| 1. |
- Brownstein, Catherine A., et al.
(författare)
-
An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
|
|
| 2. |
- Hammarsjö, A., et al.
(författare)
-
High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses
- 2021
-
Ingår i: Journal of Human Genetics. - : Springer Nature. - 1434-5161 .- 1435-232X. ; 66:10, s. 995-1008
-
Tidskriftsartikel (refereegranskat)abstract
- Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.
|
|
| 3. |
|
|
| 4. |
- Lundström, Ulla, et al.
(författare)
-
Advances in understanding the podzolization process resulting from a multidisciplinary study of three coniferous forest soils in the Nordic Countries
- 2000
-
Ingår i: Geoderma. - 0016-7061 .- 1872-6259. ; 94:04-feb, s. 335-353
-
Tidskriftsartikel (refereegranskat)abstract
- Geochemical, mineralogical, micromorphological, microbiological, hydrochemical and hpdrological joint investigations were performed at two coniferous podzolic sites in the north of Sweden and at one in the south of Finland. Mycorrhizal fungi were found to create numerous pens (3-10-mu m diameter) in many weatherable mineral grains in the eluvial (E) horizon. During the growing season, identified low molecular weight (LMW) organic acids such as citric, shikimic, oxalic and fumaric acids comprised 0.5-5% of the DOC and 0.5-15% of the total acidity in soil solutions. Between 20% and 40% of the dissolved Al was bound to the identified LMW organic acids. Mineral dissolution via complexing LMW acids, probably exuded in part by the mycorrhiza hyphae, is likely to be a major weathering process in podzols. We found no evidence for a decreasing C/metal ratio of the migrating organo-metal complexes that could explain the precipitation of secondary Fe and AL in the illuvial (B) horizon. Instead, microbial degradation of organic ligands resulting in the release of ionic,Al and Fe to the soil solution may he an important process facilitating the formation of solid Al-SI-OH and Fe-OH phases in the podzol B horizon. However, within the B horizon transport as proto-imogilite (PI) sols might be possible. In the B horizon, the extractable,Al and Fe was predominantly inorganic. The large specific surface area (SSA) removable by oxalate extraction, the high point of zero charge salt effect (PZSE), the low cation exchange capacity (CEC) and the high sulphate exchange capacity (SEC), painted to the presence of short-range ordered variable charge phases. Imogolite type material (ITM) was indeed identified in all B horizons by IR spectroscopy and crystalline imogolite was found in the deep B horizon of one profile. Mossbauer spectroscopy indicated that Fe in the form of ferrihydrite was formed by intergrowth with an Al-Si-OH phase. The high amounts of Fe and Al transported from the O to the E horizon indicate that there could be an upward transport of these elements before they are leached to the B horizon. We hypothesize that the LMW Al complexes an transported by hyphae to the mor (O) layer, partly released and subsequently complexed by high molecular weight (HMW) acids.
|
|
| 5. |
- Bissal, A., et al.
(författare)
-
Hybrid multi-physics modeling of an ultra-fast electro-mechanical actuator
- 2015
-
Ingår i: Actuators. - : MDPI AG. - 2076-0825. ; 4:4, s. 314-335
-
Tidskriftsartikel (refereegranskat)abstract
- The challenges of an HVDC breaker are to generate impulsive forces in the order of hundreds of kilonewtons within fractions of a millisecond, to withstand the arising internal mechanical stresses and to transmit these forces via an electrically-insulating device to the contact system with minimum time delay. In this work, several models were developed with different levels of complexity, computation time and accuracy. Experiments were done with two mushroom-shaped armatures to validate the developed simulation models. It was concluded that although the electromagnetic force generation mechanism is highly sensitive to the mechanical response of the system, the developed first order hybrid model is able to predict the performance of the breaker with good accuracy.
|
|
| 6. |
- Björnsson, H., et al.
(författare)
-
Velocities in the plume of the 2010 Eyjafjallajökull eruption
- 2013
-
Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202 .- 2169-897X. ; 118:20, s. 11698-11711
-
Tidskriftsartikel (refereegranskat)abstract
- The eruption of the Icelandic volcano Eyjafjallajökull in the spring of 2010 lasted for 39 days with an explosive phase (14-18 April), an effusive phase (18 April to 4 May) and a phase with renewed explosive activity (5-17 May). Images every 5 s from a camera mounted 34 km from the volcano are available for most of the eruption. Applying the maximum cross-correlation method (MCC) on these images, the velocity structure of the eruption cloud has been mapped in detail for four time intervals covering the three phases of the eruption. The results show that on average there are updrafts in one part of the cloud and lateral motion or downdrafts in another. Even within the updraft part, there are alternating motions of strong updrafts, weak updrafts, and downward motion. These results show a highly variable plume driven by intermittent explosions. The results are discussed in the context of integral plume models and in terms of elementary parcel theory. Key Points Velocities in a volcanic cloud based on analysis of image data from the eruption Velocities in the eruption cloud are inhomogeneous and updrafts intermittent Intermittent updrafts are important for the dynamics and the lofting of ash.
|
|
| 7. |
- Blau, Helen M., et al.
(författare)
-
Elastic substrates and methods of use in cell manipulation and culture
- 2010
-
Patent (populärvet., debatt m.m.)abstract
- Methods are provided for the ex vivo manipulation of cells, stem cells and other reproductive cells, by manipulating the cells in a container or device comprising an elastic substrate, wherein the substrate has an elasticity that mimics the elasticity of a native microenvironment of the cell.
|
|
| 8. |
- Bogers, M., et al.
(författare)
-
The open innovation research landscape : established perspectives and emerging themes across different levels of analysis
- 2017
-
Ingår i: Industry and Innovation. - : Routledge. - 1366-2716 .- 1469-8390. ; 24:1, s. 8-40
-
Tidskriftsartikel (refereegranskat)abstract
- This paper provides an overview of the main perspectives and themes emerging in research on open innovation (OI). The paper is the result of a collaborative process among several OI scholars–having a common basis in the recurrent Professional Development Workshop on ‘Researching Open Innovation’ at the Annual Meeting of the Academy of Management. In this paper, we present opportunities for future research on OI, organised at different levels of analysis. We discuss some of the contingencies at these different levels, and argue that future research needs to study OI–originally an organisational-level phenomenon–across multiple levels of analysis. While our integrative framework allows comparing, contrasting and integrating various perspectives at different levels of analysis, further theorising will be needed to advance OI research. On this basis, we propose some new research categories as well as questions for future research–particularly those that span across research domains that have so far developed in isolation.
|
|
| 9. |
- Cepeda, D., et al.
(författare)
-
CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer
- 2013
-
Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 5:7, s. 999-1018
-
Tidskriftsartikel (refereegranskat)abstract
- SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors.
|
|
| 10. |
- Chenouard, Nicolas, et al.
(författare)
-
Objective comparison of particle tracking methods
- 2014
-
Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:3, s. 281-U247
-
Tidskriftsartikel (refereegranskat)abstract
- Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers.
|
|
