| 1. |
- Alvarsson, Jonathan, et al.
(författare)
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Benchmarking Study of Parameter Variation When Using Signature Fingerprints Together with Support Vector Machines
- 2014
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 54:11, s. 3211-3217
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Tidskriftsartikel (refereegranskat)abstract
- QSAR modeling using molecular signatures and support vector machines with a radial basis function is increasingly used for virtual screening in the drug discovery field. This method has three free parameters: C, ?, and signature height. C is a penalty parameter that limits overfitting, ? controls the width of the radial basis function kernel, and the signature height determines how much of the molecule is described by each atom signature. Determination of optimal values for these parameters is time-consuming. Good default values could therefore save considerable computational cost. The goal of this project was to investigate whether such default values could be found by using seven public QSAR data sets spanning a wide range of end points and using both a bit version and a count version of the molecular signatures. On the basis of the experiments performed, we recommend a parameter set of heights 0 to 2 for the count version of the signature fingerprints and heights 0 to 3 for the bit version. These are in combination with a support vector machine using C in the range of 1 to 100 and gamma in the range of 0.001 to 0.1. When data sets are small or longer run times are not a problem, then there is reason to consider the addition of height 3 to the count fingerprint and a wider grid search. However, marked improvements should not be expected.
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| 2. |
- Alvarsson, Jonathan, et al.
(författare)
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Brunn : an open source laboratory information system for microplates with a graphical plate layout design process
- 2011
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background:Compound profiling and drug screening generates large amounts of data and is generally based on microplate assays. Current information systems used for handling this are mainly commercial, closed source, expensive, and heavyweight and there is a need for a flexible lightweight open system for handling plate design, and validation and preparation of data.Results:A Bioclipse plugin consisting of a client part and a relational database was constructed. A multiple-step plate layout point-and-click interface was implemented inside Bioclipse. The system contains a data validation step, where outliers can be removed, and finally a plate report with all relevant calculated data, including dose-response curves.Conclusions:Brunn is capable of handling the data from microplate assays. It can create dose-response curves and calculate IC50 values. Using a system of this sort facilitates work in the laboratory. Being able to reuse already constructed plates and plate layouts by starting out from an earlier step in the plate layout design process saves time and cuts down on error sources.
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| 3. |
- Andersson, Björn, et al.
(författare)
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Genetic analysis of Phytophthora infestans populations in the Nordic European countries reveals high genetic variability
- 2011
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Ingår i: Fungal Biology. - : Elsevier BV. - 1878-6146. ; 115, s. 335-342
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Tidskriftsartikel (refereegranskat)abstract
- Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum). The pathogen is highly adaptable and to get an overview of the genetic variation in the Nordic countries, Denmark, Finland, Norway and Sweden we have analyzed 200 isolates from different fields using nine simple-sequence repeat (SSR) markers. Forty-nine alleles were detected among the nine SSR loci and isolates from all four Nordic countries shared the most common alleles across the loci. In total 169 multi-locus genotypes (based on seven loci) were identified among 191 isolates. The genotypic diversities, quantified by a normalized Shannon's diversity index (H(s)), were 0.95 for the four Nordic countries. The low F(ST) value of 0.04 indicates that the majority of variation is found within the four Nordic countries. The large number of genotypes and the frequency distribution of mating types (60% A1) support the hypothesis that sexual reproduction is contributing notably to the genetic variation of P. infestans in the Nordic countries. (C) 2011 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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| 4. |
- Andersson, Sofia A, et al.
(författare)
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Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 364:1-2, s. 36-45
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Tidskriftsartikel (refereegranskat)abstract
- Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
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| 5. |
- Baldwin, Scott A., et al.
(författare)
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Intraclass correlation associated with therapists : estimates and applications in planning psychotherapy research
- 2011
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Ingår i: Cognitive Behaviour Therapy. - : Routledge, Taylor and Francis Group. - 1650-6073 .- 1651-2316. ; 40:1, s. 15-33
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Tidskriftsartikel (refereegranskat)abstract
- It is essential that outcome research permit clear conclusions to be drawn about the efficacy of interventions. The common practice of nesting therapists within conditions can pose important methodological challenges that affect interpretation, particularly if the study is not powered to account for the nested design. An obstacle to the optimal design of these studies is the lack of data about the intraclass correlation coefficient (ICC), which measures the statistical dependencies introduced by nesting. To begin the development of a public database of ICC estimates, the authors investigated ICCs for a variety outcomes reported in 20 psychotherapy outcome studies. The magnitude of the 495 ICC estimates varied widely across measures and studies. The authors provide recommendations regarding how to select and aggregate ICC estimates for power calculations and show how researchers can use ICC estimates to choose the number of patients and therapists that will optimize power. Attention to these recommendations will strengthen the validity of inferences drawn from psychotherapy studies that nest therapists within conditions.
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| 6. |
- Blandón-Díaz, Jorge Ulises, et al.
(författare)
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Phenotypic Variation Within a Clonal Lineage of Phytophthora infestans Infecting both Tomato and Potato in Nicaragua
- 2012
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Ingår i: Phytopathology. - 0031-949X .- 1943-7684. ; 102, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Late blight caused by Phytophthora infestans (Mont.) de Bary is a constraint to both potato and tomato crops in Nicaragua. The hypothesis that the Nicaraguan population of P. infestans is genotypically and phenotypically diverse and potentially subdivided based on host association was tested. A collection of isolates was analyzed using genotypic markers (microsatellites and mitochondrial DNA haplotype) and phenotypic markers (mating type, virulence, and fungicide sensitivity). The genotypic analysis revealed no polymorphism in 121 of 132 isolates of P. infestans tested. Only the Ia haplotype and the A2 mating type were detected. Most of the tested isolates were resistant to metalaxyl. The virulence testing showed variation among isolates of P. infestans. No evidence was found of population differentiation among potato and tomato isolates of P. infestans based on the genotypic and phenotypic analysis. We conclude that the Nicaraguan population of P. infestans consists of a single clonal lineage (NI-1) which belongs to the A2 mating type and the Ia mitochondrial DNA haplotype. Moreover, based on the markers used, this population of P. infestans does not resemble the population in countries from which potato seed is imported to Nicaragua or the population in neighboring countries. The data presented here indicate that the NI-1 clonal lineage is the primary pathogen on both potato and tomato, and its success on both host species is unique in a South American context.
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| 7. |
- Chehrenegar, Pirooz, 1964, et al.
(författare)
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Design and characterization of a highly linear 3 GHz GaN HEMT amplifier
- 2011
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Ingår i: 2011 Workshop on Integrated Nonlinear Microwave and Millimetre-Wave Circuits, INMMiC 2011. Vienna, 18-19 April 2011. - 9781457706493
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Konferensbidrag (refereegranskat)abstract
- In this paper a highly linear amplifier using an in-house gallium nitride (GaN) high electron mobility transistor (HEMT) technology is presented. A 3 dB bandwidth of 2.7-3.6 GHz with a maximum gain of 18 dB was measured. The output third-order intercept point (OIP3) was measured to 39 dBm with a maximum power consumption of 2.1 W. With a reduction of power consumption to 1 W the noise figure was improved by 0.6 dB while the OIP3 was degraded 3 dB.
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| 8. |
- Dupont, Chris L., et al.
(författare)
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Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549-
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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| 9. |
- Haggblade, Steven, et al.
(författare)
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Cassava Commercialization in Southeastern Africa
- 2012
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Ingår i: Journal of Agribusiness in Developing and Emerging Economies. - : Emerald. - 2044-0839 .- 2044-0847. ; 2:1, s. 4-40
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – Cassava production surged noticeably in Southeastern Africa beginning in the 1990s. The purpose of this paper is to examine the commercial responses and food security consequences of cassava production growth in the region. Design/methodology/approach – The paper incorporates a mix of quantitative analysis, based primarily on original analysis of national farm household survey data, together with key informant interviews with value chain participants in the three neighboring countries of Malawi, Mozambique and Zambia. Findings – In the cassava production zones, cassava's high productivity translates into per kilogram carbohydrate costs 60 per cent to 70 per cent of the cost of cereals such as maize and wheat, thereby opening up a range of profitable opportunities for commercialization of cassava-based foods, feeds and industrial products. Despite this potential, cassava commercialization in Southeastern Africa remains in its formative stages, with only 10 per cent to 30 per cent of production currently marketed. Unlike West Africa, where cassava commercialization has centered on marketing prepared cassava-based convenience foods, the emerging cassava markets in Southeastern Africa have centered on fresh cassava, low value-added cassava flour, and experiments in industrial processing of cassava-based starches, biofuels and feeds. Strategic investment in a set of key public goods (breeding, training in food sciences and food safety, and research on in-ground cassava storage) can help to shape this transition in ways that benefit both commercial interests and the food security of vulnerable households. Originality/value – The paper compares cassava commercialization across differing agro-climatic zones, policy environments and food staple zones.
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| 10. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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