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In this paper, we introduce a membership function used to form the fuzzy Mandelbric set and investigate the structural effects of additive and multiplicative dynamic noises on it. The newly defined membership function of this fuzzy set and its perturbations is a generalization of the indicator function for the classical Mandelbric set. We present an algorithm for detecting each complex number's fuzzy membership degree. Through the use of the membership degrees of each complex number and experimental mathematics based on the visualizations of a variety of versions by utilizing computer-aided design, we gain a deep foresight for the structure characteristics of the additive and multiplicative perturbed fuzzy Mandelbric sets. Our novel approach allows us to identify the symmetry states of the Mandelbric set and its perturbations by the membership degrees of complex numbers, unlike the existing methods described in the literature. [ABSTRACT FROM AUTHOR]

In this study, we investigate coupled real and complex dispersionless equations for curve families, even if they have singular points. Even though the connections with the differential equations and regular curves were considered in various ways in the past, since each curve does not need to be regular, we establish the connections for framed base curves, which generalize regular curves with linear independent conditions. Also, we give the Lax pairs of the real and complex coupled dispersionless equations from the motions of any framed curve. These give us significant conditions based on the framed curvatures and associated curvatures of the framed curves for integrability since it is well known that the Lax pair provides the integrability of differential equations. [ABSTRACT FROM AUTHOR]

Stochastic gene expression in regulatory networks is conventionally modelled via the chemical master equation (CME). As explicit solutions to the CME, in the form of so-called propagators, are oftentimes not readily available, various approximations have been proposed. A recently developed analytical method is based on a separation of time scales that assumes significant differences in the lifetimes of mRNA and protein in the network, allowing for the efficient approximation of propagators from asymptotic expansions for the corresponding generating functions. Here, we showcase the applicability of that method to simulated data from a 'telegraph' model for gene expression that is extended with an autoregulatory mechanism. We demonstrate that the resulting approximate propagators can be applied successfully for parameter inference in the non-regulated model; moreover, we show that, in the extended autoregulated model, autoactivation or autorepression may be refuted under certain assumptions on the model parameters. These results indicate that our approach may allow for successful parameter inference and model identification from longitudinal single cell data. [ABSTRACT FROM AUTHOR]

The paper considers utilization of rocket motor propellant grains that consist of two propellants. The idea is to achieve approximately neutral burning using an outer surface inhibited cylindrical shape and complex contact surface between propellants. An existing propellant grain with complex geometry has been analytically modeled in terms of determination of evolution of corresponding burning surface areas. The analytical and experimental results' diagrams of this grain have been found to have a saw-tooth shape because of the segments that separate the two propellants, causing potential problems in the burning process during the relatively short active phase, showing an obvious need for further optimization. This has created an opportunity for development of improved propellant grain geometry and corresponding mathematical model for determination of main interior ballistic parameters. Comparison between calculation results based on both models and experimentally determined chamber pressure data shows very good agreement. Therefore, two-component propellant grains have significant application possibilities using the suggested modeling approaches. [ABSTRACT FROM AUTHOR]

We study the three-timescale dynamics of a model that describes the El Niño Southern Oscillation (ENSO) phenomenon, which was proposed in Roberts et al. (2016). While ENSO phenomena are inherently characterised by the presence of multiple distinct timescales, the above model has previously been studied in a two-timescale context only. Here, we uncover the geometric mechanisms that are responsible for complex oscillatory dynamics in a three-timescale regime, and we demonstrate that the model exhibits a variety of qualitatively different behaviours in that regime, such as mixed-mode oscillation (MMO) with "plateaus" – trajectories where epochs of quiescence alternate with dramatic excursions – and relaxation oscillation. The latter, although emergent also in the two-timescale context in appropriate parameter regimes, had not been documented previously for this particular model. Moreover, we show that these mechanisms are relevant to models from other fields of ecological and population dynamics, as the underlying geometry is similar to the unfolding of Rosenzweig–MacArthur-type models in three dimensions. • Studied geometrically a three-timescale model for the ENSO (El Niño Southern Oscillation) phenomenon. • Associated possible configurations of singular geometric objects to qualitatively different oscillatory dynamics. • Related delayed loss of stability in the model to the presence of a self-intersecting critical manifold. [ABSTRACT FROM AUTHOR]

Micro-Electro Mechanical Systems (MEMS) are defined as very small structures that combine electrical and mechanical components on a common substrate. Here, the electrostatic-elastic case is considered, where an elastic membrane is allowed to deflect above a ground plate under the action of an electric potential, whose strength is proportional to a parameter \lambda. Such devices are commonly described by a parabolic partial differential equation that contains a singular nonlinear source term. The singularity in that term corresponds to the so-called touchdown phenomenon, where the membrane establishes contact with the ground plate. ''Touchdown"" is known to imply the non-existence of steady-state solutions and blow-up of solutions in finite time. We study a recently proposed extension of that canonical model, where such singularities are avoided due to the introduction of a regularizing term involving a small ''regularization"" parameter varepsilon. Methods from dynamical systems and geometric singular perturbation theory, in particular the desingularization technique known as ''blow-up"", allow for a precise description of steady-state solutions of the regularized model, as well as for a detailed resolution of the resulting bifurcation diagram. The interplay between the two main model parameters varepsilon and \lambda is emphasized; in particular, the focus is on the singular limit as both parameters tend to zero. [ABSTRACT FROM AUTHOR]

Yogurt represent one of the oldest fermented foods containing viable lactic acid bacteria and many bioactive compounds that could exhibit beneficial effects on human health and train our immune system to better respond to invading pathogens. Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus are commonly used for yogurt preparation under controlled temperature and environmental conditions. In this study, we investigated probiotic features of S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21 strains isolated from artisanal sour milk and yogurt by using Caenorhabditis elegans as an in vivo model system. Further, we evaluated content of total fat, saturated fatty acids, proteins, and lactose, as well as vitamins and AA of yogurt prepared from above-mentioned starter cultures during 21 d of storage at 4°C to get insights of final product stability. We showed that S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21 strains applied in combination upregulated the expression of autophagy-related genes in C. elegans. Beside autophagy, we observed activation of TIR-1-dependent transcription of lysozyme-like antimicrobial genes involved in the immune defense of C. elegans. Upregulation of these genes strongly correlates with an increase in the longevity of the worms fed with yogurt culture bacteria. Further, we showed that yogurt prepared with S. thermophilus BGKMJ1-36 and L. bulgaricus BGVLJ1-21, as a final product, is rich with vitamin B 2 and dominant AA known by their prolongevity properties. Taken together, our study pointed to the beneficial features of the tested starter cultures and yogurt and highlighted their potential to be used as a fermented food with added-value properties. [Display omitted] [ABSTRACT FROM AUTHOR]

We consider a system of coupled partial differential equations modeling the interaction of mussels and algae in advective environments. A key parameter in the equations is the ratio of the diffusion rate of the mussel species and the advection rate of the algal concentration. When advection dominates diffusion, one observes large-amplitude solutions representing bands of mussels propagating slowly in the upstream direction. Here, we prove the existence of a family of such periodic wavetrain solutions. Our proof relies on geometric singular perturbation theory to construct these solutions as periodic orbits of the associated traveling wave equations in the large-advection{small-diffusion limit. The construction encounters a number of mathematical obstacles which necessitate a compactification of phase space, geometric desingularization to remedy a loss of normal hyperbolicity, and the application of a generalized exchange lemma at a loss-of-stability turning point. In particular, our analysis uncovers logarithmic (switchback) corrections to the leading-order solution. [ABSTRACT FROM AUTHOR]

Stochastic models for gene expression frequently exhibit dynamics on several different scales. One potential time-scale separation is caused by significant differences in the lifetimes of mRNA and protein; the ratio of the two degradation rates gives a natural small parameter in the resulting chemical master equation, allowing for the application of perturbation techniques. Here, we develop a framework for the analysis of a family of 'fast-slow' models for gene expression that is based on geometric singular perturbation theory. We illustrate our approach by giving a complete characterisation of a standard two-stage model which assumes transcription, translation, and degradation to be first-order reactions. In particular, we present a systematic expansion procedure for the probability-generating function that can in principle be taken to any order in the perturbation parameter, allowing for an approximation of the corresponding propagator probabilities to that same order. For illustrative purposes, we perform this expansion explicitly to first order, both on the fast and the slow time-scales; then, we combine the resulting asymptotics into a composite fast-slow expansion that is uniformly valid in time. In the process, we extend, and prove rigorously, results previously obtained by Shahrezaei and Swain (Proc Natl Acad Sci USA 105(45):17256-17261, ) and Bokes et al. (J Math Biol 64(5):829-854, ; J Math Biol 65(3):493-520, ). We verify our asymptotics by numerical simulation, and we explore its practical applicability and the effects of a variation in the system parameters and the time-scale separation. Focussing on biologically relevant parameter regimes that induce translational bursting, as well as those in which mRNA is frequently transcribed, we find that the first-order correction can significantly improve the steady-state probability distribution. Similarly, in the time-dependent scenario, inclusion of the first-order fast asymptotics results in a uniform approximation for the propagator probabilities that is superior to the slow dynamics alone. Finally, we discuss the generalisation of our geometric framework to models for regulated gene expression that involve additional stages. [ABSTRACT FROM AUTHOR]

Industrialization of agricultural production and depopulation of areas that are recognized by traditional products, reached its peak during the last few decades. This represents a significant risk that the technology of traditional agricultural products, especially cheeses, can go into oblivion. Njeguši cheese is one of the famous Montenegrin traditional dairy products which originates from the mountain Lovćen and its peripheral areas. Produced by traditional technology, it belongs to a group of full fat, hard cheeses. Owing to its characteristic, spicy taste and pleasant odour, Njeguši cheese can be compared with some of the most famous hard cheeses. Originally it is made from ewe’s milk, but also, cow's, goat's and their mixture in different proportions, are increasingly used, which may be the treat to the originality of Njeguši cheese. The present study offers a description of original Njeguši cheese technology, followed by analysis of the chemical quality of ewe’s milk, cheese and whey. Thereat milk, cheese and whey samples were taken from 5 households located at the place of cheese origin - the Njeguši village. Chemical quality of ewe’s milk, cheese and whey was determined by method of FTIR spectrophotometry. Milk fat in the dry matter and moisture in cheese non-fat basis were mathematically calculated. The average content of milk fat in ewe’s milk was 4.92 %, proteins 4.59 %, lactose 4.14 % and total solids non-fat 9.46 %. Accordingly, the analysed cheeses belonged to full fat, semi-hard cheese due to 51.73 % fat in total solids and 60.07 % moisture in non-fat basis. The only deviation from original technology was shortening of the ripening period. Apart from the main objective - the preservation of the original technology, this study could significantly contribute to the process of protection of origin of Njeguši cheese, because the technology of cheese fulfilled the requirements listed in the National Law on the protection of designations of origin. [ABSTRACT FROM AUTHOR]

Noise in gene expression can lead to reversible phenotypic switching. Several experimental studies have shown that the abundance distributions of proteins in a population of isogenic cells may display multiple distinct maxima. Each of these maxima may be associated with a subpopulation of a particular phenotype, the quantification of which is important for understanding cellular decision-making. Here, we devise a methodology which allows us to quantify multimodal gene expression distributions and single-cell power spectra in gene regulatory networks. Extending the commonly used linear noise approximation, we rigorously show that, in the limit of slow promoter dynamics, these distributions can be systematically approximated as a mixture of Gaussian components in a wide class of networks. The resulting closed-form approximation provides a practical tool for studying complex nonlinear gene regulatory networks that have thus far been amenable only to stochastic simulation. We demonstrate the applicability of our approach in a number of genetic networks, uncovering previously unidentified dynamical characteristics associated with phenotypic switching. Specifically, we elucidate how the interplay of transcriptional and translational regulation can be exploited to control the multimodality of gene expression distributions in two-promoter networks. We demonstrate how phenotypic switching leads to birhythmical expression in a genetic oscillator, and to hysteresis in phenotypic induction, thus highlighting the ability of regulatory networks to retain memory. [ABSTRACT FROM AUTHOR]

Abstract: We investigate the effects of a linear cut-off on front propagation in the Nagumo equation at a so-called Maxwell point, where the corresponding front solution in the absence of a cut-off is stationary. We show that the correction to the propagation speed induced by the cut-off is positive in this case; moreover, we determine the leading-order asymptotics of that correction in terms of the cut-off parameter, and we calculate explicitly the corresponding coefficient. Our analysis is based on geometric techniques from dynamical systems theory and, in particular, on the method of geometric desingularization (‘blow-up’). [Copyright &y& Elsevier]

Abstract: We consider front propagation in a family of scalar reaction–diffusion equations in the asymptotic limit where the polynomial degree of the potential function tends to infinity. We investigate the Gevrey properties of the corresponding critical propagation speed, proving that the formal series expansion for that speed is Gevrey-1 with respect to the inverse of the degree. Moreover, we discuss the question of optimal truncation. Finally, we present a reliable numerical algorithm for evaluating the coefficients in the expansion with arbitrary precision and to any desired order, and we illustrate that algorithm by calculating explicitly the first ten coefficients. Our analysis builds on results obtained previously in [F. Dumortier, N. Popović, T.J. Kaper, The asymptotic critical wave speed in a family of scalar reaction–diffusion equations, J. Math. Anal. Appl. 326 (2) (2007) 1007–1023], and makes use of the blow-up technique in combination with geometric singular perturbation theory and complex analysis, while the numerical evaluation of the coefficients in the expansion for the critical speed is based on rigorous interval arithmetic. [Copyright &y& Elsevier]

We investigate the effects of a Heaviside cutoff on the dynamics of traveling fronts in a family of scalar reaction-diffusion equations with degenerate polynomial potential that includes the classical Zeldovich equation. We prove the existence and uniqueness of front solutions in the presence of the cutoff, and we derive the leading-order asymptotics of the corresponding propagation speed in terms of the cutoff parameter. For the Zeldovich equation, an explicit solution to the equation without cutoff is known, which allows us to calculate higher-order terms in the resulting expansion for the front speed; in particular, we prove the occurrence of logarithmic (switchback) terms in that case. Our analysis relies on geometric methods from dynamical systems theory and, in particular, on the desingularization technique known as 'blow-up.' [ABSTRACT FROM AUTHOR]

Abstract: ‘Cut-offs’ were introduced to model front propagation in reaction–diffusion systems in which the reaction is effectively deactivated at points where the concentration lies below some threshold. In this article, we investigate the effects of a cut-off on fronts propagating into metastable states in a class of bistable scalar equations. We apply the method of geometric desingularization from dynamical systems theory to calculate explicitly the change in front propagation speed that is induced by the cut-off. We prove that the asymptotics of this correction scales with fractional powers of the cut-off parameter, and we identify the source of these exponents, thus explaining the structure of the resulting expansion. In particular, we show geometrically that the speed of bistable fronts increases in the presence of a cut-off, in agreement with results obtained previously via a variational principle. We first discuss the classical Nagumo equation as a prototypical example of bistable front propagation. Then, we present corresponding results for the (equivalent) cut-off Schlögl equation. Finally, we extend our analysis to a general family of reaction–diffusion equations that support bistable fronts, and we show that knowledge of an explicit front solution to the associated problem without cut-off is necessary for the correction induced by the cut-off to be computable in closed form. [ABSTRACT FROM AUTHOR]

Mixed-mode dynamics is a complex type of dynamical behavior that is characterized by a combination of small-amplitude oscillations and large-amplitude excursions. Mixed-mode oscillations (MMOs) have been observed both experimentally and numerically in various prototypical systems in the natural sciences. In the present article, we propose a mathematical model problem which, though analytically simple, exhibits a wide variety of MMO patterns upon variation of a control parameter. One characteristic feature of our model is the presence of three distinct time-scales, provided a singular perturbation parameter is sufficiently small. Using geometric singular perturbation theory and geometric desingularization, we show that the emergence of MMOs in this context is caused by an underlying canard phenomenon. We derive asymptotic formulae for the return map induced by the corresponding flow, which allows us to obtain precise results on the bifurcation (Farey) sequences of the resulting MMO periodic orbits. We prove that the structure of these sequences is determined by the presence of secondary canards. Finally, we perform numerical simulations that show good quantitative agreement with the asymptotics in the relevant parameter regime. [ABSTRACT FROM AUTHOR]

The mathematical and physical analysis of magnetoelastic phenomena is a topic of ongoing research. Different formulae have been proposed to describe the magnetic forces in macroscopic systems. We discuss several of these formulae in the context of rigid magnetized bodies. In case the bodies are in contact, we consider formulae both in the framework of macroscopic electrodynamics and via a multiscale approach, i.e., in a discrete setting of magnetic dipole moments. We give mathematically rigorous proofs for domains of polygonal shape (as well as for more general geometries) in two and three space dimensions. In an accompanying second article, we investigate the formulae in a number of numerical experiments, where we focus on the dependence of the magnetic force on the distance between the bodies and on the case when the two bodies are in contact. The aim of the analysis as well as of the numerical simulation is to contribute to the ongoing debate about which formula describes the magnetic force between macroscopic bodies best and to stimulate corresponding real-life experiments. [ABSTRACT FROM AUTHOR]

The analysis of magnetoelastic phenomena is a field of active research. Formulae for the magnetic force in macroscopic systems have been under discussion for some time. In Popović et al. (Continum. Mech. Thermodyn. 2007), we rigorously justify several of the available formulae in the context of rigid bodies in two and three space dimensions. In the present, second part of our study, we investigate these formulae in a series of numerical experiments in which the magnetic force is computed in dependence on the geometries of the bodies as well as on the distance between them. In case the two bodies are in contact, i.e., in the limit as their distance tends to zero, we focus especially on a formula obtained in a discrete-to-continuum approximation. The aim of our study is to help clarify the question which force formula is the correct one in the sense that it describes nature most accurately and to suggest adequate real-life experiments for a comparison with the provided numerical data. [ABSTRACT FROM AUTHOR]

Abstract: We study traveling wave solutions for the class of scalar reaction–diffusion equations where the family of potential functions is given by . For each real, there is a critical wave speed that separates waves of exponential structure from those which decay only algebraically. We derive a rigorous asymptotic expansion for in the limit as . This expansion also seems to provide a useful approximation to over a wide range of m-values. Moreover, we prove that is -smooth as a function of . Our analysis relies on geometric singular perturbation theory, as well as on the blow-up technique, and confirms the results obtained by means of asymptotic methods in [D.J. Needham, A.N. Barnes, Reaction–diffusion and phase waves occurring in a class of scalar reaction–diffusion equations, Nonlinearity 12 (1) (1999) 41–58; T.P. Witelski, K. Ono, T.J. Kaper, Critical wave speeds for a family of scalar reaction–diffusion equations, Appl. Math. Lett. 14 (1) (2001) 65–73]. [Copyright &y& Elsevier]

The present work is a continuation of the geometric singular perturbation analysis of the Lagerstrom model problem which was commenced in J. Differential Equations (199 (2) (2004) 290–325). We establish the same framework here, reinterpreting Lagerstrom''s equation as a dynamical system which is subsequently analyzed by means of methods from dynamical systems theory as well as of the blow-up technique. We show how rigorous asymptotic expansions for the Lagerstrom problem can be obtained using geometric methods, thereby establishing a connection to the method of matched asymptotic expansions. We explain the structure of these expansions and demonstrate that the occurrence of the well-known logarithmic (switchback) terms therein is caused by a resonance phenomenon. [Copyright &y& Elsevier]

Lagerstrom''s model problem is a classical singular perturbation problem which was introduced to illustrate the ideas and subtleties involved in the analysis of viscous flow past a solid at low Reynolds number by the method of matched asymptotic expansions. In this paper the corresponding boundary value problem is analyzed geometrically by using methods from the theory of dynamical systems, in particular invariant manifold theory. As an essential part of the dynamics takes place near a line of non-hyperbolic equilibria, a blow-up transformation is introduced to resolve these singularities. This approach leads to a constructive proof of existence and local uniqueness of solutions and to a better understanding of the singular perturbation nature of the problem. In particular, the source of the logarithmic switchback phenomenon is identified. [Copyright &y& Elsevier]

We study a singularly perturbed model for a cyclic adenosine monophosphate (cAMP) signalling system that controls aggregation of the amoeboid microorganism Dictyostelium discoideum. The model, which is based on a classical model due to Martiel and Goldbeter [16] , takes the form of a planar system of ordinary differential equations with two singular perturbation parameters which manifest very differently: while one parameter encodes the separation of scales between the slow and fast variables, the other induces a non-uniformity in the corresponding vector field in the singular limit. We apply geometric singular perturbation theory and the desingularisation technique known as "blow-up" to construct a family of attracting, periodic (relaxation-type) orbits; in the process, we elucidate the novel singular structure of the model, and we describe in detail the resulting oscillatory dynamics. [ABSTRACT FROM AUTHOR]

Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection. [ABSTRACT FROM AUTHOR]

The inherent stochasticity of gene expression in the context of regulatory networks profoundly influences the dynamics of the involved species. Mathematically speaking, the propagators which describe the evolution of such networks in time are typically defined as solutions of the corresponding chemical master equation (CME). However, it is not possible in general to obtain exact solutions to the CME in closed form, which is due largely to its high dimensionality. In the present article, we propose an analytical method for the efficient approximation of these propagators. We illustrate our method on the basis of two categories of stochastic models for gene expression that have been discussed in the literature. The requisite procedure consists of three steps: a probability-generating function is introduced which transforms the CME into (a system of) partial differential equations (PDEs); application of the method of characteristics then yields (a system of) ordinary differential equations (ODEs) which can be solved using dynamical systems techniques, giving closed-form expressions for the generating function; finally, propagator probabilities can be reconstructed numerically from these expressions via the Cauchy integral formula. The resulting ‘library’ of propagators lends itself naturally to implementation in a Bayesian parameter inference scheme, and can be generalised systematically to related categories of stochastic models beyond the ones considered here. [ABSTRACT FROM AUTHOR]

We study delayed loss of stability in a class of fast–slow systems with two fast variables and one slow one, where the linearisation of the fast vector field along a one-dimensional critical manifold has two real eigenvalues which intersect before the accumulated contraction and expansion are balanced along any individual eigendirection. That interplay between eigenvalues and eigendirections renders the use of known entry–exit relations unsuitable for calculating the point at which trajectories exit neighbourhoods of the given manifold. We illustrate the various qualitative scenarios that are possible in the class of systems considered here, and we propose novel formulae for the entry–exit functions that underlie the phenomenon of delayed loss of stability therein. [ABSTRACT FROM AUTHOR]

Background: Genus Clostridium accompanies more than 200 known species and at least 30 among them are associated with human and animal diseases. At the moment, the treatment of clostridial infections is based on use of antibiotics. However, due to the European ban on the use of antibiotics in livestock production, novel therapeutic strategies for treatment of these hardly curable infections have been evaluated. Hence, in this study the antimicrobial effect of newly designed probiotic culture consisted of natural isolates Lactobacillus helveticus BGRA43, Lactobacillus fermentum BGHI14 and Streptococcus thermophilus BGVLJ1-44 against Clostridium difficile and Clostridium perfringens was analyzed. Results: The probiotic culture showed strong in vitro antimicrobial effect on C. difficile (human clinical isolate). In addition, individual strains and the probiotic combination exhibited immunomodulatory activity. The probiotic combination significantly increased the proliferation of GALT lymphocytes. At the other hand, none of the bacterial treatments (individual strains and the combination) induced the production of proinflammatory cytokines IL-6 and IL-1β by intestinal epithelial cells, Caco-2. Interestingly, Caco-2 cells exposed to the probiotic combination produced significantly elevated amount of TGFβ pointing to potential protecting effect of the probiotic. In addition, the results of field trial on spontaneously infected goats revealed reduction of C. perfringens in goats (below the detection threshold) after the probiotic treatment. Conclusions: The results of this study indicated that the novel probiotic deserves to be further investigated as a promising antimicrobial agent against C. difficile and C. perfringens. [ABSTRACT FROM AUTHOR]

The chemical master equation (CME) represents the accepted stochastic description of chemical reaction kinetics in mesoscopic systems. As its exact solution-which gives the corresponding probability density function-is possible only in very simple cases; there is a clear need for approximation techniques. Here, we propose a novel perturbative three-step approach, which draws heavily on graph theory: (i) we expand the eigenvalues of the transition state matrix in the CME as a series in a nondimensional parameter that depends on the reaction rates and the reaction volume; (ii) we derive an analogous series for the corresponding eigenvectors via a graph-based algorithm; (iii) we combine the resulting expansions into an approximate solution to the CME. We illustrate our approach by applying it to a reversible dimerization reaction; then we formulate a set of conditions, which ensure its applicability to more general reaction networks, and we verify those conditions for two common catalytic mechanisms. Comparing our results with the linear-noise approximation (LNA), we find that our methodology is consistently more accurate for sufficiently small values of the nondimensional parameter. This superior accuracy is particularly evident in scenarios characterized by small molecule numbers, which are typical of conditions inside biological cells. [ABSTRACT FROM AUTHOR]

The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat-inactivated probiotic strain Lactobacillus curvatus BGMK2-41 stimulates immune response and resistance of the Caenorhabditis elegans against Staphylococcus aureus and Pseudomonas aeruginosa. By employing qRT-PCR and western blot analysis we showed that heat-inactivated BGMK2-41 activated PMK-1/p38 MAPK immunity pathway which prolongs the survival of C. elegans exposed to pathogenic bacteria in nematode killing assays. The C. elegans pmk-1 mutant was used to demonstrate a mechanistic basis for the antimicrobial potential of BGMK2-41, showing that BGMK2-41 upregulated PMK-1/p38 MAPK dependent transcription of C-type lectins, lysozymes and tight junction protein CLC-1. Overall, this study suggests that PMK-1/p38 MAPK‐dependent immune regulation by BGMK2-41 is essential for probiotic-mediated C. elegans protection against gram-positive and gram-negative bacteria and could be further explored for development of probiotics with the potential to increase resistance of the host towards pathogens. [ABSTRACT FROM AUTHOR]

This manuscript has come as a result of an efficient breeding program in Serbian cattle populations for some economically important traits. Genomic selection in the last two decades has been the main challenge in animal breeding programs and genetics. Many SNP markers are used in statistical analysis in predicting the accuracy of breeding values for young animals without their performance. The new breeding tendency in the selection of young animals allows their genetic progress with reducing cost. In this study, 92 Holstein cows from various regions in Serbia were analyzed based on SNP molecular markers. Within this investigation, an empirical model was developed for the prediction of Yield Traits and Fertility Traits variables, according to Key traits data for dairy cattle. The developed model gave a reasonable fit to the data and successfully predicted Yield Traits (such as Fat and Protein Percent, Cheese Merit, Fluid Merit, and Cow Livability) and Fertility Traits variables (such as Sire Calving Ease, Heifer Conception Rate, Cow Conception Rate, Daughter Stillbirth, Sire Stillbirth, and Gestation Length). A total of 92 dairy cattle data were used to build a prediction model for the prediction of Yield Traits and Fertility Traits variables. The artificial neural network model, based on the Broyden-Fletcher-Goldfarb-Shanno iterative algorithm, showed good prediction capabilities (the r² values during the training cycle for the before mentioned output variables were in the range between 0.444 and 0.989). [ABSTRACT FROM AUTHOR]

In this study changes during fermentation of spontaneously fermented modern and ancient (spelt, emmer, and khorasan) wheat sourdoughs and their feasibility to act as leavening agents in breadmaking were evaluated. During 6 h of fermentation, sourdough was characterized for lactic acid bacteria and yeasts counts, pH, total titratable acidity (TTA), proteolytic activity, rheological and electrophoretic profiles. The effects of 25 and 50 g/100g sourdough addition on physico-chemical and sensory properties of refined wheat flour bread were also investigated. Although in all sourdoughs a pH drop, increase in proteolytic activity, gliadin and glutenin degradation with fermentation were recorded, due to different flour composition and microbial activity, tested sourdoughs significantly differed in rheological properties and breadmaking quality. Wheat sourdough being characterized by the highest acidification, increase in proteolytic activity, and the most extensive hydrolysis of gliadins, resulted in bread with the lowest specific volume and hardest crumb texture. Emmer sourdough, having the highest TTA, ash and wet gluten content, exhibited the highest extensibility, the least pronounced changes in proteolytic activity and the electrophoretic pattern which produced bread with the highest volume and softest texture. In general, ancient wheat varieties have shown great potential in sourdough breadmaking in comparison to modern wheat. • Ancient wheat varieties were used to prepare spontaneously fermented sourdoughs. • Wheat, spelt, emmer and khorasan sourdough behaved differently during fermentation. • Wheat sourdough had increased proteolytic activity and high gliadins hydrolysis. • Emmer sourdough exhibited high extensibility and low changes in gluten structure. • Unlike wheat, emmer resulted in bread with the highest volume and softest texture. [ABSTRACT FROM AUTHOR]

Background/Aim. The prosthetic-orthotic rehabilitation (POR) of amputees with head injury within the polytrauma presents a specific entity. The number of traumas caused by the traffic and the low-intensity war conflicts, increases constantly. The aim of our study was to examine the influence of complications on the POR duration and outcome in polytrauma amputees with head injury (PTAHI) recording complications at the beginning and during the POR. Methods. The study was carried out on the patients divided into two groups of 35 polytrauma male patients each of corresponding age with unilateral transfemoral amputation caused by the war injury. The experimental group consisted of the amputees with head injury. Standard clinical techniques and procedures, as well as special functional evaluation techniques were used. Results. The PATHI started POR with a greater number of complications (average rate 7.29 vs 5.11 per patient; W = 928.000: Z = 3.730: p = 0.000). There was a highly significant positive correlation between this number and the Barthel Score value change (Fx, H, p < 0.01), and negative significant correlation considering prosthetic use and functional capacity test values (Fx, H p < 0.05). On admision, the amount of complications defined for the value 4 of POR outcome was significantly higher than values 2 and 3, respectively (H = 8.948; df = 2; p = 0.011). The PTAHI developed significantly more frequently complications during rehabilitation (X² = 1.061; df = 1; p < 0.01). The proportion of the examinees with the value 4 who developed complications during rehabilitations was significantly higher than those with value 2 (Fp = 3.406; df1 = 2; df2 = 67; p = 0.038). The rehabilitation of the PTAHI lasted significantly longer (average 259.09 vs 183.63 days; W = 923.500; Z = -3.748; p = 0.000). Conclusion. The PTAHI including head injuries started prostheticorthotic rehabilitation with more prosthetic complications and their psychological status was worse, resulting in the longer duration of rehabilitation whereas the outcome itself was poor. The value 4 of the prosthetic-orthotic rehabilitation outcome can be expected more often in patients developing complications during rehabilitation. [ABSTRACT FROM AUTHOR]

• Lactic acid bacteria from artisanal dairy products of the Western Balkan were tested. • White brined, fresh and hard cheeses, yogurt, cream and kajmak were analyzed. • Over 3000 isolates were characterized and 28 species were identified. • Many strains had one, two or more probiotic properties. The aim of this review was to summarize the data regarding diversity of non-starter lactic acid bacteria (NSLAB) isolated from various artisanal dairy products manufactured in Western Balkan Countries. The dairy products examined were manufactured from raw cow's, sheep's or goat's milk or mixed milk, in the traditional way without the addition of commercial starter cultures. Dairy products such as white brined cheese, fresh cheese, hard cheese, yogurt, sour cream and kajmak were sampled in the households of Serbia, Croatia, Slovenia, Bosnia and Herzegovina, Montenegro, and North Macedonia. It has been established that the diversity of lactic acid bacteria (LAB) from raw milk artisanal dairy products is extensive. In the reviewed literature, 28 LAB species and a large number of strains belonging to the Lactobacillus, Lactococcus, Enterococcus, Streptococcus, Pediococcus, Leuconostoc and Weissella genera were isolated from various dairy products. Over 3000 LAB strains were obtained and characterized for their technological and probiotic properties including: acidification and coagulation of milk, production of aromatic compounds, proteolytic activity, bacteriocins production and competitive exclusion of pathogens, production of exopolysaccharides, aggregation ability and immunomodulatory effect. Results show that many of the isolated NSLAB strains had one, two or more of the properties mentioned. The data presented emphasize the importance of artisanal products as a valuable source of NSLAB with unique technological and probiotic features important both as a base for scientific research as well as for designing novel starter cultures for functional dairy food. [ABSTRACT FROM AUTHOR]