Statistical ensemble of gene regulatory networks of macrophage differentiation

Background: Macrophages cover a major role in the immune system, being the most plastic cell yielding several key immune functions. Methods: Here we derived a minimalistic gene regulatory network model for the differentiation of macrophages into the two phenotypes M1 (pro-) and M2 (anti-inflammatory). Results: To test the model, we simulated a large number of such networks as in a statistical ensemble. In other words, to enable the inter-cellular crosstalk required to obtain an immune activation in which the macrophage plays its role, the simulated networks are not taken in isolation but combined with other cellular agents, thus setting up a discrete minimalistic model of the immune system at the microscopic/intracellular (i.e., genetic regulation) and mesoscopic/intercellular scale. Conclusions: We show that within the mesoscopic level description of cellular interaction and cooperation, the gene regulatory logic is coherent and contributes to the overall dynamics of the ensembles that shows, statistically, the expected behaviour

A Mathematical Framework for Agent Based Models of Complex Biological Networks

Agent-based modeling and simulation is a useful method to study biological phenomena in a wide range of fields, from molecular biology to ecology. Since there is currently no agreed-upon standard way to specify such models it is not always easy to use published models. Also, since model descriptions are not usually given in mathematical terms, it is difficult to bring mathematical analysis tools to bear, so that models are typically studied through simulation. In order to address this issue, Grimm et al. proposed a protocol for model specification, the so-called ODD protocol, which provides a standard way to describe models. This paper proposes an addition to the ODD protocol which allows the description of an agent-based model as a dynamical system, which provides access to computational and theoretical tools for its analysis. The mathematical framework is that of algebraic models, that is, time-discrete dynamical systems with algebraic structure. It is shown by way of several examples how this mathematical specification can help with model analysis.Comment: To appear in Bulletin of Mathematical Biolog

Mixing & solidification Processing of AI-AI2o3 Composite

In the present investigation, mixing has been carried out by dispersing fine alumina particles (Avg. size- 25 µm) in molten Al-Mg alloy using a turbine blade stirrer with impeller diameter 'd'. The molten alloy has a depth of H when kept in a crucible of diameter D and the stirrer is placed at height 'h' from its bottom. The dimensionless variables. d/D and h/H, have been varied to observe the dependence of optimum values of these variables on stirrer geometry. These studies are expected to contribute to optimum processing route for stircasting of composites. In the current investigation, it has been observed that a turbine stirrer incorporates higher aunount of particles in the ingot cast out of a slurry mixed by it as compared to a flat blade stirrer in the range of experimental parameters used. But the pore-particle ratio is also higher in the cast ingot processed by a turbine stirrer. In the cast ingots processed by a turbine stirrer the particle content increases when d/D ratio increased from 0.33 to 0.48 but a further increase of d/D to 0.62 did not change significantly the particle content. A similar trend in pore-particle ratio is also observed and the lowest poreparticle ratio was observed for d/D=0.62. For mixing a slurry of molten alloy with poorly wetting particles it appears that the recommendation of chemical engineers to keep the stirrer at h/H=0.35 may not work as well from the point of view of particle content in the ingot cast with the slurry. By enhancing h/H to 0.5, the particle content increased significantly and a lower pore-particle ratio was also achieved.The microstructural evidence clearly indicates formation of bubbles with particles adhering to it and even their coalescence during processing. Some of these bubbles are eventually invaded by the molten alloy. When the manner of stirring is changed from continuous four minutes to an interrupted one of two minutes each intervened by a two minute period of cessation of tirring, it has been observed that the particle content at the top reduces but that at the bottom increases making particle content more uniform along the length of the ingot. This has been attributed to enhanced floatation of bubbles containing particles and reincorporation of the latter. During interrupted stirring the porosity did not reduce as unuch as the particles and the poreparticle ratio at the top increased. Enhanced processing time may have contributed to 10increased dissolution of gases contributing to porosity and so3 a reduced extent of bubble-particle combine did not reduce the overall porosity as much as it was expected. When the stirring was interrupted fora longer time of 10 minutes the uniformity of the ingot in respect of particle content improved to an extent but the overall porosity increased significantly. These facts possibly indicate that most of bubbleparticle combines form during mixing and not during solidification

In Defence of Absolutes: The Evolution of Aphra Behns Political Views

The evolution of Aphra Behns political views is a point of scholarly contention. The analysis of her dramatic works starts with her early tragicomedies, like The Young King and The Amorous Prince, and continues through her well- known Exclusion Crisiss sexual comedies, like The Roundheads and Sir Patient Fancy. This paper argues that Behns on- stage royalism was considerably diverse, reflecting various degrees of support for the monarchy. Behn altered her political positions in response to the development of the fierce rivalry between different political parties. Following her concerns and discontent about the kings ability to rule the country in her early plays, Behn developed a remarkable tendency for supporting Charles II and created an image of an impeccable king beyond any criticism. The results suggest that Behn’s Toryism did not reflect an unwavering and unchanging support for the newly restored monarchy, as was assumed previously

Gene regulatory network modeling of macrophage differentiation corroborates the continuum hypothesis of polarization states

Macrophages derived from monocyte precursors undergo specific polarization processes which are influenced by the local tissue environment: classically activated (M1) macrophages, with a pro-inflammatory activity and a role of effector cells in Th1 cellular immune responses, and alternatively activated (M2) macrophages, with anti-inflammatory functions and involved in immunosuppression and tissue repair. At least three different subsets of M2 macrophages, namely, M2a, M2b, and M2c, are characterized in the literature based on their eliciting signals. The activation and polarization of macrophages is achieved through many, often intertwined, signaling pathways. To describe the logical relationships among the genes involved in macrophage polarization, we used a computational modeling methodology, namely, logical (Boolean) modeling of gene regulation. We integrated experimental data and knowledge available in the literature to construct a logical network model for the gene regulation driving macrophage polarization to the M1, M2a, M2b, and M2c phenotypes. Using the software GINsim and BoolNet, we analyzed the network dynamics under different conditions and perturbations to understand how they affect cell polarization. Dynamic simulations of the network model, enacting the most relevant biological conditions, showed coherence with the observed behavior of in vivo macrophages. The model could correctly reproduce the polarization toward the four main phenotypes as well as to several hybrid phenotypes, which are known to be experimentally associated to physiological and pathological conditions. We surmise that shifts among different phenotypes in the model mimic the hypothetical continuum of macrophage polarization, with M1 and M2 being the extremes of an uninterrupted sequence of states. Furthermore, model simulations suggest that anti-inflammatory macrophages are resilient to shift back to the pro-inflammatory phenotype

q-Sumudu transforms pertaining to the product of family of q-polynomials and generalized basic hypergeometric functions

The prime objective of commenced article is to determine q-Sumudu transforms of a product of unified family of q-polynomials with basic (or q-) analog of Fox’s H-function and q-analog of I-functions. Specialized cases of the leading outcome are further evaluated as q-Sumudu transform of general class of q-polynomials and q-Sumudu transforms of the basic analogs of Fox’s H-function and I-functions

Parallel Implementation of Systolic Array Design for Developing Medical Image Rotation

Many image-processing algorithms are particularly suited to parallel computing, as they process images that are difficult and time consuming to analyse. In particular, medical images of tissues tend to be very complex with great irregularity and variability in shapes. Furthermore, existing algorithms contain explicit parallelism, which can be efficiently exploited by processing arrays. A good example of an image processing operation is the geometric rotation of a rectangular bitmap. This paper presents a set of systolic array designs for implementing the geometric rotation algorithms of images on VLSI processing arrays. The examined algorithm performs a trigonometric transformation on each pixel in an image.  The design is implemented as a distributed computing system of networked computers using Parallel Virtual Machine (PVM) model. Each node (computer) in the network takes part in the task in hand – such as image processing – using message passing. Comments and conclusions about the implementation of the design as a distributed computing system are discussed. Keywords: parallel computing, distributed computing. PVM, image rotation, systolic array

Clinical and inheritance profiles of Kallmann syndrome in Jordan

BACKGROUND: Proper management of patients with Kallmann syndrome (KS) allows them to attain a normal reproductive health. The purpose of this study is to demonstrate the presentation modalities, phenotypes and the modes of inheritance among 32 patients with Kallmann syndrome in Jordan. Recognition of the syndrome allows for prompt proper management and provision of genetic counselling. SUBJECTS: Over a period of five years (1999–2004), the clinical and inheritance profiles of 26 male and 6 female patients with Kallmann syndrome from 12 families were evaluated at the National Center for Diabetes, Endocrinology and Genetics in Jordan. RESULTS: The patients belonged to twelve Jordanian and Palestinian families and their age at presentation ranged from 4 – 46 years. Nine boys aged 4–14 years presented with cryptorchidism and microphallus, all other males presented with delayed puberty, hypogonadism and/or infertility. The main presentation among six female patients was primary amenorrhea. Intrafamilial variability in clinical phenotype was specifically evident for renal abnormalities and sensorineural hearing impairment. Familial KS was diagnosed in 27 patients belonging to five families with the X-linked mode of inheritance and two families with the autosomal recessive mode of inheritance. CONCLUSIONS: (1) the majority of cases in this study represented the X-linked form of KS, which might point to a high prevalence of Kal 1 gene in the population. (2) Genetic counselling helps these families to reach a diagnosis at an early age and to decide about their reproductive options. (3) Children presenting with cryptorchidism and microphallus in our population should be investigated for KS

Dynamic risk spillovers between gold, oil prices and conventional, sustainability and Islamic equity aggregates and sectors with portfolio implications

This paper investigates the time-varying equicorrelations and risk spillovers between crude oil, gold and the Dow Jones conventional, sustainability and Islamic stock index aggregates and 10 associated disaggregated Islamic sector stock indexes (basic materials, consumer services, consumer goods, energy, financials, health care, technology, industrials, telecommunications and utilities), using the multivariate DECO-FIAPARCH model and the spillover index of Diebold and Yilmaz (2012). We also conduct a risk management analysis at the sector level for commodity-Islamic stock sector index portfolios, using different risk exposure measures. For comparison purposes, we add the aggregate conventional Dow Jones global index and the Dow Jones sustainability world index. The results show evidence of time-varying risk spillovers between these markets. Moreover, there are increases in the correlations among the markets in the aftermath of the 2008–2009 GFC. Further, the oil, gold, energy, financial, technology and telecommunications sectors are net receivers of risk spillovers, while the sustainability and conventional aggregate DJIM indexes as well as the remaining Islamic stock sectors are net contributors of risk spillovers. Finally, we provide evidence that gold offers better portfolio diversification benefits and downside risk reductions than oil. © 2017 Elsevier B.V