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1.	Estrada, Karol, et al. (författare) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. 2012 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501 Tidskriftsartikel (refereegranskat)abstract Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
2.	Zheng, Hou-Feng, et al. (författare) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112- Tidskriftsartikel (refereegranskat)abstract The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
3.	Erlinge, David, et al. (författare) Prasugrel 5-mg in the very elderly attenuates platelet inhibition but maintains non-inferiority to prasugrel 10-mg in non-elderly patients: The GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. 2013 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 62:7, s. 577-583 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: We assessed pharmacodynamic (PD) response for the reduced prasugrel 5-mg maintenance dose in very elderly (≥75y; VE) patients. BACKGROUND: In TRITON-TIMI 38, prasugrel 10-mg reduced ischemic events versus clopidogrel 75-mg, but increased bleeding in VE patients. METHODS: We examined PD and active-metabolite pharmacokinetics with prasugrel 5-mg and 10-mg and clopidogrel 75-mg in a three-period (12 days each), blinded, cross-over study in VE (n=73, mean 79±3y) or non-elderly (≥45-<65y, NE) (n=82, 56±5y) stable coronary artery disease (CAD) patients on background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow(®) P2Y12 (VN-P2Y12), and VASP. The primary comparison was non-inferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5-mg in VE versus the 75th percentile for prasugrel 10-mg in NE, using a prespecified one-sided 97.5% confidence interval for the difference <15%. RESULTS: Prasugrel 5-mg in VE met the primary pharmacodynamic non-inferiority criterion versus prasugrel 10-mg in NE. For prasugrel 5-mg, MPA was significantly lower (mean±SD, 57±14%) than clopidogrel (63±14%) (p<0.001) in VE, but higher than prasugrel 10-mg in NE (46±12%) (p<0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5-mg resulted in fewer VE poor responders versus clopidogrel. Rates of mild bleeding were higher with prasugrel 10-mg, but similar for prasugrel 5-mg versus clopidogrel 75-mg. CONCLUSIONS: In aspirin-treated stable CAD patients, prasugrel 5-mg in VE attenuated platelet inhibition while meeting prespecified non-inferiority criterion versus prasugrel 10-mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75-mg in VE.
4.	Erlinge, David, et al. (författare) Prasugrel 5 mg in the Very Elderly Attenuates Platelet Inhibition But Maintains Noninferiority to Prasugrel 10 mg in Nonelderly Patients 2013 Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:7, s. 577-583 Tidskriftsartikel (refereegranskat)abstract Objectives This study assessed pharmacodynamic (PD) response to the reduced prasugrel maintenance dose of 5 mg in very elderly (VE) patients (andgt;= 75 years of age). less thanbrgreater than less thanbrgreater thanBackground In the TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction 38) study prasugrel 10 mg reduced ischemic events versus clopidogrel 75 mg, but increased bleeding in VE patients. less thanbrgreater than less thanbrgreater thanMethods We examined PD and active metabolite pharmacokinetics (PKs) with prasugrel 5 and 10 mg and clopidogrel 75 mg in a 3-period (12 days each) blinded, crossover study in VE (n = 73; mean: 79 +/- 3 years of age) or (n 82) nonelderly (NE) (andgt;= 45 to andlt;65 years of age; mean: 56 +/- 5 years of age) stable coronary artery disease (CAD) patients receiving background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN-P2Y12), and vasodilator-associated stimulated phosphoprotein (VASP). The primary comparison was noninferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5 mg in VE versus the 75th percentile for prasugrel 10 mg in NE, using a pre-specified 1-sided 97.5% confidence interval for the difference andlt;15%. less thanbrgreater than less thanbrgreater thanResults Prasugrel 5 mg in VE met the primary PD noninferiority criterion versus prasugrel 10 mg in NE. For prasugrel 5 mg, MPA was significantly lower (57 +/- 14%) than clopidogrel (63 +/- 14%; p andlt; 0.001) in VE but higher than prasugrel 10 mg in NE (46 +/- 12%; p andlt; 0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5 mg resulted in fewer VE poor responders than clopidogrel. Rates of mild bleeding were higher with prasugrel 10 mg but similar for prasugrel 5 mg versus clopidogrel 75 mg. less thanbrgreater than less thanbrgreater thanConclusions In aspirin-treated stable CAD patients, prasugrel 5 mg in VE attenuated platelet inhibition while meeting pre-specified noninferiority criterion versus prasugrel 10 mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75 mg in VE. (Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease [GENERATIONS]; NCT01107912)
5.	Oei, Ling, et al. (författare) A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus 2014 Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
6.	Svensson, Henrik, et al. (författare) Contributions of amino acid side chains to the kinetics and thermodynamics of the bivalent binding of protein L to Ig kappa light chain. 2004 Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 43:9, s. 2445-2457 Tidskriftsartikel (refereegranskat)
7.	Ambrazaitis, Gilbert, et al. (författare) Multimodal levels of prominence : a preliminary analysis of head and eyebrow movements in Swedish news broadcasts 2015 Ingår i: Proceedings from Fonetik 2015 : Lund, June 8-10, 2015. Working Papers 55. 2015. - Lund, June 8-10, 2015. Working Papers 55. 2015.. - Lund : Centre for Languages and Literature, Lund University. - 0280-526X. ; 55, s. 11-16, s. 11-16 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract This paper presents a first analysis of the distribution of head and eyebrow movements as a function of (a) phonological prominence levels (focal, non-focal) and (b) word accent (Accent 1, Accent 2) in Swedish news broadcasts. Our corpus consists of 31 brief news readings, comprising speech from four speakers and 986 words in total. A head movement was annotated for 229 (23.2%) of the words, while eyebrow movements occurred much more sparsely (67 cases or 6.8%). Results of χ2-tests revealed a dependency of the distribution of movements on the one hand and focal accents on the other, while no systematic effect of the word accent type was found. However, there was an effect of the word accent type on the annotation of ‘double’ head movements. These occurred very sparsely, and predominantly in connection with focally accented compounds (Accent 2), which are characterized by two lexical stresses. Overall, our results suggests that head beats might have a closer association with phonological prosodic structure, while eyebrow movements might be more restricted to higher-level prominence and information-structure coding. Hence, head and eyebrow movements can represent two quite different modalities of prominence cuing, both from a formal and functional point of view, rather than just being cumulative prominence markers.
8.	Charalampopoulos, Dimitrios, et al. (författare) Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes 2018 Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 41:6, s. 1180-1187 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.
9.	Cherian, Dennis, 1989-, et al. (författare) Flexible Organic Electronic Ion Pump Fabricated Using Inkjet Printing and Microfabrication for Precision In Vitro Delivery of Bupivacaine 2023 Ingår i: Advanced Healthcare Materials. - : John Wiley and Sons Inc. - 2192-2640 .- 2192-2659. ; 12:24, s. 2300550- Tidskriftsartikel (refereegranskat)abstract The organic electronic ion pump (OEIP) is an on-demand electrophoretic drug delivery device, that via electronic to ionic signal conversion enables drug delivery without additional pressure or volume changes. The fundamental component of OEIPs is their polyelectrolyte membranes which are shaped into ionic channels that conduct and deliver ionic drugs, with high spatiotemporal resolution. The patterning of these membranes is essential in OEIP devices and is typically achieved using laborious microprocessing techniques. Here, the development of an inkjet printable formulation of polyelectrolyte is reported, based on a custom anionically functionalized hyperbranched polyglycerol (i-AHPG). This polyelectrolyte ink greatly simplifies the fabrication process and is used in the production of free-standing OEIPs on flexible polyimide (PI) substrates. Both i-AHPG and the OEIP devices are characterized, exhibiting favorable iontronic characteristics of charge selectivity and the ability to transport aromatic compounds. Further, the applicability of these technologies is demonstrated by the transport and delivery of the pharmaceutical compound bupivacaine to dorsal root ganglion cells with high spatial precision and effective nerve blocking, highlighting the applicability of these technologies for biomedical scenarios. © 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
10.	Cresswell, Fiona, V, et al. (författare) High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults : A Phase II Open-Label Randomized Controlled Trial 2021 Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:5, s. 876-884 Tidskriftsartikel (refereegranskat)abstract Background: High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in human immunodeficiency virus (HIV) coinfection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods: In this phase II open-label trial, Ugandan adults with suspected TBM were randomized to standard-of-care control (PO-10, rifampicin 10 mg/kg/day), intravenous rifampicin (IV-20, 20 mg/kg/day), or high-dose oral rifampicin (PO-35, 35 mg/kg/day). We performed PK sampling on days 2 and 14. The primary outcomes were total exposure (AUC(0-24)), maximum concentration (C-max), CSF concentration, and grade 3-5 adverse events. Results: We enrolled 61 adults, 92% were living with HIV, median CD4 count was 50 cells/mu L (interquartile range [IQR] 46-56). On day 2, geometric mean plasma AUC(0-24hr) was 42.9.h mg/L with standard-of-care 10 mg/kg dosing, 249.h mg/L for IV-20 and 327.h mg/L for PO-35 (P<.001). In CSF, standard of care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC(0-24hr) 0.27 mg/L, compared with 1.74 mg/L (95% confidence interval [CI] 1.2-2.5) for IV-20 and 2.17 mg/L (1.6-2.9) for PO-35 regimens (P<.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (P=.34). Conclusions: Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe and respectively resulted in exposures similar to 6- and similar to 8-fold higher than standard of care, and CSF levels above the MIC.
11.	Crouse, David F., et al. (författare) The Set MHT 2011 Ingår i: 14th International Conference on Information Fusion, Fusion 2011; Chicago, IL; 5 July 2011 through 8 July 2011. - 9781457702679 Konferensbidrag (refereegranskat)abstract Abstract—We introduce the Set MHT, a tracking algorithmthat maintains multiple hypotheses and produces “smooth”estimates without the track coalescence often associated withMinimum Mean Squared Error (MMSE) estimation or thejitter associated with Maximum Likelihood (ML) estimation.It does this by utilizing Minimum Mean Optimal SubpatternAssignment (MMOSPA) estimation techniques coupled with atheoretically-grounded approach for probabilistically determiningthe identities of the state estimates. Unlike traditional MHTalgorithms, the Set MHT does not “forget” uncertainty in targetidentities, i.e. display an unjustifiably high confidence level inthe target identities, as a result of pruning out competinghypotheses. Rather, it uses merging techniques while avoiding theshortcomings of traditional Gaussian mixture reduction trackers.
12.	Gurbel, Paul A., et al. (författare) The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease 2014 Ingår i: Thrombosis and Haemostasis. - : Schattauer. - 0340-6245 .- 2567-689X. ; 112:3, s. 589-597 Tidskriftsartikel (refereegranskat)abstract CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC([0-tlast])), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator-stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], 2-8 non-carriers, vs reduced metaboliser [RM; N=41],2-8 carriers/*17 non-carriers). AUC((0-tlast)) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [Cl]: 0.86,1.17, p>0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p<0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VN-PRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p<0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p<0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p<0.001), and comparable effects in EMs (all p >= 0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.
13.	Heiden, Marina, 1974-, et al. (författare) Mismatch between actual and preferred extent of telework: cross-sectional and prospective associations with well-being and burnout 2023 Ingår i: BMC Public Health. - : Springer. - 1471-2458. ; 23 Tidskriftsartikel (refereegranskat)abstract Background: This study aimed to determine whether telework mismatch, i.e., lack of fit between actual and preferred extent of telework, is cross-sectionally and prospectively associated with well-being and burnout.Methods: A questionnaire was sent to employees in a Swedish manufacturing company in November 2020 (baseline) and September 2021 (follow-up). It contained questions about well-being (WHO-5 Well-Being Index) and burnout (Copenhagen Psychosocial Questionnaire III), as well as the preferred extent of telework and extent of telework performed. Telework mismatch was calculated as the difference between the actual and preferred extent of telework. Change in mismatch over time was categorized as 1) less mismatch at follow-up than at baseline, 2) more mismatch at follow-up, and 3) identical levels of mismatch at baseline and follow-up. Multivariate and univariate analyses of variance were used to determine the effects of mismatch and change in mismatch over time on baseline ratings and changes in ratings of well-being and burnout. All analyses were performed with and without adjustment for age, sex, marital status, children, type of employment, commuting time and extent of telework performed.Results: The response rate was 39% at baseline (n=928, 67% men, mean(SD) age: 45(11) years) and 60% at follow-up (n=556, 64% men, mean(SD) age: 46(11) years). A cross-sectional association was found between telework mismatch and well-being, showing that employees who teleworked more than they would like reported worse well-being than those who teleworked less than they would like. No statistically significant association was found between telework mismatch and burnout. The ability of telework mismatch at baseline to predict changes in well-being or burnout over 10 months was small and non-significant. No association was found between change in telework mismatch over the 10-month period and corresponding changes in well-being or burnout.Conclusion: Our results suggest that telework should be thoughtfully practiced in companies/organizations to avoid negative consequences for employees who already telework more than they prefer. Studies are needed to determine how long-term changes in match between preferred and actual extent of telework is associated with employee well-being, including how the association is modified by the nature of the job and the work environment.
14.	Hess, Georg, 1996, et al. (författare) Masked Autoencoder for Self-Supervised Pre-Training on Lidar Point Clouds 2023 Ingår i: Proceedings - 2023 IEEE/CVF Winter Conference on Applications of Computer Vision Workshops, WACVW 2023. ; , s. 350-359 Konferensbidrag (refereegranskat)abstract Masked autoencoding has become a successful pretraining paradigm for Transformer models for text, images, and, recently, point clouds. Raw automotive datasets are suitable candidates for self-supervised pre-training as they generally are cheap to collect compared to annotations for tasks like 3D object detection (OD). However, the development of masked autoencoders for point clouds has focused solely on synthetic and indoor data. Consequently, existing methods have tailored their representations and models toward small and dense point clouds with homogeneous point densities. In this work, we study masked autoencoding for point clouds in an automotive setting, which are sparse and for which the point density can vary drastically among objects in the same scene. To this end, we propose Voxel-MAE, a simple masked autoencoding pre-training scheme designed for voxel representations. We pre-train the backbone of a Transformer-based 3D object detector to reconstruct masked voxels and to distinguish between empty and non-empty voxels. Our method improves the 3D OD performance by 1.75 mAP points and 1.05 NDS on the challenging nuScenes dataset. Further, we show that by pre-training with Voxel-MAE, we require only 40 of the annotated data to outperform a randomly initialized equivalent. Code is available at https://github.com/georghess/voxel-mae.
15.	Hofmann, Robin, et al. (författare) Oxygen therapy in ST-elevation myocardial infarction. 2018 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:29, s. 2730-2739 Tidskriftsartikel (refereegranskat)abstract Aims: To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes.Methods and results: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days.Conclusions: Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.
16.	Hofmann, Robin, et al. (författare) Oxygen therapy in suspected acute myocardial infarction 2017 Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 377:13, s. 1240-1249 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110.)
17.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
18.	Roger, S., et al. (författare) Sustainable Mobility in B5G/6G: V2X Technology Trends and use Cases 2024 Ingår i: IEEE Open Journal of Vehicular Technology. - 2644-1330. ; 5, s. 459-472 Tidskriftsartikel (refereegranskat)abstract The concept of sustainability has been recently extended to cover economic and social factors besides the traditional environmental ones. This paper reflects on the potential of mobile communication standards towards achieving sustainable mobility, with focus on vehicular communications and use cases in smart cities scenarios. In this context, intelligent transportation systems, including connected and autonomous vehicles, will be key for developing affordable and sustainable infrastructures and services. We start by identifying three current technology trends, namely, towards climate neutral; cloudification and edge computing; and big data and artificial intelligence, and then we examine their capability to enable sustainable Vehicle-to-Everything (V2X) communication systems in beyond 5G and 6G networks. In the second part of the paper, a set of selected use case categories involving connected and autonomous vehicles is presented, showcasing the potential impact of the selected technology trends. Finally, a review of the estimates of the quantitative savings that could be achieved in environmental-related parameters such as energy/fuel consumption and greenhouse gas emissions is provided.
19.	Rohmer, Laurence, et al. (författare) Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains 2007 Ingår i: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X. ; 8:6 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans. RESULTS: Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation. CONCLUSION: The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.
20.	Roy, Arghyamalya, 1992-, et al. (författare) Electrophoretic Delivery of Clinically Approved Anesthetic Drug for Chronic Pain Therapy 2023 Ingår i: Advanced Therapeutics. - : John Wiley and Sons Inc. - 2366-3987. ; 6:7 Tidskriftsartikel (refereegranskat)abstract Despite a range of available pain therapies, most patients report so-called “breakthrough pain.” Coupled with global issues like opioid abuse, there is a clear need for advanced therapies and technologies for safe and effective pain management. Here the authors demonstrate a candidate for such an advanced therapy: precise and fluid-flow-free electrophoretic delivery via organic electronic ion pumps (OEIPs) of the commonly used anesthetic drug bupivacaine. Bupivacaine is delivered to dorsal root ganglion (DRG) neurons in vitro. DRG neurons are a good proxy for pain studies as they are responsible for relaying ascending sensory signals from nociceptors (pain receptors) in the peripheral nervous system to the central nervous system. Capillary based OEIPs are used due to their probe-like and free-standing form factor, ideal for interfacing with cells. By delivering bupivacaine with the OEIP and recording dose versus response (Ca2+ imaging), it is observed that only cells close to the OEIP outlet (≤75 µm) are affected (“anaesthetized”) and at concentrations up to 10s of thousands of times lower than with bulk/bolus delivery. These results demonstrate the first effective OEIP deliveryof a clinically approved and widely used analgesic pharmaceutical, and thus are a major translational milestone for this technology. © 2023 The Authors.
21.	Saxena, Richa, et al. (författare) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels 2007 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336 Tidskriftsartikel (refereegranskat)abstract New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
22.	Scott, James S., et al. (författare) Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists 2014 Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 57:21, s. 8984-8998 Tidskriftsartikel (refereegranskat)abstract Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.
23.	Sunduru, Naresh, et al. (författare) N-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors 2017 Ingår i: Journal of enzyme inhibition and medicinal chemistry (Print). - : Informa UK Limited. - 1475-6366 .- 1475-6374. ; 32:1, s. 513-521 Tidskriftsartikel (refereegranskat)abstract Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b] pyri-din-2-yl) phenyl) acetamide, 4g, with an IC50 of 2.6 mu M as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b] pyridin-2-yl)phenyl) acetamide, 4i, with an IC50 of 0.35 mu M.
24.	Svensson, Daniel, 1979, et al. (författare) The multitarget Set JPDA filter with target identity 2011 Ingår i: Proceedings of SPIE: Signal Processing, Sensor Fusion, and Target Recognition XX. Conference on Signal Processing, Sensor Fusion, and Target Recognition XX Orlando, FL, APR 25-27, 2011. - : SPIE. - 0277-786X. - 9780819486240 ; 8050 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract The Set JPDA (SJPDA) filter is a recently developed multi-target tracking filter that utilizes the relationbetween the density of a random finite set and the ordinary density of a state vector to improve on the JointProbabilistic Data Association (JPDA) filter. One advantage to the filter is the improved accuracy of the Gaussianapproximations of the JPDA, which result in avoidance of track coalescence. In the original presentation of theSJPDA filter, the focus was on problems where target identity is not relevant, and it was shown that the filterperforms better than the JPDA filter for such problems. The improved performance of the SJPDA is due toits relaxation of the labeling constraint that hampers most tracking approaches. However, if track identity isof interest a record of it may be kept even with a label-free approach such as the SJPDA: label-free targets arelocalized via the SJPDA, and then the identities are recalled as an overlay.
25.	Svensson, Daniel, 1979, et al. (författare) The Set IMMJPDA filter for multitarget tracking 2011 Ingår i: Proceedings of SPIE: Signal Processing, Sensor Fusion, and Target Recognition XX. Conference on Signal Processing, Sensor Fusion, and Target Recognition XX Orlando, FL, APR 25-27, 2011. - : SPIE. - 0277-786X. - 9780819486240 ; 8050 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract The Set JPDA (SJPDA) filter is a recently developed multi-target tracking filter that utilizes the relationbetween the density of a random finite set and the ordinary density of a state vector to improve on the JointProbabilistic Data Association (JPDA) filter. One advantage to the filter is the improved accuracy of theGaussian approximations of the JPDA, which results in avoidance of track coalescence. Another advantage is animproved estimation accuracy in terms of a measure which disregards target identity. In this paper we extend thefilter to also consider multiple motion models. As a basis for the extension we use the Interacting Multiple Model(IMM) algorithm. We derive three alternative filters that we jointly refer to as Set IMMJPDA (SIMMJPDA).They are based on two alternative descriptions of the IMMJPDA filter. In the paper, we also present simulationresults for a two-target tracking scenario, which show improved tracking performance for the Set IMMJPDAfilter when evaluated with a measure that disregards target identity.
26.	Svensson, Julia, et al. (författare) alpha-Amylase-catalysed synthesis of alkyl glycosides 2005 Ingår i: Journal of Molecular Catalysis B: Enzymatic. - : Elsevier BV. - 1873-3158 .- 1381-1177. ; 37:1-6, s. 84-87 Tidskriftsartikel (refereegranskat)abstract Alkyl glycosides were synthesised from starch and alcohols using Aspergillus oryzae a-amylase as catalyst. In the degradation of starch by a-amylase, the alcohols competed with water as glycosyl acceptors. In the reaction with methanol, methyl maltoside and methyl maltotrioside were the main alcoholysis products. Conversion of 45 g/1 starch in 30% methanol resulted in a product mixture containing 26 mM maltooligosaccharides and 3.6 mM methyl glycosides. With ethanol, propanol and butanol, alkyl maltosides and alkyl maltotetraosides were detected, and with benzyl alcohol, benzyl glycosides having two, three or five glucose units were formed. No alcoholysis reaction occurred with hexanol or octanol. In conclusion, alpha-amylase is promising for the one-step synthesis of alkyl glycosides having more than one monosaccharide unit, which are difficult to synthesise in other ways.
27.	Svensson, Maria C, et al. (författare) High infiltration of CD68+/CD163- macrophages is an adverse prognostic factor after neoadjuvant chemotherapy in esophageal and gastric adenocarcinoma 2022 Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 14:6, s. 615-628 Tidskriftsartikel (refereegranskat)abstract Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163−, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163− TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163−TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.
28.	Svensson, Mattias N D, et al. (författare) Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal. 2020 Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:26 Tidskriftsartikel (refereegranskat)abstract Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression. Here, we assessed the potential of immunoglobulin-like domains 1 and 2 (Ig1&2), a decoy protein that activates the receptor tyrosine phosphatase sigma (PTPRS) on FLS, for RA therapy. We report that PTPRS expression is enriched in synovial lining RA FLS and that Ig1&2 reduces migration of RA but not osteoarthritis FLS. Administration of an Fc-fusion Ig1&2 attenuated arthritis in mice without affecting innate or adaptive immunity. Furthermore, PTPRS was down-regulated in FLS by tumor necrosis factor (TNF) via a phosphatidylinositol 3-kinase-mediated pathway, and TNF inhibition enhanced PTPRS expression in arthritic joints. Combination of ineffective doses of TNF inhibitor and Fc-Ig1&2 reversed arthritis in mice, providing an example of synergy between FLS-targeted and immunosuppressive DMARD therapies.
29.	Svensson, Peter, et al. (författare) Om samhällsvetenskapens natur 2022. - 3 Ingår i: Handbok i kvalitativa metoder. - 9789147140077 ; , s. 17-23 Bokkapitel (övrigt vetenskapligt/konstnärligt)
30.	Wiitavaara, Birgitta, 1959-, et al. (författare) Like a fire brigade, but without pay - Experiences of temporary employment among workers in Swedish elderly care 2022 Ingår i: Geriatric Nursing. - : Taylor & Francis. - 0197-4572 .- 1528-3984. Tidskriftsartikel (refereegranskat)abstract This study investigates experiences of temporary work among care personnel in elderly care. Semi-structured interviews were performed with fifteen temporarily employed men and women working as care personnel in municipal nursing homes or home care and analyzed using a phenomenographic approach. The informants’ experiences of having a temporary employment were characterized by either a sense of flexibility or, more common, uncertainty, lack of control over life, time and economy, as well as difficulties associated with always being available. The informants’ experiences of working as a temporary employed were characterized by enjoyment of work and job satisfaction, differing experiences regarding the division of work and communication, but also being in an exposed position. The results presented reflect an experience of temporary employment as being in a vulnerable position. This vulnerability varies with resources and can take different forms.
31.	Wuttke, Matthias, et al. (författare) A catalog of genetic loci associated with kidney function from analyses of a million individuals 2019 Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972 Tidskriftsartikel (refereegranskat)abstract Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
32.	Zamora, Juan Carlos, et al. (författare) Considerations and consequences of allowing DNA sequence data as types of fungal taxa 2018 Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185 Tidskriftsartikel (refereegranskat)abstract Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
33.	Ziels, Ryan M., et al. (författare) Monitoring the dynamics of syntrophic beta-oxidizing bacteria during anaerobic degradation of oleic acid by quantitative PCR 2015 Ingår i: FEMS Microbiology Ecology. - : Oxford University Press (OUP): Policy B - Oxford Open Option D. - 0168-6496 .- 1574-6941. ; 91:4 Tidskriftsartikel (refereegranskat)abstract The ecophysiology of long-chain fatty acid-degrading syntrophic beta-oxidizing bacteria has been poorly understood due to a lack of quantitative abundance data. Here, TaqMan quantitative PCR (qPCR) assays targeting the 16S rRNA gene of the known mesophilic syntrophic beta-oxidizing bacterial genera Syntrophomonas and Syntrophus were developed and validated. Microbial community dynamics were followed using qPCR and Illumina-based high-throughput amplicon sequencing in triplicate methanogenic bioreactors subjected to five consecutive batch feedings of oleic acid. With repeated oleic acid feeding, the initial specific methane production rate significantly increased along with the relative abundances of Syntrophomonas and methanogenic archaea in the bioreactor communities. The novel qPCR assays showed that Syntrophomonas increased from 7 to 31% of the bacterial community 16S rRNA gene concentration, whereas that of Syntrophus decreased from 0.02 to less than 0.005%. High-throughput amplicon sequencing also revealed that Syntrophomonas became the dominant genus within the bioreactor microbiomes. These results suggest that increased specific mineralization rates of oleic acid were attributed to quantitative shifts within the microbial communities toward higher abundances of syntrophic beta-oxidizing bacteria and methanogenic archaea. The novel qPCR assays targeting syntrophic beta-oxidizing bacteria may thus serve as monitoring tools to indicate the fatty acid beta-oxidization potential of anaerobic digester communities.
34.	Ziels, Ryan, et al. (författare) Microbial community adaptation influences long-chain fatty acid conversion during anaerobic codigestion of fats, oils, and grease with municipal sludge 2016 Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 103, s. 372-382 Tidskriftsartikel (refereegranskat)abstract Codigesting fats, oils, and greases with municipal wastewater sludge can greatly improve biomethanerecovery at wastewater treatment facilities. Process loading rates of fats, oils, and greases have beenpreviously tested with little knowledge of the digester microbial community structure, and high transientfat loadings have led to long chain fatty acid (LCFA) accumulation and digester upsets. This studyutilized recently-developed quantitative PCR assays for syntrophic LCFA-degrading bacteria along with16S amplicon sequencing to relate changes in microbial community structure to LCFA accumulationduring transient loading increases to an anaerobic codigester receiving waste restaurant oil andmunicipal wastewater sludge. The 16S rRNA gene concentration of the syntrophic b-oxidizing genusSyntrophomonas increased to ~15% of the Bacteria community in the codigester, but stayed below 3% inthe control digester that was fed only wastewater sludge. Methanosaeta and Methanospirillum were thedominant methanogenic genera enriched in the codigester, and together comprised over 80% of theArchaea community by the end of the experimental period. Constrained ordination showed that changesin the codigester Bacteria and Archaea community structures were related to measures of digester performance.Notably, the effluent LCFA concentration in the codigester was positively correlated to thespecific loading rate of waste oil normalized to the Syntrophomonas 16S rRNA concentration. Specificloading rates of 0e1.5 1012 g VS oil/16S gene copies-day resulted in LCFA concentrations below 30 mg/g TS, whereas LCFA accumulated up to 104 mg/g TS at higher transient loading rates. Based on thecommunity-dependent loading limitations found, enhanced biomethane production from high loadingsof fats, oils and greases can be achieved by promoting a higher biomass of slow-growing syntrophicconsortia, such as with longer digester solids retention times. This work also demonstrates the potentialfor controlling the loading rate of fats, oils, and greases based on the analysis of the codigester communitystructure, such as with quantitative PCR measurements of syntrophic LCFA-degrading bacteriaabundance.
35.	Abdollahi Sani, Negar, et al. (författare) All-printed diode operating at 1.6 GHz 2014 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:33, s. 11943-11948 Tidskriftsartikel (refereegranskat)abstract Printed electronics are considered for wireless electronic tags and sensors within the future Internet-of-things (IoT) concept. As a consequence of the low charge carrier mobility of present printable organic and inorganic semiconductors, the operational frequency of printed rectifiers is not high enough to enable direct communication and powering between mobile phones and printed e-tags. Here, we report an all-printed diode operating up to 1.6 GHz. The device, based on two stacked layers of Si and NbSi2 particles, is manufactured on a flexible substrate at low temperature and in ambient atmosphere. The high charge carrier mobility of the Si microparticles allows device operation to occur in the charge injection-limited regime. The asymmetry of the oxide layers in the resulting device stack leads to rectification of tunneling current. Printed diodes were combined with antennas and electrochromic displays to form an all-printed e-tag. The harvested signal from a Global System for Mobile Communications mobile phone was used to update the display. Our findings demonstrate a new communication pathway for printed electronics within IoT applications.
36.	Abel, I, et al. (författare) Overview of the JET results with the ITER-like wall 2013 Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002- Tidskriftsartikel (refereegranskat)abstract Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
37.	Aevarsson, Arnthór, et al. (författare) Going to extremes - a metagenomic journey into the dark matter of life 2021 Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12 Forskningsöversikt (refereegranskat)abstract The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
38.	Aggarwal, MM, et al. (författare) Centrality and transverse momentum dependence of collective flow in 158 A GeV Pb+Pb collisions measured via inclusive photons 2005 Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 762:1-2, s. 129-146 Tidskriftsartikel (refereegranskat)abstract Directed and elliptic flow of inclusive photons near mid-rapidity in 158 A GeV Pb + Pb collisions has been studied. The data have been obtained with the photon spectrometer LEDA of the WA98 experiment at the CERN SPS. The flow strength has been measured for various centralities as a function of p(T) and rapidity over 0. 18 < p(T) < 1.5 GeV/c and 2.3 < y < 2.9. The angular anisotropy has been studied relative to an event plane obtained in the target fragmentation region that shows the elliptic flow to be in-plane. The elliptic flow has also been studied using two-particle correlations and shown to give similar results. A small directed flow component is observed. Both the directed and elliptic flow strengths increase with p(T). The photon flow results are used to estimate the corresponding neutral pion flow.
39.	Aggarwal, MM, et al. (författare) Event-by-event fluctuations in particle multiplicities and transverse energy produced in 158A GeVPb plus Pb collisions 2002 Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 65:5 Tidskriftsartikel (refereegranskat)abstract Event-by-event fluctuations in the multiplicities of charged particles and photons, and the total transverse energy in 158A GeV Pb+Pb collisions are studied for a wide range of centralities. For narrow centrality bins the multiplicity and transverse energy distributions are found to be near perfect Gaussians. The effect of detector acceptance on the multiplicity fluctuations has been studied and demonstrated to follow statistical considerations. The centrality dependence of the charged particle multiplicity fluctuations in the measured data has been found to agree reasonably well with those obtained from a participant model. However, for photons the multiplicity fluctuations have been found to be lower compared to those obtained from a participant model. The multiplicity and transverse energy fluctuations have also been compared to those obtained from the VENUS event generator.
40.	Aggarwal, MM, et al. (författare) Interferometry of direct photons in central 208Pb+208Pb collisions at 158A GeV 2004 Ingår i: Physical Review Letters. - 1079-7114. ; 93:2 Tidskriftsartikel (refereegranskat)abstract Two-particle correlations of direct photons were measured in central (208Pb+208Pb collisions at 158A GeV. The invariant interferometric radii were extracted for 100
41.	Aggarwal, M M, et al. (författare) Azimuthal anisotropy of photon and charged particle emission in Pb-208+Pb-208 collisions at 158 center dot A GeV/c 2005 Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 41:3, s. 287-296 Tidskriftsartikel (refereegranskat)abstract The azimuthal distributions of photons and charged particles with respect to the event plane are investigated as a function of centrality in Pb-208 + Pb-208 collisions at 158 (.) A GeV/c in the WA98 experiment at the CERN SPS. The anisotropy of the azimuthal distributions is characterized using a Fourier analysis. For both the photon and charged particle distributions the first two Fourier coefficients are observed to decrease with increasing centrality. The observed anisotropies of the photon distributions compare well with the expectations from the charged particle measurements for all centralities.
42.	Aggarwal, M. M., et al. (författare) Event-by-event charged-neutral fluctuations in Pb plus Pb collisions at 158 A GeV 2011 Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 701:3, s. 300-305 Tidskriftsartikel (refereegranskat)abstract Charged particles and photons have been measured in central Pb + Pb collisions at 158 A GeV in a common (eta-phi)-phase space region in the WA98 experiment at the CERN SPS. The measured distributions have been analyzed to quantify the frequency with which phase space regions of varying sizes have either small or large neutral pion fraction. The measured results are compared with VENUS model simulated events and with mixed events. Events with both large and small charged-neutral fluctuations are observed to occur more frequently than expected statistically, as deduced from mixed events, or as predicted by model simulations, with the difference becoming more prominent with decreasing size of the A Delta eta-Delta phi region. (C) 2011 Elsevier B.V. All rights reserved.
43.	Aggarwal, M. M., et al. (författare) Photon and eta production in p plus Pb and p plus C collisions at root(NN)-N-S=17.4 GeV 2013 Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 898, s. 14-23 Tidskriftsartikel (refereegranskat)abstract Measurements of direct photon production in p + Pb and p + C collisions at root(NN)-N-s = 17.4 GeV are presented. Upper limits on the direct photon yield as a function of p(T) are derived and compared to the results for Pb + Pb collisions at root(NN)-N-s = 17.3 GeV. The production of the eta meson, which is an important input to the direct photon signal extraction, has been determined in the eta -> 2 gamma channel for p + C collisions at root(NN)-N-s = 17.4 GeV. (c) 2012 Elsevier B.V. All rights reserved.
44.	Aggarwal, M. M., et al. (författare) Pion freeze-out time in Pb plus Pb collisions at 158 AGeV/c studied via pi(-)/pi(+) and K-/K+ ratios 2006 Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:2, s. 343-352 Tidskriftsartikel (refereegranskat)abstract The effect of the final state Coulomb interaction on particles produced in Pb + Pb collisions at 158AGeV/c has been investigated in the WA98 experiment through the study of the pi(-)/pi(+) and K-/K+ ratios measured as a function of T-m- (m)0. While the ratio for kaons shows no significant T-m dependence, the pi(-)/pi(+) ratio is enhanced at small T-m - (m)0 values with an enhancement that increases with centrality. A silicon pad detector located near the target is used to estimate the contribution of hyperon decays to the pi(-)/pi(+) ratio. The comparison of results with predictions of the RQMD model in which the Coulomb interaction has been incorporated allows to place constraints on the time of the pion freeze-out.
45.	Aggarwal, M. M., et al. (författare) Suppression of high-p(T) neutral pion production in central Pb+Pb collisions at root s(NN)=17.3 GeV relative to p+C and p+Pb collisions 2008 Ingår i: Physical Review Letters. - 1079-7114. ; 100:24 Tidskriftsartikel (refereegranskat)abstract Neutral pion transverse momentum spectra were measured in p+C and p+Pb collisions at root s(NN) = 17.4 GeV at midrapidity (2.3 less than or similar to eta(lab)less than or similar to 3.0) over the range 0.7 less than or similar to p(T)less than or similar to 3.5 GeV/c. The spectra are compared to pi(0) spectra measured in Pb+Pb collisions at root s(NN) = 17.3 GeV in the same experiment. For a wide range of Pb+Pb centralities (N-part less than or similar to 300), the yield of pi(0)'s with p(T)greater than or similar to 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled with the number of nucleon-nucleon collisions (N-coll), while for central Pb+Pb collisions with N-part greater than or similar to 350, the pi(0) yield is suppressed.
46.	Ahmed, Aisha S., et al. (författare) Activation of NF-kappa B in Synovium versus Cartilage from Patients with Advanced Knee Osteoarthritis : A Potential Contributor to Inflammatory Aspects of Disease Progression 2018 Ingår i: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 201:7, s. 1918-1927 Tidskriftsartikel (refereegranskat)abstract The aim was to assess the activation and association of the NF-kappa B system across synovial membrane (SM) and articular cartilage (AC) in patients with knee osteoarthritis (OA) and ascertain its potential effects on catabolic mediator expression in advanced OA. SM and AC were obtained from 40 OA patients undergoing total knee arthroplasty and from 19 postmortem control subjects. NF-kappa B subunit RelA in nuclear and cytosolic fractions and NF-kappa B1-DNA binding in nuclear extracts was assessed by ELISA, whereas NFKB1, RELA, IL-8, IL-6, and MMP3 gene expression were analyzed by reverse transcriptase-quantitative PCR in tissues. We observed higher SM nuclear RelA protein levels and upregulated NF-kappa B1-DNA binding in OA patients compared with postmortem controls. However, in AC, lower nuclear RelA levels were observed compared with cytosolic extracts in patients. Nuclear RelA levels correlated positively with NF-kappa B1-DNA binding in SM and AC in patients. SM RELA and MMP3 mRNA levels were upregulated, whereas IL-8 and IL-6 as well as AC RELA were downregulated in patients compared with controls. In SM, nuclear RelA levels correlated positively with MMP3 gene expression in patients. A negative correlation was observed between SM nuclear RelA levels and AC NF-kappa B1-DNA binding, and SM nuclear NF-kappa B1-DNA binding correlated negatively with AC MMP3 and NFKB1 mRNA levels in patients. These findings highlight NF-kappa B-triggered cross-talk and feedback mechanisms between SM and AC in OA. Further, our findings strongly support a role for an activated NF-kappa B system in the transcriptional mechanism of inflammatory processes, especially in SM of patients with advanced OA.
47.	Ahmed, Aisha S, et al. (författare) NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease. 2019 Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:3 Tidskriftsartikel (refereegranskat)abstract The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1⁻DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1⁻DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1⁻DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1⁻DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients.
48.	Ahrén, Bo, et al. (författare) Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. 2004 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:5, s. 2078-84 Tidskriftsartikel (refereegranskat)
49.	Ainsworth, Richard I, et al. (författare) Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function. 2022 Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Rheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted activepathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity.
50.	Althoff, David M., et al. (författare) The influence of interaction type and feeding location on the phylogeographic structure of the yucca moth community associated with Hesperoyucca whipplei 2007 Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1095-9513 .- 1055-7903. ; 43:2, s. 398-406 Tidskriftsartikel (refereegranskat)abstract The interactions between herbivorous insects and their host plants have been central in generating diversification in both groups. We used a community of four yucca moth species, monophagous on the host plant Hesperoyucca whipplei (Agavaceae), to examine how the type of interaction and where insects feed within a plant influence phylogeographic structure of herbivorous insects. These four species included two fruit-feeders, one mutualistic and one commensalistic, and two commensalistic stalk-feeders. Surveys based on mtDNA cytochrome oxidase I sequence data demonstrated that the moth species differed in phylogeographic history. Populations of the mutualist pollinator, Tegeticula maculata, exhibited the most subdivision in comparison to the three commensal Prodoxus species (both genera in Lepidoptera, Prodoxidae). Feeding location was also correlated with differences in phylogeographic history through its influence on population sizes and the probability of gene flow. The results suggest that both the outcome of interactions and where insects feed may influence population structure. (C) 2006 Elsevier Inc. All rights reserved.

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