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1.
PLoS Comput Biol ; 20(3): e1011835, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38427695

ABSTRACT

From mathematical models of growth to computer simulations of pigmentation, the study of shell formation has given rise to an abundant number of models, working at various scales. Yet, attempts to combine those models have remained sparse, due to the challenge of combining categorically different approaches. In this paper, we propose a framework to streamline the process of combining the molecular and tissue scales of shell formation. We choose these levels as a proxy to link the genotype level, which is better described by molecular models, and the phenotype level, which is better described by tissue-level mechanics. We also show how to connect observations on shell populations to the approach, resulting in collections of molecular parameters that may be associated with different populations of real shell specimens. The approach is as follows: we use a Quality-Diversity algorithm, a type of black-box optimization algorithm, to explore the range of concentration profiles emerging as solutions of a molecular model, and that define growth patterns for the mechanical model. At the same time, the mechanical model is simulated over a wide range of growth patterns, resulting in a variety of spine shapes. While time-consuming, these steps only need to be performed once and then function as look-up tables. Actual pictures of shell spines can then be matched against the list of existing spine shapes, yielding a potential growth pattern which, in turn, gives us matching molecular parameters. The framework is modular, such that models can be easily swapped without changing the overall working of the method. As a demonstration of the approach, we solve specific molecular and mechanical models, adapted from available theoretical studies on molluscan shells, and apply the multiscale framework to evaluate the characteristics of spines from three distinct populations of Turbo sazae.


Subject(s)
Models, Theoretical , Mollusca , Animals , Computer Simulation , Algorithms
3.
BMC Geriatr ; 22(1): 746, 2022 09 12.
Article in English | MEDLINE | ID: mdl-36096722

ABSTRACT

BACKGROUND: Frailty and falls are two adverse characteristics of aging that impair the quality of life of senior people and increase the burden on the healthcare system. Various methods exist to evaluate frailty, but none of them are considered the gold standard. Technological methods have also been proposed to assess the risk of falling in seniors. This study aims to propose an objective method for complementing existing methods used to identify the frail state and risk of falling in older adults. METHOD: A total of 712 subjects (age: 71.3 ± 8.2 years, including 505 women and 207 men) were recruited from two Japanese cities. Two hundred and three people were classified as frail according to the Kihon Checklist. One hundred and forty-two people presented with a history of falling during the previous 12 months. The subjects performed a 45 s standing balance test and a 20 m round walking trial. The plantar pressure data were collected using a 7-sensor insole. One hundred and eighty-four data features were extracted. Automatic learning random forest algorithms were used to build the frailty and faller classifiers. The discrimination capabilities of the features in the classification models were explored. RESULTS: The overall balanced accuracy for the recognition of frail subjects was 0.75 ± 0.04 (F1-score: 0.77 ± 0.03). One sub-analysis using data collected for men aged > 65 years only revealed accuracies as high as 0.78 ± 0.07 (F1-score: 0.79 ± 0.05). The overall balanced accuracy for classifying subjects with a recent history of falling was 0.57 ± 0.05 (F1-score: 0.62 ± 0.04). The classification of subjects relative to their frailty state primarily relied on features extracted from the plantar pressure series collected during the walking test. CONCLUSION: In the future, plantar pressures measured with smart insoles inserted in the shoes of senior people may be used to evaluate aspects of frailty related to the physical dimension (e.g., gait and balance alterations), thus allowing assisting clinicians in the early identification of frail individuals.


Subject(s)
Frailty , Accidental Falls/prevention & control , Aged , Algorithms , Feasibility Studies , Female , Frail Elderly , Frailty/diagnosis , Frailty/epidemiology , Geriatric Assessment/methods , Humans , Male , Quality of Life
4.
BMC Ecol Evol ; 22(1): 53, 2022 04 28.
Article in English | MEDLINE | ID: mdl-35484499

ABSTRACT

BACKGROUND: Canalization, or buffering, is defined as developmental stability in the face of genetic and/or environmental perturbations. Understanding how canalization works is important in predicting how species survive environmental change, as well as deciphering how development can be altered in the evolutionary process. However, how developmental gene expression is linked to buffering remains unclear. We addressed this by co-expression network analysis, comparing gene expression changes caused by heat stress during development at a whole-embryonic scale in reciprocal hybrid crosses of sibling species of the ascidian Ciona that are adapted to different thermal environments. RESULTS: Since our previous work showed that developmental buffering in this group is maternally inherited, we first identified maternal developmental buffering genes (MDBGs) in which the expression level in embryos is both correlated to the level of environmental canalization and also differentially expressed depending on the species' gender roles in hybrid crosses. We found only 15 MDBGs, all of which showed high correlation coefficient values for expression with a large number of other genes, and 14 of these belonged to a single co-expression module. We then calculated correlation coefficients of expression between MDBGs and transcription factors in the central nervous system (CNS) developmental gene network that had previously been identified experimentally. We found that, compared to the correlation coefficients between MDBGs, which had an average of 0.96, the MDBGs are loosely linked to the CNS developmental genes (average correlation coefficient 0.45). Further, we investigated the correlation of each developmental to MDBGs, showing that only four out of 62 CNS developmental genes showed correlation coefficient > 0.9, comparable to the values between MDBGs, and three of these four genes were signaling molecules: BMP2/4, Wnt7, and Delta-like. CONCLUSIONS: We show that the developmental pathway is not centrally located within the buffering network. We found that out of 62 genes in the developmental gene network, only four genes showed correlation coefficients as high as between MDBGs. We propose that loose links to MDBGs stabilize spatiotemporally dynamic development.


Subject(s)
Ciona intestinalis , Ciona , Adaptation, Physiological , Animals , Biological Evolution , Ciona/genetics , Ciona intestinalis/genetics , Gene Regulatory Networks
5.
Micromachines (Basel) ; 13(2)2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35208369

ABSTRACT

In this article, we study the coupling of a collection of molecular oscillators, called repressilators, interacting indirectly through enzymatic saturation. We extended a measure of autocorrelation to identify the period of the whole system and to detect coupling behaviors. We explored the parameter space of concentrations of molecular species in each oscillator versus enzymatic saturation, and observed regions of uncoupled, partially, or fully coupled systems. In particular, we found a region that provided a sharp transition between no coupling, two coupled oscillators, and full coupling. In practical applications, signals from the environment can directly affect parameters such as local enzymatic saturation, and thus switch the system from a coupled to an uncoupled regime and vice-versa. Our parameter exploration can be used to guide the design of complex molecular systems, such as active materials or molecular robot controllers.

6.
PeerJ ; 8: e10170, 2020.
Article in English | MEDLINE | ID: mdl-33194400

ABSTRACT

BACKGROUND: Wearable activity trackers are regarded as a new opportunity to deliver health promotion interventions. Indeed, while the prediction of active behaviors is currently primarily relying on the processing of accelerometer sensor data, the emergence of smart clothes with multi-sensing capacities is offering new possibilities. Algorithms able to process data from a variety of smart devices and classify daily life activities could therefore be of particular importance to achieve a more accurate evaluation of physical behaviors. This study aims to (1) develop an activity recognition algorithm based on the processing of plantar pressure information provided by a smart-shoe prototype and (2) to determine the optimal hardware and software configurations. METHOD: Seventeen subjects wore a pair of smart-shoe prototypes composed of plantar pressure measurement insoles, and they performed the following nine activities: sitting, standing, walking on a flat surface, walking upstairs, walking downstairs, walking up a slope, running, cycling, and completing office work. The insole featured seven pressure sensors. For each activity, at least four minutes of plantar pressure data were collected. The plantar pressure data were cut in overlapping windows of different lengths and 167 features were extracted for each window. Data were split into training and test samples using a subject-wise assignment method. A random forest model was trained to recognize activity. The resulting activity recognition algorithms were evaluated on the test sample. A multi hold-out procedure allowed repeating the operation with 5 different assignments. The analytic conditions were modulated to test (1) different window lengths (1-60 seconds), (2) some selected sensor configurations and (3) different numbers of data features. RESULTS: A window length of 20 s was found to be optimum and therefore used for the rest of the analysis. Using all the sensors and all 167 features, the smart shoes predicted the activities with an average success of 89%. "Running" demonstrated the highest sensitivity (100%). "Walking up a slope" was linked with the lowest performance (63%), with the majority of the false negatives being "walking on a flat surface" and "walking upstairs." Some 2- and 3-sensor configurations were linked with an average success rate of 87%. Reducing the number of features down to 20 does not alter significantly the performance of the algorithm. CONCLUSION: High-performance human behavior recognition using plantar pressure data only is possible. In the future, smart-shoe devices could contribute to the evaluation of daily physical activities. Minimalist configurations integrating only a small number of sensors and computing a reduced number of selected features could maintain a satisfying performance. Future experiments must include a more heterogeneous population.

7.
Micromachines (Basel) ; 11(9)2020 Sep 22.
Article in English | MEDLINE | ID: mdl-32971889

ABSTRACT

DNA nanotechnology offers a fine control over biochemistry by programming chemical reactions in DNA templates. Coupled to microfluidics, it has enabled DNA-based reaction-diffusion microsystems with advanced spatio-temporal dynamics such as traveling waves. The Finite Element Method (FEM) is a standard tool to simulate the physics of such systems where boundary conditions play a crucial role. However, a fine discretization in time and space is required for complex geometries (like sharp corners) and highly nonlinear chemistry. Graphical Processing Units (GPUs) are increasingly used to speed up scientific computing, but their application to accelerate simulations of reaction-diffusion in DNA nanotechnology has been little investigated. Here we study reaction-diffusion equations (a DNA-based predator-prey system) in a tortuous geometry (a maze), which was shown experimentally to generate subtle geometric effects. We solve the partial differential equations on a GPU, demonstrating a speedup of ∼100 over the same resolution on a 20 cores CPU.

8.
Orig Life Evol Biosph ; 49(3): 111-145, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31399826

ABSTRACT

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the "bottom up" approach) and (4) how to infer the nature of the last universal common ancestor (the "top down" approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin. We also describe another family of paths motivated by a" circularity" approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question.


Subject(s)
Biology/history , Chemistry/history , Historiography , Informatics/history , Origin of Life , Paleontology/history , Philosophy/history , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , Molecular Biology/history
9.
Nat Protoc ; 12(9): 1912-1932, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28837132

ABSTRACT

Biochemical systems in which multiple components take part in a given reaction are of increasing interest. Because the interactions between these different components are complex and difficult to predict from basic reaction kinetics, it is important to test for the effect of variations in the concentration for each reagent in a combinatorial manner. For example, in PCR, an increase in the concentration of primers initially increases template amplification, but large amounts of primers result in primer-dimer by-products that inhibit the amplification of the template. Manual titration of biochemical mixtures rapidly becomes costly and laborious, forcing scientists to settle for suboptimal concentrations. Here we present a droplet-based microfluidics platform for mapping of the concentration space of up to three reaction components followed by detection with a fluorescent readout. The concentration of each reaction component is read through its internal standard (barcode), which is fluorescent but chemically orthogonal. We describe in detail the workflow, which comprises the following: (i) production of the microfluidics chips, (ii) preparation of the biochemical mixes, (iii) their mixing and compartmentalization into water-in-oil emulsion droplets via microfluidics, (iv) incubation and imaging of the fluorescent barcode and reporter signals by fluorescence microscopy and (v) image processing and data analysis. We also provide recommendations for choosing the appropriate fluorescent markers, programming the pressure profiles and analyzing the generated data. Overall, this platform allows a researcher with a few weeks of training to acquire ∼10,000 data points (in a 1D, 2D or 3D concentration space) over the course of a day from as little as 100-1,000 µl of reaction mix.


Subject(s)
Biological Assay/instrumentation , Biological Assay/methods , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Titrimetry/instrumentation , Titrimetry/methods , Equipment Design , Fluorescent Dyes/analysis , Fluorescent Dyes/chemistry , Image Processing, Computer-Assisted/methods , Surface-Active Agents/chemistry
10.
Astrobiology ; 15(12): 1031-42, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26684503

ABSTRACT

Contents 1. Introduction 1.1. A workshop and this document 1.2. Framing origins of life science 1.2.1. What do we mean by the origins of life (OoL)? 1.2.2. Defining life 1.2.3. How should we characterize approaches to OoL science? 1.2.4. One path to life or many? 2. A Strategy for Origins of Life Research 2.1. Outcomes-key questions and investigations 2.1.1. Domain 1: Theory 2.1.2. Domain 2: Practice 2.1.3. Domain 3: Process 2.1.4. Domain 4: Future studies 2.2. EON Roadmap 2.3. Relationship to NASA Astrobiology Roadmap and Strategy documents and the European AstRoMap Appendix I Appendix II Supplementary Materials References.


Subject(s)
Interdisciplinary Communication , Natural Science Disciplines , Origin of Life , Research , Consensus , Exobiology , Life , Metabolic Networks and Pathways , Models, Theoretical , Physical Phenomena , Planets , RNA
11.
PLoS One ; 10(10): e0140663, 2015.
Article in English | MEDLINE | ID: mdl-26480478

ABSTRACT

We propose a metric which can be used to compute the amount of heritable variation enabled by a given dynamical system. A distribution of selection pressures is used such that each pressure selects a particular fixed point via competitive exclusion in order to determine the corresponding distribution of potential fixed points in the population dynamics. This metric accurately detects the number of species present in artificially prepared test systems, and furthermore can correctly determine the number of heritable sets in clustered transition matrix models in which there are no clearly defined genomes. Finally, we apply our metric to the GARD model and show that it accurately reproduces prior measurements of the model's heritability.


Subject(s)
Heredity , Models, Genetic , Origin of Life , Evolution, Molecular , Selection, Genetic
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