Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Data-driven Fault Detection and Diagnosis for HVAC water chillers

Faulty operations of Heating, Ventilation and Air Conditioning (HVAC) chiller systems can lead to discomfort for the users, energy wastage, system unreliability and shorter equipment life. Faults need to be early diagnosed to prevent further deterioration of the system behaviour and energy losses. Since it is not a common practice to collect historical data regarding unforeseen phenomena and abnormal behaviours for HVAC installations, in this paper, a semi-supervised data-driven approach is employed for fault detection and isolation that makes no use of a priori knowledge about abnormal phenomena. The proposed method exploits Principal Component Analysis (PCA) to distinguish anomalies from normal operation variability and a reconstruction-based contribution approach to isolate variables related to faults. The diagnosis task is then tackled by means of a decision table that associates the influence of faults to certain characteristic features. The Fault Detection and Diagnosis (FDD) algorithm performance is assessed by exploiting experimental datasets from two types of water chiller systems

Leveraging demand flexibility by exploiting prosumer response to price signals in microgrids

The diffusion of distributed energy resources in distribution networks requires new approaches to exploit the users' capabilities of providing ancillary services. Of particular interest will be the coordination of microgrids operating as an aggregate of demand and supply units. This work reports a model predictive control (MPC) application in microgrids for the efficient energy management of energy storage systems and photovoltaic units. The MPC minimizes the economic cost of aggregate prosumers into a prediction horizon by forecasting generation and absorption profiles. The MPC is compared in realistic conditions with a heuristic strategy that acts in a instant manner, without taking into account signals prediction. The work aims at investigating the effect that different types of energy tariffs have in enhancing the end-users' flexibility, based on three examples of currently applied tariffs, comparing the two storage control modes. The MPC always achieves a better solution than the heuristic approach in all considered scenarios from the cost minimization point of view, with an improvement that is amplified by increasing the energy price variations between peak and off-peak periods. Furthermore, the MPC approach provides a cost saving when compared to the case considering a microgrid endowed with only photovoltaic units, in which no storage is installed. Findings in this work confirm that storage units better perform when some knowledge of future demand and supply trends is provided, ensuring an economic cost saving and an important service for the overall community

Evolutionarily conserved requirement of Cdx for post-occipital tissue emergence

Mouse Cdx genes are involved in axial patterning and partial Cdx mutants exhibit posterior embryonic defects. We found that mouse embryos in which all three Cdx genes are inactivated fail to generate any axial tissue beyond the cephalic and occipital primordia. Anterior axial tissues are laid down and well patterned in Cdx null embryos, and a 3' Hox gene is initially transcribed and expressed in the hindbrain normally. Axial elongation stops abruptly at the post-occipital level in the absence of Cdx, as the posterior growth zone loses its progenitor activity. Exogenous Fgf8 rescues the posterior truncation of Cdx mutants, and the spectrum of defects of Cdx null embryos matches that resulting from loss of posterior Fgfr1 signaling. Our data argue for a main function of Cdx in enforcing trunk emergence beyond the Cdx-independent cephalo-occipital region, and for a downstream role of Fgfr1 signaling in this function. Cdx requirement for the post-head section of the axis is ancestral as it takes place in arthropods as well