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Highlights d Activation of the mitochondrial ClpP induces p53independent cancer cell lethality d Imipridones are allosteric agonists of ClpP, being tested in human clinical trials d ClpP activation increases proteolysis of mitochondrial proteins d ClpP-mediated mitochondrial proteolysis impairs mitochondrial respiratory function

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General interest paragraph (max 200 words)Energy-efficient water desalination is essential for the economical use of groundwater and other water resources for industry, agriculture, human consumption and household applications. Here, an extensive data set is presented for the energy consumption of a novel water desalination technology, called membrane capacitive deionization (MCDI). This data set is an essential tool to assess the economic viability of MCDI. Also, we introduce an improved operation mode of MCDI in which freshwater of a constant salt concentration is produced, i.e., unvarying in time. The salt level in the produced freshwater can be tuned precisely using the electrical current and water flow rate as direct control parameters. AbstractMembrane capacitive deionization (MCDI) is a water desalination technology based on applying a cell voltage between two oppositely placed porous electrodes sandwiching a spacer channel that transports the water to be desalinated. In the salt removal step, ions are adsorbed at the carbon-water interface within the micropores inside the porous electrodes. After the electrodes reach a certain adsorption capacity, the cell voltage is reduced or even reversed, which leads to ion release from the electrodes and a concentrated salt solution in the spacer channel, which is flushed out, after which the cycle can start over again. Ion-exchange membranes are positioned in front of each porous electrode which has the advantage that co-ions are prevented from leaving the electrode region during ion adsorption, while also allowing for ion desorption at reversed voltage. Both effects significantly increase the salt removal capacity of the system per cycle.The classical operation mode of MCDI at a constant cell voltage results in an effluent stream of desalinated water of which the salt concentration varies with time. In this paper, we propose a different operational mode for MCDI, whereby desalination is driven by a constant electrical current, which leads to a constant salt concentration in the desalinated stream over long periods of time. Furthermore, we show how the salt concentration of the desalinated stream can be accurately adjusted to a certain setpoint, by either varying the electrical current level and/or the water flowrate.Finally, we present an extensive data set for the energy requirements of MCDI, both for operation at constant voltage, and at constant current, and in both cases also for the related technology in which membranes are not included (CDI). We find consistently that in MCDI the energy consumption per mole of salt removed is lower than in CDI. Within the range 10-200 mM ionic strength of the water to be 2 treated, we find for MCDI a constant energy consumption of ~22 kT per ion removed. Results in this work are an essential tool to evaluate the economic viability of MCDI for the treatment of saltwater.

T-cell costimulation and coinhibition generated by engagement of the B7 family and their receptor CD28 family are of central importance in regulating the T-cell response, making these pathways very attractive therapeutic targets. Here we describe HERV-H LTRassociating protein 2 (HHLA2) as a member of the B7 family that shares 10-18% amino acid identity and 23-33% similarity to other human B7 proteins and phylogenetically forms a subfamily with B7x and B7-H3 within the family. HHLA2 is expressed in humans but not in mice, which is unique within the B7 and CD28 families. HHLA2 protein is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation with LPS and IFN-γ. HHLA2 does not interact with other known members of the CD28 family or the B7 family, but does bind a putative receptor that is constitutively expressed not only on resting and activated CD4 and CD8 T cells but also on antigen-presenting cells. HHLA2 inhibits proliferation of both CD4 and CD8 T cells in the presence of T-cell receptor signaling. In addition, HHLA2 significantly reduces cytokine production by T cells including IFN-γ, TNF-α, IL-5, IL-10, IL-13, IL-17A, and IL-22. Thus, we have identified a unique B7 pathway that is able to inhibit human CD4 and CD8 T-cell proliferation and cytokine production. This unique human T-cell coinhibitory pathway may afford unique strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may help to design better vaccines. Interactions between members of the B7 ligand and CD28 receptor families generate positive costimulation and negative coinhibition, which are of central importance in regulating T-cell responses (1-3). B7-1/B7-2/CD28/CTLA-4 is the most extensively characterized of these pathways. Ligands B7-1 (CD80) and B7-2 (CD86) on antigen-presenting cells (APCs) bind to CD28 on naïve T cells and provide a major costimulatory signal to activate naïve T cells. After the initial activation, coinhibitory molecule cytotoxic T lymphocyte antigen-4 (CTLA-4, CD152) is induced on T cells and engages the same B7-1 and B7-2 ligands to restrain T-cell function. In contrast to the costimulatory activity of CD28, the interaction of B7-1 or B7-2 with CTLA-4 is essential for limiting the proliferative response of recently activated T cells to antigen and CD28-mediated costimulation.During the past decade, several new pathways in the B7 and CD28 families have been identified, including B7h/ICOS, PD-L1/PD-L2/PD-1, B7-H3/receptor, and B7x/receptor. B7h (4) (also called ICOS-L, B7RP-1 (5), GL50 (6), B7H2 (7), LCOS (8), and CD275) binds to the inducible costimulator (ICOS, CD278) on activated T cells (9), which induces strong phosphatidylinositol 3-kinase activity (10, 11) and leads to the expression of transcription factors involved in follicular helper CD4 T (Tfh) differentiation (12). Therefore, the B7h/ICOS pathway provides critical T-cell help to B cells. Deficiencies in this pathway result in substantially reduced numbers of mem...