The use of a formal sensitivity analysis on epidemic models with immune protection from maternally acquired antibodies

This paper considers the outcome of a formal sensitivity analysis on a series of epidemic model structures developed to study the population level effects of maternal antibodies. The analysis is used to compare the potential influence of maternally acquired immunity on various age and time domain observations of infection and serology, with and without seasonality. The results of the analysis indicate that time series observations are largely insensitive to variations in the average duration of this protection, and that age related empirical data are likely to be most appropriate for estimating these characteristics

Parameter identifiability of fundamental pharmacodynamic models

Issues of parameter identifiability of routinely used pharmacodynamics models are considered in this paper. The structural identifiability of 16 commonly applied pharmacodynamic model structures was analyzed analytically, using the input-output approach. Both fixed-effects versions (non-population, no between-subject variability) and mixed-effects versions (population, including between-subject variability) of each model structure were analyzed. All models were found to be structurally globally identifiable under conditions of fixing either one of two particular parameters. Furthermore, an example was constructed to illustrate the importance of sufficient data quality and show that structural identifiability is a prerequisite, but not a guarantee, for successful parameter estimation and practical parameter identifiability. This analysis was performed by generating artificial data of varying quality to a structurally identifiable model with known true parameter values, followed by re-estimation of the parameter values. In addition, to show the benefit of including structural identifiability as part of model development, a case study was performed applying an unidentifiable model to real experimental data. This case study shows how performing such an analysis prior to parameter estimation can improve the parameter estimation process and model performance. Finally, an unidentifiable model was fitted to simulated data using multiple initial parameter values, resulting in highly different estimated uncertainties. This example shows that although the standard errors of the parameter estimates often indicate a structural identifiability issue, reasonably “good” standard errors may sometimes mask unidentifiability issues

Analysis of two-player quantum games in an EPR setting using geometric algebra

The framework for playing quantum games in an Einstein-Podolsky-Rosen (EPR) type setting is investigated using the mathematical formalism of Clifford geometric algebra (GA). In this setting, the players' strategy sets remain identical to the ones in the classical mixed-strategy version of the game, which is then obtained as proper subset of the corresponding quantum game. As examples, using GA we analyze the games of Prisoners' Dilemma and Stag Hunt when played in the EPR type setting.Comment: 20 pages, no figure, revise

Patterns of Diatom Diversity Correlate With Dissolved Trace Metal Concentrations and Longitudinal Position in the Notheast Pacific Coastal Offshore Transition Zone

Diatoms are important primary producers in the northeast Pacific Ocean, with their productivity closely linked to pulses of trace elements in the western high nitrate, low chlorophyll (HNLC) region of the oceanographic time series transect \u27Line P.\u27 Recently, the coastal-HNLC transition zone of the Line P transect was identified as a hotspot of phytoplankton productivity, potentially controlled by a combination of trace element and macronutrient concentrations. Here we describe diatom community composition in the eastern Line P transect, including the coastal- HNLC transition zone, with a method using high-throughput sequencing of diatom 18S gene amplicons. We identified significant correlations between shifting diatom community composition and longitude combined with concentrations of dissolved copper and 2 other dissolved trace metals (dissolved Fe [dFe] and/or dissolved zinc) and/or a physical factor (salinity or density). None of these variables on its own was significantly correlated with shifts in community composition, and 3 of the factors (dFe, salinity, and density) correlated with one another. Longitude could incorporate multiple factors that may influence diatom communities, including distance from shore, proximity of sampling stations, and an integration of previous pulses of macro- and micro-nutrients. We also evaluated in situ Fe limitation of the diatom Thalassiosira oceanica using a quantitative reverse-transcription polymerase chain reaction method, and found biological evidence of Fe stress in samples from the coastal-HNLC transition zone. Combined, our results support a prior hypothesis that dissolved trace metals as well as longitudinal distance may be important to diatom diversity in the coastal-HNLC transition zone of the Line P transect

Preferential Depletion of Zinc Within Costa Rica Upwelling Dome Creates Conditions for Zinc Co-Limitation of Primary Production

The Costa Rica Dome (CRD) is a wind-driven feature characterized by high primary production and an unusual cyanobacterial bloom in surface waters. It is not clear whether this bloom arises from top-down or bottom-up processes. Several studies have argued that trace metal geochemistry within the CRD contributes to the composition of the phytoplankton assemblages, since cyanobacteria and eukaryotic phytoplankton have different transition metal requirements. Here, we report that total dissolved zinc (Zn) is significantly depleted relative to phosphate (P) and silicate (Si) within the upper water column of the CRD compared with other oceanic systems, and this may create conditions favorable for cyanobacteria, which have lower Zn requirements than their eukaryotic competitors. Shipboard grow-out experiments revealed that while Si was a limiting factor under our experimental conditions, additions of Si and either iron (Fe) or Zn led to higher biomass than Si additions alone. The addition ofFe and Zn alone did not lead to significant enhancements. Our results suggest that the depletion of Zn relative to P in upwelled waters may create conditions in the near-surface waters that favor phytoplankton with low Zn requirements, including cyanobacteria

Structural identifiability analyses of candidate models for in vitro Pitavastatin hepatic uptake

In this paper a review of the application of four different techniques (a version of the similarity transformation approach for autonomous uncontrolled systems, a non-differential input/output observable normal form approach, the characteristic set differential algebra and a recent algebraic input/output relationship approach) to determine the structural identifiability of certain in vitro nonlinear pharmacokinetic models is provided. The Organic Anion Transporting Polypeptide (OATP) substrate, Pitavastatin, is used as a probe on freshly isolated animal and human hepatocytes. Candidate pharmacokinetic non-linear compartmental models have been derived to characterise the uptake process of Pitavastatin. As a prerequisite to parameter estimation, structural identifiability analyses are performed to establish that all unknown parameters can be identified from the experimental observations available

N-player quantum games in an EPR setting

The $N$-player quantum game is analyzed in the context of an Einstein-Podolsky-Rosen (EPR) experiment. In this setting, a player's strategies are not unitary transformations as in alternate quantum game-theoretic frameworks, but a classical choice between two directions along which spin or polarization measurements are made. The players' strategies thus remain identical to their strategies in the mixed-strategy version of the classical game. In the EPR setting the quantum game reduces itself to the corresponding classical game when the shared quantum state reaches zero entanglement. We find the relations for the probability distribution for $N$-qubit GHZ and W-type states, subject to general measurement directions, from which the expressions for the mixed Nash equilibrium and the payoffs are determined. Players' payoffs are then defined with linear functions so that common two-player games can be easily extended to the $N$-player case and permit analytic expressions for the Nash equilibrium. As a specific example, we solve the Prisoners' Dilemma game for general $N \ge 2$. We find a new property for the game that for an even number of players the payoffs at the Nash equilibrium are equal, whereas for an odd number of players the cooperating players receive higher payoffs.Comment: 26 pages, 2 figure

Analyzing three-player quantum games in an EPR type setup

We use the formalism of Clifford Geometric Algebra (GA) to develop an analysis of quantum versions of three-player non-cooperative games. The quantum games we explore are played in an Einstein-Podolsky-Rosen (EPR) type setting. In this setting, the players' strategy sets remain identical to the ones in the mixed-strategy version of the classical game that is obtained as a proper subset of the corresponding quantum game. Using GA we investigate the outcome of a realization of the game by players sharing GHZ state, W state, and a mixture of GHZ and W states. As a specific example, we study the game of three-player Prisoners' Dilemma.Comment: 21 pages, 3 figure

Targeting prostate cancer based on signal transduction and cell cycle pathways

Prostate cancer remains a leading cause of death in men despite increased capacity to diagnose at earlier stages. After prostate cancer has become hormone independent, which often occurs after hormonal ablation therapies, it is difficult to effectively treat. Prostate cancer may arise from mutations and dysregulation of various genes involved in regulation signal transduction (e.g., PTEN, Akt, etc.,) and the cell cycle (e.g., p53, p21Cip1, p27Kip1, Rb, etc.,). This review focuses on the aberrant interactions of signal transduction and cell cycle genes products and how they can contribute to prostate cancer and alter therapeutic effectiveness. Originally published Cell Cycle, Vol. 7, No. 12, June 200