An investigation into the effect of scour on the natural frequency of an offshore wind turbine

Rapid expansion of the offshore wind industry has stimulated a renewed interest in the behaviour of offshore piles. There is widespread acceptance in practice that pile design methods developed for the offshore oil and gas industry may not be appropriate for designing wind turbine foundations. To date, the majority of offshore wind turbines are supported by large diameter monopiles. These foundations are sensitive to scour which can reduce their ultimate capacity and alter their dynamic response. In this paper, the use of a vibration-based method to monitor scour is investigated. The effect of scour on the natural frequency of a model monopile was measured in a scale model test. A spring–beam finite element numerical model was developed to examine the foundation response. The model, which used springs tuned to the small-strain stiffness of the sand, was shown to be capable of capturing the change in frequency observed in the scale test. This numerical procedure was extended to investigate the response of a full-scale wind turbine over a range of soil densities, which might be experienced at offshore development sites. Results suggest that wind turbines founded in loose sand would exhibit the largest relative reductions in natural frequency resulting from scour

Chronic exposure to KATP channel openers results in attenuated glucose sensing in hypothalamic GT1-7 neurons

Individuals with Type 1 diabetes (T1D) are often exposed to recurrent episodes of hypoglycaemia. This reduces hormonal and behavioural responses that normally counteract low glucose in order to maintain glucose homeostasis, with altered responsiveness of glucose sensing hypothalamic neurons implicated. Although the molecular mechanisms are unknown, pharmacological studies implicate hypothalamic ATP-sensitive potassium channel (KATP) activity, with KATP openers (KCOs) amplifying, through cell hyperpolarization, the response to hypoglycaemia. Although initial findings, using acute hypothalamic KCO delivery, in rats were promising, chronic exposure to the KCO NN414 worsened the responses to subsequent hypoglycaemic challenge. To investigate this further we used GT1-7 cells to explore how NN414 affected glucose-sensing behaviour, the metabolic response of cells to hypoglycaemia and KATP activity. GT1-7 cells exposed to 3 or 24 h NN414 exhibited an attenuated hyperpolarization to subsequent hypoglycaemic challenge or NN414, which correlated with diminished KATP activity. The reduced sensitivity to hypoglycaemia was apparent 24 h after NN414 removal, even though intrinsic KATP activity recovered. The NN414-modified glucose responsiveness was not associated with adaptations in glucose uptake, metabolism or oxidation. KATP inactivation by NN414 was prevented by the concurrent presence of tolbutamide, which maintains KATP closure. Single channel recordings indicate that NN414 alters KATP intrinsic gating inducing a stable closed or inactivated state. These data indicate that exposure of hypothalamic glucose sensing cells to chronic NN414 drives a sustained conformational change to KATP, probably by binding to SUR1, that results in loss of channel sensitivity to intrinsic metabolic factors such as MgADP and small molecule agonists.We thank Novo Nordisk for providing NN414. This study was funded by grants from Diabetes UK (to MLJA, RJM) and the Juvenile Diabetes Research Foundation (postdoctoral fellowship 3-576-2010 to CB and 1-2008-728 to RJM)

Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes

AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus

Oleate induces K_ATP channel-dependent hyperpolarisation in mouse hypothalamic glucose-excited neurones without altering cellular energy charge

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The unsaturated fatty acid, oleate exhibits anorexigenic properties reducing food intake and hepatic glucose output. However, its mechanism of action in the hypothalamus has not been fully determined. This study investigated the effects of oleate and glucose on GT1-7 mouse hypothalamic cells (a model of glucose-excited (GE) neurons) and mouse arcuate nucleus (ARC) neurons. Whole-cell and perforated patch-clamp recordings, immunoblotting and cell energy status measures were used to investigate oleate- and glucose-sensing properties of mouse hypothalamic neurons. Oleate or lowered glucose concentration caused hyperpolarization and inhibition of firing of GT1-7 cells by the activation of ATP-sensitive K(+) channels (KATP). This effect of oleate was not dependent on fatty acid oxidation or raised AMP-activated protein kinase activity or prevented by the presence of the UCP2 inhibitor genipin. Oleate did not alter intracellular calcium, indicating that CD36/fatty acid translocase may not play a role. However, oleate activation of KATP may require ATP metabolism. The short-chain fatty acid octanoate was unable to replicate the actions of oleate on GT1-7 cells. Although oleate decreased GT1-7 cell mitochondrial membrane potential there was no change in total cellular ATP or ATP/ADP ratios. Perforated patch and whole-cell recordings from mouse hypothalamic slices demonstrated that oleate hyperpolarized a subpopulation of ARC GE neurons by KATP activation. Additionally, in a separate small population of ARC neurons, oleate application or lowered glucose concentration caused membrane depolarization. In conclusion, oleate induces KATP-dependent hyperpolarization and inhibition of firing of a subgroup of GE hypothalamic neurons without altering cellular energy charge.This work was supported by: grants from the Wellcome Trust (grant number 068692) to M.L.J. Ashford; from Juvenile Diabetes Research Foundation (JDRF) to R.J. McCrimmon and Fellowships to C. Beall (JDRF; 3-576-2010 and Diabetes UK 13/0004647

A comparison of initial stiffness formulations for small-strain soil–pile dynamic Winkler modelling

Dynamic Soil-Structure Interaction (DSSI) is an area of much ongoing research and has wide and varied applications from seismic response analysis to offshore wind foundation response. DSSI covers a wide range of load regimes from small-strain vibrations to large strain cyclic loading. One of the most common ways to model DSSI uses the Winkler model, which considers the soil as a series of mutually independent springs. The difficulty with modelling DSSI arises with the inelastic and nonlinear load–displacement response of soil with increasing strain, therefore modelling of large-strain DSSI relies on the specification of many interrelated parameters. The relative magnitude of these parameters can have a significant effect on the modelled response. In this paper, the specification of an initial stiffness coefficient to model the elastic (small-strain) response of a soil–pile system is investigated. The coefficient of subgrade reaction method can be used to generate spring stiffness moduli for Winkler type models. A number of subgrade reaction theories have been proposed and their application to the problem of static loading has been widely studied. However, relatively little research concerning the application of these models for small-strain dynamic loading has been undertaken. This paper describes a sensitivity study in which a number of subgrade reaction models were used to estimate the frequency response at smallstrain levels for a range of pile geometries and ground conditions. A field investigation was undertaken on two piles with different slenderness ratios to estimate the frequency response and damping ratios. The experimental results were compared to predictions of damped natural frequency obtained from numerical models using the force input and measured damping ratio from each experiment. The ability of each subgrade reaction formulation to model the response at small-strain levels is evaluated

Probabilistic examination of the change in eigenfrequencies of an offshore wind turbine under progressive scour incorporating soil spatial variability

The trend for development in the offshore wind sector is towards larger turbines in deeper water. This results in higher wind and wave loads on these dynamically sensitive structures. Monopiles are the preferred foundation solution for offshore wind structures and have a typical expected design life of 20 years. These foundations have strict serviceability tolerances (e.g. mudline rotation of less than 0.25° during operation). Accurate determination of the system frequency is critical in order to ensure satisfactory performance over the design life, yet determination of the system stiffness and in particular the operational soil stiffness remains a significant challenge. Offshore site investigations typically focus on the determination of the soil conditions using Cone Penetration Test (CPT) data. This test gives large volumes of high quality data on the soil conditions at the test location, which can be correlated to soil strength and stiffness parameters and used directly in pile capacity models. However, a combination of factors including; parameter transformation, natural variability, the relatively small volume of the overall sea bed tested and operational effects such as the potential for scour development during turbine operation lead to large uncertainties in the soil stiffness values used in design. In this paper, the effects of scour erosion around unprotected foundations on the design system frequencies of an offshore wind turbine is investigated numerically. To account for the uncertainty in soil-structure interaction stiffness for a given offshore site, a stochastic ground model is developed using the data resulting from CPTs as inputs. Results indicate that the greater the depth of scour, the less certain a frequency-based SHM technique would be in accurately assessing scour magnitude based solely on first natural frequency measurements. However, using Receiver Operating Characteristic (ROC) curve analysis, the chance of detecting the presence of scour from the output frequencies is improved significantly and even modest scour depths of 0.25 pile diameters can be detected