| 1. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 2. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 3. |
- Zhukova, Nataliya, et al.
(författare)
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WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
- 2014
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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| 4. |
- Ayyala, Sekhar, et al.
(författare)
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Aggregate Characteristics in Coagulation and Flocculation
- 1993
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Ingår i: Mineral Processing and Extractive Metallurgy Review. - : Informa UK Limited. - 0882-7508 .- 1547-7401. ; 12:2-4, s. 165-184
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Tidskriftsartikel (refereegranskat)abstract
- Physical characteristics of mineral aggregates (such as density, size, shape, structure and strength) formed by either electrolytic coagulation or polymeric flocculation, need to be critically controlled by optimum conditioning in mineral processing. The present paper discusses the various experimental techniques used to determine these properties. In addition, physical and chemical factors that determine the rates of floe growth and which subsequently influence the floe morphology are summarised. This review also elucidates the hydrodynamic aspects of creeping flow and summarises the various settling velocity equations pertaining to the calcuation of floe density.
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| 5. |
- Furukawa, Toshi A., et al.
(författare)
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Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
- 2021
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Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
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Forskningsöversikt (refereegranskat)abstract
- Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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| 6. |
- Ata, S., et al.
(författare)
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The influence of interfacial ageing and temperature on the coalescence of oil droplets in water
- 2011
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Ingår i: Colloids and Surfaces A. - : Elsevier BV. - 0927-7757 .- 1873-4359. ; 374:1-3, s. 96-101
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the coalescence behaviour of two single droplets of industrial kerosene oil is an important precursor for predicting the stability of a concentrated kerosene emulsion system. In taking such an approach, distinct differences in the dynamic coalescence of fresh and aged binary droplets of analytical and technical grade kerosene was observed which we believe to be important with regard to the stability of concentrated systems. It was shown from induction time measurements (the time from first contact to rupture of the thin film separating the droplets) that the analytical grade kerosene binary droplets are considerable more stable than the technical grade at higher temperature (up to 65 degrees C) but the analytical grade shows a gradual decrease in stability up to 65 degrees C. At 75 degrees C, both grades of kerosene droplets remained stable to coalescence. After this initial rupture, coalescence proceeded as a series of dynamic oscillations and further insight into the fusion behaviour could be obtained by analysis of the change in the surface area of the aggregated droplets as a function of time. The longer induction times correlated with the more vigorous post rupture oscillations (less damping resulting from an increase in interfacial elasticity) which were recorded during the drop fusion. These experiments reveal preliminary steps in the coalescence of oil droplets where measurements from first contact to final damped equilibrium are quantified. This aspect of coalescence has not been well represented in the earlier literature. (C) 2010 Elsevier B.V. All rights reserved.
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| 7. |
- Blute, Irena, et al.
(författare)
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Industrial manufactured silica nanoparticle sols. 2 : Surface tension, particle concentration, foam generation and stability
- 2009
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Ingår i: Colloids and Surfaces A. - : Elsevier BV. - 0927-7757 .- 1873-4359. ; 337:1-3, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- Several earlier papers have revealed that several key parameters, such as hydrophobicity (contact angle), size, shape and degree of agglomeration, have an important influence on the behavior of particles at the air/water interface. However, the origin of foaming with particles is still not clear. In this article, we have tentatively related surface tension measurements and particle concentrations to the generation and stability of foam produced from industrial manufactured silica nanoparticle sols. Surprisingly, only slight reductions in surface tension were observed and the differences between the hydrophophilic and partially modified hydrophobic sols were small. However, in the case of the partially modified hydrophobic sol, the surface tension/concentration gradient was found to be pH and concentration responsive. Also, the greatest reduction in Surface tension was found to occur at low pH (in the region of the pH(pzc)) and could be related to the highest foamability (foam generation) as determined in our earlier publication [1. Blute, R.J. Pugh, J. van de Pas, I. Callaghan, Silica nanoparticle sols. 1. Surface chemical characterization and evaluation of the foam generation (foamability), J. Colloid Interface Sci. 313 (2007) 645-655]. Also, after centrifugation of the moderately hydrophobic modified concentrated sols, foaming tests carried out on the supernatant indicated that the particle concentration had a dominant influence on foamability and foam stability. Since only transient foams, with relatively short lifetimes, could be produced with these modified silica nanoparticles then (a) further surface modification or the reduction of pH to increase the Surface activity or (b) the addition of a cosurfactant Would be needed to increase the foamability and achieve foams with extended lifetimes.
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| 8. |
- Blute, Irena, et al.
(författare)
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Silica nanoparticle sols 1 : Surface chemical characterization and evaluation of the foam generation (foamability)
- 2007
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 313:2, s. 645-655
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Tidskriftsartikel (refereegranskat)abstract
- Surface characterization and foaming studies were carried out with nine industrially manufactured, colloidal silica dispersions with particles sizes from 5-40 nm. All the silica sols produced transient foams with short decay times and the dynamic foam generation (foamability) was found to vary according to the sol type with the greatest foamability occurring for the hydrophobically modified sol and the deionized hydrophilic sol. However, it was found that improved foamability of all the sols could be achieved by changing the pH to within the region of the pH(pzc) which corresponds to the region of lowest hydrophilicity. An increase in pH (and build-up of negative charge) enhances the surface hydrophilicity and caused a decrease in foamability. In addition, for selected hydrophilic sols, it was shown that the foamability (a) increased with decrease in particle size (within the 6-40 nm range) and (b) increased with particle concentration (within the range of 1-15 wt%). Overall, it was concluded that the foamability was primary controlled by hydrophobicity (and hence by pH) and also by the particle concentration, the particle size and the degree of agglomeration.
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| 9. |
- Blute, Irena, et al.
(författare)
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Silica nanoparticle sols. Part 3 : Monitoring the state of agglomeration at the air/water interface using the Langmuir-Blodgett technique
- 2009
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 336:2, s. 584-591
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Tidskriftsartikel (refereegranskat)abstract
- Langmuir-Blodgett films were prepared at the air/water interface from dispersions of hydrophilic and partially, hydrophobically modified industrially manufactured silica nanoparticles. The hydrophilic particles featured expanded, fairly easily compressible, surface pressure (pi)-area (A) isotherms with well defined collapse pressures which appeared to be caused by the formation of loosely structured agglomerates which exhibited elastic behavior at low surface pressure and inelastic behavior at high surface pressure. Lateral electrostatic interparticle interactions seemingly played an important role in this hydrophilic system. This contrasted with the hydrophobically modified particles which were more difficult to disperse in the ethanol/chloroform spreading solvent and appeared to be in the semi-agglomerated state at low surface pressures and exhibited a more difficult to compress compacted film. Both types of particulate films were shown to be sensitive to the spreading environment and changes in pH were found to increase particle agglomeration which drastically reduced the particulate area for the hydrophilic sol but less so, in the case of the moderately hydrophobically modified sol. In general, the LB technique proved to be a useful method to monitor changes in the state of aggregation of narrosized silica particles at the air/water interface. These results also appear to give some support of our ideas, presented in earlier publications [1,2] in which it was suggested that the major role of the hydrophobically modified hydrophilic particles in foaming was to produce an aggregated particulate film surrounding the air/water interface which provides a physical barrier preventing coalescence of bubbles.
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| 10. |
- Camargo-Alvarez, Hector, et al.
(författare)
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Modelling crop yield and harvest index : the role of carbon assimilation and allocation parameters
- 2023
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Ingår i: Modeling Earth Systems and Environment. - : Springer Science and Business Media LLC. - 2363-6203 .- 2363-6211. ; 9:2, s. 2617-2635
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Tidskriftsartikel (refereegranskat)abstract
- Crop yield improvement during the last decades has relied on increasing the ratio of the economic organ to the total aboveground biomass, known as the harvest index (HI). In most crop models, HI is set as a parameter; this empirical approach does not consider that HI not only depends on plant genotype, but is also affected by the environment. An alternative is to simulate allocation mechanistically, as in the LPJ-GUESS crop model, which simulates HI based on daily growing conditions and the crop development stage. Simulated HI is critical for agricultural research due to its economic importance, but it also can validate the robust representation of production processes. However, there is a challenge to constrain parameter values globally for the allocation processes. Therefore, this paper aims to evaluate the sensitivity of yield and HI of wheat and maize simulated with LPJ-GUESS to eight production allocation-related parameters and identify the most suitable parameter values for global simulations. The nitrogen demand reduction after anthesis, the minimum leaf carbon to nitrogen ratio (C:N) and the range of leaf C:N strongly affected carbon assimilation and yield, while the retranslocation of labile stem carbon to grains and the retranslocation rate of nitrogen and carbon from vegetative organs to grains after anthesis mainly influenced HI. A global database of observed HI for both crops was compiled for reference to constrain simulations before calibrating parameters for yield against reference data. Two high- and low-yielding maize cultivars emerged from the calibration, whilst spring and winter cultivars were found appropriate for wheat. The calibrated version of LPJ-GUESS improved the simulation of yield and HI at the global scale for both crops, providing a basis for future studies exploring crop production under different climate and management scenarios.
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