The Input Signal Step Function (ISSF), a Standard Method to Encode Input Signals in SBML Models with Software Support, Applied to Circadian Clock Models

LetterThis is the final version of the article. Available from SAGE Publications via the DOI in this record.Time-dependent light input is an important feature of computational models of the circadian clock. However, publicly available models encoded in standard representations such as the Systems Biology Markup Language (SBML) either do not encode this input or use different mechanisms to do so, which hinders reproducibility of published results as well as model reuse. The authors describe here a numerically continuous function suitable for use in SBML for models of circadian rhythms forced by periodic light-dark cycles. The Input Signal Step Function (ISSF) is broadly applicable to encoding experimental manipulations, such as drug treatments, temperature changes, or inducible transgene expression, which may be transient, periodic, or mixed. It is highly configurable and is able to reproduce a wide range of waveforms. The authors have implemented this function in SBML and demonstrated its ability to modify the behavior of publicly available models to accurately reproduce published results. The implementation of ISSF allows standard simulation software to reproduce specialized circadian protocols, such as the phase-response curve. To facilitate the reuse of this function in public models, the authors have developed software to configure its behavior without any specialist knowledge of SBML. A community-standard approach to represent the inputs that entrain circadian clock models could particularly facilitate research in chronobiology.K.S. was supported by the UK BBSRC grant BB/E015263/1. SynthSys Edinburgh is a Centre for Integrative Systems Biology (CISB) funded by BBSRC and EPSRC, reference BB/D019621/1

Modified sorting technique to mitigate the collateral mortality of trawled school prawns (Metapenaeus macleayi)

The potential for changes to onboard handling practices in order to improve the fate of juvenile school prawns (Metapenaeus macleayi) discarded during trawling were investigated in two Australian rivers (Clarence and Hunter) by comparing a purpose-built, water-filled sorting tray against a conventional dry tray across various conditions, including the range of typical delays before the start of sorting the catch (2 min vs. 15 min). Juvenile school prawns (n= 5760), caught during 32 and 16 deployments in each river, were caged and sacrificed at four times: immediately (T0), and at 24 (T24), 72 (T72), and 120 (T12 0) hours after having been discarded. In both rivers, most mortalities occurred between T0 and T24 and, after adjusting for control deaths (<12%), were greatest for the 15-min conventional treatment (up to 41% at T120). Mixed-effects logistic models revealed that in addition to the sampling time, method of sorting, and delay in sorting, the weight of the catch, salinity, and percentage cloud cover were significant predictors of mortality. Although trawling caused some mortalities and comparable stress (measured as L -lactate) in all school prawns, use of the water tray lessened the negative impacts of some of the above factors across both the 2-min and 15-min delays in sorting so that the overall discard mortality was reduced by more than a third. When used in conjunction with selective trawls, widespread application of the water tray should help to improve the sustainability of trawling for school prawns

Parameter inference in mechanistic models of cellular regulation and signalling pathways using gradient matching

A challenging problem in systems biology is parameter inference in mechanistic models of signalling pathways. In the present article, we investigate an approach based on gradient matching and nonparametric Bayesian modelling with Gaussian processes. We evaluate the method on two biological systems, related to the regulation of PIF4/5 in Arabidopsis thaliana, and the JAK/STAT signal transduction pathway

Meeting the design challenges of nano-CMOS electronics: an introduction to an upcoming EPSRC pilot project

The years of ‘happy scaling’ are over and the fundamental challenges that the semiconductor industry faces, at both technology and device level, will impinge deeply upon the design of future integrated circuits and systems. This paper provides an introduction to these challenges and gives an overview of the Grid infrastructure that will be developed as part of a recently funded EPSRC pilot project to address them, and we hope, which will revolutionise the electronics design industry

Towards a grid-enabled simulation framework for nano-CMOS electronics

The electronics design industry is facing major challenges as transistors continue to decrease in size. The next generation of devices will be so small that the position of individual atoms will affect their behaviour. This will cause the transistors on a chip to have highly variable characteristics, which in turn will impact circuit and system design tools. The EPSRC project "Meeting the Design Challenges of Nano-CMOS Electronics" (Nana-CMOS) has been funded to explore this area. In this paper, we describe the distributed data-management and computing framework under development within Nano-CMOS. A key aspect of this framework is the need for robust and reliable security mechanisms that support distributed electronics design groups who wish to collaborate by sharing designs, simulations, workflows, datasets and computation resources. This paper presents the system design, and an early prototype of the project which has been useful in helping us to understand the benefits of such a grid infrastructure. In particular, we also present two typical use cases: user authentication, and execution of large-scale device simulations

Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body, weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle, but DES, OP, and BBP caused reductions of 10-21% (p < 0.05 to p < 0.001) in daily sperm production. Humans are exposed to phthalates, such as BBP, and to alkylphenol polyethoxylates, such as OP, but to what extent is unknown. More detailed studies are warranted to assess the possible risk to the development of the human testis from exposure to these and other environmental estrogens

MicroR159 regulation of most conserved targets in Arabidopsis has negligible phenotypic effects

BACKGROUND A current challenge of microRNA (miRNA) research is the identification of biologically relevant miRNA:target gene relationships. In plants, high miRNA:target gene complementarity has enabled accurate target predictions, and slicing of target mRNAs has facilitated target validation through rapid amplification of 5' cDNA ends (5'-RACE) analysis. Together, these approaches have identified more than 20 targets potentially regulated by the deeply conserved miR159 family in Arabidopsis, including eight MYB genes with highly conserved miR159 target sites. However, genetic analysis has revealed the functional specificity of the major family members, miR159a and miR159b is limited to only two targets, MYB33 and MYB65. Here, we examine the functional role of miR159 regulation for the other potential MYB target genes. RESULTS For these target genes, functional analysis failed to identify miR159 regulation that resulted in any major phenotypic impact, either at the morphological or molecular level. This appears to be mainly due to the quiescent nature of the remaining family member, MIR159c. Although its expression overlaps in a temporal and spatial cell-specific manner with a subset of these targets in anthers, the abundance of miR159c is extremely low and concomitantly a mir159c mutant displays no anther defects. Examination of potential miR159c targets with conserved miR159 binding sites found neither their spatial or temporal expression domains appeared miR159 regulated, despite the detection of miR159-guided cleavage products by 5'-RACE. Moreover, expression of a miR159-resistant target (mMYB101) resulted predominantly in plants that are indistinguishable from wild type. Plants that displayed altered morphological phenotypes were found to be ectopically expressing the mMYB101 transgene, and hence were misrepresentative of the in vivo functional role of miR159. CONCLUSIONS This study presents a novel explanation for a paradox common to plant and animal miRNA systems, where among many potential miRNA-target relationships usually only a few appear physiologically relevant. The identification of a quiescent miR159c:target gene regulatory module in anthers provides a likely rationale for the presence of conserved miR159 binding sites in many targets for which miR159 regulation has no obvious functional role. Remnants from the demise of such modules may lead to an overestimation of miRNA regulatory complexity when investigated using bioinformatic, 5'-RACE or transgenic approaches.RSA was funded by an ANU postgraduate scholarship and by a CSIRO Emerging Science Initiative. JL is the recipient of an ANU international student postgraduate scholarship. This research was supported by an Australian Research Council grant DP0773270

CS Lines Profiles in Hot Cores

We present a theoretical study of CS line profiles in archetypal hot cores. We provide estimates of line fluxes from the CS(1-0) to the CS(15-14) transitions and present the temporal variation of these fluxes. We find that \textit{i)} the CS(1-0) transition is a better tracer of the Envelope of the hot core whereas the higher-J CS lines trace the ultra-compact core; \textit{ii)} the peak temperature of the CS transitions is a good indicator of the temperature inside the hot core; \textit{iii)} in the Envelope, the older the hot core the stronger the self-absorption of CS; \textit{iv)} the fractional abundance of CS is highest in the innermost parts of the ultra-compact core, confirming the CS molecule as one of the best tracers of very dense gas.Comment: 17 pages, 5 figures, 1 table, In press in Ap