| 1. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Aad, G., et al.
(författare)
-
- 2012
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 5. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 6. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 7. |
- Romanelli, F, et al.
(författare)
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Overview of the JET results
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
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Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 8. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 9. |
- Connolly, Stuart J, et al.
(författare)
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Dronedarone in High-Risk Permanent Atrial Fibrillation
- 2011
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:24, s. 2268-2276
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Tidskriftsartikel (refereegranskat)abstract
- Background Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular anti-arrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. Methods We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. Results After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). Conclusions Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients.
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| 10. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 11. |
- Aaltonen, T., et al.
(författare)
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Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
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Tidskriftsartikel (refereegranskat)abstract
- We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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| 12. |
- Crosby, Jacy, et al.
(författare)
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Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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| 13. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 14. |
- Gorlova, Olga, et al.
(författare)
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Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (IcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and autoantibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
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| 15. |
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| 16. |
- Mayes, Maureen D, et al.
(författare)
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Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
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Tidskriftsartikel (refereegranskat)abstract
- In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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| 17. |
- Pienkowski, Martin, et al.
(författare)
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A review of hyperacusis and future directions : part II. Measurement, mechanisms, and treatment.
- 2014
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Ingår i: American Journal of Audiology. - : American Speech-Language-Hearing Association. - 1059-0889 .- 1558-9137. ; 23:4, s. 420-436
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: Hyperacusis can be extremely debilitating, and at present, there is no cure. In this detailed review of the field, we consolidate present knowledge in the hope of facilitating future research.METHOD: We review and reference the literature on hyperacusis and related areas. This is the 2nd of a 2-part review.RESULTS: Hyperacusis encompasses a wide range of reactions to sounds, which can be grouped into the categories of excessive loudness, annoyance, fear, and pain. Reasonable approaches to assessing the different forms of hyperacusis are emerging, including brain-imaging studies. Researchers are only beginning to understand the many mechanisms at play, and valid animal models are still evolving. There are many counseling and sound-therapy approaches that some patients find helpful, but well-controlled studies are needed to measure their long-term efficacy and to test new approaches.CONCLUSIONS: Hyperacusis can make life difficult in this increasingly noisy world, forcing sufferers to dramatically alter their work and social habits. We believe this is an opportune time to explore approaches to better understand and treat hyperacusis.
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| 18. |
- Radstake, Timothy R. D. J., et al.
(författare)
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Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 71-426
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Tidskriftsartikel (refereegranskat)abstract
- Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.
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| 19. |
- Shimokawa, Noriaki, et al.
(författare)
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CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice
- 2010
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Ingår i: EMBO Journal. - : European Molecular Biology Organization. - 0261-4189 .- 1460-2075. ; 29:14, s. 2421-2432
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive investigations of Cbl-interacting protein of 85 kDa (CIN85) in receptor trafficking and cytoskeletal dynamics, little is known about its functions in vivo. Here, we report the study of a mouse deficient of the two CIN85 isoforms expressed in the central nervous system, exposing a function of CIN85 in dopamine receptor endocytosis. Mice lacking CIN85 exon 2 (CIN85(Deltaex2)) show hyperactivity phenotypes, characterized by increased physical activity and exploratory behaviour. Interestingly, CIN85(Deltaex2) animals display abnormally high levels of dopamine and D2 dopamine receptors (D2DRs) in the striatum, an important centre for the coordination of animal behaviour. Importantly, CIN85 localizes to the post-synaptic compartment of striatal neurons in which it co-clusters with D2DRs. Moreover, it interacts with endocytic regulators such as dynamin and endophilins in the striatum. Absence of striatal CIN85 causes insufficient complex formation of endophilins with D2DRs in the striatum and ultimately decreased D2DR endocytosis in striatal neurons in response to dopamine stimulation. These findings indicate an important function of CIN85 in the regulation of dopamine receptor functions and provide a molecular explanation for the hyperactive behaviour of CIN85(Deltaex2) mice.
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| 20. |
- Tyler, Richard S, et al.
(författare)
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A review of hyperacusis and future directions : part I. Definitions and manifestations.
- 2014
-
Ingår i: American Journal of Audiology. - : American Speech-Language-Hearing Association. - 1059-0889 .- 1558-9137. ; 23:4, s. 402-19
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: Hyperacusis can be extremely debilitating, and at present, there is no cure. We provide an overview of the field, and possible related areas, in the hope of facilitating future research.METHOD: We review and reference literature on hyperacusis and related areas. We have divided the review into 2 articles. In Part I, we discuss definitions, epidemiology, different etiologies and subgroups, and how hyperacusis affects people. In Part II, we review measurements, models, mechanisms, and treatments, and we finish with some suggestions for further research.RESULTS: Hyperacusis encompasses a wide range of reactions to sound, which can be grouped into the categories of excessive loudness, annoyance, fear, and pain. Many different causes have been proposed, and it will be important to appreciate and quantify different subgroups. Reasonable approaches to assessing the different forms of hyperacusis are emerging, including psychoacoustical measures, questionnaires, and brain imaging.CONCLUSIONS: Hyperacusis can make life difficult for many, forcing sufferers to dramatically alter their work and social habits. We believe this is an opportune time to explore approaches to better understand and treat hyperacusis.
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| 21. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 22. |
- Aristov, Victor Yu., et al.
(författare)
-
Graphene Synthesis on Cubic SiC/Si Wafers. Perspectives for Mass Production of Graphene-Based Electronic Devices
- 2010
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 10:3, s. 992-995
-
Tidskriftsartikel (refereegranskat)abstract
- The outstanding properties of graphene, a single graphite layer, render it a top candidate for substituting silicon in future electronic devices, The so far exploited synthesis approaches, however, require conditions typically achieved in specialized laboratories and result in graphene sheets whose electronic properties are often altered by interactions with substrate materials. The development of graphene-based technologies requires an economical fabrication method compatible with mass production. Here we demonstrate for the fist Lime the feasibility of graphene synthesis on commercially available cubic SiC/Si substrates of >300 mm in diameter, which result in graphene flakes electronically decoupled from the substrate. After optimization of the preparation procedure, the proposed synthesis method can represent a further big step toward graphene-based electronic technologies.
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| 23. |
- Berg, Martin, et al.
(författare)
-
InAs nanowire MOSFETs in three-transistor configurations: single balanced RF down-conversion mixers.
- 2014
-
Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 25:48
-
Tidskriftsartikel (refereegranskat)abstract
- Integration of III-V semiconductors on Si substrates allows for the realization of high-performance, low power III-V electronics on the Si-platform. In this work, we demonstrate the implementation of single balanced down-conversion mixer circuits, fabricated using vertically aligned InAs nanowire devices on Si. A thin, highly doped InAs buffer layer has been introduced to reduce the access resistance and serve as a bottom electrode. Low-frequency voltage conversion gain is measured up to 7 dB for a supply voltage of 1.5V. Operation of these mixers extends into the GHz regime with a [Formula: see text] cut-off frequency of 2 GHz, limited by the optical lithography system used. The circuit dc power consumption is measured at 3.9 mW.
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| 24. |
- Buchholt, Kristina, et al.
(författare)
-
Growth and characterization of epitaxial Ti3GeC2 thin films on 4H-SiC(0001)
- 2012
-
Ingår i: Journal of Crystal Growth. - : Elsevier. - 0022-0248 .- 1873-5002. ; 343:1, s. 133-137
-
Tidskriftsartikel (refereegranskat)abstract
- Epitaxial Ti3GeC2 thin films were deposited on 4 degrees off-cut 4H-SiC(0001) using magnetron sputtering from high purity Ti, C, and Ge targets. Scanning electron microscopy and helium ion microscopy show that the Ti3GeC2 films grow by lateral step-flow with {11 (2) over bar0} faceting on the SiC surface. Using elastic recoil detection analysis, atomic force microscopy, and X-Ray diffraction the films were found to be substoichiometric in Ge with the presence of small Ge particles at the surface of the film.
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| 25. |
- Buchholt, Kristina, et al.
(författare)
-
Ohmic contact properties of magnetron sputtered Ti3SiC2 on n- and p-type 4H-silicon carbide
- 2011
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 98:4, s. 042108-
-
Tidskriftsartikel (refereegranskat)abstract
- Epitaxial Ti3SiC2 (0001) thin film contacts were grown on doped 4H-SiC (0001) using magnetron sputtering in an ultra high vacuum system. The specific contact resistance was investigated using linear transmission line measurements. Rapid thermal annealing at 950 degrees C for 1 min of as-deposited films yielded ohmic contacts to n-type SiC with contact resistances in the order of 10(-4) Omega cm(2). Transmission electron microscopy shows that the interface between Ti3SiC2 and n-type SiC is atomically sharp with evidence of interfacial ordering after annealing. (c) 2011 American Institute of Physics.
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| 26. |
- Chen, Jun, et al.
(författare)
-
Clinal Variation at Phenology-Related Genes in Spruce : Parallel Evolution in FTL2 and Gigantea?
- 2014
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 197:3, s. 1025-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Parallel clines in different species, or in different geographical regions of the same species, are an important source of information on the genetic basis of local adaptation. We recently detected latitudinal clines in SNPs frequencies and gene expression of candidate genes for growth cessation in Scandinavian populations of Norway spruce (Picea abies). Here we test whether the same clines are also present in Siberian spruce (P. obovata), a close relative of Norway spruce with a different Quaternary history. We sequenced nine candidate genes and 27 control loci and genotyped 14 SSR loci in six populations of P. obovata located along the Yenisei river from latitude 56 N to latitude 67 N. In contrast to Scandinavian Norway spruce that both departs from the standard neutral model (SNM) and shows a clear population structure, Siberian spruce populations along the Yenisei do not depart from the SNM and are genetically unstructured. Nonetheless, as in Norway spruce, growth cessation is significantly clinal. Polymorphisms in photoperiodic (FTL2) and circadian clock (Gigantea, GI, PRR3) genes also show significant clinal variation and/or evidence of local selection. In GI, one of the variants is the same as in Norway spruce. Finally, a strong cline in gene expression is observed for FTL2, but not for GI. These results, together with recent physiological studies, confirm the key role played by FTL2 and circadian clock genes in the control of growth cessation in spruce species and suggest the presence of parallel adaptation in these two species.
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| 27. |
- Chen, Jun
(författare)
-
Conifer Evolution, from Demography and Local Adaptation to Evolutionary Rates : Examples from the Picea genus
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Evolutionary process can be inferred at three different levels: the species level, the population level and the molecular level. In this thesis, I applied approaches at these three levels and aimed to get a comprehensive picture of conifer evolution, from speciation and demography to geographic variation and local adaptation, and then to the molecular evolution of proteins and small regulatory RNAs.Spruce species have been observed to possess a large number of trans-species shared polymorphisms. Using an “Isolation with migration” model, we found that the large effective population size of spruce retained these shared polymorphisms, inheriting them from the common ancestor. Post-divergence gene flow only existed between Picea abies and P. glauca, and between P. wilsonii and P. schrenkiana. The combination of Tajima’s D and Fay & Wu’s H at most of loci suggested an ancient and severe bottleneck for most species except P. breweriana.Furthermore, I investigated the effect of local selection in two parallel clines, which is one of the major forces that can cause divergence or even speciation. The timing of bud set and growth cessation was found correlated with latitude in populations of P. abies and P. obovata. Using allele frequency spectrum analyses we identified three genes under local selection in both species including two circadian-clock genes GI and PRR7, and one photoperiodic gene FTL2. This indicated that parallel evolution could occur through groups of genes within related pathways. Clinal variation at expression level provided stronger evidence of selection in FTL2, which has previously been associated with bud set in P. abies.Finally we focused on the molecular evolution of mRNA and small regulatory RNAs in P. abies. With the help of Next-Generation sequencing, we have achieved in spruce the first de novel assembly of the needle transcriptome and a preliminary characterization of sRNA populations. Along with features common in plants, spruce also exhibited novelties in many aspects including lower substitution rate and protein evolutionary rate, dominance of 21-nt sRNA, and a large proportion of TIR-NBS-LRR genes as sRNA sources and targets.
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| 28. |
- Chen, Jun, et al.
(författare)
-
Disentangling the Roles of History and Local Selection in Shaping Clinal Variation of Allele Frequencies and Gene Expression in Norway Spruce (Picea abies)
- 2012
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 191:3, s. 865-881
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic basis of local adaptation is challenging due to the subtle balance among conflicting evolutionary forces that are involved in its establishment and maintenance. One system with which to tease apart these difficulties is clines in adaptive characters. Here we analyzed genetic and phenotypic variation in bud set, a highly heritable and adaptive trait, among 18 populations of Norway spruce (Picea abies), arrayed along a latitudinal gradient ranging from 47°N to 68°N. We confirmed that variation in bud set is strongly clinal, using a subset of five populations. Genotypes for 137 single-nucleotide polymorphisms (SNPs) chosen from 18 candidate genes putatively affecting bud set and 308 control SNPs chosen from 264 random genes were analyzed for patterns of genetic structure and correlation to environment. Population genetic structure was low (F(ST) = 0.05), but latitudinal patterns were apparent among Scandinavian populations. Hence, part of the observed clinal variation should be attributable to population demography. Conditional on patterns of genetic structure, there was enrichment of SNPs within candidate genes for correlations with latitude. Twenty-nine SNPs were also outliers with respect to F(ST). The enrichment for clinal variation at SNPs within candidate genes (i.e., SNPs in PaGI, PaPhyP, PaPhyN, PaPRR7, and PaFTL2) indicated that local selection in the 18 populations, and/or selection in the ancestral populations from which they were recently derived, shaped the observed cline. Validation of these genes using expression studies also revealed that PaFTL2 expression is significantly associated with latitude, thereby confirming the central role played by this gene in the control of phenology in plants.
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| 29. |
- Chen, Jun, et al.
(författare)
-
Sequencing of the needle transcriptome from Norway spruce (Picea abies Karst L.) reveals lower substitution rates, but similar selective constraints in gymnosperms compared to angiosperms
- 2012
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13, s. 589-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: A detailed knowledge about which genes are expressed in which tissues and at which developmental stage is important for understanding both the function of genes and their evolution. For the vast majority of species, transcriptomes are still largely uncharacterized and even in those where substantial information is available it is often in the form of partially sequenced transcriptomes. With the development of next generation sequencing, a single experiment can now give both a snap-shot of the transcribed part of a species genome and simultaneously estimate levels of gene expression.Results: mRNA from actively growing needles of Norway spruce (Picea abies) was sequenced using next generation sequencing technology. In total, close to 70 million fragments with a length of 76 bp were sequenced resulting in 5 Gbp of raw data. A de novo assembly of these reads were, together with publicly available expressed sequence tag (EST) data from Norway spruce, used to create a reference transcriptome. Of the 38,419 PUTs (putative unique transcripts) longer than 150 bp in this reference assembly, 59% show similarity to ESTs from other spruce species and of the remaining PUTs, 3,704 show similarity to protein sequences from other plant species, leaving 4,167 PUTs with limited similarity to currently available plant proteins. By predicting coding frames and comparing not only the Norway spruce PUTs, but also PUTs from the close relatives Picea glauca and Picea sitchensis to both Pinus taeda and Taxus mairei, we obtained estimates of synonymous and non-synonymous divergence among conifer species. In addition, we detected close to 15,000 SNPs of high quality and estimated gene expression difference between samples collected during dark and light conditions.Conclusions: Our study yielded a large number of single nucleotide polymorphisms as well as estimates of gene expression on transcriptome scale. In agreement with a recent study we find that the synonymous substitution rate per year (0.6 × 10-09 and 1.1 × 10-09) is an order of magnitude smaller than values reported for angiosperm herbs, but if one takes generation time in to account, most of this difference disappear. The estimates of the non-synonymous over the synonymous divergence (dN/dS ratio) reported here is in general much lower than 1 and only a few genes showed a ratio larger than 1.
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| 30. |
- Eklund, Per, et al.
(författare)
-
Discovery of the Ternary Nanolaminated Compound Nb2GeC by a Systematic Theoretical-Experimental Approach
- 2012
-
Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 109:3, s. 035502-
-
Tidskriftsartikel (refereegranskat)abstract
- Since the advent of theoretical materials science some 60 years ago, there has been a drive to predict and design new materials in silicio. Mathematical optimization procedures to determine phase stability can be generally applicable to complex ternary or higher-order materials systems where the phase diagrams of the binary constituents are sufficiently known. Here, we employ a simplex-optimization procedure to predict new compounds in the ternary Nb-Ge-C system. Our theoretical results show that the hypothetical Nb2GeC is stable, and excludes all reasonably conceivable competing hypothetical phases. We verify the existence of the Nb2GeC phase by thin film synthesis using magnetron sputtering. This hexagonal nanolaminated phase has a and c lattice parameters of similar to 3.24 angstrom and 12.82 angstrom.
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| 31. |
- Furlan, Andrej, et al.
(författare)
-
Crystallization characteristics and chemical bonding properties of nickel carbide thin film nanocomposites
- 2014
-
Ingår i: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 26:41
-
Tidskriftsartikel (refereegranskat)abstract
- The crystal structure and chemical bonding of magnetron-sputtering deposited nickel carbide Ni1−xCx (0.05 ⩽ x⩽0.62) thin films have been investigated by high-resolution x-ray diffraction, transmission electron microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, and soft x-ray absorption spectroscopy. By using x-ray as well as electron diffraction, we found carbon-containing hcp-Ni (hcp-NiCy phase), instead of the expected rhombohedral-Ni3C. At low carbon content (4.9 at%), the thin film consists of hcp-NiCy nanocrystallites mixed with a smaller amount of fcc-NiCx. The average grain size is about 10–20 nm. With the increase of carbon content to 16.3 at%, the film contains single-phase hcp-NiCy nanocrystallites with expanded lattice parameters. With a further increase of carbon content to 38 at%, and 62 at%, the films transform to x-ray amorphous materials with hcp-NiCy and fcc-NiCx nanodomain structures in an amorphous carbon-rich matrix. Raman spectra of carbon indicate dominant sp2 hybridization, consistent with photoelectron spectra that show a decreasing amount of C–Ni phase with increasing carbon content. The Ni 3d–C 2p hybridization in the hexagonal structure gives rise to the salient double-peak structure in Ni 2p soft x-ray absorption spectra at 16.3 at% that changes with carbon content. We also show that the resistivity is not only governed by the amount of carbon, but increases by more than a factor of two when the samples transform from crystalline to amorphous.
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| 32. |
- Halim, Joseph, 1985-
(författare)
-
Synthesis and Characterization of 2D Nanocrystals and Thin Films of Transition Metal Carbides (MXenes)
- 2014
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Two dimensional (2D) materials have received growing interest because of their unique properties compared to their bulk counterparts. Graphene is the archetype 2D solid, but other materials beyond graphene, such as MoS2 and BN have become potential candidates for several applications. Recently, a new family of 2D materials of early transition metal carbides and carbonitrides (Ti2CTx, Ti3C2Tx, Ti3CNTx, Ta4C3Tx, and more), labelled MXenes, has been discovered, where T stands for the surface-terminating groups.Before the present work, MXenes had only been synthesized in the form of exfoliated and delaminated powders, which is not suitable for electronic applications. In this thesis, I demonstrate the synthesis of MXenes as epitaxial thin films, a more suitable form for electronic and photonic applications. Results show that 2D epitaxial Ti3C2Tx films - produced by HF and NH4HF2 etching of magnetron sputter-grown Ti3AlC2 - exhibit metallic conductive behaviour down to 100 K and are 90% transparent to light in the visible-infrared range. The results from this work may open the door for MXenes as potential candidates for transparent conductive electrodes as well as in electronic, photonic and sensing applications.MXenes have been shown to intercalate cations and molecules between their layers that in turn can alter the surface termination groups. There is therefore a need to study the surface chemistries of synthetized MXenes to be able to study the effect of intercalation as well as altering the surface termination groups on the electronic structure and chemical states of the elements present in MXene layers. X-ray Photoelectron Spectroscopy (XPS) in-depth characterization was used to investigate surface chemistries of Ti3C2Tx and Ti2CTx. This thesis includes the discussion of the effect of Ar+ sputtering and the number of layers on the surface chemistry of MXenes. This study serves as a baseline for chemical modification and tailoring of the surface chemistry groups to potential uses and applications.New MXene phases, Nb2CTx and V2CTx, are shown in this thesis to be produced from HF chemical etching of Nb2AlC and V2AlC powders. Characterization of the produced MXenes was carried out using Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Transmission Electron Microscope (TEM) and XPS. Nb2CTx and V2CTx showed promising performance as electrodes for Li-ion batteries.In this thesis, electrochemical etching was used in an attempt to produce 2D metal carbides (MXene) from their ternary metal carbides, Ti3SiC2, Ti3AlC2 and Ti2AlC MAX phases. MAX phases in the form of highly dense bulk produced by Hot Isostatic Press. Several etching solutions were used such as HF, NaCl and HCl. Unlike the HF chemical etching of MAX phases, which results in MXenes, the electrochemical etching resulted in Carbide Derived Carbon (CDC). Here, I show the characterization of the produced CDC using several techniques such as XRD, TEM, Raman spectroscopy, and XPS. Electrochemical characterization was performed in the form of cyclic voltammetry, which sheds light on the etching mechanism.
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| 33. |
- Huang, Hui-Run, et al.
(författare)
-
Flowering time and transcriptome variation in Capsella bursa-pastoris (Brassicaceae)
- 2012
-
Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 194:3, s. 676-689
-
Forskningsöversikt (refereegranskat)abstract
- Flowering is a major developmental transition and its timing in relation to environmental conditions is of crucial importance to plant fitness. Understanding the genetic basis of flowering time variation is important to determining how plants adapt locally. Here, we investigated flowering time variation of Capsella bursa-pastoris collected from different latitudes in China. We also used a digital gene expression ( DGE) system to generate partial gene expression profiles for 12 selected samples. We found that flowering time was highly variable and most strongly correlated with day length and winter temperature. Significant differences in gene expression between early-and late-flowering samples were detected for 72 candidate genes for flowering time. Genes related to circadian rhythms were significantly overrepresented among the differentially expressed genes. Our data suggest that circadian rhythms and circadian clock genes play an important role in the evolution of flowering time, and C. bursa-pastoris plants exhibit expression differences for candidate genes likely to affect flowering time across the broad range of environments they face in China.
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| 34. |
- Lange, Leslie A, et al.
(författare)
-
Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
- 2014
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
-
Tidskriftsartikel (refereegranskat)abstract
- Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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| 35. |
- Li, Yuan, et al.
(författare)
-
Demographic histories of four spruce (Picea) species of the Qinghai-Tibetan Plateau and neighboring areas inferred from multiple nuclear loci
- 2010
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 27:5, s. 1001-1014
-
Tidskriftsartikel (refereegranskat)abstract
- Nucleotide variation at 12 to 16 nuclear loci was studied in three spruce species from the Qinghai-Tibetan Plateau (QTP), Picea likiangensis, P. wilsonii and P. purpurea, and one species from the Tian Shan mountain range, P. schrenkiana. Silent nucleotide diversity was limited in P. schrenkiana and high in the three species from the QTP, with values higher than in boreal spruce species, despite their much more restricted distributions compared to that of the boreal species. In contrast to European boreal species that have experienced severe bottlenecks in the past, coalescent-based analysis suggests that DNA polymorphism in the species from the QTP and adjacent areas is compatible with the standard neutral model (P. likiangensis, P. wilsonii, P. schrenkiana) or with population growth (P. purpurea). In order to test if P. purpurea is a diploid hybrid of P. likiangensis and P. wilsonii, we used a combination of approaches, including model based inference of population structure, Isolation-with-Migration models and recent theoretical results on the effect of introgression on the geographic distribution of diversity. In contrast to the three other species, each of which was predominantly assigned to a single cluster in the Structure analysis, P. purpurea individuals were scattered over the three main clusters and not, as we had expected, confined to the P. likiangensis and P. wilsonii clusters. Furthermore the contribution of P. schrenkiana was by far the largest one. In agreement with this, the divergence between P. purpurea and P. schrenkiana was lower than the divergence of either P. likiangensis or P. wilsonii from P. schrenkiana. These results, together with previous ones showing that P. purpurea and P. wilsonii share the same haplotypes at both chloroplast and mitochondrial markers, suggest that P. purpurea has a complex origin, possibly involving additional species.
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| 36. |
- Lind, Mårten, et al.
(författare)
-
A Picea abies Linkage Map Based on SNP Markers Identifies QTLs for Four Aspects of Resistance to Heterobasidion parviporum Infection
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7, s. e101049-
-
Tidskriftsartikel (refereegranskat)abstract
- A consensus linkage map of Picea abies, an economically important conifer, was constructed based on the segregation of 686 SNP markers in a F-1 progeny population consisting of 247 individuals. The total length of 1889.2 cM covered 96.5% of the estimated genome length and comprised 12 large linkage groups, corresponding to the number of haploid P. abies chromosomes. The sizes of the groups (from 5.9 to 9.9% of the total map length) correlated well with previous estimates of chromosome sizes (from 5.8 to 10.8% of total genome size). Any locus in the genome has a 97% probability to be within 10 cM from a mapped marker, which makes the map suited for QTL mapping. Infecting the progeny trees with the root rot pathogen Heterobasidion parviporum allowed for mapping of four different resistance traits: lesion length at the inoculation site, fungal spread within the sapwood, exclusion of the pathogen from the host after initial infection, and ability to prevent the infection from establishing at all. These four traits were associated with two, four, four and three QTL regions respectively of which none overlapped between the traits. Each QTL explained between 4.6 and 10.1% of the respective traits phenotypic variation. Although the QTL regions contain many more genes than the ones represented by the SNP markers, at least four markers within the confidence intervals originated from genes with known function in conifer defence; a leucoanthocyanidine reductase, which has previously been shown to upregulate during H. parviporum infection, and three intermediates of the lignification process; a hydroxycinnamoyl CoA shikimate/quinate hydroxycinnamoyltransferase, a 4-coumarate CoA ligase, and a R2R3-MYB transcription factor.
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| 37. |
- Litvak, M.L., et al.
(författare)
-
Local variations of bulk hydrogen and chlorine-equivalent neutron absorption content measured at the contact between the Sheepbed and Gillespie Lake units in Yellowknife Bay, Gale Crater, using the DAN instrument onboard Curiosity
- 2014
-
Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:6, s. 1259-1275
-
Tidskriftsartikel (refereegranskat)abstract
- Data gathered with the Dynamic Albedo of Neutron (DAN) instrument onboard rover Curiosity were analyzed for variations in subsurface neutron flux and tested for possible correlation with local geological context. A special DAN observation campaign was executed, in which 18 adjacent DAN active measurements were acquired every 0.75–1.0 m to search for the variations of subsurface hydrogen content along a 15 m traverse across geologic contacts between the Sheepbed and Gillespie Lake members of the Yellowknife Bay formation. It was found that several subunits in Sheepbed and Gillespie Lake could be characterized with different depth distributions of water-equivalent hydrogen (WEH) and different chlorine-equivalent abundance responsible for the distribution of neutron absorption elements. The variations of the average WEH at the top 60 cm of the subsurface are estimated at up to 2–3%. Chlorine-equivalent neutron absorption abundances ranged within 0.8–1.5%. The largest difference in WEH and chlorine-equivalent neutron absorption distribution is found between Sheepbed and Gillespie Lake.
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| 38. |
- Lu, Jun, et al.
(författare)
-
Ebsulfur is a benzisothiazolone cytocidal inhibitor targeting the trypanothione reductase of Trypanosoma brucei
- 2013
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:38, s. 27456-27468
-
Tidskriftsartikel (refereegranskat)abstract
- Trypanosoma brucei is the causing agent of African trypanosomiasis. These parasites possess a unique thiol redox system required for DNA synthesis and defense against oxidative stress. It includes trypanothione and trypanothione reductase (TryR) instead of the thioredoxin and glutaredoxin systems of mammalian hosts. Here, we show that the benzisothiazolone compound ebsulfur (EbS), a sulfur analogue of ebselen, is a potent inhibitor of T. brucei growth with a favorable selectivity index over mammalian cells. EbS inhibited the TryR activity and decreased non-protein thiol levels in cultured parasites. The inhibition of TryR by EbS was irreversible and NADPH-dependent. EbS formed a complex with TryR and caused oxidation and inactivation of the enzyme. EbS was more toxic for T. brucei than for Trypanosoma cruzi, probably due to lower levels of TryR and trypanothione in T. brucei. Furthermore, inhibition of TryR produced high intracellular reactive oxygen species. Hydrogen peroxide, known to be constitutively high in T. brucei, enhanced the EbS inhibition of TryR. The elevation of reactive oxygen species production in parasites caused by EbS induced a programmed cell death. Soluble EbS analogues were synthesized and cured T. brucei brucei infection in mice when used together with nifurtimox. Altogether, EbS and EbS analogues disrupt the trypanothione system, hampering the defense against oxidative stress. Thus, EbS is a promising lead for development of drugs against African trypanosomiasis.
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| 39. |
- Lu, Xin, et al.
(författare)
-
The sensitivity of respondent-driven sampling
- 2012
-
Ingår i: Journal of the Royal Statistical Society. - 0964-1998 .- 1467-985X. ; 175:1, s. 191-216
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Tidskriftsartikel (refereegranskat)abstract
- Researchers in many scientific fields make inferences from individuals to larger groups. For many groups, however, there is no list of members from which to draw a random sample. Respondent-driven sampling (RDS) is a relatively new sampling methodology that circumvents this difficulty by using the social networks of the groups under study. The RDS method has been shown to provide unbiased estimates of population proportions given certain conditions. The method is now widely used in human immunodeficiency virus related studies among high risk populations globally. We test the RDS methodology by simulating RDS studies on the social networks of a large Lesbian, gay, bisexual and transgender Web community. The robustness of the RDS method is tested by violating, one by one, the conditions under which the method provides unbiased estimates. Simulations indicate that the bias is large if networks are directed or respondents choose to invite people on the basis of characteristics that are correlated with the study outcomes. The bias and variance increase if participants invite close as opposed to more distant friends whereas sampling in denser networks sharply reduces variance. However, the RDS method shows strong resistance to sampling without replacement, low response rates and certain errors in the participants reporting of their network sizes, as well as the selection criteria of seeds. The effects of network structure and the number of seeds and coupons are also discussed.
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| 40. |
- Ma, Tao, et al.
(författare)
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Genomic insights into salt adaptation in a desert poplar
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2797-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.
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| 41. |
- Magnuson, Martin, 1965-, et al.
(författare)
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Electronic Structure and Chemical Bonding of AmorphousChromium Carbide Thin Films
- 2012
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Ingår i: Journal of Physics. - IOP Publishing : IOP Publishing. - 0953-8984 .- 1361-648X. ; 24, s. 225004-
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Tidskriftsartikel (refereegranskat)abstract
- The microstructure, electronic structure, and chemical bonding of chromium carbidethin films with different carbon contents have been investigated with high-resolutiontransmission electron microscopy, electron energy loss spectroscopy and soft x-rayabsorption-emission spectroscopies. Most of the films can be described as amorphousnanocomposites with non-crystalline CrCx in an amorphous carbon matrix. At highcarbon contents, graphene-like structures are formed in the amorphous carbon matrix.At 47 at% carbon content, randomly oriented nanocrystallites are formed creating acomplex microstructure of three components. The soft x-ray absorption-emissionstudy shows additional peak structures exhibiting non-octahedral coordination andbonding.
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| 42. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 43. |
- Persson, Karl-Magnus, et al.
(författare)
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Extrinsic and Intrinsic Performance of Vertical InAs Nanowire MOSFETs on Si Substrates
- 2013
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Ingår i: IEEE Transactions on Electron Devices. - 0018-9383. ; 60:9, s. 2761-2767
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents DC and RF characterization as well as modeling of vertical InAs nanowire MOSFETs with LG = 200 nm and Al2O3/HfO2 high-κ dielectric. Measurements at VDS = 0.5 V show that high transconductance (gm = 1.37 mS/μm), high drive current (IDS = 1.34 mA/μm), and low on-resistance (RON = 287 Ωμm) can be realized using vertical InAs nanowires on Si substrates. By measuring the 1/f-noise, the gate area normalized gate voltage noise spectral density, SVG·LG·WG, is determined to be lowered one order of magnitude compared to similar devices with a high-κ film consisting of HfO2 only. Additionally, with a virtual source model we are able to determine the intrinsic transport properties. These devices (LG = 200 nm) show a high injection velocity (vinj = 1.7·107 cm/s) with a performance degradation for array FETs predominantly due to an increase in series resistance.
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| 44. |
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| 45. |
- Petruhins, Andrejs, et al.
(författare)
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Phase stability of Crn+1GaCn MAX phases from first principles and Cr2GaC thin-film synthesis using magnetron sputtering from elemental targets
- 2013
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Ingår i: Physica Status Solidi. Rapid Research Letters. - : Wiley-VCH Verlag. - 1862-6254 .- 1862-6270. ; 7:11, s. 971-974
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Tidskriftsartikel (refereegranskat)abstract
- Ab-initio calculations have been used to investigate the phase stability and magnetic state of Crn+ 1GaCn MAX phase. Cr2GaC (n = 1) was predicted to be stable, with a ground state corresponding to an antiferromagnetic spin configuration. Thin-film synthesis by magnetron sputtering from elemental targets, including liquid Ga, shows the formation of Cr2GaC, previously only attained from bulk synthesis methods. The films were deposited at 650 degrees C on MgO(111) substrates. X-ray diffraction and high-resolution transmission electron microscopy show epitaxial growth of (000) MAX phase.
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| 46. |
- Renno, N.O., et al.
(författare)
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Ground-atmosphere interactions at Gale
- 2013
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Konferensbidrag (refereegranskat)abstract
- We analyze variations in environmental parameters and regolith properties along Curiosity’s track to determine the possible causes of an abrupt change in the thermal properties of the ground and the atmosphere observed around Sol 120, as the rover transitioned from an area of sandy soil (Rocknest) to an area of fractured bedrock terrain (Yellowknife). Curiosity is instrumented with the Rover Environmental Monitoring Station (REMS) and the Dynamic Albedo of Neutrons (DAN) sensors to measure the air temperature, the ground temperature, and the hydrogen content of the shallow subsurface along Curiosity’s track. Analysis of the REMS data is used to estimate the regolith’s heat budget. This analysis suggests that the abrupt decrease in the ground and atmosphere temperature and the difference between ground and air temperatures observed around Sol 120 is likely caused by an increase in the soil thermal inertia. The changes in thermal inertia have been known for some time so confirming this by the REMS package provides ground truthing. A new unexpected finding is that the regolith water content, as indicated by DAN’s detection of hydrogen content, is higher in the Yellowknife soil. Another interesting finding at this site are the holes and other signs of recent geological activity in the area of fractured terrain that may reflect large volumetric variations and facilitate gas exchange between the ground and atmosphere. Near-surface volumetric changes in soil and bedrock could reflect changes in the volume of subsurface H2O, or in the partitioning of H2O among its three phases. Volume increases could also result from salt crystal growth in rock pores and soil pores associated with the adsorption of water vapor. Crystallization in pores is a significant weathering process on Earth; it could well be active on Mars. Salts also inhibits the exchange of moisture between the ground and the atmosphere, and cements the soils of arid places such as in the McMurdo Dry Valleys in Antarctica. Indeed, salts might be responsible for the ubiquitous martian duricrust. More importantly, salt crusts have the potential to create pockets of wet regolith in the shallow martian subsurface that could be habitable. A better understanding of ground-atmosphere interactions has the potential to shed new light into aqueous processes in the shallow martian subsurface.
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| 47. |
- Skedung, Lisa, et al.
(författare)
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Feeling small : Exploring the Tactile Perception Limits
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. 2617-
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Tidskriftsartikel (refereegranskat)abstract
- The human finger is exquisitely sensitive in perceiving different materials, but the question remains as to what length scales are capable of being distinguished in active touch. We combine material science with psychophysics to manufacture and haptically explore a series of topographically patterned surfaces of controlled wavelength, but identical chemistry. Strain-induced surface wrinkling and subsequent templating produced 16 surfaces with wrinkle wavelengths ranging from 300 nm to 90 mu m and amplitudes between 7 nm and 4.5 mu m. Perceived similarities of these surfaces (and two blanks) were pairwise scaled by participants, and interdistances among all stimuli were determined by individual differences scaling (INDSCAL). The tactile space thus generated and its two perceptual dimensions were directly linked to surface physical properties - the finger friction coefficient and the wrinkle wavelength. Finally, the lowest amplitude of the wrinkles so distinguished was approximately 10 nm, demonstrating that human tactile discrimination extends to the nanoscale.
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| 48. |
- Stajich, Jason E., et al.
(författare)
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Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus)
- 2010
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:26, s. 11889-11894
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Tidskriftsartikel (refereegranskat)abstract
- The mushroom Coprinopsis cinerea is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10(8) synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of C. cinerea was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of C. cinerea and Laccaria bicolor, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of C. cinerea is an essential resource in understanding the evolution of multicellularity in the fungi.
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| 49. |
- Wikberg, J. Magnus, et al.
(författare)
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Magnetic order and frustrated dynamics in Li(Ni0.8Co0.1Mn0.1)O-2 : a study by mu+SR and SQUID magnetometry
- 2012
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Ingår i: 12TH INTERNATIONAL CONFERENCE ON MUON SPIN ROTATION, RELAXATION AND RESONANCE (MUSR2011). - : Elsevier BV. ; , s. 202-205
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Konferensbidrag (refereegranskat)abstract
- Recently, the mixed transition metal oxides of the form Li(Ni1-y-zCoyMnz)O-2, have become the center of attention as promising candidates for novel battery material. These materials have also revealed very interesting magnetic properties due to the alternate stacking of planes of metal oxides on a 2D triangular lattice and the Li-layers. The title compound, Li(Ni0.8Co0.1Mn0.1)O-2, has been investigated by both magnetometry and measurements and mu+SR. We find the evolution of localized magnetic moments with decreasing temperature below 70 K. The magnetic ground state (T = 2 K) is, however, shown to be a frustrated system in 3D, followed by a transition into a possible 2D spin-glass above 22 K. With further increasing temperature the compound show the presence of remaining correlations with increasing effective dimensionality all the way up to the ferrimagnetic transition at T-C = 70 K.
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| 50. |
- Wu, Jun, et al.
(författare)
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Al2O3/InAs metal-oxide-semiconductor capacitors on (100) and (111)B substrates
- 2012
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 100:13, s. 3-132905
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Tidskriftsartikel (refereegranskat)abstract
- The influence of InAs orientations and high-k oxide deposition conditions on the electrical and structural quality of Au/W/Al2O3/InAs metal-oxide-semiconductor capacitors was investigated using capacitance-voltage (C-V) and x-ray photoemission spectroscopy techniques. The results suggest that the interface traps around the conduction band edge are correlated to the As-oxide amount, while less to those of As-As bonds and In-oxides. The quality of the deposited Al oxide determines the border trap density, hence the capacitance frequency dispersion. The comparison of different processing conditions is discussed, favoring a 350 C high-k oxide deposition on (111)B substrates followed by an annealing procedure at 400 oC.
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