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| 2. |
- Patra, B., et al.
(författare)
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A genome wide dosage suppressor network reveals genomic robustness
- 2017
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Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 45:1, s. 255-270
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Tidskriftsartikel (refereegranskat)abstract
- Genomic robustness is the extent to which an organism has evolved to withstand the effects of deleterious mutations. We explored the extent of genomic robustness in budding yeast by genome wide dosage suppressor analysis of 53 conditional lethal mutations in cell division cycle and RNA synthesis related genes, revealing 660 suppressor interactions of which 642 are novel. This collection has several distinctive features, including high cooccurrence of mutant-suppressor pairs within protein modules, highly correlated functions between the pairs and higher diversity of functions among the co-suppressors than previously observed. Dosage suppression of essential genes encoding RNA polymerase subunits and chromosome cohesion complex suggests a surprising degree of functional plasticity of macromolecular complexes, and the existence of numerous degenerate pathways for circumventing the effects of potentially lethal mutations. These results imply that organisms and cancer are likely able to exploit the genomic robustness properties, due the persistence of cryptic gene and pathway functions, to generate variation and adapt to selective pressures. © 2016 The Author(s).
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| 3. |
- Aerts, Arend, et al.
(författare)
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A Tool Prototype for Model-Based Testing of Cyber-Physical Systems
- 2015
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Ingår i: Theoretical Aspects of Computing – ICTAC 2015. - Cham : Springer. - 9783319251493 - 9783319251509 ; , s. 563-572
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Konferensbidrag (refereegranskat)abstract
- We report on a tool prototype for model-based testing of cyber-physical systems. Our starting point is a hybrid-system model specified in a domain-specific language called Acumen. Our prototype tool is implemented in Matlab and covers three stages of model-based testing, namely, test-case generation, test-case execution, and conformance analysis. We have applied our implementation to a number of typical examples of cyber-physical systems in order to analyze its applicability. In this paper, we report on the result of applying the prototype tool on a DC-DC boost converter. © Springer International Publishing Switzerland 2015
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| 4. |
- Aerts, Arend, et al.
(författare)
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Model-Based Testing of Cyber-Physical Systems
- 2016
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Ingår i: Cyber-Physical Systems. - Saint Louis : Elsevier. - 9780128038017 ; , s. 287-304
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Bokkapitel (refereegranskat)abstract
- Cyber-physical systems (CPSs) are the result of the integration of connected computer systems with the physical world. They feature complex interactions that go beyond traditional communication schemes and protocols in computer systems. One distinguished feature of such complex interactions is the tight coupling between discrete and continuous interactions, captured by hybrid system models.Due to the complexity of CPSs, providing rigorous and model-based analysis methods and tools for verifying correctness of such systems is of the utmost importance. Model-based testing (MBT) is one such verification technique that can be used for checking the conformance of an implementation of a system to its specification (model).In this chapter, we first review the main concepts and techniques in MBT. Subsequently, we review the most common modeling formalisms for CPSs, with focus on hybrid system models. Subsequently, we provide a brief overview of conformance relations and conformance testing techniques for CPSs. © 2017 Elsevier Inc. All rights reserved.
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| 5. |
- Bermejo-Velasco, Daniel, 1985-, et al.
(författare)
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Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging
- 2018
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 197, s. 641-648
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring hydrogel degradation in real time using noninvasive imaging techniques is of great interest for designing a scaffold in tissue engineering. We report the preparation of gadolinium (Gd)-labeled and injectable hyaluronic acid (HA) hydrogels that can be visualized using T-1- and T-2-weighted magnetic resonance imaging (MRI). An HA derivative functionalized with thiol and hydrazide was labeled using a diethylenetriaminepentaacetate complex modified with "clickable" dithiopyridyl functionalities (degree of modification was 3.77% with respect to HA repeat units). The HA derivative modified with cross-linkable groups and Gd complex exhibited relaxivities r(1) = 3.78 mM(-1)s(-1) and r(2) = 56.3 mM(-1)s(-1). A hydrazone hydrogel network was obtained by mixing Gd-labeled HA-hydrazide and HA-aldehyde derivatives. Enzymatic hydrogel degradation could be followed using MRI because the MR images showed great correlation with the hydrogel mass loss. Ex vivo MRI of injected Gd-labeled hydrogels demonstrated that they show a significant contrast difference (SNRcoronal = 456; SNRaxial = 459) from the surrounding tissues. These results indicate that our Gd-labeled HA hydrogel has great potential as an injectable biocompatible hydrogel that can be used for longitudinal tracking in vivo using MRI.
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| 6. |
- Delanaye, Pierre, et al.
(författare)
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CKD : A Call for an Age-Adapted Definition
- 2019
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 30:10, s. 1785-1805
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Forskningsöversikt (refereegranskat)abstract
- Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m2, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m2 Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
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| 7. |
- den Bakker, Emil, et al.
(författare)
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Accurate eGFR reporting for children without anthropometric data
- 2017
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 474, s. 38-43
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Reporting estimated glomerular filtration rate (eGFR) instead of serum concentrations is advised in current guidelines. Most creatinine-based eGFR equations for children require height, a parameter not readily available to laboratories. Combining height-dependent creatinine- and cystatin C-based eGFR improves performance. Recently, a height-independent creatinine-based eGFR equation has been developed. Aim To compare the combination of height-independent creatinine- and cystatin C-based equations with a combination of equations using anthropometric data. Methods Retrospective analysis of 408 pediatric inulin clearance studies with simultaneous height, creatinine, cystatin C and urea measurements. eGFR calculation using the recalibrated Schwartzcrea (height-dependent), FASage (height-independent) and the Schwartzcys equation. The means (Schwartzcrea + Schwartzcys) / 2 and (FASage + Schwartzcys) / 2 were compared with the CKiD3 equation incorporating cystatin C, creatinine, urea, height and gender in terms of %prediction error and accuracy. Results All three single parameter equations performed similarly (P30 accuracy around 80%). (FASage + Schwartzcys) / 2 (P30 89.2%) and (Schwartzcrea + Schwartzcys) / 2 (P30 89.0%), performed comparably to CKiD3 (P30 90.0%). If the difference between the creatinine- and the cystatine C based eGFR was < 40%, P30 accuracy of the mean exceeded 90%. Conclusion Combining the height-independent FASage and SchwartzCys equations substantially improves accuracy and performs comparably to height-dependent equations. This allows laboratories to directly report eGFR in children.
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| 8. |
- Goldsby, H. J., et al.
(författare)
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Serendipitous scaffolding to improve a genetic algorithm's speed and quality
- 2018
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Ingår i: GECCO 2018 - Proceedings of the 2018 Genetic and Evolutionary Computation Conference. - New York, NY, USA : Association for Computing Machinery, Inc. - 9781450356183 ; , s. 959-966
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Konferensbidrag (refereegranskat)abstract
- A central challenge to evolutionary computation is enabling techniques to evolve increasingly complex target end products. Frequently, direct approaches that reward only the target end product itself are not successful because the path between the starting conditions and the target end product traverses through a complex fitness landscape, where the directly accessible intermediary states may be require deleterious or even simply neutral mutations. As such, a host of techniques have sprung up to support evolutionary computation techniques taking these paths. One technique is scaffolding where intermediary targets are used to provide a path from the starting state to the end state. While scaffolding can be successful within well-understood domains it also poses the challenge of identifying useful intermediaries. Within this paper we first identify some shortcomings of scaffolding approaches ' namely, that poorly selected intermediaries may in fact hurt the evolutionary computation's chance of producing the desired target end product. We then describe a light-weight approach to selecting intermediate scaffolding states that improve the efficacy of the evolutionary computation. © 2018 Association for Computing Machinery.
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| 9. |
- Ortiz, A., et al.
(författare)
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Episode forecasting in bipolar disorder : Is energy better than mood?
- 2018
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Ingår i: Bipolar Disorders. - : Blackwell Publishing Inc.. - 1398-5647 .- 1399-5618. ; 20:5, s. 470-476
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Bipolar disorder is a severe mood disorder characterized by alternating episodes of mania and depression. Several interventions have been developed to decrease high admission rates and high suicides rates associated with the illness, including psychoeducation and early episode detection, with mixed results. More recently, machine learning approaches have been used to aid clinical diagnosis or to detect a particular clinical state; however, contradictory results arise from confusion around which of the several automatically generated data are the most contributory and useful to detect a particular clinical state. Our aim for this study was to apply machine learning techniques and nonlinear analyses to a physiological time series dataset in order to find the best predictor for forecasting episodes in mood disorders. Methods: We employed three different techniques: entropy calculations and two different machine learning approaches (genetic programming and Markov Brains as classifiers) to determine whether mood, energy or sleep was the best predictor to forecast a mood episode in a physiological time series. Results: Evening energy was the best predictor for both manic and depressive episodes in each of the three aforementioned techniques. This suggests that energy might be a better predictor than mood for forecasting mood episodes in bipolar disorder and that these particular machine learning approaches are valuable tools to be used clinically. Conclusions: Energy should be considered as an important factor for episode prediction. Machine learning approaches provide better tools to forecast episodes and to increase our understanding of the processes that underlie mood regulation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 10. |
- Wagenaar, Kim P., et al.
(författare)
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Effectiveness of the European Society of Cardiology/Heart Failure Association website heartfailurematters.org and an e-health adjusted care pathway in patients with stable heart failure: results of the e-Vita HF randomized controlled trial
- 2019
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 21:2, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- Background Efficient incorporation of e-health in patients with heart failure (HF) may enhance health care efficiency and patient empowerment. We aimed to assess the effect on self-care of (i) the European Society of Cardiology/Heart Failure Association website on top of usual care, and (ii) an e-health adjusted care pathway leaving out in person routine HF nurse consultations in stable HF patients. Methods and results In a three-group parallel-randomized trial in stable HF patients from nine Dutch outpatient clinics, we compared two interventions ( website and an e-health adjusted care pathway) to usual care. The primary outcome was self-care measured with the European Heart Failure Self-care Behaviour Scale. Secondary outcomes were health status, mortality, and hospitalizations. In total, 450 patients were included. The mean age was 66.8 +/- 11.0 years, 74.2% were male, and 78.8% classified themselves as New York Heart Association I or II at baseline. After 3 months of follow-up, the mean score on the self-care scale was significantly higher in the groups using the website and the adjusted care pathway compared to usual care (73.5 vs. 70.8, 95% confidence interval 0.6-6.2; and 78.2 vs. 70.8, 95% confidence interval 3.8- 9.4, respectively). The effect attenuated, until no differences after 1 year between the groups. Quality of life showed a similar pattern. Other secondary outcomes did not clearly differ between the groups. Conclusions Both the website and an e-health adjusted care pathway improved self-care in HF patients on the short term, but not on the long term. Continuous updating of e-health facilities could be helpful to sustain effects.
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