A Mathematical Model Supports a Key Role for Ae4 (Slc4a9) in Salivary Gland Secretion

We develop a mathematical model of a salivary gland acinar cell with the objective of investigating the role of two \(\mathrm{Cl}^-/\mathrm{HCO}_3^-\) exchangers from the solute carrier family 4 (Slc4), Ae2 (Slc4a2) and Ae4 (Slc4a9), in fluid secretion. Water transport in this type of cell is predominantly driven by \(\mathrm{Cl}^-\) movement. Here, a basolateral \(\mathrm{Na}^+/ \mathrm{K}^+\) adenosine triphosphatase pump (NaK-ATPase) and a \(\mathrm{Na}^+\)–\(\mathrm{K}^+\)–\(2 \mathrm{Cl}^-\) cotransporter (Nkcc1) are primarily responsible for concentrating the intracellular space with \(\mathrm{Cl}^-\) well above its equilibrium potential. Gustatory and olfactory stimuli induce the release of \(\mathrm{Ca}^{2+}\) ions from the internal stores of acinar cells, which triggers saliva secretion. \(\mathrm{Ca}^{2+}\)-dependent \(\mathrm{Cl}^-\) and \(\mathrm{K}^+\) channels promote ion secretion into the luminal space, thus creating an osmotic gradient that promotes water movement in the secretory direction. The current model for saliva secretion proposes that \(\mathrm{Cl}^-/ \mathrm{HCO}_3^-\) anion exchangers (Ae), coupled with a basolateral \(\mathrm{Na}^+/\hbox {proton}\) (\(\hbox {H}^+\)) (Nhe1) antiporter, regulate intracellular pH and act as a secondary \(\mathrm{Cl}^-\) uptake mechanism (Nauntofte in Am J Physiol Gastrointest Liver Physiol 263(6):G823–G837, 1992; Melvin et al. in Annu Rev Physiol 67:445–469, 2005.  https://doi.org/10.1146/annurev.physiol.67.041703.084745). Recent studies demonstrated that Ae4 deficient mice exhibit an approximate \(30\%\) decrease in gland salivation (Peña-Münzenmayer et al. in J Biol Chem 290(17):10677–10688, 2015). Surprisingly, the same study revealed that absence of Ae2 does not impair salivation, as previously suggested. These results seem to indicate that the Ae4 may be responsible for the majority of the secondary \(\mathrm{Cl}^-\) uptake and thus a key mechanism for saliva secretion. Here, by using ‘in-silico’ Ae2 and Ae4 knockout simulations, we produced mathematical support for such controversial findings. Our results suggest that the exchanger’s cotransport of monovalent cations is likely to be important in establishing the osmotic gradient necessary for optimal transepithelial fluid movement.     

Self-complementary circular codes in coding theory

Self-complementary circular codes are involved in pairing genetic processes. A maximal \(C^3\) self-complementary circular code X of trinucleotides was identified in genes of bacteria, archaea, eukaryotes, plasmids and viruses (Michel in Life 7(20):1–16 2017, J Theor Biol 380:156–177, 2015; Arquès and Michel in J Theor Biol 182:45–58 1996). In this paper, self-complementary circular codes are investigated using the graph theory approach recently formulated in Fimmel et al. (Philos Trans R Soc A 374:20150058, 2016). A directed graph \(\mathcal {G}(X)\) associated with any code X mirrors the properties of the code. In the present paper, we demonstrate a necessary condition for the self-complementarity of an arbitrary code X in terms of the graph theory. The same condition has been proven to be sufficient for codes which are circular and of large size \(\mid X \mid \ge 18\) trinucleotides, in particular for maximal circular codes (\(\mid X \mid = 20\) trinucleotides). For codes of small-size \(\mid X \mid \le 16\) trinucleotides, some very rare counterexamples have been constructed. Furthermore, the length and the structure of the longest paths in the graphs associated with the self-complementary circular codes are investigated. It has been proven that the longest paths in such graphs determine the reading frame for the self-complementary circular codes. By applying this result, the reading frame in any arbitrary sequence of trinucleotides is retrieved after at most 15 nucleotides, i.e., 5 consecutive trinucleotides, from the circular code X identified in genes. Thus, an X motif of a length of at least 15 nucleotides in an arbitrary sequence of trinucleotides (not necessarily all of them belonging to X) uniquely defines the reading (correct) frame, an important criterion for analyzing the X motifs in genes in the future.     

Superbubbles revisited

Background

Superbubbles are distinctive subgraphs in direct graphs that play an important role in assembly algorithms for high-throughput sequencing (HTS) data. Their practical importance derives from the fact they are connected to their host graph by a single entrance and a single exit vertex, thus allowing them to be handled independently. Efficient algorithms for the enumeration of superbubbles are therefore of important for the processing of HTS data. Superbubbles can be identified within the strongly connected components of the input digraph after transforming them into directed acyclic graphs. The algorithm by Sung et al. (IEEE ACM Trans Comput Biol Bioinform 12:770–777, 2015) achieves this task in \(\mathcal {O}(m~log(m))\)-time. The extraction of superbubbles from the transformed components was later improved to by Brankovic et al. (Theor Comput Sci 609:374–383, 2016) resulting in an overall \(\mathcal {O}(m+n)\)-time algorithm.

Results

A re-analysis of the mathematical structure of superbubbles showed that the construction of auxiliary DAGs from the strongly connected components in the work of Sung et al. missed some details that can lead to the reporting of false positive superbubbles. We propose an alternative, even simpler auxiliary graph that solved the problem and retains the linear running time for general digraph. Furthermore, we describe a simpler, space-efficient \(\mathcal {O}(m+n)\)-time algorithm for detecting superbubbles in DAGs that uses only simple data structures.

Implementation

We present a reference implementation of the algorithm that accepts many commonly used formats for the input graph and provides convenient access to the improved algorithm. https://github.com/Fabianexe/Superbubble.

     

Stability of a Stochastic Model of an SIR Epidemic with Vaccination

We prove almost sure exponential stability for the disease-free equilibrium of a stochastic differential equations model of an SIR epidemic with vaccination. The model allows for vertical transmission. The stochastic perturbation is associated with the force of infection and is such that the total population size remains constant in time. We prove almost sure positivity of solutions. The main result concerns especially the smaller values of the diffusion parameter, and describes the stability in terms of an analogue \(\mathcal{R}_\sigma\) of the basic reproduction number \(\mathcal{R}_0\) of the underlying deterministic model, with \(\mathcal{R}_\sigma \le \mathcal{R}_0\). We prove that the disease-free equilibrium is almost sure exponentially stable if \(\mathcal{R}_\sigma <1\).     

Delay decomposition approach to $$\mathcal {H}_{\infty }$$ filtering analysis of genetic oscillator networks with time-varying delays

In this paper, the \(\mathcal {H}_{\infty }\) filtering problem is treated for N coupled genetic oscillator networks with time-varying delays and extrinsic molecular noises. Each individual genetic oscillator is a complex dynamical network that represents the genetic oscillations in terms of complicated biological functions with inner or outer couplings denote the biochemical interactions of mRNAs, proteins and other small molecules. Throughout the paper, first, by constructing appropriate delay decomposition dependent Lyapunov–Krasovskii functional combined with reciprocal convex approach, improved delay-dependent sufficient conditions are obtained to ensure the asymptotic stability of the filtering error system with a prescribed \(\mathcal {H}_{\infty }\) performance. Second, based on the above analysis, the existence of the designed \(\mathcal {H}_{\infty }\) filters are established in terms of linear matrix inequalities with Kronecker product. Finally, numerical examples including a coupled Goodwin oscillator model are inferred to illustrate the effectiveness and less conservatism of the proposed techniques.     

Strong Comma-Free Codes in Genetic Information

Comma-free codes constitute a class of circular codes, which has been widely studied, in particular by Golomb et al. (Biologiske Meddelelser, Kongelige Danske Videnskabernes Selskab 23:1–34, 1958a, Can J Math 10:202–209, 1958b), Michel et al. (Comput Math Appl 55:989–996, 2008a, Theor Comput Sci 401:17–26, 2008b, Inf Comput 212:55–63, 2012), Michel and Pirillo (Int J Comb 2011:659567, 2011), and Fimmel and Strüngmann (J Theor Biol 389:206–213, 2016). Based on a recent approach using graph theory to study circular codes Fimmel et al. (Philos Trans R Soc 374:20150058, 2016), a new class of circular codes, called strong comma-free codes, is identified. These codes detect a frameshift during the translation process immediately after a reading window of at most two nucleotides. We describe several combinatorial properties of strong comma-free codes: enumeration, maximality, self-complementarity and \(CF^3\)-property (comma-free property in all the three possible frames). These combinatorial results also highlight some new properties of the genetic code and its evolution. Each amino acid in the standard genetic code is coded by at least one strong comma-free code of size 1. There are 9 amino acids \(S=\{Asn,Asp,Gln,Gly,Lys,Met,Phe,Pro,Trp\}\) among 20 such that for each amino acid from S, its synonymous trinucleotide set (excluding the necessary periodic trinucleotides \(\{AAA,CCC,GGG,TTT\}\)) is a strong comma-free code. The primeval comma-free RNY code of Eigen and Schuster (Naturwissenschaften 65:341–369, 1978) is a self-complementary \(CF^3\)-code of size 16. Furthermore, it is the union of two strong comma-free codes of size 8 which are complementary to each other.     

A Mathematical Model of Anthrax Transmission in Animal Populations

A general mathematical model of anthrax (caused by Bacillus anthracis) transmission is formulated that includes live animals, infected carcasses and spores in the environment. The basic reproduction number \(\mathcal {R}_0\) is calculated, and existence of a unique endemic equilibrium is established for \(\mathcal {R}_0\) above the threshold value 1. Using data from the literature, elasticity indices for \(\mathcal {R}_0\) and type reproduction numbers are computed to quantify anthrax control measures. Including only herbivorous animals, anthrax is eradicated if \(\mathcal {R}_0 < 1\). For these animals, oscillatory solutions arising from Hopf bifurcations are numerically shown to exist for certain parameter values with \(\mathcal {R}_0>1\) and to have periodicity as observed from anthrax data. Including carnivores and assuming no disease-related death, anthrax again goes extinct below the threshold. Local stability of the endemic equilibrium is established above the threshold; thus, periodic solutions are not possible for these populations. It is shown numerically that oscillations in spore growth may drive oscillations in animal populations; however, the total number of infected animals remains about the same as with constant spore growth.     

Seasonal transmission dynamics of measles in China

Measles, a highly contagious infection caused by the measles virus, is a major public health problem in China. The reported measles cases decreased dramatically from 2004 to 2012 due to the mandatory measles vaccine program started in 2005 and the goal of eliminating measles by 2012. However, after reaching its lowest level in 2012, measles has resurged again since 2013. Since the monthly data of measles cases exhibit a seasonally fluctuating pattern, based on the measles model in Earn et al. (Science 287:667–670, 2000), we propose a susceptible, exposed, infectious, and recovered model with periodic transmission rate to investigate the seasonal measles epidemics and the effect of vaccination. We calculate the basic reproduction number \({\mathcal {R}}_{0}\), analyze the dynamical behavior of the model, and use the model to simulate the monthly data of measles cases reported in China. We also carry out some sensitivity analysis of \({\mathcal {R}}_{0}\) in the terms of various model parameters which shows that measles can be controlled and eventually eradicated by increasing the immunization rate, improving the effective vaccine management, and enhancing the awareness of people about measles.     

Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs

Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, \(A_\mathrm{R}\) and \(B_\mathrm{R}\), each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for \(A_\mathrm{R}\) and \(B_\mathrm{R}\), we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point, T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e., \(f \Delta t\)-long for DrugA and \((1-f) \Delta t\)-long for DrugB with \(0 \le f \le 1\) and \(\Delta t \ge 0\)). We prove that the optimal duration of the initial stage, in which the first drug is administered, T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, \(\mathcal {A/B} = A_\mathrm{R}/B_\mathrm{R}\), and the effect of each drug. We determine a critical ratio, which we term \(\mathcal {(A/B)}^{*}\), at which the two drugs are equally effective. As the first stage of the optimal strategy is applied, \(\mathcal {A/B}\) changes monotonically to \(\mathcal {(A/B)}^{*}\) and then, during the second stage, remains at \(\mathcal {(A/B)}^{*}\) thereafter. Beyond our analytic results, we explored an individual-based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.     

Cell Volume Regulation in the Proximal Tubule of Rat Kidney

We developed a dynamic model of a rat proximal convoluted tubule cell in order to investigate cell volume regulation mechanisms in this nephron segment. We examined whether regulatory volume decrease (RVD), which follows exposure to a hyposmotic peritubular solution, can be achieved solely via stimulation of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)–\(\hbox {HCO}_3^-\) cotransporters. We also determined whether regulatory volume increase (RVI), which follows exposure to a hyperosmotic peritubular solution under certain conditions, may be accomplished by activating basolateral \(\hbox {Na}^+\)/H\(^+\) exchangers. Model predictions were in good agreement with experimental observations in mouse proximal tubule cells assuming that a 10% increase in cell volume induces a fourfold increase in the expression of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)–\(\hbox {HCO}_3^-\) cotransporters. Our results also suggest that in response to a hyposmotic challenge and subsequent cell swelling, \(\hbox {Na}^+\)–\(\hbox {HCO}^-_3\) cotransporters are more efficient than basolateral K\(^+\) and \(\hbox {Cl}^-\) channels at lowering intracellular osmolality and reducing cell volume. Moreover, both RVD and RVI are predicted to stabilize net transcellular \(\hbox {Na}^+\) reabsorption, that is, to limit the net \(\hbox {Na}^+\) flux decrease during a hyposmotic challenge or the net \(\hbox {Na}^+\) flux increase during a hyperosmotic challenge.     

Cellular mechanosensitivity to substrate stiffness decreases with increasing dissimilarity to cell stiffness

Computational modelling has received increasing attention to investigate multi-scale coupled problems in micro-heterogeneous biological structures such as cells. In the current study, we investigated for a single cell the effects of (1) different cell-substrate attachment (2) and different substrate modulus \(\textit{E}_\mathrm{s}\) on intracellular deformations. A fibroblast was geometrically reconstructed from confocal micrographs. Finite element models of the cell on a planar substrate were developed. Intracellular deformations due to substrate stretch of \(\lambda =1.1\), were assessed for: (1) cell-substrate attachment implemented as full basal contact (FC) and 124 focal adhesions (FA), respectively, and \(\textit{E}_\mathrm{s}\,=\,\)140 KPa and (2) \(\textit{E}_\mathrm{s}\,=\,10\), 140, 1000, and 10,000 KPa, respectively, and FA attachment. The largest strains in cytosol, nucleus and cell membrane were higher for FC (1.35\(\text {e}^{-2}\), 0.235\(\text {e}^{-2}\) and 0.6\(\text {e}^{-2}\)) than for FA attachment (0.0952\(\text {e}^{-2}\), 0.0472\(\text {e}^{-2}\) and 0.05\(\text {e}^{-2}\)). For increasing \(\textit{E}_\mathrm{s}\), the largest maximum principal strain was 4.4\(\text {e}^{-4}\), 5\(\text {e}^{-4}\), 5.3\(\text {e}^{-4}\) and 5.3\(\text {e}^{-4}\) in the membrane, 9.5\(\text {e}^{-4}\), 1.1\(\text {e}^{-4}\), 1.2\(\text {e}^{-3}\) and 1.2\(\text {e}^{-3}\) in the cytosol, and 4.5\(\text {e}^{-4}\), 5.3\(\text {e}^{-4}\), 5.7\(\text {e}^{-4}\) and 5.7\(\text {e}^{-4}\) in the nucleus. The results show (1) the importance of representing FA in cell models and (2) higher cellular mechanical sensitivity for substrate stiffness changes in the range of cell stiffness. The latter indicates that matching substrate stiffness to cell stiffness, and moderate variation of the former is very effective for controlled variation of cell deformation. The developed methodology is useful for parametric studies on cellular mechanics to obtain quantitative data of subcellular strains and stresses that cannot easily be measured experimentally.     

A viscoplastic model for the active component in cardiac muscle

The HMK model (Hunter et al. in Prog Biophys Mol Biol 69:289–331, 1998) proposes mechanobiological equations for the influence of intracellular calcium concentration \(\hbox {Ca}_\mathrm{i}\) on the evolution of bound calcium concentration \(\hbox {Ca}_\mathrm{b}\) and the tropomyosin kinetics parameter z, which model processes in the active component of the tension in cardiac muscle. The inelastic response due to actin-myosin crossbridge kinetics is modeled in the HMK model with a function Q that depends on the history of the rate of total stretch of the muscle fiber. Here, an alternative model is proposed which models the active component of the muscle fiber as a viscoplastic material. In particular, an evolution equation is proposed for the elastic stretch \(\lambda _\mathrm{a} \) in the active component. Specific forms of the constitutive equations are proposed and used to match experimental data. The proposed viscoplastic formulation allows for separate modeling of three processes: the high rate deactivation of crossbridges causing rapid reduction in active tension; the high but lower rate reactivation of crossbridges causing recovery of active tension; and the low rate relaxation effects characterizing the Hill model of muscles.     

Generalized enhanced suffix array construction in external memory

Background

Suffix arrays, augmented by additional data structures, allow solving efficiently many string processing problems. The external memory construction of the generalized suffix array for a string collection is a fundamental task when the size of the input collection or the data structure exceeds the available internal memory.

Results

In this article we present and analyze \(\mathsf {eGSA}\) [introduced in CPM (External memory generalized suffix and \(\mathsf {LCP}\) arrays construction. In: Proceedings of CPM. pp 201–10, 2013)], the first external memory algorithm to construct generalized suffix arrays augmented with the longest common prefix array for a string collection. Our algorithm relies on a combination of buffers, induced sorting and a heap to avoid direct string comparisons. We performed experiments that covered different aspects of our algorithm, including running time, efficiency, external memory access, internal phases and the influence of different optimization strategies. On real datasets of size up to 24 GB and using 2 GB of internal memory, \(\mathsf {eGSA}\) showed a competitive performance when compared to \(\mathsf {eSAIS}\) and \(\mathsf {SAscan}\), which are efficient algorithms for a single string according to the related literature. We also show the effect of disk caching managed by the operating system on our algorithm.

Conclusions

The proposed algorithm was validated through performance tests using real datasets from different domains, in various combinations, and showed a competitive performance. Our algorithm can also construct the generalized Burrows-Wheeler transform of a string collection with no additional cost except by the output time.

     

Glutathione <Emphasis Type="BoldItalic">S</Emphasis>-transferase P1 gene polymorphisms and susceptibility to coronary artery disease in a subgroup of north Indian population

The present study aimed to investigate the association of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) polymorphisms of GSTP1 with coronary artery disease (CAD) in a subgroup of north Indian population. In the present case–control study, CAD patients (\(n = 200\)) and age-matched, sex-matched and ethnicity-matched healthy controls (\(n = 200\)) were genotyped for polymorphisms in GSTP1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype distribution of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) polymorphisms of GSTP1 gene was significantly different between cases and controls (\(P = 0.005\) and 0.024, respectively). Binary logistic regression analysis showed significant association of A/G (odds ratio (OR): 1.6, 95% CI: 1.08–2.49, \(P = 0.020\)) and G/G (OR: 3.1, 95% CI: 1.41–6.71, P \(=\) 0.005) genotypes of GSTP1 \(\hbox {g}.313\hbox {A}{\!>\!}\hbox {G}\), and C/T (OR: 5.8, 95% CI: 1.26–26.34, \(P = 0.024\)) genotype of GSTP1 \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) with CAD. The A/G and G/G genotypes of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and C/T genotype of \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) conferred 6.5-fold increased risk for CAD (OR: 6.5, 95% CI: 1.37–31.27, \(P = 0.018\)). Moreover, the recessive model of GSTP1 \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) is the best fit inheritance model to predict the susceptible gene effect (OR: 2.3, 95% CI: 1.11–4.92, \(P = 0.020\)). In conclusion, statistically significant associations of GSTP1 \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) (A/G, G/G) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) (C/T) genotypes with CAD were observed.     

Competition between phytoplankton and bacteria: exclusion and coexistence

Resource-based competition between microorganisms species in continuous culture has been studied extensively both experimentally and theoretically, mostly for bacteria through Monod and Contois “constant yield” models, or for phytoplankton through the Droop “variable yield” models. For homogeneous populations of N bacterial species (Monod) or N phytoplanktonic species (Droop), with one limiting substrate and under constant controls, the theoretical studies indicated that competitive exclusion occurs: only one species wins the competition and displaces all the others (Armstrong and McGehee in Am Nat 115:151, 1980; Hsu and Hsu in SIAM J Appl Math 68:1600–1617, 2008). The winning species expected from theory is the one with the lowest “substrate subsistence concentration” \(s^{\star }\), such that its corresponding equilibrium growth rate is equal to the dilution rate \(D\). This theoretical result was validated experimentally with phytoplankton (Tilman and Sterner in Oecologia 61(2):197–200, 1984) and bacteria (Hansen and Hubell in Science 207(4438):1491–1493, 1980), and observed in a lake with microalgae (Tilman in Ecology 58(22):338–348, 1977). On the contrary for aggregating bacterial species described by a Contois model, theory predicts coexistence between several species (Grognard et al. in Discrete Contin Dyn Syst Ser B 8(1):73–93, 2007). In this paper we present a generalization of these results by studying a competition between three different types of microorganisms: planktonic (or free) bacteria (represented by a generalized Monod model), aggregating bacteria (represented by a Contois model) and free phytoplankton (represented by a Droop model). We prove that the outcome of the competition is a coexistence between several aggregating bacterial species with a free species of bacteria or phytoplankton, all the other free species being washed out. This demonstration is based mainly on the study of the substrate concentration’s evolution caused by competition; it converges towards the lowest subsistence concentration \(s^{\star }\), leading to three different types of competition outcomes: (1) the best free bacteria or phytoplankton competitor excludes all other species; (2) only some aggregating bacterial species coexist in the chemostat; (3) A coexistence between the single best free species, with one or several aggregating species.     

Study of the Population Dynamics of <Emphasis Type="Italic">Busseola fusca</Emphasis>, Maize Pest

Busseola fusca is a maize and sorghum pest that can cause significant damage to both crops. Given that maize is one of the main cereals grown in the worldwide, this pest is a major challenge for maize production and therefore for the economies of several countries . In this paper , based on the life cycle of B. fusca, we propose a mathematical model to study the population dynamics of this insect pest . A sensitivity analysis using the eFast method was performed to show the most important parameters of the model. We present the theoretical analysis of the model. More precisely, we derive a threshold parameter \({\mathcal {N}}_0\), called basic offspring number and show that the trivial equilibrium is globally asymptotically stable whenever \({\mathcal {N}}_0\le 1\), while if \({\mathcal {N}}_0>1\), the non trivial equilibrium is globally asymptotically stable. The theoretical results are supported by numerical simulations.     

When is a Phylogenetic Network Simply an Amalgamation of Two Trees?

Phylogenetic networks generalise phylogenetic (evolutionary) trees by allowing for the representation of reticulation (non-treelike) events. The structure of such networks is often viewed by the phylogenetic trees they embed. In this paper, we determine when a phylogenetic network \({\mathcal {N}}\) has two phylogenetic tree embeddings which collectively contain all of the edges of \({\mathcal {N}}\). This determination leads to a polynomial-time algorithm for recognising such networks and an unexpected characterisation of the class of reticulation-visible networks.     

Mathematical Analysis of the Transmission Dynamics of HIV Syphilis Co-infection in the Presence of Treatment for Syphilis

The re-emergence of syphilis has become a global public health issue, and more persons are getting infected, especially in developing countries. This has also led to an increase in the incidence of human immunodeficiency virus (HIV) infections as some studies have shown in the recent decade. This paper investigates the synergistic interaction between HIV and syphilis using a mathematical model that assesses the impact of syphilis treatment on the dynamics of syphilis and HIV co-infection in a human population where HIV treatment is not readily available or accessible to HIV-infected individuals. In the absence of HIV, the syphilis-only model undergoes the phenomenon of backward bifurcation when the associated reproduction number (\({\mathcal {R}}_{T}\)) is less than unity, due to susceptibility to syphilis reinfection after recovery from a previous infection. The complete syphilis–HIV co-infection model also undergoes the phenomenon of backward bifurcation when the associated effective reproduction number (\({\mathcal {R}}_{C}\)) is less than unity for the same reason as the syphilis-only model. When susceptibility to syphilis reinfection after treatment is insignificant, the disease-free equilibrium of the syphilis-only model is shown to be globally asymptotically stable whenever the associated reproduction number (\({\mathcal {R}}_{T}\)) is less than unity. Sensitivity and uncertainty analysis show that the top three parameters that drive the syphilis infection (with respect to the associated response function, \({\mathcal {R}}_{T}\)) are the contact rate (\(\beta _S\)), modification parameter that accounts for the increased infectiousness of syphilis-infected individuals in the secondary stage of the infection (\(\theta _1\)) and treatment rate for syphilis-only infected individuals in the primary stage of the infection (\(r_1\)). The co-infection model was numerically simulated to investigate the impact of various treatment strategies for primary and secondary syphilis, in both singly and dually infected individuals, on the dynamics of the co-infection of syphilis and HIV. It is observed that if concerted effort is exerted in the treatment of primary and secondary syphilis (in both singly and dually infected individuals), especially with high treatment rates for primary syphilis, this will result in a reduction in the incidence of HIV (and its co-infection with syphilis) in the population.