| 1. |
- Almstedt, Elin, 1988-, et al.
(författare)
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Integrative discovery of treatments for high-risk neuroblastoma
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.
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| 2. |
- Antinyan, Vard, 1984, et al.
(författare)
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Monitoring Evolution of Code Complexity and Magnitude of Changes
- 2014
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Ingår i: Acta Cybernetica. - 0324-721X. ; 21:3, s. 367-382
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Tidskriftsartikel (refereegranskat)abstract
- Background: Complexity management has become a crucial activity in continuous software development. While the overall perceived complexity of a product grows rather insignificantly, the small units, such as functions and files, can have noticeable complexity growth with every increment of product features. This kind of evolution triggers risks of escalating fault-proneness and deteriorating maintainability. Goal: The goal of this research was to develop a measurement system which enables effective monitoring of complexity evolution. Method: An action research has been conducted in two large software development organiza-tions. We have measured three complexity and two change properties of code for two large industrial products. The complexity growth has been measured for five consecutive releases of products. Different patterns of growth have been identified and evaluated with software engi-neers in industry. Results: The results show that monitoring cyclomatic complexity evolution of functions and number of revisions of files focuses the attention of designers to potentially problematic files and functions for manual assessment and improvement. A measurement system was developed at Ericsson to support the monitoring process.
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| 3. |
- Henriksson, Niklas, 1976-
(författare)
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Poly(A)-specific Ribonuclease (PARN) : Structural and Functional Studies of Poly(A) Recognition and Degradation
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Regulation of mRNA degradation is a powerful way for the cell to regulate gene expression. A critical step in eukaryotic mRNA degradation is the removal of the poly(A) tail at the 3'-end of the mRNA. Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive and cap-interacting 3'-5' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. In addition to the exonuclease domain, PARN harbors two RNA-binding domains, a classical RNA recognition motif (RRM) and an R3H-domain. In this project we have studied mechanisms by which PARN specifically recognizes and degrades poly(A). We investigated the RNA binding properties of PARN by using electrophoretic mobility shift assays and filter-binding analysis and we could show that PARN binds poly(A) with high affinity and specificity. Furthermore, we showed that the RRM and R3H domains of PARN separately could bind to poly(A). To investigate specificity for and recognition of poly(A) in the active site of PARN, we performed a kinetic analysis on a repertoire of trinucleotide substrates in vitro. We showed that PARN harbors affinity for adenosines in the active site and that both the penultimate and the 3' end located nucleotide play an important role for providing adenosine-specificity in the active site of PARN. Moreover, we solved a crystal structure of PARN in complex with m7GpppG cap analogue and showed that the cap binding and active sites overlap both structurally and functionally. By mutational analysis we identified residues in the active site that specifically recognize adenosines. Furthermore, biochemical data showed that the adenosine specificity in the active site is lost when Mn2+ is used instead of Mg2+ as divalent metal ion. Taken together, these results demonstrate that both RNA-binding properties of the RRM and R3H-domains in addition to base recognition in the active site contributes to PARN poly(A)-specificity.
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| 4. |
- Skoog, Susann, et al.
(författare)
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A prospective study comparing the quality of coronary computed tomography angiography images from photon counting and energy integrating detector systems
- 2023
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Ingår i: Acta Radiologica. - : SAGE PUBLICATIONS LTD. - 0284-1851 .- 1600-0455. ; 64:11, s. 2957-2966
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Tidskriftsartikel (refereegranskat)abstract
- Background: As guidelines endorse the use of computed tomography (CT) for examining coronary artery disease (CAD), it is important to compare the advantages and disadvantages of the novel photon counting detector CT (PCD-CT) technology with the established energy integrating detector CT (EID-CT). Purpose: To compare the image quality of coronary computed tomography angiography (CCTA) and the Agatston scores (AS) derived from EID-CT and PCD-CT. Material and Methods: In this prospective observational study, 28 patients underwent clinical calcium score and CCTA scans on an EID-CTand a PCD-CT scanner. CCTA images were qualitatively analyzed by five observers using visual grading characteristics. The correlation and agreement of the AS were assessed using Spearmans rank correlation and Bland-Altman plots. Results: This qualitative analyses demonstrated a high fraction of " good" or "excellent" ratings for the image criteria in both CT systems. The sharpness of the distal lumen and image quality regarding motion artifacts were rated significantly higher for EID-CT (P < 0.05). However, the sharpness of coronary calcification was rated significantly higher for PCD-CT (P < 0.05). Spearmans rank correlation and Bland-Altman plots showed good correlation (P = 0.95) and agreement regarding the AS between EID-CT and PCD-CT. Conclusion: Both CT systems exhibited high CCTA image quality. The sharpness of calcifications was rated significantly higher for PCD-CT. A good correlation was observed between the AS derived from the two systems.
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| 5. |
- Staron, Miroslaw, 1977, et al.
(författare)
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Measuring and Visualizing Code Stability - A Case Study at Three Companies
- 2013
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Ingår i: IWSM/Mensura, Conference proceedings, IEEE. - : IEEE.
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Konferensbidrag (refereegranskat)abstract
- Monitoring performance of software development organizations can be achieved from a number of perspectives – e.g. using such tools as Balanced Scorecards or corporate dashboards. However, automated monitoring through quantitative metrics usually gives the best cost-benefit trade-off. In this paper we present results from a study on using code stability indicators as a tool for product stability and organizational performance, conducted at three different software development companies – Ericsson AB, Saab AB Electronic Defense Systems (Saab) and Volvo Group Trucks Technology (Volvo Group). The results show that visualizing the source code changes using heatmaps and linking these visualizations to defect inflow profiles provide indicators of how stable the product under development is and whether quality assurance efforts should be directed to specific parts of the product. Observing the indicator and making decisions based on its visualization leads to shorter feedback loops between development and test, thus resulting in lower development costs, shorter lead time and increased quality. The industrial case study in the paper shows that the indicator and its visualization can show whether the modifications of software products are focused on parts of the code base or are spread widely throughout the product.
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