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Monitoring a large population of dynamic processes with limited resources presents a significant challenge across various industrial sectors. This is due to 1) the inherent disparity between the available monitoring resources and the extensive number of processes to be monitored and 2) the unpredictable and heterogeneous dynamics inherent in the progression of these processes. Online learning approaches, commonly referred to as bandit methods, have demonstrated notable potential in addressing this issue by dynamically allocating resources and effectively balancing the exploitation of high-reward processes and the exploration of uncertain ones. However, most online learning algorithms are designed for 1) a centralized setting that requires data sharing across processes for accurate predictions or 2) a homogeneity assumption that estimates a single global model from decentralized data. To overcome these limitations and enable online learning in a heterogeneous population under a decentralized setting, we propose a federated collaborative online monitoring method. Our approach utilizes representation learning to capture the latent representative models within the population and introduces a novel federated collaborative UCB algorithm to estimate these models from sequentially observed decentralized data. This strategy facilitates informed monitoring of resource allocation. The efficacy of our method is demonstrated through theoretical analysis, simulation studies, and its application to decentralized cognitive degradation monitoring in Alzheimer’s disease. 

Abstract Androgen-independent prostate cancers, correlated with heightened aggressiveness and poor prognosis, are caused by mutations or deletions in the androgen receptor (AR) or expression of truncated variants of AR that are constitutively activated. Currently, drugs and drug candidates against AR target the steroid-binding domain to antagonize or degrade AR. However, these compounds cannot therapeutically access largely intrinsically disordered truncated splice variants of AR, such as AR-V7, that only possess the DNA binding domain and are missing the ligand binding domain. Targeting intrinsically disordered regions within transcription factors has remained challenging and is considered “undruggable”. Herein, we leveraged a cysteine-reactive covalent ligand library in a cellular screen to identify degraders of AR and AR-V7 in androgen-independent prostate cancer cells. We identified a covalent compound EN1441 that selectively degrades AR and AR-V7 in a proteasome-dependent manner through direct covalent targeting of an intrinsically disordered cysteine C125 in AR and AR-V7. EN1441 causes significant and selective destabilization of AR and AR-V7, leading to aggregation of AR/AR-V7 and subsequent proteasome-mediated degradation. Consistent with targeting both AR and AR-V7, we find that EN1441 completely inhibits total AR transcriptional activity in androgen-independent prostate cancer cells expressing both AR and AR-V7 compared to AR antagonists or degraders that only target the ligand binding domain of full-length AR, such as enzalutamide and ARV-110. Our results put forth a pathfinder molecule EN1441 that targets an intrinsically disordered cysteine within AR to destabilize, degrade, and inhibit both AR and AR-V7 in androgen-independent prostate cancer cells and highlights the utility of covalent ligand discovery approaches in directly targeting, destabilizing, inhibiting, and degrading classically undruggable transcription factor targets. 

Abstract The penstemons are ornamental annual flowering plants native to the Intermountain West and Rocky Mountains and commonly used for urban landscaping. Elite commercial penstemons are generally susceptible to abiotic stresses, including drought, root rot, cold, and high salinity. Firecracker penstemon (Penstemon eatonii), however, is much more tolerant to these stresses than most elite cultivars. Importantly, firecracker penstemon has been reported to hybridize with many other penstemons and therefore provides the opportunity to develop more tolerant elite cultivars through strategic crossing. To facilitate the study and utilization of firecracker penstemon, we sequenced and annotated the genome of a P. eatonii accession collected from Utah, United States. We also performed low-coverage whole-genome sequencing of 26 additional accessions from three different varieties of P. eatonii. This chromosome-scale genome assembly is the most contiguous and complete Penstemon genome sequenced to date. 

Abstract Manipulating surface charge, electric field, and plasma afterglow in a non-equilibrium plasma is critical to control plasma-surface interaction for plasma catalysis and manufacturing. Here, we show enhancements of surface charge, electric field during breakdown, and afterglow by ferroelectric barrier discharge. The results show that the ferroelectrics manifest spontaneous electric polarization to increase the surface charge by two orders of magnitude compared to discharge with an alumina barrier. Time-resolved in-situ electric field measurements reveal that the fast polarization of ferroelectrics enhances the electric field during the breakdown in streamer discharge and doubles the electric field compared to the dielectric barrier discharge. Moreover, due to the existence of surface charge, the ferroelectric electrode extends the afterglow time and makes discharge sustained longer when alternating the external electric field polarity. The present results show that ferroelectric barrier discharge offers a promising technique to tune plasma properties for efficient plasma catalysis and electrified manufacturing. 

Abstract Leaves of the carnivorous sundew plants (Droseraspp.) secrete mucilage that hosts microorganisms, but whether this microbiota contributes to prey digestion is unclear. We identified the acidophilic fungusAcrodontium crateriformeas the dominant species in the mucilage microbial communities, thriving in multiple sundew species across the global range. The fungus grows and sporulates on sundew glands as its preferred acidic environment, and its presence in traps increased the prey digestion process.A. crateriformehas a reduced genome similar to other symbiotic fungi. DuringA. crateriforme–Drosera spatulatacoexistence and digestion of prey insects, transcriptomes revealed significant gene co-option in both partners. Holobiont expression patterns during prey digestion further revealed synergistic effects in several gene families including fungal aspartic and sedolisin peptidases, facilitating prey digestion in leaves, as well as nutrient assimilation and jasmonate signalling pathway expression. This study establishes that botanical carnivory is defined by adaptations involving microbial partners and interspecies interactions. 

Abstract The theory of topological modular forms (TMF) predicts that elliptic genera of physical theories satisfy a certain divisibility property, determined by the theory’s gravitational anomaly. In this note we verify this prediction in Duncan’s supermoonshine module, as well as in tensor products and orbifolds thereof. Along the way we develop machinery for computing the elliptic genera of general alternating orbifolds and discuss the relation of this construction to the elusive “periodicity class” of TMF. 

Hydroxyl radical (·OH)-initiated oxidation of isoprene, the most abundant nonmethane hydrocarbon in the atmosphere, is responsible for substantial amounts of secondary organic aerosol (SOA) within ambient fine particles. Fine particulate 2-methyltetrol sulfate diastereoisomers (2-MTSs) are abundant SOA products formed via acid-catalyzed multiphase chemistry of isoprene-derived epoxydiols with inorganic sulfate aerosols under low-nitric oxide conditions. We recently demonstrated that heterogeneous ·OH oxidation of particulate 2-MTSs leads to the particle-phase formation of multifunctional organosulfates (OSs). However, it remains uncertain if atmospheric chemical aging of particulate 2-MTSs induces toxic effects within human lung cells. We show that inhibitory concentration-50 (IC50) values decreased from exposure to fine particulate 2-MTSs that were heterogeneously aged for 0 to 22 days by ·OH, indicating increased particulate toxicity in BEAS-2B lung cells. Lung cells further exhibited concentration-dependent modulation of oxidative stress- and inflammatory-related gene expression. Principal component analysis was carried out on the chemical mixtures and revealed positive correlations between exposure to aged multifunctional OSs and altered expression of targeted genes. Exposure to particulate 2-MTSs alone was associated with an altered expression of antireactive oxygen species (ROS)-related genes (NQO-1, SOD-2, and CAT) indicative of a response to ROS in the cells. Increased aging of particulate 2-MTSs by ·OH exposure was associated with an increased expression of glutathione pathway related genes (GCLM and GCLC) and an anti-inflammatory gene (IL-10). 

Abstract Non-equilibrium plasmas derive their low temperature reactivity from producing and driving energetic electrons and active species under large electric fields. Therefore, the impact of reactants on the plasma properties including electron number density, electric field, and electron temperature is critical for applications such as plasma methane (CH 4 ) reforming. Due to experimental complexity, electron properties and the electric field are rarely measured together in the same discharge. In this work, we combine time-resolved Thomson scattering and electric field induced second harmonic generation to probe electron temperature, electron density, and electric field strength in a 60 Torr CH 4 /Ar nanosecond-pulsed dielectric barrier discharge while varying the CH 4 mole fraction from 0% to 8%. These measurements are compared to a 1D numerical model to benchmark its predictions and identify areas of uncertainty. Nonlinear coupling between CH 4 addition, electron temperature, electron density, and the electric field was directly observed. Contrary to previous measurements in He, the electron temperature increased with CH 4 mole fraction. This rise in electron temperature is identified as electron heating by residual electric fields that increased with larger CH 4 mole fraction. Moreover, the electron number density has been found to decrease rapidly with the increase of methane mole fraction. Comparison of these measurements with the model yielded better agreement at higher CH 4 mole fractions and with the usage of ab initio calculated Ar electron-impact cross-sections from the B-spline R-matrix database. Furthermore, the calculated plasma properties are shown to be sensitive to the residual surface charge implanted on the quartz dielectric surfaces. Without considering surface charge in the simulations, the calculated electric field profiles agreed well with the measurements, but the electron properties were underpredicted by more than a factor of three. Therefore, measurements of either the electric field or electron properties measurements alone are insufficient to fully validate modeling predictions.