Theoretical Biology and Medical Modelling via MedWorm.com

Cancer dynamics for identical twin brothers

Theoretical Biology and Medical Modelling — Mon, 06 Feb 2012 05:00:00 +0100

In this paper, a new mathematical model is developed to represent the interaction between healthy and cancer cells in the human body, focusing on the role of environmental factors and quality of life in the progression of cancer. We have investigated the dynamic effects of inputs on cancer growth, and provide an explanation of how cancer has variable behavior patterns throughout the lives of different patients. The behavior of the system with input and its trajectory patterns are investigated using trajectory patterns and stability analysis. The analysis suggests that a proper treatment method should change the dynamics of the cancer instead of only reducing the population of cancer cells and treatment burden. (Source: Theoretical Biology and Medical Modelling)

Dysmorphometrics: the modelling of morphological abnormalities

Theoretical Biology and Medical Modelling — Mon, 06 Feb 2012 05:00:00 +0100

Conclusion: The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice and research. (Source: Theoretical Biology and Medical Modelling)

Mathematical modeling of solid cancer growth with angiogenesis

Theoretical Biology and Medical Modelling — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: Cancer can be settled in an organ if the following combination matches: better fitness of cancercells, decrease in the effciency of the repairing systems, increase in the capacity of sprouting from existingvascularization, and higher capacity of mounting up new vascularization. However, we show that cancer is rarelyinduced in organs (or tissues) displaying an efficient (numerically and functionally) reparative or regenerativemechanism. (Source: Theoretical Biology and Medical Modelling)

A molecular diffusion based utility model for Drosophila larval phototaxis

Theoretical Biology and Medical Modelling — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: Our model provides new insights into decision making mechanisms in general. From an engineering viewpoint, we propose that the model could be applied to a wider range of decision making practices. (Source: Theoretical Biology and Medical Modelling)

Neural Network Assessment of Herbal Protection against Chemotherapeutic-Induced Reproductive Toxicity

Theoretical Biology and Medical Modelling — Tue, 24 Jan 2012 05:00:00 +0100

The aim of this study is to assess the protective effects of Ginkgo biloba's (GB) extract against chemotherapeutic-induced reproductive toxicity using a data mining tool, namely Neural Network Clustering (NNC) on two types of data: biochemical & fertility indicators and Texture Analysis (TA) parameters. GB extract (1 g/kg/day) was given orally to male albino rats for 26 days. This period began 21 days before a single cisplatin (CIS) intraperitoneal injection (10 mg/kg body weight). GB given orally significantly restored reproductive function. Tested extract also notably reduced the CIS-induced reproductive toxicity, as evidenced by restoring normal morphology of testes. In GB, the attenuation of CIS-induced damage was associated with less apoptotic cell death both in the testicular tissue ...

Non-Stem Cancer Cell Kinetics Modulate Solid Tumor Progression

Theoretical Biology and Medical Modelling — Fri, 30 Dec 2011 05:00:00 +0100

Conclusions: Our study suggests that variability in the growth rate and CSC content of solid tumors may be, in part, attributable to the proliferative capacity of the non-stem cancer cell population that arises during asymmetric division of CSCs. In our model, intermediate proliferative capacities give rise to the fastest-growing tumors, resulting in self-metastatic expansion driven by a balance between symmetric CSC division and expansion of the non-stem cancer population. Our results highlight the importance of non-stem cancer cell dynamics in the CSC hypothesis, and may offer a novel explanation for the large variations in CSC fractions reported in vivo. (Source: Theoretical Biology and Medical Modelling)

Modularity analysis based on predicted protein-protein interactions provides new insights into pathogenicity and cellular process of Escherichia coli O157:H7

Theoretical Biology and Medical Modelling — Thu, 22 Dec 2011 05:00:00 +0100

Conclusions: This article provides the first modularity analysis of a pathogen and sheds new light on the study of pathogens and cellular processes. Our study also provides a strategy for applying modularity analysis to any sequenced organism. (Source: Theoretical Biology and Medical Modelling)

Developing a multiscale, multi-resolution agent-based brain tumor model by graphics processing units

Theoretical Biology and Medical Modelling — Fri, 16 Dec 2011 05:00:00 +0100

Multiscale agent-based modeling (MABM) has been widely used to simulate Glioblastoma Multiforme (GBM) and its progression. At the intracellular level, the MABM approach employs a system of ordinary differential equations to describe quantitatively specific intracellular molecular pathways that determine phenotypic switches among cells (e.g. from migration to proliferation and vice versa). At the intercellular level, MABM describes cell-cell interactions by a discrete module. At the tissue level, partial differential equations are employed to model the diffusion of chemoattractants, which are the input factors of the intracellular molecular pathway. Moreover, multiscale analysis makes it possible to explore the molecules that play important roles in determining the cellular phenotypic switc...

A systems-based mathematical modelling framework for investigating the effect of drugs on solid tumours

Theoretical Biology and Medical Modelling — Wed, 07 Dec 2011 05:00:00 +0100

Conclusions: We have created a predictive systems platform integrating drug transport and cellular response which can be systematically augmented to include additional layers of cellular complexity. Our results indicate that intracellular signalling models which are qualitatively different can give rise to similar behaviour to simple (and typical) stimuli, and that validating intracellular descriptions must be performed with care by considering a variety of drug stimuli. (Source: Theoretical Biology and Medical Modelling)

The feasibility of age-specific travel restrictions during influenza pandemics

Theoretical Biology and Medical Modelling — Fri, 11 Nov 2011 05:00:00 +0100

Conclusions: Selectively restricting children from traveling overseas during a pandemic may potentially delay its arrival for a few weeks, depending on the characteristics of the pandemic strain, but could have less of an impact on the economy compared to restricting adult travelers. However, as long as adults have at least a moderate potential to trigger an epidemic, selectively restricting the higher risk group (children) may not be a practical option to delay the arrival of an epidemic substantially. (Source: Theoretical Biology and Medical Modelling)

A parametric method for cumulative incidence modeling with a new four-parameter log-logistic distribution

Theoretical Biology and Medical Modelling — Fri, 11 Nov 2011 05:00:00 +0100

Conclusions: The results of simulation studies showed that the estimated cumulative incidence function was more accurate than non-parametric estimates in some settings. Analyses of real data indicated that the proposed distribution showed a much better fit to the data than the other distributions tested. Therefore, the new distribution is recommended for practical applications to parameterize the cumulative incidence function in competing risk settings. (Source: Theoretical Biology and Medical Modelling)

Modelling Ultrasound-Induced Mild Hyperthermia of Hyperplasia in Vascular Grafts

Theoretical Biology and Medical Modelling — Thu, 03 Nov 2011 04:00:00 +0100

Conclusions: Modelling shows that ultrasound can selectively heat ePTFE grafts and produce temperatures that cause cell death on the graft. The temperature increase in blood is negligible and that in the adjacent soft tissues may be minimized by skin cooling and using appropriate transducers. Therefore, ultrasound heating may have the potential to reduce neointimal hyperplasia and failure of ePTFE vascular grafts. (Source: Theoretical Biology and Medical Modelling)

Protein-x of hepatitis B virus in interaction with CCAAT/ enhancer-binding protein alpha (C/EBP alpha) - An in silico analysis approach

Theoretical Biology and Medical Modelling — Fri, 28 Oct 2011 04:00:00 +0100

Conclusion: In this study, we predicted the structure of protein-x of HBV in interaction with C/EBP alpha. The docking results showed that protein-x has an interaction synergy with C/EBP alpha. However, despite previous experimental data, protein-x was found to interact with DNA. This can lead to a better understanding of the function of protein-x and may provide an opportunity to use it as a therapeutic target. (Source: Theoretical Biology and Medical Modelling)

Time series analysis as input for clinical predictive modeling: Modeling cardiac arrest in a pediatric ICU

Theoretical Biology and Medical Modelling — Mon, 24 Oct 2011 04:00:00 +0100

Conclusions: We have proposed a ten step process that results in data sets that contain time series features and are suitable for predictive modeling by a number of methods. We illustrated the process through an example of cardiac arrest prediction in a pediatric intensive care setting. (Source: Theoretical Biology and Medical Modelling)

Canalization Effect in the Coagulation Cascade and the Interindividual Variability of Oral Anticoagulant Response. A Simulation Study

Theoretical Biology and Medical Modelling — Wed, 12 Oct 2011 04:00:00 +0100

No description available (Source: Theoretical Biology and Medical Modelling)

Availability of a pediatric trauma center in a disaster surge decreases triage time of the pediatric surge population: a population kinetics model

Theoretical Biology and Medical Modelling — Wed, 12 Oct 2011 04:00:00 +0100

Conclusions: Our model provides a mathematical justification for aggressive inclusion of PTCs in planning for disasters by public health agencies. (Source: Theoretical Biology and Medical Modelling)

Relational Grounding Facilitates Development of Scientifically Useful Multiscale Models

Theoretical Biology and Medical Modelling — Tue, 27 Sep 2011 04:00:00 +0100

We review grounding issues that influence the scientific usefulness of any biomedical multiscale model (MSM). Groundings are the collection of units, dimensions, and/or objects to which a variable or model constituent refers. To date, models that primarily use continuous mathematics rely heavily on absolute grounding, whereas those that primarily use discrete software paradigms (e.g., object-oriented, agent-based, actor) typically employ relational grounding. We review grounding issues and identify strategies to address them. We maintain that grounding issues should be addressed at the start of any MSM project and should be reevaluated throughout the model development process. We make the following points. Grounding decisions influence model flexibility, adaptability, and thus reusability....

A network model for biofilm development in Escherichia coli K-12

Theoretical Biology and Medical Modelling — Thu, 22 Sep 2011 04:00:00 +0100

Conclusions: The different phenotypes obtained demonstrate that the network model of biofilm formation can simulate the formation or repression of biofilm efficiently in E. coli K-12. (Source: Theoretical Biology and Medical Modelling)

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis

Theoretical Biology and Medical Modelling — Mon, 19 Sep 2011 04:00:00 +0100

Conclusions/Significance: Agent-based modeling can account for the spatio-temporal dynamics of an HPI, and, even when carried out with a relatively high degree of abstraction, can be useful in the investigation of system-level consequences of putative mechanisms operating at the individual agent level. We suggest that an integrated and iterative heuristic relationship between computational modeling and more traditional laboratory and clinical investigations, with a focus on identifying useful and sufficient degrees of abstraction, will enhance the efficiency and translational productivity of biomedical research. (Source: Theoretical Biology and Medical Modelling)

A reaction-diffusion model of the receptor-toxin-antibody interaction

Theoretical Biology and Medical Modelling — Wed, 07 Sep 2011 04:00:00 +0100

Conclusions: The proposed refinement of the RTA model may become important for the consistent evaluation ofprotective potential of an antibody and for the estimation of the time period during which the application of thisantibody becomes the most effective. It can be a useful tool for in vitro selection of potential protectiveantibodies for progression to in vivo evaluation. (Source: Theoretical Biology and Medical Modelling)

Mathematical model insights into arsenic detoxification

Theoretical Biology and Medical Modelling — Thu, 25 Aug 2011 23:00:00 +0100

Conclusions: The analysis of the Bangladesh data using the model suggests that folate supplementation may be more effective at reducing whole body arsenic than previously expected. There is almost no data on the upregulation of arsenic methyltransferase in populations chronically exposed to arsenic. Our model predicts upregulation by a factor of two in the Bangladesh population studied. This prediction should be verified since it could have important public health consequences both for treatment strategies and for setting appropriate limits on arsenic in drinking water. Our model has compartments for the binding of arsenicals to proteins inside of cells and we show that these comparments are necessary to obtain good fits to data. Protein-binding of arsenicals should be explored in future b...

Cancer as a dynamical phase transition

Theoretical Biology and Medical Modelling — Wed, 24 Aug 2011 23:00:00 +0100

This paper discusses the properties of cancer cells from a new perspective based on an analogy with phase transitions in physical systems. Similarities in terms of instabilities and attractor states are outlined and differences discussed. While physical phase transitions typically occur at or near thermodynamic equilibrium, a normal-to-cancer (NTC) transition is a dynamical non-equilibrium phenomenon, which depends on both metabolic energy supply and local physiological conditions. A number of implications for preventative and therapeutic strategies are outlined. (Source: Theoretical Biology and Medical Modelling)

Defining the Buffering Process by a Triprotic Acid Without Relying on Stewart-Electroneutrality Considerations

Theoretical Biology and Medical Modelling — Tue, 16 Aug 2011 23:00:00 +0100

Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that...

Formation of translational risk score based on correlation coefficients as an alternative to Cox regression models for predicting outcome in patients with NSCLC

Theoretical Biology and Medical Modelling — Tue, 26 Jul 2011 23:00:00 +0100

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Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

Theoretical Biology and Medical Modelling — Mon, 25 Jul 2011 23:00:00 +0100

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Proviral HIV-genome-wide and pol-gene specific Zinc Finger Nucleases: Usability for targeted HIV gene therapy

Theoretical Biology and Medical Modelling — Thu, 21 Jul 2011 23:00:00 +0100

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Optimizing automated characterization of liver fibrosis histological images by investigating color spaces at different resolutions

Theoretical Biology and Medical Modelling — Wed, 13 Jul 2011 23:00:00 +0100

Texture analysis (TA) of histological images has recently received attention as an automated method of characterizing liver fibrosis. The colored staining methods used to identify different tissue components reveal various patterns that contribute in different ways to the digital texture of the image. A histological digital image can be represented with various color spaces. The approximation processes of pixel values that are carried out while converting between different color spaces can affect image texture and subsequently could influence the performance of TA. Conventional TA is carried out on gray scale images, which are a luminance approximation to the original RGB (Red, Green, and Blue) space. Currently, gray scale is considered sufficient for characterization of fibrosis but this ...

A biochemical hypothesis on the formation of fingerprints using a Turing patterns approach

Theoretical Biology and Medical Modelling — Mon, 27 Jun 2011 23:00:00 +0100

Conclusions: The numerical examples showed that the model could represent the formation of different types of fingerprint characteristics in each individual. (Source: Theoretical Biology and Medical Modelling)

A nucleotide binding rectification Brownian ratchet model for translocation of Y-family DNA polymerases

Theoretical Biology and Medical Modelling — Thu, 23 Jun 2011 23:00:00 +0100

Y-family DNA polymerases are characterized by low-fidelity synthesis on undamaged DNA and ability to catalyze translesion synthesis over the damaged DNA. Their translocation along the DNA template is an important event during processive DNA synthesis. In this work we present a Brownian ratchet model for this translocation, where the directed translocation is rectified by the nucleotide binding to the polymerase. Using the model, different features of the available structures for Dpo4, Dbh and polymerase iota in binary and ternary forms can be easily explained. Other dynamic properties of the Y-family polymerases such as the fast translocation event upon dNTP binding for Dpo4 and the considerable variations of the processivity among the polymerases can also be well explained by using the mo...

Identity of zinc finger nucleases with specificity to Herpes simplex virus type II genomic DNA: novel HSV-2 vaccine/ therapy precursors

Theoretical Biology and Medical Modelling — Thu, 23 Jun 2011 23:00:00 +0100

Conclusion: ZFNs with specificity to HSV-2 genomic DNA that are precursors of novel host-genome expressed HSV-2 gene-therapeutics or vaccines were identified. (Source: Theoretical Biology and Medical Modelling)

Review and application of group theory to molecular systems biology

Theoretical Biology and Medical Modelling — Tue, 21 Jun 2011 23:00:00 +0100

In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possible in the 64-dimensional space-time manifold of the evolving genome.With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a s...

A Local Glucose- and Oxygen Concentration-Based Insulin Secretion Model for Pancreatic Islets

Theoretical Biology and Medical Modelling — Mon, 20 Jun 2011 23:00:00 +0100

Conclusions: An insulin secretion model was implemented by coupling local consumption and release rates to calculations of the spatial distributions of all species of interest. The resulting glucose-insulin control system fits in the general framework of a sigmoid proportional-integral-derivative controller, a generalized PID controller, more suitable for biological systems, which are always nonlinear due to the maximum response being limited. Because of the general framework of the implementation, simulations can be carried out for arbitrary geometries including cultured, perifused, transplanted, and encapsulated islets. (Source: Theoretical Biology and Medical Modelling)

Interactomes, manufacturomes and relational biology: analogies between systems biology and manufacturing systems

Theoretical Biology and Medical Modelling — Sun, 19 Jun 2011 23:00:00 +0100

Conclusions: We show that the relevant mapping relations may not be Abelian, and that these problems cannot yet be resolved because the interactomes and manufacturomes are incomplete. (Source: Theoretical Biology and Medical Modelling)

The function of 7D-cadherins: A mathematical model predicts physiological importance for water transport through simple epithelia

Theoretical Biology and Medical Modelling — Thu, 09 Jun 2011 23:00:00 +0100

Conclusions: Our simple model clearly predicts that changes of the width of the lateral intercellular cleft can regulate the direction and efficiency of water transport through a simple epithelium. In a narrow cleft the cells can increase the concentration of osmotic active substances easily by active transport whereas if the cleft is wide, friction is reduced but the cells can hardly build up high osmotic gradients. It is now tempting to speculate that 7D-cadherins, owing to their location and their Ca2+-dependence, will adapt their binding activity and thereby the width of the lateral intercellular cleft automatically as the Ca2+-concentration is coupled to the overall electrolyte concentration in the lateral intercellular cleft. This could provide a way to regulate the water resorption ...

Self-organization of developing embryo using scale-invariant approach

Theoretical Biology and Medical Modelling — Thu, 02 Jun 2011 23:00:00 +0100

In this study, a scale-invariant power law (SIPL) method has been used to study self-organization in developing embryos. The SIPL coefficient was calculated using a centro-axial skew symmetrical matrix (CSSM) generated by entering the components of the Cartesian coordinates; for each component, one CSSM was generated. A basic square matrix (BSM) was constructed and the determinant was calculated in order to estimate the SIPL coefficient. This was applied to developing C. elegans during early stages of embryogenesis. The power law property of the method was evaluated using the straight line and Koch curve and the results were consistent with fractal dimensions (fd). Diffusion-limited aggregation (DLA) was used to validate the SIPL method.Results and conclusion: The fractal dimensions of bot...

Can Molecular Cell Biology Explain Chromosome Motions?

Theoretical Biology and Medical Modelling — Thu, 26 May 2011 23:00:00 +0100

Conclusion: We question here why cells would prefer complex molecular mechanisms to move chromosomes when direct electrostatic interactions between known bound charge distributions can accomplish the same task much more simply. (Source: Theoretical Biology and Medical Modelling)

Improving the prediction of yeast protein function using weighted protein-protein interactions

Theoretical Biology and Medical Modelling — Tue, 26 Apr 2011 23:00:00 +0100

Conclusions: A new method for weighting the interactions in protein-protein interaction networks is presented. Experimental results concerning yeast proteins demonstrated that weighting interactions integrated with the neighbor counting method improved the sensitivity and specificity of prediction in terms of two functional categories: cellular role and cell locations. (Source: Theoretical Biology and Medical Modelling)

Safe uses of Hill's model: an exact comparison with the Adair-Klotz model

Theoretical Biology and Medical Modelling — Mon, 25 Apr 2011 23:00:00 +0100

Conclusions: A strongly cooperative Adair-Klotz model can be replaced by a suitable Hill model in such a way that any property computed from the two models, even the one describing stochastic features, is approximately the same. The quantitative analysis showed that boundaries of the regions in the parameter space where the models behave in the same way exhibit a rather rich structure. (Source: Theoretical Biology and Medical Modelling)

The effects of low-impact mutations in digital organisms

Theoretical Biology and Medical Modelling — Sun, 17 Apr 2011 23:00:00 +0100

Conclusions: Avidian organisms evolve new logic operations only when mutations producing them are assigned high-impact fitness effects. Furthermore, purifying selection cannot protect operations with low-impact benefits from mutational deterioration. These results suggest that selection breaks down for low-impact mutations below a certain fitness effect, the selection threshold. Experiments using biologically relevant parameter settings show the tendency for increasing genetic load to lead to loss of biological functionality. An understanding of such genetic deterioration is relevant to human disease, and may be applicable to the control of pathogens by use of lethal mutagenesis. (Source: Theoretical Biology and Medical Modelling)

A mathematical model of quorum sensing regulated EPS production in biofilm communities

Theoretical Biology and Medical Modelling — Sat, 09 Apr 2011 23:00:00 +0100

Conclusions: A biofilm will benefit from using quorum sensing-induced EPS production if bacteria cells have theobjective of acquiring a thick, protective layer of EPS, or if they wish to clog their environment with biomass asa means of securing nutrient supply and outcompeting other colonies in the channel, of their own or a different species. (Source: Theoretical Biology and Medical Modelling)

Proof-of-principle investigation of an algorithmic model of adenosine-mediated angiogenesis

Theoretical Biology and Medical Modelling — Thu, 07 Apr 2011 23:00:00 +0100

Conclusions: The proposed model can support the exploration of hypotheses about the role of different molecular entities and experimental conditions in angiogenesis. Future expansions can also be applied to assist research planning in this and other biomedical domains. (Source: Theoretical Biology and Medical Modelling)

Module-based multiscale simulation of angiogenesis in skeletal muscle

Theoretical Biology and Medical Modelling — Sun, 03 Apr 2011 23:00:00 +0100

Conclusions: This systems biology strategy can be applied to larger scale integration of computational models of angiogenesis in skeletal muscle, or other complex processes in other tissues under physiological and pathological conditions. (Source: Theoretical Biology and Medical Modelling)

Disruption of cell wall fatty acid biosynthesis in Mycobacterium tuberculosis using a graph theoretic approach

Theoretical Biology and Medical Modelling — Wed, 30 Mar 2011 23:00:00 +0100

Fatty acid biosynthesis of Mycobacterium tuberculosis was analyzed using graph theory and influential (impacting) proteins were identified. The graphs (digraphs) representing this biological network provide information concerning the connectivity of each protein or metabolite in a given pathway, providing an insight into the importance of various components in the pathway, and this can be quantitatively analyzed. Using a graph theoretic algorithm, the most influential set of proteins (sets of {1, 2, 3}, etc.), which when eliminated could cause a significant impact on the biosynthetic pathway, were identified. This set of proteins could serve as drug targets. In the present study, the metabolic network of Mycobacterium tuberculosis was constructed and the fatty acid biosynthesis pathway was...

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

Theoretical Biology and Medical Modelling — Mon, 28 Mar 2011 23:00:00 +0100

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self...

Theoretical basis to measure the impact of short-lasting control of an infectious disease on the epidemic peak

Theoretical Biology and Medical Modelling — Wed, 26 Jan 2011 00:00:00 +0100

Conclusions: The proposed modeling approaches offer methodological avenues to assess empirical data and to objectively estimate required control effort to lower and delay an epidemic peak. Analytical findings support a critical need to conduct population-wide serological survey as a prior requirement for estimating the time of peak. (Source: Theoretical Biology and Medical Modelling)

Modeling the clonal heterogeneity of stem cells

Theoretical Biology and Medical Modelling — Wed, 17 Nov 2010 00:00:00 +0100

Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells, the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties, reflecting proliferation, a...

Population genetics of cancer cell clones: possible implications of cancer stem cells.

Theoretical Biology and Medical Modelling — Tue, 09 Nov 2010 00:00:00 +0100

Conclusions: The presence of cancer stem cells may result in more rapid clonal evolution. Specific predictions from theoretical population genetics may lead to a greater understanding of this process. (Source: Theoretical Biology and Medical Modelling)

Assessing the effects of multiple infections and long latency in the dynamics of tuberculosis

Theoretical Biology and Medical Modelling — Mon, 08 Nov 2010 00:00:00 +0100

In order to achieve a better understanding of multiple infections and long latency in the dynamics of Mycobacterium tuberculosis infection, we analyze a simple model. Since backward bifurcation is well documented in the literature with respect to the model we are considering, our aim is to illustrate this behavior in terms of the range of variations of the model's parameters. We show that backward bifurcation disappears (and forward bifurcation occurs) if: (a) the latent period is shortened below a critical value; and (b) the rates of super-infection and re-infection are decreased. This result shows that among immunosuppressed individuals, super-infection and/or changes in the latent period could act to facilitate the onset of tuberculosis. When we decrease the incubation period below the ...

A danger of low copy numbers for inferring incorrect cooperativity degree

Theoretical Biology and Medical Modelling — Mon, 01 Nov 2010 00:00:00 +0100

Conclusions: The Hill function cannot describe dose-response curves in a low particle limit. First, dose-response curves are not solely parameterized by the dissociation constant and the Hill coefficient. In general, the shape of a dose-response curve depends on the variables that describe how an experiment (ensemble) is designed. Second, dose-response curves are multi-valued in a rather non-trivial way. (Source: Theoretical Biology and Medical Modelling)

A plague on five of your houses - statistical re-assessment of three pneumonic plague outbreaks that occurred in Suffolk, England, between 1906 and 1918.

Theoretical Biology and Medical Modelling — Sun, 24 Oct 2010 23:00:00 +0100

Conclusions: The symptomatic period was approximately 1 day longer on average than in an earlier study but the serial interval was in close agreement with 2 previously reported values. 2 of the 3 outbreaks ended without explicit public health interventions; however, non-professional caregivers were particularly vulnerable - an important public health consideration for any future outbreak of pneumonic plague. (Source: Theoretical Biology and Medical Modelling)

Immunologgical self-tolerance in allophenic and embryo-aggregated mice

Theoretical Biology and Medical Modelling — Sun, 19 Sep 2010 23:00:00 +0100

Allophenic mice, supposedly containing almost equal numbers of cells derived from embryos of mouse strains C57Bl and FVB, were shown in a recent paper to grow the B16 melanoma, a long transplanted tumor of C57Bl origin, much better than did mice of either the parental C57Bl strain or the C57Bl x FVB F1 hybrid. Mice containing smaller proportions of C57Bl cells rejected the tumor. A reconsideration of these suprising data, in light of the current literature, suggests that the better growth of the tumor in the 50-50% allophenics than in the C57Bl parental strain was probably caused by the tumor stimulation engendered by a weak anti-C57Bl immune reaction in the overtly healthy allophenic mice. (Source: Theoretical Biology and Medical Modelling)

Pathological axes of wound repair: Gastrulation revisited

Theoretical Biology and Medical Modelling — Mon, 13 Sep 2010 23:00:00 +0100

Post-traumatic inflammation is formed by molecular and cellular complex mechanisms whose final goal seems to be injured tissue regeneration.In the skin -an exterior organ of the body- mechanical or thermal injury induces the expression of different inflammatory phenotypes that resemble similar phenotypes expressed during embryo development. Particularly, molecular and cellular mechanisms involved in gastrulation return. This is a developmental phase that delineates the three embryonic germ layers: ectoderm, endoderm and mesoderm. Consequently, in the post-natal wounded skin, primitive functions related with the embryonic mesoderm, i.e. amniotic and yolk sac-derived, are expressed. Neurogenesis and hematogenesis stand out among the primitive function mechanisms involved.Interestingly, in th...

Dynamic models of immune responses: what is the ideal level of detail?

Theoretical Biology and Medical Modelling — Thu, 19 Aug 2010 23:00:00 +0100

Conclusions: Models of sub-systems or simplified immune response can be used to hypothesize phenomena of host-pathogen interactions and to estimate rates and parameters. Nevertheless, to study the pathogenesis of an infection we need to develop models describing the dynamics of the immune components involved in the progression of the disease. Incorporation of the large number and variety of immune processes involved in pathogenesis requires tradeoffs in modeling. (Source: Theoretical Biology and Medical Modelling)

Characterization of vascular strain during in-vitro angioplasty with high-resolution ultrasound speckle tracking

Theoretical Biology and Medical Modelling — Thu, 19 Aug 2010 23:00:00 +0100

Conclusion: These results validate the ability of ultrasound elasticity imaging to measure localized mechanical changes in vascular tissue. (Source: Theoretical Biology and Medical Modelling)

Serotonin synthesis, release and reuptake in terminals: a mathematical model

Theoretical Biology and Medical Modelling — Wed, 18 Aug 2010 23:00:00 +0100

Conclusions: Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions. (Source: Theoretical Biology and Medical Modelling)

A novel approach to modelling water transport and drug diffusion through the stratum corneum

Theoretical Biology and Medical Modelling — Mon, 16 Aug 2010 23:00:00 +0100

Conclusions: Our results support the possibility for designing arbitrary drugs capable of diffusing through the skin, the time-delivery of which is solely restricted by their diffusion and solubility properties. (Source: Theoretical Biology and Medical Modelling)

Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system

Theoretical Biology and Medical Modelling — Tue, 10 Aug 2010 23:00:00 +0100

Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful ne...

Diet as prophylaxis and treatment for venous thromboembolism?

Theoretical Biology and Medical Modelling — Tue, 10 Aug 2010 23:00:00 +0100

Conclusions: Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials. (Source: Theoretical Biology and Medical Modelling)

Network, degeneracy and bow tie Integrating paradigms and architectures to grasp the complexity of the immune system

Theoretical Biology and Medical Modelling — Tue, 10 Aug 2010 23:00:00 +0100

Tracking tumor evolution via prostate-specific antigen: an individual post-operative study

Theoretical Biology and Medical Modelling — Thu, 29 Jul 2010 23:00:00 +0100

Conclusions: Such studies may help determine the appropriate time window for postoperative therapies in order to increase the life expectancy of the patient. (Source: Theoretical Biology and Medical Modelling)

Stochasticity of flow through microcirculation as a regulator of oxygen delivery.

Theoretical Biology and Medical Modelling — Thu, 08 Jul 2010 23:00:00 +0100

Conclusion: By variation of vasomotion activity it is possible to change delivery of oxygen to a tissue by up to 8 times. (Source: Theoretical Biology and Medical Modelling)

Complex life forms may arise from electrical processes

Theoretical Biology and Medical Modelling — Wed, 23 Jun 2010 23:00:00 +0100

There is still not an appealing and testable model to explain how single-celled organisms, usually following fusion of male and female gametes, proceed to grow and evolve into multi-cellular, complexly differentiated systems, a particular species following virtually an invariant and unique growth pattern. An intrinsic electrical oscillator, remembling the cardiac pacemaker, may explain the process. Highly auto-correlated, it could live independently of ordinary thermodynamic processes which mandate increasing disorder, and could coordinate growth and differentiation of organ anlage. (Source: Theoretical Biology and Medical Modelling)

How is the balance between protein synthesis and degradation achieved?

Theoretical Biology and Medical Modelling — Tue, 22 Jun 2010 23:00:00 +0100

Unlike most substances that cells manufacture, proteins are not produced and broken down by a common series of chemical reactions, but by completely different (independent and disconnected) mechanisms that possess no intrinsic means of making the rates of the two processes equal and attaining steady state concentrations. Balance between them is achieved extrinsically and is often imagined today to be the result of the actions of chemical feedback agents. But however instantiated, chemical feedback or any similar mechanism can only rectify induced imbalances in a system previously balanced by other means. Those "other means" necessarily involve reversible mass action or equilibrium-based interactions between native and altered forms of protein molecules somewhere in time and space between t...

Skeletal muscle contraction. The thorough definition of the contractile event requires both load acceleration and load mass to be known

Theoretical Biology and Medical Modelling — Thu, 17 Jun 2010 23:00:00 +0100

Conclusions: We urge that in the study of muscle contraction both the mass and the acceleration of the load are specified. (Source: Theoretical Biology and Medical Modelling)

Transperineal prostate biopsy: analysis of a uniform core sampling pattern that yields data on tumor volume limits in negative biopsies

Theoretical Biology and Medical Modelling — Wed, 16 Jun 2010 23:00:00 +0100

Conclusions: Distributing transperineal biopsy cores so they are evenly spaced provides a means to calculate the probability that a tumor of given volume could be present when the biopsy is negative, and can improve detection efficiency. (Source: Theoretical Biology and Medical Modelling)

In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1, 5-benzothiazepine against BChE in the formation of beta-amyloid plaques associated with Alzheimer's disease

Theoretical Biology and Medical Modelling — Tue, 15 Jun 2010 23:00:00 +0100

Conclusion: Molecular docking studies revealed that the potential of Compound A to inhibit cholinesterases was attributable to the cumulative effects of strong hydrogen bonds, cationic-pi, pi-pi interactions and hydrophobic interactions. A comparison of the docking results of Compound A against both cholinesterases showed that amino acid residues in different sub-sites were engaged to stabilize the docked complex. The relatively high affinity of Compound A for butyrylcholinesterase was due to the additional hydrophobic interaction between the 2-thiophene moiety of Compound A and Ile69. The involvement of one catalytic triad residue (His438) of butyrylcholinesterase with the 3' -hydroxy group on ring A increases the selectivity of Compound A. C-C bond rotation around ring A also stabilizes ...

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

Theoretical Biology and Medical Modelling — Mon, 14 Jun 2010 23:00:00 +0100

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which distributed decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effec...

Native aggregation as a cause of origin of temporary cellular structures needed for all forms of cellular activity, signaling and transformations

Theoretical Biology and Medical Modelling — Tue, 08 Jun 2010 23:00:00 +0100

According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions. It is assumed that Anfinsen's dogma may be extended to protein aggregation: composition and amino acid sequence determine not only the secondary and tertiary structure of single protein, but also the structure of protein aggregates (associates). Cell function is considered as a transition between two states (two states model), the resting state and state of activity (this applies to the cell as a whole and to its individual structures). In the resting state, the key proteins are found in the following inactive forms: natively unfolded and globular. When t...

ChIP-PaM: an algorithm to identify protein-DNA interaction using ChIP-Seq data

Theoretical Biology and Medical Modelling — Wed, 02 Jun 2010 23:00:00 +0100

Conclusions: In a comparison with other existing methods, we found that our algorithm provides more accurate binding site discovery while maintaining comparable statistical power. (Source: Theoretical Biology and Medical Modelling)

A generalized physiologically-based toxicokinetic modeling system for chemical mixtures containing metals

Theoretical Biology and Medical Modelling — Tue, 01 Jun 2010 23:00:00 +0100

Conclusions: The application of GTMM to different individual metals and metal compounds showed that it explains available observational data as well as replicates the results from models that have been optimized for individual chemicals. The GTMM also made it feasible to model toxicokinetics of complex, interacting mixtures of multiple metals and nonmetals in humans, based on available literature information. The GTMM provides a central component in the development of a "source-to-dose-to-effect" framework for modeling population health risks from environmental contaminants. As new data become available on interactions of multiple chemicals, the GTMM can be iteratively parameterized to improve mechanistic understanding of human health risks from exposures to complex mixtures of chemicals. ...

Glucose sensing in the pancreatic beta cell: a computational systems analysis

Theoretical Biology and Medical Modelling — Sun, 23 May 2010 23:00:00 +0100

Conclusion: This comprehensive model predicts a special role for mitochondrial control mechanisms in insulin secretion and ROS generation in the beta cell. The model can be used for testing and generating control hypotheses and will help to provide a more complete understanding of beta-cell glucose-sensing central to the physiology and pathology of pancreatic beta-cells. (Source: Theoretical Biology and Medical Modelling)

Order without Design

Theoretical Biology and Medical Modelling — Tue, 13 Apr 2010 23:00:00 +0100

Experimental reality in molecular and cell biology, as revealed by advanced research technologies and methods, is manifestly inconsistent with the design perspective on the cell, thus creating an apparent paradox: where do order and reproducibility in living systems come from if not from design?I suggest that the very idea of biological design (whether evolutionary or intelligent) is a misconception rooted in the time-honored and thus understandably precious error of interpreting living systems/organizations in terms of classical mechanics and equilibrium thermodynamics. This error, introduced by the founders and perpetuated due to institutionalization of science, is responsible for the majority of inconsistencies, contradictions, and absurdities plaguing modern sciences, including one of ...

A thalamic reticular networking model of consciousness

Theoretical Biology and Medical Modelling — Mon, 29 Mar 2010 23:00:00 +0100

Conclusions] I propose that the thalamocortical integrative communication across first- and higher-order information circuits and repeated feedback looping may account for our conscious awareness. This TRN-modulation hypothesis for conscious awareness provides a comprehensive rationale regarding previously reported psychological phenomena and neurological symptoms such as blindsight, neglect, the priming effect, the threshold/duration problem, and TRN-impairment resembling coma. This hypothesis can be tested by neurosurgical investigations of thalamocortical loops via the TRN, while simultaneously evaluating the degree to which conscious perception depends on the severity of impairment in a TRN-modulated network. (Source: Theoretical Biology and Medical Modelling)

Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test

Theoretical Biology and Medical Modelling — Thu, 18 Mar 2010 00:00:00 +0100

Background: The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative. Methods: The SDM was applied to 74 IVGTTs from lean (19), overweight (22), obese (22) and morbidly obese (11) subjects. Estimates from the SDM (KxgI) were compared with the corresponding MM (SI), 1/HOMA-IR index and Euglycemic-Hyperinsulinemic Clamp (M-EHC over 7 subjects) estimates. Results: KxgI was identifiable (CV< 52%) in 73 out of 74 subjects (CV=69% in the 74th subject) and ranged from 1.25E-05 to 4.36E-04 1/(min pM); SI CV was >52% in 36 subjects (u...

Theoretical analysis of the mechanisms of a gender differentiation in the propensity for orthostatic intolerance after spaceflight

Theoretical Biology and Medical Modelling — Thu, 18 Mar 2010 00:00:00 +0100

Conclusions: The analysis demonstrated that a 15% lowering of the longitudinal center of gravity in the anatomic structure of the model was all that was necessary to prevent the physiologic compensatory mechanisms from overcoming the propensity for reentry orthostasis leading to syncope. (Source: Theoretical Biology and Medical Modelling)

Propagation of kinetic uncertainties through a canonical topology of the TLR4 signaling network in different regions of biochemical reaction space

Theoretical Biology and Medical Modelling — Mon, 15 Mar 2010 00:00:00 +0100

Conclusions: Overall, our in silico study suggests that biologically relevant and non-intuitive aspects on the general behavior of a complex biomolecular network can be elucidated only when taking into account a wide spectrum of dynamical regimes attainable by the system. Most importantly, this strategy provides the means for a suitable assessment of the inherent variational constraints imposed by the structure of the system when systematically probing its parameter space. (Source: Theoretical Biology and Medical Modelling)

Degeneracy: a link between evolvability, robustness and complexity in biological systems

Theoretical Biology and Medical Modelling — Thu, 18 Feb 2010 00:00:00 +0100

A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of future adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology.This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we...

Hypofractionated radiotherapy has the potential for second cancer reduction

Theoretical Biology and Medical Modelling — Thu, 11 Feb 2010 00:00:00 +0100

Conclusions: It was found that carcinoma as well as sarcoma risk decreases with increasing fractionation dose. The reduction of sarcoma risk is even more pronounced than carcinoma risk. Hypofractionation is potentially beneficial with regard to second cancer induction. (Source: Theoretical Biology and Medical Modelling)

A comparative approach for the investigation of biological information processing: An examination of the structure and function of computer hard drives and DNA

Theoretical Biology and Medical Modelling — Thu, 21 Jan 2010 00:00:00 +0100

Conclusions: The comparison of functional and structural characteristics of the DNA complex and thecomputer hard drive leads to a new descriptive paradigm that identifies the DNA as a dynamic storage system ofbiological information. This system is embodied in an autonomous operating system that inductively followsorganizational structures, data hierarchy and executable operations that are well understood in the computerscience industry. Characterizing the "DNA hard drive" in this fashion can lead to insights arising fromdiscrepancies in the descriptive framework, particularly with respect to positing the role of epigenetic processesin an information-processing context. Further expansions arising from this comparison include the view of cellsas parallel computing machines and a new approach...

Cancer proliferation and therapy: the Warburg effect and quantum metabolism

Theoretical Biology and Medical Modelling — Tue, 19 Jan 2010 00:00:00 +0100

Conclusion: The regulatory interventions proposed on the basis of quantum metabolism have applications in therapeutic strategies to combat cancer. These procedures, based on metabolic regulation, are non-invasive, and complement the standard therapeutic methods involving radiation and chemotherapy (Source: Theoretical Biology and Medical Modelling)

Pros and cons of estimating the reproduction number from early epidemic growth rate of influenza A (H1N1) 2009

Theoretical Biology and Medical Modelling — Thu, 07 Jan 2010 00:00:00 +0100

Conclusions: In order to quantify R from the growth rate of cases, it is essential that the selected model captures the underlying transmission dynamics embedded in the data. Exploring additional epidemiological information will be useful for assessing the temporal dynamics. Although the simple concept of R is more easily grasped by the general public than that of the next-generation matrix, the matrix incorporating detailed information (e.g., age-specificity) is essential for reducing the levels of uncertainty in predictions and for assisting public health policymaking. Model-based prediction and policymaking are best described by sharing fundamental notions of heterogeneous risks of infection and death with non-experts to avoid potential confusion and/or possible misuse of modelling resu...

Editorial: hypotheses about protein folding - the proteomic code and wonderfolds

Theoretical Biology and Medical Modelling — Thu, 24 Dec 2009 00:00:00 +0100

Theoretical biology journals can contribute in many ways to the progress of knowledge. They are particularly well-placed to encourage dialogue and debate about hypotheses addressing problematical areas of research. An online journal provides an especially useful forum for such debate because of the option of posting comments within days of the publication of a contentious article. (Source: Theoretical Biology and Medical Modelling)

Correction: Utility of a single adjusting compartment: a novel methodology for whole body physiologically-based pharmacokinetic modelling

Theoretical Biology and Medical Modelling — Tue, 08 Dec 2009 00:00:00 +0100

After our work was published, we found that some of the terms in the equations were incorrect and that there were some typographical errors in the abbreviations.In the section 'Single adjusting compartment' in Materials and Methods, VS should be VSAC.In the last paragraph of Results, QSAC should be QSAC.The correct equations are included in this article.These corrections will not affect the results of this study. (Source: Theoretical Biology and Medical Modelling)

In silico analysis of chimeric espA, eae and tir fragments of Escherichia coli O157:H7 for oral immunogenic applications

Theoretical Biology and Medical Modelling — Tue, 08 Dec 2009 00:00:00 +0100

Conclusions: a structural model for a chimeric gene from LEE antigenic determinants of EHEC is presented. It may define accessibility, solubility and immunogenecity. (Source: Theoretical Biology and Medical Modelling)

The Universal Plausibility Metric (UPM) & Principle (UPP)

Theoretical Biology and Medical Modelling — Thu, 03 Dec 2009 00:00:00 +0100

Conclusion: No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (xi < 1). (Source: Theoretical Biology and Medical Modelling)

A mechanistic model of infection: why duration and intensity of contacts should be included in models of disease spread

Theoretical Biology and Medical Modelling — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: The importance of highly connected individuals, so-called super-spreaders, for disease spread seems to be overestimated when a constant per-contact transmission probability is assumed. This holds particularly for diseases with low basic reproduction numbers. Simulations of disease spread should weight contacts by duration and intensity. (Source: Theoretical Biology and Medical Modelling)

Formal kinetics of H1N1 epidemic

Theoretical Biology and Medical Modelling — Mon, 14 Sep 2009 23:00:00 +0100

Conclusion: We are probably only at the initial stage of development of the H1N1 epidemic. Increasing the number of H1N1-resistant people in future (e.g. due to vaccination) may influence the dynamics of epidemic development. At present, the development of the epidemic depends only on the number of people in the population who are initially resistant to the virus. (Source: Theoretical Biology and Medical Modelling)

Comparative modeling of DNA and RNA polymerases from Moniliophthora perniciosa mitochondrial plasmid

Theoretical Biology and Medical Modelling — Wed, 09 Sep 2009 23:00:00 +0100

Conclusion: This work contributes to the development of new alternatives for controlling the fungal agent of witches' broom disease. (Source: Theoretical Biology and Medical Modelling)

Homeostatic mechanisms in dopamine synthesis and release: a mathematical model

Theoretical Biology and Medical Modelling — Wed, 09 Sep 2009 23:00:00 +0100

Conclusions: Dopaminergic systems must respond robustly to important biological signals such as bursts, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of tyrosine hydroxylase, the dopamine transporters, and the dopamine autoreceptors. (Source: Theoretical Biology and Medical Modelling)

Binding site of ABC transporter homology models confirmed by ABCB1 crystal structure

Theoretical Biology and Medical Modelling — Thu, 03 Sep 2009 23:00:00 +0100

The human ATP-binding cassette (ABC) transporters ABCB1, ABCC4 and ABCC5 are involved in resistance to chemotherapeutic agents. Here we present molecular models of ABCB1, ABCC4 and ABCC5 by homology based on a wide open inward-facing conformation of Escherichia coli MsbA, which were constructed in order to elucidate differences in the electrostatic and molecular features of their drug recognition conformations. As a quality assurance of the methodology, the ABCB1 model was compared to an ABCB1 X-ray crystal structure, and with published cross-linking and site directed mutagenesis data of ABCB1. Amino acids Ile306 (TMH5), Ile340 (TMH6), Phe343 (TMH6), Phe728 (TMH7), and Val982 (TMH12), form a putative substrate recognition site in the ABCB1 model, which is confirmed by both the ABCB1 X-ray ...

A model analysis of static stress in the vestibular membranes

Theoretical Biology and Medical Modelling — Mon, 31 Aug 2009 23:00:00 +0100

Conclusions: Static hoop stress disparities are likely to exist in the vestibular membranes given their complex physical configurations. Such stress disparities may contribute to the development of membrane pathologies as seen in Meniere's Disease. They may also factor in the evolutionary development of other derivative membrane structures such as the saccule, the lagena, and the cochlea found in higher animals. (Source: Theoretical Biology and Medical Modelling)

The terrestrial evolution of metabolism and life - by the numbers

Theoretical Biology and Medical Modelling — Wed, 26 Aug 2009 23:00:00 +0100

Conclusions: The equation models the longevity extending affects of caloric restriction, and shows where those affects wane. The equation models the immortality of some types of cells, and supports the argument for the origins of life being at submarine volcanic vents and black smokers. The equation clarifies how early life had to change to survive drifting to the surface, and what drove mutations in its ascent. The equation does not deal with cause and affect; it deals with variables in the essentials of all life, and treats life as an epiphenomenon of these variables. The equation describes how battery discharge into the body can increase muscle mass, promote fitness, and extend life span, amongst other things. (Source: Theoretical Biology and Medical Modelling)

A tumor cord model for doxorubicin delivery and dose optimization in solid tumors

Theoretical Biology and Medical Modelling — Sat, 08 Aug 2009 23:00:00 +0100

Conclusions: Drug infusion time has a significant effect on the spatial profile of cell mortality within tumor cord systems. Therefore, extending infusion times (up to 2 hours) and fractionating large doses are two strategies that may preserve or increase anti-tumor activity and reduce cardiotoxicity by decreasing peak plasma concentration. However, even under optimal conditions, doxorubicin may have limited delivery into advanced solid tumors. (Source: Theoretical Biology and Medical Modelling)

Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

Theoretical Biology and Medical Modelling — Wed, 05 Aug 2009 23:00:00 +0100

Conclusion: Our modeling study of cardiac tamponade dissects the roles played by septal motion, atrioventricular and right-left ventricular interactions, pulmonary blood pooling, and the depth of respiration. The study fully describes the physiological basis of pulsus paradoxus. Our detailed analysis provides biophysically-based insights helpful for future experimental and clinical study of cardiac tamponade and related pericardial diseases. (Source: Theoretical Biology and Medical Modelling)

In silico evidence for the species-specific conservation of mosquito retroposons: Implications as a molecular biomarker

Theoretical Biology and Medical Modelling — Tue, 28 Jul 2009 23:00:00 +0100

Conclusions: We offer evidence to support the species-specific conservation of mosquito retroposons among lower taxa. Our findings suggest that retroposons may therefore constitute a unique biomarker for mosquito species that may be exploited in molecular entomology. Mosquito RST-specific MAbs may possibly permit synthesis of DDT immunoconjugates that could be used to achieve species-tailored toxicity. (Source: Theoretical Biology and Medical Modelling)

Examination of effects of GSK3-[beta] phosphorylation, [beta]-catenin phosphorylation, and [beta]-catenin degradation in kinetics of Wnt signaling pathway using computational method

Theoretical Biology and Medical Modelling — Tue, 21 Jul 2009 23:00:00 +0100

Conclusions: The phosphorylations of [beta]-catenin by kinases other than GSK3[beta] should take place at free unphorphorylated [beta]-catenin instead of the GSK3[beta]-phosphorylated [beta]-catenin *. In order to account for observed enhanced TCF activity, the step of [beta]-catenin dephosphorylation is essential, and the kinetic parameters of [beta]-catenin phosphorylation and degradation need to meet a condition, describing in the text below. These findings should be useful for future experiments. (Source: Theoretical Biology and Medical Modelling)

Ranking candidate genes in rat models of type 2 diabetes

Theoretical Biology and Medical Modelling — Thu, 02 Jul 2009 23:00:00 +0100

Conclusions: The very good agreement between CGC gene rankings and manual ratings confirms that CGC is as a reliable tool for interpreting textual information. This, together with the possibility to select many different sub-phenotypes, makes CGC a versatile tool for finding candidate genes. CGC is publicly available at http://ratmap.org/CGC. (Source: Theoretical Biology and Medical Modelling)

Models of epidemics: when contact repetition and clustering should be included

Theoretical Biology and Medical Modelling — Sun, 28 Jun 2009 23:00:00 +0100

Conclusions: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model. (Source: Theoretical Biology and Medical Modelling)

Antimicrobial breakpoint estimation accounting for variability in pharmacokinetics

Theoretical Biology and Medical Modelling — Thu, 25 Jun 2009 23:00:00 +0100

Conclusion: Compared to traditional methods, our weighted AUC approach gives a more powerful PK/PD link and revealed, through some examples, interesting issues about uniqueness of therapeutic outcome indices and antibiotic resistance problems. (Source: Theoretical Biology and Medical Modelling)

Theoretical study of the Usutu virus helicase 3D structure, by means of computer-aided homology modelling

Theoretical Biology and Medical Modelling — Wed, 24 Jun 2009 23:00:00 +0100

Background: Usutu virus belongs to the Flaviviridae viral family and constitutes an important pathogen. The viral helicase is an ideal target for inhibitor design, since this enzyme is essential for the survival, proliferation and transmission of the virus. Results: Towards a drug-design approach, the 3D model of the Usutu virus helicase structure has been designed, using conventional homology modelling techniques and the known 3D-structure of the Murray Valley Encephalitis virus helicase, of the same viral family, as template. The model was then subjected to extended molecular dynamics simulations in a periodic box, filled with explicit water molecules for 10 nanoseconds. The reliability of the model was confirmed by obtaining acceptable scores from a variety of in silico scoring tools, i...

Computational investigation of epithelial cell dynamic phenotype in vitro

Theoretical Biology and Medical Modelling — Thu, 28 May 2009 04:00:00 +0100

Conclusions: We documented the causal chains of events, and their relative roles, responsible for simulated cystogenesis. The results stand as an early hypothesis--a theory--of how individual MDCK cell actions give rise to consistently roundish, cystic organoids. (Source: Theoretical Biology and Medical Modelling)

Extension of Murray's law using a non-Newtonian model of blood flow

Theoretical Biology and Medical Modelling — Fri, 15 May 2009 04:00:00 +0100

Conclusion: It is demonstrated that the entropy generated in all the daughter vessels is greater than the entropy generated in the parent vessel. Furthermore, it is shown that the difference of entropy generation between the parent and daughter vessels is smaller for a non-Newtonian fluid than for a Newtonian fluid. (Source: Theoretical Biology and Medical Modelling)

Scale-free flow of life: on the biology, economics, and physics of the cell

Theoretical Biology and Medical Modelling — Tue, 05 May 2009 04:00:00 +0100

The present work is intended to demonstrate that most of the paradoxes, controversies, and contradictions accumulated in molecular and cell biology over many years of research can be readily resolved if the cell and living systems in general are re-interpreted within an alternative paradigm of biological organization that is based on the concepts and empirical laws of nonequilibrium thermodynamics. In addition to resolving paradoxes and controversies, the proposed re-conceptualization of the cell and biological organization reveals hitherto unappreciated connections among many seemingly disparate phenomena and observations, and provides new and powerful insights into the universal principles governing the emergence and organizational dynamics of living systems on each and every scale of bi...

FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

Theoretical Biology and Medical Modelling — Thu, 16 Apr 2009 04:00:00 +0100

Conclusions: Results of the computational models are, as a first estimate, in good quantitative agreement with existing experimental evidence, and they confirm that during culture, hypoxia is often a problem for non-vascularised islet and can lead to considerable cell death (necrosis), especially in the core region of larger islets. Such models are of considerable interest to improve the function and viability of cultured, transplanted, or encapsulated islets. The present implementation allows convenient extension to true multiphysics applications that solve coupled physics phenomena such as diffusion and consumption with convection due to flowing or moving media. (Source: Theoretical Biology and Medical Modelling)

Theoretical basis for reducing time-lines to the determination of positive Mycobacterium tuberculosis cultures using thymidylate kinase (TMK) assays

Theoretical Biology and Medical Modelling — Wed, 18 Mar 2009 04:00:00 +0100

Conclusions: TMKmyc assays may be useful for reducing the time-lines to positive identification of Mycobacterium tuberculosis (M.tb) cultures, thereby accelerating disease diagnosis and drug resistance profiling. Incorporating "chemiluminiscent or fluorescent" strategies may enable "photo-detection of TMKmyc changes" and hence automation of the entire assay. (Source: Theoretical Biology and Medical Modelling)

Binding of long-chain α-neurotoxin would stabilize the resting state of nAChR: A comparative study with α-conotoxin

Theoretical Biology and Medical Modelling — Wed, 11 Feb 2009 05:00:00 +0100

Conclusion: These observations could support the claim that alpha neurotoxins stabilize the nAChR resting state. (Source: Theoretical Biology and Medical Modelling)

Binding of long-chain alpha-neurotoxin would stabilize the resting state of nAChR: A comparative study with alpha-conotoxin

Theoretical Biology and Medical Modelling — Wed, 11 Feb 2009 05:00:00 +0100

Conclusion: These observations could support the claim that alpha neurotoxins stabilize the nAChR resting state. (Source: Theoretical Biology and Medical Modelling)

Mitochondrial concept of leukemogenesis: key role of oxygen-peroxide effects

Theoretical Biology and Medical Modelling — Tue, 11 Nov 2008 05:00:00 +0100

Conclusions: The argument described in this article is used to explain the causes of congenital and children's leukemia, and the induction of leukemia by certain agents (vitamin K3, benzene, etc.). Specific research is required to validate the proposals made in this article. This will require accurate and accessible methods for measuring and assessing oxidative stress in different types of cells in general, and in hemopoietic cells in particular, in their different functional states. (Source: Theoretical Biology and Medical Modelling)

Feature context-dependency and complexity-reduction in probability landscapes for integrative genomics

Theoretical Biology and Medical Modelling — Wed, 10 Sep 2008 04:00:00 +0100

Conclusion: These two advances in our understanding of the properties of probability landscapes not only simplify subsequent cross-correlation analysis in hypothesis-driven model building and testing, but also provide additional insights into the biological gene regulatory problems studied. Furthermore, insights into the nature of individual features and a classification of features according to their minimal context-dependency are achieved. The formal structure proposed contributes to a concrete and tangible basis for attempting to formulate novel mathematical structures for describing gene regulation in eukaryotes on a genome-wide scale. (Source: Theoretical Biology and Medical Modelling)

Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: Inherent potential for biosynthetic versus live recombinant microbicides

Theoretical Biology and Medical Modelling — Thu, 07 Aug 2008 04:00:00 +0100

Conclusion: Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission. (Source: Theoretical Biology and Medical Modelling)

Does codon bias have an evolutionary origin?

Theoretical Biology and Medical Modelling — Wed, 30 Jul 2008 04:00:00 +0100

Conclusions: The results put the concept of "codon bias" into a novel perspective. The internal connectivity of codons indicates that all synonymous codons might be integrated parts of the Genetic Code with equal importance in maintaining its functional integrity. (Source: Theoretical Biology and Medical Modelling)

Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases.

Theoretical Biology and Medical Modelling — Tue, 29 Jul 2008 04:00:00 +0100

Conclusion: Synonymous codons are not interchangable with regard to their role in determining the mRNA FE and the relative amounts of amino acids in the translated protein, even if they are indistinguishable in respect of amino acid coding. (Source: Theoretical Biology and Medical Modelling)

The velocity of the arterial pulse wave: a viscous-fluid shock wave in an elastic tube

Theoretical Biology and Medical Modelling — Tue, 29 Jul 2008 04:00:00 +0100

Conclusions: Contrary to the theory used for more than fifty years to predict the PWV, it speeds up as arteries become smaller and smaller. Furthermore, an increase in the PWV in small arteries may in some cases be due to decreasing force of myocardial contraction rather than arterial stiffness. (Source: Theoretical Biology and Medical Modelling)

Heterogeneity in multistage carcinogenesis and mixture modeling

Theoretical Biology and Medical Modelling — Mon, 21 Jul 2008 04:00:00 +0100

Carcinogenesis is commonly described as a multistage process, in which stem cells are transformed into cancer cells via a series of mutations. In this article, we consider extensions of the multistage carcinogenesis model by mixture modeling. This approach allows us to describe population heterogeneity in a biologically meaningful way. We focus on finite mixture models, for which we prove identifiability. These models are applied to human lung cancer data from several birth cohorts. Maximum likelihood estimation does not perform well in this application due to the heavy censoring in our data. We thus use analytic graduation instead. Very good fits are achieved for models that combine a small high risk group with a large group that is quasi immune. (Source: Theoretical Biology and Medical M...

Fractal parameters and vascular networks: facts & artifacts

Theoretical Biology and Medical Modelling — Thu, 17 Jul 2008 04:00:00 +0100

Conclusion: The fractal dimension Df is likely to be the most promising tool for monitoring the effectiveness of anti-angiogenic therapies in various clinical contexts. (Source: Theoretical Biology and Medical Modelling)

Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation

Theoretical Biology and Medical Modelling — Tue, 27 May 2008 04:00:00 +0100

Conclusions: A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior in the intensive care setting. The ABMs all utilize cell-level agents that encapsulate specific mechanistic knowledge extracted from in vitro experiments. The execution of the ABMs results in a dynamic representation of the multi-scale conceptual models derived from those experiments. These models represent a qualitative means of integrating basic scientific information on acute inflammation in a multi-scale, modular architecture as a means of conceptual model verification that can potentially be used to concatenate, communicate and advance community-wide knowledge. (Source: Theoretical Biology and Medical Modelling)

Origin of the blood hyperserotonemia of autism

Theoretical Biology and Medical Modelling — Thu, 22 May 2008 04:00:00 +0100

Conclusions: The models yields platelet 5-HT concentrations that are consistent with values reported in experimental studies. If the parameters are considered independent, the model predicts that platelet 5-HT levels should be sensitive to changes in the platelet 5-HT uptake rate constant, the proportion of free 5-HT cleared in the liver and lungs, the gut 5-HT production rate and its regulation, and the volume of the gut wall. Linear and non-linear interactions among these and other parameters are specified in the equation, which may facilitate the design and interpretation of experimental studies. (Source: Theoretical Biology and Medical Modelling)

A mathematical model of glutathione metabolism

Theoretical Biology and Medical Modelling — Mon, 28 Apr 2008 04:00:00 +0100

Conclusions: We show that the glutathione pools in hepatic cells and in the blood are quite insensitive to fluctuations in amino acid input and offer an explanation based on model predictions. In contrast, we show that hepatic glutathione pools are highly sensitive to the level of oxidative stress. The model shows that trisomy 21, an increase in oxidative stress, and subsequent increased transport of GSH precursors by peripheral cells can explain the metabolic profile of Down syndrome. The model also correctly simulates the metabolic profile of autism when oxidative stress is substantially increased, the adenosine concentration is raised, and the uptake of GSH precursors by peripheral tissues is increased. Finally, we discuss how individual variation arises and its consequences for one-car...

A statistical model for the identification of genes governing the incidence of cancer with age

Theoretical Biology and Medical Modelling — Wed, 16 Apr 2008 04:00:00 +0100

The cancer incidence increases with age. This epidemiological pattern of cancer incidence can be attributed to molecular and cellular processes of individual subjects. Also, the incidence of cancer with ages can be controlled by genes. Here we present a dynamic statistical model for explaining the epidemiological pattern of cancer incidence based on individual genes that regulate cancer formation and progression. We incorporate the mathematical equations of age-specific cancer incidence into a framework for functional mapping aimed at identifying quantitative trait loci (QTLs) for dynamic changes of a complex trait. The mathematical parameters that specify differences in the curve of cancer incidence among QTL genotypes are estimated within the context of maximum likelihood. The model prov...

Functional mapping imprinted quantitative trait loci underlying developmental characteristics

Theoretical Biology and Medical Modelling — Mon, 17 Mar 2008 04:00:00 +0100

Conclusions: The functional iQTL mapping approach developed here provides a quantitative and testable framework for assessing the interplay between imprinted genes and a developmental process, and will have important implications for elucidating the genetic architecture of imprinted traits. (Source: Theoretical Biology and Medical Modelling)

Scaling, growth and cyclicity in biology: a new computational approach

Theoretical Biology and Medical Modelling — Fri, 29 Feb 2008 05:00:00 +0100

Conclusions: As an example of its implementation, the method is applied to the analysis of human growth curves. The excellent quality of the results (R**2=0.998) demonstrates the usefulness and reliability of the approach. (Source: Theoretical Biology and Medical Modelling)

Sampling and sensitivity analyses tools (SaSAT) for computational modelling

Theoretical Biology and Medical Modelling — Wed, 27 Feb 2008 05:00:00 +0100

SaSAT (Sampling and Sensitivity Analysis Tools) is a user-friendly software package for applying uncertainty and sensitivity analyses to mathematical and computational models of arbitrary complexity and context. The toolbox is built in Matlab, a numerical mathematical software package, and utilises algorithms contained in the Matlab Statistics Toolbox. However, Matlab is not required to use SaSAT as the software package is provided as an executable file with all the necessary supplementary files. The SaSAT package is also designed to work seamlessly with Microsoft Excel but no functionality is forfeited if that software is not available. A comprehensive suite of tools is provided to enable the following tasks to be easily performed: efficient and equitable sampling of parameter space by va...

Variance in multiplex suspension array assays: a distribution generation machine for multiplex counts

Theoretical Biology and Medical Modelling — Mon, 28 Jan 2008 05:00:00 +0100

Conclusion: Using larger numbers of microspheres per classifier highlights a fundamental stochastic distribution of bead counts issue complicated by other factors. The more classifiers and the higher the count required per classifier there are, the more apparent the distribution of counts per classifier will be, and the more microspheres are required. Additional problems have been identified. Alternate methods of improving precision and reliability are recommended such as intraplexing and multi-well sample replicates to improve precision and confidence. (Source: Theoretical Biology and Medical Modelling)

A mathematical model of venous neointimal hyperplasia formation

Theoretical Biology and Medical Modelling — Wed, 23 Jan 2008 05:00:00 +0100

Conclusions: The proposed model describes the formation of venous neointimal hyperplasia, based on pathogenic mechanisms. The results suggest that interventions aimed at specific growth factors may be successful in prolonging the life of the vascular access, while reducing the costs of vascular access maintenance. The model may also provide indication of when invasive access surveillance to repair stenosis should be undertaken. (Source: Theoretical Biology and Medical Modelling)

The Peter Pan paradigm

Theoretical Biology and Medical Modelling — Tue, 08 Jan 2008 05:00:00 +0100

Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis. (Source: Theoretical Biol...

Simulating non-small cell lung cancer with a multiscale agent-based model

Theoretical Biology and Medical Modelling — Fri, 21 Dec 2007 05:00:00 +0100

Conclusions: Our in silico results indicate that, in NSCLC, in the presence of a strong extrinsic chemotactic stimulus, and depending on the cell's location, downstream EGFR-ERK signaling may be processed more efficiently, thereby yielding a migration-dominant cell phenotype and overall, an accelerated spatio-temporal expansion rate. (Source: Theoretical Biology and Medical Modelling)

A unified framework of immunological and epidemiological dynamics for the spread of viral infections in a simple network-based population

Theoretical Biology and Medical Modelling — Thu, 20 Dec 2007 05:00:00 +0100

Conclusions: Future infectious disease research would benefit by striving to not only continue to understand the properties of an invading microbe, or the body's response to infections, but how these properties, jointly, affect the propagation of an infection throughout a population. These initial results offer a refinement to current immuno-epidemiological modelling methodology, and reinforce how coupling principles of immunology with epidemiology can provide insight into a multi-scaled description of an ecological system. Overall, we anticipate these results to as a further step towards articulating an integrated, more refined epidemiological theory of the reciprocal influences between host-pathogen interactions, epidemiological mixing, and disease spread. (Source: Theoretical Biology an...

Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

Theoretical Biology and Medical Modelling — Mon, 10 Dec 2007 05:00:00 +0100

Conclusions: The predictive power of the constructed model for the key flux distributions, especially central carbon metabolism and glutamate-glutamine cycle fluxes, and its application to hypoxia is promising. The resultant acceptable predictions strengthen the power of such stoichiometric models in the analysis of mammalian cell metabolism. (Source: Theoretical Biology and Medical Modelling)

Measuring the functional sequence complexity of proteins

Theoretical Biology and Medical Modelling — Thu, 06 Dec 2007 05:00:00 +0100

Conclusion: For future extensions, measures of functional bioinformatics may provide a means to evaluate potential evolving pathways from effects such as mutations, as well as analyzing the internal structural and functional relationships within the 3-D structure of proteins. (Source: Theoretical Biology and Medical Modelling)

Inflammation: a way to understanding the evolution of portal hypertension

Theoretical Biology and Medical Modelling — Tue, 13 Nov 2007 05:00:00 +0100

Conclusion: Low-grade inflammation, related to prehepatic portal hypertension, switches to high-grade inflammation with the development of severe and life-threatening complications when associated with chronic liver disease. (Source: Theoretical Biology and Medical Modelling)

The Proteomic Code: a molecular recognition code for proteins

Theoretical Biology and Medical Modelling — Tue, 13 Nov 2007 05:00:00 +0100

Background: The Proteomic Code is a set of rules by which information in genetic material is transferred into the physico-chemical properties of amino acids. It determines how individual amino acids interact with each other during folding and in specific protein-protein interactions. The Proteomic Code is part of the redundant Genetic Code. Review The 25-year-old history of this concept is reviewed from the first independent suggestions by Biro and Mekler, through the works of Blalock, Root-Bernstein, Siemion, Miller and others, followed by the discovery of a Common Periodic Table of Codons and Nucleic Acids in 2003 and culminating in the recent conceptualization of partial complementary coding of interacting amino acids as well as the theory of the nucleic acid-assisted protein folding. ...

Analysis of arterial intimal hyperplasia: review and hypothesis

Theoretical Biology and Medical Modelling — Wed, 31 Oct 2007 04:00:00 +0100

Conclusions: Two questions should inform the priorities of our research: (1) what controls switch the single cell-layer intimal phenotype into normal hyperplasia? (2) how is normal (benign) hyperplasia maintained? We would be hard-pressed to gain practical insights without scrutinizing our premises. (Source: Theoretical Biology and Medical Modelling)

Coordination of the dynamics of yeast sphingolipid metabolism during the diauxic shift

Theoretical Biology and Medical Modelling — Wed, 31 Oct 2007 04:00:00 +0100

Conclusions: The results indicate that yeast coordinates sphingolipid mediated changes during the diauxic shift through an array of small changes in many genes and enzymes, rather than relying on a strategy involving a few select genes with high sensitivity. This study also highlights a novel approach in coupling data mining with mathematical modeling in order to evaluate specific metabolic pathways. (Source: Theoretical Biology and Medical Modelling)

Regular mosaic pattern development: A study of the interplay between lateral inhibition, apoptosis and differential adhesion

Theoretical Biology and Medical Modelling — Wed, 31 Oct 2007 04:00:00 +0100

Conclusions: Patterning the embryo requires collaboration between multiple mechanisms that operate iteratively. Interlacing these mechanisms into feedback loops not only refines the output patterns, but also increases the robustness of patterning to varying initial cell states. (Source: Theoretical Biology and Medical Modelling)

Hypertabastic Survival Model

Theoretical Biology and Medical Modelling — Fri, 26 Oct 2007 04:00:00 +0100

A new two-parameter probability distribution called hypertabastic is introduced to model the survival or time-to-event data. A simulation study was carried out to evaluate the performance of the hypertabastic distribution in comparison with popular distributions. We then demonstrate the application of the hypertabastic survival model by applying it to data from two motivating studies. The first one demonstrates the proportional hazards version of the model by applying it to a data set from multiple myeloma study. The second one demonstrates an accelerated failure time version of the model by applying it to data from a randomized study of glioma patients who underwent radiotherapy treatment with and without radiosensitizer misonidazole. Based on the results from the simulation study and two...

The Basic Immune Simulator: An agent-based model to study the interactions between innate and adaptive immunity

Theoretical Biology and Medical Modelling — Thu, 27 Sep 2007 04:00:00 +0100

Conclusions: The behavior of the BIS matches both normal and pathological behavior patterns in a generic viral infection scenario. Thus, the BIS effectively translates mechanistic cellular and molecular knowledge regarding the innate and adaptive immune response and reproduces the immune system's complex behavioral patterns. The BIS can be used both as an educational tool to demonstrate the emergence of these patterns and as a research tool to systematically identify potential targets for more effective treatment strategies for diseases processes including hypersensitivity reactions (allergies, asthma), autoimmunity and cancer. We believe that the BIS can be a useful addition to the growing suite of in-silico platforms used as an adjunct to traditional research efforts. (Source: Theoretica...

Cable properties and propagation velocity in a long single chain of simulated myocardial cells

Theoretical Biology and Medical Modelling — Fri, 14 Sep 2007 04:00:00 +0100

Conclusions: Thus, when there were only 0, 1, or 10 gj-channels, thetaov increased with increase in chain length, whereas at 100 gj-channels or higher, thetaov did not increase with chain length. When there were only 0, 10, or 30 gj-channels, there was a very sharp decrease in DeltaVm in the two contiguous cells on either side of the injected cell, whereas at 300, 1000, or 3000 gj-channels, the voltage decay was exponential along the length of the chain. The effect of increasing the number of gj-channels on spread of current was relatively small compared to the large effect on thetaov. (Source: Theoretical Biology and Medical Modelling)

A discrete Single Delay Model for the Intra-Venous Glucose Tolerance Test

Theoretical Biology and Medical Modelling — Wed, 12 Sep 2007 04:00:00 +0100

Conclusion: The SDM is theoretically sound and practically robust, and can routinely be considered for the determination of insulin sensitivity from the IVGTT. Free software for estimating the SDM parameters is available. (Source: Theoretical Biology and Medical Modelling)

Variance in multiplex suspension array assays: microsphere size variation impact

Theoretical Biology and Medical Modelling — Thu, 23 Aug 2007 04:00:00 +0100

Conclusion: A probable significant cause of variance in suspended microsphere assay results is variation in microsphere diameter. This can potentially be addressed by changes in the manufacturing process. Provision to users of mean size, median size, skew, the number of standard deviations that half the size range represents (sigma multiple), and standard deviation is recommended. Establishing a higher sigma multiple for microsphere production is likely to deliver a significant improvement in precision of raw instrument readings. Further research is recommended on the molecular architecture of microsphere coatings. (Source: Theoretical Biology and Medical Modelling)

A continuum mathematical model of endothelial layer maintenance and senescence

Theoretical Biology and Medical Modelling — Fri, 10 Aug 2007 04:00:00 +0100

Conclusions: The proposed model describes the aging of the endothelium as being driven by cellular senescence, with a rate that does not necessarily correspond to the chronological aging of a person. It is shown that the age of the endothelium depends sensitively on the homing rates of EC progenitor cells. (Source: Theoretical Biology and Medical Modelling)

Could increased axial wall stress be responsible for the development of atheroma in the proximal segment of myocardial bridges ?

Theoretical Biology and Medical Modelling — Thu, 09 Aug 2007 04:00:00 +0100

Conclusion: The proposed mechanical explanation of atherosclerosis in bridged coronary arteries indicates that angioplasty and other similar interventions will not stop the development of atherosclerosis at the bridge entrance and in the proximal epicardial segment if the decrease of the lumen of the tunneled segment during systole is not considerably reduced. (Source: Theoretical Biology and Medical Modelling)

Can a single model explain both breast cancer and prostate cancer?

Theoretical Biology and Medical Modelling — Wed, 01 Aug 2007 04:00:00 +0100

Conclusion: By minimizing bcl-2 and maximizing apoptotic proteins, new systemic treatments for BC and PC can be developed that may be more effective than existing treatments. (Source: Theoretical Biology and Medical Modelling)

Numerical modelling of label-structured cell population growth using CFSE distribution data

Theoretical Biology and Medical Modelling — Tue, 24 Jul 2007 04:00:00 +0100

Conclusions: Once the initial distribution of the proliferating cell population with respect to the CFSE intensity is given, the distributed parameter modelling allows one to work directly with the histograms of the CFSE fluorescence without the need to specify the marker ranges. The label-structured model and the elaborated computational approach establish a quantitative basis for more informative interpretation of the flow cytometry CFSE systems. (Source: Theoretical Biology and Medical Modelling)

A general framework for quantifying the effects of DNA repair inhibitors on radiation sensitivity as a function of dose

Theoretical Biology and Medical Modelling — Thu, 19 Jul 2007 04:00:00 +0100

Conclusions: The proposed approach improves on current methods of analysing effects of DNA repair modification on radiation response. Furthermore, it may be generalised to account for other parameters such as proliferation or dose rate to enable its use in the context of fractionated or continuous radiation exposures. (Source: Theoretical Biology and Medical Modelling)

The relationship between twitch depression and twitch fade during neuromuscular block produced by vecuronium: correlation with the release of acetylcholine

Theoretical Biology and Medical Modelling — Mon, 16 Jul 2007 04:00:00 +0100

Conclusions: The hysteresis in the fade between onset and offset appears to be caused by a delayed decrease of A4/A1 as compared with the decrease in T1. Tentative estimates of the decrease in A4/A1 during fade produced by vecuronium are offered. However, the validity of these estimates is dependent on the validity of the assumptions made in simulations. (Source: Theoretical Biology and Medical Modelling)

Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference

Theoretical Biology and Medical Modelling — Sat, 09 Jun 2007 04:00:00 +0100

Conclusion: It seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems. (Source: Theoretical Biology and Medical Modelling)

Optimization principles of dendritic structure

Theoretical Biology and Medical Modelling — Fri, 08 Jun 2007 04:00:00 +0100

Background: Dendrites are the most conspicuous feature of neurons. However, the principles determining their structure are poorly understood. By employing cable theory and, for the first time, graph theory, we describe dendritic anatomy solely on the basis of optimizing synaptic efficacy with minimal resources. Results: We show that dendritic branching topology can be well described by minimizing the path length from the neuron's dendritic root to each of its synaptic inputs while constraining the total length of wiring. Tapering of diameter toward the dendrite tip - a feature of many neurons - optimizes charge transfer from all dendritic synapses to spike initiation zone while housekeeping the amount of dendrite volume. As an example, we show how dendrites of fly neurons can be closely re...

Lens stem cells may reside outside the lens capsule: an hypothesis

Theoretical Biology and Medical Modelling — Fri, 08 Jun 2007 04:00:00 +0100

In this paper, we consider the ocular lens in the context of contemporary developments in biological ideas. We attempt to reconcile lens biology with stem cell concepts and a dearth of lens tumors. Historically, the lens has been viewed as a closed system, in which cells at the periphery of the lens epithelium differentiate into fiber cells. Theoretical considerations led us to question whether the intracapsular lens is indeed self-contained. Since stem cells generate tumors and the lens does not naturally develop tumors, we reasoned that lens stem cells may not be present within the capsule. We hypothesize that lens stem cells reside outside the lens capsule, in the nearby ciliary body. Our ideas challenge the existing lens biology paradigm. We begin our discussion with lens background i...

Time variations in the transmissibility of pandemic influenza in Prussia, Germany, from 1918-19

Theoretical Biology and Medical Modelling — Mon, 04 Jun 2007 04:00:00 +0100

Conclusions: The present findings suggest that in order to offer robust assessments it is critically important to clarify in detail the natural history of a disease (e.g. including the serial interval) as well as heterogeneous patterns of transmission. In addition, given that human contact behavior probably influences transmissibility, individual countermeasures (e.g. household quarantine and mask-wearing) need to be explored to construct effective non-pharmaceutical interventions. (Source: Theoretical Biology and Medical Modelling)

Does the immune reaction cause malignant transformation by disrupting cell-to-cell or cell-to-matrix communications?

Theoretical Biology and Medical Modelling — Fri, 04 May 2007 04:00:00 +0100

Tumor Progression - In many (perhaps in all) tumor systems, a malignant cancer is preceded by a benign lesion. Most benign lesions do not transform to malignancy and many regress. The final transformative step to malignancy differs from the preceding steps in that it often occurs in the absence of the original carcinogenic stimulus. Mechanism of Immunostimulation - Relatively low titers of specific immune reactants are known to stimulate tumor growth, but cell-to-cell interactions appear to be a major inhibitor of tumor-growth. Therefore, it seems reasonable to hypothesize that the mechanism of immunostimulation may be an interference with cell-to-cell communication by a sub-lethal immune-reaction. While the above hypothesis remains unproven, some evidence suggests that immunity may have a...