A parameterized-background data-weak approach to variational data assimilation: formulation, analysis, and application to acoustics

We present a parameterized-background data-weak (PBDW) formulation of the variational data assimilation (state estimation) problem for systems modeled by partial differential equations. The main contributions are a constrained optimization weak framework informed by the notion of experimentally observable spaces; a priori and a posteriori error estimates for the field and associated linear-functional outputs; weak greedy construction of prior (background) spaces associated with an underlying potentially high-dimensional parametric manifold; stability-informed choice of observation functionals and related sensor locations; and finally, output prediction from the optimality saddle in O(M[superscript 3) operations, where M is the number of experimental observations. We present results for a synthetic Helmholtz acoustics model problem to illustrate the elements of the methodology and confirm the numerical properties suggested by the theory. To conclude, we consider a physical raised-box acoustic resonator chamber: we integrate the PBDW methodology and a Robotic Observation Platform to achieve real-time in situ state estimation of the time-harmonic pressure field; we demonstrate the considerable improvement in prediction provided by the integration of a best-knowledge model and experimental observations; we extract, even from these results with real data, the numerical trends indicated by the theoretical convergence and stability analyses.Fondation Sciences Mathematiques de ParisUnited States. Air Force Office of Scientific Research. Multidisciplinary University Research Initiative (Grant FA9550-09-1-0613)United States. Office of Naval Research (Grant N00014-11-1-0713)SUTD-MIT International Design Centr

Multi-functional layered structure having structural and radiation shielding attributes

A cosmic and solar radiation shielding structure that also has structural attributes is comprised of three layers. The first layer is 30-42 percent by volume of ultra-high molecular weight (UHMW) polyethylene fibers, 18-30 percent by volume of graphite fibers, and a remaining percent by volume of an epoxy resin matrix. The second layer is approximately 68 percent by volume of UHMW polyethylene fibers and a remaining percent by volume of a polyethylene matrix. The third layer is a ceramic material

Cold Feet: trackways and burrows in ice-marginal strata of the end-Ordovician glaciation (Table Mountain Group, South Africa)

New observations from an outcrop of Upper Ordovician Table Mountain Group strata (Matjiesgoedkloof, Western Cape Province, South Africa) have revealed an unexpected ichnofauna, hosted within diamictites and sandstones that were deposited by a retreating low-latitude (c. 30{degree sign}S) ice sheet during the Hirnantian glaciation. The locality provides a rare window onto animal-sediment interactions in an early Paleozoic ice-marginal shallow marine environment and contains a trace fossil community with a surprising ichnodiversity and ichnodisparity of burrows, trackways and trails (Archaeonassa, Diplichnites, Heimdallia, Metaichna, ?Multina, Planolites, Protovirgularia, Skolithos). Exceptional phenomena preserved in the strata include evidence for direct colonization of glacial diamictites by deep-burrowing Heimdallia infauna, and interactions between trackways and dropstones on substrates. Observations from the newly-recognized outcrop dramatically expand our understanding of deep time glacial habitats, demonstrating that deglaciating ice-margins had already been colonized by the latest Ordovician. The freshwater influx that would have been associated with such settings implies that faunal associations which were tolerant of brackish water were also established by that time. The locality has further significance because it records the activity of a nearshore animal community contemporaneous with the fauna of the nearby Soom Shale lägerstatte. Combined, these reveal a paleoecological transect of the diverse marine life that inhabited cold-climate, low-latitude shallow seas around the time of the end-Ordovician deglaciation

Rituximab in rheumatology: single-centre SARS-CoV-2 infection and COVID-19 prevalence.

We describe a coronavirus disease 2019 (COVID-19) prevalence of 20% in rheumatic disease patients treated with rituximab, with 10.3% of these (2% of the entire cohort) having died of COVID-19-related causes

Individual variation in 3-methylbutanal: A putative link between human leukocyte antigen and skin microflora

The human derma emits volatile compounds whose interaction with a receiver's olfactory sensory system may affect individual recognition and mating preferences. Studies suggest that both genes and environmental factors determine characteristic odor of an individual. Here, we use solid phase micro-extraction and GC-MS to identify 3-methylbutanal (3-MB) in human axillary odor, show that the abundance of this volatile compound varies significantly between individuals and demonstrate in vitro that its formation may be influenced by interaction between human leukocyte antigen peptide and dermal microflora

The impact of sex-role reversal on the diversity of the major histocompatibility complex: Insights from the seahorse (Hippocampus abdominalis)

Background: Both natural and sexual selection are thought to influence genetic diversity, but the study of the relative importance of these two factors on ecologically-relevant traits has traditionally focused on species with conventional sex-roles, with male-male competition and female-based mate choice. With its high variability and significance in both immune function and olfactory-mediated mate choice, the major histocompatibility complex(MHC/MH) is an ideal system in which to evaluate the relative contributions of these two selective forces to genetic diversity. Intrasexual competition and mate choice are both reversed in sex-role reversed species, and sexrelated differences in the detection and use of MH-odor cues are expected to influence the intensity of sexual selection in such species. The seahorse, Hippocampus abdominalis, has an exceptionally highly developed form of male parental care, with female-female competition and male mate choice. Results: Here, we demonstrate that the sex-role reversed seahorse has a single MH class II beta-chain gene and that the diversity of the seahorse MHIIb locus and its pattern of variation are comparable to those detected in species with conventional sex roles. Despite the presence of only a single gene copy, intralocus MHIIb allelic diversity in this species exceeds that observed in species with multiple copies of this locus. The MHIIb locus of the seahorse exhibits a novel expression domain in the male brood pouch. Conclusions: The high variation found at the seahorse MHIIb gene indicates that sex-role reversed species are capable of maintaining the high MHC diversity typical in most vertebrates. Whether such species have evolved the capacity to use MH-odor cues during mate choice is presently being investigated using mate choice experiments. If this possibility can be rejected, such systems would offer an exceptional opportunity to study the effects of natural selection in isolation, providing powerful comparative models for understanding the relative importance of selective factors in shaping patterns of genetic variation

Impact of Upadacitinib on laboratory parameters and related adverse events in patients with RA: Integrated data up to 6.5 years

Introduction: Upadacitinib (UPA) is a Janus kinase inhibitor that has demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA) with an acceptable safety profile. We investigated laboratory parameter changes in UPA RA clinical trials. Methods: Pooled data from six randomized trials in the SELECT phase 3 program were included. Key laboratory parameters and safety data were measured for UPA 15 and 30 mg once daily (QD), adalimumab (ADA) 40 mg every other week + methotrexate (MTX), and MTX monotherapy. Exposure-adjusted event rates (EAERs) of adverse events were calculated. Results: A total of 3209 patients receiving UPA 15 mg QD (10 782.7 patient-years [PY]), 1204 patients receiving UPA 30 mg QD (3162.5 PY), 579 patients receiving ADA + MTX (1573.2 PY), and 314 patients receiving MTX monotherapy (865.1 PY) were included, representing up to 6.5 years of total exposure. Decreases in mean levels of hemoglobin, neutrophils, and lymphocytes, and increases in mean levels of liver enzymes and creatinine phosphokinase were observed with UPA, with grade 3 or 4 changes observed in some patients. Mean low- and high-density lipoprotein cholesterol ratios remained stable for patients receiving UPA 15 mg QD. EAERs of anemia and neutropenia occurred at generally consistent rates between UPA and active comparators (3.1–4.3 and 1.7–5.0 events [E]/100 PY across treatment groups, respectively). Rates of hepatic disorder were higher with MTX monotherapy, UPA 15 mg and UPA 30 mg (10.8, 9.7, and 11.0 E/100 PY, respectively) versus ADA + MTX (6.4 E/100 PY). Rates of lymphopenia were highest with MTX monotherapy (3.2 E/100 PY). Treatment discontinuations due to laboratory-related events were rare, occurring in 1.1% and 2.2% of patients treated with UPA 15 and 30 mg QD, respectively. Conclusions: The results of this integrated long-term analysis of laboratory parameters continue to support an acceptable safety profile of UPA 15 mg QD for moderate-to-severe RA

p38-γ–dependent gene silencing restricts entry into the myogenic differentiation program

The regenerative capacity of muscle is regulated by p38-γ, which phosphorylates MyoD and leads to formation of a complex that represses myogenin transcription