Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbalpha pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbalpha target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbalpha pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Feedback design for regularizing descriptor systems

This paper surveys numerical techniques for the regularization of descriptor (generalized state-space) systems by proportional and derivative feedback. We review generalizations of controllability and observability to descriptor systems along with definitions of regularity and index in terms of the Weierstraß canonical form. Three condensed forms display the controllability and observability properties of a descriptor system. The condensed forms are obtained through orthogonal equivalence transformations and rank decisions, so they may be computed by numerically stable algorithms. In addition, the condensed forms display whether a descriptor system is regularizable, i.e., when the system pencil can be made to be regular by derivative and/or proportional output feedback, and, if so, what index can be achieved. Also included is a a new characterization of descriptor systems that can be made to be regular with index 1 by proportional and derivative output feedback.

Duality, observability, and controllability for linear time-varying descriptor systems

A characterization of observability for linear time-varying descriptor systemsE(t)x(t)+F(t)x(t)=B(t)u(t), y(t)=C(t)x(t) was recently developed. NeitherE norC were required to have constant rank. This paper defines a dual system, and a type of controllability so that observability of the original system is equivalent to controllability of the dual system. Criteria for observability and controllability are given in terms of arrays of derivatives of the original coefficients. In addition, the duality results of this paper lead to an improvement on a previous fundamental structure result for solvable systems of the formE(t)x(t)+F(t)x(t)=f(tt).

Parkinson’s Disease tremor classification – a comparison between Support Vector Machines and neural networks

Deep Brain Stimulation has been used in the study of and for treating Parkinson’s Disease (PD) tremor symptoms since the 1980s. In the research reported here we have carried out a comparative analysis to classify tremor onset based on intraoperative microelectrode recordings of a PD patient’s brain Local Field Potential (LFP) signals. In particular, we compared the performance of a Support Vector Machine (SVM) with two well known artificial neural network classifiers, namely a Multiple Layer Perceptron (MLP) and a Radial Basis Function Network (RBN). The results show that in this study, using specifically PD data, the SVM provided an overall better classification rate achieving an accuracy of 81% recognition.

Simulation models in farming systems research : potential and challenges

Integrated simulation models can be useful tools in farming system research. This chapter reviews three commonly used approaches, i.e. linear programming, system dynamics and agent-based models. Applications of each approach are presented and strengths and drawbacks discussed. We argue that, despite some challenges, mainly related to the integration of different approaches, model validation and the representation of human agents, integrated simulation models contribute important insights to the analysis of farming systems. They help unravelling the complex and dynamic interactions and feedbacks among bio-physical, socio-economic, and institutional components across scales and levels in farming systems. In addition, they can provide a platform for integrative research, and can support transdisciplinary research by functioning as learning platforms in participatory processes.

Organocatalytic domino reaction of cyanosulfones: access to complex cyclohexane systems with quaternary carbon centers

When ε-nitro-a,β-unsaturated esters are added to conjugated cyanosulfones in the presence of a bifunctional thiourea catalyst, a highly stereoselective domino reaction occurs to generate complex cyclohexanes with up to four stereogenic centers, one of which is quaternary in nature. Therefore, it is demonstrated that, like nitro compounds, sulfones can undergo an asymmetric intramolecular conjugate addition to r,β- unsaturated esters in the presence of a bifunctional organocatalyst.

Characterising the energy performance of centralised HVAC&R systems in the UK

Heating, ventilation, air conditioning and refrigeration (HVAC&R) systems account for more than 60% of the energy consumption of buildings in the UK. However, the effect of the variety of HVAC&R systems on building energy performance has not yet been taken into account within the existing building energy benchmarks. In addition, the existing building energy benchmarks are not able to assist decision-makers with HVAC&R system selection. This study attempts to overcome these two deficiencies through the performance characterisation of 36 HVAC&R systems based on the simultaneous dynamic simulation of a building and a variety of HVAC&R systems using TRNSYS software. To characterise the performance of HVAC&R systems, four criteria are considered; energy consumption, CO2 emissions, thermal comfort and indoor air quality. The results of the simulations show that, all the studied systems are able to provide an acceptable level of indoor air quality and thermal comfort. However, the energy consumption and amount of CO2 emissions vary. One of the significant outcomes of this study reveals that combined heating, cooling and power systems (CCHP) have the highest energy consumption with the lowest energy related CO2 emissions among the studied HVAC&R systems.

A general method for finding extremal states of Hamiltonian dynamical systems, with applications to perfect fluids

In addition to the Hamiltonian functional itself, non-canonical Hamiltonian dynamical systems generally possess integral invariants known as ‘Casimir functionals’. In the case of the Euler equations for a perfect fluid, the Casimir functionals correspond to the vortex topology, whose invariance derives from the particle-relabelling symmetry of the underlying Lagrangian equations of motion. In a recent paper, Vallis, Carnevale & Young (1989) have presented algorithms for finding steady states of the Euler equations that represent extrema of energy subject to given vortex topology, and are therefore stable. The purpose of this note is to point out a very general method for modifying any Hamiltonian dynamical system into an algorithm that is analogous to those of Vallis etal. in that it will systematically increase or decrease the energy of the system while preserving all of the Casimir invariants. By incorporating momentum into the extremization procedure, the algorithm is able to find steadily-translating as well as steady stable states. The method is applied to a variety of perfect-fluid systems, including Euler flow as well as compressible and incompressible stratified flow.

Aspect selection in adult L2 Spanish and the competing systems hypothesis: when pedagogical and linguistic rules conflict.

Native-like use of preterit and imperfect morphology in all contexts by English learners of L2 Spanish is the exception rather than the rule, even for successful learners. Nevertheless, recent research has demonstrated that advanced English learners of L2 Spanish attain a native-like morphosyntactic competence for the preterit/imperfect contrast, as evidenced by their native-like knowledge of associated semantic entailments (Goodin-Mayeda and Rothman 2007, Montrul and Slabakova 2003, Slabakova and Montrul 2003, Rothman and Iverson 2007). In addition to an L2 disassociation of morphology and syntax (e.g., Bruhn de Garavito 2003, Lardiere 1998, 2000, 2005, Prévost and White 1999, 2000, Schwartz 2003), I hypothesize that a system of learned pedagogical rules contributes to target-deviant L2 performance in this domain through the most advanced stages of L2 acquisition via its competition with the generative system. I call this hypothesis the Competing Systems Hypothesis. To test its predictions, I compare and contrast the use of the preterit and imperfect in two production tasks by native, tutored (classroom), and naturalistic learners of L2 Spanish.

On the power amplifier nonlinearity in MIMO transmit beamforming systems

In this paper, single-carrier multiple-input multiple-output (MIMO) transmit beamforming (TB) systems in the presence of high-power amplifier (HPA) nonlinearity are investigated. Specifically, due to the suboptimality of the conventional maximal ratio transmission/maximal ratio combining (MRT/MRC) under HPA nonlinearity, we propose the optimal TB scheme with the optimal beamforming weight vector and combining vector, for MIMO systems with nonlinear HPAs. Moreover, an alternative suboptimal but much simpler TB scheme, namely, quantized equal gain transmission (QEGT), is proposed. The latter profits from the property that the elements of the beamforming weight vector have the same constant modulus. The performance of the proposed optimal TB scheme and QEGT/MRC technique in the presence of the HPA nonlinearity is evaluated in terms of the average symbol error probability and mutual information with the Gaussian input, considering the transmission over uncorrelated quasi-static frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects on the performance of several system parameters, namely, the HPA parameters, numbers of antennas, quadrature amplitude modulation modulation order, number of pilot symbols, and cardinality of the beamforming weight vector codebook for QEGT.

Cross-layer design for multiuser MIMO MRC systems with feedback constraints

Cross-layer techniques represent efficient means to enhance throughput and increase the transmission reliability of wireless communication systems. In this paper, a cross-layer design of aggressive adaptive modulation and coding (A-AMC), truncated automatic repeat request (T-ARQ), and user scheduling is proposed for multiuser multiple-input-multiple-output (MIMO) maximal ratio combining (MRC) systems, where the impacts of feedback delay (FD) and limited feedback (LF) on channel state information (CSI) are also considered. The A-AMC and T-ARQ mechanism selects the appropriate modulation and coding schemes (MCSs) to achieve higher spectral efficiency while satisfying the service requirement on the packet loss rate (PLR), profiting from the feasibility of using different MCSs to retransmit a packet, which is destined to a scheduled user selected to exploit multiuser diversity and enhance the system's performance in terms of both transmission efficiency and fairness. The system's performance is evaluated in terms of the average PLR, average spectral efficiency (ASE), outage probability, and average packet delay, which are derived in closed form, considering transmissions over Rayleigh-fading channels. Numerical results and comparisons are provided and show that A-AMC combined with T-ARQ yields higher spectral efficiency than the conventional scheme based on adaptive modulation and coding (AMC), while keeping the achieved PLR closer to the system's requirement and reducing delay. Furthermore, the effects of the number of ARQ retransmissions, numbers of transmit and receive antennas, normalized FD, and cardinality of the beamforming weight vector codebook are studied and discussed.

Optimal beamforming in MIMO systems with HPA nonlinearity

In this paper, multiple-input multiple-output (MIMO) transmit beamforming (TB) systems under the consideration of nonlinear high-power amplifiers (HPAs) are investigated. The optimal beamforming scheme, with the optimal beamforming weight vector and combining vector, is proposed for MIMO systems with HPA nonlinearity. The performance of the proposed MIMO beamforming scheme in the presence of HPA nonlinearity is evaluated in terms of average symbol error probability (SEP), outage probability and system capacity, considering transmission over uncorrelated quasi-static frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, namely, parameters of nonlinear HPA, numbers of transmit and receive antennas, and modulation order of phase-shift keying (PSK), on performance.

Impact of HPA nonlinearity on MIMO systems with quantized equal gain transmission

In this paper, we investigate the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems in the presence of nonlinear high-power amplifiers (HPAs). Due to the suboptimality of maximal ratio transmission/maximal ratio combining (MRT/MRC) under HPA nonlinearity, quantized equal gain transmission (QEGT) is suggested as a feasible TB scheme. The effect of HPA nonlinearity on the performance of MIMO QEGT/MRC is evaluated in terms of the average symbol error probability (SEP) and system capacity, considering transmission over uncorrelated quasi-static frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, such as the parameters of nonlinear HPA, cardinality of the beamforming weight vector codebook, and modulation order of quadrature amplitude modulation (QAM), on performance.

Antipathogenic activity of probiotics against Salmonella Typhimurium and Clostridium difficile in anaerobic batch culture systems: is it due to synergies in probiotic mixtures or the specificity of single strains?

Probiotics are currently being investigated for prevention of infections caused by enteric pathogens. The aim of this in vitro study was to evaluate the influence of three single probiotics: Lactobacillus casei NCIMB 30185 (PXN 37), Lactobacillus acidophilus NCIMB 30184 (PXN 35), Bifidobacterium breve NCIMB 30180 (PXN 25) and a probiotic mixture containing the above strains plus twelve other strains belonging to the Lactobacillus, Bifidobacterium, Lactococcus, Streptococcus and Bacillus genera on the survival of Salmonella Typhimurium and Clostridium difficile using pH-controlled anaerobic batch cultures containing mixed fecal bacteria. Changes in relevant bacterial groups and effects of probiotic addition on survival of the two pathogens were assessed over 24 h. Quantitative analysis of bacterial populations revealed that there was a significant increase in lactobacilli and/or bifidobacteria numbers, depending on probiotic addition, compared with the control (no added probiotic). There was also a significant reduction in S. Typhimurium and C. difficile numbers in the presence of certain probiotics compared with controls. Of the probiotic treatments, two single strains namely L. casei NCIMB 30185 (PXN 37), and B. breve NCIMB 30180 (PXN 25) were the most potent in reducing the numbers of S. Typhimurium and C. difficile. In addition, the supplementation with probiotics into the systems influenced some fermentations parameters. Acetate was found in the largest concentrations in all vessels and lactate and formate were generally detected in higher amounts in vessels with probiotic addition compared to controls.

Potential of legume-based grassland-livestock systems in Europe

European grassland-based livestock production systems are challenged to produce more milk and meat to meet increasing world demand and to achieve this by using fewer resources. Legumes offer great potential for coping with such requests. They have numerous features that can act together at different stages in the soil-plant-animal-atmosphere system and these are most effective in mixed swards with a legume abundance of 30-50%. The resulting benefits are a reduced dependency on fossil energy and industrial N fertilizer, lower quantities of harmful emissions to the environment (greenhouse gases and nitrate), lower production costs, higher productivity and increased protein self-sufficiency. Some legume species offer opportunities for improving animal health with less medication due to bioactive secondary metabolites. In addition, legumes may offer an option for adapting to higher atmospheric CO2 concentrations and to climate change. Legumes generate these benefits at the level of the managed land area unit and also at the level of the final product unit. However, legumes suffer from some limitations, and suggestions are made for future research in order to exploit more fully the opportunities that legumes can offer. In conclusion, the development of legume-based grassland-livestock systems undoubtedly constitutes one of the pillars for more sustainable and competitive ruminant production systems, and it can only be expected that legumes will become more important in the future.