| 1. |
- Gaulton, Kyle J, et al.
(författare)
-
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
-
Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
|
|
| 2. |
- Willems, S. M., et al.
(författare)
-
Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
|
|
| 3. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 4. |
- Karmin, Monika, et al.
(författare)
-
A recent bottleneck of Y chromosome diversity coincides with a global change in culture.
- 2015
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:4
-
Tidskriftsartikel (refereegranskat)abstract
- It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
|
|
| 5. |
- Agarwal, Girish, et al.
(författare)
-
Light, the universe and everything-12 Herculean tasks for quantum cowboys and black diamond skiers
- 2018
-
Ingår i: Journal of Modern Optics. - : Informa UK Limited. - 0950-0340 .- 1362-3044. ; 65:11, s. 1261-1308
-
Tidskriftsartikel (refereegranskat)abstract
- The Winter Colloquium on the Physics of Quantum Electronics (PQE) has been a seminal force in quantum optics and related areas since 1971. It is rather mind-boggling to recognize how the concepts presented at these conferences have transformed scientific understanding and human society. In January 2017, the participants of PQE were asked to consider the equally important prospects for the future, and to formulate a set of questions representing some of the greatest aspirations in this broad field. The result is this multi-authored paper, in which many of the world's leading experts address the following fundamental questions: (1) What is the future of gravitational wave astronomy? (2) Are there new quantum phases of matter away from equilibrium that can be found and exploited - such as the time crystal? (3) Quantum theory in uncharted territory: What can we learn? (4) What are the ultimate limits for laser photon energies? (5) What are the ultimate limits to temporal, spatial and optical resolution? (6) What novel roles will atoms play in technology? (7) What applications lie ahead for nitrogen-vacancy centres in diamond? (8) What is the future of quantum coherence, squeezing and entanglement for enhanced super-resolution and sensing? (9) How can we solve (some of) humanity's biggest problems through new quantum technologies? (10) What new understanding of materials and biological molecules will result from their dynamical characterization with free-electron lasers? (11) What new technologies and fundamental discoveries might quantum optics achieve by the end of this century? (12) What novel topological structures can be created and employed in quantum optics?
|
|
| 6. |
- Doyle, Catherine M., et al.
(författare)
-
Surface Mediated Synthesis of 2D Covalent Organic Networks : 1,3,5-Tris(4-bromophenyl)benzene on Au(111)
- 2019
-
Ingår i: Physica Status Solidi (B) Basic Research. - : Wiley. - 0370-1972. ; 256:2
-
Tidskriftsartikel (refereegranskat)abstract
- Covalent organic networks derived from surface-mediated self-assembly of 1,3,5-tris(4-bromophenyl)benzene into two-dimensional networks on Au(111) have been studied by scanning tunneling microscopy (STM) and by X-ray spectroscopic methods. High resolution soft X-ray photoemission spectroscopy (SXPS) using synchrotron radiation have been used to study the formation of the 1,3,5-tris(4-bromophenyl)benzene-derived 2D networks by observing temperature-dependent C 1s and Br 3d core level XPS spectra. X-ray absorption (XA) measurements of the formation of these 2D networks have been obtained at the C K-edge where their temperature and angular dependence are examined. The results of these XPS and XA spectroscopic measurements are compared to detailed ab initio electronic structure calculations of 1,3,5-tris(4-bromophenyl)benzene molecules to aid the interpretation of the features of these spectra.
|
|
| 7. |
- Honma, Masamitsu, et al.
(författare)
-
Improvement of quantitative structure-activity relationship (QSAR) tools for predicting Ames mutagenicity : outcomes of the Ames/QSAR International Challenge Project
- 2019
-
Ingår i: Mutagenesis. - Oxford : Oxford University Press (OUP). - 0267-8357 .- 1464-3804. ; 34:1, s. 3-16
-
Tidskriftsartikel (refereegranskat)abstract
- The International Conference on Harmonization (ICH) M7 guideline allows the use of in silico approaches for predicting Ames mutagenicity for the initial assessment of impurities in pharmaceuticals. This is the first international guideline that addresses the use of quantitative structure-activity relationship (QSAR) models in lieu of actual toxicological studies for human health assessment. Therefore, QSAR models for Ames mutagenicity now require higher predictive power for identifying mutagenic chemicals. To increase the predictive power of QSAR models, larger experimental datasets from reliable sources are required. The Division of Genetics and Mutagenesis, National Institute of Health Sciences (DGM/NIHS) of Japan recently established a unique proprietary Ames mutagenicity database containing 12140 new chemicals that have not been previously used for developing QSAR models. The DGM/NIHS provided this Ames database to QSAR vendors to validate and improve their QSAR tools. The Ames/QSAR International Challenge Project was initiated in 2014 with 12 QSAR vendors testing 17 QSAR tools against these compounds in three phases. We now present the final results. All tools were considerably improved by participation in this project. Most tools achieved >50% sensitivity (positive prediction among all Ames positives) and predictive power (accuracy) was as high as 80%, almost equivalent to the inter-laboratory reproducibility of Ames tests. To further increase the predictive power of QSAR tools, accumulation of additional Ames test data is required as well as re-evaluation of some previous Ames test results. Indeed, some Ames-positive or Ames-negative chemicals may have previously been incorrectly classified because of methodological weakness, resulting in false-positive or false-negative predictions by QSAR tools. These incorrect data hamper prediction and are a source of noise in the development of QSAR models. It is thus essential to establish a large benchmark database consisting only of well-validated Ames test results to build more accurate QSAR models.
|
|
| 8. |
- Ilina, Elena L., et al.
(författare)
-
Lateral root initiation and formation within the parental root meristem of Cucurbita pepo : is auxin a key player?
- 2018
-
Ingår i: Annals of Botany. - : Oxford University Press (OUP). - 0305-7364 .- 1095-8290. ; 122:5, s. 873-888
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims In some plant families. including Cucurbitaceae, initiation and development of lateral roots (LRs) occur in the parental root apical meristem. The objective of this study was to identify the general mechanisms underlying LR initiation (LRI). Therefore, the first cellular events leading to LRI as well as the role of auxin in this process were studied in the Cucurbita pepo root apical meristem.Methods Transgenic hairy roots harbouring the auxin-responsive promoter DR5 fused to different reporter genes were used for visualizing of cellular auxin response maxima (ARMs) via confocal laser scanning microscopy and 3-D imaging. The effects of exogenous auxin and auxin transport inhibitors on root branching were analysed.Key Results The earliest LRI event involved a group of symmetric anticlinal divisions in pericycle cell files at a distance of 250-350 pm from the initial cells. The visualization of the ARMs enabled the precise detection of cells involved in determining the site of LR primordium formation. A local ARM appeared in sister cells of the pericycle and endodermis files before the first division. Cortical cells contributed to LR development after the anticlinal divisions in the pericycle via the formation of an ARM. Exogenous auxins did not increase the total number of LRs and did not affect the LRI index. Although exogenous auxin transport inhibitors acted in different ways. they all reduced the number of LRs formed.Conclusions Literature data, as well as results obtained in this study, suggest that the formation of a local ARM before the first anticlinal formative divisions is the common mechanism underlying LRI in flowering plants. We propose that the mechanisms of the regulation of root branching are independent of the position of the LRI site relative to the parental root tip.
|
|
| 9. |
- Jacobsson, Jesper, 1984-, et al.
(författare)
-
Extending the Compositional Space of Mixed Lead Halide Perovskites by Cs, Rb, K, and Na Doping
- 2018
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 122:25, s. 13548-13557
-
Tidskriftsartikel (refereegranskat)abstract
- A trend in high performing lead halide perovskite solar cell devices has been increasing compositional complexity by successively introducing more elements, dopants, and additives into the structure; and some of the latest top efficiencies have been achieved with a quadruple cation mixed halide perovskite Cs(x)FA(y)MA(z)Rb(1-x-y-z)PbBr(q)I(3-9). This paper continues this trend by exploring doping of mixed lead halide perovskites, FA(0.83)MA(0.17)PbBr(0.51)I(2.49), with an extended set of alkali cations, i.e., Cs+, Rb+, K+, and Na+, as well as combinations of them. The doped perovskites were investigated with X-ray diffraction, energy-dispersive X-ray spectroscopy, scanning electron microscopy, hard X-ray photoelectron spectroscopy, UV-vis, steady state fluorescence, and ultrafast transient absorption spectroscopy. Solar cell devices were made as well. Cs+ can replace the organic cations in the perovskite structure, but Rb+, K+, and Na+ do not appear to do that. Despite this, samples doped with K and Na have substantially longer fluorescence lifetimes, which potentially could be beneficial for device performance.
|
|
| 10. |
- Korolev, Nikolay, et al.
(författare)
-
A systematic analysis of nucleosome core particle and nucleosome-nucleosome stacking structure
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Chromatin condensation is driven by the energetically favourable interaction between nucleosome core particles (NCPs). The close NCP-NCP contact, stacking, is a primary structural element of all condensed states of chromatin in vitro and in vivo. However, the molecular structure of stacked nucleosomes as well as the nature of the interactions involved in its formation have not yet been systematically studied. Here we undertake an investigation of both the structural and physico-chemical features of NCP structure and the NCP-NCP stacking. We introduce an NCP-centred set of parameters (NCP-NCP distance, shift, rise, tilt, and others) that allows numerical characterisation of the mutual positions of the NCPs in the stacking and in any other structures formed by the NCP. NCP stacking in more than 140 published NCP crystal structures were analysed. In addition, coarse grained (CG) MD simulations modelling NCP condensation was carried out. The CG model takes into account details of the nucleosome structure and adequately describes the long range electrostatic forces as well as excluded volume effects acting in chromatin. The CG simulations showed good agreement with experimental data and revealed the importance of the H2A and H4 N-terminal tail bridging and screening as well as tail-tail correlations in the stacked nucleosomes.
|
|
| 11. |
- Korolev, Nikolay, et al.
(författare)
-
Multiscale coarse-grained modelling of chromatin components : DNA and the nucleosome
- 2016
-
Ingår i: Advances in Colloid and Interface Science. - : Elsevier BV. - 0001-8686 .- 1873-3727. ; 232, s. 36-48
-
Tidskriftsartikel (refereegranskat)abstract
- To model large biomolecular systems, such as cell and organelles an atomistic description is not currently achievable and is not generally practical. Therefore, simplified coarse-grained (CG) modelling becomes a necessity. One of the most important cellular components is chromatin, a large DNA-protein complex where DNA is highly compacted. Recent progress in coarse graining modelling of the major chromatin components, double helical DNA and the nucleosome core particle (NCP) is presented. First, general principles and approaches allowing rigorous bottom-to-top generation of interaction potentials in the CG models are presented. Then, recent CG models of DNA are reviewed and their adequacy is benchmarked against experimental data on the salt dependence of DNA flexibility (persistence length). Furthermore, a few recent CG models of the NCP are described and their application for studying salt-dependent NCP-NCP interaction is discussed. An example of a multiscale approach to CG modelling of chromatin is presented where interactions and self-assembly of thousands of NCPs in solution are observed.
|
|
| 12. |
- Lyubartsev, Alexander P., et al.
(författare)
-
Multiscale modelling of nucleosome core particle aggregation
- 2015
-
Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 27:6
-
Tidskriftsartikel (refereegranskat)abstract
- The nucleosome core particle (NCP) is the basic building block of chromatin. Under the influence of multivalent cations, isolated mononucleosomes exhibit a rich phase behaviour forming various columnar phases with characteristic NCP-NCP stacking. NCP stacking is also a regular element of chromatin structure in vivo. Understanding the mechanism of nucleosome stacking and the conditions leading to self-assembly of NCPs is still incomplete. Due to the complexity of the system and the need to describe electrostatics properly by including the explicit mobile ions, novel modelling approaches based on coarse-grained (CG) methods at the multiscale level becomes a necessity. In this work we present a multiscale CG computer simulation approach to modelling interactions and self-assembly of solutions of NCPs induced by the presence of multivalent cations. Starting from continuum simulations including explicit three-valent cobalt(III) hexammine (CoHex(3+)) counterions and 20 NCPs, based on a previously developed advanced CG NCP model with one bead per amino acid and five beads per two DNA base pair unit (Fan et al 2013 PLoS One 8 e54228), we use the inverse Monte Carlo method to calculate effective interaction potentials for a 'super-CG' NCP model consisting of seven beads for each NCP. These interaction potentials are used in large-scale simulations of up to 5000 NCPs, modelling self-assembly induced by CoHex(3+). The systems of 'super-CG' NCPs form a single large cluster of stacked NCPs without long-range order in agreement with experimental data for NCPs precipitated by the three-valent polyamine, spermidine(3+).
|
|
| 13. |
- Palmtag, Juri, 1980-, et al.
(författare)
-
Storage, Landscape Distribution, and Burial History of Soil Organic Matter in Contrasting Areas of Continuous Permafrost
- 2015
-
Ingår i: Arctic, Antarctic and Alpine research. - 1523-0430 .- 1938-4246. ; 47:1, s. 71-88
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes and compares soil organic matter (SOM) quantity and characteristics in two areas of continuous permafrost, a mountainous region in NE Greenland (Zackenberg study site) and a lowland region in NE Siberia (Cherskiy and Shalaurovo study sites). Our assessments are based on stratified-random landscape-level inventories of soil profiles down to 1 m depth, with physico-chemical, elemental, and radiocarbon-dating analyses. The estimated mean soil organic carbon (SOC) storage in the upper meter of soils in the NE Greenland site is 8.3 ± 1.8 kg C m-2 compared to 20.3 ± 2.2 kg C m-2 and 30.0 ± 2.0 kg C m-2 in the NE Siberian sites (95% confidence intervals). The lower SOC storage in the High Arctic site in NE Greenland can be largely explained by the fact that 59% of the study area is located at higher elevation with mostly barren ground and thus very low SOC contents. In addition, SOC-rich fens and bogs occupy a much smaller proportion of the landscape in NE Greenland (∼3%) than in NE Siberia (∼20%). The contribution of deeper buried C-enriched material in the mineral soil horizons to the total SOC storage is lower in the NE Greenland site (∼13%) compared to the NE Siberian sites (∼24%–30%). Buried SOM seems generally more decomposed in NE Greenland than in NE Siberia, which we relate to different burial mechanisms prevailing in these regions.
|
|
| 14. |
- Peiris, Heshan, et al.
(författare)
-
A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes
- 2016
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D.
|
|
| 15. |
- Sandholm, Niina, et al.
(författare)
-
The genetic landscape of renal complications in type 1 diabetes
- 2017
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 28:2, s. 557-574
-
Tidskriftsartikel (refereegranskat)abstract
- Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4310-3). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associatedvariants.Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2310-5) and the risk of type 2 diabetes (P=6.1310-4) associated with the risk of diabetic kidney disease.Wealso found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1310-4). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0310-6), and pentose and glucuronate interconversions (P=3.0310-6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.
|
|
| 16. |
- Schewe, Jacob, et al.
(författare)
-
State-of-the-art global models underestimate impacts from climate extremes
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.
|
|
| 17. |
- Schütte, Bernd, et al.
(författare)
-
Slow electrons from intense laser-cluster interactions
- 2016
-
Ingår i: International Conference on Ultrafast Phenomena, UP 2016. - 9781943580187
-
Konferensbidrag (refereegranskat)abstract
- A surprisingly dominant contribution of slow electrons is observed following NIR strong-field ionization of clusters. This is consistent with highly efficient intra-Rydberg correlated electronic decay processes, from which the emission of low-energy electrons is expected.
|
|
| 18. |
|
|
| 19. |
- Simonov, Konstantin A., et al.
(författare)
-
From Graphene Nanoribbons on Cu(111) to Nanographene on Cu(110) : Critical Role of Substrate Structure in the Bottom-Up Fabrication Strategy
- 2015
-
Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 9:9, s. 8997-9011
-
Tidskriftsartikel (refereegranskat)abstract
- Bottom-up strategies can be effectively implemented for the fabrication of atomically precise graphene nanoribbons. Recently, using 10,10'-dibromo-9,9'-bianthracene (DBBA) as a molecular precursor to grow armchair nanoribbons on Au(111) and Cu(111), we have shown that substrate activity considerably affects the dynamics of ribbon formation, nonetheless without significant modifications in the growth mechanism. In this paper we compare the on-surface reaction pathways for DBBA molecules on Cu(111) and Cu(110). Evolution of both systems has been studied via a combination of core-level X-ray spectroscopies, scanning tunneling microscopy, and theoretical calculations. Experimental and theoretical results reveal a significant increase in reactivity for the open and anisotropic Cu(110) surface in comparison with the close-packed Cu(111). This increased reactivity results in a predominance of the molecular substrate interaction over the intermolecular one, which has a critical impact on the transformations of DBBA on Cu(110). Unlike DBBA on Cu(111), the Ullmann coupling cannot be realized for DBBA/Cu(110) and the growth of nanoribbons via this mechanism is blocked. Instead, annealing of DBBA on Cu(110) at 250 degrees C results in the formation of a new structure: quasi-zero-dimensional flat nanographenes. Each nanographene unit has dehydrogenated zigzag edges bonded to the underlying Cu rows and oriented with the hydrogen-terminated armchair edge parallel to the [1-10] direction. Strong bonding of nanographene to the substrate manifests itself in a high adsorption energy of -12.7 eV and significant charge transfer of 3.46e from the copper surface. Nanographene units coordinated with bromine adatoms are able to arrange in highly regular arrays potentially suitable for nanotemplating.
|
|
| 20. |
- Sun, Tiedong, et al.
(författare)
-
A multiscale analysis of DNA phase separation : from atomistic to mesoscale level
- 2019
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 47:11, s. 5550-5562
-
Tidskriftsartikel (refereegranskat)abstract
- DNA condensation and phase separation is of utmost importance for DNA packing in vivo with important applications in medicine, biotechnology and polymer physics. The presence of hexagonally ordered DNA is observed in virus capsids, sperm heads and in dinoflagellates. Rigorous modelling of this process in all-atom MD simulations is presently difficult to achieve due to size and time scale limitations. We used a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA phase separation induced by the three-valent cobalt(III)-hexammine (CoHex(3+)). Solvent-mediated effective potentials for a CG model of DNA were extracted from all-atom MD simulations. Simulations of several hundred 100-bp-long CG DNA oligonucleotides in the presence of explicit CoHex(3+) ions demonstrated aggregation to a liquid crystalline hexagonally ordered phase. Following further coarse-graining and extraction of effective potentials, we conducted modelling at mesoscale level. In agreement with electron microscopy observations, simulations of an 10.2-kblong DNA molecule showed phase separation to either a toroid or a fibre with distinct hexagonal DNA packing. The mechanism of toroid formation is analysed in detail. The approach used here is based only on the underlying all-atom force field and uses no adjustable parameters and may be generalised to modelling chromatin up to chromosome size.
|
|
| 21. |
- Sun, Tiedong, et al.
(författare)
-
All-Atom MD Simulation of DNA Condensation Using Ab lnitio Derived Force Field Parameters of Cobalt(III)-Hexammine
- 2017
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 121:33, s. 7761-7770
-
Tidskriftsartikel (refereegranskat)abstract
- It is well established that the presence of the trivalent cobalt(III)-hexammine cation (CoHex(3+)) at submillimolar concentrations leads to bundling (condensation) of double stranded DNA molecules, which is caused by DNA DNA attraction induced by the multivalent counterions. However, the detailed mechanism of this process is still not fully understood. Furthermore, in all-atom molecular dynamics (MD) simulations, spontaneous aggregation of several DNA oligonucleotides in the presence of CoHex(3+) has previously not been, demonstrated. In order to obtain a rigorous description of CoHex(3+)-nucleic acid interactions and CoHex(3+)-induced DNA condensation to be used in MD siniulations, we have derived optimized force field parameters of the CoHex(3+) ion. They were obtained from Car Parrinello molecular dynamics simulation of a single CoHex3+ ion in the presence of 126 water molecules. The new set,of force field parameters reproduces the experimentally known transition of DNA from B- to A-form; and qualitatively describes changes of DNA and RNA persistence lengths. We then carried out a 2 mu s long atomistic simulation of four DNA oligomers each consisting of 36 base pairs in the presence of CoHex(3+). We demonstrate that, in this system, DNA molecules display attractive interactions and aggregate into bundle-like structures. This behavior depends critically on the details of the CoHex(3+) interaction with DNA. A control simulation with a similar setup but in the presence of Mg2+ does not induce DNA DNA attraction, which is also in agreement with experiment.
|
|
| 22. |
- Wartenburger, Richard, et al.
(författare)
-
Evapotranspiration simulations in ISIMIP2a-Evaluation of spatio-temporal characteristics with a comprehensive ensemble of independent datasets
- 2018
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 13:7
-
Tidskriftsartikel (refereegranskat)abstract
- Actual land evapotranspiration (ET) is a key component of the global hydrological cycle and an essential variable determining the evolution of hydrological extreme events under different climate change scenarios. However, recently available ET products show persistent uncertainties that are impeding a precise attribution of human-induced climate change. Here, we aim at comparing a range of independent global monthly land ET estimates with historical model simulations from the global water, agriculture, and biomes sectors participating in the second phase of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2a). Among the independent estimates, we use the EartH2Observe Tier-1 dataset (E2O), two commonly used reanalyses, a pre-compiled ensemble product (LandFlux-EVAL), and an updated collection of recently published datasets that algorithmically derive ET from observations or observations-based estimates (diagnostic datasets). A cluster analysis is applied in order to identify spatio-temporal differences among all datasets and to thus identify factors that dominate overall uncertainties. The clustering is controlled by several factors including the model choice, the meteorological forcing used to drive the assessed models, the data category (models participating in the different sectors of ISIMIP2a, E2O models, diagnostic estimates, reanalysis-based estimates or composite products), the ET scheme, and the number of soil layers in the models. By using these factors to explain spatial and spatio-temporal variabilities in ET, we find that the model choice mostly dominates (24%-40% of variance explained), except for spatio-temporal patterns of total ET, where the forcing explains the largest fraction of the variance (29%). The most dominant clusters of datasets are further compared with individual diagnostic and reanalysis-based estimates to assess their representation of selected heat waves and droughts in the Great Plains, Central Europe and western Russia. Although most of the ET estimates capture these extreme events, the generally large spread among the entire ensemble indicates substantial uncertainties.
|
|
| 23. |
- Yeung, Andy Wai Kan, et al.
(författare)
-
Resveratrol, a popular dietary supplement for human and animal health : Quantitative research literature analysis - a review
- 2019
-
Ingår i: Animal Science Papers and Reports. - : POLSKA AKAD NAUK, INST GENETYKI I HODOWLI ZWIERZAT. - 0860-4037. ; 37:2, s. 103-118
-
Forskningsöversikt (refereegranskat)abstract
- Resveratrol is a stilbene-type bioactive molecule with a broad spectrum of reported biological effects. In this sense, the current work provides a comprehensive literature analysis on resveratrol, representing a highly-researched commercially available dietary ingredient. Bibliometric data were identified by means of the search string TOPIC=("resveratrol*") and analyzed with the VOSviewer software, which yielded 17,561 publications extracted from the Web of Science Core Collection electronic database. 'I'he ratio of original articles to reviews was 9.5:1. More than half of the overall manuscripts have been published since 2013. Major contributing countries were USA, China, Italy, South Korea, and Spain. Most of the publications appeared in journals specialized in biochemistry and molecular biology, pharmacology and pharmacy, food science technology, cell biology, or oncology. The phytochemicals or phytochemical classes that were frequently mentioned in the keywords of analyzed publications included, in descending order: resveratrol, trans-resveratrol, polyphenols, flavonoids, quercetin, stilbenes, curcumin, piceatannol, cis-resveratrol, and anthocyanins.
|
|
| 24. |
- Zhang, R. Y., et al.
(författare)
-
Lysozyme's lectin-like characteristics facilitates its immune defense function
- 2017
-
Ingår i: Quarterly Reviews of Biophysics. - : Cambridge University Press (CUP). - 0033-5835 .- 1469-8994. ; 50, s. 1-12
-
Forskningsöversikt (refereegranskat)abstract
- Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.
|
|
