: Composite structures. - : Elsevier. - 0263-8223 .- 1879-1085. ; 94:5, s. 1524-1532
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Tidskriftsartikel (refereegranskat)abstract
- Three-point flexure loading of sandwich beams with a core consisting of discrete ceramic tiles (DTSS) is considered. The tile gaps may be bonded or unbonded (open gaps). The analysis utilizes a layer-wise beam theory approach. The general formulation for the displacements and stresses in the face sheets, face/core adhesive layer, and core is derived. Solutions for stresses and displacements of the beam constituents are obtained from finite element formulation based on analytical solution of the face sheet/tile unit cell. The approach is verified by comparison to stress results obtained from ordinary finite element analysis where each layer is modeled discretely. Effects of load introduction and support conditions on the effective flexural stiffness are examined. It is demonstrated that the face sheets experience substantial stress concentrations at the tile joint locations, especially if the gaps are unfilled. Analysis of beam compliance reveals sensitivity to details of load introduction and support conditions, especially when the span length becomes comparable to the tile length.
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| 2. |
- Alfredsson, K. Svante, et al.
(författare)
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Stress analysis of axially and thermally loaded discontinuous tile core sandwich with and without adhesive filled core gaps
- 2011
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Ingår i: Composite structures. - : Elsevier. - 0263-8223 .- 1879-1085. ; 93:7, s. 1621-1630
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Tidskriftsartikel (refereegranskat)abstract
- An analytical study is performed to investigate the stress states in an axially and thermally loaded sandwich structure with a discontinuous ceramic tile core. General and simplified models are developed to determine stresses in the constituents of the sandwich structure with and without adhesive in the gaps between adjacent tiles. A general model that allows local bending of the face sheet and a simplified model which assumes uniform through-thickness stress distribution in the face sheets are developed. It is shown that the normal stress in the face sheet decreases when the gap is filled by adhesive, although the tile stress increases. The analytical model shows that normal and shear stresses at the face/core interface can be reduced by filling the gaps between tiles. Filled gaps also elevate the axial stiffness of the structure. Model results are verified by comparison to a previously developed analytical model and finite element analysis. (C) 2011 Elsevier Ltd. All rights reserved.
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| 3. |
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| 4. |
- Tolboom, N., et al.
(författare)
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The Dopamine Stabilizer (-)-OSU6162 Occupies a Subpopulation of Striatal Dopamine D2/D3 Receptors: An C-11 Raclopride PET Study in Healthy Human Subjects
- 2015
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 40:2, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- (-)-OSU6162 is a dopamine stabilizer that can counteract both hyperdopaminergic and hypodopaminergic states. In this study, D2/D3 receptor occupancy of (-)-OSU6162 in the human brain was investigated using positron emission tomography (PET). Twelve male healthy volunteers underwent [C-11] raclopride PET scanning before and 1 h after a single oral dose of (-)-OSU6162 (15-90 mg). Blood samples for determination of (-)-OSU6162 and prolactin plasma levels were collected at T-max. Parametric images of [ 11 C] raclopride binding potential relative to nondisplaceable tissue (cerebellar grey matter) uptake (BPND) at baseline and after (-)-OSU6162 administration were generated using the simplified reference tissue model. MRI-based regions of interest were defined for the striatum, composed of caudate nucleus and putamen, and projected onto the co-registered parametric [C-11] raclopride BPND image. Furthermore, three striatal subregions, ie, anterior dorsal caudate, anterior dorsal putamen, and ventral striatum, were defined manually and additionally analyzed. Plasma concentrations of (-)-OSU6162, ranging from 0.01 to 0.9 mu M, showed a linear relationship with prolactin levels, reflecting blockade of pituitary D2 receptors. A concentration-dependent increase in striatal D2/D3 receptor occupancy was observed, reaching a value of about 20% at an (-)-OSU6162 plasma level of 0.2 mu M, and which for higher concentrations leveled off to a maximal occupancy of about 40%. Findings were similar in the striatal subregions. The present data corroborate the notion that (-)-OSU6162 binds preferentially to a subpopulation of D2/D3 receptors, possibly predominantly extrasynaptic, and this may form the basis for the dopamine-stabilizing properties of (-)-OSU6162.
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| 5. |
- Alfredsson, Svante, et al.
(författare)
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Flexure analysis of unsymmetric orthotropic beams with an interlayer
- 2009
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Ingår i: International Journal of Solids and Structures. - : Elsevier. - 0020-7683 .- 1879-2146. ; 46:10, s. 2093-2110
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a layer-wise stress and deformation analysis of a three-layer beam configuration consisting of two dissimilar orthotropic adherends of different thicknesses that are joined together by a deformable interlayer of finite thickness. Analytical solutions for the case of three-point flexure loading are presented for both compressible and incompressible interlayers. Parametric analysis reveals the influences of asymmetry of moduli and adherend thicknesses, interlayer thickness, and overhang of the beams on the beam compliance. Analytical predictions of beam compliance show very good agreement with finite element results. Experimental measurements of compliance of various unsymmetric beams consisting of aluminum adherends separated by a rubber interlayer were performed in order to validate the analysis. Excellent agreement between measured and predicted compliance values was observed.
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| 6. |
- Alfredsson, Svante, et al.
(författare)
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Flexure of beams with an interlayer : symmetric beams with orthotropic adherends
- 2008
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Ingår i: Journal of Mechanics of Materials and Structures. - : Mathematical Sciences Publishers. - 1559-3959 .- 2157-5428. ; 3:1, s. 45-62
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of the three-point flexure loading of a symmetric beam configurationconsisting of two identical adherends joined by a flexible layer is presented. Aclosed-form solution is presented in the form of a layer-wise approach, andshows excellent agreement with finite element results. Particular emphasis isgiven to the global beam compliance. The results show that a thin, sheardeformable layer may effectively decouple the responses of the two beams.Furthermore, in contrast to ordinary beams, the presence of an overhangreduces the beam compliance. These effects are quantified and discussed.Experiments on aluminum adherends joined by a rubber layer were conductedover a range of overhang lengths in a three-point flexure fixture, and verygood agreement between measured and predicted beam compliance was noted.
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| 7. |
- Boguszewski, C L, et al.
(författare)
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Circulating non-22-kilodalton growth hormone isoforms in acromegalic men before and after transsphenoidal surgery.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 82:5, s. 1516-21
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Tidskriftsartikel (refereegranskat)abstract
- GH represents several molecular isoforms in addition to the main 22-kDa (22K) GH. There have been reports suggesting that circulating non-22K GH isoforms are increased in acromegaly, but the possible implications of such observations in the management of the disease have not been addressed. The aim of this study was to evaluate the proportion of circulating non-22K GH isoforms in acromegaly. In addition, the relationships between the amount of non-22K GH and tumor size, biochemical measurements, and body composition also were investigated. Samples with different GH levels were selected from 24-h GH profiles from 15 acromegalic men evaluated before and 1 yr after transsphenoidal surgery and from 13 healthy men. The serum non-22K GH levels, expressed as percentage of total GH concentration, were determined by the 22K GH exclusion assay, which is based on immunomagnetic extraction of 22K GH from serum and quantitation of non-22K GH using a polyclonal GH assay. The proportion of non-22K GH isoforms was fairly constant in different samples from the same patient, regardless of the GH level. However, a wide variation of values was observed among acromegalics, both before (14-51%) and after surgery (8-62%). The proportion of non-22K GH isoforms was increased in untreated patients, compared with controls (26.6 vs. 17.4%; P < 0.01), and the values correlated significantly to tumor size, mean 24-h GH concentration, serum PRL, and extracellular water. After surgery, patients not truly cured, with mean 24-h GH concentration of 1 microg/L or more, had an increased proportion of non-22K GH, compared with those with levels less than 1 microg/L (P < 0.01). In the former group, the median values were similar than those in untreated acromegalics (34 vs. 26.6%, respectively), whereas in the latter, they were comparable with those in the controls (15.2 vs. 17.4%, respectively). We conclude that acromegalics have an increased proportion of circulating non-22K GH isoforms. The values are fairly constant in different samples from an individual, regardless of GH level, but a large spectrum can be observed among patients. This variability suggests that different pituitary adenomas secrete GH isoforms in variable amounts. Our observation that a higher proportion of non-22K GH isoforms is present in patients not truly cured after surgery suggests that the evaluation of non-22K GH isoforms can be useful in the follow-up of acromegalic patients.
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| 8. |
- Gan, Li-Ming, 1969, et al.
(författare)
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Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Chemically modified mRNA is an efficient, biocompatible modality for therapeutic protein expression. We report a first-time-in-human study of this modality, aiming to evaluate safety and potential therapeutic effects. Men with type 2 diabetes mellitus (T2DM) received intradermal injections of modified mRNA encoding vascular endothelial growth factor A (VEGF-A) or buffered saline placebo (ethical obligations precluded use of a non-translatable mRNA control) at randomized sites on the forearm. The only causally treatment-related adverse events were mild injection-site reactions. Skin microdialysis revealed elevated VEGF-A protein levels at mRNA-treated sites versus placebo-treated sites from about 4-24 hours post-administration. Enhancements in basal skin blood flow at 4 hours and 7 days post-administration were detected using laser Doppler fluximetry and imaging. Intradermal VEGF-A mRNA was well tolerated and led to local functional VEGF-A protein expression and transient skin blood flow enhancement in men with T2DM. VEGF-A mRNA may have therapeutic potential for regenerative angiogenesis.
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| 9. |
- Matikas, A., et al.
(författare)
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Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer
- 2021
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Ingår i: ESMO open. - : Elsevier BV. - 2059-7029. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r= 0.814), but not with the diagnostic samples (r= 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P= 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj= 0.50, 95% CI 0.26-0.97, P= 0.04) and OS (HRadj= 0.46, 95% CI 0.95, P= 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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