Microdosimetry: Principles and applications

Aim

to present the most important aspects of Microdosimetry, a research field in radiation biophysics.

Background

microdosimetry is the branch of radiation biophysics that systematically studies the spatial, temporal and spectral aspects of the stochastic nature of the energy deposition processes in microscopic structures.

Materials and Methods

we briefly review its history, the people, the formalism and the theories and devices that allowed researchers to begin to understand the true nature of radiation action on living matter.

Results and Conclusions

we outline some of its applications, especially to Boron Neutron Capture Therapy, attempting to explain the biological effectiveness of the boron thermal neutron capture reaction.     

Nonadaptive Fluctuation in an Adaptive Sensory System: Bacterial Chemoreceptor

Background

Sensory systems often exhibit an adaptation or desensitization after a transient response, making the system ready to receive a new signal over a wide range of backgrounds. Because of the strong influence of thermal stochastic fluctuations on the biomolecules responsible for the adaptation, such as many membrane receptors and channels, their response is inherently noisy, and the adaptive property is achieved as a statistical average.

Methodology/Principal Findings

Here, we study a simple kinetic model characterizing the essential aspects of these adaptive molecular systems and show theoretically that, while such an adaptive sensory system exhibits a perfect adaptation property on average, its temporal stochastic fluctuations are able to be sensitive to the environmental conditions. Among the adaptive sensory systems, an extensively studied model system is the bacterial receptor responsible for chemotaxis. The model exhibits a nonadaptive fluctuation sensitive to the environmental ligand concentration, while perfect adaptation is achieved on average. Furthermore, we found that such nonadaptive fluctuation makes the bacterial behavior dependent on the environmental chemoattractant concentrations, which enhances the chemotactic performance.

Conclusions/Significance

This result indicates that adaptive sensory systems can make use of such stochastic fluctuation to carry environmental information, which is not possible by means of the average, while keeping responsive to the changing stimulus.     

Contrasting Microbial Community Assembly Hypotheses: A Reconciling Tale from the Río Tinto

Background

The Río Tinto (RT) is distinguished from other acid mine drainage systems by its natural and ancient origins. Microbial life from all three domains flourishes in this ecosystem, but bacteria dominate metabolic processes that perpetuate environmental extremes. While the patchy geochemistry of the RT likely influences the dynamics of bacterial populations, demonstrating which environmental variables shape microbial diversity and unveiling the mechanisms underlying observed patterns, remain major challenges in microbial ecology whose answers rely upon detailed assessments of community structures coupled with fine-scale measurements of physico-chemical parameters.

Methodology/Principal Findings

By using high-throughput environmental tag sequencing we achieved saturation of richness estimators for the first time in the RT. We found that environmental factors dictate the distribution of the most abundant taxa in this system, but stochastic niche differentiation processes, such as mutation and dispersal, also contribute to observed diversity patterns.

Conclusions/Significance

We predict that studies providing clues to the evolutionary and ecological processes underlying microbial distributions will reconcile the ongoing debate between the Baas Becking vs. Hubbell community assembly hypotheses.     

Adults with Down syndrome have reduced cardiac response after light exercise testing

Objective

Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS.

Design

Case controlled before-after trial.

Setting

Residential centre for people with intellectual disabilities.

Participants

96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls.

Interventions

Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends.

Main outcome measure

Exercise testing

Results

At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m², p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m², p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response.

Conclusions

CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent.     

Unmasking Chaotic Attributes in Time Series of Living Cell Populations

Background

Long-range oscillations of the mammalian cell proliferation rate are commonly observed both in vivo and in vitro. Such complicated dynamics are generally the result of a combination of stochastic events and deterministic regulation. Assessing the role, if any, of chaotic regulation is difficult. However, unmasking chaotic dynamics is essential for analysis of cellular processes related to proliferation rate, including metabolic activity, telomere homeostasis, gene expression, and tumor growth.

Methodology/Principal Findings

Using a simple, original, nonlinear method based on return maps, we previously found a geometrical deterministic structure coordinating such fluctuations in populations of various cell types. However, nonlinearity and determinism are only necessary conditions for chaos; they do not by themselves constitute a proof of chaotic dynamics. Therefore, we used the same analytical method to analyze the oscillations of four well-known, low-dimensional, chaotic oscillators, originally designed in diverse settings and all possibly well-adapted to model the fluctuations of cell populations: the Lorenz, Rössler, Verhulst and Duffing oscillators. All four systems also display this geometrical structure, coordinating the oscillations of one or two variables of the oscillator. No such structure could be observed in periodic or stochastic fluctuations.

Conclusion/Significance

Theoretical models predict various cell population dynamics, from stable through periodically oscillating to a chaotic regime. Periodic and stochastic fluctuations were first described long ago in various mammalian cells, but by contrast, chaotic regulation had not previously been evidenced. The findings with our nonlinear geometrical approach are entirely consistent with the notion that fluctuations of cell populations can be chaotically controlled.     

A Quantitative Image Cytometry Technique for Time Series or Population Analyses of Signaling Networks

Background

Modeling of cellular functions on the basis of experimental observation is increasingly common in the field of cellular signaling. However, such modeling requires a large amount of quantitative data of signaling events with high spatio-temporal resolution. A novel technique which allows us to obtain such data is needed for systems biology of cellular signaling.

Methodology/Principal Findings

We developed a fully automatable assay technique, termed quantitative image cytometry (QIC), which integrates a quantitative immunostaining technique and a high precision image-processing algorithm for cell identification. With the aid of an automated sample preparation system, this device can quantify protein expression, phosphorylation and localization with subcellular resolution at one-minute intervals. The signaling activities quantified by the assay system showed good correlation with, as well as comparable reproducibility to, western blot analysis. Taking advantage of the high spatio-temporal resolution, we investigated the signaling dynamics of the ERK pathway in PC12 cells.

Conclusions/Significance

The QIC technique appears as a highly quantitative and versatile technique, which can be a convenient replacement for the most conventional techniques including western blot, flow cytometry and live cell imaging. Thus, the QIC technique can be a powerful tool for investigating the systems biology of cellular signaling.     

Hierarchical effector protein transport by the Salmonella Typhimurium SPI-1 type III secretion system

Background

Type III secretion systems (TTSS) are employed by numerous pathogenic and symbiotic bacteria to inject a cocktail of different “effector proteins” into host cells. These effectors subvert host cell signaling to establish symbiosis or disease.

Methodology/Principal Findings

We have studied the injection of SipA and SptP, two effector proteins of the invasion-associated Salmonella type III secretion system (TTSS-1). SipA and SptP trigger different host cell responses. SipA contributes to triggering actin rearrangements and invasion while SptP reverses the actin rearrangements after the invasion has been completed. Nevertheless, SipA and SptP were both pre-formed and stored in the bacterial cytosol before host cell encounter. By time lapse microscopy, we observed that SipA was injected earlier than SptP. Computer modeling revealed that two assumptions were sufficient to explain this injection hierarchy: a large number of SipA and SptP molecules compete for transport via a limiting number of TTSS; and the TTSS recognize SipA more efficiently than SptP.

Conclusions/Significance

This novel mechanism of hierarchical effector protein injection may serve to avoid functional interference between SipA and SptP. An injection hierarchy of this type may be of general importance, allowing bacteria to precisely time the host cell manipulation by type III effectors.     

Quantitative characterization of clumping in Scots pine crowns

Background and Aims

Proper characterization of the clumped structure of forests is needed for calculation of the absorbed radiation and photosynthetic production by a canopy. This study examined the dependency of crown-level clumping on tree size and growth conditions in Scots pine (Pinus sylvestris), and determined the ability of statistical canopy radiation models to quantify the degree of self-shading within crowns as a result of the clumping effect.

Methods

Twelve 3-D Scots pine trees were generated using an application of the LIGNUM model, and the crown-level clumping as quantified by the crown silhouette to total needle area ratio (STAR_crown) was calculated. The results were compared with those produced by the stochastic approach of modelling tree crowns as geometric shapes filled with a random medium.

Key Results

Crown clumping was independent of tree height, needle area and growth conditions. The results supported the capability of the stochastic approach in characterizing clumping in crowns given that the outer shell of the tree crown is well represented.

Conclusions

Variation in the whole-stand clumping index is induced by differences in the spatial pattern of trees as a function of, for example, stand age rather than by changes in the degree of self-shading within individual crowns as they grow bigger.     

Reshaping of bulbar odor response by nasal flow rate in the rat

Background

The impact of respiratory dynamics on odor response has been poorly studied at the olfactory bulb level. However, it has been shown that sniffing in the behaving rodent is highly dynamic and varies both in frequency and flow rate. Bulbar odor response could vary with these sniffing parameter variations. Consequently, it is necessary to understand how nasal airflow can modify and shape odor response at the olfactory bulb level.

Methodology and Principal Findings

To assess this question, we used a double cannulation and simulated nasal airflow protocol on anesthetized rats to uncouple nasal airflow from animal respiration. Both mitral/tufted cell extracellular unit activity and local field potentials (LFPs) were recorded. We found that airflow changes in the normal range were sufficient to substantially reorganize the response of the olfactory bulb. In particular, cellular odor-evoked activities, LFP oscillations and spike phase-locking to LFPs were strongly modified by nasal flow rate.

Conclusion

Our results indicate the importance of reconsidering the notion of odor coding as odor response at the bulbar level is ceaselessly modified by respiratory dynamics.     

Climate Variability and Nonstationary Dynamics of Mycoplasma pneumoniae Pneumonia in Japan

Background

A stationary association between climate factors and epidemics of Mycoplasma pneumoniae (M. pneumoniae) pneumonia has been widely assumed. However, it is unclear whether elements of the local climate that are relevant to M. pneumoniae pneumonia transmission have stationary signatures of climate factors on their dynamics over different time scales.

Methods

We performed a cross-wavelet coherency analysis to assess the patterns of association between monthly M. pneumoniae cases in Fukuoka, Japan, from 2000 to 2012 and indices for the Indian Ocean Dipole (IOD) and El Niño Southern Oscillation (ENSO).

Results

Monthly M. pneumoniae cases were strongly associated with the dynamics of both the IOD and ENSO for the 1–2-year periodic mode in 2005–2007 and 2010–2011. This association was non-stationary and appeared to have a major influence on the synchrony of M. pneumoniae epidemics.

Conclusions

Our results call for the consideration of non-stationary, possibly non-linear, patterns of association between M. pneumoniae cases and climatic factors in early warning systems.     

Multivariable Logistic Regression Model: A Novel Mathematical Model that Predicts Visual Field Sensitivity from Macular Ganglion Cell Complex Thickness in Glaucoma

Purpose

To design a mathematical model that can predict the relationship between the ganglion cell complex (GCC) thickness and visual field sensitivity (VFS) in glaucoma patients.

Design

Retrospective cross-sectional case series.

Method

Within 3 months from VFS measurements by the Humphrey field analyzer 10-2 program, 83 eyes underwent macular GCC thickness measurements by spectral-domain optical coherence tomography (SD-OCT). Data were used to construct a multiple logistic model that depicted the relationship between the explanatory variables (GCC thickness, age, sex, and spherical equivalent of refractive errors) determined by a regression analysis and the mean VFS corresponding to the SD-OCT scanned area. Analyses were performed in half or 8 segmented local areas as well as in whole scanned areas. A simple logistic model that included GCC thickness as the single explanatory variable was also constructed. The ability of the logistic models to depict the real GCC thickness/VFS in SAP distribution was analyzed by the χ² test of goodness-of-fit. The significance of the model effect was analyzed by analysis of variance (ANOVA).

Results

Scatter plots between the GCC thickness and the mean VFS showed sigmoid curves. The χ² test of goodness-of-fit revealed that the multiple logistic models showed a good fit for the real GCC thickness/VFS distribution in all areas except the nasal-inferior-outer area. ANOVA revealed that all of the multiple logistic models significantly predicted the VFS based on the explanatory variables. Although simple logistic models also exhibited significant VFS predictability based on the GCC thickness, the model effect was less than that observed for the multiple logistic models.

Conclusions

The currently proposed logistic models are useful methods for depicting relationships between the explanatory variables, including the GCC thickness, and the mean VFS in glaucoma patients.     

Modelling fruit-temperature dynamics within apple tree crowns using virtual plants

Background and Aims

Fruit temperature results from a complex system involving the climate, the tree architecture, the fruit location within the tree crown and the fruit thermal properties. Despite much theoretical and experimental evidence for large differences (up to 10 °C in sunny conditions) between fruit temperature and air temperature, fruit temperature is never used in horticultural studies. A way of modelling fruit-temperature dynamics from climate data is addressed in this work.

Methods

The model is based upon three-dimensional virtual representation of apple trees and links three-dimensional virtual trees with a physical-based fruit-temperature dynamical model. The overall model was assessed by comparing model outputs to field measures of fruit-temperature dynamics.

Key Results

The model was able to simulate both the temperature dynamics at fruit scale, i.e. fruit-temperature gradients and departure from air temperature, and at the tree scale, i.e. the within-tree-crown variability in fruit temperature (average root mean square error value over fruits was 1·43 °C).

Conclusions

This study shows that linking virtual plants with the modelling of the physical plant environment offers a relevant framework to address the modelling of fruit-temperature dynamics within a tree canopy. The proposed model offers opportunities for modelling effects of the within-crown architecture on fruit thermal responses in horticultural studies.     

Projected Demographic Profile of People Living with HIV in Australia: Planning for an Older Generation

Background

Advances in HIV antiretroviral therapy (ART) has reduced mortality in people living with HIV (PLHIV), resulting in an ageing population of PLHIV. Knowledge of demographic details such as age, geographical location and sex, will aid in the planning of training and resource allocation to effectively care for the future complex health needs of PLHIV.

Methods

An agent-based, stochastic, geographical model was developed to determine the current and future demographic of PLHIV in Australia. Data and parameters were sourced from Australia''s National HIV Registry and peer reviewed literature. Processes that were simulated include progression to AIDS, mortality and internal migration.

Findings

The model estimates the mean age of PLHIV in Australia is increasing at a rate of 0.49 years each year. The expected proportion of PLHIV in over 55 years is estimated to increase from 25.3% in 2010 to 44.2% in 2020. Median age is lower in inner-city areas of the capital cities than in rural areas. The areas with the highest prevalence of HIV will continue to be capital cities; however, other areas will have greater percentage growth from 2010 to 2020.

Conclusions

The age of the population of people living with HIV is expected to increase considerably in the future. As the population of PLHIV ages, specialist clinical training and resource provision in the aged care sector will also need to be addressed.     

A novel interhemispheric interaction: modulation of neuronal cooperativity in the visual areas

Background

The cortical representation of the visual field is split along the vertical midline, with the left and the right hemi-fields projecting to separate hemispheres. Connections between the visual areas of the two hemispheres are abundant near the representation of the visual midline. It was suggested that they re-establish the functional continuity of the visual field by controlling the dynamics of the responses in the two hemispheres.

Methods/Principal Findings

To understand if and how the interactions between the two hemispheres participate in processing visual stimuli, the synchronization of responses to identical or different moving gratings in the two hemi-fields were studied in anesthetized ferrets. The responses were recorded by multiple electrodes in the primary visual areas and the synchronization of local field potentials across the electrodes were analyzed with a recent method derived from dynamical system theory. Inactivating the visual areas of one hemisphere modulated the synchronization of the stimulus-driven activity in the other hemisphere. The modulation was stimulus-specific and was consistent with the fine morphology of callosal axons in particular with the spatio-temporal pattern of activity that axonal geometry can generate.

Conclusions/Significance

These findings describe a new kind of interaction between the cerebral hemispheres and highlight the role of axonal geometry in modulating aspects of cortical dynamics responsible for stimulus detection and/or categorization.