2,302 research outputs found

    Developmental Exposure of Rats to Chlorpyrifos Elicits Sex-Selective Hyperlipidemia and Hyperinsulinemia in Adulthood

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    Developmental exposure to chlorpyrifos alters cell signaling both in the brain and in peripheral tissues, affecting the responses to a variety of neurotransmitters and hormones. We administered 1 mg/kg/day chlorpyrifos to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, chlorpyrifos-exposed animals displayed elevations in plasma cholesterol and triglycerides, without underlying alterations in nonesterified free fatty acids and glycerol. This effect was restricted to males. Similarly, in the postprandial state, male rats showed hyperinsulinemia in the face of normal circulating glucose levels but demonstrated appropriate reduction of circulating insulin concentrations after fasting. These outcomes and sex selectivity resemble earlier findings at the cellular level, which identified hepatic hyperresponsiveness to gluconeogenic inputs from β-adrenoceptors or glucagon receptors. Our results thus indicate that apparently subtoxic neonatal chlorpyrifos exposure, devoid of effects on viability or growth but within the parameters of human fetal or neonatal exposures, produce a metabolic pattern for plasma lipids and insulin that resembles the major adult risk factors for atherosclerosis and type 2 diabetes mellitus

    "Checks and Balances Reflections on the Development of the Doctrine of Separation of Powers under the South African Constitution"

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    Constitutional Principle VI, of the constitutional principles negotiated at the Multi-Party negotiating process in the early 1990s and annexed to the Interim Constitution1, provided that:           There shall be a separation of powers between the legislature, executive and judiciary, with appropriate checks and balances to ensure accountability, responsiveness and openness.  &nbsp

    Haptics for the development of fundamental rhythm skills, including multi-limb coordination

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    This chapter considers the use of haptics for learning fundamental rhythm skills, including skills that depend on multi-limb coordination. Different sensory modalities have different strengths and weaknesses for the development of skills related to rhythm. For example, vision has low temporal resolution and performs poorly for tracking rhythms in real-time, whereas hearing is highly accurate. However, in the case of multi-limbed rhythms, neither hearing nor sight are particularly well suited to communicating exactly which limb does what and when, or how the limbs coordinate. By contrast, haptics can work especially well in this area, by applying haptic signals independently to each limb. We review relevant theories, including embodied interaction and biological entrainment. We present a range of applications of the Haptic Bracelets, which are computer-controlled wireless vibrotactile devices, one attached to each wrist and ankle. Haptic pulses are used to guide users in playing rhythmic patterns that require multi-limb coordination. One immediate aim of the system is to support the development of practical rhythm skills and multi-limb coordination. A longer-term goal is to aid the development of a wider range of fundamental rhythm skills including recognising, identifying, memorising, retaining, analysing, reproducing, coordinating, modifying and creating rhythms – particularly multi-stream (i.e. polyphonic) rhythmic sequences. Empirical results are presented. We reflect on related work, and discuss design issues for using haptics to support rhythm skills. Skills of this kind are essential not just to drummers and percussionists but also to keyboards players, and more generally to all musicians who need a firm grasp of rhythm

    Review of parameterisation and a novel database (LiionDB) for continuum Li-ion battery models

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    The Doyle–Fuller–Newman (DFN) framework is the most popular physics-based continuum-level description of the chemical and dynamical internal processes within operating lithium-ion-battery cells. With sufficient flexibility to model a wide range of battery designs and chemistries, the framework provides an effective balance between detail, needed to capture key microscopic mechanisms, and simplicity, needed to solve the governing equations at a relatively modest computational expense. Nevertheless, implementation requires values of numerous model parameters, whose ranges of applicability, estimation, and validation pose challenges. This article provides a critical review of the methods to measure or infer parameters for use within the isothermal DFN framework, discusses their advantages or disadvantages, and clarifies limitations attached to their practical application. Accompanying this discussion we provide a searchable database, available at www.liiondb.com, which aggregates many parameters and state functions for the standard DFN model that have been reported in the literature

    Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

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    Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials
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