Research synthesis, translation and implementation of non-invasive liver tests

The development of medical diagnostic tests has been an exciting field of research, filled with enormous potential and, at the same time, uncertainty. Despite the great enthusiasm and substantial investment in the biomarker development, there is a paucity of approved diagnostic tests in the clinic. One explanation for this imbalance can be the complicated path for biomarkers from bench to bedside. This lengthy and costly process can be challenging and even frustrating, not only for the test developers, but also for researchers and clinicians. This thesis report studies that highlighted the challenges in the biomarker evaluation field. We observed that in addition to the common methodological challenges in health research, evidence synthesis for evaluating medical tests may face added challenges in many cases. For instance, when more than one threshold is reported by each primary study in a meta-analysis of accuracy studies or when a reference standard is imperfect, or a gold standard is missing (Chapter 2-4). We also observed that in addition to the limitations of risk-of-bias assessments in comparative accuracy studies, these studies commonly miss or incompletely report essential information about comparisons, which may mislead the interpretation of the findings (Chapter 5-7). Moreover, our findings showed that implementation of the medical diagnostic tests in clinical practice is a complex and challenging process, which can be promoted and hindered by different factors (Chapter 8). These resulting findings offer a starting point for improving current research practices in evaluation and implementation of biomarker-based tests

Model Predictive Active Power Control for Optimal Structural Load Equalization in Waked Wind Farms

In this paper, we propose a model predictive active power control (APC) enhanced by the optimal coordination of the structural loadings of wind turbines operating with fully developed wind farm flows that have extensive interactions with the atmospheric boundary layer. In general, the APC problem, that is, distributing a wind farm power reference among the operating wind turbines, does not have a unique solution; this fact can be exploited for structural load alleviation of the individual wind turbines. Therefore, we formulated a constrained optimization problem to simultaneously minimize the wind farm power reference tracking errors and the structural load deviations of the wind turbines from their mean value. Thewind power plant is represented by a dynamic 3D large&ndash;eddy simulation model, whereas the predictive controller employs a simplified, computationally inexpensive model to predict the dynamic power and load responses of the turbines that experience turbulent wind farm flows and wakes. An adjoint approach is an efficient tool used to iteratively compute the gradient of the formulated parameter-varying optimal control problem over a finite prediction horizon. We have discussed the applicability, key features, and computational complexity of the controller by using a wind farm example consisting of 3�4 turbines with different wake interactions for each row. The performance of the proposed adjoint&ndash;based model predictive control for APC was evaluated by measuring power reference tracking errors and the corresponding damage equivalent fatigue loads of the wind turbine towers; we compared our proposed control design with recently published proportional&ndash;integral&ndash;based APC approaches.</p

An active power control approach for wake-induced load alleviation in a fully developed wind farm boundary layer

This paper studies a closed-loop wind farm control framework for active power control (APC) with a simultaneous reduction of wake-induced structural loads within a fully developed wind farm flow interacting with the atmospheric boundary layer. The main focus is on a classical feedback control, which features a simple control architecture and a practical measurement system that are realizable for real-time control of large wind farms. We demonstrate that the wake-induced structural loading of the downstream turbines can be alleviated, while the wind farm power production follows a reference signal. A closed-loop APC is designed first to improve the power-tracking performance against wake-induced power losses of the downwind turbines. Then, the nonunique solution of APC for the wind farm is exploited for aggregated structural load alleviation. The axial induction factors of the individual wind turbines are considered control inputs to limit the power production of the wind farm or to switch to greedy control when the demand exceeds the power available in the wind. Furthermore, the APC solution domain is enlarged by an adjustment of the power set-points according to the locally available power at the waked wind turbines. Therefore, the controllability of the wind turbines is improved for rejecting the intensified load fluctuations inside the wake. A large-eddy simulation model is employed for resolving the turbulent flow, the wake structures, and its interaction with the atmospheric boundary layer. The applicability and key features of the controller are discussed with a wind farm example consisting of 3×4 turbines with different wake interactions for each row. The performance of the proposed APC is evaluated using the accuracy of the wind farm power tracking and the wake-induced damage equivalent fatigue loads of the towers of the individual wind turbines.</p

Peroxisome division in the yeast Yarrowia lipolytica is regulated by a signal from inside the peroxisome

We describe an unusual mechanism for organelle division. In the yeast Yarrowia lipolytica, only mature peroxisomes contain the complete set of matrix proteins. These mature peroxisomes assemble from several immature peroxisomal vesicles in a multistep pathway. The stepwise import of distinct subsets of matrix proteins into different immature intermediates along the pathway causes the redistribution of a peroxisomal protein, acyl-CoA oxidase (Aox), from the matrix to the membrane. A significant redistribution of Aox occurs only in mature peroxisomes. Inside mature peroxisomes, the membrane-bound pool of Aox interacts with Pex16p, a membrane-associated protein that negatively regulates the division of early intermediates in the pathway. This interaction inhibits the negative action of Pex16p, thereby allowing mature peroxisomes to divide

An active power control approach for wake-induced load alleviation in a fully developed wind farm boundary layer

This paper studies a closed-loop wind farm control framework for active power control (APC) with a simultaneous reduction of wake-induced structural loads within a fully developed wind farm flow interacting with the atmospheric boundary layer. The main focus is on a classical feedback control, which features a simple control architecture and a practical measurement system that are realizable for real-time control of large wind farms. We demonstrate that the wake-induced structural loading of the downstream turbines can be alleviated, while the wind farm power production follows a reference signal. A closed-loop APC is designed first to improve the power-tracking performance against wake-induced power losses of the downwind turbines. Then, the nonunique solution of APC for the wind farm is exploited for aggregated structural load alleviation. The axial induction factors of the individual wind turbines are considered control inputs to limit the power production of the wind farm or to switch to greedy control when the demand exceeds the power available in the wind. Furthermore, the APC solution domain is enlarged by an adjustment of the power set-points according to the locally available power at the waked wind turbines. Therefore, the controllability of the wind turbines is improved for rejecting the intensified load fluctuations inside the wake. A large-eddy simulation model is employed for resolving the turbulent flow, the wake structures, and its interaction with the atmospheric boundary layer. The applicability and key features of the controller are discussed with a wind farm example consisting of 3&times;4 turbines with different wake interactions for each row. The performance of the proposed APC is evaluated using the accuracy of the wind farm power tracking and the wake-induced damage equivalent fatigue loads of the towers of the individual wind turbines. </div

Adjoint-based model predictive control for optimal energy extraction in waked wind farms

In this paper, a model predictive control (MPC) is proposed for wind farms to minimize wake-induced power losses. A constrained optimization problem is formulated to maximize the total power production of a wind farm. The developed controller employs a two-dimensional dynamic wind farm model to predict wake interactions in advance. An adjoint approach as an efficient tool is utilized to compute the gradient of the performance index for such a large-scale system. The wind turbine axial induction factors are considered as the control inputs to influence the overall performance by taking the wake interactions into account. A layout of a 2 &times; 3 wind farm is considered in this study. The parameterization of the controller is discussed in detail for a practical optimal energy extraction. The performance of the adjoint-based model predictive control (AMPC) is investigated with time-varying changes in wind direction. The simulation results show the effectiveness of the proposed approach. The computational complexity of the developed AMPC is also outlined with respect to the real time control implementation. </div

The relativistic Sagnac Effect: two derivations

The phase shift due to the Sagnac Effect, for relativistic matter and electromagnetic beams, counter-propagating in a rotating interferometer, is deduced using two different approaches. From one hand, we show that the relativistic law of velocity addition leads to the well known Sagnac time difference, which is the same independently of the physical nature of the interfering beams, evidencing in this way the universality of the effect. Another derivation is based on a formal analogy with the phase shift induced by the magnetic potential for charged particles travelling in a region where a constant vector potential is present: this is the so called Aharonov-Bohm effect. Both derivations are carried out in a fully relativistic context, using a suitable 1+3 splitting that allows us to recognize and define the space where electromagnetic and matter waves propagate: this is an extended 3-space, which we call "relative space". It is recognized as the only space having an actual physical meaning from an operational point of view, and it is identified as the 'physical space of the rotating platform': the geometry of this space turns out to be non Euclidean, according to Einstein's early intuition.Comment: 49 pages, LaTeX, 3 EPS figures. Revised (final) version, minor corrections; to appear in "Relativity in Rotating Frames", ed. G. Rizzi and M.L. Ruggiero, Kluwer Academic Publishers, Dordrecht, (2003). See also http://digilander.libero.it/solciclo

The relevance of nanoscale biological fragments for ice nucleation in clouds

Most studies of the role of biological entities as atmospheric ice-nucleating particles have focused on relatively rare supermicron particles such as bacterial cells, fungal spores and pollen grains. However, it is not clear that there are sufficient numbers of these particles in the atmosphere to strongly influence clouds. Here we show that the ice-nucleating activity of a fungus from the ubiquitous genus Fusarium is related to the presence of nanometre-scale particles which are far more numerous, and therefore potentially far more important for cloud glaciation than whole intact spores or hyphae. In addition, we quantify the ice-nucleating activity of nano-ice nucleating particles (nano-INPs) washed off pollen and also show that nano-INPs are present in a soil sample. Based on these results, we suggest that there is a reservoir of biological nano-INPs present in the environment which may, for example, become aerosolised in association with fertile soil dust particles

Thermodynamics of heterogeneous crystal nucleation in contact and immersion modes

One of most intriguing problems of heterogeneous crystal nucleation in droplets is its strong enhancement in the contact mode (when the foreign particle is presumably in some kind of contact with the droplet surface) compared to the immersion mode (particle immersed in the droplet). Many heterogeneous centers have different nucleation thresholds when they act in contact or immersion modes, indicating that the mechanisms may be actually different for the different modes. Underlying physical reasons for this enhancement have remained largely unclear. In this paper we present a model for the thermodynamic enhancement of heterogeneous crystal nucleation in the contact mode compared to the immersion one. To determine if and how the surface of a liquid droplet can thermodynamically stimulate its heterogeneous crystallization, we examine crystal nucleation in the immersion and contact modes by deriving and comparing with each other the reversible works of formation of crystal nuclei in these cases. As a numerical illustration, the proposed model is applied to the heterogeneous nucleation of Ih crystals on generic macroscopic foreign particles in water droplets at T=253 K. Our results show that the droplet surface does thermodynamically favor the contact mode over the immersion one. Surprisingly, our numerical evaluations suggest that the line tension contribution to this enhancement from the contact of three water phases (vapor-liquid-crystal) may be of the same order of magnitude as or even larger than the surface tension contribution