| 1. |
- Singh, B. P., et al.
(författare)
-
Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
- 2015
-
Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
-
Tidskriftsartikel (refereegranskat)abstract
- Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
|
|
| 2. |
- Adam, A, et al.
(författare)
-
Abstracts from Hydrocephalus 2016.
- 2017
-
Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Ose, J., et al.
(författare)
-
Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort
- 2015
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 112:1, s. 162-166
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n = 565 cases). Multivariable conditional logistic regression models were used to estimate associations. Results: We observed no association between IGF-I and EOC overall or by tumour characteristics. Conclusions: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.
|
|
| 4. |
- Strandberg, B., et al.
(författare)
-
Compton scattering from the deuteron above pion-production threshold
- 2018
-
Ingår i: Physical Review C. - 2469-9985. ; 98:1
-
Tidskriftsartikel (refereegranskat)abstract
- The electromagnetic polarizabilities of the nucleon are fundamental nucleon-structure observables that characterize its response to external electromagnetic fields. The neutron polarizabilities can be accessed from Compton-scattering data on light nuclear targets. Recent measurements of the differential cross section for Compton scattering on the deuteron below the pion-production threshold have decreased the uncertainties in the neutron polarizabilities, yet the proton polarizabilities remain known substantially more accurately. As the sensitivity of the cross section to the polarizabilities increases with incident photon energy, measurements above the pion threshold may offer a way for an improved determination of the neutron polarizabilities. In this Rapid Communiciation, the first measurement of the cross section for coherent Compton scattering on the deuteron above the pion-production threshold is presented.
|
|
| 5. |
|
|
| 6. |
- Idahl, Annika, 1965-, et al.
(författare)
-
Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk : results from the EPIC cohort
- 2019
-
Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29, s. A473-A474
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction/Background Sexually transmitted infections (STI) and pelvic inflammatory disease may cause damage to the fallopian tube where a substantial proportion of epithelial ovarian cancer (EOC) likely arises. The aim of this study was to determine whether Chlamydia trachomatis antibodies are associated with higher EOC risk. As secondary objectives, we investigated Mycoplasma genitalium,herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 and EOC risk.Methodology In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort,791 cases and 1,669 matched controls with pre-diagnosis blood samples were analyzed. Cases and controls were matched on study center, and at blood collection age, time of day, fasting status, exogenous hormone use, menopausal status, and menstrual cycle phase. Antibodies against C. trachomatis, M. genitalium, HSV-2, and HPV 16, 18 and 45 (E6, E7, L1) were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals [CI] comparing women with positive vs. negative serology.Results A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but was associated with higher risk of the mucinous histotype (RR=2.56 [95% CI=1.3–5.05]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1), produced during persistent infection, was associated with higher risk of EOC overall (1.33 [1.09–1.62]) and of the serous subtype (1.42 [1.09–1.84]). None of the other evaluated STIs were associated with EOC risk overall; in analyses by histotype, HSV-2 was associated with higher risk of endometrioid EOC (2.93 [1.50–5.74]).Conclusion C. trachomatis infection may influence carcinogenesis of serous and mucinous EOC, while HSV-2 might promote endometrioid disease. Mechanisms linking STIs to EOC need to be further elucidated.
|
|
| 7. |
- Nilsson, D., et al.
(författare)
-
From cytogenetics to cytogenomics : whole genome sequencing as a comprehensive genetic test in rare disease diagnostics
- 2019
-
Ingår i: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 27, s. 1666-1667
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rare genetic diseases are caused by different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements. Recent data indicates that whole genome sequencing (WGS) may be used as a comprehensive test to identify multiple types of pathologic genetic aberrations in a single analysis.We present FindSV, a bioinformatic pipeline for detection of balanced (inversions and translocations) and unbalanced (deletions and duplications) structural variants (SVs). First, FindSV was tested on 106 validated deletions and duplications with a median size of 850 kb (min: 511 bp, max: 155 Mb). All variants were detected. Second, we demonstrated the clinical utility in 138 monogenic WGS panels. SV analysis yielded 11 diagnostic findings (8%). Remarkably, a complex structural rearrangement involving two clustered deletions disrupting SCN1A, SCN2A, and SCN3A was identified in a three months old girl with epileptic encephalopathy. Finally, 100 consecutive samples referred for clinical microarray were also analyzed by WGS. The WGS data was screened for large (>2 kbp) SVs genome wide, processed for visualization in our clinical routine arrayCGH workflow with the newly developed tool vcf2cytosure, and for exonic SVs and SNVs in a panel of 700 genes linked to intellectual disability. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. The diagnostic rate (29%) was doubled compared to clinical microarray (12%).In conclusion, using WGS we have detected a wide range of structural variation with high accuracy, confirming it a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
|
|
| 8. |
- Feldman, G., et al.
(författare)
-
New results for Compton scattering on deuterium : A better determination of the neutron electromagnetic polarizabilities
- 2015
-
Ingår i: Proceedings of Science. - 1824-8039.
-
Tidskriftsartikel (refereegranskat)abstract
- The electric and magnetic polarizabilities of the proton are now well known, owing to Compton scattering measurements on hydrogen targets; however, the neutron polarizabilities are still relatively uncertain, compared to the proton values. To address this problem, a multiinstitutional collaboration has conducted a program of elastic Compton scattering experiments on deuterium at the MAX IV Laboratory in Lund, Sweden using tagged photons in the energy range Eγ= 65-115 MeV. We assembled at one laboratory, for the first time, three of the world's largest NaI detectors, each having better than ΔE/E ∼ 2% photon energy resolution. We have measured elastic Compton scattering cross sections at lab angles of θγ= 60°, 120° and 150° over this energy range in 8 MeV steps. This effectively doubles the world's set of elastic Compton scattering data from deuterium and provides valuable input for chiral effective field theory (χEFT) calculations. These new deuterium data overlap previous measurements and extend them by 20 MeV to higher energies. Based on χEFT fits to the expanded world data set, new values for the neutron electric and magnetic polarizabilities have been obtained with greater accuracy than previously achieved, decreasing the statistical error by more than 30%.
|
|
| 9. |
- Li, K., et al.
(författare)
-
An epidemiologic risk prediction model for ovarian cancer in Europe : the EPIC study
- 2015
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:7, s. 1257-1265
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. Results: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. Conclusion: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.
|
|
| 10. |
- Li, M., et al.
(författare)
-
Model validation and uncertainty analysis in the wear prediction of a wet clutch
- 2016
-
Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 364-365, s. 112-121
-
Tidskriftsartikel (refereegranskat)abstract
- An uncertainty quantification analysis is performed to further investigate the nature of the “two-stage” wear process of the paper-based friction lining in a wet clutch. In this approach, the results of a computerized wear prediction model are examined through sensitivity analysis and a model validation that utilizes the Monte Carlo (MC) method. Extensive computational results that take into account the uncertainty and variability in the input data are presented to gain insight into the evolution of temperature and wear during the engagement process.
|
|
| 11. |
- Manco-Johnson, M. J., et al.
(författare)
-
Effect of late prophylaxis in hemophilia on joint status : A randomized trial
- 2017
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 15:11, s. 2115-2124
-
Tidskriftsartikel (refereegranskat)abstract
- Essentials: High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. Summary: Background: Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives: To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods: Males aged 12-50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results: Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, - 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus - 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions: Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible.
|
|
| 12. |
- Wentzensen, Nicolas, et al.
(författare)
-
Ovarian Cancer Risk Factors by Histologic Subtype : An Analysis From the Ovarian Cancer Cohort Consortium
- 2016
-
Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 34:24, s. 2888-2898
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).Patients and Methods: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.Results: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.Conclusion: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
|
|
| 13. |
- Bunse, Carina, et al.
(författare)
-
Response of marine bacterioplankton pH homeostasis gene expression to elevated CO2
- 2016
-
Ingår i: Nature Climate Change. - : Macmillan Publishers Ltd.. - 1758-678X .- 1758-6798. ; 6:5, s. 483-487
-
Tidskriftsartikel (refereegranskat)abstract
- Human-induced ocean acidification impacts marine life. Marine bacteria are major drivers of biogeochemical nutrient cycles and energy fluxes1; hence, understanding their performance under projected climate change scenarios is crucial for assessing ecosystem functioning. Whereas genetic and physiological responses of phytoplankton to ocean acidification are being disentangled2, 3, 4, corresponding functional responses of bacterioplankton to pH reduction from elevated CO2 are essentially unknown. Here we show, from metatranscriptome analyses of a phytoplankton bloom mesocosm experiment, that marine bacteria responded to lowered pH by enhancing the expression of genes encoding proton pumps, such as respiration complexes, proteorhodopsin and membrane transporters. Moreover, taxonomic transcript analysis showed that distinct bacterial groups expressed different pH homeostasis genes in response to elevated CO2. These responses were substantial for numerous pH homeostasis genes under low-chlorophyll conditions (chlorophyll a <2.5 μg l−1); however, the changes in gene expression under high-chlorophyll conditions (chlorophyll a >20 μg l−1) were low. Given that proton expulsion through pH homeostasis mechanisms is energetically costly, these findings suggest that bacterioplankton adaptation to ocean acidification could have long-term effects on the economy of ocean ecosystems.
|
|
| 14. |
- Bychkov, D, et al.
(författare)
-
Deep learning based tissue analysis predicts outcome in colorectal cancer
- 2018
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 3395-
-
Tidskriftsartikel (refereegranskat)abstract
- Image-based machine learning and deep learning in particular has recently shown expert-level accuracy in medical image classification. In this study, we combine convolutional and recurrent architectures to train a deep network to predict colorectal cancer outcome based on images of tumour tissue samples. The novelty of our approach is that we directly predict patient outcome, without any intermediate tissue classification. We evaluate a set of digitized haematoxylin-eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer patients with clinicopathological and outcome data available. The results show that deep learning-based outcome prediction with only small tissue areas as input outperforms (hazard ratio 2.3; CI 95% 1.79–3.03; AUC 0.69) visual histological assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28–2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30–2.15; AUC 0.57) in the stratification into low- and high-risk patients. Our results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.
|
|
| 15. |
- Fortner, Renée T., et al.
(författare)
-
Ovarian cancer risk factors by tumor aggressiveness : An analysis from the Ovarian Cancer Cohort Consortium
- 2019
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:1, s. 58-69
-
Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
|
|
| 16. |
- Geny, Sylvain, et al.
(författare)
-
Next-generation bis-locked nucleic acids with stacking linker and 2 '-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes
- 2016
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:5, s. 2007-2019
-
Tidskriftsartikel (refereegranskat)abstract
- Targeting and invading double-stranded DNA with synthetic oligonucleotides under physiological conditions remain a challenge. Bis-locked nucleic acids (bisLNAs) are clamp-forming oligonucleotides able to invade into supercoiled DNA via combined Hoogsteen and Watson-Crick binding. To improve the bisLNA design, we investigated its mechanism of binding. Our results suggest that bisLNAs bind via Hoogsteen-arm first, followed by Watson-Crick arm invasion, initiated at the tail. Based on this proposed hybridization mechanism, we designed next-generation bisLNAs with a novel linker able to stack to adjacent nucleobases, a new strategy previously not applied for any type of clamp-constructs. Although the Hoogsteen-arm limits the invasion, upon incorporation of the stacking linker, bisLNA invasion is significantly more efficient than for non-clamp, or nucleotide-linker containing LNA-constructs. Further improvements were obtained by substituting LNA with 2'-glycylamino-LNA, contributing a positive charge. For regular bisLNAs a 14-nt tail significantly enhances invasion. However, when two stacking linkers were incorporated, tail-less bisLNAs were able to efficiently invade. Finally, successful targeting of plasmids inside bacteria clearly demonstrates that strand invasion can take place in a biologically relevant context.
|
|
| 17. |
|
|
| 18. |
- Myers, L. S., et al.
(författare)
-
Compton scattering from the deuteron below pion-production threshold
- 2015
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:2
-
Tidskriftsartikel (refereegranskat)abstract
- Differential cross sections for elastic scattering of photons from the deuteron have recently been measured at the Tagged-Photon Facility at the MAX IV Laboratory in Lund, Sweden. These first new measurements in more than a decade further constrain the isoscalar electromagnetic polarizabilities of the nucleon and provide the first-ever results above 100 MeV, where the sensitivity to the polarizabilities is increased. We add 23 points between 70 and 112 MeV, at angles 60 degrees, 120 degrees, and 150 degrees. Analysis of these data using a chiral effective field theory indicates that the cross sections are both self-consistent and consistent with previous measurements. Extracted values of alpha(s) = [12.1 +/- 0.8(stat) +/- 0.2(BSR) +/- 0.8(th)] x 10(-4) fm(3) and beta(s) = [2.4 +/- 0.8(stat) +/- 0.2(BSR) +/- 0.8(th)] x 10(-4) fm(3) are obtained from a fit to these 23 new data points. This paper presents in detail the experimental conditions and the data analysis used to extract the cross sections.
|
|
| 19. |
|
|
| 20. |
- Nilsson, Hans, et al.
(författare)
-
Evolution of the ion environment of comet 67P/Churyumov-Gerasimenko
- 2015
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 583
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The Rosetta spacecraft is escorting comet 67P/Churyumov-Gerasimenko from a heliocentric distance of >3.6 AU, where the comet activity was low, until perihelion at 1.24 AU. Initially, the solar wind permeates the thin comet atmosphere formed from sublimation. Aims. Using the Rosetta Plasma Consortium Ion Composition Analyzer (RPC-ICA), we study the gradual evolution of the comet ion environment, from the first detectable traces of water ions to the stage where cometary water ions accelerated to about 1 keV energy are abundant. We compare ion fluxes of solar wind and cometary origin. Methods. RPC-ICA is an ion mass spectrometer measuring ions of solar wind and cometary origins in the 10 eV-40 keV energy range. Results. We show how the flux of accelerated water ions with energies above 120 eV increases between 3.6 and 2.0 AU. The 24 h average increases by 4 orders of magnitude, mainly because high-flux periods become more common. The water ion energy spectra also become broader with time. This may indicate a larger and more uniform source region. At 2.0 AU the accelerated water ion flux is frequently of the same order as the solar wind proton flux. Water ions of 120 eV-few keV energy may thus constitute a significant part of the ions sputtering the nucleus surface. The ion density and mass in the comet vicinity is dominated by ions of cometary origin. The solar wind is deflected and the energy spectra broadened compared to an undisturbed solar wind. Conclusions. The flux of accelerated water ions moving from the upstream direction back toward the nucleus is a strongly nonlinear function of the heliocentric distance.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Tariq, M., et al.
(författare)
-
Homozygosity for a missense variant in COMP gene associated with severe pseudoachondroplasia
- 2018
-
Ingår i: Clinical Genetics. - : WILEY. - 0009-9163 .- 1399-0004. ; 93:1, s. 182-186
-
Tidskriftsartikel (refereegranskat)abstract
- The phenotypic spectrum associated with heterozygous mutations in cartilage oligomeric matrix protein gene (COMP) range from a mild form of multiple epiphyseal dysplasia (MED) to pseudoachondroplasia (PSACH). However, the phenotypic effect from biallelic COMP variants is unclear. We investigated a large consanguineous Pakistani family with a severe form of PSACH in 2 individuals. Another 14 family members presented with a mild PSACH phenotype similar to MED. Using exome sequencing and subsequent segregation analysis, we identified homozygosity for a COMP missense variant [c.1423G>A; p.(D475N)] in the 2 severely affected individuals, whereas family members with the mild PSACH phenotype were heterozygous. Our observations show for the first time that a biallelic COMP variant may be associated with pronounced and widespread skeletal malformations suggesting an additive effect of the 2 mutated alleles.
|
|
| 24. |
- Trotta, A., et al.
(författare)
-
Serine and threonine residues of plant STN7 kinase are differentially phosphorylated upon changing light conditionsandspecificallyinfluence the activity and stability of the kinase
- 2016
-
Ingår i: The Plant Journal. - : Wiley. - 0960-7412 .- 1365-313X. ; 87:5, s. 484-494
-
Tidskriftsartikel (refereegranskat)abstract
- STN7 kinase catalyzes the phosphorylation of the globally most common membrane proteins, the light-harvesting complex II (LHCII) in plant chloroplasts. STN7 itself possesses one serine (Ser) and two threonine (Thr) phosphosites. We show that phosphorylation of the Thr residues protects STN7 against degradation in darkness, low light and red light, whereas increasing light intensity and far red illumination decrease phosphorylation and induce STN7 degradation. Ser phosphorylation, in turn, occurs under red and low intensity white light, coinciding with the client protein (LHCII) phosphorylation. Through analysis of the counteracting LHCII phosphatase mutant tap38/pph1, we show that Ser phosphorylation and activation of the STN7 kinase for subsequent LHCII phosphorylation are heavily affected by pre-illumination conditions. Transitions between the three activity states of the STN7 kinase (deactivated in darkness and far red light, activated in low and red light, inhibited in high light) are shown to modulate the phosphorylation of the STN7 Ser and Thr residues independently of each other. Such dynamic regulation of STN7 kinase phosphorylation is crucial for plant growth and environmental acclimation. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Chaudhry, U., et al.
(författare)
-
Idiopathic ventricular fibrillation – Long term prognosis in relation to clinical findings and ECG patterns in a Swedish cohort
- 2019
-
Ingår i: Journal of Electrocardiology. - Philadephia : Churchill Livingstone Inc. Medical Publishers. - 0022-0736 .- 1532-8430. ; 56, s. 46-51
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Idiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest which may pose therapeutic and prognostic challenges. To date, the only effective treatment for survivors of cardiac arrest is the insertion of an implantable cardioverter-defibrillator (ICD). We sought to review the long-term outcome of a Swedish cohort with IVF.Methods and results: Fifty patients with IVF diagnosis between 1988 and 2016 (mean age at index 34.3, 56% male), were followed for a median 13.8 years in this retrospective multicenter observational study. No cardiac mortality was reported. 32% (n = 16) of patients had recurrence of ventricular fibrillation or sustained ventricular tachycardia, requiring ICD therapy, at a median time of 1.9 years (range 0.1–20.3) from the index event. Annual incidence rate of ventricular tachyarrhythmia was 3.1%. Abnormal ECG at baseline did not predict appropriate ICD therapy (p = 0.56). During the follow-up period, 14% (n = 7) patients received a cardiac diagnosis. Follow-up genetic testing was low (26%), however did confirm pathogenic mutations in three cases.Conclusion: Idiopathic VF is a rare diagnosis with a relatively good prognosis provided ICD therapy is initiated. Routine clinical follow-up is recommended due to potential late emerging cardiac pathology. ECG changes are common, but have no prognostic value in determining the risk of ventricular arrhythmias recurrence. Screening for genetic diseases has previously been low, and this calls for improvement, especially since cheaper and more comprehensive genetic panels are now readily available.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
- Frank, Damian, et al.
(författare)
-
Effects of Agar Gel Strength and Fat on Oral Breakdown, Volatile Release, and Sensory Perception Using in Vivo and in Vitro Systems
- 2015
-
Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 63:41, s. 9093-9102
-
Tidskriftsartikel (refereegranskat)abstract
- The density and composition of a food matrix affect the rates of oral breakdown and in-mouth flavor release as well as the overall sensory experience. Agar gels of increasing concentration (1.0, 1.7, 2.9, and 5% agarose) with and without added fat (0, 2, 5, and 10%) were spiked with seven aroma volatiles. Differences in oral processing and sensory perception were systematically measured by a trained panel using a discrete interval time intensity method. Volatile release was measured in vivo and in vitro by proton transfer reaction mass spectrometry. Greater oral processing was required as agar gel strength increased, and the intensity of flavor-related sensory attributes decreased. Volatile release was inversely related to gel strength, showing that physicochemical phenomena were the main mechanisms underlying the perceived sensory changes. Fat addition reduced the amount of oral processing and had differential effects on release, depending on the fat solubility or lipophilicity of the volatiles.
|
|
| 32. |
- Fristedt, R., et al.
(författare)
-
PSB33 sustains photosystem II D1 protein under fluctuating light conditions
- 2017
-
Ingår i: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 68:15, s. 4281-4293
-
Tidskriftsartikel (refereegranskat)abstract
- On Earth, solar irradiance varies as the sun rises and sets over the horizon, and sunlight is thus in constant fluctuation, following a slow dark-low-high-low-dark curve. Optimal plant growth and development are dependent on the capacity of plants to acclimate and regulate photosynthesis in response to these changes of light. Little is known of regulative processes for photosynthesis during nocturnal events. The nucleus-encoded plant lineage-specific protein PSB33 has been described as stabilizing the photosystem II complex, especially under light stress conditions, and plants lacking PSB33 have a dysfunctional state transition. To clarify the localization and function of this protein, we used phenomic, biochemical and proteomics approaches in the model plant Arabidopsis. We report that PSB33 is predominantly located in non-appressed thylakoid regions and dynamically associates with a thylakoid protein complex in a light-dependent manner. Moreover, plants lacking PSB33 show an accelerated D1 protein degradation in nocturnal periods, and show severely stunted growth when challenged with fluctuating light. We further show that the function of PSB33 precedes the STN7 kinase to regulate or balance the excitation energy of photosystems I and II in fluctuating light conditions.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Jiao, Xiang, et al.
(författare)
-
PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
- 2017
-
Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 102769-102782
-
Tidskriftsartikel (refereegranskat)abstract
- Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
- Kutin, Yury, et al.
(författare)
-
Chemical flexibility of heterobimetallic Mn/Fe cofactors : R2lox and R2c proteins
- 2019
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 294:48, s. 18372-18386
-
Tidskriftsartikel (refereegranskat)abstract
- A heterobimetallic Mn/Fe cofactor is present in the R2 subunit of class Ic ribonucleotide reductases (R2c) and in R2-like ligand-binding oxidases (R2lox). Although the protein-derived metal ligands are the same in both groups of proteins, the connectivity of the two metal ions and the chemistry each cofactor performs are different: in R2c, a one-electron oxidant, the Mn/Fe dimer is linked by two oxygen bridges (?-oxo/?-hydroxo), whereas in R2lox, a two-electron oxidant, it is linked by a single oxygen bridge (?-hydroxo) and a fatty acid ligand. Here, we identified a second coordination sphere residue that directs the divergent reactivity of the protein scaffold. We found that the residue that directly precedes the N-terminal carboxylate metal ligand is conserved as a glycine within the R2lox group but not in R2c. Substitution of the glycine with leucine converted the resting-state R2lox cofactor to an R2c-like cofactor, a ?-oxo/?-hydroxo?bridged Mn-III/Fe-III dimer. This species has recently been observed as an intermediate of the oxygen activation reaction in WT R2lox, indicating that it is physiologically relevant. Cofactor maturation in R2c and R2lox therefore follows the same pathway, with structural and functional divergence of the two cofactor forms following oxygen activation. We also show that the leucine-substituted variant no longer functions as a two-electron oxidant. Our results reveal that the residue preceding the N-terminal metal ligand directs the cofactor's reactivity toward one- or two-electron redox chemistry, presumably by setting the protonation state of the bridging oxygens and thereby perturbing the redox potential of the Mn ion.
|
|
| 40. |
- Lundin, C., et al.
(författare)
-
Sexual function and combined oral contraceptives: a randomised, placebo-controlled trial
- 2018
-
Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:11, s. 1208-1216
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The effect of combined oral contraceptives (COCs) on female sexuality has long been a matter of discussion, but placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate if an oestradiol-containing COC influences sexual function. Design: Investigator-initiated, randomised, double-blinded, placebo-controlled clinical trial where 202 healthy women were randomised to a combined oral contraceptive (1.5 mg oestradiol and 2.5 mg nomegestrol acetate) or placebo for three treatment cycles. Methods: Sexual function at baseline and during the last week of the final treatment cycle was evaluated by the McCoy Female Sexuality Questionnaire. Serum and hair testosterone levels were assessed at the same time points. Results: Compared to placebo, COC use was associated with a small decrease in sexual interest (COC median change score: -2.0; interquartile range (IQR): -5.0 to 0.5 vs placebo: -1.0; IQR: -3.0 to 2.0, P=0.019), which remained following adjustment for change in self-rated depressive symptoms (B= -0.80 +/- 0.30, Wald =7.08, P=0.008). However, the proportion of women who reported a clinically relevant deterioration in sexual interest did not differ between COC or placebo users (COC 18 (22.2%) vs placebo 16 (17.8%), P=0.47). Change in other measured aspects of sexual function as well as total score of sexual function did not differ between the two treatments. Conclusions: This study suggests that use of oestradiol-based COCs is associated with reduced sexual interest. However, the changes are minute, and probably not of clinical relevance.
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
- Paulussen, Aimee D C, et al.
(författare)
-
Rare novel variants in the ZIC3 gene cause X-linked heterotaxy
- 2016
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 24:12, s. 1783-1791
-
Tidskriftsartikel (refereegranskat)abstract
- Variants in the ZIC3 gene are rare, but have demonstrated their profound clinical significance in X-linked heterotaxy, affecting in particular male patients with abnormal arrangement of thoracic and visceral organs. Several reports have shown relevance of ZIC3 gene variants in both familial and sporadic cases and with a predominance of mutations detected in zinc-finger domains. No studies so far have assessed the functional consequences of ZIC3 variants in an in vivo model organism. A study population of 348 patients collected over more than 10 years with a large variety of congenital heart disease including heterotaxy was screened for variants in the ZIC3 gene. Functional effects of three variants were assessed both in vitro and in vivo in the zebrafish. We identified six novel pathogenic variants (1,7%), all in either male patients with heterotaxy (n=5) or a female patient with multiple male deaths due to heterotaxy in the family (n=1). All variants were located within the zinc-finger domains or leading to a truncation before these domains. Truncating variants showed abnormal trafficking of mutated ZIC3 proteins, whereas the missense variant showed normal trafficking. Overexpression of wild-type and mutated ZIC protein in zebrafish showed full non-functionality of the two frame-shift variants and partial activity of the missense variant compared with wild-type, further underscoring the pathogenic character of these variants. Concluding, we greatly expanded the number of causative variants in ZIC3 and delineated the functional effects of three variants using in vitro and in vivo model systems.
|
|
| 46. |
- Scherzinger, J., et al.
(författare)
-
Tagging fast neutrons from an 241Am/9Be source
- 2015
-
Ingår i: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043 .- 1872-9800. ; 98, s. 74-79
-
Tidskriftsartikel (refereegranskat)abstract
- Shielding, coincidence, and time-of-flight measurement techniques are employed to tag fast neutrons emitted from an 241Am/9Be source resulting in a continuous polychromatic energy-tagged beam of neutrons with energies up to 7MeV. The measured energy structure of the beam agrees qualitatively with both previous measurements and theoretical calculations.
|
|
| 47. |
- Scherzinger, J., et al.
(författare)
-
The light-yield response of a NE-213 liquid-scintillator detector measured using 2–6 MeV tagged neutrons
- 2016
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 840, s. 121-127
-
Tidskriftsartikel (refereegranskat)abstract
- The response of a NE-213 liquid-scintillator detector has been measured using tagged neutrons from 2 to 6 MeV originating from an Am/Be neutron source. The neutron energies were determined using the time-of-flight technique. Pulse-shape discrimination was employed to discern between gamma-rays and neutrons. The behavior of both the fast (35 ns) and the combined fast and slow (475 ns) components of the neutron scintillation-light pulses were studied. Three different prescriptions were used to relate the neutron maximum energy-transfer edges to the corresponding recoil-proton scintillation-light yields, and the results were compared to simulations. The overall normalizations of parametrizations which predict the fast or total light yield of the scintillation pulses were also tested. Our results agree with both existing data and existing parametrizations. We observe a clear sensitivity to the portion and length of the neutron scintillation-light pulse considered.
|
|
| 48. |
- Srinivas, Vivek, et al.
(författare)
-
Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens
- 2018
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 563:7731, s. 416-420
-
Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductase (RNR) catalyses the only known de novo pathway for the production of all four deoxyribonucleotides that are required for DNA synthesis(1,2). It is essential for all organisms that use DNA as their genetic material and is a current drug target(3,4). Since the discovery that iron is required for function in the aerobic, class I RNR found in all eukaryotes and many bacteria, a dinuclear metal site has been viewed as necessary to generate and stabilize the catalytic radical that is essential for RNR activity(5-7). Here we describe a group of RNR proteins in Mollicutes-including Mycoplasma pathogens-that possess a metal-independent stable radical residing on a modified tyrosyl residue. Structural, biochemical and spectroscopic characterization reveal a stable 3,4-dihydroxyphenylalanine (DOPA) radical species that directly supports ribonucleotide reduction in vitro and in vivo. This observation overturns the presumed requirement for a dinuclear metal site in aerobic ribonucleotide reductase. The metal-independent radical requires new mechanisms for radical generation and stabilization, processes that are targeted by RNR inhibitors. It is possible that this RNR variant provides an advantage under metal starvation induced by the immune system. Organisms that encode this type of RNR-some of which are developing resistance to antibiotics-are involved in diseases of the respiratory, urinary and genital tracts. Further characterization of this RNR family and its mechanism of cofactor generation will provide insight into new enzymatic chemistry and be of value in devising strategies to combat the pathogens that utilize it. We propose that this RNR subclass is denoted class Ie.
|
|
| 49. |
- Stenler, S, et al.
(författare)
-
Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses.
- 2017
-
Ingår i: Human Vaccines & Immunotherapeutics. - : Taylor & Francis. - 2164-5515 .- 2164-554X. ; 13:12, s. 2849-2858
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid. In addition, three conventional plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20 in their gp41 sequences were also tested.RESULTS: All combinations induced HIV-specific antibodies and cellular responses. The addition of T20 as a peptide and as an expression cassette in the three DNA vectors enhanced antibody responses. The highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This demonstrates that besides its known antiviral activity, T20 promotes immune responses. We also confirm that the combination of slightly divergent antigens improves immune responses.CONCLUSIONS: The antiretroviral T20 HIV-1 sequence can be used as an immunogen to elicit binding and neutralizing antibodies against HIV-1. These, or similarly modified gp41 genes/peptides, can be used as priming or boosting components for induction of broadly neutralizing anti-HIV antibodies. Future comparative studies will reveal the optimal mode of T20 administration.
|
|
| 50. |
|
|
