| 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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| 11. |
- Petrone, Luigi, et al.
(författare)
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Chemistry-specific surface adsorption of the barnacle settlement-inducing protein complex
- 2015
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Ingår i: Interface Focus. - : Royal Society, The. - 2042-8898 .- 2042-8901. ; 5:1, s. 20140047-
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Tidskriftsartikel (refereegranskat)abstract
- Gregarious settlement in barnacle larvae (cyprids) is induced by a contact pheromone, the settlement-inducing protein complex (SIPC). The SIPC has been identified both in the cuticle of adult barnacles and in the temporary adhesive secretion (footprint) of cyprids. Besides acting as a settlement inducer, the presence of the SIPC in footprints points to its additional involvement in the adhesion process. SIPC adsorption behaviour was therefore investigated on a series of self-assembled monolayers (SAMs) by surface plasmon resonance at the pH of seawater (8.3). Fibrinogen and alpha(2)-macroglobulin (A2M) (blood complement protease inhibitors with which the SIPC shares 29% sequence homology) were used in the adsorption experiments as positive and negative standards, respectively. The mass uptake of the SIPC was comparable to that of fibrinogen, with adsorption observed even on the protein-resistant oligo(ethylene glycol) surface. Notably, on the positively charged SAM the SIPC showed a kinetic overshoot, indicating a metastable configuration causing the amount of adsorbed protein to temporarily exceed its equilibrium value. A2M adsorption was low or negligible on all SAMs tested, except for the positively charged surface, indicating that A2M adsorption is mainly driven by electrostatics. Evaluation of SIPC non-specific adsorption kinetics revealed that it adsorbed irreversibly and non-cooperatively on all surfaces tested.
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| 12. |
- Rohwedder, A., et al.
(författare)
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Cloudbuster: a Python-based open source application for three-dimensional reconstruction and quantification of stacked biological imaging samples
- 2022
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Ingår i: Interface Focus. - : ROYAL SOC. - 2042-8898 .- 2042-8901. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional (3D) spheroid cultures are generating increasing interest in cancer research, e.g. for the evaluation of pharmacological effects of novel small molecule inhibitors. This is mainly due to the fact that such 3D structures reflect physiological characteristics of tumours and the cellular microenvironments they reside in more faithfully than two-dimensional (2D) cell cultures; in addition, they allow the reduction of animal experiments while providing significantly relevant human-based models. Quantification of such organoid structures as well as the mainly slice-based acquisition and thus forced 2D representation of 3D spheroids provide a challenge for the interpretation of the associated generated data. Here, we provide a novel open-source workflow to reconstruct a 3D entity from slice-recorded microscopical images with or without treatment with anti-migratory small molecule inhibitors. This reconstruction produces distinct point clouds as basis for subsequent comparison of basic readout parameters using average computer processor, memory and graphics resources within an acceptable time frame. We were able to validate the usefulness of this workflow using 3D data generated by various imaging techniques, including z-stacks from confocal microscopy and histochemically labelled spheroid sectioning, and demonstrate the possibility to accurately characterize inhibitor effects in great detail.
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| 13. |
- Sumpter, David J. T., et al.
(författare)
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The modelling cycle for collective animal behaviour
- 2012
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Ingår i: INTERFACE FOCUS. - : The Royal Society. - 2042-8898 .- 2042-8901. ; 2:6, s. 764-773
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Forskningsöversikt (refereegranskat)abstract
- Collective animal behaviour is the study of how interactions between individuals produce group level patterns, and why these interactions have evolved. This study has proved itself uniquely interdisciplinary, involving physicists, mathematicians, engineers as well as biologists. Almost all experimental work in this area is related directly or indirectly to mathematical models, with regular movement back and forth between models, experimental data and statistical fitting. In this paper, we describe how the modelling cycle works in the study of collective animal behaviour. We classify studies as addressing questions at different levels or linking different levels, i.e. as local, local to global, global to local or global. We also describe three distinct approaches-theory-driven, data-driven and model selection-to these questions. We show, with reference to our own research on species across different taxa, how we move between these different levels of description and how these various approaches can be applied to link levels together.
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| 14. |
- Tsao, K., et al.
(författare)
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Effects of regional differences and demography in modelling foot-and-mouth disease in cattle at the national scale
- 2020
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Ingår i: Interface Focus. - : Royal Society Publishing. - 2042-8898 .- 2042-8901. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Foot-and-mouth disease (FMD) is a fast-spreading viral infection that can produce large and costly outbreaks in livestock populations. Transmission occurs at multiple spatial scales, as can the actions used to control outbreaks. The US cattle industry is spatially expansive, with heterogeneous distributions of animals and infrastructure. We have developed a model that incorporates the effects of scale for both disease transmission and control actions, applied here in simulating FMD outbreaks in US cattle. We simulated infection initiating in each of the 3049 counties in the contiguous US, 100 times per county. When initial infection was located in specific regions, large outbreaks were more likely to occur, driven by infrastructure and other demographic attributes such as premises clustering and number of cattle on premises. Sensitivity analyses suggest these attributes had more impact on outbreak metrics than the ranges of estimated disease parameter values. Additionally, although shipping accounted for a small percentage of overall transmission, areas receiving the most animal shipments tended to have other attributes that increase the probability of large outbreaks. The importance of including spatial and demographic heterogeneity in modelling outbreak trajectories and control actions is illustrated by specific regions consistently producing larger outbreaks than others. © 2019 The Author(s) Published by the Royal Society. All rights reserved.
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| 15. |
- Wiesner, K., et al.
(författare)
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Haematopoietic stem cells : Entropic landscapes of differentiation
- 2018
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Ingår i: Interface Focus. - : The Royal Society. - 2042-8898 .- 2042-8901. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- The metaphor of a potential epigenetic differentiation landscape broadly suggests that during differentiation a stem cell approaches a stable equilibrium state from a higher free energy towards a stable equilibrium state which represents the final cell type. It has been conjectured that there is an analogy to the concept of entropy in statistical mechanics. In this context, in the undifferentiated state, the entropy would be large since fewer constraints exist on the gene expression programmes of the cell. As differentiation progresses, gene expression programmes become more and more constrained and thus the entropy would be expected to decrease. In order to assess these predictions, we compute the Shannon entropy for time-resolved single-cell gene expression data in two different experimental set-ups of haematopoietic differentiation. We find that the behaviour of this entropy measure is in contrast to these predictions. In particular, we find that the Shannon entropy is not a decreasing function of developmental pseudo-time but instead it increases towards the time point of commitment before decreasing again. This behaviour is consistent with an increase in gene expression disorder observed in populations sampled at the time point of commitment. Single cells in these populations exhibit different combinations of regulator activity that suggest the presence of multiple configurations of a potential differentiation network as a result of multiple entry points into the committed state.
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| 16. |
- Hammarlund, Emma U.
(författare)
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Harnessing hypoxia as an evolutionary driver of complex multicellularity : Hypoxia drives multicellular evolution
- 2020
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Ingår i: Interface Focus. - 2042-8898. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Animal tissue requires low-oxygen conditions for its maintenance. The need for low-oxygen conditions contrasts with the idea of an evolutionary leap in animal diversity as a result of expanding oxic conditions. To accommodate tissue renewal at oxic conditions, however, vertebrate animals and vascular plants demonstrate abilities to access hypoxia. Here, I argue that multicellular organisms sustain oxic conditions first after internalizing hypoxic conditions. The 'harnessing' of hypoxia has allowed multicellular evolution to leave niches that were stable in terms of oxygen concentrations for those where oxygen fluctuates. Since oxygen fluctuates in most settings on Earth's surface, the ancestral niche would have been a deep marine setting. The hypothesis that 'large life' depends on harnessing hypoxia is illustrated in the context of conditions that promote the immature cell phenotype (stemness) in animal physiology and tumour biology and offers one explanation for the general rarity of diverse multicellularity over most of Earth's history.
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