Ensemble Therapeutics (United States)

We analyze the thermal and electrical characteristics of the metasurface composed of a coplanar interdigital array of the graphene microribbons (GMRs) connected by nanobridges (NBs). These nanobridges could be implemented using graphene nanoribbons (GNRs) or black-arsenic-phosphorus (b-AsP) nanostructures. When a bias voltage applied between neighboring GMRs, it induces electron and hole two-dimensional systems within the GMRs, leading to thermionic currents that flow through the connecting NB resulting in the self-heating effect. This self-heating effect increases the thermionic currents, creating an effective positive feedback loop between the carrier effective temperature and the injected currents, and the bias voltage. This mechanism may lead to thermal breakdown enabling threshold behavior of current–voltage characteristics and yielding an S-shaped response. The devices based on the GMR/GNR and GMR/AsP metasurface structures can serve as fast voltage-controlled current switches, sensors, thermal terahertz and infrared sources, and among other applications.

The production of fibrous oxides, particularly V2O5, by intensive stirring in water is examined through the framework of driven systems, an approach developed in the 1980s by Georges Martin et al. for systems under irradiation or severe plastic deformation. Instead of ballistic diffusion, the model introduces ballistic detachments of atoms from the oxide surface under stirring. A simplified Monte Carlo scheme is proposed for crystal evolution within the terrace-ledge-kink (TLK) model. This scheme accounts for anisotropy and additional athermal detachment probabilities. An individual cluster within a limited volume becomes elongated in a steady state or dissolves. For an ensemble of clusters, the total number decreases (similar to common ripening), but the mean length of the fibers grows. This leads to an increase in the total surface energy, which is contrary to the behavior observed in common ripening.

Abstract Background Salt-inducible kinases (SIKs) amplify proinflammatory gene expression in myeloid cells via phosphorylation of transcriptional coregulators.1 Genetic loss-of-function (LOF) of SIKs in mice or use of pan-SIK inhibitors decreases proinflammatory cytokines (TNFα, IL-12/23, IL-6, and IL-1β) induced by Toll-like receptor (TLR) or IL-1 receptor (IL-1R) agonists. Among the three SIK isoforms, SIK2 exhibits the highest activity in myeloid cells and uniquely enhances the production of anti-inflammatory cytokine IL-10 when selectively inactivated, distinguishing it from SIK1 or SIK3 LOF.2 To date, the lack of highly selective SIK2 inhibitors has prevented the characterization of pharmacological SIK2 inhibition and its therapeutic potential,3,4 particularly in human tissues. Methods Using structure-based drug design, first-in-class SIK2 inhibitors were developed with nanomolar cellular potency and >300-fold selectivity over SIK1 and SIK3. Whole blood from ten healthy volunteers was preincubated with SIK2 selective inhibitors, challenged ex vivo with the TLR4 agonist LPS, and supernatants analyzed by MSD assays and Olink (Target 96 Inflammatory Panel). To assess SIK2 inhibition in diseased tissue, colon explants from Ulcerative Colitis patients were collected and cultured ex vivo with the JAK1 inhibitor upadacitinib or SIK2 selective inhibitors for 18 hours. Cytokines in supernatants were quantified by MSD assays, and biopsy RNA was extracted for bulk transcriptomic profiling. Results In human whole blood, selective SIK2 inhibitors reduced LPS-stimulated proinflammatory cytokines, including TNFα and IL-23. Among ten donors, inter-donor variability was moderate, with nanomolar IC50 values for TNFα and IL-23. Olink profiling revealed broad suppression of additional inflammatory mediators relevant to Inflammatory Bowel Disease, including IL-1β, CCL3, and CXCL10. In inflamed Ulcerative Colitis explants, SIK2 inhibitors matched or surpassed upadacitinib in reducing TNFα and CCL3 secretion. Further, bulk RNA-seq confirmed SIK2 selective inhibitors downregulated inflammatory pathways associated with Inflammatory Bowel Disease, but importantly upregulated expression of genes linked to mucosal repair, including mucin-2 and occludin. Conclusion Our first-in-class, selective SIK2 inhibitors suppress key proinflammatory cytokines while promoting expression of genes related to tissue repair in human ex vivo models of Ulcerative Colitis. These findings support SIK2 as a novel oral therapeutic approach for Inflammatory Bowel Disease, conferring both anti-inflammatory and tissue reparative benefits for patients.

With a rapidly growing amount of data generated and processed, a search for more efficient components and architectures such as neuromorphic computing that can perform increasingly complex operations in more efficient way continue. Here we show that thin films of chalcogenide phase change materials (PCMs) (Semiconductors) can serve as building blocks for novel type of plasmonic photodetectors and activation function units that operate seamlessly in both electrical and optical domains without the need for repeated electrical-to-optical conversions. Different arrangements and heating configurations are considered to provide a most efficient mechanism for detection and thresholding. Depending on the operation conditions, the same device can operate either as a photodetector or an activation function unit. In consequence it provides flexibility in an on-chip signal processing.

This paper presents a Framework for understanding the field of teaching artists (also known by other terms such as community artist, participatory artist, social practice artist, civic practice artist, artist-in-residence and more) in the U.S. and around the world. This paper describes the current state of the field, which is disparate and disorganized and suggests that previous ways of describing it have proved unhelpful. This pioneering Framework was developed in partnership with practitioners in many communities over years, and was vetted by practitioners in communities around the world to affirm its validity. This Framework was introduced by the author about a decade ago, categorizing the field according to the purposes for which these artists are hired, which turn out to be seven identifiable threads that contain almost all employment in the U.S. and in other countries. This Framework has proven useful in clarifying and advancing the field in a variety of communities, for administrators, for practitioners, for funders, and for those discovering, entering, and advancing in the field. This paper introduces the Purpose Threads and describes each one, giving community-based examples of organizations that employ teaching artists to achieve their goals, and suggesting ways in which one might evaluate whether each purpose is achieved. This paper acknowledges that the seven purposes do not play out discretely in practice, but naturally overlap, and the author identifies a series of basic teaching artist tools that apply across all threads. The author also discusses teaching artist work in digital media, a reality that has burst into prominence during the Covid pandemic. The author invites readers to apply this material in whatever ways are useful.

Nikodijević's piece for symphony orchestra cvetić, kućica.../la lugubre gondola: funeral music after franz liszt -in memoriam (2009), which won him the Gaudeamus Award in 2010, achieved a well-deserved breakthrough in improving his oeuvre's visibility on the international music scene.In this work he "treated Liszt's score like a kind of 'archive' of sorrowful motives.He imported Liszt's motives in his composition randomly, remediated them, developed them, deconstructed them, disfigured them, listened to them again and again, carefully, to finally see if and how they would reflect sadness in the new environment". 3This type of "close reading" and almost fractal observation and rethinking of carefully selected specific musical utterances from the past may be detected in almost every score by Nikodijević.

et de quelque manière que ce soit, est interdite sauf accord préalable et écrit de l'éditeur, en dehors des cas prévus par la législation en vigueur en France.Il est précisé que son stockage dans une base de données est également interdit.