| 1. |
- Lalkovski, S., et al.
(författare)
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Core-coupled states and split proton-neutron quasiparticle multiplets in Ag122-126
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:3, s. 034308-
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Tidskriftsartikel (refereegranskat)abstract
- Neutron-rich silver isotopes were populated in the fragmentation of a Xe-136 beam and the relativistic fission of U-238. The fragments were mass analyzed with the GSI Fragment Separator and subsequently implanted into a passive stopper. Isomeric transitions were detected by 105 high-purity germanium detectors. Eight isomeric states were observed in Ag122-126 nuclei. The level schemes of Ag-122,Ag-123,Ag-125 were revised and extended with isomeric transitions being observed for the first time. The excited states in the odd-mass silver isotopes are interpreted as core-coupled states. The isomeric states in the even-mass silver isotopes are discussed in the framework of the proton-neutron split multiplets. The results of shell-model calculations, performed for the most neutron-rich silver nuclei are compared to the experimental data.
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| 2. |
- Naqvi, F., et al.
(författare)
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Isomer spectroscopy of (127)Cd
- 2010
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 82:3, s. 034323-
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Tidskriftsartikel (refereegranskat)abstract
- The spin and configurational structure of excited states of (127)Cd, the two-proton and three-neutron hole neighbor of (132)Sn, has been studied. An isomeric state with a half-life of 17.5(3) mu s was populated in the fragmentation of a (136)Xe beam on a (9)Be target at a beam energy of 750 MeV/u. Time distributions of the delayed gamma transitions and gamma gamma coincidence relations were exploited to construct a decay scheme. The observed yrast (19/2)(+) isomer is proposed to have dominant configurations of nu(h(11/2)(-3))pi(g(9/2)(-1), p(1/2)(-1)), nu(h(11/2)(-2)d(3/2)(-1))pi(g(9/2)(-2)), and nu(h(11/2)(-2), s(1/2)(-1))pi(g(9/2)(-2)) and to decay by two competing stretched M2 and E3 transitions. Experimental results are compared with the isotone (129)Sn. The new information provides input for the proton-neutron interaction and the evolution of neutron hole energies in nuclei around the doubly magic (132)Sn core.
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| 3. |
- Hoischen, Robert, et al.
(författare)
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Isomeric Mirror States as Probes for Effective Charges in the Lower pf Shell
- 2011
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 38:3
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Tidskriftsartikel (refereegranskat)abstract
- Following the fragmentation of a 550 MeV u(-1)primary beam of Ni-58, time-and energy-correlated gamma decays from isomeric states in neutron-deficient nuclei in the 1f(7/2) shell have been identified using the GSI fragment separator in combination with the RISING Ge-detector array. The results on isomers in the mirror pairs Ti-43(22)21-Sc-43(21)22 (I-pi = 3/2(+) and 19/2(-)), Cr-45(24)21-Sc-45(21)24 (I-pi = 3/2(+)) and V-45(23)22-Ti-45(22)23 (I-pi = 3/2(-)) are discussed in the framework of large scale pf and sdpf shell-model calculations, the former in conjunction with isospin symmetry breaking effects with emphasis on effective charges.
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| 4. |
- Høyerup, P., et al.
(författare)
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Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser Doppler flowmetry in end-jejunostomy short bowel syndrome patients
- 2013
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 180:1, s. 12-16
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Tidskriftsartikel (refereegranskat)abstract
- Background: In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunostomy short bowel syndrome (SBS) patients. Methods: In five SBS patients with end-jejunostomy a specially designed laser Doppler probe was inserted into the stoma nipple, and blood flow measured directly on the jejunal mucosa for 105. min in relation to no treatment, systemic saline infusion, topical adrenaline application and a subcutaneous injection of 800μg native GLP-2. Results: The GLP-2 injection increased jejunal mucosal blood flow by 79 ± 37% compared to conditions, where no treatment was given (p < 0.001). The significant effect was present at least 105. min. Systemic saline infusion and topical, mucosal adrenaline application did not affect mucosal microcirculation. Conclusions: GLP-2 raises jejunal microcirculation in SBS patients with end-jejunostomy. This may explain the redness and increase in the end-jejunostomy nipple size imminently after commencing GLP-2 injections. The potential beneficial effects of this GLP-2-mediated increase of blood flow in the mesenteric bed should be investigated in clinical conditions other than the short bowel syndrome.
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| 5. |
- Pietri, S., et al.
(författare)
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First observation of the decay of a 15(-) seniority v=4 isomer in Sn-128
- 2011
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 83:4, s. 044328-
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Tidskriftsartikel (refereegranskat)abstract
- Isomeric states in the semimagic Sn128-130 isotopes were populated in the fragmentation of a Xe-136 beam on a Be-9 target at an energy of 750 A.MeV. The decay of an isomeric state in Sn-128 at an excitation energy of 4098 keV has been observed. Its half live has been determined to be T-1/2 = 220(30) ns from the time distributions of the delayed gamma rays emitted in its decay. gamma gamma coincidence relations were analyzed in order to establish the decay pattern of the newly established state toward the known (7(-)) and (10(+)) isomers at excitation energies of 2092 and 2492 keV, respectively. Based on a comparison with results of state-of-the-art shell-model calculations the new isomeric state is proposed to have the nu h(11/2)(-3)d(3/2)(-1) configuration with the four neutron holes in Sn-132 maximally aligned to a total spin of I-pi = 15(-).
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| 6. |
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| 7. |
- Edholm, T., et al.
(författare)
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Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1191-e315
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Tidskriftsartikel (refereegranskat)abstract
- Background Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. Methods Randomized crossover single-blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg−1 min−1, n = 8), GLP-1 (0.75 pmol kg−1 min−1, n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C-peptide, peptide YY (PYY) and ghrelin. Key Results Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg−1 min−1 decreased gastric half-emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg−1 min−1 decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon-like peptide-1 0.75 pmol kg−1 min−1 increased half-emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05–0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). Conclusion & Inferences The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.
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| 8. |
- Gaengel, K., et al.
(författare)
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The Sphingosine-1-Phosphate Receptor S1PR1 Restricts Sprouting Angiogenesis by Regulating the Interplay between VE-Cadherin and VEGFR2
- 2012
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Ingår i: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 23:3, s. 587-599
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis, the process by which new blood vessels arise from preexisting ones, is critical for embryonic development and is an integral part of many disease processes. Recent studies have provided detailed information on how angiogenic sprouts initiate, elongate, and branch, but less is known about how these processes cease. Here, we show that S1PR1, a receptor for the blood-borne bioactive lipid sphingosine-1-phosphate (S1P), is critical for inhibition of angiogenesis and acquisition of vascular stability. Loss of S1PR1 leads to increased endothelial cell sprouting and the formation of ectopic vessel branches. Conversely, S1PR1 signaling inhibits angiogenic sprouting and enhances cell-to-cell adhesion. This correlates with inhibition of vascular endothelial growth factor-A (VEGF-A)-induced signaling and stabilization of vascular endothelial (VE)-cadherin localization at endothelial junctions. Our data suggest that S1PR1 signaling acts as a vascular-intrinsic stabilization mechanism, protecting developing blood vessels against aberrant angiogenic responses.
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| 9. |
- Klinge, P., et al.
(författare)
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One-year outcome in the European multicentre study on iNPH
- 2012
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 126:3, s. 145-153
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess the 1-year outcome after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods Patients (n = 142) were prospectively included in the European multicentre study by 13 centres. Diagnoses were based solely on clinical and radiological findings. All received a programmable ventriculoperitoneal shunt. Re-examinations, 12 months after surgery, were performed in 115 patients, and the outcome was assessed by the modified Rankin scale (mRs) and a new iNPH grading scale. Improvement was defined as =1 step on the mRs and =5 points on the iNPH scale. Results The scores on both scales were significantly improved after 1 year of shunt treatment (Ps < 0.001). Sixty-nine per cent of the patients were improved according to the mRs and 84% according to the iNPH scale. The proportion able to live independently (scores 02 on the mRs) was increased from 53% before to 82% 12 months after surgery (P < 0.001). Neither classification (typical or questionable) nor comorbidity affected the level of improvement. Patients not completing the study were worse off with regard to their clinical condition at entry than completers. Twenty-eight per cent of the patients experienced complications and were either conservatively (13%) or surgically (15%) treated. Conclusion The results of this prospective multicentre study on patients with iiNPH diagnosed solely on clinical and radiological criteria support shunt surgery in patients presenting with symptoms and signs and MRI findings suggestive of iNPH.
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| 10. |
- Naska, A, et al.
(författare)
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Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study.
- 2011
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 35:3, s. 416-426
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. SUBJECTS: This study included a representative sample of 24,310 randomly selected EPIC participants. METHODS: Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders. RESULTS: In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (β=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (β=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake. CONCLUSION: Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.
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| 11. |
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| 12. |
- Thomas, S. M., et al.
(författare)
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On the role of Coulomb scattering in hafnium-silicate gated silicon n and p-channel metal-oxide-semiconductor-field-effect-transistors
- 2011
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 110:12, s. 124503-
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Tidskriftsartikel (refereegranskat)abstract
- In this work, the impact of the local and remote Coulomb scattering mechanisms on electron and hole mobility are investigated. The effective mobilities in quasi-planar finFETs with TiN/Hf(0.4)Si(0.6)O/SiO(2) gate stacks have been measured at 300 K and 4 K. At 300 K, electron mobility is degraded below that of bulk MOSFETs in the literature, whereas hole mobility is comparable. The 4 K electron and hole mobilities have been modeled in terms of ionized impurity, local Coulomb, remote Coulomb and local roughness scattering. An existing model for remote Coulomb scattering from a polycrystalline silicon gate has been adapted to model remote Coulomb scattering from a high-kappa/SiO(2) gate stack. Subsequently, remote charge densities of 8 x 10(12) cm(-2) at the Hf(0.4)Si(0.6)O/SiO(2) interface were extracted and shown to be the dominant Coulomb scattering mechanism for both electron and hole mobilities at 4 K. Finally, a Monte Carlo simulation showed remote Coulomb scattering was responsible for the degraded 300 K electron mobility.
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| 13. |
- Andersson, J. Y., et al.
(författare)
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Quantum structure based infrared detector research and development within Acreo's centre of excellence IMAGIC
- 2010
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Ingår i: Infrared physics & technology. - : Elsevier BV. - 1350-4495 .- 1879-0275. ; 53:4, s. 227-230
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Tidskriftsartikel (refereegranskat)abstract
- Acreo has a long tradition of working with quantum structure based infrared (IR) detectors and arrays. This includes QWIP (quantum well infrared photodetector), QDIP (quantum dot infrared photodetector), and InAs/GaInSb based photon detectors of different structure and composition. It also covers R&D on uncooled microbolometers. The integrated thermistor material of such detectors is advantageously based on quantum structures that are optimised for high temperature coefficient and low noise. Especially the SiGe material system is preferred due to the compatibility with silicon technology. The R&D work on IR detectors is a prominent part of Acreo's centre of excellence "IMAGIC" on imaging detectors and systems for non-visible wavelengths. IMAGIC is a collaboration between Acreo, several industry partners and universities like the Royal Institute of Technology (KTH) and Linkoping University. (C) 2010 Elsevier B.V. All rights reserved.
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| 14. |
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| 15. |
- Blennow, Kaj, 1958, et al.
(författare)
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No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 123, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- Blennow K, Jonsson M, Andreasen N, Rosengren L, Wallin A, Hellström PA, Zetterberg H. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01408.x .(c) 2010 John Wiley & Sons A/S. Background - Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. Objective - To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Materials and methods - Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. Results - The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Discussion - Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons.
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| 16. |
- Bolten, J., et al.
(författare)
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Fabrication of Nanowires
- 2014
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Ingår i: Beyond CMOS Nanodevices 1. - Hoboken, NJ, USA : Wiley Blackwell. - 9781118984772 - 9781848216549 ; , s. 5-23
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Several fabrication processes of silicon nanowires have been developed in the research community. They can be divided into bottom-up or top-down approaches. This chapter describes top-down fabrication of silicon nanowires using electron beam lithography (EBL), which combined with optical lithography can be a viable approach if not too many silicon nanowires need to be patterned on a wafer. It also describes the sidewall transfer lithography (STL) technique using I-line stepper lithography to pattern a vast amount of silicon nanowires on a silicon wafer. In addition the chapter examines how bottom-up Si nanowires synthesized by vapor-liquid-solid (VLS)-chemical vapor deposition (CVD) can be assembled at low cost in an efficient way for further use as a sensing material. Among the solution-based assembly methods for the nanostructured network (nanonet) fabrication, the vacuum filtration method is highly simple, versatile, low cost and scalable to large areas.
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| 17. |
- Englund, Mats P., et al.
(författare)
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Beware how you compare : comparison direction dictates stimulus-valence-modulated presentation-order effects in preference judgment
- 2013
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Ingår i: Attention, Perception & Psychophysics. - : Springer Science and Business Media LLC. - 1943-3921 .- 1943-393X. ; 75:5, s. 1001-1011
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Tidskriftsartikel (refereegranskat)abstract
- Englund and Hellstrom (Journal of Behavioral Decision Making 25: 82-94, 2012a) found a tendency to prefer the left (first-read) of two attractive alternatives but the right (second-read) of two unattractive alternatives-a valence-dependent word-order effect (WOE). They used stimulus pairs spaced horizontally, and preference was indicated by choosing one of several written statements (e. g., apple I like more than pear). The results were interpreted as being due to stimulus position, with the magnitude of the left stimulus having a greater impact on the comparison outcome than the magnitude of the right. Here we investigated the effects of the positioning of the stimuli versus the semantics of the response alternatives (i.e., comparison direction) on the relative impacts of the stimuli. Participants rated preferences for stimuli spaced horizontally with the response alternatives not dictating a comparison direction (Exp. 1), and stimuli spaced vertically using Englund and Hellstrom's (Journal of Behavioral Decision Making 25: 82-94, 2012a) response alternatives, which dictate a comparison direction semantically (Exp. 2). The results showed that the valence-dependent WOE found by Englund and Hellstrom (Journal of Behavioral Decision Making 25: 82-94, 2012a) was not due to the horizontal stimulus positioning per se, but to the induced comparison direction, with the effect probably being mediated by attention directed at the subject of the comparison. We concluded that a set comparison direction is required for the valence-dependent WOE to appear, and that using Hellstrom's sensation-weighting model to determine stimulus weights is a way to verify the comparison direction.
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| 18. |
- Englund, Mats P., 1979-, et al.
(författare)
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If you have a choice, you have trouble : Stimulus valence modulates presentation-order effects in preference judgment
- 2012
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Ingår i: Journal of Behavioral Decision Making. - : Wiley. - 0894-3257 .- 1099-0771. ; 25:1, s. 82-94
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that the presentation order of choice options often affects decision outcomes to a significant degree. However, despite the significance and wide occurrence of the effects, they are ignored in most preference models. Furthermore, psychophysical findings of stimulus-magnitude dependent presentation-order effects have not been acknowledged previously in the cognitive literature on preference judgments. Thus, the potential moderating effect of the level of stimulus magnitude (here, valence) on the direction and size of order effects in preference judgment has not been investigated previously. In two experiments, participants (117 and 204, respectively) rated their preference for pairs of everyday-type objects and phenomena (e.g., apple–pear, headache–stomachache). Stimuli were spaced horizontally, and each participant received them in one of two opposite within-pair presentation orders. Participants also rated the stimuli's valence on a scale from very bad to very good. The results showed a positive correlation between the rated valence and the tendency to prefer the first-mentioned (left) stimulus; that is, the effect was greatest, and opposite, for choices between the most attractive and the most unattractive options, respectively. In terms of Hellström's (1979) sensation-weighting model, the positive correlation is caused by a higher weight (i.e., impact on the preference judgment) for the left stimulus than for the right, which is possibly due to the left stimulus being compared to the right. The results suggest that researchers may have failed previously to find important moderators of presentation-order effects in preference judgment due to the failure to use sufficiently attractive or unattractive stimuli.
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| 19. |
- Englund, Mats P., 1979-, et al.
(författare)
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Presentation-order effects for aesthetic stimulus preference
- 2012
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Ingår i: Attention, Perception & Psychophysics. - : Springer Science and Business Media LLC. - 1943-3921 .- 1943-393X. ; 74:7, s. 1499-1511
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Tidskriftsartikel (refereegranskat)abstract
- For preference comparisons of paired successive musical excerpts, Koh (American Journal of Psychology, 80, 171-185, 1967) found time-order effects (TOEs) that correlated negatively with stimulus valence-the first (vs. the second) of two unpleasant (vs. two pleasant) excerpts tended to be preferred. We present three experiments designed to investigate whether valence-level-dependent order effects for aesthetic preference (a) can be accounted for using Hellstrom's (e.g., Journal of Experimental Psychology: Human Perception and Performance, 5, 460-477, 1979) sensation-weighting (SW) model, (b) can be generalized to successive and to simultaneous visual stimuli, and (c) vary, in accordance with the stimulus weighting, with interstimulus interval (ISI; for successive stimuli) or stimulus duration (for simultaneous stimuli). Participants compared paired successive jingles (Exp. 1), successive color patterns (Exp. 2), and simultaneous color patterns (Exp. 3), selecting the preferred stimulus. The results were well described by the SW model, which provided a better fit than did two extended versions of the Bradley-Terry-Luce model. Experiments 1 and 2 revealed higher weights for the second stimulus than for the first, and negatively valence-level-dependent TOEs. In Experiment 3, there was no laterality effect on the stimulus weighting and no valence-level-dependent space-order effects (SOEs). In terms of the SW model, the valence-level-dependent TOEs can be explained as a consequence of differential stimulus weighting in combination with stimulus valence varying from low to high, and the absence of valence-level-dependent SOEs as a consequence of the absence of differential weighting. For successive stimuli, there were no important effects of ISI on weightings and TOEs, and, for simultaneous stimuli, duration had only a small effect on the weighting.
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| 20. |
- Englund, Mats P., 1979-
(författare)
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Valence-Level Dependent Presentation-Order Effects in Preference Judgments
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Reversal of the stimulus-presentation order often affects the outcome in paired stimulus comparison. Psychophysicists have found that the size and direction of the order effects depend on the compared stimuli’s magnitudes, but this magnitude dependence does not seem to have been recognized previously in cognitive research on preference judgment. The main objective of the present doctoral thesis was to investigate whether analogous valence-level dependent order effects exist for preference judgments of aesthetic preference of visual and of auditory stimuli (Study I) and of everyday objects and phenomena (e.g., Apple-Pear, Headache-Stomachache) denoted by labels and presented in a simple survey-questionnaire format (Studies II-III). An additional objective was to investigate if potential valence-level dependent order effects in Studies I-III could be accounted for using Hellström’s (1979, 2000) sensation weighting (SW) model. In Study I, there were valence-level dependent order effects favoring the second of two pleasant stimuli but the first of two unpleasant stimuli presented successively, but there were none for stimuli presented simultaneously. In Study II, there were valence-level dependent word-order effects (WOEs) favoring the left and first-read of two attractive stimuli but the right and last-read of two unattractive ones. Results were well accounted for using the SW model with a higher weight (i.e., greater impact on the comparison) for the second and the left stimulus in Studies I and II, respectively, and the valence level varying from low to high. Results of Study III indicate that the valence-level dependent WOEs in Study II were not due to the spatial positioning (left-right) of the stimuli but to the comparison being directed; the first read stimulus was compared to the second read, yielding a higher weight for the first read stimulus. The present results demonstrate robust order effects large enough to be of theoretical as well as practical relevance.
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| 21. |
- Falkén, Y., et al.
(författare)
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Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:6, s. e192-e200
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Tidskriftsartikel (refereegranskat)abstract
- Background Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. Methods Ghrelin (15 pmol kg−1 min−1) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. Key Results The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 ± 3.9 vs 59.9 ± 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. Conclusions & Inferences The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders.
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| 22. |
- George, Zandra, 1985, et al.
(författare)
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The Influence of Alkoxy Substitutions on the Properties of Diketopyrrolopyrrole-Phenyl Copolymers for Solar Cells
- 2013
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 6:7, s. 3022-3034
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Tidskriftsartikel (refereegranskat)abstract
- A previously reported diketopyrrolopyrrole (DPP)-phenyl copolymer is modified by adding methoxy or octyloxy side chains on the phenyl spacer. The influence of these alkoxy substitutions on the physical, opto-electronic properties, and photovoltaic performance were investigated. It was found that the altered physical properties correlated with an increase in chain flexibility. Well-defined oligomers were synthesized to verify the observed structure-property relationship. Surprisingly, methoxy substitution on the benzene spacer resulted in higher melting and crystallization temperatures in the synthesized oligomers. This trend is not observed in the polymers, where the improved interactions are most likely counteracted by the larger conformational possibilities in the polymer chain upon alkoxy substitution. The best photovoltaic performance was obtained for the parent polymer: fullerene blends whereas the modifications on the other two polymers result in reduced open-circuit voltage and varying current densities under similar processing conditions. The current densities could be related to different polymer: fullerene blend morphologies. These results show that supposed small structural alterations such as methoxy substitution already significantly altered the physical properties of the parent polymer and also that oligomers and polymers respond divergent to structural alterations made on a parent structure.
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| 23. |
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| 24. |
- Gillberg, L., et al.
(författare)
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Effective treatment of mouse experimental colitis by alpha 2 integrin antibody : comparison with alpha 4 antibody and conventional therapy
- 2013
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 207:2, s. 326-336
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Tidskriftsartikel (refereegranskat)abstract
- Aim To compare the therapeutic effect of a2 and a4 integrin-blocking antibodies to conventional inflammatory bowel disease drugs methotrexate, 5-aminosalicylic acid and azathioprine in the dextran sulphate sodium mouse colitis model. Methods Colitis was induced in balb/c mice with 2.53.0% dextran sulphate sodium. Treatment was given daily for 7 days after the onset of colitis, by rectal installation. Clinical signs of disease were assessed daily using a disease activity index. After 19 days, all animals were killed and colon samples collected for histological grading and mRNA/protein analysis. All treatment groups were compared with an untreated control group and a treatment group receiving dextran sulphate sodium alone to monitor the potential degree of clinical remission. Results Treatment with anti-a2 antibodies and methotrexate reduced the body weight loss. At the end of treatment, anti-a2 antibodies reduced rectal bleeding, while methotrexate reduced the disease activity index score. Histological evaluation showed that anti-a2 antibodies, methotrexate, 5-aminosalicylic acid and azathioprine treatment reduced the acute inflammation; methotrexate was the only treatment with effect on the crypt score. Compared with the dextran sulphate sodium alone group, the methotrexate group showed down-regulation of IL-1 beta at the mRNA level, while the anti-a2 antibody group displayed decreased protein expression of iNOS and IL-1 beta. Conclusions Specific blocking of extravascular trafficking of leucocytes with a2-antibodies could be a new beneficial drug target in inflammatory bowel disease.
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| 25. |
- Gomeniuk, Y. Y., et al.
(författare)
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Electrical properties of high-k LaLuO3 gate oxide for SOI MOSFETs
- 2011
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Ingår i: 6th International Workshop on Semiconductor-on-Insulator Materials and Devices. - 9783037851784 ; , s. 87-93
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Konferensbidrag (refereegranskat)abstract
- The paper presents the results of electrical characterization of MOS capacitors and SOI MOSFETs with novel high-? LaLuO3 dielectric as a gate oxide. The energy distribution of interface state density at LaLuO 3/Si interface is presented and typical maxima of 1.2×10 11 eV-1cm-2 was found at about 0.25 eV from the silicon valence band. The output and transfer characteristics of the n- and p-MOSFET (channel length and width were 1 μm and 50 μm, respectively) are presented. The front channel mobility appeared to be 126 cm2V -1s-1 and 70 cm2V-1s-1 for n- and p-MOSFET, respectively. The front channel threshold voltages as well as the density of states at the back interface are presented.
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| 26. |
- Gudmundsson, Valur, et al.
(författare)
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Simulation of low Schottky barrier MOSFETs using an improved Multi-subband Monte Carlo model
- 2013
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Ingår i: Solid-State Electronics. - : Elsevier BV. - 0038-1101 .- 1879-2405. ; 79, s. 172-178
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Tidskriftsartikel (refereegranskat)abstract
- We present a simple and efficient approach to implement Schottky barrier contacts in a Multi-subband Monte Carlo simulator by using the subband smoothening technique to mimic tunneling at the Schottky junction. In the absence of scattering, simulation results for Schottky barrier MOSFETs are in agreement with ballistic Non-Equilibrium Green's Functions calculations. We then include the most relevant scattering mechanisms, and apply the model to the study of double gate Schottky barrier MOSFETs representative of the ITRS 2015 high performance device. Results show that a Schottky barrier height of less than approximately 0.15 eV is required to outperform the doped source/drain structure.
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| 27. |
- Gustavsson, Anders, et al.
(författare)
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Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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| 28. |
- Haller, B K, et al.
(författare)
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Therapeutic efficacy of a DNA vaccine targeting the endothelial tip cell antigen delta-like ligand 4 in mammary carcinoma.
- 2010
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 29:30, s. 4276-86
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Tidskriftsartikel (refereegranskat)abstract
- The Notch ligand delta-like ligand 4 (DLL4) is an essential component expressed by endothelial tip cells during angiogenic sprouting. We have described a conceptually novel therapeutic strategy for targeting tumor angiogenesis and endothelial tip cells based on DNA vaccination against DLL4. Immunization with DLL4-encoding plasmid DNA by in vivo electroporation severely retarded the growth of orthotopically implanted mammary carcinomas in mice by induction of a nonproductive angiogenic response. Mechanistically, vaccination brought about a break in tolerance against the self-antigen, DLL4, as evidenced by the production of inhibitory and inherently therapeutic antibodies against mouse DLL4. Importantly, no evidence for a delayed wound healing response, or for toxicity associated with pharmacological blockade of DLL4 signaling, was noted in mice immunized with the DLL4 vaccine. We have thus developed a well-tolerated DNA vaccination strategy targeting the endothelial tip cells and the antigen DLL4 with proven therapeutic efficacy in mouse models of mammary carcinoma; a disease that has been reported to dramatically induce the expression of DLL4. Conceivably, induction of immunity toward principal mediators of pathological angiogenesis could provide protection against recurrent malignant disease in the adjuvant setting.
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| 29. |
- Hellström, Per, et al.
(författare)
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A new scale for assessment of severity and outcome in iNPH
- 2012
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 126:4, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- Objective To present a new, continuous, calibrated and norm-based scale for the grading of severity and assessment of treatment outcome in idiopathic normal pressure hydrocephalus (iNPH). Patients and methods A scale designed for the assessment of the four domains, gait, neuropsychology, balance and continence, using ordinal ratings and continuous measures, was developed. Data from a series of 181 consecutive iNPH patients were used to calibrate the continuous parts of the scale and to describe the distributional properties of the ordinal ratings. Data from normative studies were used to determine the limits for normal scores. Results The construction of the scale made it well equipped to separate iNPH patients at baseline, and the total scores assumed a bell-shaped, approximately normal distribution. All four domain scores correlated significantly with each other, underscoring the well-known syndromatic nature of iNPH, and justifying the use of a total score to describe the patients. Reliability [Cronbach's a for the total score = 0.74, and for the domains of gait and neuropsychology, 0.86 and 0.89, respectively) and validity estimates (convergent validity evaluated by Spearman rank correlations for the scale and the modified Rankin scale (? = -0.61) and the mini mental state examination (? = 0.57)] are satisfying. Conclusion The iNPH scale covers the four most important symptom domains and the full range of severity of the iNPH syndrome. The scale is sensitive, reliable, valid and feasible. We recommend that it should be used in future iNPH research.
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| 30. |
- Hellström, Per M., et al.
(författare)
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Receptor-mediated inhibition of small bowel migrating complex by GLP-1 analog ROSE-010 delivered via pulmonary and systemic routes in the conscious rat
- 2012
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 179:1-3, s. 71-76
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Tidskriftsartikel (refereegranskat)abstract
- Background: ROSE-010, a Glucagon-Like Peptide-1 (GLP-1) analog, reduces gastrointestinal motility and relieves acute pain in patients with irritable bowel syndrome (IBS). The rat small bowel migrating myoelectric complex (MMC) is a reliable model of pharmacological effects on gastrointestinal motility. Accordingly, we investigated whether ROSE-010 works through GLP-1 receptors in gut musculature and its effectiveness when administered by pulmonary inhalation. Materials and methods: Rats were implanted with bipolar electrodes at 5, 15 and 25 cm distal to pylorus and myoelectric activity was recorded. First, intravenous or subcutaneous injections of ROSE-010 or GLP-1 (1, 10, 100 mu g/kg) with or without the GLP-1 receptor blocker exendin(9-39)amide (300 mu g/kg.h), were studied. Second, ROSE-010 (100, 200 mu g/kg) Technosphere (R) powder was studied by inhalation. Results: The baseline MMC cycle length was 17.5 +/- 0.8 min. GLP-1 and ROSE-010. administered intravenously or subcutaneously, significantly inhibited myoelectric activity and prolonged MMC cycling; 100 mu g/kg completely inhibited spiking activity for 49.1 +/- 4.2 and 73.3 +/- 7.7 min, while the MMC cycle length increased to 131.1 +/- 11.4 and 149.3 +/- 15.5 min, respectively. Effects of both drugs were inhibited by exendin(9-39) amide. Insufflation of ROSE-010 (100, 200 mu g/kg) powder formulation totally inhibited myoelectric spiking for 52.6 +/- 5.8 and 70.1 +/- 5.4 min, and increased MMC cycle length to 102.6 +/- 18.3 and 105.9 +/- 9.5 min, respectively. Conclusions: Pulmonary delivery of ROSE-010 inhibits gut motility through the GLP-1R similar to natural GLP-1. ROSE-010 causes receptor-mediated inhibition of MMC comparable to that of intravenous or subcutaneous administration. This suggests that ROSE-010 administered as a Technosphere (R) inhalation powder has potential in IBS pain management and treatment.
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| 31. |
- Holgersson, G., et al.
(författare)
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Molecular profiling using tissue microarrays as a tool to identify predictive biomarkers in laryngeal cancer treated with radiotherapy
- 2010
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Ingår i: Cancer Genomics & Proteomics. - 1109-6535 .- 1790-6245. ; 7:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore the usefulness of the expression of five potential cancer biomarkers in predicting outcome in patients with laryngeal cancer. Materials and Methods: In the present study, the Swedish National Cancer Registry databases were used to identify patients with laryngeal cancer diagnosed during the years 1978-2004 in the Uppsala-Örebro region and treated with radiotherapy. The expression of Ki-67, MutS homolog 2, (MSH2), p53, B-cell CLL/lymphoma 2 (Bcl-2) and cyclin D1 in the cancer cells was assessed immunohistochemically using tissue microarrays (TMAs) and its predictve value on survival and relapse was analyzed using Cox regression models. Results: A total of 39 patients were included in the present study. Nuclear MSH2 staining was statistically significantly correlated to Ki-67 expression (p=0.022). However, univariate and multivariate Cox analyses showed no statistically significant association between the expression of the investigated biomarkers and overall survival or relapse. Conclusion: The present exploratory study does not show any significant predictive value of the biomarkers examined with respect to survival or relapse. However, with larger patient cohorts, we believe that protein profiling using TMAs and immunohistochemistry is a feasible strategy for prognostic and predictive biomarker screening in laryngeal cancer.
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| 32. |
- Hopkins, M., et al.
(författare)
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The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake
- 2014
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 68:5, s. 581-586
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: A decline in resting energy expenditure (SEE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (El). SUBJECTS/METHODS: Thirty overweight and obese women (body mass index (BMI) =30.6 +/- 3.6 kg/m(2)) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, El and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured SEE was also calculated post intervention (MA(post)), with SEE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI =31.0 +/- 3.9 kg/m(2)). RESULTS: Although mean predicted and measured SEE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in SEE ( 102.9 +/- 77.5 kcal per day). MA(post) was associated with the change in leptin (r= 0.47; P=0.04), and the change in resting fat (r= 0.52; P=0.01) and carbohydrate oxidation (r= 0.44;P= 0.02). Furthermore, MApost was also associated with the change in El following EX (r= 0.44; P=0.01). CONCLUSIONS: Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in SEE also experienced an upregulation in El, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.
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| 33. |
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| 34. |
- Lundén, P., et al.
(författare)
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Psychoacoustic evaluation as a tool for optimization in the development of an urban soundscape simulator
- 2010
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Ingår i: Proceedings of the 5th Audio Mostly - A Conference on Interaction With Sound, AM '10. - New York, NY, USA : ACM. - 9781450300469 ; , s. 1859802-
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Konferensbidrag (refereegranskat)abstract
- This paper will discuss the use of psychoacoustic evaluation as a tool for optimization of the soundscape simulator developed in the Listen project. The listen project is a three-year research project focused around developing a demonstrator, which auralizes the sound environment produced by road and railway traffic. The resolution of the parameter space of the simulator heavily influences the performance of the simulator. The perceptual resolution of the parameter space is investigated and the resolution is adjusted accordingly. The most important parameter is velocity. Adjustments of the resolution of this parameter alone gives a 60% reduction of the usage of memory.
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| 35. |
- Mitrovic, I. Z., et al.
(författare)
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Interface engineering of Ge using thulium oxide : Band line-up study
- 2013
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Ingår i: Microelectronic Engineering. - : Elsevier. - 0167-9317 .- 1873-5568. ; 109, s. 204-207
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the band line-up and optical properties (dielectric function) of Tm2O3/Ge gate stacks deposited by atomic layer deposition. X-ray photoelectron spectroscopy has been performed to ascertain the shallow core levels (Ge3d and Tm4d) in ultra-thin and bulk Tm2O3/Ge stacks as well as valence band maxima in Ge and bulk Tm2O3. The valence band offset of Tm2O3/Ge has been found to be 2.95 +/- 0.08 eV. Vacuum ultra violet variable angle spectroscopic ellipsometry studies reveal the indirect band gap nature of Tm2O3, with the value extracted from the Tauc method of 5.3 +/- 0.1 eV. A distinct absorption feature is observed at similar to 3.2 eV below the band gap of Tm2O3, and clearly distinguished from the Si and Ge critical points. A dielectric constant of 14 to 15 has been derived from the electrical measurements on 5 nm Tm2O3/epi Ge/Si gate stacks. The band line-up study of Tm2O3/Ge implies an acceptable barrier for holes (2.95 eV) and electrons (greater than 1.7 eV) for Ge MOSFET engineering.
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| 36. |
- Mitrovic, I. Z., et al.
(författare)
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Interface engineering routes for a future cmos ge-based technology
- 2014
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Ingår i: ECS Transactions. - : The Electrochemical Society. - 1938-5862 .- 1938-6737. ; , s. 73-88
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Konferensbidrag (refereegranskat)abstract
- We present an overview study of two germanium interface engineering routes, firstly a germanate formation via La2O3 and Y2O3, and secondly a barrier layer approach using Al2O3 and Tm2O3. The interfacial composition, uniformity, thickness, band gap, crystallinity, absorption features and valence band offset are determined using X-ray photoelectron spectroscopy, ultra violet variable angle spectroscopic ellipsometry, and high resolution transmission electron microscopy. The correlation of these results with electrical characterization data make a case for Ge interface engineering with rare-earth inclusion as a viable route to achieve high performance Ge CMOS.
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| 37. |
- Patching, Geoffrey, et al.
(författare)
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Time- and space-order effects in timed discrimination of brightness and size of paired visual stimuli
- 2012
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Ingår i: Journal of Experimental Psychology. - : American Psychological Association (APA). - 0096-1523 .- 1939-1277. ; 38:4, s. 915-940
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Tidskriftsartikel (refereegranskat)abstract
- Despite the importance of both response probability and response time for testing models of choice there is a dearth of chronometric studies examining systematic asymmetries that occur over time- and space-orders in the method of paired comparisons. In this study, systematic asymmetries in discriminating the magnitude of paired visual stimuli are examined by way of log-odds ratios of binary responses as well as by signed response speed. Hierarchical Bayesian modeling is used to map response probabilities and response speed onto constituent psychological process, and processing capacity is also assessed using response time distribution hazard functions. The findings include characteristic order effects that change systematically in magnitude and direction with changes in the magnitude and separation of the stimuli. After Hellström (1979, 2000), Sensation Weighting (SW) model analyses show that such order effects are reflected in the weighted accumulation of noisy information about the difference between stimulus values over time, and interindividual differences in weightings asymmetries are related to the relative processing capacity of participants. An account of sensation weighting based on the use of reference level information and maximization of signal-to-noise ratios is posited, which finds support from theoretically driven analyses of behavioral data.
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| 38. |
- Pixton, Tonya S., et al.
(författare)
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Perceived degree of facial happiness and the role of the particular stimuli
- 2010
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Ingår i: Fechner Day 10. - Padua, Italy : International Society for Psychophysics. ; , s. 501-504
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Konferensbidrag (refereegranskat)abstract
- The purpose of the present study was to elucidate further Pixton’s and colleagues (2007, 2008, 2009) results with a between-group study. Two groups (happy, angry) viewed pictures of facial expressions (Tottenham et al., 2009) with three presentation times (12.50, 18.75, 25.00 ms) and completed a detection (Part 1) and a rating (Part 2) task. In Part 1, participants answered “yes” if they thought the face was happy (happy-group) or angry (angry-group and “no” if not. In Part 2, they rated each face stimulus on each of three scales (angriness, happiness, emotionality). The d′ values were higher for the happy-face group than for the angry-face group for the two longest times. “Neutral” faces were not rated equally neutral by the different groups. Together with Pixton and colleagues’ results, when investigating the detectability of emotions, account must be taken of the particular stimuli used, which has now been demonstrated in a between-groups and a within-participants study.
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| 39. |
- Shao, Z., et al.
(författare)
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Cytochrome P450 2C8 omega 3-Long-Chain Polyunsaturated Fatty Acid Metabolites Increase Mouse Retinal Pathologic Neovascularization-Brief Report
- 2014
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 34:3, s. 581-586
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Tidskriftsartikel (refereegranskat)abstract
- Objective Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary 3-long-chain polyunsaturated fatty acids (3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. Approach and Results The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a 3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both 3LCPUFA and 6LCPUFA and antiangiogenic role of sEH in 3LCPUFA metabolism were corroborated in aortic ring assays. Conclusions Our results suggest that CYP2C 3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization.
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| 40. |
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| 41. |
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| 42. |
- Sylvan, Staffan P. E., et al.
(författare)
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Modulation of Serum Interleukin-18 Concentrations and Hepatitis B Virus DNA Levels During Interferon Therapy in Patients with Hepatitis B e-Antigen-Positive Chronic Hepatitis B
- 2010
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Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 30:12, s. 901-908
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was (1) to determine plasma values of interleukin-18 (IL-18) in patients with different clinical manifestations of hepatitis B (HB) and (2) to analyze the correlation between presence of circulatory levels of IL-18 and levels of HB virus (HBV) DNA during interferon-alpha (IFN-alpha)-induced HBe seroconversion in patients with chronic HB (CHB). The IL-18 levels in serum did not significantly differ between healthy control subjects (99+/-25 pg/mL), HB-immune patients (85+/-33), and asymptomatic carriers of HB surface antigen (144+/-44 pg/mL). In contrast, anti-HBe (HBV DNA <10(4) copies/mL, 555+/-248, P<0.05), anti-HBe (HBV DNA >10(4) copies/mL, 280+/-85, P<0.05), and HBe-antigen-reactive (373+/-108, P<0.0001) patients with symptomatic CHB had significantly elevated levels in circulation compared with healthy control subjects (99+/-25 pg/mL). An inverse correlation was found between serum HBV DNA copies and IL-18 levels during therapy (r--0.54, P<0.001). We consistently observed an IFN-alpha-induced suppression of viral replication, which was followed by the alanine aminotransferase (ALT) flare. There was a significant increase in IL-18 production after the ALT flare, where the peak of IL-18 preceded or coincided with the time of HBe seroconversion in patients who cleared the virus. These results suggest that IL-18 is involved in the pathogenesis of CHB and that IFN-alpha therapy can augment the production of IL-18 in patients with CHB.
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| 43. |
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| 44. |
- Wo, J. M., et al.
(författare)
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Randomised clinical trial : ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting - randomised clinical study subset data
- 2011
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 33:6, s. 679-688
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Tidskriftsartikel (refereegranskat)abstract
- Background: Limited therapeutic options exist for severe gastroparesis, where severe nausea and vomiting can lead to weight loss, dehydration and malnutrition due to inadequate caloric and fluid intake. TZP-101 (ulimorelin) is a ghrelin receptor agonist that accelerates gastric emptying and improves upper gastrointestinal symptoms in diabetic patients with gastroparesis. Aim To assess effects of TZP-101 in diabetic gastroparesis patients with severe nausea/vomiting and baseline severity scores of >= 3.5 (range: 0-5) on the Gastroparesis Cardinal Symptom Index (GCSI) Nausea/Vomiting subscale. Methods Patients were hospitalised and received four single daily 30-min infusions of one of six TZP-101 doses (range 20-600 mu g/kg) or placebo. Efficacy was assessed by symptom improvement. Results At baseline, 23 patients had a mean severity score for GCSI Nausea/Vomiting of 4.45 +/- 0.44. Statistically significant improvements over placebo occurred in the 80 mu g/kg group for end of treatment changes from baseline in GCSI Nausea/Vomiting subscale (reduction in score of -3.82 +/- 0.76, P = 0.011) and the GCSI Total score (-3.14 +/- 0.78, P = 0.016) and were maintained at the 30-day follow-up assessment (-2.02 +/- 1.63, P = 0.073 and -1.99 +/- 1.33, P = 0.032 respectively). The proportion of days with vomiting was reduced significantly (P = 0.05) in the 80 mu g/kg group (mean of 1.2 days of vomiting for four treatment days) compared with placebo (mean of 3.2 days of vomiting across 4 treatment days). Conclusions TZP-101 substantially reduced the frequency and severity of nausea and vomiting as well as overall gastroparesis symptoms. The results are consistent with gastrointestinal motility effects of TZP-101, supporting further investigation of TZP-101 in the management of severe gastroparesis.
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