Phytoplankton composition from sPACE: Requirements, opportunities, and challenges

Ocean color satellites have provided a synoptic view of global phytoplankton for over 25 years through near surface measurements of the concentration of chlorophyll a. While remote sensing of ocean color has revolutionized our understanding of phytoplankton and their role in the oceanic and freshwater ecosystems, it is important to consider both total phytoplankton biomass and changes in phytoplankton community composition in order to fully understand the dynamics of the aquatic ecosystems. With the upcoming launch of NASA\u27s Plankton, Aerosol, Clouds, ocean Ecosystem (PACE) mission, we will be entering into a new era of global hyperspectral data, and with it, increased capabilities to monitor phytoplankton diversity from space. In this paper, we analyze the needs of the user community, review existing approaches for detecting phytoplankton community composition in situ and from space, and highlight the benefits that the PACE mission will bring. Using this three-pronged approach, we highlight the challenges and gaps to be addressed by the community going forward, while offering a vision of what global phytoplankton community composition will look like through the “eyes” of PACE

Using run-time predictions to estimate queue wait times and improve scheduler performance

On many computers, a request to run a job is not serviced immediately but instead is placed in a queue and serviced only when resources are released bypreceding jobs. In this paper, we build on run-time prediction techniques that we developed inprevious research to explore two problems. The rst problem is to predict how long applications will wait in a queue until they receive resources. We show that run-time estimates can be used for this and that using our run-time estimates result in more accurate wait-time predictions than when the run-time prediction techniques of other researches are used. The second problem we investigate is improving scheduling performance. We use run-time predictions to improve the performance of the least work rst and back ll scheduling algorithms. We nd that using our run-time predictor results in lower mean wait times for the workloads with higher o ered loads when compared to alternative run-time predictors.

First‐in‐human study of deucravacitinib: A selective, potent, allosteric small‐molecule inhibitor of tyrosine kinase 2

Abstract This randomized, double‐blind, single‐ and multiple‐ascending dose study assessed the pharmacokinetics (PKs), pharmacodynamics, and safety of deucravacitinib (Sotyktu™), a selective and potent small‐molecule inhibitor of tyrosine kinase 2, in 100 (75 active, 25 placebo) healthy volunteers (NCT02534636). Deucravacitinib was rapidly absorbed, with a half‐life of 8–15 h, and 1.4–1.9‐fold accumulation after multiple dosing. Deucravacitinib inhibited interleukin (IL)‐12/IL‐18‐induced interferon (IFN)γ production ex vivo in a dose‐ and concentration‐dependent manner. Following in vivo challenge with IFNα‐2a, deucravacitinib demonstrated dose‐dependent inhibition of lymphocyte count decreases and expression of 53 IFN‐regulated genes. There were no serious adverse events (AEs); the overall frequency of AEs was similar in the deucravacitinib (64%) and placebo (68%) groups. In this first‐in‐human study, deucravacitinib inhibited IL‐12/IL‐23 and type I IFN pathways in healthy volunteers, with favorable PK and safety profiles. Deucravacitinib is a promising therapeutic option for immune‐mediated diseases, including Crohn's disease, psoriasis, psoriatic arthritis, and systemic lupus erythematosus

Phase 2 Trial of Deucravacitinib in Psoriatic Arthritis: Biomarkers Associated With Disease Activity, Pharmacodynamics, and Clinical Responses.

OBJECTIVE: To evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and relationship between biomarkers and clinical responses to deucravacitinib. METHODS: The phase 2 trial (NCT03881059) randomized 203 patients with PsA 1:1:1 to placebo, deucravacitinib 6 mg once daily (QD), or deucravacitinib 12 mg QD. Serum biomarkers associated with the IL-23 pathway (IL-17A, BD-2, and IL-19), Type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (=75% improvement from baseline in Psoriasis Area and Severity Index [PASI 75] and =20% improvement from baseline in American College of Rheumatology [ACR 20] criteria responses) were measured at week 16. Hematologic variables were also assessed. RESULTS: IL-17A, BD-2, and IL-19 had a modest association with PASI scores (r=0.4, r=0.56, and r=0.5, respectively) at baseline. In deucravacitinib groups, IL-17A, BD-2, IL-19, CXCL-9, CXCL-10, CRP, MMP3, and C4M levels were significantly reduced at week 16 versus baseline (P CONCLUSION: Deucravacitinib significantly impacted biomarkers associated with TYK2 signaling pathways of key inflammatory cytokines, including IL-23 and Type I IFN, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib

Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Objective: To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE). Methods: Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI-4) response at week 32. Secondary outcomes assessed at week 48 included SRI-4, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts. Results: At week 32, the percentage of patients achieving SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95% confidence interval (95% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50% with 6 mg twice daily (OR 1.9 [95% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45% with 12 mg once daily (OR 1.6 [95% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported. Conclusion: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE