Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal ...leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis MS and Crohn disease) clearance and alpha4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood-brain barrier (ivBBB).
Twelve patients with MS receiving natalizumab underwent three 1.5-volume PLEX sessions over 5 or 8 days. Natalizumab concentrations and alpha4-integrin saturation were assessed daily throughout PLEX and three times over the subsequent 2 weeks, comparing results with the same patients the previous month. Peripheral blood mononuclear cell (PBMC) migration (induced by the chemokine CCL2) across an ivBBB was assessed in a subset of six patients with and without PLEX.
Serum natalizumab concentrations were reduced by a mean of 92% from baseline to 1 week after three PLEX sessions (p < 0.001). Although average alpha4-integrin saturation was not reduced after PLEX, it was reduced to less than 50% when natalizumab concentrations were below 1 mug/mL. PBMC transmigratory capacity increased 2.2-fold after PLEX (p < 0.006).
Plasma exchange (PLEX) accelerated clearance of natalizumab, and at natalizumab concentrations below 1 mug/mL, desaturation of alpha4-integrin was observed. Also, CCL2-induced leukocyte transmigration across an in vitro blood-brain barrier was increased after PLEX. Therefore, PLEX may be effective in restoring immune effector function in natalizumab-treated patients.
Alloparental care is central to human life history, which integrates exceptionally short interbirth intervals and large birth size with an extended period of juvenile dependency and increased ...longevity. Formal models, previous comparative research, and palaeoanthropological evidence suggest that humans evolved higher levels of cooperative childcare in response to increasingly harsh environments. Although this hypothesis remains difficult to test directly, the relative importance of alloparental care varies across human societies, providing an opportunity to assess how local social and ecological factors influence the expression of this behaviour. We therefore, investigated associations between alloparental infant care and socioecology across 141 non-industrialized societies. We predicted increased alloparental care in harsher environments, due to the fitness benefits of cooperation in response to shared ecological challenges. We also predicted that starvation would decrease alloparental care, due to prohibitive energetic costs. Using Bayesian phylogenetic multilevel models, we tested these predictions while accounting for potential confounds as well as for population history. Consistent with our hypotheses, we found increased alloparental infant care in regions characterized by both reduced climate predictability and relatively lower average temperatures and precipitation. We also observed reduced alloparental care under conditions of high starvation. These results provide evidence of plasticity in human alloparenting in response to ecological contexts, comparable to previously observed patterns across avian and mammalian cooperative breeders. This suggests convergent social evolutionary processes may underlie both inter- and intraspecific variation in alloparental care.
Abstract
This paper aims to present a numerical investigation of the two-phase flow in unbaffled uncovered stirred tanks equipped with a Rushton turbine. The shaft is positioned eccentrically. As ...simulation software, the Simcenter Star CCM+ 2021.2 is used to carry out multiphase unsteady simulations. Next, the numerical results are compared with results obtained on a test bench.
A phase-field theory of brittle fracture in elastoplastic solids hosting mobile interstitial solute species is developed in this paper. The theory, which is formulated within the framework of modern ...continuum mechanics, provides a systematic way to describe the interplay between solute migration and solid deformation and fracture. A specialization of the theory, which accounts for both solute-induced deformation and solute-assisted fracture as well as for their mutual effects on solute migration, is selected for numerical studies. Toward this end, a numerical model based on the finite-element method for spatial discretization and a splitting scheme with sub-stepping for the time integration is proposed. The model is applied to the study of hydrogen-assisted crack propagation of high-strength steel specimens under sustained loads. The solutions obtained are compared with numerical and experimental results reported in the literature. It is shown that the proposed model has the capability to capture important features presented in the studied phenomenon.
•A general theory coupling deformation, species migration and fracture in elasto-plastic solids is presented.•The general theory is formulated within a modern continuum mechanics framework.•The theory is then specialized for modeling hydrogen assisted cracking problems of high strength steel specimens.•A numerical strategy using finite elements and phase field model is proposed and implemented.•The solutions obtained with the phase-field model are validated by comparing them with numerical and experimental results.
Eukaryotic steranes are typically absent or occur in very low concentrations in Precambrian sedimentary rocks. However, it is as yet unclear whether this may reflect low source inputs or a ...preservational bias. For instance, it has been proposed that eukaryotic lipids were profoundly degraded in benthic microbial mats that were ubiquitous prior to the advent of vertical bioturbation in the Cambrian (“mat‐seal effect”). It is therefore important to test the microbial turnover and degradation of eukaryotic steroids in real‐world microbial mats. Here we assessed steroid inventories in different layers of a microbial mat from a hypersaline lake on Kiritimati (Central Pacific). Various eukaryote‐derived C27‐C30 steroids were detected in all mat layers. These compounds most likely entered the mat system as unsaturated sterols from the water column or the topmost mat, and were progressively altered during burial in the deeper, anoxic mat layers over c. 103 years. This is reflected by increasing proportions of saturated sterols and sterenes, as well as the presence of thiosteranes in certain horizons. Sterol alteration can partly be assigned to microbial transformation but is also due to chemical reactions promoted by the reducing environment in the deeper mat layers. Notably, however, compounds with a sterane skeleton were similarly abundant in all mat layers and their absolute concentrations did not show any systematic decrease. The observed decrease of steroid/hopanoid ratios with depth may thus rather indicate a progressive “dilution” by lipids derived from heterotrophic bacteria. Further, pyrolysis revealed that steroids, in contrast to hopanoids, were not sequestered into non‐extractable organic matter. This may lead to a preservational bias against steroids during later stages of burial. Taken together, steroid preservation in the microbial mat is not only controlled by heterotrophic degradation, but rather reflects a complex interplay of taphonomic processes.
We present a theory for coupled deformation and liquid permeation in polymer gels, allowing for large strains and rotations in conjunction with sharp interfaces separating regions of high and low ...polymer volume fraction. The theory is applied to pressure-driven liquid flow through a gel-filled rectangular channel, with the aim of investigating how the elastic and osmotic properties of the gel influence the resulting permeation process. Apart from streamwise flow in the direction of the applied pressure drop, the permeation process may involve transverse flow if the elastic response of the gel allows the normal stress acting on a plane parallel to the channel walls to be affected by the shear stress acting on the same plane. For certain elastic energy densities, including those of neo-Hookean and Mooney type, liquid permeation takes place exclusively in the direction of the applied pressure drop. Otherwise, spanwise permeation driven by the contribution to the normal stress distributed on planes parallel to the channel walls is also present. In contrast to the downstream flow, the transverse flow is transient and is accompanied by changes in composition leading to a nonuniform polymer distribution across the channel and thereby influencing the downstream flow profile. By analyzing the instantaneous response of the gel, we determine the driving force for the transverse flow and show that for strain-stiffening networks the transverse motion of the interstitial liquid is directed inward from the channel walls and that the polymer network motion spreads outward from the center of the channel toward the walls. The opposite occurs for strain-slackening networks. By analyzing the steady-state response, we demonstrate that the applied pressure gradient leads to nonuniform transverse distributions of polymer chains than can be continuous or discontinuous. Discontinuous distributions occur for an effective osmotic response involving attractive interactions and are accompanied by the formation of regions of high and low polymer volume fraction separated by sharp interfaces. Finally, we provide illustrative examples for a gel whose elastic and osmotic responses are modeled by the Gent elastic energy density and the Flory–Huggins mixing energy density, respectively.
•Derivation of a finite-strain theory of liquid permeation and interface motion.•Treatment of the liquid-induced compressibility condition as an internal constraint.•Derivation of the Maxwell coexistence condition from an extra force balance.•Formulation and analysis of a problem of liquid flow through gels.•Derivation of conditions for the occurrence of spanwise flow and sharp interfaces.
•Black bedded barite from the 3.5 Ga Dresser Formation.•Hydrothermal cycling of biogenic Paleoarchean organic material.•High-resolution structural analysis of carbonaceous matter (NEXAFS, NMR)
...Carbonaceous matter (CM) in Archean rocks represents a valuable archive for the reconstruction of early life. Here we investigate the nature of CM preserved in ∼ 3.5 Ga old black bedded barites from the Dresser Formation (Pilbara Carton, Western Australia). Using light microscopy and high-resolution Raman mapping, three populations of CM were recognized: (i) CM at the edges of single growth bands of barite crystals (most frequent), (ii) CM within the barite matrix, and (iii) CM in 50–300 µm wide secondary quartz veins that cross-cut the black bedded barite. Raman spectra of CM inside black bedded barite indicated peak metamorphic temperatures of ∼ 350 °C, consistent with those reached during the main metamorphic event in the area ∼ 3.3 Ga ago. By contrast, CM in quartz veins yielded much lower temperatures of ∼ 220 °C, suggesting that quartz-vein associated CM entered the barite after 3.3 Ga. Near edge X-ray absorption fine structure (NEXAFS) and solid-state nuclear magnetic resonance (NMR) revealed a highly aromatic nature of the CM with a lower aliphatic content, which is in line with the relatively elevated thermal maturity. Catalytic hydropyrolysis (HyPy) did not yield any hydrocarbons detectable with gas chromatography–mass spectrometry (GC–MS). Secondary ion mass spectrometry (SIMS) based δ13C values of individual CM particles ranged from − 33.4 ± 1.2 ‰ to − 16.5 ± 0.6 ‰ and are thus in accordance with a biogenic origin, which is also consistent with stromatolitic microbialites associated with the black bedded barite. Based on these results we conclude that CM at growth bands and inside the barite matrix is syngenetic and only the CM inside quartz veins, which represents a minor portion of the total CM, is a later addition to the system. Furthermore, we discuss different pathways for the input of CM into the barite-forming environment, including the cycling of biological organic material within the hydrothermal system.
We develop a constrained theory for constituent migration in bodies with microstructure described by a scalar phase field. The distinguishing features of the theory stem from a systematic treatment ...and characterization of the reactions needed to maintain the internal constraint given by the coincidence of the mass fraction and the phase field. We also develop boundary conditions for situations in which the interface between the body and its environment is structureless and cannot support constituent transport. In addition to yielding a new derivation of the Cahn–Hilliard equation, the theory affords an interpretation of that equation as a limiting variant of an Allen–Cahn type diffusion system arising from the unconstrained theory obtained by considering the mass fraction and the phase field as independent quantities. We corroborate that interpretation with three-dimensional numerical simulations of a recently proposed benchmark problem.
Algal bioindicators, such as diatoms, often show subdued responses to eutrophication in Arctic lakes because climate‐related changes (e.g., ice cover) tend to be the overriding factors influencing ...assemblage composition. Here, we examined how sub‐Arctic ponds historically receiving high nutrient inputs from nesting seabirds have responded to recent climate change. We present diatom data obtained from 12 sediment cores in seaduck‐affected ponds located on islands through Hudson Strait, Canada. All study cores show consistently elevated values of sedimentary ẟ15N, an established proxy for tracking marine‐derived nutrients, indicating seabirds have been present on these islands for at least the duration of the sediment records (~100 to 400 years). We document diverse epiphytic diatom assemblages to the base of all sediment cores, which is in marked contrast to seabird‐free Arctic ponds—these oligotrophic sites typically record epilithic diatom flora prior to recent warming. Diatoms are likely responding indirectly to seabird nutrients via habitat as nutrients promote the growth of mosses supporting epiphytic diatom communities. This masks the typical diatom response to increased warming in the Arctic, which also results in habitat changes and the growth of mosses around the pond edges. Changes in sedimentary chlorophyll a were not consistently synchronous with large changes in ẟ15N values, suggesting that primary production in ponds is not responding linearly to changes in seabird‐derived nitrogen. Across all ponds, we recorded shifts in diatom epiphytic assemblages (e.g., increases in % relative abundance of many Nitzschia species) that often align with increases in chlorophyll a. The changes in diatoms and chlorophyll a, although variable, are most likely driven by climate change as they are generally consistent with longer ice‐free conditions and growing seasons. Together, our results show that to effectively use diatoms in animal population reconstructions across the sub‐Arctic and Arctic, a strong understanding of eutrophication and climate change, based on supplementary proxies, is also required.
We document diverse epiphytic diatom assemblages to the base of all sediment cores, which is in marked contrast to seabird‐free Arctic ponds—these oligotrophic sites typically record epilithic diatom flora prior to recent warming. Diatoms are likely responding indirectly to seabird nutrients via habitat as nutrients promote the growth of mosses supporting epiphytic diatom communities. Changes in sedimentary chlorophyll a were not consistently synchronous with large changes in ẟ15N values, suggesting that primary production in ponds is not responding linearly to changes in seabird‐derived nitrogen.
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