A simple regional-scale model for forecasting sorghum yield across North-Eastern Australia

Sorghum is the main dryland summer crop in NE Australia and a number of agricultural businesses would benefit from an ability to forecast production likelihood at regional scale. In this study we sought to develop a simple agro-climatic modelling approach for predicting shire (statistical local area) sorghum yield. Actual shire yield data, available for the period 1983-1997 from the Australian Bureau of Statistics, were used to train the model. Shire yield was related to a water stress index (SI) that was derived from the agro-climatic model. The model involved a simple fallow and crop water balance that was driven by climate data available at recording stations within each shire. Parameters defining the soil water holding capacity, maximum number of sowings (MXNS) in any year, planting rainfall requirement, and critical period for stress during the crop cycle were optimised as part of the model fitting procedure. Cross-validated correlations (CVR) ranged from 0.5 to 0.9 at shire scale. When aggregated to regional and national scales, 78-84% of the annual variation in sorghum yield was explained. The model was used to examine trends in sorghum productivity and the approach to using it in an operational forecasting system was outlined. (c) 2005 Elsevier B.V. All rights reserved.

Review of tropospheric bomb C-14 data for carbon cycle modeling and age calibration purposes

Comprehensive published radiocarbon data from selected atmospheric records, tree rings, and recent organic matter were analyzed and grouped into 4 different zones (three for the Northern Hemisphere and one for the whole Southern Hemisphere). These C-14 data for the summer season of each hemisphere were employed to construct zonal, hemispheric, and global data sets for use in regional and global carbon model calculations including calibrating and comparing carbon cycle models. In addition, extended monthly atmospheric C-14 data sets for 4 different zones were compiled for age calibration purposes. This is the first time these data sets were constructed to facilitate the dating of recent organic material using the bomb C-14 curves. The distribution of bomb C-14 reflects the major zones of atmospheric circulation.

Patched1 functions as a gatekeeper by promoting cell cycle progression

Mutations in the Hedgehog receptor, Patched 1 (Ptch1), have been linked to both familial and sporadic forms of basal cell carcinoma (BCC), leading to the hypothesis that loss of Ptch1 function is sufficient for tumor progression. By combining conditional knockout technology with the inducible activity of the Keratin6 promoter, we provide in vivo evidence that loss of Ptch1 function from the basal cell population of mouse skin is sufficient to induce rapid skin tumor formation, reminiscent of human BCC. Elimination of Ptch1 does not promote the nuclear translocation of beta-catenin and does not induce ectopic activation or expression of Notch pathway constituents. In the absence of Ptch1, however, a large proportion of basal cells exhibit nuclear accumulation of the cell cycle regulators cyclin D1 and B1. Collectively, our data suggest that Ptch1 likely functions as a tumor suppressor by inhibiting G(1)-S phase and G(2)-M phase cell cycle progression, and the rapid onset of tumor progression clearly indicates Ptch1 functions as a gatekeeper. In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors.

Type III secretion contact-dependent model for the intracellular development of Chlamydia

The medically significant genus Chlamydia is a class of obligate intracellular bacterial pathogens that replicate within vacuoles in host eukaryotic cells termed inclusions. Chlamydia's developmental cycle involves two forms; an infectious extracellular form, known as an elementary body (EB), and a non-infectious form, known as the reticulate body (RB), that replicates inside the vacuoles of the host cells. The RB surface is covered in projections that are in intimate contact with the inclusion membrane. Late in the developmental cycle, these reticulate bodies differentiate into the elementary body form. In this paper, we present a hypothesis for the modulation of these developmental events involving the contact-dependent type III secretion (TTS) system. TTS surface projections mediate intimate contact between the RB and the inclusion membrane. Below a certain number of projections, detachment of the RB provides a signal for late differentiation of RB into EB. We use data and develop a mathematical model investigating this hypothesis. If the hypothesis proves to be accurate, then we have shown that increasing the number of inclusions per host cell will increase the number of infectious progeny EB until some optimal number of inclusions. For more inclusions than this optimum, the infectious yield is reduced because of spatial restrictions. We also predict that a reduction in the number of projections on the surface of the RB (and as early as possible during development) will significantly reduce the burst size of infectious EB particles. Many of the results predicted by the model can be tested experimentally and may lead to the identification of potential targets for drug design. © Society for Mathematical Biology 2006.

Simulation of air traffic controllers' behaviour using the operator choice model

The Operator Choice Model (OCM) was developed to model the behaviour of operators attending to complex tasks involving interdependent concurrent activities, such as in Air Traffic Control (ATC). The purpose of the OCM is to provide a flexible framework for modelling and simulation that can be used for quantitative analyses in human reliability assessment, comparison between human computer interaction (HCI) designs, and analysis of operator workload. The OCM virtual operator is essentially a cycle of four processes: Scan Classify Decide Action Perform Action. Once a cycle is complete, the operator will return to the Scan process. It is also possible to truncate a cycle and return to Scan after each of the processes. These processes are described using Continuous Time Probabilistic Automata (CTPA). The details of the probability and timing models are specific to the domain of application, and need to be specified using domain experts. We are building an application of the OCM for use in ATC. In order to develop a realistic model we are calibrating the probability and timing models that comprise each process using experimental data from a series of experiments conducted with student subjects. These experiments have identified the factors that influence perception and decision making in simplified conflict detection and resolution tasks. This paper presents an application of the OCM approach to a simple ATC conflict detection experiment. The aim is to calibrate the OCM so that its behaviour resembles that of the experimental subjects when it is challenged with the same task. Its behaviour should also interpolate when challenged with scenarios similar to those used to calibrate it. The approach illustrated here uses logistic regression to model the classifications made by the subjects. This model is fitted to the calibration data, and provides an extrapolation to classifications in scenarios outside of the calibration data. A simple strategy is used to calibrate the timing component of the model, and the results for reaction times are compared between the OCM and the student subjects. While this approach to timing does not capture the full complexity of the reaction time distribution seen in the data from the student subjects, the mean and the tail of the distributions are similar.

Self-reported risk perception, mood and risk behaviour across the human menstrual cycle

Normally ovulating women exhibit a decline in risk behaviours that may lead to sexual assault during the fertile phase of the menstrual cycle, whereas women using the Pill do not. The current study tests two explanatory models: the mood and fertility models. Self-reported risk and non-risk behaviours, mood, and risk perception in sexual assault and physical risk domains were assessed by testing fiftyone women at menstruation and during their fertile period. Based on the decline in risk behaviours shown in past research, the fertility model predicts that normally ovulating women will display greater risk perception during the fertile phase of their cycle. The mood model predicts that at menstruation, when negative mood is highest, risk perception will be increased and risk behaviours correspondingly reduced. Risk behaviours did not vary over the cycle or between groups. Overall, results support the mood model. Negative mood was greater at menstruation and positive mood during the fertile period for both groups, rational risk perception was correspondingly greater at menstruation. The fertility model was not supported as risk perception ratings did not vary in the expected direction and ratings were not specific to the sexual assault domain.

Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin

The number of new chemical entities (NCE) is increasing every day after the introduction of combinatorial chemistry and high throughput screening to the drug discovery cycle. One third of these new compounds have aqueous solubility less than 20µg/mL [1]. Therefore, a great deal of interest has been forwarded to the salt formation technique to overcome solubility limitations. This study aims to improve the drug solubility of a Biopharmaceutical Classification System class II (BCS II) model drug (Indomethacin; IND) using basic amino acids (L-arginine, L-lysine and L-histidine) as counterions. Three new salts were prepared using freeze drying method and characterised by FT-IR spectroscopy, proton nuclear magnetic resonance ((1)HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). The effect of pH on IND solubility was also investigated using pH-solubility profile. Both arginine and lysine formed novel salts with IND, while histidine failed to dissociate the free acid and in turn no salt was formed. Arginine and lysine increased IND solubility by 10,000 and 2296 fold, respectively. An increase in dissolution rate was also observed for the novel salts. Since these new salts have improved IND solubility to that similar to BCS class I drugs, IND salts could be considered for possible waivers of bioequivalence.

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

Using a simulation model for capacity management

A simulation model has been constructed of a valve manufacturing plant with the aim of assessing capacity requirements in response to a forecast increase in demand. The plant provides a weekly cycle of valves of varying types, based on a yearly production plan. Production control is provided by a just-in-time type system to minimise inventory. The simulation model investigates the effect on production lead time of a range of valve sequences into the plant. The study required the collection of information from a variety of sources, and a model that reflected the true capabilities of the production system. The simulation results convinced management that substantial changes were needed in order to meet demand. The case highlights the use of simulation in enabling a manager to quantify operational scenarios and thus provide a rational basis on which to take decisions on meeting performance criteria.

A critique of a model for an academic staff activity database developed to aid a department in strategic and operational decision making

This paper discusses the use of a Model developed by Aston Business School to record the work load of its academic staff. By developing a database to register annual activity in all areas of teaching, administration and research the School has created a flexible tool which can be used for facilitating both day-to-day managerial and longer term strategic decisions. This paper gives a brief outline of the Model and discusses the factors which were taken into account when setting it up. Particular attention is paid to the uses made of the Model and the problems encountered in developing it. The paper concludes with an appraisal of the Model’s impact and of additional developments which are currently being considered. Aston Business School has had a Load Model in some form for many years. The Model has, however, been refined over the past five years, so that it has developed into a form which can be used for a far greater number of purposes within the School. The Model is coordinated by a small group of academic and administrative staff, chaired by the Head of the School. This group is responsible for the annual cycle of collecting and inputting data, validating returns, carrying out analyses of the raw data, and presenting the mater ial to different sections of the School. The authors of this paper are members of this steer ing group.

A novel concentration dependent amino acid ion pair strategy to mediate drug permeation using indomethacin as a model insoluble drug

Assessment of oral drug bioavailability is an important parameter for new chemical entities (NCEs) in drug development cycle. After evaluating the pharmacological response of these new molecules, the following critical stage is to investigate their in vitro permeability. Despite the great success achieved by prodrugs, covalent linking the drug molecule with a hydrophobic moiety might result in a new entity that might be toxic or ineffective. Therefore, an alternative that would improve the drug uptake without affecting the efficacy of the drug molecule would be advantageous. The aim of the current study is to investigate the effect of ion-pairing on the permeability profile of a model drug: indomethacin (IND) to understand the mechanism behind the permeability improvement across Caco-2 monolayers. Arginine and lysine formed ion-pairs with IND at various molar ratios 1:1, 1:2, 1:4 and 1:8 as reflected by the double reciprocal graphs. The partitioning capacities of the IND were evaluated using octanol/water partitioning studies and the apparent permeabilities (P app) were measured across Caco-2 monolayers for the different formulations. Partitioning studies reflected the high hydrophobicity of IND (Log P = 3) which dropped upon increasing the concentrations of arginine/lysine in the ion pairs. Nevertheless, the prepared ion pairs improved IND permeability especially after 60 min of the start of the experiment. Coupling partitioning and permeability results suggest a decrease in the passive transcellular uptake due to the drop in IND portioning capacities and a possible involvement of active carriers. Future work will investigate which transport gene might be involved in the absorption of the ion paired formulations using molecular biology technologies. © 2014 Elsevier B.V. All rights reserved.

The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein

Structural evidence has demonstrated that P-glycoprotein (P-gp) undergoes considerable conformational changes during catalysis, and these alterations are important in drug interaction. Knowledge of which regions in P-gp undergo conformational alterations will provide vital information to elucidate the locations of drug binding sites and the mechanism of coupling. A number of investigations have implicated transmembrane segment six (TM6) in drug-P-gp interactions, and a cysteine-scanning mutagenesis approach was directed to this segment. Introduction of cysteine residues into TM6 did not disturb basal or drug-stimulated ATPase activity per se. Under basal conditions the hydrophobic probe coumarin maleimide readily labeled all introduced cysteine residues, whereas the hydrophilic fluorescein maleimide only labeled residue Cys-343. The amphiphilic BODIPY-maleimide displayed a more complex labeling profile. The extent of labeling with coumarin maleimide did not vary during the catalytic cycle, whereas fluorescein maleimide labeling of F343C was lost after nucleotide binding or hydrolysis. BODIPY-maleimide labeling was markedly altered during the catalytic cycle and indicated that the adenosine 5'-(beta,gamma-imino)triphosphate-bound and ADP/vanadate-trapped intermediates were conformationally distinct. Our data are reconciled with a recent atomic scale model of P-gp and are consistent with a tilting of TM6 in response to nucleotide binding and ATP hydrolysis.

A Two Layered Model for Evolving Web Resources

In this paper the key features of a two-layered model for describing the semantic of dynamical web resources are introduced. In the current Semantic Web proposal [Berners-Lee et al., 2001] web resources are classified into static ontologies which describes the semantic network of their inter-relationships [Kalianpur, 2001][Handschuh & Staab, 2002] and complex constraints described by logical quantified formula [Boley et al., 2001][McGuinnes & van Harmelen, 2004][McGuinnes et al., 2004], the basic idea is that software agents can use techniques of automatic reasoning in order to relate resources and to support sophisticated web application. On the other hand, web resources are also characterized by their dynamical aspects, which are not adequately addressed by current web models. Resources on the web are dynamical since, in the minimal case, they can appear or disappear from the web and their content is upgraded. In addition, resources can traverse different states, which characterized the resource life-cycle, each resource state corresponding to different possible uses of the resource. Finally most resources are timed, i.e. they information they provide make sense only if contextualised with respect to time, and their validity and accuracy is greatly bounded by time. Temporal projection and deduction based on dynamical and time constraints of the resources can be made and exploited by software agents [Hendler, 2001] in order to make previsions about the availability and the state of a resource, for deciding when consulting the resource itself or in order to deliberately induce a resource state change for reaching some agent goal, such as in the automated planning framework [Fikes & Nilsson, 1971][Bacchus & Kabanza,1998].

Dimensioning BCH codes for coherent DQPSK systems with laser phase noise and cycle slips

Forward error correction (FEC) plays a vital role in coherent optical systems employing multi-level modulation. However, much of coding theory assumes that additive white Gaussian noise (AWGN) is dominant, whereas coherent optical systems have significant phase noise (PN) in addition to AWGN. This changes the error statistics and impacts FEC performance. In this paper, we propose a novel semianalytical method for dimensioning binary Bose-Chaudhuri-Hocquenghem (BCH) codes for systems with PN. Our method involves extracting statistics from pre-FEC bit error rate (BER) simulations. We use these statistics to parameterize a bivariate binomial model that describes the distribution of bit errors. In this way, we relate pre-FEC statistics to post-FEC BER and BCH codes. Our method is applicable to pre-FEC BER around 10-3 and any post-FEC BER. Using numerical simulations, we evaluate the accuracy of our approach for a target post-FEC BER of 10-5. Codes dimensioned with our bivariate binomial model meet the target within 0.2-dB signal-to-noise ratio.

EPQ Model with Imperfect Quality Raw Material

MSC 2010: 26A33, 33E12, 33C60, 44A20