93-0.98)), and had more contacts to general practice (IRR = 1.14 (95% CI 1.07-1.21)) and hospitals for lung diseases (IRR = 2.39 (95% CI 1.96-5.85)) compared to the reference group. We found an association between lung function and the future burden of lung diseases throughout 27 years of follow-up. In particular, adults with an FEV1/FVC 70-75 need extra attention in the case finding.Near-infrared (NIR) fluorescent probes are among the most attractive chemical tools for biomedical imaging. However, their in vivo applications are hindered by albumin binding, generating unspecific fluorescence that masks the specific signal from the analyte. Here, combining experimental and docking methods, we elucidate that the reason for this problem is an acceptor (A) group-mediated capture of the dyes into hydrophobic pockets of albumin. This pocket-capturing phenomenon commonly applies to dyes designed under the twisted intramolecular charge-transfer (TICT) principle and, therefore, represents a generic but previously unidentified backdoor problem. Accordingly, we create a new A group that avoids being trapped into the albumin pockets (pocket-escaping) and thereby construct a NIR probe, BNLBN, which effectively prevents this backdoor problem with increased imaging accuracy for liver fibrosis in vivo. Overall, our study explains and overcomes a fundamental problem for the in vivo application of a broad class of bioimaging tools.Cities evolve through phases of construction, demolition, vacancy, and redevelopment, each impacting water movement at the land surface by altering soil hydrologic properties, land cover, and topography. Currently unknown is whether the variable physical and vegetative characteristics associated with vacant parcels and introduced by demolition may absorb rainfall and thereby diminish stormwater runoff. To investigate this, we evaluate how vacant lots modulate citywide hydrologic partitioning by synthesizing a novel field dataset across 500+ parcels in Buffalo, New York, USA. Vacant lot infiltration rates vary widely (0.001 to 5.39 cm h-1), though parcels are generally well-vegetated and gently sloped. Extending field estimates to 2400 vacant parcels, we estimate that vacant lands citywide may cumulatively infiltrate 51-54% additional annual rainfall volume as compared to pre-demolition state, in part by reducing and disconnecting impervious areas. Our findings differentiate vacant lots as purposeful landscapes that can alleviate large water fluxes into aging wastewater infrastructure.Voltage-gated K+ channels function in macromolecular complexes with accessory subunits to regulate brain function. Here, we describe a peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1)-dependent mechanism that regulates the association of the A-type K+ channel subunit Kv4.2 with its auxiliary subunit dipeptidyl peptidase 6 (DPP6), and thereby modulates neuronal excitability and cognitive flexibility. We show that activity-induced Kv4.2 phosphorylation triggers Pin1 binding to, and isomerization of, Kv4.2 at the pThr607-Pro motif, leading to the dissociation of the Kv4.2-DPP6 complex.  https://www.selleckchem.com/products/ms-275.html  We generated a novel mouse line harboring a knock-in Thr607 to Ala (Kv4.2TA) mutation that abolished dynamic Pin1 binding to Kv4.2. CA1 pyramidal neurons of the hippocampus from these mice exhibited altered Kv4.2-DPP6 interaction, increased A-type K+ current, and reduced neuronal excitability. Behaviorally, Kv4.2TA mice displayed normal initial learning but improved reversal learning in both Morris water maze and lever press paradigms. These findings reveal a Pin1-mediated mechanism regulating reversal learning and provide potential targets for the treatment of neuropsychiatric disorders characterized by cognitive inflexibility.CCL5 is a unique chemokine with distinct stage and cell-type specificities for regulating inflammation, but how these specificities are achieved and how CCL5 modulates immune responses is not well understood. Here we identify two stage-specific enhancers the proximal enhancer mediates the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35 Mb from the promoter induces CCL5 expression in activated cells. Both enhancers are antagonized by RUNX/CBFβ complexes, and SATB1 further mediates the long-distance interaction of the distal enhancer with the promoter. Deletion of the proximal enhancer decreases CCL5 expression and augments the cytotoxic activity of tissue-resident T and NK cells, which coincides with reduced melanoma metastasis in mouse models. By contrast, increased CCL5 expression resulting from RUNX3 mutation is associated with more tumor metastasis in the lung. Collectively, our results suggest that RUNX3-mediated CCL5 repression is critical for modulating anti-tumor immunity.Spiking neural networks exploit spatiotemporal processing, spiking sparsity, and high interneuron bandwidth to maximize the energy efficiency of neuromorphic computing. While conventional silicon-based technology can be used in this context, the resulting neuron-synapse circuits require multiple transistors and complicated layouts that limit integration density. Here, we demonstrate unprecedented electrostatic control of dual-gated Gaussian heterojunction transistors for simplified spiking neuron implementation. These devices employ wafer-scale mixed-dimensional van der Waals heterojunctions consisting of chemical vapor deposited monolayer molybdenum disulfide and solution-processed semiconducting single-walled carbon nanotubes to emulate the spike-generating ion channels in biological neurons. Circuits based on these dual-gated Gaussian devices enable a variety of biological spiking responses including phasic spiking, delayed spiking, and tonic bursting. In addition to neuromorphic computing, the tunable Gaussian response has significant implications for a range of other applications including telecommunications, computer vision, and natural language processing.Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important to breast physiology and tumorigenesis, remains unclear. Here we report that both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche. In vitro, ADAMTS18 cleaves fibronectin; in vivo, Adamts18 deletion causes increased collagen deposition during puberty, which results in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell function. Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation.