| 1. |
- Antila, Kari, et al.
(författare)
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The PredictAD project : development of novel biomarkers and analysis software for early diagnosis of the Alzheimer's disease
- 2013
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Ingår i: Interface Focus. - : The Royal Society Publishing. - 2042-8898 .- 2042-8901. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common cause of dementia affecting 36 million people worldwide. As the demographic transition in the developed countries progresses towards older population, the worsening ratio of workers per retirees and the growing number of patients with age-related illnesses such as AD will challenge the current healthcare systems and national economies. For these reasons AD has been identified as a health priority, and various methods for diagnosis and many candidates for therapies are under intense research. Even though there is currently no cure for AD, its effects can be managed. Today the significance of early and precise diagnosis of AD is emphasized in order to minimize its irreversible effects on the nervous system. When new drugs and therapies enter the market it is also vital to effectively identify the right candidates to benefit from these. The main objective of the PredictAD project was to find and integrate efficient biomarkers from heterogeneous patient data to make early diagnosis and to monitor the progress of AD in a more efficient, reliable and objective manner. The project focused on discovering biomarkers from biomolecular data, electrophysiological measurements of the brain and structural, functional and molecular brain images. We also designed and built a statistical model and a framework for exploiting these biomarkers with other available patient history and background data. We were able to discover several potential novel biomarker candidates and implement the framework in software. The results are currently used in several research projects, licensed to commercial use and being tested for clinical use in several trials.
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| 2. |
- Budd, Graham E., et al.
(författare)
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Survival and selection biases in early animal evolution and a source of systematic overestimation in molecular clocks
- 2020
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Ingår i: Interface Focus. - : ROYAL SOC. - 2042-8898 .- 2042-8901. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Important evolutionary events such as the Cambrian Explosion have inspired many attempts at explanation: why do they happen when they do? What shapes them, and why do they eventually come to an end? However, much less attention has been paid to the idea of a 'null hypothesis'-that certain features of such diversifications arise simply through their statistical structure. Such statistical features also appear to influence our perception of the timing of these events. Here, we show in particular that study of unusually large clades leads to systematic overestimates of clade ages from some types of molecular clocks, and that the size of this effect may be enough to account for the puzzling mismatches seen between these molecular clocks and the fossil record. Our analysis of the fossil record of the late Ediacaran to Cambrian suggests that it is likely to be recording a true evolutionary radiation of the bilaterians at this time, and that explanations involving various sorts of cryptic origins for the bilaterians do not seem to be necessary.
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| 3. |
- Corkery, Robert W., et al.
(författare)
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On the colour of wing scales in butterflies : Iridescence and preferred orientation of single gyroid photonic crystals
- 2017
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Ingår i: Interface Focus. - : Royal Society. - 2042-8898 .- 2042-8901. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Lycaenid butterflies from the genera Callophrys, Cyanophrys and Thecla have evolved remarkable biophotonic gyroid nanostructures within their wing scales that have only recently been replicated by nanoscale additive manufacturing. These nanostructures selectively reflect parts of the visible spectrum to give their characteristic non-iridescent, matte-green appearance, despite a distinct blue-green-yellow iridescence predicted for individual crystals from theory. It has been hypothesized that the organism must achieve its uniform appearance by growing crystals with some restrictions on the possible distribution of orientations, yet preferential orientation observed in Callophrys rubi confirms that this distribution need not be uniform. By analysing scanning electron microscope and optical images of 912 crystals in three wing scales, we find no preference for their rotational alignment in the plane of the scales. However, crystal orientation normal to the scale was highly correlated to their colour at low (conical) angles of view and illumination. This correlation enabled the use of optical images, each containing up to 104-105 crystals, for concluding the preferential alignment seen along the k100l at the level of single scales, appears ubiquitous. By contrast, k110l orientations were found to occur at no greater rate than that expected by chance. Above a critical cone angle, all crystals reflected bright green light indicating the dominant light scattering is due to the predicted band gap along the k110l direction, independent of the domain orientation. Together with the natural variation in scale and wing shapes, we can readily understand the detailed mechanism of uniform colour production and iridescence suppression in these butterflies. It appears that the combination of preferential alignment normal to the wing scale, and uniform distribution within the plane is a near optimal solution for homogenizing the angular distribution of the k110l band gap relative to the wings. Finally, the distributions of orientations, shapes, sizes and degree of order of crystals within single scales provide useful insights for understanding the mechanisms at play in the formation of these biophotonic nanostructures.
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| 4. |
- Coveney, PV, et al.
(författare)
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Integrative approaches to computational biomedicine
- 2013
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Ingår i: INTERFACE FOCUS. - : The Royal Society. - 2042-8898 .- 2042-8901. ; 3:2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The new discipline of computational biomedicine is concerned with the application of computer-based techniques and particularly modelling and simulation to human health. Since 2007, this discipline has been synonymous, in Europe, with the name given to the European Union's ambitious investment in integrating these techniques with the eventual aim of modelling the human body as a whole: the virtual physiological human. This programme and its successors are expected, over the next decades, to transform the study and practice of healthcare, moving it towards the priorities known as ‘4P's’: predictive, preventative, personalized and participatory medicine.
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| 5. |
- Dabkowska, Aleksandra P., et al.
(författare)
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Non-lamellar lipid assembly at interfaces : controlling layer structure by responsive nanogel particles
- 2017
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Ingår i: Interface Focus. - : ROYAL SOC. - 2042-8898 .- 2042-8901. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Biological membranes do not only occur as planar bilayer structures, but depending on the lipid composition, can also curve into intriguing three-dimensional structures. In order to fully understand the biological implications as well as to reveal the full potential for applications, e.g. for drug delivery and other biomedical devices, of such structures, well-defined model systems are required. Here, we discuss the formation of lipid non-lamellar liquid crystalline (LC) surface layers spin-coated from the constituting lipids followed by hydration of the lipid layer. We demonstrate that hybrid lipid polymer films can be formed with different properties compared with the neat lipid LC layers. The nanostructure and morphologies of the lipid films formed reflect those in the bulk. Most notably, mixed lipid layers, which are composed of glycerol monooleate and diglycerol monooleate with poly(N-isopropylacrylamide) nanogels, can form films of reverse cubic phases that are capable of responding to temperature stimulus. Owing to the presence of the nanogel particles, changing the temperature not only regulates the hydration of the cubic phase lipid films, but also the lateral organization of the lipid domains within the lipid self-assembled film. This opens up the possibility for new nanostructured materials based on lipid-polymer responsive layers.
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| 6. |
- Firouznia, Marjan, et al.
(författare)
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FK-means: automatic atrial fibrosis segmentation using fractal-guided K-means clustering with Voronoi-clipping feature extraction of anatomical structures
- 2023
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Ingår i: Interface Focus. - : ROYAL SOC. - 2042-8898 .- 2042-8901. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of left atrial (LA) fibrosis from late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) adds to the management of patients with atrial fibrillation. However, accurate assessment of fibrosis in the LA wall remains challenging. Excluding anatomical structures in the LA proximity using clipping techniques can reduce misclassification of LA fibrosis. A novel FK-means approach for combined automatic clipping and automatic fibrosis segmentation was developed. This approach combines a feature-based Voronoi diagram with a hierarchical 3D K-means fractal-based method. The proposed automatic Voronoi clipping method was applied on LGE-MRI data and achieved a Dice score of 0.75, similar to the score obtained by a deep learning method (3D UNet) for clipping (0.74). The automatic fibrosis segmentation method, which uses the Voronoi clipping method, achieved a Dice score of 0.76. This outperformed a 3D UNet method for clipping and fibrosis classification, which had a Dice score of 0.69. Moreover, the proposed automatic fibrosis segmentation method achieved a Dice score of 0.90, using manual clipping of anatomical structures. The findings suggest that the automatic FK-means analysis approach enables reliable LA fibrosis segmentation and that clipping of anatomical structures in the atrial proximity can add to the assessment of atrial fibrosis.
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| 7. |
- Gomez-Cabrero, D, et al.
(författare)
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Workflow for generating competing hypothesis from models with parameter uncertainty
- 2011
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Ingår i: Interface focus. - : The Royal Society. - 2042-8901 .- 2042-8898. ; 1:3, s. 438-449
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Tidskriftsartikel (refereegranskat)abstract
- Mathematical models are increasingly used in life sciences. However, contrary to other disciplines, biological models are typically over-parametrized and loosely constrained by scarce experimental data and prior knowledge. Recent efforts on analysis of complex models have focused on isolated aspects without considering an integrated approach—ranging from model building to derivation of predictive experiments and refutation or validation of robust model behaviours. Here, we develop such an integrative workflow, a sequence of actions expanding upon current efforts with the purpose of setting the stage for a methodology facilitating an extraction of core behaviours and competing mechanistic hypothesis residing within underdetermined models. To this end, we make use of optimization search algorithms, statistical (machine-learning) classification techniques and cluster-based analysis of the state variables' dynamics and their corresponding parameter sets. We apply the workflow to a mathematical model of fat accumulation in the arterial wall (atherogenesis), a complex phenomena with limited quantitative understanding, thus leading to a model plagued with inherent uncertainty. We find that the mathematical atherogenesis model can still be understood in terms of a few key behaviours despite the large number of parameters. This result enabled us to derive distinct mechanistic predictions from the model despite the lack of confidence in the model parameters. We conclude that building integrative workflows enable investigators to embrace modelling of complex biological processes despite uncertainty in parameters.
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| 8. |
- KleinHeerenbrink, Marco, et al.
(författare)
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Wake analysis of drag components in gliding flight of a jackdaw (Corvus monedula) during moult
- 2017
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Ingår i: Interface Focus. - : The Royal Society. - 2042-8898 .- 2042-8901. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- To maintain the quality of the feathers, birds regularly undergo moult. It is widely accepted that moult affects flight performance, but the specific aerodynamic consequences have received relatively little attention. Here we measured the components of aerodynamic drag from the wake behind a gliding jackdaw (Corvus monedula) at different stages of its natural wing moult. We found that span efficiency was reduced (lift induced drag increased) and the wing profile drag coefficient was increased. Both effects best correlated with the corresponding reduction in spanwise camber. The negative effects are partially mitigated by adjustments of wing posture to minimize gaps in the wing, and by weight loss to reduce wing loading. By studying the aerodynamic consequences of moult, we can refine our understanding of the emergence of various moulting strategies found among birds.
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| 9. |
- Miyasaka, Keiichi, et al.
(författare)
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The role of curvature in silica mesoporous crystals
- 2012
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Ingår i: Interface Focus. - : The Royal Society. - 2042-8898 .- 2042-8901. ; 2:5, s. 634-644
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Tidskriftsartikel (refereegranskat)abstract
- Silica mesoporous crystals (SMCs) offer a unique opportunity to study micellar mesophases. Replication of non-equilibrium mesophases into porous silica structures allows the characterization of surfactant phases under a variety of chemical and physical perturbations, through methods not typically accessible to liquid crystal chemists. A poignant example is the use of electron microscopy and crystallography, as discussed herein, for the purpose of determining the fundamental role of amphiphile curvature, namely mean curvature and Gaussian curvature, which have been extensively studied in various fields such as polymer, liquid crystal, biological membrane, etc. The present work aims to highlight some current studies devoted to the interface curvature on SMCs, in which electron microscopy and electron crystallography (EC) are used to understand the geometry of silica wall surface in bicontinuous and cage-type mesostructures through the investigation of electrostatic potential maps. Additionally, we show that by altering the synthesis conditions during the preparation of SMCs, it is possible to isolate particles during micellar mesophase transformations in the cubic bicontinuous system, allowing us to view and study epitaxial relations under the specific synthesis conditions. By studying the relationship between mesoporous structure, interface curvature and micellar mesophases using electron microscopy and EC, we hope to bring new insights into the formation mechanism of these unique materials but also contribute a new way of understanding periodic liquid crystal systems.
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| 10. |
- Nyman, Elin, et al.
(författare)
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Requirements for multi-level systems pharmacology models to reach end-usage : the case of type 2 diabetes
- 2016
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Ingår i: Interface Focus. - London, UK : The Royal Society. - 2042-8898 .- 2042-8901. ; 6:2
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Forskningsöversikt (refereegranskat)abstract
- We are currently in the middle of a major shift in biomedical research: unprecedented and rapidly growing amounts of data may be obtained today, from in vitro, in vivo and clinical studies, at molecular, physiological and clinical levels. To make use of these large-scale, multi-level datasets, corresponding multi-level mathematical models are needed, i.e. models that simultaneously capture multiple layers of the biological, physiological and disease-level organization (also referred to as quantitative systems pharmacology-QSP-models). However, today's multi-level models are not yet embedded in end-usage applications, neither in drug research and development nor in the clinic. Given the expectations and claims made historically, this seemingly slow adoption may seem surprising. Therefore, we herein consider a specific example-type 2 diabetes-and critically review the current status and identify key remaining steps for these models to become mainstream in the future. This overview reveals how, today, we may use models to ask scientific questions concerning, e.g., the cellular origin of insulin resistance, and how this translates to the whole-body level and short-term meal responses. However, before these multi-level models can become truly useful, they need to be linked with the capabilities of other important existing models, in order to make them 'personalized' (e.g. specific to certain patient phenotypes) and capable of describing long-term disease progression. To be useful in drug development, it is also critical that the developed models and their underlying data and assumptions are easily accessible. For clinical end-usage, in addition, model links to decisionsupport systems combined with the engagement of other disciplines are needed to create user-friendly and cost-efficient software packages.
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