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1.
  • Ericsson, Olle, et al. (author)
  • Clinical validation of a novel automated cell-free DNA screening assay for trisomies 21, 13, and 18 in maternal plasma.
  • 2019
  • In: Prenatal diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 39:11, s. 1011-1015
  • Journal article (peer-reviewed)abstract
    • To evaluate clinical performance of a new automated cell-free (cf)DNA assay in maternal plasma screening for trisomies 21, 18, and 13, and to determine fetal sex.Maternal plasma samples from 1200 singleton pregnancies were analyzed with a new non-sequencing cfDNA method, which is based on imaging and counting specific chromosome targets. Reference outcomes were determined by either cytogenetic testing, of amniotic fluid or chorionic villi, or clinical examination of neonates.The samples examined included 158 fetal aneuploidies. Sensitivity was 100% (112/112) for trisomy 21, 89% (32/36) for trisomy 18, and 100% (10/10) for trisomy 13. The respective specificities were 100%, 99.5%, and 99.9%. There were five first pass failures (0.4%), all in unaffected pregnancies. Sex classification was performed on 979 of the samples and 99.6% (975/979) provided a concordant result.The new automated cfDNA assay has high sensitivity and specificity for trisomies 21, 18, and 13 and accurate classification of fetal sex, while maintaining a low failure rate. The study demonstrated that cfDNA testing can be simplified and automated to reduce cost and thereby enabling wider population-based screening.
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2.
  • Larsson, Bengt, et al. (author)
  • Molecular oxygen in the rho Ophiuchi cloud
  • 2007
  • In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 466:3, s. 5-
  • Journal article (peer-reviewed)abstract
    • Context: Molecular oxygen, O2, has been expected historically to be an abundant component of the chemical species in molecular clouds and, as such, an important coolant of the dense interstellar medium. However, a number of attempts from both ground and from space have failed to detect O2 emission.Aims: The work described here uses heterodyne spectroscopy from space to search for molecular oxygen in the interstellar medium. Methods: The Odin satellite carries a 1.1 m sub-millimeter dish and a dedicated 119 GHz receiver for the ground state line of O2. Starting in 2002, the star forming molecular cloud core ρ Oph A was observed with Odin for 34 days during several observing runs.Results: We detect a spectral line at v_LSR =+3.5 km s-1 with Δ v_FWHM=1.5 km s-1, parameters which are also common to other species associated with ρ Oph A. This feature is identified as the O2 (NJ = 11 - 1_0) transition at 118 750.343 MHz.Conclusions: The abundance of molecular oxygen, relative to H{2} , is 5 × 10-8 averaged over the Odin beam. This abundance is consistently lower than previously reported upper limits.Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Étude Spatiale (CNES). The Swedish Space Corporation has been the industrial prime contractor and also is operating the satellite. Appendix A is only available in electronic form at http://www.aanda.org
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3.
  • Claesson Lingehall, Helena, 1965-, et al. (author)
  • Is a hyperosmolar pump prime for cardiopulmonary bypass a risk factor for postoperative delirium? : A double blinded randomised controlled trial
  • 2023
  • In: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 57:1
  • Journal article (peer-reviewed)abstract
    • Objective: Postoperative delirium (POD) is common after cardiac surgery. We have previously identified plasma sodium concentration and the volume of infused fluids during surgery as possible risk factors. Both are linked to the selection and composition of the pump prime used for cardiopulmonary bypass (CPB). Present study aims to examine whether hyperosmolality increases the risk for POD.Design: Patients ≥65 years (n = 195) scheduled for cardiac surgery were prospectively enrolled into this double blinded randomised clinical trial. Study group received a pump prime containing mannitol and ringer-acetate (966 mOsmol) (n = 98) vs. ringer-acetate (388 mOsmol) (n = 97) in the control group. Postoperative delirium was defined according to DSM-5 criteria based on a test-battery pre- and postoperatively (days 1–3). Plasma osmolality was measured on five occasions and coordinated with the POD assessments. The primary outcome was the POD incidence related to hyperosmolality as the secondary outcome.Results: The incidence of POD was 36% in the study group and 34% in the control group, without intergroup difference (p=.59). The plasma osmolality was significantly higher in the study group, both on days 1 and 3 and after CPB (p<.001). Post hoc analysis indicated that high osmolality levels increased the risk for delirium on day 1 by 9% (odds ratio (OR) 1.09, 95% CI 1.03–1.15) and by 10% on day 3 (OR 1.10, 95% CI 1.04–1.16).Conclusions: Use of a prime solution with high osmolality did not increase the incidence of POD. However, the influence of hyperosmolality as a risk factor for POD warrants further investigation.
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4.
  • Gad, Helge, et al. (author)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Journal article (peer-reviewed)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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5.
  • Hersi, Abdi-Fatah, et al. (author)
  • Optimizing Dose and Timing in Magnetic Tracer Techniques for Sentinel Lymph Node Detection in Early Breast Cancers: The Prospective Multicenter SentiDose Trial
  • 2021
  • In: Cancers. - : MDPI AG. - 2072-6694. ; 13:4
  • Journal article (peer-reviewed)abstract
    • Simple Summary Superparamagnetic iron oxide (SPIO) nanoparticles have comparable performance to the combination of radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) biopsy in breast cancer. In this multicenter prospective study, lower SPIO doses (undiluted 1.5 vs. 1.0 mL) in different timeframes (perioperative vs. 1-7 days preoperative) and injection sites (subareolar vs. peritumoral) were compared to the previous standard (diluted 2.0 mL perioperatively) from the earlier Nordic trial. RI + BD were co-administered as background. In total, 534 patients were analyzed. SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and respectively non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 mL and the Nordic cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Thus, SPIO at 1.5 and 1.0 mL was non-inferior to both Sienna+(R) and the dual technique for SLN detection. Superparamagnetic iron oxide nanoparticles (SPIO) are non-inferior to radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) detection. Previously, 2 mL SPIO (Sienna+(R)) in 3 mL NaCl was used. In this dose-optimizing study, lower doses of a new refined SPIO solution (Magtrace(R)) (1.5 vs. 1.0 mL) were tested in different timeframes (0-24 h perioperative vs. 1-7 days preoperative) and injections sites (subareolar vs. peritumoral). Two consecutive breast cancer cohorts (n = 328) scheduled for SLN-biopsy were included from 2017 to 2019. All patients received isotope +/- blue dye as back-up. SLNs were identified primarily with the SentiMag(R) probe and thereafter a gamma-probe. The primary endpoint was SLN detection rate with SPIO. Analyses were performed as a one-step individual patient-level meta-analysis using patient-level data from the previously published Nordic Trial (n = 206) as a third, reference cohort. In 534 patients, the SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 and the 2.0 mL cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Lower SPIO volumes injected up to 7 days before the operation have comparable efficacy to standard SPIO dose and RI + BD for SLN detection.
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6.
  • Karakatsanis, Andreas, et al. (author)
  • Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study)
  • 2019
  • In: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:6
  • Journal article (peer-reviewed)abstract
    • Background: One-fifth of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) have invasive breast cancer (IBC) on definitive histology. Sentinel lymph node dissection (SLND) is performed in almost half of women having surgery for DCIS in Sweden. The aim of the present study was to try to minimize unnecessary SLND by injecting superparamagnetic iron oxide (SPIO) nanoparticles at the time of primary breast surgery, enabling SLND to be performed later, if IBC is found in the primary specimen. Methods: Women with DCIS at high risk for the presence of invasion undergoing breast conservation, and patients with DCIS undergoing mastectomy were included. The primary outcome was whether this technique could reduce SLND. Secondary outcomes were number of SLNDs avoided, detection rate and procedure-related costs. Results: This was a preplanned interim analysis of 189 procedures. IBC was found in 47 and a secondary SLND was performed in 41 women. Thus, 78.3 per cent of patients avoided SLND (P<0.001). At reoperation, SPIO plus blue dye outperformed isotope and blue dye in detection of the sentinel node (40 of 40 versus 26 of 40 women; P<0.001). Costs were reduced by a mean of 24.5 per cent in women without IBC (3990 versus 5286; P<0.001). Conclusion: Marking the sentinel node with SPIO in women having surgery for DCIS was effective at avoiding unnecessary SLND in this study. Registration number: ISRCTN18430240 (http://www.isrctn.com).
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7.
  • Karakatsanis, Andreas, et al. (author)
  • SentiNot : A way to avoid sentinel node biopsy (SNB) in patients with a preoperative diagnosis of ductal cancer in situ (DCIS)
  • 2017
  • In: Cancer Research. - Univ Uppsala Hosp, Sect Endocrine & Breast Surg, Uppsala, Sweden. Univ Uppsala Hosp, Uppsala, Sweden. Vastmanland Cty Hosp, Vasteras, Vasteras, Sweden. Uppsala Clin Res Ctr, Uppsala, Sweden. Kalmar Cty Hosp, Sect Breast Surg, Kalmar, Sweden. Univ Uppsala Hosp, Inst Radiol Oncol & Radiotherapy, Uppsala, Sweden. Norrlands Univ Hosp, Umea, Sweden. : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 77
  • Journal article (peer-reviewed)
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8.
  • Olofsson, Jonas, et al. (author)
  • Arbetslivets omreglering, arbetsmarknadens reglering och lärlingsutbildningens betydelse
  • 2018
  • In: Unga inför arbetslivet : – om utanförskap, lärande och delaktighet - – om utanförskap, lärande och delaktighet. - Lund : Studentlitteratur AB. - 9789144119298 ; , s. 205-228
  • Book chapter (peer-reviewed)abstract
    • I kapitlet är syftet att vidga perspektivet på regleringar och diskutera den omreglering som har skett i arbetslivet under de tre-fyra senaste decennierna. Förändringarna i arbetslivet hänger samman med nya konkurrensvillkor, ny teknik och förändrade arbetsorganisationer. Det handlar om en utveckling bort från det som brukar kallas industrisamhället till det post-industriella samhället. Hur påverkar dessa långsiktiga förändringar av anställningarnas reglering och kraven på arbetskraften ungas etableringsvillkor? Med ökande flexibilitet följer både större krav på ansvar och omställningsförmåga. För delar av arbetskraften leder arbetslivets förändringar i en riktning som ger rikare utvecklingsmöjligheter och inflytande över arbetet (funktionell flexibilitet), för andra tar sig flexibilitetskraven framför allt uttryck i en ökad utbytbarhet (numerär flexibilitet). Hur påverkar dessa omställningskrav i arbetslivet ungas etableringsmöjligheter? Och vad är det för behov av kompetenser och färdigheter unga behöver för att kunna möta de nya villkoren i arbetslivet?
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9.
  • Ramstedt, S., et al. (author)
  • Imaging the circumstellar dust around AGB stars with PolCor
  • 2011
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531
  • Journal article (peer-reviewed)abstract
    • Aims. The aim of this paper is to investigate how the new imaging Polarimeter and Coronograph (PolCor) at the Nordic Optical Telescope** (NOT) can be used in the study of circumstellar structures around AGB stars. The purpose is to prepare for a study of a larger sample. Methods. We have observed two types of AGB stars using the PolCor instrument on the NOT: the binary S-type star W Aql and two carbon stars with detached shells, U Cam and DR Ser. The polarized light traces the dust distribution around the stars. From the polarimeter images the polarized intensity, the polarization degree, and the polarization angle over the images are calculated. The location and extent of dust structures are examined in the images. The total dust mass and the dust-to-gas ratios of the detached shells are also calculated. Results. The images of the circumstellar envelope of W Aql show what seems to be an elongated structure in the south-west direction. The detached shells of U Cam and DR Ser are clearly seen in the images. This is the first time the detached shell around DR Ser has been imaged. The radii (R(sh)) and widths (Delta R(sh)) of the shells are determined and found to be R(sh) = 7 ''.9 and 7 ''.6, and Delta R(sh) = 0 ''.9 and 1 ''.2, for U Cam and DR Ser, respectively. This is consistent with previous results. The dust masses of the feature south-west of W Aql, and in the shells of U Cam and DR Ser are also estimated and found to be 1 x 10(-6), 5 x 10(-7), and 2 x 10(-6) M(circle dot), respectively. Conclusions. W Aql is a known binary and the shape of the circumstellar envelope seems to be in line with what could be expected from binary interaction on these scales. For the shells, the results are in agreement with previous investigations. Ages and formation time-scales are also estimated for the detached shells and found to be consistent with the thermal-pulse-formation scenario.
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11.
  • Xiong, Anqi, 1986-, et al. (author)
  • Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression
  • 2020
  • In: Cancers. - : MDPI AG. - 2072-6694. ; 12:6
  • Journal article (peer-reviewed)abstract
    • Pseudokinases, comprising 10% of the human kinome, are emerging as regulators of canonical kinases and their functions are starting to be defined. We previously identified the pseudokinase Nuclear Receptor Binding Protein 2 (NRBP2) in a screen for genes regulated during neural differentiation. During mouse brain development,NRBP2is expressed in the cerebellum, and in the adult brain, mainly confined to specific neuronal populations. To study the role of NRBP2 in brain tumors, we stained a brain tumor tissue array for NRPB2, and find its expression to be low, or absent, in a majority of the tumors. This includes medulloblastoma (MB), a pediatric tumor of the cerebellum. Using database mining of published MB data sets, we also find that NRBP2 is expressed at a lower level in MB than in the normal cerebellum. Recent studies indicate that MB exhibits frequent epigenetic alternations and we therefore treated MB cell lines with drugs inhibiting DNA methylation or histone deacetylation, which leads to an upregulation of NRBP2 mRNA expression, showing that it is under epigenetic regulation in cultured MB cells. Furthermore, forced overexpression of NRBP2 in MB cell lines causes a dramatic decrease in cell numbers, increased cell death, impaired cell migration and inhibited cell invasion in vitro. Taken together, our data indicate that downregulation of NRBP2 may be a feature by which MB cells escape growth regulation.
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12.
  • Åberg, Veronica, 1976-, et al. (author)
  • Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of A beta-peptide aggregation inhibitors
  • 2005
  • In: Organic and biomolecular chemistry. - London, U.K. : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 3:15, s. 2817-2823
  • Journal article (peer-reviewed)abstract
    • A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on A beta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer A beta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric A beta-peptide.
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13.
  • Adamo, Karin, et al. (author)
  • Risk for developing perianal abscess in type 1 and type 2 diabetes and the impact of poor glycemic control
  • 2021
  • In: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 36:5, s. 999-1005
  • Journal article (peer-reviewed)abstract
    • Purpose: The primary aim of this study was to see whether perianal abscess rate differs between patients with type 1 and type 2 diabetes. A secondary aim was to determine whether poor glycemic control increases the risk for perianal abscess.Methods: Data from the Swedish National Diabetes Registry and the Swedish National Patient Registry between January 2008 and June 2015 were matched. The risk for anal abscess was evaluated in univariate and multivariate analyses with type of diabetes, HbA1c level, BMI, and various diabetes complications as independent factors.Results: Patients with type 1 diabetes had a lower rate of perianal abscess than patients with type 2 diabetes when adjusted for HbA1c, sex, and age (OR 0.65; 95% CI 0.57–0.73). The risk for perianal abscess increased with higher HbA1c. Incidence of perianal abscess was also elevated in diabetes patients with complications related to poor glycemic control such as ketoacidosis and coma (OR 2.63; 95% CI 2.06–3.35), gastroparesis, and polyneuropathy (OR 1.81; 95% CI 1.41–2.32).Conclusions: The prevalence of perianal abscess was higher among patients with type 2 diabetes than those with type 1, suggesting that metabolic derangement may be more important than autoimmune factors. Poor glycemic control was associated with higher risk for perianal abscess.
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14.
  • Adolfsson, Dan E., 1989-, et al. (author)
  • Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine fused 2-Pyridone Polyheterocycles Binding to α-Synuclein and Amyloid-β fibrils
  • 2020
  • In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 85:21, s. 14174-14189
  • Journal article (other academic/artistic)abstract
    • A BF3×OEt2 catalyzed intramolecular Povarov reaction was used to synthesize a library of 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with a range of O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycles with diverse substitution. The synthesized compounds were screened for their ability to bind α-synuclein and amyloid β fibrils in vitro. Analogs substituted with a nitro group bind to mature amyloid fibrils, and the activity moreover depends on the positioning of this functional group.
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16.
  • Alcolea, J., et al. (author)
  • HIFISTARS Herschel/HIFI observations of VY Canis Majoris. Molecular-line inventory of the envelope around the largest known star
  • 2013
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 559, s. (article nr.) A93-
  • Journal article (peer-reviewed)abstract
    • Aims.The study of the molecular gas in the circumstellar envelopes of evolved stars is normally undertaken by observing lines ofCO (and other species) in the millimetre-wave domain. In general, the excitation requirements of the observed lines are low at thesewavelengths, and therefore these observations predominantly probe the cold outer envelope while studying the warm inner regions ofthe envelopes normally requires sub-millimetre (sub-mm) and far-infrared (FIR) observational data.Methods.To gain insight into the physical conditions and kinematics of the warm (100–1000 K) gas around the red hyper-giantVY CMa, we performed sensitive high spectral resolution observations of molecular lines in the sub-mm/FIR using the HIFI instru-ment of theHerschelSpace Observatory. We observed CO, H2O, and other molecular species, sampling excitation energies from afew tens to a few thousand K. These observations are part of theHerschelguaranteed time key program HIFISTARS.Results.We detected theJ=6–5,J=10–9, andJ=16–15 lines of12CO and13CO at∼100, 300, and 750 K above the groundstate (and the13COJ=9–8 line). These lines are crucial for improving the modelling of the internal layers of the envelope aroundVY CMa. We also detected 27 lines of H2O and its isotopomers, and 96 lines of species such as NH3,SiO,SO,SO2HCN, OH andothers, some of them originating from vibrationally excited levels. Three lines were not unambiguously assigned.Conclusions.Our observations confirm that VY CMa’s envelope must consist of two or more detached components. The molecularexcitation in the outer layers is significantly lower than in the inner ones, resulting in strong self-absorbed profiles in molecular linesthat are optically thick in this outer envelope, for instance, low-lying lines of H2O. Except for the most abundant species, CO and H2O,most of the molecular emission detected at these sub-mm/FIR wavelengths arise from the central parts of the envelope. The spectrumof VY CMa is very prominent in vibrationally excited lines, which are caused by the strong IR pumping present in the central regions.Compared with envelopes of other massive evolved stars, VY CMa’s emission is particularly strong in these vibrationally excitedlines, as well as in the emission from less abundant species such as H13CN, SO, and NH3.
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17.
  • Andersson, Anders-Petter, 1969-, et al. (author)
  • Designing sound for recreation and well-being
  • 2014
  • In: Proceedings of the International Conference on New Interfaces for Musical Expression (NIME 2014). - 9781906897291 ; , s. 529-532
  • Conference paper (peer-reviewed)abstract
    • In this paper we explore how we compose sound for an interactive tangible and mobile interface, where the goal is to improve health and well-being for families with children with disabilities. We describe the composition process of how we decompose a linear beat-based and vocal sound material and recompose it with real-time audio synthesis and composition rules into interactive Scenes. Scenes that make it possible for the users to select, explore and recreate different sound worlds. In order to recreate, the users interact with the tangible interface in different ways, as instrument, play with it as a friend, improvise and create music and relax with it as ambient sounding furniture. We discuss composition techniques for mixing sound, tangible-physical and lighting elements in the Scenes. Based on observations we explore how a diverse audience in the family and at school can recreate and improvise their own sound experience and play together in open and non-therapeutic everyday situations. We conclude by discussing the possible impact of our findings for the NIME-community; how the techniques of decomposing, recomposing and recreating sound, based on a relational perspective, could contribute to the design of new instruments for musical expression.
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18.
  • Andersson, Anders-Petter, et al. (author)
  • Designing sound for recreation and well-being
  • 2014
  • Conference paper (other academic/artistic)abstract
    • In this paper we explore how we compose sound for an interactive tangible and mobile interface, where the goal is to improve health and well-being for families with children with disabilities. We describe the composition process of how we decompose a linear beat-based and vocal sound material and recompose it with real-time audio synthesis and composition rules into interactive Scenes. Scenes that make it possible for the users to select, explore and recreate different sound worlds. In order to recreate, the users interact with the tangible interface in different ways, as instrument, play with it as a friend, improvise and create music and relax with it as ambient sounding furniture. We discuss composition techniques for mixing sound, tangible-physical and lighting elements in the Scenes. Based on observations we explore how a diverse audience in the family and at school can recreate and improvise their own sound experience and play together in open and non-therapeutic everyday situations. We conclude by discussing the possible impact of our findings for the NIME-community; how the techniques of decomposing, recomposing and recreating sound, based on a relational perspective, could contribute to the design of new instruments for musical expression.
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19.
  • Arshamian, Artin, 1979-, et al. (author)
  • Sniff Your Way to Clarity : The Case of Olfactory Imagery
  • 2008
  • In: CHEMOSENSORY PERCEPTION. - : Springer Science and Business Media LLC. - 1936-5802 .- 1936-5810. ; 1:4, s. 242-246
  • Journal article (peer-reviewed)abstract
    • This study addressed the effects of blocking spontaneous sniffing during olfactory imagery. A group of subjects (n=40) who scored high in olfactory focus and imagery ability rated the vividness in olfactory and visual imagery content under conditions of blocked sniffing, blocked vision, and a nonblocked control. The imagery stimuli consisted of 90 common words that could represent either an odor or a visual object. Blocked sniffing was expected to impair olfactory imagery vividness, but since visual imagery entails eye movements, which was not affected by the ""blocked vision"" manipulation, visual imagery ratings were effectively used as a placebo control. Confirming our hypotheses, the results showed that preventing sniffing resulted in a selectively poorer olfactory but not visual vividness, whereas blocked vision showed no effect on either the visual or olfactory vividness ratings. These observations confirm that sensorimotor activity is an important aspect for the quality of evoked olfactory images.
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20.
  • Bekkhus, Tove, et al. (author)
  • Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells
  • 2021
  • In: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
  • Journal article (peer-reviewed)abstract
    • Simple Summary Tumor draining lymph nodes (TDLNs) are the most common metastatic sites in human cancer but are also essential sites for induction of tumor immunity. How different types of primary tumors affect the anti-tumor immune response in the LNs is not fully understood. By analyzing biobank tissue from breast cancer patients, we demonstrate that invasive breast cancer induce dramatic pre-metastatic LN changes affecting the structure and function of the specialized LN vasculature and associated stromal cells, required for recruitment of T-lymphocytes into the LNs. These changes could not be seen in patients with non-invasive breast cancer and provide new insights of how invasive tumors can disrupt essential functions within the immune system. The data also shows promise of LN stromal and vascular changes as possible future biomarkers for prediction of disease progression in human cancer. The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.
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22.
  • Bharate, Jaideep B., et al. (author)
  • K2S2O8-mediated coupling of 6-amino-7-aminomethyl-thiazolino-pyridones with aldehydes to construct amyloid affecting pyrimidine-fused thiazolino-2-pyridones
  • 2021
  • In: Organic and biomolecular chemistry. - : The Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 19:44, s. 9758-9772
  • Journal article (peer-reviewed)abstract
    • We herein present the synthesis of diversely functionalized pyrimidine fused thiazolino-2-pyridones via K2S2O8-mediated oxidative coupling of 6-amino-7-(aminomethyl)-thiazolino-2-pyridones with aldehydes. The developed protocol is mild, has wide substrate scope, and does not require transition metal catalyst or base. Some of the synthesized compounds have an ability to inhibit the formation of Amyloid-β fibrils associated with Alzheimer's disease, while others bind to mature amyloid-β and α-synuclein fibrils.
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23.
  • Björk, Fredrik, et al. (author)
  • An Ecosystem for Social Innovation in Sweden : A strategic research and innovation agenda
  • 2014
  • Reports (other academic/artistic)abstract
    • This report represents the continuation of a national dialog among actors across Sweden with the aim of identifying promising areas of development for the social innovation system. The output of this dialog is a list of suggestions that would support the advancement of social innovation knowledge and practice within academia, the public sector, civil society and business. The recommendations put forward in this agenda aim to leverage the growth of individuals and organizations wanting to develop social innovations that assist in addressing societal challenges in line with the European Union’s and Sweden’s innovation policy strategies (the explicit targets of addressing grand societal challenges).
  •  
24.
  • Buchwald, Pamela, et al. (author)
  • Standard protocol for assessment of colon cancer improves the quality of pathology.
  • 2011
  • In: Colorectal Disease. - : Wiley. - 1462-8910. ; 13, s. 33-36
  • Journal article (peer-reviewed)abstract
    • Aim: Tumour stage is the most important prognostic factor in colon cancer. The aim of this study was to examine the impact on the quality of pathology by the use of a standardized PAD protocol. Method: A standardized PAD protocol for colorectal cancer was developed and all patients subjected to colon resection due to adenocarcinomas between 2004 and 2006 were analyzed concerning lymph node status, circumferential resection margin (CRM), intravascular and perineural growth. Moreover, usage of the PAD protocol and whether a pathologist or biomedicine analytic technician (BMA) performed the lymph node dissection was noted and also if the surgical procedure was elective or acute. Results: During the study period 302 colon resections were carried out. The standard protocol was employed in 68% of the cases varying from 0-100% between pathologists. The median number of investigated lymph nodes was 16 ± 11. When the lymph node dissection was performed by a BMA, significantly more lymph nodes were examined; 22 ± 15 and 14 ± 9 respectively (p<0.01). There was a positive correlation between application of the standard protocol and the number of analyzed lymph nodes (<0.05). Comments on CRM, perineural growth and intravascular growth were also significantly more frequent when the protocol was used. Emergency surgery did not influence the handling of the specimens. Conclusion: Minor efforts in terms of a standard protocol for pathology and specimen dissection by BMAs, leading to an increased quality of the PAD-report may also improve long term outcome for patients.
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25.
  • Buckland, Philip I., et al. (author)
  • Integrating human dimensions of Arctic palaeoenvironmental science : SEAD – the strategic environmental archaeology database
  • 2011
  • In: Journal of Archaeological Science. - : Elsevier. - 0305-4403 .- 1095-9238. ; 38:2, s. 345-351
  • Journal article (peer-reviewed)abstract
    • Environmental change has a human dimension, and has had so for at least the last 10 000 years. The prehistoric impact of people on the Arctic landscape has occasionally left visible traces, such as house and field structures. More often than not, however, the only evidence available is at the microscopic or geochemical level, such as fossil insect and seed assemblages or changes in the physical and chemical properties of soils and sediments. These records are the subject of SEAD, a multidisciplinary database and software project currently underway at Umeå University, Sweden, which aims to create an online database and set of tools for investigating these traces, as part of an international research infrastructure for palaeoecology and environmental archaeology.
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26.
  • Bujarrabal, V., et al. (author)
  • Herschel/HIFI observations of high-J CO transitions in the protoplanetary nebula CRL 618
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L3-
  • Journal article (peer-reviewed)abstract
    • Aims. We aim to study the physical conditions, particularly the excitation state, of the intermediate-temperature gas components in the protoplanetary nebula CRL 618. These components are particularly important for understanding the evolution of the nebula. Methods. We performed Herschel/HIFI observations of several CO lines in the far-infrared/sub-mm in the protoplanetary nebula CRL 618. The high spectral resolution provided by HIFI allows measurement of the line profiles. Since the dynamics and structure of the nebula is well known from mm-wave interferometric maps, it is possible to identify the contributions of the different nebular components (fast bipolar outflows, double shells, compact slow shell) to the line profiles. The observation of these relatively high-energy transitions allows an accurate study of the excitation conditions in these components, particularly in the warm ones, which cannot be properly studied from the low-energy lines. Results. The (CO)-C-12 J = 16-15, 10-9, and 6-5 lines are easily detected in this source. Both (CO)-C-13 J = 10-9 and 6-5 are also detected. Wide profiles showing spectacular line wings have been found, particularly in (CO)-C-12 J = 16-15. Other lines observed simultaneously with CO are also shown. Our analysis of the CO high-J transitions, when compared with the existing models, confirms the very low expansion velocity of the central, dense component, which probably indicates that the shells ejected during the last AGB phases were driven by radiation pressure under a regime of maximum transfer of momentum. No contribution of the diffuse halo found from mm-wave data is identified in our spectra, because of its low temperature. We find that the fast bipolar outflow is quite hot, much hotter than previously estimated; for instance, gas flowing at 100 km s(-1) must have a temperature higher than similar to 200 K. Probably, this very fast outflow, with a kinematic age
  •  
27.
  • Bujarrabal, V., et al. (author)
  • Herschel/HIFI observations of molecular emission in protoplanetary nebulae and young planetary nebulae
  • 2012
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. Article Number: A8-
  • Journal article (peer-reviewed)abstract
    • Aims. We aim to study the physical conditions, particularly the excitation state, of the intermediate-temperature gas in protoplanetary nebulae and young planetary nebulae (PPNe, PNe). The information that the observations of the different components deliver is of particular importance for understanding the evolution of these objects. Methods. We performed Herschel/HIFI observations of intermediate-excitation molecular lines in the far-infrared/submillimeter range in a sample of ten nebulae. The high spectral resolution provided by HIFI allows the accurate measurement of the line profiles. The dynamics and evolution of these nebulae are known to result from the presence of several gas components, notably fast bipolar outflows and slow shells (that often are the fossil AGB shells), and the interaction between them. Because of the diverse kinematic properties of the different components, their emissions can be identified in the line profiles. The observation of these high-energy transitions allows an accurate study of the excitation conditions, particularly in the warm gas, which cannot be properly studied from the low-energy lines. Results. We have detected FIR/sub-mm lines of several molecules, in particular of (CO)-C-12, (CO)-C-13, and H2O. Emission from other species, like NH3, OH, (H2O)-O-18, HCN, SiO, etc., has been also detected. Wide profiles showing sometimes spectacular line wings have been found. We have mainly studied the excitation properties of the high-velocity emission, which is known to come from fast bipolar outflows. From comparison with general theoretical predictions, we find that CRL 618 shows a particularly warm fast wind, with characteristic kinetic temperature T-k greater than or similar to 200 K. In contrast, the fast winds in OH 231.8+4.2 and NGC 6302 are cold, T-k similar to 30 K. Other nebulae, like CRL 2688, show intermediate temperatures, with characteristic values around 100 K. We also discuss how the complex structure of the nebulae can affect our estimates, considering two-component models. We argue that the differences in temperature in the different nebulae can be caused by cooling after the gas acceleration (that is probably caused by shocks); for instance, CRL 618 is a case of very recent acceleration, less than similar to 100 yr ago, while the fast gas in OH 231.8+4.2 was accelerated similar to 1000 yr ago. We also find indications that the densest gas tends to be cooler, which may be explained by the expected increase of the radiative cooling efficiency with the density.
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28.
  • Börjesson, Fredrik, 1965- (author)
  • Approaches to Modularity in Product Architecture
  • 2012
  • Licentiate thesis (other academic/artistic)abstract
    • Modular product architecture is characterized by the existence of standardized interfaces between the physical building blocks. A module is a collection of technical solutions that perform a function, with interfaces selected for company-specific strategic reasons. Approaches to modularity are the structured methods by which modular product architectures are derived. The approaches include Modular Function Deployment (MFD), Design Structure Matrix (DSM), Function Structure Heuristics and many other, including hybrids. The thesis includes a survey of relevant theory and a discussion of four challenges in product architecture research, detailed in the appended papers. One common experience from project work is structured methods such as DSM or MFD often do not yield fully conclusive results. This is usually because the algorithms used to generate modules do not have enough relevant data. Thus, we ask whether it is possible to introduce new data to make the output more conclusive. A case study is used to answer this question. The analysis indicates that with additional properties to capture product geometry, and flow of matter, energy, or information, the output is more conclusive. If product development projects even have an architecture definition phase, very little time is spent actually selecting the most suitable tool. Several academic models are available, but they use incompatible criteria, and do not capture experience-based or subjective criteria we may wish to include. The research question is whether we can define selection criteria objectively using academic models and experience-based criteria. The author gathers criteria from three academic models, adds experience criteria, performs a pairwise comparison of all available criteria and applies a hierarchical cluster analysis, with subsequent interpretation. The resulting evaluation model is tested on five approaches to modularity. Several conclusions are discussed. One is that of the five approaches studied, MFD and DSM have the most complementary sets of strengths and weaknesses, and that hybrids between these two fundamental approaches would be particularly interesting. The majority of all product development tries to improve existing products. A common criticism against all structured approaches to modularity is they work best for existing products. Is this perhaps a misconception? We ask whether MFD and DSM can be used on novel product types at an early phase of product development. MFD and DSM are applied to the hybrid drive train of a Forwarder. The output of the selected approaches is compared and reconciled, indicating that conclusions about a suitable modular architecture can be derived, even when many technical solutions are unknown. Among several conclusions, one is the electronic inverter must support several operating modes that depend on high-level properties of the drive train itself (such as whether regeneration is used). A modular structure for the electronic inverter is proposed. Module generation in MFD is usually done with Hierarchical Cluster Analysis (HCA), where the results are presented in the form of a Dendrogram. Statistical software can generate a Dendrogram in a matter of seconds. For DSM, the situation is different. Most available algorithms require a fair amount of processing time. One popular algorithm, the Idicula-Gutierrez-Thebeau Algorithm (IGTA), requires a total time of a few hours for a problem of medium complexity (about 60 components). The research question is whether IGTA can be improved to execute faster, while maintaining or improving quality of output. Two algorithmic changes together reduce execution time required by a factor of seven to eight in the trials, and improve quality of output by about 15 percent.
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29.
  • Castro-Carrizo, A., et al. (author)
  • Mapping the 12CO J = 1-0 and J = 2-1 emission in AGB and early post-AGB circumstellar envelopes. I. The COSAS program, first sample
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 523:4, s. A59-
  • Journal article (peer-reviewed)abstract
    • We present COSAS (CO Survey of late AGB Stars), a project to map and analyze the 12CO J = 1−0 and J = 2−1 line emission in a representative sample of circumstellar envelopes around AGB and post-AGB stars. The survey was undertaken with the aim of investigating small- and large-scale morphological and kinematical properties of the molecular environment surrounding stars in the late AGB and early post-AGB phases. For this, COSAS combines the high sensitivity and spatial resolving power of the IRAM Plateau de Bure interferometer with the better capability of the IRAM 30 m telescope to map extended emission. The global sample encompasses 45 stars selected to span a range in chemical type, variability type, evolutionary state, and initial mass. COSAS provides means to quantify variations in the mass-loss rates, assess morphological and kinematical features, and to investigate the appearance of fast aspherical winds in the early post-AGB phase. This paper, which is the first of a series of COSAS papers, presents the results from the analyses of a first sample of 16 selected sources. The envelopes around late AGB stars are found to be mostly spherical, often mingled with features such as concentric arcs (R Cas and TX Cam), a broken spiral density pattern (TX Cam), molecular patches testifying to aspherical mass-loss (WX Psc, IK Tau, V Cyg, and S Cep), and also with well-defined axisymmetric morphologies and kinematical patterns (X Her and RX Boo). The sources span a wide range of angular sizes, from relatively compact (CRL 2362, OH 104.9+2.4 and CRL 2477) to very large (χ Cyg and TX Cam) envelopes, sometimes partially obscured by self-absorption features, which particularly for IK Tau and χ Cyg testifies to the emergence of aspherical winds in the innermost circumstellar regions. Strong axial structures with more or less complex morphologies are detected in four early post-AGB stars (IRAS 20028+3910, IRAS 23321+6545, IRAS 19475+3119 and IRAS 21282+5050) of the sub-sample.
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30.
  • Chin, Kian, et al. (author)
  • Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study.
  • 2024
  • In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 207:1, s. 49-63
  • Journal article (peer-reviewed)abstract
    • Tumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients.Clinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and ΔTIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS).Two hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02-4.05; p=0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14-0.76; p=0.009) and increased ΔTILs (OR 0.25, 95% CI 0.08-0.79; p=0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS.This study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT.
  •  
31.
  • Chin, Kian, et al. (author)
  • Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study
  • 2024
  • In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217.
  • Journal article (peer-reviewed)abstract
    • Purpose Tumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients.Methods Clinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and Delta TIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS).Results Two hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02-4.05; p = 0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14-0.76; p = 0.009) and increased Delta TILs (OR 0.25, 95% CI 0.08-0.79; p = 0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS.Conclusions This study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT.
  •  
32.
  • Claussen, M. J., et al. (author)
  • A Pilot Imaging Line Survey of RW LMi and IK Tau Using the Expanded Very Large Array
  • 2011
  • In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 739:1, s. L5-
  • Journal article (peer-reviewed)abstract
    • We report on a pilot imaging line survey (36.0-37.0 GHz, with ~1 km s–1 spectral channels) with the Expanded Very Large Array for two asymptotic giant branch stars, RW LMi (= CIT6, which has a carbon-rich circumstellar envelope, CSE) and IK Tau (=NML Tau, with an oxygen-rich CSE). Radio continuum emission consistent with photospheric emission was detected from both stars. From RW LMi we imaged the HC3N (J = 4→3) emission. The images show several partial rings of emission; these multiple shells trace the evolution of the CSE from 400 to 1200 years. SiS (J = 2→1) emission was detected from both RW LMi and IK Tau. For both stars the SiS emission is centrally condensed with the peak line emission coincident with the stellar radio continuum emission. In addition, we have detected weak HC7N (J = 32→31) emission from RW LMi.
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33.
  • Cornell Kärnekull, Stina, et al. (author)
  • Affected by Smells? : Environmental Chemical Responsivity Predicts Odor Perception
  • 2011
  • In: Chemical Senses. - Oxford : Oxford University Press. - 0379-864X .- 1464-3553. ; 36:7, s. 641-648
  • Journal article (peer-reviewed)abstract
    • Strong negative reactions, physical symptoms, and behavioral disruptions due to environmental odors are common in the adult population. We investigated relationships among such environmental chemosensory responsivity (CR), personality traits, affective states, and odor perception. Study 1 showed that CR and neuroticism were positively correlated in a sample of young adults (n = 101), suggesting that persons high in neuroticism respond more negatively to environmental odors. Study 2 explored the relationships among CR, noise responsivity (NR), neuroticism, and odor perception (i.e., pleasantness and intensity) in a subset of participants (n = 40). High CR was associated with high NR. Regression analyses indicated that high CR predicted higher odor intensity ratings and low olfactory threshold (high sensitivity) predicted lower pleasantness ratings. However, neuroticism was not directly associated with odor ratings or thresholds. Overall, the results suggest that CR and odor thresholds predict perceptual ratings of odors and that high CR is associated with nonchemosensory affective traits.
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34.
  • Cöster, Maria, et al. (author)
  • Enkel senförflyttning kan ge ökad funktion vid droppfot efter stroke
  • 2021
  • In: Lakartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 118
  • Journal article (peer-reviewed)abstract
    • Foot drop (FD) can be caused by a variety of diseases and injuries. FD leads to walking difficulties and reduced balance which also can lead to a higher risk of falling. Patient with a stroke often have an equinovarus deformity of the foot together with the DF. There is a need to optimize and standardize the treatment for patients with FD across different medical specialities. Surgical interventions, with goals of producing a balanced functional foot, have been shown to improve the function and quality of life and decrease the use of braces and walking aids in patients with FD after a CVI. In Sweden data regarding FD surgery is collected in the National Quality Registry for Foot and Ankle Surgery (Riksfot), but there is also an ongoing multicentre study, investigating the patient-reported and functional results of surgery due to FD caused by a CVI.
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35.
  • De Vadder, Filipe, et al. (author)
  • Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks
  • 2018
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:25, s. 6458-6463
  • Journal article (peer-reviewed)abstract
    • The enteric nervous system (ENS) is crucial for essential gastrointestinal physiologic functions such as motility, fluid secretion, and blood flow. The gut is colonized by trillions of bacteria that regulate host production of several signaling molecules including serotonin (5-HT) and other hormones and neurotransmitters. Approximately 90% of 5-HT originates from the intestine, and activation of the 5-HT4 receptor in the ENS has been linked to adult neurogenesis and neuroprotection. Here, we tested the hypothesis that the gut micro-biota could induce maturation of the adult ENS through release of 5-HT and activation of 5-HT4 receptors. Colonization of germ-free mice with a microbiota from conventionally raised mice modified the neuroanatomy of the ENS and increased intestinal transit rates, which was associated with neuronal and mucosal 5-HT production and the proliferation of enteric neuronal progenitors in the adult intestine. Pharmacological modulation of the 5-HT4 receptor, as well as depletion of endogenous 5-HT, identified a mechanistic link between the gut microbiota and maturation of the adult ENS through the release of 5-HT and activation of the 5-HT4 receptor. Taken together, these findings show that the microbiota modulates the anatomy of the adult ENS in a 5-HT-dependent fashion with concomitant changes in intestinal transit.
  •  
36.
  • Decin, L., et al. (author)
  • Water content and wind acceleration in the envelope around the oxygen-rich AGB star IK Tauri as seen by Herschel/HIFI
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L4-
  • Journal article (peer-reviewed)abstract
    • During their asymptotic giant branch evolution, low-mass stars lose a significant fraction of their mass through an intense wind, enriching the interstellar medium with products of nucleosynthesis. We observed the nearby oxygen-rich asymptotic giant branch star IK Tau using the high-resolution HIFI spectrometer onboard Herschel. We report on the first detection of (H2O)-O-16 and the rarer isotopologues (H2O)-O-17 and (H2O)-O-18 in both the ortho and para states. We deduce a total water content (relative to molecular hydrogen) of 6.6 x 10(-5), and an ortho-to-para ratio of 3:1. These results are consistent with the formation of H2O in thermodynamical chemical equilibrium at photospheric temperatures, and does not require pulsationally induced non-equilibrium chemistry, vaporization of icy bodies or grain surface reactions. High-excitation lines of (CO)-C-12, (CO)-C-13, (SiO)-Si-28, (SiO)-Si-29, (SiO)-Si-30, HCN, and SO have also been detected. From the observed line widths, the acceleration region in the inner wind zone can be characterized, and we show that the wind acceleration is slower than hitherto anticipated.
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37.
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38.
  • Dieterich, Lothar C., et al. (author)
  • Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization
  • 2012
  • In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 228:3, s. 378-390
  • Journal article (peer-reviewed)abstract
    • Glioblastoma are aggressive astrocytic brain tumours characterized by microvascular proliferation and an abnormal vasculature, giving rise to brain oedema and increased patient morbidity. Here, we have characterized the transcriptome of tumour-associated blood vessels and describe a gene signature clearly associated with pleomorphic, pathologically altered vessels in human glioblastoma (grade IV glioma). We identified 95 genes differentially expressed in glioblastoma vessels, while no significant differences in gene expression were detected between vessels in non-malignant brain and grade II glioma. Differential vascular expression of ANGPT2, CD93, ESM1, ELTD1, FILIP1L and TENC1 in human glioblastoma was validated by immunohistochemistry, using a tissue microarray. Through qPCR analysis of gene induction in primary endothelial cells, we provide evidence that increased VEGF-A and TGFβ2 signalling in the tumour microenvironment is sufficient to invoke many of the changes in gene expression noted in glioblastoma vessels. Notably, we found an enrichment of Smad target genes within the distinct gene signature of glioblastoma vessels and a significant increase of Smad signalling complexes in the vasculature of human glioblastoma in situ. This indicates a key role of TGFβ signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGFβ2 may represent a new target for vascular normalization therapy.
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39.
  •  
40.
  • Ferletta, Maria, et al. (author)
  • Sox10 Has a Broad Expression Pattern in Gliomas and Enhances Platelet-Derived Growth Factor-B–Induced Gliomagenesis
  • 2007
  • In: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 5:9, s. 891-897
  • Journal article (peer-reviewed)abstract
    • In a previously published insertional mutagenesis screen for candidate brain tumor genes in the mouse using a Moloney mouse leukemia virus encoding platelet-derived growth factor (PDGF)-B, the Sox10 gene was tagged in five independent tumors. The proviral integrations suggest an enhancer effect on Sox10. All Moloney murine leukemia virus/PDGFB tumors had a high protein expression of Sox10 independently of malignant grade or tumor type. To investigate the role of Sox10 in gliomagenesis, we used the RCAS/tv-a mouse model in which the expression of retroviral-encoded genes can be directed to glial progenitor cells (Ntv-a mice). Both Ntv-a transgenic mice, wild-type, and Ntv-a p19Arf null mice were injected with RCAS-SOX10 alone or in combination with RCAS-PDGFB. Infection with RCAS-SOX10 alone did not induce any gliomas. Combined infection of RCAS-SOX10 and RCAS-PDGFB in wild-type Ntv-a mice yielded a tumor frequency of 12%, and in Ntv-a Arf−/− mice the tumor frequency was 30%. This indicates that Sox10 alone is not sufficient to induce gliomagenesis but acts synergistically with PDGFB in glioma development. All induced tumors displayed characteristics of PNET-like structures and oligodendroglioma. The tumors had a strong and widely distributed expression of Sox10 and PDGFR-α. We investigated the expression of Sox10 in other human tumors and in a number of gliomas. The Sox10 expression was restricted to gliomas and melanomas. All glioma types expressed Sox10, and tumors of low-grade glioma had a much broader distribution of Sox10 compared with high-grade gliomas.
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41.
  • Fluitman, K. S., et al. (author)
  • Gut microbial characteristics in poor appetite and undernutrition: a cohort of older adults and microbiota transfer in germ-free mice
  • 2022
  • In: Journal of Cachexia Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 13:4, s. 2188-2201
  • Journal article (peer-reviewed)abstract
    • Background Older adults are particularly prone to the development of poor appetite and undernutrition. Possibly, this is partly due to the aged gut microbiota. We aimed to evaluate the gut microbiota in relation to both poor appetite and undernutrition in community-dwelling older adults. Furthermore, we studied the causal effects of the microbiota on body weight and body composition by transferring faecal microbiota from cohort participants into germ-free mice. Methods First, we conducted a cross-sectional cohort study of 358 well-phenotyped Dutch community-dwelling older adults from the Longitudinal Aging Study Amsterdam. Data collection included body measurements, a faecal and blood sample, as well as extensive questionnaires on appetite, dietary intake, and nutritional status. Appetite was assessed by the Council of Nutrition Appetite Questionnaire (CNAQ) and undernutrition was defined by either a low body mass index (BMI) (BMI < 20 kg/m(2) if <70 years or BMI < 22 kg/m(2) if >= 70 years) or >5% body weight loss averaged over the last 2 years. Gut microbiota composition was determined with 16S rRNA sequencing. Next, we transferred faecal microbiota from 12 cohort participants with and without low BMI or recent weight loss into a total of 41 germ-free mice to study the potential causal effects of the gut microbiota on host BMI and body composition. Results The mean age (range) of our cohort was 73 (65-93); 58.4% was male. Seventy-seven participants were undernourished and 21 participants had poor appetite (CNAQ < 28). A lower abundance of the genus Blautia was associated with undernutrition (log2 fold change = -0.57, Benjamini-Hochberg-adjusted P = 0.008), whereas higher abundances of taxa from Lachnospiraceae, Ruminococcaceae UCG-002, Parabacteroides merdae, and Dorea formicigenerans were associated with poor appetite. Furthermore, participants with poor appetite or undernutrition had reduced levels of faecal acetate (P = 0.006 and 0.026, respectively). Finally, there was a trend for the mice that received faecal microbiota from older adults with low BMI to weigh 1.26 g less after 3 weeks (P = 0.086) and have 6.13% more lean mass (in % body weight, P = 0.067) than the mice that received faecal microbiota from older adults without low BMI or recent weight loss. Conclusions This study demonstrates several associations of the gut microbiota with both poor appetite and undernutrition in older adults. Moreover, it is the first to explore a causal relation between the aged gut microbiota and body weight and body composition in the host. Possibly, microbiota-manipulating strategies will benefit older adults prone to undernutrition.
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42.
  • Folke, Fredrik, et al. (author)
  • Behavioral activation in acute inpatient psychiatry : A multiple baseline evaluation
  • 2015
  • In: Journal of Behavior Therapy and Experimental Psychiatry. - : Elsevier BV. - 0005-7916 .- 1873-7943. ; 46, s. 170-181
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND OBJECTIVES: The present study employed a multiple baseline study design with repeated measures to explore clinical outcomes, therapy mechanisms, and feasibility of Behavioral Activation for persons admitted to inpatient psychiatry.METHODS: Six adult inpatients with depressive symptoms and different psychiatric disorders were randomized to different lengths of baseline standard inpatient treatment. Subsequently a 5-day, 10-session Behavioral Activation protocol was added. Daily self-report outcome and process measures were administered and supplemented with hourly self-reports and clinician assessments before and after each study phase.RESULTS: After a relatively stable baseline, at least four participants showed marked gradual improvements both in terms of outcome as well as activation and avoidance as Behavioral Activation was initiated. The temporal relation between process and outcome differed somewhat across metrics. In most instances however, change in activation and avoidance either coincided or preceded decreased depression.LIMITATIONS: We did not include some relatively common disorders, did not control for the effects of increased attention, did not investigate treatment integrity, and did not conduct follow-up after discharge. Raters were not blind and measures were mainly focused on depressive symptoms. All received concurrent medical treatment.CONCLUSIONS: This preliminary study further supports the promise of Behavioral Activation as an inpatient treatment for persons with a variety of psychiatric disorders. Results also lends preliminary support for the purported mechanisms of Behavioral Activation.
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43.
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44.
  • Gutte, Henrik, et al. (author)
  • Automated interpretation of PET/CT images in patients with lung cancer.
  • 2007
  • In: Nuclear Medicine Communications. - 1473-5628. ; 28:2, s. 79-84
  • Journal article (peer-reviewed)abstract
    • Purpose: To develop a completely automated method based on image processing techniques and artificial neural networks for the interpretation of combined [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) images for the diagnosis and staging of lung cancer. Methods: A total of 87 patients who underwent PET/CT examinations due to suspected lung cancer comprised the training group. The test group consisted of PET/CT images from 49 patients suspected with lung cancer. The consensus interpretations by two experienced physicians were used as the 'gold standard' image interpretation. The training group was used in the development of the automated method. The image processing techniques included algorithms for segmentation of the lungs based on the CT images and detection of lesions in the PET images. Lung boundaries from the CT images were used for localization of lesions in the PET images in the feature extraction process. Eight features from each examination were used as inputs to artificial neural networks trained to classify the images. Thereafter, the performance of the network was evaluated in the test set. Results: The performance of the automated method measured as the area under the receiver operating characteristic curve, was 0.97 in the test group, with an accuracy of 92%. The sensitivity was 86% at a specificity of 100%. Conclusions: A completely automated method using artificial neural networks can be used to detect lung cancer with such a high accuracy that the application as a clinical decision support tool appears to have significant potential.
  •  
45.
  • Hammer, Neal D, et al. (author)
  • The C-terminal repeating units of CsgB direct bacterial functional amyloid nucleation
  • 2012
  • In: Journal of Molecular Biology. - : Elsevier. - 0022-2836 .- 1089-8638. ; 422:3, s. 376-389
  • Journal article (peer-reviewed)abstract
    • Curli are functional amyloids produced by enteric bacteria. The major curli fiber subunit, CsgA, self-assembles into an amyloid fiber in vitro. The minor curli subunit protein, CsgB, is required for CsgA polymerization on the cell surface. Both CsgA and CsgB are composed of five predicted β–strand-loop-β–strand-loop repeating units that feature conserved glutamine and asparagine residues. Because of this structural homology, we proposed that CsgB might form an amyloid template that initiates CsgA polymerization on the cell surface. To test this model, we purified wild-type CsgB, and found that it self-assembled into amyloid fibers in vitro. Preformed CsgB fibers seeded CsgA polymerization as did soluble CsgB added to the surface of cells secreting soluble CsgA. To define the molecular basis of CsgB nucleation, we generated a series of mutants that removed each of the five repeating units. Each of these CsgB deletion mutants was capable of self-assembly in vitro. In vivo, membrane-localized mutants lacking the 1st, 2nd or 3rd repeating units were able to convert CsgA into fibers. However, mutants missing either the 4th or 5th repeating units were unable to complement a csgB mutant. These mutant proteins were not localized to the outer membrane, but were instead secreted into the extracellular milieu. Synthetic CsgB peptides corresponding to repeating units 1, 2 and 4 self assembled into ordered amyloid polymers, while peptides corresponding to repeating units 3 and 5 did not, suggesting that there are redundant amyloidogenic domains in CsgB. Our results suggest a model where the rapid conversion of CsgB from unstructured protein to a β-sheet-rich amyloid template anchored to the cell surface is mediated by the C-terminal repeating units.
  •  
46.
  • Hardalupas, Y, et al. (author)
  • Chemiluminescence sensor for local equivalence ratio of reacting mixtures of fuel and air (FLAMESEEK)
  • 2004
  • In: Applied Thermal Engineering. - : Elsevier BV. - 1359-4311. ; 24:11-12, s. 1619-1632
  • Journal article (peer-reviewed)abstract
    • This paper describes a Cassegrain optics-based chemiluminescence sensor (CS) for measurements in gas turbine combustors. The chemiluminescence sensor measures the equivalence ratio of reacting fuel and air mixtures, and can identify the flame location, in partially premixed flames. It has the potential for monitoring the degree of premixedness of reacting fuel and air in industrial gas turbine combustors, where operation with lean premixed mixtures is important for reduction of NO, emissions. The spatial resolution of the sensor is evaluated by comparing OH* chemiluminescence measurement from the CS with laser induced OH fluorescence, in the cone-shaped premixed flame of a Bunsen burner. The ability of the sensor to measure in a modified micro-gas turbine environment burning a methane/air, as well as, a methane/ water/air flame (humidified flame) is also demonstrated.
  •  
47.
  • Harwit, M., et al. (author)
  • Polarisation observations of VY Canis Majoris H2O 532-441 620.701 GHz maser emission with HIFI
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L51-
  • Journal article (peer-reviewed)abstract
    • Context. Water vapour maser emission from evolved oxygen-rich stars remains poorly understood. Additional observations, including polarisation studies and simultaneous observation of different maser transitions may ultimately lead to greater insight. Aims. We have aimed to elucidate the nature and structure of the VY CMa water vapour masers in part by observationally testing a theoretical prediction of the relative strengths of the 620.701 GHz and the 22.235 GHz maser components of ortho H2O. Methods. In its high-resolution mode (HRS) the Herschel Heterodyne Instrument for the Far Infrared (HIFI) offers a frequency resolution of 0.125 MHz, corresponding to a line-of-sight velocity of 0.06 km s(-1), which we employed to obtain the strength and linear polarisation of maser spikes in the spectrum of VY CMa at 620.701 GHz. Simultaneous ground based observations of the 22.235 GHz maser with the Max-Planck-Institut fur Radioastronomie 100-m telescope at Effelsberg, provided a ratio of 620.701 GHz to 22.235 GHz emission. Results. We report the first astronomical detection to date of H2O maser emission at 620.701 GHz. In VY CMa both the 620.701 and the 22.235 GHz polarisation are weak. At 620.701 GHz the maser peaks are superposed on what appears to be a broad emission component, jointly ejected from the star. We observed the 620.701 GHz emission at two epochs 21 days apart, both to measure the potential direction of linearly polarised maser components and to obtain a measure of the longevity of these components. Although we do not detect significant polarisation levels in the core of the line, they rise up to approximately 6% in its wings.
  •  
48.
  •  
49.
  • Heiss, Christina, et al. (author)
  • The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism
  • 2021
  • In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 35:8
  • Journal article (peer-reviewed)abstract
    • Mice lacking a microbiota are protected from diet-induced obesity. Previous studies have shown that feeding a Western diet causes hypothalamic inflammation, which in turn can lead to leptin resistance and weight gain. Here, we show that wild-type (WT) mice with depleted gut microbiota, i.e., germ-free (GF) and antibiotic-treated mice, have elevated levels of glucagon-like peptide-1 (GLP-1), are protected against diet-induced hypothalamic inflammation, and have enhanced leptin sensitivity when fed a Western diet. Using GLP-1 receptor (GLP-1R)-deficient mice and pharmacological inhibition of the GLP-1R in WT mice, we demonstrate that intact GLP-1R signaling is required for preventing hypothalamic inflammation and enhancing leptin sensitivity. Furthermore, we show that astrocytes express the GLP-1R, and deletion of the receptor in glial fibrillary acidic protein (GFAP)-expressing cells diminished the antibiotic-induced protection against diet-induced hypothalamic inflammation. Collectively, our results suggest that depletion of the gut microbiota attenuates diet-induced hypothalamic inflammation and enhances leptin sensitivity via GLP-1R-dependent mechanisms.
  •  
50.
  • Horvath, Istvan, et al. (author)
  • Mechanisms of Protein Oligomerization : Inhibitor of Functional Amyloids Templates α-Synuclein Fibrillation
  • 2012
  • In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 134:7, s. 3439-3444
  • Journal article (peer-reviewed)abstract
    • Small organic molecules that inhibit functional bacterial amyloid fibers, curli, are promising new antibiotics. Here we investigated the mechanism by which the ring-fused 2-pyridone FN075 inhibits fibrillation of the curli protein CsgA. Using a variety of biophysical techniques, we found that FN075 promotes CsgA to form off-pathway, non-amyloidogenic oligomeric species. In light of the generic properties of amyloids, we tested whether FN075 would also affect the fibrillation reaction of human α-synuclein, an amyloid-forming protein involved in Parkinson's disease. Surprisingly, FN075 stimulates α-synuclein amyloid fiber formation as measured by thioflavin T emission, electron microscopy (EM), and atomic force microscopy (AFM). NMR data on (15)N-labeled α-synuclein show that upon FN075 addition, α-synuclein oligomers with 7 nm radius form in which the C-terminal 40 residues remain disordered and solvent exposed. The polypeptides in these oligomers contain β-like secondary structure, and the oligomers are detectable by AFM, EM, and size-exclusion chromatography (SEC). Taken together, FN075 triggers oligomer formation of both proteins: in the case of CsgA, the oligomers do not proceed to fibers, whereas for α-synuclein, the oligomers are poised to rapidly form fibers. We conclude that there is a fine balance between small-molecule inhibition and templation that depends on protein chemistry.
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