Dynamical Models of Biology and Medicine

Mathematical and computational modeling approaches in biological and medical research are experiencing rapid growth globally. This Special Issue Book intends to scratch the surface of this exciting phenomenon. The subject areas covered involve general mathematical methods and their applications in biology and medicine, with an emphasis on work related to mathematical and computational modeling of the complex dynamics observed in biological and medical research. Fourteen rigorously reviewed papers were included in this Special Issue. These papers cover several timely topics relating to classical population biology, fundamental biology, and modern medicine. While the authors of these papers dealt with very different modeling questions, they were all motivated by specific applications in biology and medicine and employed innovative mathematical and computational methods to study the complex dynamics of their models. We hope that these papers detail case studies that will inspire many additional mathematical modeling efforts in biology and medicin

Differentiating between V‐ and G‐series nerve agent and simulant vapours using fluorescent film responses

In-field rapid and reliable identification of nerve agents is critical for the protection of Defence and National Security personnel as well as communities. Fluorescence-based detectors can be portable and provide rapid detection of chemical threats. However, most current approaches cannot differentiate between dilute vapors of nerve agent classes and are susceptible to false positives due to the presence of common acids. Here a fluorescence-based method is shown for rapid differentiation between the V-series and phosphonofluoridate G-series nerve agents and avoids false positives due to common acids. Differentiation is achieved through harnessing two different mechanisms. Detection of the V-series is achieved using photoinduced hole transfer whereby the fluorescence of the sensing material is quenched in the presence of the V-series agent. The G-series is detected using a turn-on mechanism in which a silylated excited state intramolecular proton transfer sensing molecule is selectively deprotected by hydrogen fluoride, which is typically found as a contaminant and/or breakdown product in G-series agents such as sarin. The strategy provided discrimination between classes, as the sensor for the G-series agent class is insensitive to the V-series agent, and vice versa, and neither responded to common acids

Mixed Eucalyptus plantations in subtropical China enhance phosphorus accumulation and transformation in soil aggregates

IntroductionThe production of Eucalyptus, a principal economic tree genus in China, is faced with challenges related to soil phosphorus (P) limitations. In this study, we explore variations in phosphorus content, storage, and transformation in Eucalyptus forests. We hypothesize that mixed forests augment soil aggregate stability and P content and that microaggregates are pivotal in determining P differences between mixed and pure forests. Additionally, we posit that mixed forests foster P transformation, enhancing its efficacy in the soil. Current research on the distribution and transformation of soil total P (TP) and P fractions at the soil aggregate level is limited.MethodsIn this study, we selected soil from a Eucalyptus-Mytilaria laosensis Lecomte mixed forest, Eucalyptus-Erythrophleum fordii Oliv mixed forest, and pure Eucalyptus forest in Chongzuo County, Guangxi, China, as the research objects. Using a dry-sieving method, we divided the soil collected in situ from the 0–40 cm layer into aggregates of >2, 1–2, 0.25–1, and <0.25 mm particle sizes, measured the TP and P fractions (resin-extractable inorganic P, bicarbonate-extractable inorganic P, bicarbonate-extractable organic P, sodium hydroxide-extractable inorganic P, sodium hydroxide-extractable organic P, dilute hydrochloric acid-extractable P, concentrated hydrochloric acid extractable inorganic P, concentrated hydrochloric acid-extractable organic P and residue-P) in different aggregates, and used redundancy analysis and PLS SEM to reveal key factors affecting soil P accumulation and transformation.ResultsThe results showed that compared to pure Eucalyptus forests, mixed Eucalyptus forests significantly enhanced the stability of soil aggregates and the content and storage of phosphorus, especially the Eucalyptus-Mytilaria laosensis mixed forest. The content of total soil phosphorus and its fractions decreased with increasing aggregate particle size, while the opposite trend was observed for stored P, with aggregates <0.25 mm being the main fraction influencing soil phosphorus accumulation. The transformation process of P fractions was primarily constrained by dissolution rates, mineralization rates, biological activity, including the action of microbes, fungi, and plant–root interactions, and other factors.DiscussionMixed forests increased the transformation of phosphorus in soil aggregates, effectivel enhancing the availability of soil phosphorus. In summary, this study provides important evidence for the systematic management of subtropical artificia Eucalyptus forests and the sustainable utilization of soil resources

Tree–litter–soil system C:N:P stoichiometry and tree organ homeostasis in mixed and pure Chinese fir stands in south subtropical China

IntroductionCultivation of Chinese fir (Cunninghamia lanceolata) have alleviated timber shortages and mixed stands with Chinese fir and indigenous species represent a sustainable forestry model. Studying system nutrient balance and tree nutrient homeostasis can provide insights into the ecological advantages of Chinese fir mixed stands and guide the management of plantations.MethodsMixed Chinese fir plantations with two native broadleaf species (Michelia macclurei and Mytilaria laosensis) and pure Chinese fir stands were examined for our study. The responses in carbon (C), nitrogen (N), and phosphorus (P) distribution and their stoichiometric characterization in the tree–litter–soil system to stand changes were evaluated. In addition, the ecological stoichiometric homeostasis of leaves, branches, trunks, bark and roots was used to measure the trees’ adaptive capacity to stand changes.ResultsThe results showed that the mixed stands of Michelia macclurei and Chinese fir significantly increased soil OC, TN, and TP, and improved the carbon sequestration and nutrient storage functions of the plantations. The mixed stands improved the litter mass and C:N and C:P to different degrees. The soil N and P imbalance reduced the leaf N:P, resulting in N limitation of different trees, while the principal component analysis showed that the improvement of soil TN in the mixed plantation alleviated the N limitation. In addition, mixed stands reduced N, P, and N:P homeostasis in branch, trunk, and bark of some Chinese fir trees, whereas mixed species showed flexibility in leaf N:P homeostasis.DiscussionTherefore, the selection of mixed species for mixed forests is a critical factor to consider when creating mixed plantations. These results contribute to our understanding of the ecological stoichiometry of fir plantations and are of considerable importance for the sustainable development of plantations as well as for the response to global climate change

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Preface for the Special Issue on Dynamical Models of Biology and Medicine

Mathematical and computational modeling approaches in biological and medical research are experiencing rapid growth globally [...

Photophysics of detection of explosive vapours via luminescence quenching of thin films: impact of inter-molecular interactions

Fluorescence-based detection of explosive analytes requires an understanding of the nature of the excited state responsible for the luminescence response of a sensing material. Many measurements are carried out to elucidate the fundamental photophysical properties of an emissive material in solution. However, simple transfer of the understanding gained from the solution measurements to the solid-state can lead to errors. This is in part due to the absence of inter-molecular interactions of the chromophores in solution, which are present in the solid-state. To understand the role of inter-molecular interactions on the detection of explosive analytes we have chosen dendrimers from two different families, D1 and D2, which allow facile control of the inter-molecular interactions through the choice of dendrons and emissive chromophores. Using ultrafast transient absorption spectroscopy we find that the solution photoinduced absorption (PA) for both materials can be explained in terms of the generation of singlet excitons, which decay to the ground state, or intersystem cross (ISC) to form a triplet exciton. In neat films however, we observe different photophysical behaviours; first, ISC to the triplet state does not occur, and second, depending on the chromophore, charge transfer and charge separated states are formed. Furthermore, we find that when either dendrimer is interfaced with analyte vapour, the singlet state is strongly quenched, generating a charge transfer state that undergoes geminate recombination

Solid-state fluorescence-based sensing of TATP via hydrogen peroxide detection

Fluorenylboronate ester chromophore-based thin films were investigated for the detection of triacetone triperoxide (TATP) vapors via the decomposition product, hydrogen peroxide. Sensing with a high level of sensitivity was achieved using a fluorescence "turn-on" mechanism based on the significant shifts in the absorption and photoluminescence spectra that occurs when the boronate esters were converted to phenoxides by hydrogen peroxide under basic conditions. The addition of an organic base was found to be critical for achieving fast conversion reactions and the formation of the phenoxide anions. Addition of a nitrile group to the fluorenyl boronate ester moiety improved the stability of the material to photooxidation, increased the photoluminescence quantum yields, and enhanced the absorption and emission shifts to longer wavelengths. In real-time sensing measurements, films comprising the cyanofluorenyl boronate ester moiety and tetra- n-butylammonium hydroxide had a response time to acid-decomposed TATP vapor of seconds and a limit of detection of 40 ppb in 60 s