| 1. |
- Ovegård, Erik, et al.
(författare)
-
Operational Guidance with Respect to Pure Loss of Stability and Parametric Rolling
- 2012
-
Ingår i: Proceedings of the 11<sup>th</sup> International Conference on the Stability of Ships and Ocean Vehicles (STAB2012).
-
Konferensbidrag (refereegranskat)abstract
- This paper reviews two previously presented simplified methods for assessment of pure loss of stability and parametric rolling based on linear signal theory. The methods are evaluated in relation to full-scale incidents and time-domain simulations. Underlying assumptions and tuning of the critical levels in the simplified methods with reference to time-domain simulations is discussed. Given proper tuning the methods are concluded to provide a feasible basis for ship specific on-board operational guidance.
|
|
| 2. |
|
|
| 3. |
- Rosén, Anders, et al.
(författare)
-
Experience from Parametric Rolling of Ships
- 2012
-
Ingår i: Parametric Resonance in Dynamical Systems. - New York, NY : Springer. - 9781461410423 ; , s. 147-165
-
Bokkapitel (refereegranskat)abstract
- This chapter reviews three recent full-scale events with parametric rolling for Ro–Ro Large Car and Truck Carriers (LCTC). The events represent three principally different modes of parametric rolling: principal parametric resonance where the period of encounter is half of the roll natural period in following seas (I) and in head seas (II), and fundamental parametric resonance where the period of encounter coincides with the roll natural period in following seas (III). Roll motion, course, and speed recorded during the events are presented and analyzed together with the present weather situation based on recordings, forecasts, and re-analysis. Different aspects of on-board operational guidance for assisting crews in avoiding parametric rolling are discussed in relation to the presented events. Involved complexities and considerations that are normally not included in well defined model tests or numerical simulations are exposed.
|
|
| 4. |
- Abdellah, Tebani, et al.
(författare)
-
Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
|
|
| 5. |
- Avican, Kemal, et al.
(författare)
-
Reprogramming of Yersinia from Virulent to Persistent Mode Revealed by Complex In Vivo RNA-seq Analysis
- 2015
-
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding.
|
|
| 6. |
- Bersani, Cinzia, et al.
(författare)
-
Genome-wide identification of Wig-1 mRNA targets by RIP-Seq analysis
- 2016
-
Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:2, s. 1895-1911
-
Tidskriftsartikel (refereegranskat)abstract
- RNA-binding proteins (RBPs) play important roles in the regulation of gene expression through a variety of post-transcriptional mechanisms. The p53-induced RBP Wig-1 (Zmat3) binds RNA through its zinc finger domains and enhances stability of p53 and N-Myc mRNAs and decreases stability of FAS mRNA. To identify novel Wig-1-bound RNAs, we performed RNA-immunoprecipitation followed by high-throughput sequencing (RIP-Seq) in HCT116 and Saos-2 cells. We identified 286 Wig-1-bound mRNAs common between the two cell lines. Sequence analysis revealed that AU-rich elements (AREs) are highly enriched in the 3'UTR of these Wig-1-bound mRNAs. Network enrichment analysis showed that Wig-1 preferentially binds mRNAs involved in cell cycle regulation. Moreover, we identified a 2D Wig-1 binding motif in HIF1A mRNA. Our findings confirm that Wig-1 is an ARE-BP that regulates cell cycle-related processes and provide a novel view of how Wig-1 may bind mRNA through a putative structural motif. We also significantly extend the repertoire of Wig-1 target mRNAs. Since Wig-1 is a transcriptional target of the tumor suppressor p53, these results have implications for our understanding of p53-dependent stress responses and tumor suppression.
|
|
| 7. |
- Branca, Rui M. M., et al.
(författare)
-
HiRIEF LC-MSMS enables deep proteome coverage and unbiased proteogenomics
- 2014
-
Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 11:1, s. 59-
-
Tidskriftsartikel (refereegranskat)abstract
- We present a liquid chromatography-mass spectrometry (LC-MSMS)-based method permitting unbiased (gene prediction-independent) genome-wide discovery of protein-coding loci in higher eukaryotes. Using high-resolution isoelectric focusing (HiRIEF) at the peptide level in the 3.7-5.0 pH range and accurate peptide isoelectric point (pI) prediction, we probed the six-reading-frame translation of the human and mouse genomes and identified 98 and 52 previously undiscovered protein-coding loci, respectively. The method also enabled deep proteome coverage, identifying 13,078 human and 10,637 mouse proteins.
|
|
| 8. |
- 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.
|
|
| 9. |
- Danielsson, Frida, et al.
(författare)
-
Assessing the consistency of public human tissue RNA-seq data sets
- 2015
-
Ingår i: Briefings in Bioinformatics. - : Oxford University Press. - 1467-5463 .- 1477-4054. ; 16:6, s. 941-949
-
Tidskriftsartikel (refereegranskat)abstract
- Sequencing-based gene expression methods like RNA-sequencing (RNA-seq) have become increasingly common, but it is often claimed that results obtained in different studies are not comparable owing to the influence of laboratory batch effects, differences in RNA extraction and sequencing library preparation methods and bioinformatics processing pipelines. It would be unfortunate if different experiments were in fact incomparable, as there is great promise in data fusion and meta-analysis applied to sequencing data sets. We therefore compared reported gene expression measurements for ostensibly similar samples (specifically, human brain, heart and kidney samples) in several different RNA-seq studies to assess their overall consistency and to examine the factors contributing most to systematic differences. The same comparisons were also performed after preprocessing all data in a consistent way, eliminating potential bias from bioinformatics pipelines. We conclude that published human tissue RNA-seq expression measurements appear relatively consistent in the sense that samples cluster by tissue rather than laboratory of origin given simple preprocessing transformations. The article is supplemented by a detailed walkthrough with embedded R code and figures.
|
|
| 10. |
- Danielsson, Frida, 1984-
(författare)
-
Integration of RNA and protein expression profiles to study human cells
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cellular life is highly complex. In order to expand our understanding of the workings of human cells, in particular in the context of health and disease, detailed knowledge about the underlying molecular systems is needed. The unifying theme of this thesis concerns the use of data derived from sequencing of RNA, both within the field of transcriptomics itself and as a guide for further studies at the level of protein expression. In paper I, we showed that publicly available RNA-seq datasets are consistent across different studies, requiring only light processing for the data to cluster according to biological, rather than technical characteristics. This suggests that RNA-seq has developed into a reliable and highly reproducible technology, and that the increasing amount of publicly available RNA-seq data constitutes a valuable resource for meta-analyses. In paper II, we explored the ability to extrapolate protein concentrations by the use of RNA expression levels. We showed that mRNA and corresponding steady-state protein concentrations correlate well by introducing a gene-specific RNA-to-protein conversion factor that is stable across various cell types and tissues. The results from this study indicate the utility of RNA-seq also within the field of proteomics.The second part of the thesis starts with a paper in which we used transcriptomics to guide subsequent protein studies of the molecular mechanisms underlying malignant transformation. In paper III, we applied a transcriptomics approach to a cell model for defined steps of malignant transformation, and identified several genes with interesting expression patterns whose corresponding proteins were further analyzed with subcellular spatial resolution. Several of these proteins were further studied in clinical tumor samples, confirming that this cell model provides a relevant system for studying cancer mechanisms. In paper IV, we continued to explore the transcriptional landscape in the same cell model under moderate hypoxic conditions.To conclude, this thesis demonstrates the usefulness of RNA-seq data, from a transcriptomics perspective and beyond; to guide in analyses of protein expression, with the ultimate goal to unravel the complexity of the human cell, from a holistic point of view.
|
|
