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| 8. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 9. |
- Yanez, Marianna, et al.
(författare)
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On the formation of dendrimer/nucleolipids surface films for directed self-assembly.
- 2015
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 11:10, s. 1973-1990
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Tidskriftsartikel (refereegranskat)abstract
- We describe the formation and structure of nucleolipid/dendrimer multilayer films controlled by non-covalent interactions to obtain biomaterials that exhibit molecular recognition of nucleic acids. Layers of cationic poly(amidoamine) (PAMAM) dendrimers of generation 4 and the anionic nucleolipids 1,2-dilauroyl-sn-glycero-3-phosphatidylnucleosides (DLPNs) based on uridine (DLPU) and adenosine (DLPA) were first formed at the silica-water interface. The PAMAM/DLPN layers were then exposed to short oligonucleotides, polynucleotides and single stranded DNA (ssDNA). The interfacial properties were characterized using quartz crystal microbalance with dissipation monitoring, attenuated total reflection Fourier transform infrared spectroscopy and neutron reflectometry. Both types of DLPN were found to adsorb as aggregates to preadsorbed PAMAM monolayers with a similar interfacial structure and composition before rinsing with pure aqueous solution. Nucleic acids were found to interact with PAMAM/DLPA layers due to base pairing interactions, while the PAMAM/DLPU layers did not have the same capability. This was attributed to the structure of the DLPA layer, which is formed by aggregates that extend from the interface towards the bulk after rinsing with pure solvent, while the DLPU layer forms compact structures. In complementary experiments using a different protocol, premixed PAMAM/DLPN samples adsorbed to hydrophilic silica only when the mixtures contained positively charged aggregates, which is rationalized in terms of electrostatic forces. The PAMAM/DLPA layers formed from the adsorption of these mixtures also bind ssDNA although in this case the adsorption is mediated by the opposite charges of the film and the nucleic acid rather than specific base pairing. The observed molecular recognition of nucleic acids by dendrimers functionalized via non-covalent interactions with nucleolipids is discussed in terms of biomedical applications such as gene vectors and biosensors.
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| 10. |
- Dabkowska, A. P., et al.
(författare)
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Temperature responsive lipid liquid crystal layers with embedded nanogels
- 2017
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Ingår i: Chemical Communications. - : Royal Society of Chemistry. - 1359-7345 .- 1364-548X. ; 53:8, s. 1417-1420
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Tidskriftsartikel (refereegranskat)abstract
- Polymer nanogels are embedded within layers consisting of a nonlamellar liquid crystalline lipid phase to act as thermoresponsive controllers of layer compactness and hydration. As the nanogels change from the swollen to the collapsed state via a temperature trigger, they enable on-demand release of water from the mixed polymer-lipid layer while the lipid matrix remains intact. Combining stimuli-responsive polymers with responsive lipid-based mesophase systems opens up new routes in biomedical applications such as functional biomaterials, bioanalysis and drug delivery.
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| 11. |
- Gribenski, Natacha, 1986-, et al.
(författare)
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Complex patterns of glacier advances during the late glacial in the Chagan Uzun Valley, Russian Altai
- 2016
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 149, s. 288-305
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Tidskriftsartikel (refereegranskat)abstract
- The Southern part of the Russian Altai Mountains is recognized for its evidence for catastrophic glacial lake outbursts. However, little is known about the late Pleistocene paleoglacial history, despite the interest in such reconstructions for constraining paleoclimate. In this study, we present a detailed paleoglaciological reconstruction of the Chagan Uzun Valley, in the Russian Altai Mountains, combining for the first time detailed geomorphological mapping, sedimentological logging, and in situ cosmogenic 10Be and 26Al surface exposure dating of glacially-transported boulders. The Chagan Uzun Valley exhibits the most impressive glacial landforms of this sector of the Altai, with extensive lobate moraine belts deposited in the intramontane Chuja Basin, reflecting a series of pronounced former glacial advances. Observations of “hillside-scale” folding and extensive faulting of pre-existing soft sediments within the outer moraine belts, together with the geomorphology, strongly indicate that these moraine belts were formed during surge-like events. Identification of surge-related features is essential for paleoclimate inference because these features correspond to a glacier system that is not in equilibrium with the contemporary climate, but instead largely influenced by various internal and external factors. Therefore, no strict relationship can be established between climatic variables and the pronounced distal glacial extent observed in the Chagan Uzun Valley/Chuja basin. In contrast, the inner (up-valley) glacial landforms of the Chagan Uzun valley were likely deposited during retreat of temperate valley glaciers, close to equilibrium with climate, and so most probably triggered by a general warming. Cosmogenic ages associated with the outermost, innermost, and intermediate stages all indicate deposition times clustered around 19 ka. However, the actual deposition time of the outermost moraine may slightly predate the 10Be ages due to shielding caused by subsequent lake water coverage. This chronology indicates a Marine Isotope Stage (MIS) 2 last maximum extent of the Chagan Uzun Glacier, and an onset of the deglaciation around 19 ka. This is consistent with other regional paleoclimate proxy records and with the Northern Hemisphere glaciation chronology. Finally, this study also highlights the highly dynamic environment in this area, with complex interactions between glacial events and the formation and drainage of lakes.
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| 13. |
- Peaceman, Alan M., et al.
(författare)
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Lifestyle Interventions Limit Gestational Weight Gain in Women with Overweight or Obesity : LIFE-Moms Prospective Meta-Analysis
- 2018
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 26:9, s. 1396-1404
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to evaluate the effects of varied lifestyle intervention programs designed to ameliorate excess gestational weight gain (GWG) in pregnant women with overweight or obesity compared with standard care, including effects on pregnancy outcomes. Methods: Seven clinical centers conducted separate randomized clinical trials to test different lifestyle intervention strategies to modify GWG in diverse populations. Eligibility criteria, specific outcome measures, and assessment procedures were standardized across trials. The results of the separate trials were combined using an individual-participant data meta-analysis. Results: For the 1,150 women randomized, the percent with excess GWG per week was significantly lower in the intervention group compared with the standard care group (61.8% vs. 75.0%; odds ratio [95% CI]: 0.52 [0.40 to 0.67]). Total GWG from enrollment to 36 weeks' gestation was also lower in the intervention group (8.1 ± 5.2 vs. 9.7 ± 5.4 kg; mean difference: −1.59 kg [95% CI:−2.18 to −0.99 kg]). The results from the individual trials were similar. The intervention and standard care groups did not differ in preeclampsia, gestational diabetes, cesarean delivery, or birth weight. Conclusions: Behavioral lifestyle interventions focusing primarily on diet and physical activity among women with overweight and obesity resulted in a significantly lower proportion of women with excess GWG. This modest beneficial effect was consistent across diverse intervention modalities in a large, racially and socioeconomically diverse US population of pregnant women.
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| 15. |
- Clifton, N.E., et al.
(författare)
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Schizophrenia copy number variants and associative learning
- 2017
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 22, s. 178-182
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale genomic studies have made major progress in identifying genetic risk variants for schizophrenia. A key finding from these studies is that there is an increased burden of genomic copy number variants (CNVs) in schizophrenia cases compared with controls. The mechanism through which these CNVs confer risk for the symptoms of schizophrenia, however, remains unclear. One possibility is that schizophrenia risk CNVs impact basic associative learning processes, abnormalities of which have long been associated with the disorder. To investigate whether genes in schizophrenia CNVs impact on specific phases of associative learning we combined human genetics with experimental gene expression studies in animals. In a sample of 11 917 schizophrenia cases and 16 416 controls, we investigated whether CNVs from patients with schizophrenia are enriched for genes expressed during the consolidation, retrieval or extinction of associative memories. We show that CNVs from cases are enriched for genes expressed during fear extinction in the hippocampus, but not genes expressed following consolidation or retrieval. These results suggest that CNVs act to impair inhibitory learning in schizophrenia, potentially contributing to the development of core symptoms of the disorder.
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- Gorsich, Erin E., et al.
(författare)
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Model-guided suggestions for targeted surveillance based on cattle shipments in the US
- 2018
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Ingår i: Preventive Veterinary Medicine. - : ELSEVIER SCIENCE BV. - 0167-5877 .- 1873-1716. ; 150, s. 52-59
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Tidskriftsartikel (refereegranskat)abstract
- Risk-based sampling is an essential component of livestock health surveillance because it targets resources towards sub-populations with a higher risk of infection. Risk-based surveillance in U.S. livestock is limited because the locations of high-risk herds are often unknown and data to identify high-risk herds based on shipments are often unavailable. In this study, we use a novel, data-driven network model for the shipments of cattle in the U.S. (the U.S. Animal Movement Model, USAMM) to provide surveillance suggestions for cattle imported into the U.S. from Mexico. We describe the volume and locations where cattle are imported and analyze their predicted shipment patterns to identify counties that are most likely to receive shipments of imported cattle. Our results suggest that most imported cattle are sent to relatively few counties. Surveillance at 10 counties is predicted to sample 22-34% of imported cattle while surveillance at 50 counties is predicted to sample 43%-61% of imported cattle. These findings are based on the assumption that USAMM accurately describes the shipments of imported cattle because their shipments are not tracked separately from the remainder of the U.S. herd. However, we analyze two additional datasets - Interstate Certificates of Veterinary Inspection and brand inspection data - to ensure that the characteristics of potential post-import shipments do not change on an annual scale and are not dependent on the dataset informing our analyses. Overall, these results highlight the utility of USAMM to inform targeted surveillance strategies when complete shipment information is unavailable.
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| 18. |
- Hughes, Arwel, et al.
(författare)
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Physical Properties of Bacterial Outer Membrane Models : Neutron Reflectometry & Molecular Simulation
- 2019
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 116:6, s. 1095-1104
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Tidskriftsartikel (refereegranskat)abstract
- The outer membrane (OM) of Gram-negative bacteria is an asymmetric bilayer having phospholipids in the inner leaflet and lipopolysaccharides in the outer leaflet. This unique asymmetry and the complex carbohydrates in lipopolysaccharides make it a daunting task to study the asymmetrical OM structure and dynamics, its interactions with OM proteins, and its roles in translocation of substrates, including antibiotics. In this study, we combine neutron reflectometry and molecular simulation to explore the physical properties of OM mimetics. There is excellent agreement between experiment and simulation, allowing experimental testing of the conclusions from simulations studies and also atomistic interpretation of the behavior of experimental model systems, such as the degree of lipid asymmetry, the lipid component (tail, head, and sugar) profiles along the bilayer normal, and lateral packing (i.e., average surface area per lipid). Therefore, the combination of both approaches provides a powerful new means to explore the biological and biophysical behavior of the bacterial OM.
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| 19. |
- Jo, Sunhwan, et al.
(författare)
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Multiple Conformational States Contribute to the 3D Structure of a Glucan Decasaccharide : A Combined SAXS and MD Simulation Study
- 2018
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 122:3, s. 1169-1175
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Tidskriftsartikel (refereegranskat)abstract
- The inherent flexibility of carbohydrates is dependent on stereochemical arrangements, and characterization of their influence and importance will give insight into the three-dimensional structure and dynamics. In this study, a beta-(1 -> 4)/beta-(1 -> 3)-linked glucosyl decasaccharide is experimentally investigated by synchrotron small-angle X-ray scattering from which its radius of gyration (R-g) is obtained. Molecular dynamics (MD) simulations of the decasaccharide show four populated states at each glycosidic linkage, namely, syn- and anti-conformations. The calculated R-g values from the MD simulation reveal that in addition to syn-conformers the presence of anti-psi conformational states is required to reproduce experimental scattering data, unveiling inherent glycosidic linkage flexibility. The CHARMM36 force field for carbohydrates thus describes the conformational flexibility of the decasaccharide very well and captures the conceptual importance that anti-conformers are to be anticipated at glycosidic linkages of carbohydrates.
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| 20. |
- Nolan, Jerry P, et al.
(författare)
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Intensive care medicine research agenda on cardiac arrest
- 2017
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 43:9, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- Over the last 15 years, treatment of comatose post-cardiac arrest patients has evolved to include therapeutic strategies such as urgent coronary angiography with percutaneous coronary intervention (PCI), targeted temperature management (TTM)—requiring mechanical ventilation and sedation—and more sophisticated and cautious prognostication. In 2015, collaboration between the European Resuscitation Council (ERC) and the European Society for Intensive Care Medicine (ESICM) resulted in the first European guidelines on post-resuscitation care. This review addresses the major recent advances in the treatment of cardiac arrest, recent trials that have challenged current practice and the remaining areas of uncertainty.
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| 21. |
- Owuor, John O. A., et al.
(författare)
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Concealment, communication and stigma: The perspectives of HIV-positive immigrant Black African men and their partners living in the United Kingdom
- 2016
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Ingår i: Journal of Health Psychology. - : SAGE PUBLICATIONS LTD. - 1359-1053 .- 1461-7277. ; 21:12, s. 3079-3091
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Tidskriftsartikel (refereegranskat)abstract
- This study explored the perspectives of Black men, originally from East Africa, living in the United Kingdom and their partners on what it means to live with diagnosed HIV. This article reports on concealment of HIV-positive status as a strategy adopted by the affected participants to manage the flow of information about their HIV-positive status. Analysis of the data, collected using in-depth interviews involving 23 participants, found widespread selective concealment of HIV-positive status. However, a few respondents had come out publicly about their condition. HIV prevention initiatives should recognise concealment as a vital strategy in managing communication about ones HIV-positive status.
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| 22. |
- Sharma, Ram A, et al.
(författare)
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Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly: A Longitudinal Study.
- 2018
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 197:7, s. 933-943
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence suggests that Obstructive Sleep Apnea (OSA) may be a risk factor for developing Mild Cognitive Impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood.To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly.Data was derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 to 90, were non-depressed and had a consensus clinical diagnosis of cognitively normal. CSF Amyloid beta was measured using ELISA. Subjects received Pittsburgh compound B Positron Emission Tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device.We found that severity of OSA indices (lnAHIall [F1,88=4.26, p<.05] and lnAHI4% [F1,87=4.36, p<.05]) were associated with annual rate of change of CSF Aβ42 using linear regression after adjusting for age, sex, BMI and ApoE4 status. LnAHIall and lnAHI4 were not associated with increases in ADPiB-mask most likely due to the small sample size although there was a trend for lnAHIall (F1,28=2.96, p=.09 and F1,28=2.32, n.s. respectively).In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2 year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.
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| 23. |
- Toledo, Rodrigo A., et al.
(författare)
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Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas
- 2017
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Ingår i: Nature Reviews Endocrinology. - : NATURE PUBLISHING GROUP. - 1759-5029 .- 1759-5037. ; 13:4, s. 233-247
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Tidskriftsartikel (refereegranskat)abstract
- Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance.
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