A simple unsymmetric 4‐node 12‐DOF membrane element for the modified couple stress theory

In this work, the recently proposed unsymmetric 4‐node 12‐DOF (degree‐of‐freedom) membrane element (Shang and Ouyang, Int J Numer Methods Eng 113(10): 1589‐1606, 2018), which has demonstrated excellent performance for the classical elastic problems, is further extended for the modified couple stress theory, to account for the size effect of materials. This is achieved via two formulation developments. Firstly, by using the penalty function method, the kinematic relations between the element's nodal drilling DOFs and the true physical rotations are enforced. Consequently, the continuity requirement for the modified couple stress theory is satisfied in weak sense, and the symmetric curvature test function can be easily derived from the gradients of the drilling DOFs. Secondly, the couple stress field that satisfies a priori the related equilibrium equations is adopted as the energy conjugate trial function to formulate the element for the modified couple stress theory. As demonstrated by a series of benchmark tests, the new element can efficiently capture the size‐dependent responses of materials and is robust to mesh distortions. Moreover, as the new element uses only three conventional DOFs per node, it can be readily incorporated into the standard finite element program framework and commonly available finite element programs

Specific subsystems of the inferior parietal lobule are associated with hand dysfunction following stroke: A cross-sectional resting-state fMRI study

Aim The inferior parietal lobule (IPL) plays important roles in reaching and grasping during hand movements, but how reorganizations of IPL subsystems underlie the paretic hand remains unclear. We aimed to explore whether specific IPL subsystems were disrupted and associated with hand performance after chronic stroke. Methods In this cross-sectional study, we recruited 65 patients who had chronic subcortical strokes and 40 healthy controls from China. Each participant underwent the Fugl-Meyer Assessment of Hand and Wrist and resting-state fMRI at baseline. We mainly explored the group differences in resting-state effective connectivity (EC) patterns for six IPL subregions in each hemisphere, and we correlated these EC patterns with paretic hand performance across the whole stroke group and stroke subgroups. Moreover, we used receiver operating characteristic curve analysis to distinguish the stroke subgroups with partially (PPH) and completely (CPH) paretic hands. Results Stroke patients exhibited abnormal EC patterns with ipsilesional PFt and bilateral PGa, and five sensorimotor-parietal/two parietal–temporal subsystems were positively or negatively correlated with hand performance. Compared with CPH patients, PPH patients exhibited abnormal EC patterns with the contralesional PFop. The PPH patients had one motor-parietal subsystem, while the CPH patients had one sensorimotor-parietal and three parietal-occipital subsystems that were associated with hand performance. Notably, the EC strength from the contralesional PFop to the ipsilesional superior frontal gyrus could distinguish patients with PPH from patients with CPH. Conclusions The IPL subsystems manifest specific functional reorganization and are associated with hand dysfunction following chronic stroke.Natural Science Foundation of Zhejiang Province, Grant/Award Number: LGF19H270001; Shanghai Sailing Program, Grant/Award Number: 20YF144510

Efficacy of High Dose Vitamin D Supplements for Elite Athletes.

PURPOSE: Supplementation with dietary forms of vitamin D is commonplace in clinical medicine, elite athletic cohorts and the general population, yet the response of all major vitamin D metabolites to high doses of vitamin D is poorly characterized. We aimed to identify the responses of all major vitamin D metabolites to moderate and high dose supplemental vitamin D3. METHODS: A repeated measures design was implemented in which 46 elite professional European athletes were block randomized based on their basal 25[OH]D concentration into two treatment groups. Athletes received either 35,000 or 70,000 IU.week vitamin D3 for 12 weeks and 42 athletes completed the trial. Blood samples were collected over 18 weeks to monitor the response to supplementation and withdrawal from supplementation. RESULTS: Both doses led to significant increases in serum 25[OH]D and 1,25[OH]2D3. 70,000 IU.week also resulted in a significant increase of the metabolite 24,25[OH]2D at weeks 6 and 12 that persisted following supplementation withdrawal at week 18, despite a marked decrease in 1,25[OH]2D3. Intact PTH was decreased in both groups by week 6 and remained suppressed throughout the trial. CONCLUSIONS: High dose vitamin D3 supplementation (70,000 IU.week) may be detrimental for its intended purposes due to increased 24,25[OH]2D production. Rapid withdrawal from high dose supplementation may inhibit the bioactivity of 1,25[OH]2D3 as a consequence of sustained increases in 24,25[OH]2D that persist as 25[OH]D and 1,25[OH]2D concentrations decrease. These data imply that lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable

Improving Representation of Deforestation Effects on Evapotranspiration in the E3SM Land Model

Evapotranspiration (ET) plays an important role in land-atmosphere coupling of energy, water, and carbon cycles. Following deforestation, ET is typically observed to decrease substantially as a consequence of decreases in leaf area and roots and increases in runoff. Changes in ET (latent heat flux) revise the surface energy and water budgets, which further affects large-scale atmospheric dynamics and feeds back positively or negatively to long-term forest sustainability. In this study, we used observations from a recent synthesis of 29 pairs of adjacent intact and deforested FLUXNET sites to improve model parameterization of stomatal characteristics, photosynthesis, and soil water dynamics in version 1 of the Energy Exascale Earth System Model (E3SM) Land Model (ELMv1). We found that default ELMv1 predicts an increase in ET after deforestation, likely leading to incorrect estimates of the effects of deforestation on land-atmosphere coupling. The calibrated model accurately represented the FLUXNET observed deforestation effects on ET. Importantly, the search for global optimal parameters converged at values consistent with recent observational syntheses, confirming the reliability of the calibrated physical parameters. Applying this improved model parameterization to the globe scale reduced the bias of annual ET simulation by up to ~600 mm/year. Analysis on the roles of parameters suggested that future model development to improve ET simulation should focus on stomatal resistance and soil water-related parameterizations. Finally, our predicted differences in seasonal ET changes from deforestation are large enough to substantially affect land-atmosphere coupling and should be considered in such studies

Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3.

CC chemokine ligand 5 (CCL5) and CCL3 are critical for immune surveillance and inflammation. Consequently, they are linked to the pathogenesis of many inflammatory conditions and are therapeutic targets. Oligomerization and glycosaminoglycan (GAG) binding of CCL5 and CCL3 are vital for the functions of these chemokines. Our structural and biophysical analyses of human CCL5 reveal that CCL5 oligomerization is a polymerization process in which CCL5 forms rod-shaped, double-helical oligomers. This CCL5 structure explains mutational data and offers a unified mechanism for CCL3, CCL4, and CCL5 assembly into high-molecular-weight, polydisperse oligomers. A conserved, positively charged BBXB motif is key for the binding of CC chemokines to GAG. However, this motif is partially buried when CCL3, CCL4, and CCL5 are oligomerized; thus, the mechanism by which GAG binds these chemokine oligomers has been elusive. Our structures of GAG-bound CCL5 and CCL3 oligomers reveal that these chemokine oligomers have distinct GAG-binding mechanisms. The CCL5 oligomer uses another positively charged and fully exposed motif, KKWVR, in GAG binding. However, residues from two partially buried BBXB motifs along with other residues combine to form a GAG-binding groove in the CCL3 oligomer. The N termini of CC chemokines are shown to be involved in receptor binding and oligomerization. We also report an alternative CCL3 oligomer structure that reveals how conformational changes in CCL3 N termini profoundly alter its surface properties and dimer-dimer interactions to affect GAG binding and oligomerization. Such complexity in oligomerization and GAG binding enables intricate, physiologically relevant regulation of CC chemokine functions

Seperation, identification and analysis of pigment (melanin) production in Streptomyces

Nine strains among 180 Streptomyces isolates produce a diffusible dark brown pigment on both peptone-yeast extract agar and synthetic tyrosine-agar. They also show the positive reaction to Ltyrosine or L-dopa substrates. The pigment has been referred to be as merely as dark brown watersolublepigment, as melanoid or melanin. The different carbon and nitrogen sources which influence the pigment production in the Streptomyces isolates were also investigated, and the carotenoid content in the pigment was analyzed. The melanin formation in the Streptomyces species is the key feature for the classification of the Stretomyces grou

Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study

BACKGROUND: The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures-including novel digital tracing approaches and less intensive physical distancing-might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. METHODS: For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40 162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. RESULTS: We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15 000-41 000 contacts would be newly quarantined each day. INTERPRETATION: Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. FUNDING: Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council

Weaker land–climate feedbacks from nutrient uptake during photosynthesis-inactive periods

Terrestrial carbon–climate feedbacks depend on two large and opposing fluxes—soil organic matter decomposition and photosynthesis—that are tightly regulated by nutrients . Earth system models (ESMs) participating in the Coupled Model Intercomparison Project Phase 5 represented nutrient dynamics poorly , rendering predictions of twenty-first century carbon–climate feedbacks highly uncertain. Here, we use a new land model to quantify the effects of observed plant nutrient uptake mechanisms missing in most other ESMs. In particular, we estimate the global role of root nutrient competition with microbes and abiotic processes during periods without photosynthesis. Nitrogen and phosphorus uptake during these periods account for 45 and 43%, respectively, of annual uptake, with large latitudinal variation. Globally, night-time nutrient uptake dominates this signal. Simulations show that ignoring this plant uptake, as is done when applying an instantaneous relative demand approach, leads to large positive biases in annual nitrogen leaching (96%) and N O emissions (44%). This N O emission bias has a GWP equivalent of ~2.4 PgCO yr , which is substantial compared to the current terrestrial CO sink. Such large biases will lead to predictions of overly open terrestrial nutrient cycles and lower carbon sequestration capacity. Both factors imply over-prediction of positive terrestrial feedbacks with climate in current ESMs. 1,2 1,3 −1 2 2 2

Evaluation of microflow configurations for scale inhibition and serial X-ray diffraction analysis of crystallization processes

The clean and reproducible conditions provided by microfluidic devices are ideal sample environments for in situ analyses of chemical and biochemical reactions and assembly processes. However, the small size of microchannels makes investigating the crystallization of poorly soluble materials on-chip challenging due to crystal nucleation and growth that result in channel fouling and blockage. Here, we demonstrate a reusable insert-based microfluidic platform for serial X-ray diffraction analysis and examine scale formation in response to continuous and segmented flow configurations across a range of temperatures. Under continuous flow, scale formation on the reactor walls begins almost immediately on mixing of the crystallizing species, which over time results in occlusion of the channel. Depletion of ions at the start of the channel results in reduced crystallization towards the end of the channel. Conversely, segmented flow can control crystallization, so it occurs entirely within the droplet. Consequently, the spatial location within the channel represents a temporal point in the crystallization process. Whilst each method can provide useful crystallographic information, time-resolved information is lost when reactor fouling occurs and changes the solution conditions with time. The flow within a single device can be manipulated to give a broad range of information addressing surface interaction or solution crystallization