Ultrathick battery electrodes are appealing as they reduce the fraction of inactive battery parts such as current collectors and separators. However, thick electrodes are difficult to dry and tend to crack or flake during production. Moreover, the electrochemical performance of thick electrodes is constrained by ion and electron transport as well as fast capacity degradation. Here, we report a thermally induced phase separation (TIPS) process for fabricating thick Li-ion battery electrodes, which incorporates the electrolyte directly in the electrode and alleviates the need to dry the electrode. The proposed TIPS process creates a bicontinuous electrolyte and electrode network with excellent ion and electron transport, respectively, and consequently achieves better rate performance. Using this process, electrodes with areal capacities of more than 30 mAh/cm2 are demonstrated. Capacity retentions of 87% are attained over 500 cycles in full cells with 1-mm-thick anodes and cathodes. Finally, we verified the scalability of the TIPS process by coating thick electrodes continuously on a pilot-scale roll-to-roll coating tool.A method for decision tree induction is presented. Given a set of predictor variables [Formula see text] and two outcome variables y and z associated with each x, the goal is to identify those values of x for which the respective distributions of [Formula see text] and [Formula see text], or selected properties of those distributions such as means or quantiles, are most different. Contrast trees provide a lack-of-fit measure for statistical models of such statistics, or for the complete conditional distribution [Formula see text], as a function of x. They are easily interpreted and can be used as diagnostic tools to reveal and then understand the inaccuracies of models produced by any learning method. A corresponding contrast-boosting strategy is described for remedying any uncovered errors, thereby producing potentially more accurate predictions. This leads to a distribution-boosting strategy for directly estimating the full conditional distribution of y at each x under no assumptions concerning its shape, form, or parametric representation.Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system. The IL-12 family of cytokines has four members, which are IL-12 (p40p35), IL-23 (p40p19), the p40 monomer (p40), and the p40 homodimer (p402). Since all four members contain p40 in different forms, it is important to use a specific monoclonal antibody (mAb) to characterize these molecules. Here, by using such mAbs, we describe selective loss of p40 in serum of MS patients as compared to healthy controls. Similarly, we also observed decrease in p40 and increase in IL-12, IL-23, and p402 in serum of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as compared to control mice. Interestingly, weekly supplementation of mouse and human recombinant p40 ameliorated clinical symptoms and disease progression of EAE. On the other hand, IL-12, IL-23, and p402 did not exhibit such inhibitory effect. In addition to EAE, p40 also suppressed collagen-induced arthritis in mice. Using IL-12Rβ1-/-, IL-12Rβ2-/-, and IL-12Rβ1+/-/IL-12Rβ2-/- mice, we observed that p40 required IL-12Rβ1, but not IL-12Rβ2, to suppress EAE. Interestingly, p40 arrested IL-12-, IL-23-, or p402-mediated internalization of IL-12Rβ1, but neither IL-12Rβ2 nor IL-23R, protected regulatory T cells, and suppressed Th1 and Th17 biasness. These studies identify p40 as an anti-autoimmune cytokine with a biological role different from IL-12, IL-23, and p402 in which it attenuates autoimmune signaling via suppression of IL-12Rβ1 internalization, which may be beneficial in patients with MS and other autoimmune disorders.Transitions from health to disease are characterized by dysregulation of biological networks under the influence of genetic and environmental factors, often over the course of years to decades before clinical symptoms appear.  https://www.selleckchem.com/products/oligomycin-a.html  Understanding these dynamics has important implications for preventive medicine. However, progress has been hindered both by the difficulty of identifying individuals who will eventually go on to develop a particular disease and by the inaccessibility of most disease-relevant tissues in living individuals. Here we developed an alternative approach using polygenic risk scores (PRSs) based on genome-wide association studies (GWAS) for 54 diseases and complex traits coupled with multiomic profiling and found that these PRSs were associated with 766 detectable alterations in proteomic, metabolomic, and standard clinical laboratory measurements (clinical labs) from blood plasma across several thousand mostly healthy individuals. We recapitulated a variety of known relationships (e.g., glutamatergic neurotransmission and inflammation with depression, IL-33 with asthma) and found associations directly suggesting therapeutic strategies (e.g., Ω-6 supplementation and IL-13 inhibition for amyotrophic lateral sclerosis) and influences on longevity (leukemia inhibitory factor, ceramides). Analytes altered in high-genetic-risk individuals showed concordant changes in disease cases, supporting the notion that PRS-associated analytes represent presymptomatic disease alterations. Our results provide insights into the molecular pathophysiology of a range of traits and suggest avenues for the prevention of health-to-disease transitions.
  To develop a diagnostic model based on plasma-derived extracellular vesicle (EV) subpopulations in Parkinson disease (PD) and atypical parkinsonism (AP), we applied an innovative flow cytometric multiplex bead-based platform.
 
  Plasma-derived EVs were isolated from PD, matched healthy controls, multiple system atrophy (MSA), and AP with tauopathies (AP-Tau). The expression levels of 37 EV surface markers were measured by flow cytometry and correlated with clinical scales. A diagnostic model based on EV surface markers expression was built via supervised machine learning algorithms and validated in an external cohort.
 
  Distinctive pools of EV surface markers related to inflammatory and immune cells stratified patients according to the clinical diagnosis. PD and MSA displayed a greater pool of overexpressed immune markers, suggesting a different immune dysregulation in PD and MSA vs AP-Tau. The receiver operating characteristic curve analysis of a compound EV marker showed optimal diagnostic performance for PD (area under the curve [AUC] 0.