Soft ionic conductors have enabled stretchable and transparent devices, but liquids in such devices tend to leak and evaporate. In this study, we demonstrate diodes and transistors using liquid-free ionoelastomers, in which either anions or cations are fixed to an elastomer network and the other ionic species are mobile. The junction of the two ionoelastomers of opposite polarity yields an ionic double layer, which is capable of rectifying and switching ionic currents without electrochemical reactions. The entropically driven depletion of mobile ions creates a junction of tough adhesion, and the stretchability of the junction enables electromechanical transduction. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.One-dimensional electronic systems can support exotic collective phases because of the enhanced role of electron correlations. We describe the experimental observation of a series of quantized conductance steps within strongly interacting electron waveguides formed at the lanthanum aluminate-strontium titanate (LaAlO3/SrTiO3) interface. The waveguide conductance follows a characteristic sequence within Pascal's triangle (1, 3, 6, 10, 15, …) ⋅ e 2 /h, where e is the electron charge and h is the Planck constant. This behavior is consistent with the existence of a family of degenerate quantum liquids formed from bound states of n = 2, 3, 4, … electrons. Our experimental setup could provide a setting for solid-state analogs of a wide range of composite fermionic phases. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Effector-triggered immunity (ETI), induced by host immune receptors in response to microbial effectors, protects plants against virulent pathogens. However, a systematic study of ETI prevalence against species-wide pathogen diversity is lacking. We constructed the Pseudomonas syringae Type III Effector Compendium (PsyTEC) to reduce the pan-genome complexity of 5127 unique effector proteins, distributed among 70 families from 494 strains, to 529 representative alleles. We screened PsyTEC on the model plant Arabidopsis thaliana and identified 59 ETI-eliciting alleles (11.2%) from 19 families (27.1%), with orthologs distributed among 96.8% of P. syringae strains. We also identified two previously undescribed host immune receptors, including CAR1, which recognizes the conserved effectors AvrE and HopAA1, and found that 94.7% of strains harbor alleles predicted to be recognized by either CAR1 or ZAR1. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Clonal animals do not sequester a germ line during embryogenesis. Instead, they have adult stem cells that contribute to somatic tissues or gametes. How germ fate is induced in these animals, and whether this process is related to bilaterian embryonic germline induction, is unknown. We show that transcription factor AP2 (Tfap2), a regulator of mammalian germ lines, acts to commit adult stem cells, known as i-cells, to the germ cell fate in the clonal cnidarian Hydractinia symbiolongicarpus Tfap2 mutants lacked germ cells and gonads. Transplanted wild-type cells rescued gonad development but not germ cell induction in Tfap2 mutants. Forced expression of Tfap2 in i-cells converted them to germ cells. Therefore, Tfap2 is a regulator of germ cell commitment across germ line-sequestering and germ line-nonsequestering animals. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.In the aftermath of trauma, little is known about why the unwanted and unbidden recollection of traumatic memories persists in some individuals but not others. We implemented neutral and inoffensive intrusive memories in the laboratory in a group of 102 individuals exposed to the 2015 Paris terrorist attacks and 73 nonexposed individuals, who were not in Paris during the attacks. While reexperiencing these intrusive memories, nonexposed individuals and exposed individuals without posttraumatic stress disorder (PTSD) could adaptively suppress memory activity, but exposed individuals with PTSD could not. These findings suggest that the capacity to suppress memory is central to positive posttraumatic adaptation. A generalized disruption of the memory control system could explain the maladaptive and unsuccessful suppression attempts often seen in PTSD, and this disruption should be targeted by specific treatments. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.PURPOSE To determine the pharmacodynamic relationship between target occupancy of Bruton's tyrosine kinase (BTK) and inhibition of downstream signaling. https://www.selleckchem.com/products/lw-6.html EXPERIMENTAL DESIGN Patients with Chronic Lymphocytic Leukemia (CLL) enrolled on a phase 2 clinical trial (NCT02337829) with the covalent, selective BTK inhibitor acalabrutinib donated blood samples for pharmacodynamic analyses. Study design included randomization to acalabrutinib 100mg twice daily or 200mg once daily and dose interruptions on day 4 and 5 of the first week. BTK occupancy and readouts of intracellular signaling were assessed sequentially between 4 and 48 hours from last dose. RESULTS Four hours from last dose, BTK occupancy exceeded 96% and at trough, was higher with twice daily, median 95.3%, than with once daily dosing, median 87.6% (p less than 0.0001). By 48 hours from last dose median free BTK increased to 25.6%. Due to covalent binding of acalabrutinib, free BTK is generated by de novo synthesis. The estimated rate of BTK synthesis varied widely between patients ranging from 3.6% to 31.4% per day. Acalabrutinib reduced phosphorylation of BTK and inhibited downstream BCR and NF-κB signaling. During dosing interruptions up to 48 hours, expression of BCR target genes rebounded, while phosphorylation of signaling molecules remained repressed. In vitro crosslinking of IgM on CLL cells obtained 36 to 48 hours from last dose upregulated CD69, with high correlation between cellular free BTK and response (R=0.7, p≤0.0001). CONCLUSIONS Higher BTK occupancy was achieved with twice daily over once daily dosing, resulting in deeper and more sustained inhibition of BCR signaling. Copyright ©2020, American Association for Cancer Research.