Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 164.266
Filtrar
1.
Lancet Planet Health ; 8(4): e270-e283, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38580428

RESUMO

The concurrent pressures of rising global temperatures, rates and incidence of species decline, and emergence of infectious diseases represent an unprecedented planetary crisis. Intergovernmental reports have drawn focus to the escalating climate and biodiversity crises and the connections between them, but interactions among all three pressures have been largely overlooked. Non-linearities and dampening and reinforcing interactions among pressures make considering interconnections essential to anticipating planetary challenges. In this Review, we define and exemplify the causal pathways that link the three global pressures of climate change, biodiversity loss, and infectious disease. A literature assessment and case studies show that the mechanisms between certain pairs of pressures are better understood than others and that the full triad of interactions is rarely considered. Although challenges to evaluating these interactions-including a mismatch in scales, data availability, and methods-are substantial, current approaches would benefit from expanding scientific cultures to embrace interdisciplinarity and from integrating animal, human, and environmental perspectives. Considering the full suite of connections would be transformative for planetary health by identifying potential for co-benefits and mutually beneficial scenarios, and highlighting where a narrow focus on solutions to one pressure might aggravate another.


Assuntos
Doenças Transmissíveis , Ecossistema , Animais , Humanos , Mudança Climática , Biodiversidade , Modelos Teóricos , Doenças Transmissíveis/epidemiologia
2.
Chaos ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38608314

RESUMO

The pathogen SARS-CoV-2 binds to the receptor angiotensin-converting enzyme 2 (ACE2) of the target cells and then replicates itself through the host, eventually releasing free virus particles. After infection, the CD8 T-cell response is triggered and appears to play a critical role in the defense against virus infections. Infected cells and their activated CD8 T-cells can cause tissue damage. Here, we established a mathematical model of within-host SARS-CoV-2 infection that incorporates the receptor ACE2, the CD8 T-cell response, and the damaged tissues. According to this model, we can get the basic reproduction number R0 and the immune reproduction number R1. We provide the theoretical proof for the stability of the disease-free equilibrium, immune-inactivated equilibrium, and immune-activated equilibrium. Finally, our numerical simulations show that the time delay in CD8 T-cell production can induce complex dynamics such as stability switching. These results provide insights into the mechanisms of SARS-CoV-2 infection and may help in the development of effective drugs against COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2 , Linfócitos T CD8-Positivos , Modelos Teóricos
3.
Water Sci Technol ; 89(7): 1665-1681, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619896

RESUMO

By integrating the successful case of the European Union emissions trading system, this study proposes a water emissions trading system, a novel method of reducing water pollution. Assuming that upstream governments allocate initial quotas to upstream businesses as the compensation standard, this approach defines the foundational principles of market trading mechanisms and establishes a robust watershed ecological compensation model to address challenges in water pollution prevention. To be specific, the government establishes a reasonable initial quota for upstream enterprises, which can be used to limit the emissions of upstream pollution. When enterprises exceed their allocated emissions quota, they face financial penalties. Conversely, these emissions rights can be transformed into profitable assets by participating in the trading market as a form of ecological compensation. Numerical simulations demonstrate that various pollutant emissions from upstream businesses will have various effects on the profits of other businesses. Businesses in the upstream region received reimbursement from the assigned emission rights through the market mechanism, demonstrating that ecological compensation for the watershed can be achieved through the market mechanism. This novel market trading system aims at controlling emissions management from the perspectives of individual enterprises and ultimately optimizing the aquatic environment.


Assuntos
Poluentes Ambientais , Rios , Poluição da Água/análise , Modelos Teóricos , China
4.
J Water Health ; 22(3): 487-509, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38557566

RESUMO

As a basic infrastructure, sewers play an important role in the innards of every city and town to remove unsanitary water from all kinds of livable and functional spaces. Sewer pipe failures (SPFs) are unwanted and unsafe in many ways, as the disturbance that they cause is undeniable. Sewer pipes meet manholes frequently, unlike water distribution systems, as in sewers, water movement is due to gravity and manholes are needed in every intersection as well as through pipe length. Many studies have been focused on sewer pipe failures and so on, but few investigations have been done to show the effect of manhole proximity on pipe failure. Predicting and localizing the sewer pipe failures is affected by different parameters of sewer pipe properties, such as material, age, slope, and depth of the sewer pipes. This study investigates the applicability of a support vector machine (SVM), a supervised machine learning (ML) algorithm, for the development of a prediction model to predict sewer pipe failures and the effects of manhole proximity. The results show that SVM with an accuracy of 84% can properly approximate the manhole effects on sewer pipe failures.


Assuntos
Algoritmos , Modelos Teóricos , Movimentos da Água , Aprendizado de Máquina , Água , Esgotos
5.
Water Sci Technol ; 89(6): 1497-1511, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38557714

RESUMO

Identifying vulnerable areas to erosion within the watershed and implementing best management practices (BMPs) are crucial steps in mitigating watershed degradation by minimizing sediment yields. The present study evaluates and identifies the BMPs in the Seybouse basin, northeastern Algeria, using the Soil and Water Assessment Tool (SWAT) model. After successful calibration and validation, the model demonstrated a satisfactory ability to simulate monthly discharge and sediment. Then, the calibrated model was employed to evaluate the efficacy of diverse management practices in sediment control. In the SWAT, three soil and conservation practices, as well as vegetated filter strips (VFSs), grade stabilization structures (GSSs), and terracing were evaluated. The average annual sediment yield in the Seybouse watershed is determined to be 14.43 t/ha year, constituting 71% of the total soil loss. VFS demonstrated a sediment reduction of 37.30%, GSS 20.40%, and terracing 42.30%. Among these strategies, terracing results in the greatest reduction, followed by VFS. The results of this study area can be useful for informed decision-making regarding optimal watershed management strategies.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos , Sedimentos Geológicos/química , Rios , Argélia , Modelos Teóricos , Solo , Água
6.
PeerJ ; 12: e16964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560455

RESUMO

Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as systems of differential equations, are frequently employed to study the infection dynamics of various viruses. Adopting such models for results of in vitro experiments can be beneficial in a number of aspects, such as model simplification (e.g., the absence of adaptive immune response and innate immunity cells), better measurement accuracy, and the possibility to measure additional data types in comparison with in vivo case. In this study, we consider a refinement of our previously developed and validated model based on a system of integro-differential equations. We fit the model to the experimental data of Omicron and Delta infections in Caco-2 (human intestinal epithelium model) and Calu-3 (lung epithelium model) cell lines. The data include known information on initial conditions, infectious virus titers, and intracellular viral RNA measurements at several time points post-infection. The model accurately explains the experimental data for both variants in both cell lines using only three variant- and cell-line-specific parameters. Namely, the cell entry rate is significantly lower for Omicron, and Omicron triggers a stronger cytokine production rate (i.e., innate immune response) in infected cells, ultimately making uninfected cells resistant to the virus. Notably, differences in only a single parameter (e.g., cell entry rate) are insufficient to obtain a reliable model fit for the experimental data.


Assuntos
COVID-19 , Humanos , Células CACO-2 , SARS-CoV-2 , Epitélio , Modelos Teóricos
7.
Rev Esc Enferm USP ; 58: e20230358, 2024.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-38587403

RESUMO

OBJECTIVE: To reflect on the contributions of representing nursing practice elements in the ISO 18.104:2023 standard. METHOD: This is a theoretical study with standard analysis. Categorical structures were described to represent nursing practice in terminological systems and contributions identified in the parts of the version were analyzed. RESULTS: There is innovation in the inclusion of nurse sensitive outcomes, nursing action, nursing diagnosis explanation as an indicator of nursing service demand and complexity of care, representation of concepts through mental maps and suggestion of use of restriction models for nursing actions. It describes that the Nursing Process is constituted by nursing diagnosis, nursing action and nurse sensitive outcomes. FINAL CONSIDERATIONS: Indicating a nursing diagnosis as an indicator will bring benefits for knowledge production and decision-making. Although care outcomes are not exclusive responses to nursing action, the modifiable attributes of a nursing diagnosis generate knowledge about clinical practice, nursing action effectiveness and subjects of care' health state. There is coherence in understanding the Nursing Process concept evolution.


Assuntos
Modelos Teóricos , Processo de Enfermagem , Humanos , Diagnóstico de Enfermagem
8.
Methods Mol Biol ; 2795: 247-261, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38594544

RESUMO

Increased day lengths and warm conditions inversely affect plant growth by directly modulating nuclear phyB, ELF3, and COP1 levels. Quantitative measures of the hypocotyl length have been key to gaining a deeper understanding of this complex regulatory network, while similar quantitative data are the foundation for many studies in plant biology. Here, we explore the application of mathematical modeling, specifically ordinary differential equations (ODEs), to understand plant responses to these environmental cues. We provide a comprehensive guide to constructing, simulating, and fitting these models to data, using the law of mass action to study the evolution of molecular species. The fundamental principles of these models are introduced, highlighting their utility in deciphering complex plant physiological interactions and testing hypotheses. This brief introduction will not allow experimentalists without a mathematical background to run their own simulations overnight, but it will help them grasp modeling principles and communicate with more theory-inclined colleagues.


Assuntos
Modelos Teóricos , 60485 , Plantas , Hipocótilo/fisiologia
9.
PLoS One ; 19(4): e0301217, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564571

RESUMO

BACKGROUND: Leishmaniasis are a group of diseases caused by more than 20 species of the protozoan that are transmitted through the bite of female sand fly. The disease is endemic to 98 countries of the world. It affects most commonly the poorest of the poor and mainly males. Several research has been conducted to propose disease control strategies. Effective medical care, vector control, environmental hygiene, and personal protection are the mainstays of the current preventative and control methods. The mathematical models for the transmission dynamics of the disease studied so far did not consider the sex-biased burden of the disease into consideration. METHODOLOGY: Unlike the previous VL works, this study introduces a new deterministic sex-structured model for understanding the transmission dynamics of visceral leishmaniasis. Basic properties of the model including basic reproduction number ([Formula: see text]), and conditions for the existence of backward bifurcation of the model are explored. Baseline parameter values were estimated after the model was fitted to Ethiopia's VL data. Sensitivity analysis of the model was performed to identify the parameters that significantly impact the disease threshold. Numerical simulations were performed using baseline parameter values, and scenario analysis is performed by changing some of these parameters as appropriate. CONCLUSION: The analysis of the model shows that there is a possibility for a backward bifurcation for [Formula: see text], which means bringing [Formula: see text] to less than unity may not be enough to eradicate the disease. Our numerical result shows that the implementation of disease-preventive strategies, as well as effectively treating the affected ones can significantly reduce the disease prevalence if applied for more proportion of the male population. Furthermore, the implementation of vector management strategies also can considerably reduce the total prevalence of the disease. However, it is demonstrated that putting more effort in treating affected reservoir animals may not have any significant effect on the overall prevalence of the disease as compared to other possible mechanisms. The numerical simulation infers that a maximum of 60% of extra preventative measures targeted to only male population considerably reduces the total prevalence of VL by 80%. It is also possible to decrease the total prevalence of VL by 69.51% when up to 50% additional infected males receive treatment with full efficacy. Moreover, applying a maximum of 15% additional effort to reduce the number of vectors, decreases the total VL prevalence by 57.71%. Therefore, in order to reduce the disease burden of visceral leishmaniasis, public health officials and concerned stakeholders need to give more emphasis to the proportion of male humans in their intervention strategies.


Assuntos
Leishmaniose Visceral , Phlebotomus , Psychodidae , Disfunções Sexuais Fisiológicas , Humanos , Animais , Masculino , Feminino , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Modelos Teóricos , Saúde Pública
10.
PLoS One ; 19(4): e0298318, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564574

RESUMO

Cliodynamics is a still a relatively new research area with the purpose of investigating and modelling historical processes. One of its first important mathematical models was proposed by Turchin and called "Demographic-Fiscal Model" (DFM). This DFM was one of the first and is one of a few models that link population with state dynamics. In this work, we propose a possible alternative to the classical Turchin DFM, which contributes to further model development and comparison essential for the field of cliodynamics. Our "Demographic-Wealth Model" (DWM) aims to also model link between population and state dynamics but makes different modelling assumptions, particularly about the type of possible taxation. As an important contribution, we employ tools from nonlinear dynamics, e.g., existence theory for periodic orbits as well as analytical and numerical bifurcation analysis, to analyze the DWM. We believe that these tools can also be helpful for many other current and future models in cliodynamics. One particular focus of our analysis is the occurrence of Hopf bifurcations. Therefore, a detailed analysis is developed regarding equilibria and their possible bifurcations. Especially noticeable is the behavior of the so-called coexistence point. While changing different parameters, a variety of Hopf bifurcations occur. In addition, it is indicated, what role Hopf bifurcations may play in the interplay between population and state dynamics. There are critical values of different parameters that yield periodic behavior and limit cycles when exceeded, similar to the "paradox of enrichment" known in ecology. This means that the DWM provides one possible avenue setup to explain in a simple format the existence of secular cycles, which have been observed in historical data. In summary, our model aims to balance simplicity, linking to the underlying processes and the goal to represent secular cycles.


Assuntos
Modelos Biológicos , Modelos Teóricos , Ecologia , Dinâmica não Linear , Dinâmica Populacional
11.
PLoS One ; 19(4): e0301516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38568998

RESUMO

The integration of renewable energy systems into electricity grids is a solution for strengthening electricity distribution networks (SEDNs). Renewable energies such as solar photovoltaics are suitable for reinforcing a low-voltage line by offering an electrical energy storage system. However, the integration of photovoltaic systems can lead to problems of harmonic distortion due to the presence of direct current or non-linear feedback in networks from other sources. Therefore, connection standards exist to ensure the quality of the energy before injection at a point of common coupling (PCC). In this work, particle swarm optimization (PSO) is used to control a boost converter and to evaluate the power losses and the harmonic distortion rate. The test on the IEEE 14 bus standard makes it possible to determine the allocation or integration nodes for other sources such as biomass, wind or hydrogen generators, in order to limit the impact of harmonic disturbances (LIHs). The evaluation of the harmonic distortion rate, the power losses as well as the determination of the system size is done using an objective function defined based on the integration and optimization constraints of the system. The proposed model performs better since the grid current and voltage are stabilized in phase after the photovoltaic source is injected.


Assuntos
Fontes de Energia Elétrica , Modelos Teóricos , Algoritmos , Energia Renovável , Eletricidade
12.
PLoS One ; 19(4): e0301272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593152

RESUMO

In urban stochastic transportation networks, there are specific links that hold great importance. Disruptions or failures in these critical links can lead to reduced connectivity within the road network. Under this circumstance, this manuscript proposed a novel identification of critical links mathematical optimization model based on the optimal reliable path with consideration of link correlations under demand uncertainty. The method presented in this paper offers a solution to bypass the necessity of conducting a full scan of the entire road network. Due to the non-additive and non-linear properties of the proposed model, a modified heuristic algorithm based on K-shortest algorithm and inequality technical is presented. The numerical experiments are conducted to show that improve a certain road link may not necessarily improve the overall traffic conditions. Moreover, the results indicate that if the travel time reliability is not considered, it will bring errors to the identification of key links.


Assuntos
Meios de Transporte , Viagem , Reprodutibilidade dos Testes , Modelos Teóricos , Algoritmos
13.
Sci Rep ; 14(1): 8304, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594376

RESUMO

Impaired cardiac function has been described as a frequent complication of COVID-19-related pneumonia. To investigate possible underlying mechanisms, we represented the cardiovascular system by means of a lumped-parameter 0D mathematical model. The model was calibrated using clinical data, recorded in 58 patients hospitalized for COVID-19-related pneumonia, to make it patient-specific and to compute model outputs of clinical interest related to the cardiocirculatory system. We assessed, for each patient with a successful calibration, the statistical reliability of model outputs estimating the uncertainty intervals. Then, we performed a statistical analysis to compare healthy ranges and mean values (over patients) of reliable model outputs to determine which were significantly altered in COVID-19-related pneumonia. Our results showed significant increases in right ventricular systolic pressure, diastolic and mean pulmonary arterial pressure, and capillary wedge pressure. Instead, physical quantities related to the systemic circulation were not significantly altered. Remarkably, statistical analyses made on raw clinical data, without the support of a mathematical model, were unable to detect the effects of COVID-19-related pneumonia in pulmonary circulation, thus suggesting that the use of a calibrated 0D mathematical model to describe the cardiocirculatory system is an effective tool to investigate the impairments of the cardiocirculatory system associated with COVID-19.


Assuntos
COVID-19 , Sistema Cardiovascular , Humanos , Reprodutibilidade dos Testes , Circulação Pulmonar , Modelos Teóricos
14.
PLoS Comput Biol ; 20(4): e1011993, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38557869

RESUMO

The intensification of intervention activities against the fatal vector-borne disease gambiense human African trypanosomiasis (gHAT, sleeping sickness) in the last two decades has led to a large decline in the number of annually reported cases. However, while we move closer to achieving the ambitious target of elimination of transmission (EoT) to humans, pockets of infection remain, and it becomes increasingly important to quantitatively assess if different regions are on track for elimination, and where intervention efforts should be focused. We present a previously developed stochastic mathematical model for gHAT in the Democratic Republic of Congo (DRC) and show that this same formulation is able to capture the dynamics of gHAT observed at the health area level (approximately 10,000 people). This analysis was the first time any stochastic gHAT model has been fitted directly to case data and allows us to better quantify the uncertainty in our results. The analysis focuses on utilising a particle filter Markov chain Monte Carlo (MCMC) methodology to fit the model to the data from 16 health areas of Mosango health zone in Kwilu province as a case study. The spatial heterogeneity in cases is reflected in modelling results, where we predict that under the current intervention strategies, the health area of Kinzamba II, which has approximately one third of the health zone's cases, will have the latest expected year for EoT. We find that fitting the analogous deterministic version of the gHAT model using MCMC has substantially faster computation times than fitting the stochastic model using pMCMC, but produces virtually indistinguishable posterior parameterisation. This suggests that expanding health area fitting, to cover more of the DRC, should be done with deterministic fits for efficiency, but with stochastic projections used to capture both the parameter and stochastic variation in case reporting and elimination year estimations.


Assuntos
Tripanossomíase Africana , Animais , Humanos , Tripanossomíase Africana/epidemiologia , República Democrática do Congo/epidemiologia , Modelos Teóricos , Previsões , Cadeias de Markov , Trypanosoma brucei gambiense
15.
J Environ Manage ; 357: 120762, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574708

RESUMO

Urban pluvial flooding is becoming a global concern, exacerbated by urbanization and climate change, especially in rapidly developing areas where existing sewer systems lag behind growth. In order to minimize a system's functional failures during extreme rainfalls, localized engineering solutions are required for urban areas chronically suffering from pluvial floods. This study critically evaluates the Deep Tunnel Sewer System (DTSS) as a robust grey infrastructure solution for enhancing urban flood resilience, with a case study in the Gangnam region of Seoul, South Korea. To do so, we integrated a one-dimensional sewer model with a rapid flood spreading model to identify optimal routes and conduit diameters for the DTSS, focusing on four flood-related metrics: the total flood volume, the flood duration, the peak flooding rate, and the number of flooded nodes. Results indicate that, had the DTSS been in place, it could have reduced historical flood volumes over the last decade by 50.1-99.3%, depending on the DTSS route. Regarding the conduit diameter, an 8 m diameter was found to be optimal for minimizing all flood-related metrics. Our research also developed the Intensity-Duration-Frequency (IDF) surfaces in three dimensions, providing a correlation between simulated flood-related metrics and design rainfall characteristics to distinguish the effect of DTSS on flood risk reduction. Our findings demonstrate how highly engineered solutions can enhance urban flood resilience, but they may still face challenges during extreme heavy rainfalls with a 80-year frequency or above. This study contributes to rational decision-making and emergency management in the face of increasing urban pluvial flood risks.


Assuntos
Inundações , Resiliência Psicológica , Modelos Teóricos , Urbanização , República da Coreia , Cidades
16.
J Environ Manage ; 357: 120647, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583385

RESUMO

Subsidy policies are instrumental in driving the development of new energy. However, the effective allocation of new energy subsidies over time is challenging given fiscal constraints. This study addresses this challenge by considering the learning effect associated with the new energy industry. A two-stage dynamic programming model is proposed to capture the investment decision-making process of companies under new energy subsidy policies and government subsidy setups. Theoretical findings suggest that company investment decisions in new energy are influenced by a guiding principle: The subsidy rate should be negatively correlated with the variation rate of production scale increment (VRPSI). We calibrate this investment decision principle using wind power data from 14 countries. According to this principle, excessive subsidy rates may result in a low VRPSI, thereby diminishing future investment profitability in the new energy industry and leading to subsidy inefficiency. Upon investigating the efficiency of annual subsidy allocation, we find that the subsidy rates were potentially set too high in 2014, 2016, and 2017. Furthermore, the government should exercise caution regarding an inefficient subsidy pattern whereby companies invest in new energy only when the subsidy rate exceeds a certain threshold, neglecting traditional power sources. It is crucial to note that although this study uses wind power industry data for calibration and simulation, the theoretical model can be broadly applied to other new energy industries and emerging industries with increasing marginal net profit.


Assuntos
Indústrias , Vento , Política Pública , Modelos Teóricos , Investimentos em Saúde
17.
PLoS One ; 19(4): e0298451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635576

RESUMO

The paper presents an innovative computational framework for predictive solutions for simulating the spread of malaria. The structure incorporates sophisticated computing methods to improve the reliability of predicting malaria outbreaks. The study strives to provide a strong and effective tool for forecasting the propagation of malaria via the use of an AI-based recurrent neural network (RNN). The model is classified into two groups, consisting of humans and mosquitoes. To develop the model, the traditional Ross-Macdonald model is expanded upon, allowing for a more comprehensive analysis of the intricate dynamics at play. To gain a deeper understanding of the extended Ross model, we employ RNN, treating it as an initial value problem involving a system of first-order ordinary differential equations, each representing one of the seven profiles. This method enables us to obtain valuable insights and elucidate the complexities inherent in the propagation of malaria. Mosquitoes and humans constitute the two cohorts encompassed within the exposition of the mathematical dynamical model. Human dynamics are comprised of individuals who are susceptible, exposed, infectious, and in recovery. The mosquito population, on the other hand, is divided into three categories: susceptible, exposed, and infected. For RNN, we used the input of 0 to 300 days with an interval length of 3 days. The evaluation of the precision and accuracy of the methodology is conducted by superimposing the estimated solution onto the numerical solution. In addition, the outcomes obtained from the RNN are examined, including regression analysis, assessment of error autocorrelation, examination of time series response plots, mean square error, error histogram, and absolute error. A reduced mean square error signifies that the model's estimates are more accurate. The result is consistent with acquiring an approximate absolute error close to zero, revealing the efficacy of the suggested strategy. This research presents a novel approach to solving the malaria propagation model using recurrent neural networks. Additionally, it examines the behavior of various profiles under varying initial conditions of the malaria propagation model, which consists of a system of ordinary differential equations.


Assuntos
Culicidae , Malária , Animais , Humanos , Reprodutibilidade dos Testes , Redes Neurais de Computação , Malária/epidemiologia , Modelos Teóricos
18.
Bull Math Biol ; 86(5): 60, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38641666

RESUMO

Liquid-liquid phase separation is an intracellular mechanism by which molecules, usually proteins and RNAs, interact and then rapidly demix from the surrounding matrix to form membrane-less compartments necessary for cellular function. Occurring in both the cytoplasm and the nucleus, properties of the resulting droplets depend on a variety of characteristics specific to the molecules involved, such as valency, density, and diffusion within the crowded environment. Capturing these complexities in a biologically relevant model is difficult. To understand the nuanced dynamics between proteins and RNAs as they interact and form droplets, as well as the impact of these interactions on the resulting droplet properties, we turn to sensitivity analysis. In this work, we examine a previously published mathematical model of two RNA species competing for the same protein-binding partner. We use the combined analyses of Morris Method and Sobol' sensitivity analysis to understand the impact of nine molecular parameters, subjected to three different initial conditions, on two observable LLPS outputs: the time of phase separation and the composition of the droplet field. Morris Method is a screening method capable of highlighting the most important parameters impacting a given output, while the variance-based Sobol' analysis can quantify both the importance of a given parameter, as well as the other model parameters it interacts with, to produce the observed phenomena. Combining these two techniques allows Morris Method to identify the most important dynamics and circumvent the large computational expense associated with Sobol', which then provides more nuanced information about parameter relationships. Together, the results of these combined methodologies highlight the complicated protein-RNA relationships underlying both the time of phase separation and the composition of the droplet field. Sobol' sensitivity analysis reveals that observed spatial and temporal dynamics are due, at least in part, to high-level interactions between multiple (3+) parameters. Ultimately, this work discourages using a single measurement to extrapolate the value of any single rate or parameter value, while simultaneously establishing a framework in which to analyze and assess the impact of these small-scale molecular interactions on large-scale droplet properties.


Assuntos
Modelos Biológicos , 60422 , Conceitos Matemáticos , Modelos Teóricos , RNA
19.
PLoS Biol ; 22(4): e3002583, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38598454

RESUMO

Endosymbiotic relationships are pervasive across diverse taxa of life, offering key avenues for eco-evolutionary dynamics. Although a variety of experimental and empirical frameworks have shed light on critical aspects of endosymbiosis, theoretical frameworks (mathematical models) are especially well-suited for certain tasks. Mathematical models can integrate multiple factors to determine the net outcome of endosymbiotic relationships, identify broad patterns that connect endosymbioses with other systems, simplify biological complexity, generate hypotheses for underlying mechanisms, evaluate different hypotheses, identify constraints that limit certain biological interactions, and open new lines of inquiry. This Essay highlights the utility of mathematical models in endosymbiosis research, particularly in generating relevant hypotheses. Despite their limitations, mathematical models can be used to address known unknowns and discover unknown unknowns.


Assuntos
Modelos Teóricos , Simbiose , Evolução Biológica
20.
PLoS Comput Biol ; 20(4): e1012015, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38620017

RESUMO

Recent advances in single-cell sequencing technology have provided opportunities for mathematical modeling of dynamic developmental processes at the single-cell level, such as inferring developmental trajectories. Optimal transport has emerged as a promising theoretical framework for this task by computing pairings between cells from different time points. However, optimal transport methods have limitations in capturing nonlinear trajectories, as they are static and can only infer linear paths between endpoints. In contrast, stochastic differential equations (SDEs) offer a dynamic and flexible approach that can model non-linear trajectories, including the shape of the path. Nevertheless, existing SDE methods often rely on numerical approximations that can lead to inaccurate inferences, deviating from true trajectories. To address this challenge, we propose a novel approach combining forward-backward stochastic differential equations (FBSDE) with a refined approximation procedure. Our FBSDE model integrates the forward and backward movements of two SDEs in time, aiming to capture the underlying dynamics of single-cell developmental trajectories. Through comprehensive benchmarking on multiple scRNA-seq datasets, we demonstrate the superior performance of FBSDE compared to other methods, highlighting its efficacy in accurately inferring developmental trajectories.


Assuntos
Modelos Teóricos , Processos Estocásticos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...