Identification of potential drug targets in Salmonella Typhimurium using metabolic modelling and experimental validation

almonella enterica serovar Typhimurium is an established model organism for Gram-negative, intracellular pathogens. Owing to the rapid spread of resistance to antibiotics among this group of pathogens, new approaches to identify suitable target proteins are required. Based on the genome sequence of Salmonella Typhimurium and associated databases, a genome-scale metabolic model was constructed. Output was based on an experimental determination of the biomass of Salmonella when growing in glucose minimal medium. Linear programming was used to simulate variations in energy demand, while growing in glucose minimal medium. By grouping reactions with similar flux responses, a sub-network of 34 reactions responding to this variation was identified (the catabolic core). This network was used to identify sets of one and two reactions, that when removed from the genome-scale model interfered with energy and biomass generation. 11 such sets were found to be essential for the production of biomass precursors. Experimental investigation of 7 of these showed that knock-outs of the associated genes resulted in attenuated growth for 4 pairs of reactions, while 3 single reactions were shown to be essential for growth.

Phytoplankton–zooplankton dynamics in the ‘presence’ or ‘absence’ of toxic phytoplankton

The inhibitory effects of toxin-producing phytoplankton (TPP) on zooplankton modulate the dynamics of marine plankton. In this article, we employ simple mathematical models to compare theoretically the dynamics of phytoplankton–zooplankton interaction in situations where the TPP are present with those where TPP are absent. We consider two sets of three-component interaction models: one that does not include the effect of TPP and the other that does. The negative effects of TPP on zooplankton is described by a non-linear interaction term. Extensive theoretical analyses of the models have been performed to understand the qualitative behaviour of the model systems around every possible equilibria. The results of local-stability analysis and numerical simulations demonstrate that the two model-systems differ qualitatively with regard to oscillations and stability. The model system that does not include TPP is asymptotically stable around the coexisting equilibria, whereas, the system that includes TPP oscillates for a range of parametric values associated with toxin-inhibition rate and competition coefficients. Our analysis suggests that the qualitative dynamics of the plankton–zooplankton interactions are very likely to alter due to the presence of TPP species, and therefore the effects of TPP should be considered carefully while modelling plankton dynamics.

The relationship between entrepreneurial marketing and the characteristics of Thai hotels and their managers

Purpose – The purpose of this paper is to explore empirically whether there are meaningful relationships between key entrepreneurial marketing (EM) variables and the demographic characteristics of the organization and its manager. Design/methodology/approach – The data were gathered from a sample of 369 hotels from all regions of Thailand through the use of a postal survey. Several multiple regression models were used to test the relationships in the study. Interaction terms were added to some models to test the moderating effects of major demographic variables on various EM attributes. Findings – The study shows which types of hotels and which types of managers were associated with EM characteristics. The results indicate that demographic characteristics, such as age, size, location, experience, and gender, significantly explain sets of entrepreneurial marketing variables. It was found, for instance, that both a young hotel and a large hotel are positively associated with entrepreneurial marketing, while owner management is positively associated with market orientation and negatively associated with growth aspirations but has no significant relationship with entrepreneurial orientation. Originality/value – The paper provides a comprehensive overview of selected relationships between key EM dimensions in the existing literature. It is suggested that future research involves a more in-depth exploration of some of the relationships found in this study.

The SPARC Data Initiative: Comparison of upper troposphere/lower stratosphere ozone climatologies from limb-viewing instruments and the nadir-viewing Tropospheric Emission Spectrometer

We present the first comprehensive intercomparison of currently available satellite ozone climatologies in the upper troposphere/lower stratosphere (UTLS) (300–70 hPa) as part of the Stratosphere-troposphere Processes and their Role in Climate (SPARC) Data Initiative. The Tropospheric Emission Spectrometer (TES) instrument is the only nadir-viewing instrument in this initiative, as well as the only instrument with a focus on tropospheric composition. We apply the TES observational operator to ozone climatologies from the more highly vertically resolved limb-viewing instruments. This minimizes the impact of differences in vertical resolution among the instruments and allows identification of systematic differences in the large-scale structure and variability of UTLS ozone. We find that the climatologies from most of the limb-viewing instruments show positive differences (ranging from 5 to 75%) with respect to TES in the tropical UTLS, and comparison to a “zonal mean” ozonesonde climatology indicates that these differences likely represent a positive bias for p ≤ 100 hPa. In the extratropics, there is good agreement among the climatologies regarding the timing and magnitude of the ozone seasonal cycle (differences in the peak-to-peak amplitude of <15%) when the TES observational operator is applied, as well as very consistent midlatitude interannual variability. The discrepancies in ozone temporal variability are larger in the tropics, with differences between the data sets of up to 55% in the seasonal cycle amplitude. However, the differences among the climatologies are everywhere much smaller than the range produced by current chemistry-climate models, indicating that the multiple-instrument ensemble is useful for quantitatively evaluating these models.

Simulation of a diffusion driven mobile robot

In this paper, we investigate the possibility to control a mobile robot via a sensory-motory coupling utilizing diffusion system. For this purpose, we implemented a simulation of the diffusion process of chemicals and the kinematics of the mobile robot. In comparison to the original Braitenberg vehicle in which sensorymotor coupling is tightly realised by hardwiring, our system employs the soft coupling. The mobile robot has two sets of independent sensory-motor unit, two sensors are implemented in front and two motors on each side of the robot. The framework used for the sensory-motor coupling was such that 1) Place two electrodes in the medium 2) Drop a certain amount of Chemical U and V related to the distance to the walls and the intensity of the light 3) Place other two electrodes in the medium 4) Measure the concentration of Chemical U and V to actuate the motors on both sides of the robot. The environment was constructed with four surrounding walls and a light source located at the center. Depending on the design parameters and initial conditions, the robot was able to successfully avoid the wall and light. More interestingly, the diffusion process in the sensory-motor coupling provided the robot with a simple form of memory which would not have been possible with a control framework based on a hard-wired electric circuit.

Grammatical gender and the notion of default: insights from language acquisition

The aim of this study is to investigate the contrast in the timing of acquisition of grammatical gender attested in Dutch and Greek child learners. Greek children show precocious acquisition of neuter gender in particular, while Dutch children experience a long delay in the acquisition of neuter nouns, which extends to school age. For both Dutch and Greek, neuter has been claimed to be the default gender value on grounds of syntactic distribution in contexts where gender agreement is inert. To reconcile the contrast between the learner and the language facts in Dutch, as well as the contrast in the timing between Greek and Dutch monolingual child learners, we consider two sets of criteria to define the notion of default: one set pertains to the notion of linguistic default and the other to the notion of learner default. We suggest that, whereas Greek neuter is both the linguistic and the learner default value, Dutch neuter is the linguistic but not the learner default, leading to a learnability problem.

Analysis of incoherent scatter radar data from non-thermal F-region plasma

A procedure is presented for fitting incoherent scatter radar data from non-thermal F-region ionospheric plasma, using theoretical spectra previously predicted. It is found that values of the shape distortion factor D∗, associated with deviations of the ion velocity distribution from a Maxwellian distribution, and ion temperatures can be deduced (the results being independent of the path of iteration) if the angle between the line-of-sight and the geomagnetic field is larger than about 15–20°. The procedure can be used with one or both of two sets of assumptions. These concern the validity of the adopted model for the line-of-sight ion velocity distribution in the one case or for the full three-dimensional ion velocity distribution function in the other. The distribution function employed was developed to describe the line-of-sight velocity distribution for large aspect angles, but both experimental data and Monte Carlo simulations indicate that the form of the field-perpendicular distribution can also describe the distribution at more general aspect angles. The assumption of this form for the line-of-sight velocity distribution at a general aspect angle enables rigorous derivation of values of the one-dimensional, line-of-sight ion temperature. With some additional assumptions (principally that the field-parallel distribution is always Maxwellian and there is a simple relationship between the ion temperature anisotropy and the distortion of the field-perpendicular distribution from a Maxwellian), fits to data for large aspect angles enable determination of line-of-sight temperatures at all aspect angles and hence, of the average ion temperature and the ion temperature anisotropy. For small aspect angles, the analysis is restricted to the determination of the line-of-sight ion temperature because the theoretical spectrum is insensitive to non-thermal effects when the plasma is viewed along directions almost parallel to the magnetic field. This limitation is expected to apply to any realistic model of the ion velocity distribution function and its consequences are discussed. Fit strategies which allow for mixed ion composition are also considered. Examples of fits to data from various EISCAT observing programmes are presented.

Field-perpendicular and field-aligned plasma flows observed by EISCAT during a prolonged period of northward IMF

The effect of a prolonged period of strongly northward Interplanetary Magnetic Field (IMF) on the high-latitude F-region is studied using data from the EISCAT Common Programme Zero mode of operation on 11–12 August 1982. The analysis of the raw autocorrelation functions is kept to the directly derived parameters Ne, Te, Ti and velocity, and limits are defined for the errors introduced by assumptions about ion composition and by changes in the transmitted power and system constant. Simple data-cleaning criteria are employed to eliminate problems due to coherent signals and large background noise levels. The observed variations in plasma densities, temperatures and velocities are interpreted in terms of supporting data from ISEE-3 and local riometers and magnetometers. Both field-aligned and field-perpendicular plasma flows at Tromsø showed effects of the northward IMF: convection was slow and irregular and field-aligned flow profiles were characteristic of steady-state polar wind outflow with flux of order 1012 m−2 s−1. This period followed a strongly southward IMF which had triggered a substorm. The substorm gave enhanced convection, with a swing to equatorward flow and large (5 × 1012 m−2 s−1), steady-state field-aligned fluxes, leading to the possibility of O+ escape into the magnetosphere. The apparent influence of the IMF over both field-perpendicular and field-aligned flows is explained in terms of the cross-cap potential difference and the location of the auroral oval.

Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials

There is an urgent need to treat individuals with high blood pressure (BP) with effective dietary strategies. Previous studies suggest a small, but significant decrease in BP after lactotripeptides (LTP) ingestion, although the data are inconsistent. The study aim was to perform a comprehensive meta-analysis of data from all relevant randomised controlled trials (RCT). Medline, Cochrane library, EMBASE and Web of Science were searched until May 2014. Eligibility criteria were RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP) and diastolic BP (DBP) as outcome measures. Thirty RCT met the inclusion criteria, which resulted in 33 sets of data. The pooled treatment effect for SBP was −2.95 mmHg (95% CI: −4.17, −1.73; p < 0.001), and for DBP was −1.51 mmHg (95% CI: −2.21, −0.80; p < 0.001). Sub-group analyses revealed that reduction of BP in Japanese studies was significantly greater, compared with European studies (p = 0.002 for SBP and p < 0.001 for DBP). The 24-h ambulatory BP (AMBP) response to LTP supplementation was statistically non-significant (p = 0.101 for SBP and p = 0.166 for DBP). Both publication bias and “small-study effect” were identified, which shifted the treatment effect towards less significant SBP and non-significant DBP reduction after LTP consumption. LTP may be effective in BP reduction, especially in Japanese individuals; however sub-group, meta-regression analyses and statistically significant publication biases suggest inconsistencies.

Typographic meaning: readers’ impressions of patterns of typographic differentiation

This research explores whether patterns of typographic differentiation influence readers’ impressions of documents. It develops a systematic approach to typographic investigation that considers relationships between different kinds of typographic attributes, rather than testing the influence of isolated variables. An exploratory study using multiple sort tasks and semantic differential scales identifies that readers form a variety of impressions in relation to how typographic elements are differentiated in document design. Building on the findings of the exploratory study and analysis of a sample of magazines, the research describes three patterns of typographic differentiation: high, moderate, and low. Each pattern comprises clusters of typographic attributes and organisational principles that are articulated in relation to a specified level of typographic differentiation (amplified, medium, or subtle). The patterns are applied to two sets of controlled test material. Using this purposely-designed material, the influence of patterns of typographic differentiation on readers’ impressions of documents is explored in a repertory grid analysis and a paired comparison procedure. The results of these studies indicate that patterns of typographic differentiation consistently shape readers’ impressions of documents, influencing judgments of credibility, document address, and intended readership; and suggesting particular kinds of engagement and genre associations. For example, high differentiation documents are likely to be considered casual, sensationalist, and young; moderate differentiation documents are most likely to be seen as formal and serious; and low differentiation examples are considered calm. Typographic meaning is shown to be created through complex, yet systematic, interrelationships rather than reduced to a linear model of increasing or decreasing variation. The research provides a way of describing typographic articulation that has application across a variety of disciplines and design practice. In particular, it illuminates the ways in which typographic presentation is meaningful to readers, providing knowledge that document producers can use to communicate more effectively.

Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacillus coagulans GBI-30, 6086

In advancing age, gut populations of beneficial microbes, notably Bifidobacterium spp., show a marked decline. This contributes to an environment less capable of maintaining homoeostasis. This in vitro investigation studied the possible synergistic effects of probiotic supplementation in modulating the gut microbiota enabling prebiotic therapy to in elderly persons. Single stage batch culture anaerobic fermenters were used and inoculated with fecal microbiota obtained from volunteers after taking a 28 day treatment of Bacillus coagulans GBI-30, 6086 (GanedenBC30 (BC30)) or a placebo. The response to prebiotic supplements fructooligosaccharides (FOS) and galactooligosaccharides (GOS) in the fermenters was assessed. Bacterial enumeration was carried out using fluorescent in situ hybridisation and organic acids measured by gas chromatography. Baseline populations of Faecalibacterium prausnitzii, Clostridium lituseburense and Bacillus spp. were significantly higher in those having consumed BC30 compared to the placebo. Both prebiotics increased populations of several purportedly beneficial bacterial groups in both sets of volunteers. Samples from volunteers having ingested the BC30 also increased populations of C. lituseburense, Eubacterium rectale and F. prausnitzii more so than in persons who had consumed the placebo, this also resulted in significantly higher concentrations of butyrate, acetate and propionate. This shows that consumption of BC30 and subsequent use of prebiotics resulted in elevated populations of beneficial genres of bacteria as well as organic acid production

Design of a unified data with business rules storage model for OLTP and OLAP systems

This paper reviews the literature concerning the practice of using Online Analytical Processing (OLAP) systems to recall information stored by Online Transactional Processing (OLTP) systems. Such a review provides a basis for discussion on the need for the information that are recalled through OLAP systems to maintain the contexts of transactions with the data captured by the respective OLTP system. The paper observes an industry trend involving the use of OLTP systems to process information into data, which are then stored in databases without the business rules that were used to process information and data stored in OLTP databases without associated business rules. This includes the necessitation of a practice, whereby, sets of business rules are used to extract, cleanse, transform and load data from disparate OLTP systems into OLAP databases to support the requirements for complex reporting and analytics. These sets of business rules are usually not the same as business rules used to capture data in particular OLTP systems. The paper argues that, differences between the business rules used to interpret these same data sets, risk gaps in semantics between information captured by OLTP systems and information recalled through OLAP systems. Literature concerning the modeling of business transaction information as facts with context as part of the modelling of information systems were reviewed to identify design trends that are contributing to the design quality of OLTP and OLAP systems. The paper then argues that; the quality of OLTP and OLAP systems design has a critical dependency on the capture of facts with associated context, encoding facts with contexts into data with business rules, storage and sourcing of data with business rules, decoding data with business rules into the facts with the context and recall of facts with associated contexts. The paper proposes UBIRQ, a design model to aid the co-design of data with business rules storage for OLTP and OLAP purposes. The proposed design model provides the opportunity for the implementation and use of multi-purpose databases, and business rules stores for OLTP and OLAP systems. Such implementations would enable the use of OLTP systems to record and store data with executions of business rules, which will allow for the use of OLTP and OLAP systems to query data with business rules used to capture the data. Thereby ensuring information recalled via OLAP systems preserves the contexts of transactions as per the data captured by the respective OLTP system.

Comparative analysis of performance and stability among composite cross populations, variety mixtures and pure lines of winter wheat in organic and conventional cropping systems

This study investigated the effects of increased genetic diversity in winter wheat (Triticum aestivum L.), either from hybridization across genotypes or from physical mixing of lines, on grain yield, grain quality, and yield stability in different cropping environments. Sets of pure lines (no diversity), chosen for high yielding ability or high quality, were compared with line mixtures (intermediate level of diversity), and lines crossed with each other in composite cross populations (CCPn, high diversity). Additional populations containing male sterility genes (CCPms) to increase outcrossing rates were also tested. Grain yield, grain protein content, and protein yield were measured at four sites (two organically-managed and two conventionally-managed) over three years, using seed harvested locally in each preceding year. CCPn and mixtures out-yielded the mean of the parents by 2.4% and 3.6%, respectively. These yield differences were consistent across genetic backgrounds but partly inconsistent across cropping environments and years. Yield stability measured by environmental variance was higher in CCPn and CCPms than the mean of the parents. An index of yield reliability tended to be higher in CCPn, CCPms and mixtures than the mean of the parents. Lin and Binns’ superiority values of yield and protein yield were consistently and significantly lower (i.e. better) in the CCPs than in the mean of the parents, but not different between CCPs and mixtures. However, CCPs showed greater early ground cover and plant height than mixtures. When compared with the (locally non-predictable) best-yielding pure line, CCPs and mixtures exhibited lower mean yield and somewhat lower yield reliability but comparable superiority values. Thus, establishing CCPs from smaller sets of high-performing parent lines might optimize their yielding ability. On the whole, the results demonstrate that using increased within-crop genetic diversity can produce wheat crops with improved yield stability and good yield reliability across variable and unpredictable cropping environments.

The co-development of technology and new buildings: incorporating building integrated photovoltaics

Current approaches for the reduction of carbon emissions in buildings are often predicated on the integration of renewable technologies into building projects. Building integrated photovoltaics (BIPV) is one of these technologies and brings its own set of challenges and problems with a resulting mutual articulation of this technology and the building. A Social Construction of Technology (SCOT) approach explores how negotiations between informal groups of project actors with shared interests shape the ongoing specification of both BIPV and the building. Six main groups with different interests were found to be involved in the introduction of BIPV (Cost Watchers, Design Aesthetes, Green Guardians, Design Optimizers, Generation Maximizers and Users). Their involvement around three sets of issues (design changes from lack of familiarity with the technology, misunderstandings from unfamiliar interdependencies of trades and the effects of standard firm procedure) is followed. Findings underline how BIPV requires a level of integration that typically spans different work packages and how standard contractual structures inhibit the smooth incorporation of BIPV. Successful implementation is marked by ongoing (re-)design of both the building and the technology as informal fluid groups of project actors with shared interests address the succession of problems which arise in the process of implementation.

Advanced source apportionment of size-resolved trace elements at multiple sites in London during winter

Trace element measurements in PM10–2.5, PM2.5–1.0 and PM1.0–0.3 aerosol were performed with 2 h time resolution at kerbside, urban background and rural sites during the ClearfLo winter 2012 campaign in London. The environment-dependent variability of emissions was characterized using the Multilinear Engine implementation of the positive matrix factorization model, conducted on data sets comprising all three sites but segregated by size. Combining the sites enabled separation of sources with high temporal covariance but significant spatial variability. Separation of sizes improved source resolution by preventing sources occurring in only a single size fraction from having too small a contribution for the model to resolve. Anchor profiles were retrieved internally by analysing data subsets, and these profiles were used in the analyses of the complete data sets of all sites for enhanced source apportionment. A total of nine different factors were resolved (notable elements in brackets): in PM10–2.5, brake wear (Cu, Zr, Sb, Ba), other traffic-related (Fe), resuspended dust (Si, Ca), sea/road salt (Cl), aged sea salt (Na, Mg) and industrial (Cr, Ni); in PM2.5–1.0, brake wear, other traffic-related, resuspended dust, sea/road salt, aged sea salt and S-rich (S); and in PM1.0–0.3, traffic-related (Fe, Cu, Zr, Sb, Ba), resuspended dust, sea/road salt, aged sea salt, reacted Cl (Cl), S-rich and solid fuel (K, Pb). Human activities enhance the kerb-to-rural concentration gradients of coarse aged sea salt, typically considered to have a natural source, by 1.7–2.2. These site-dependent concentration differences reflect the effect of local resuspension processes in London. The anthropogenically influenced factors traffic (brake wear and other traffic-related processes), dust and sea/road salt provide further kerb-to-rural concentration enhancements by direct source emissions by a factor of 3.5–12.7. The traffic and dust factors are mainly emitted in PM10–2.5 and show strong diurnal variations with concentrations up to 4 times higher during rush hour than during night-time. Regionally influenced S-rich and solid fuel factors, occurring primarily in PM1.0–0.3, have negligible resuspension influences, and concentrations are similar throughout the day and across the regions.