scholarly journals Inducing protein aggregation by extensional flow

2017 ◽  
Vol 114 (18) ◽  
pp. 4673-4678 ◽  
Author(s):  
John Dobson ◽  
Amit Kumar ◽  
Leon F. Willis ◽  
Roman Tuma ◽  
Daniel R. Higazi ◽  
...  

Relative to other extrinsic factors, the effects of hydrodynamic flow fields on protein stability and conformation remain poorly understood. Flow-induced protein remodeling and/or aggregation is observed both in Nature and during the large-scale industrial manufacture of proteins. Despite its ubiquity, the relationships between the type and magnitude of hydrodynamic flow, a protein’s structure and stability, and the resultant aggregation propensity are unclear. Here, we assess the effects of a defined and quantified flow field dominated by extensional flow on the aggregation of BSA, β2-microglobulin (β2m), granulocyte colony stimulating factor (G-CSF), and three monoclonal antibodies (mAbs). We show that the device induces protein aggregation after exposure to an extensional flow field for 0.36–1.8 ms, at concentrations as low as 0.5 mg mL−1. In addition, we reveal that the extent of aggregation depends on the applied strain rate and the concentration, structural scaffold, and sequence of the protein. Finally we demonstrate the in situ labeling of a buried cysteine residue in BSA during extensional stress. Together, these data indicate that an extensional flow readily unfolds thermodynamically and kinetically stable proteins, exposing previously sequestered sequences whose aggregation propensity determines the probability and extent of aggregation.

2019 ◽  
Author(s):  
Sean M. Cascarina ◽  
Eric D. Ross

ABSTRACTProtein aggregation is involved in a variety of muscular and neurodegenerative disorders. For many of these disorders, current models suggest a prion-like molecular mechanism of disease, whereby proteins aggregate and spread to neighboring cells in an infectious manner. A variety of proteins with prion-like domains (PrLDs) have recently been linked to these disorders. The development of prion prediction algorithms has facilitated the large-scale identification of PrLDs among “reference” proteomes for various organisms. However, the degree to which intraspecies protein sequence diversity influences predicted aggregation propensity for PrLDs has not been systematically examined. Here, we explore protein sequence variation introduced at genetic, post-transcriptional, and post-translational levels, and its influence on predicted aggregation propensity for human PrLDs. We find that sequence variation is relatively common among PrLDs and in some cases can result in relatively large differences in predicted aggregation propensity. Analysis of a database of sequence variants associated with human disease reveals a number of mutations within PrLDs that are predicted to increase aggregation propensity. Our analyses expand the list of candidate human PrLDs, estimate the effects of sequence variation on the aggregation propensity of PrLDs, and suggest the involvement of prion-like mechanisms in additional human diseases.


2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e16-e16
Author(s):  
Ahmed Moussa ◽  
Audrey Larone-Juneau ◽  
Laura Fazilleau ◽  
Marie-Eve Rochon ◽  
Justine Giroux ◽  
...  

Abstract BACKGROUND Transitions to new healthcare environments can negatively impact patient care and threaten patient safety. Immersive in situ simulation conducted in newly constructed single family room (SFR) Neonatal Intensive Care Units (NICUs) prior to occupancy, has been shown to be effective in testing new environments and identifying latent safety threats (LSTs). These simulations overlay human factors to identify LSTs as new and existing process and systems are implemented in the new environment OBJECTIVES We aimed to demonstrate that large-scale, immersive, in situ simulation prior to the transition to a new SFR NICU improves: 1) systems readiness, 2) staff preparedness, 3) patient safety, 4) staff comfort with simulation, and 5) staff attitude towards culture change. DESIGN/METHODS Multidisciplinary teams of neonatal healthcare providers (HCP) and parents of former NICU patients participated in large-scale, immersive in-situ simulations conducted in the new NICU prior to occupancy. One eighth of the NICU was outfitted with equipment and mannequins and staff performed in their native roles. Multidisciplinary debriefings, which included parents, were conducted immediately after simulations to identify LSTs. Through an iterative process issues were resolved and additional simulations conducted. Debriefings were documented and debriefing transcripts transcribed and LSTs classified using qualitative methods. To assess systems readiness and staff preparedness for transition into the new NICU, HCPs completed surveys prior to transition, post-simulation and post-transition. Systems readiness and staff preparedness were rated on a 5-point Likert scale. Average survey responses were analyzed using dependent samples t-tests and repeated measures ANOVAs. RESULTS One hundred eight HCPs and 24 parents participated in six half-day simulation sessions. A total of 75 LSTs were identified and were categorized into eight themes: 1) work organization, 2) orientation and parent wayfinding, 3) communication devices/systems, 4) nursing and resuscitation equipment, 5) ergonomics, 6) parent comfort; 7) work processes, and 8) interdepartmental interactions. Prior to the transition to the new NICU, 76% of the LSTs were resolved. Survey response rate was 31%, 16%, 7% for baseline, post-simulation and post-move surveys, respectively. System readiness at baseline was 1.3/5,. Post-simulation systems readiness was 3.5/5 (p = 0.0001) and post-transition was 3.9/5 (p = 0.02). Staff preparedness at baseline was 1.4/5. Staff preparedness post-simulation was 3.3/5 (p = 0.006) and post-transition was 3.9/5 (p = 0.03). CONCLUSION Large-scale, immersive in situ simulation is a feasible and effective methodology for identifying LSTs, improving systems readiness and staff preparedness in a new SFR NICU prior to occupancy. However, to optimize patient safety, identified LSTs must be mitigated prior to occupancy. Coordinating large-scale simulations is worth the time and cost investment necessary to optimize systems and ensure patient safety prior to transition to a new SFR NICU.


2021 ◽  
Vol 13 (2) ◽  
pp. 228
Author(s):  
Jian Kang ◽  
Rui Jin ◽  
Xin Li ◽  
Yang Zhang

In recent decades, microwave remote sensing (RS) has been used to measure soil moisture (SM). Long-term and large-scale RS SM datasets derived from various microwave sensors have been used in environmental fields. Understanding the accuracies of RS SM products is essential for their proper applications. However, due to the mismatched spatial scale between the ground-based and RS observations, the truth at the pixel scale may not be accurately represented by ground-based observations, especially when the spatial density of in situ measurements is low. Because ground-based observations are often sparsely distributed, temporal upscaling was adopted to transform a few in situ measurements into SM values at a pixel scale of 1 km by introducing the temperature vegetation dryness index (TVDI) related to SM. The upscaled SM showed high consistency with in situ SM observations and could accurately capture rainfall events. The upscaled SM was considered as the reference data to evaluate RS SM products at different spatial scales. In regard to the validation results, in addition to the correlation coefficient (R) of the Soil Moisture Active Passive (SMAP) SM being slightly lower than that of the Climate Change Initiative (CCI) SM, SMAP had the best performance in terms of the root-mean-square error (RMSE), unbiased RMSE and bias, followed by the CCI. The Soil Moisture and Ocean Salinity (SMOS) products were in worse agreement with the upscaled SM and were inferior to the R value of the X-band SM of the Advanced Microwave Scanning Radiometer 2 (AMSR2). In conclusion, in the study area, the SMAP and CCI SM are more reliable, although both products were underestimated by 0.060 cm3 cm−3 and 0.077 cm3 cm−3, respectively. If the biases are corrected, then the improved SMAP with an RMSE of 0.043 cm3 cm−3 and the CCI with an RMSE of 0.039 cm3 cm−3 will hopefully reach the application requirement for an accuracy with an RMSE less than 0.040 cm3 cm−3.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Sungmin O. ◽  
Rene Orth

AbstractWhile soil moisture information is essential for a wide range of hydrologic and climate applications, spatially-continuous soil moisture data is only available from satellite observations or model simulations. Here we present a global, long-term dataset of soil moisture derived through machine learning trained with in-situ measurements, SoMo.ml. We train a Long Short-Term Memory (LSTM) model to extrapolate daily soil moisture dynamics in space and in time, based on in-situ data collected from more than 1,000 stations across the globe. SoMo.ml provides multi-layer soil moisture data (0–10 cm, 10–30 cm, and 30–50 cm) at 0.25° spatial and daily temporal resolution over the period 2000–2019. The performance of the resulting dataset is evaluated through cross validation and inter-comparison with existing soil moisture datasets. SoMo.ml performs especially well in terms of temporal dynamics, making it particularly useful for applications requiring time-varying soil moisture, such as anomaly detection and memory analyses. SoMo.ml complements the existing suite of modelled and satellite-based datasets given its distinct derivation, to support large-scale hydrological, meteorological, and ecological analyses.


2021 ◽  
Vol 13 (7) ◽  
pp. 1335
Author(s):  
Ronald Souza ◽  
Luciano Pezzi ◽  
Sebastiaan Swart ◽  
Fabrício Oliveira ◽  
Marcelo Santini

The Brazil–Malvinas Confluence (BMC) is one of the most dynamical regions of the global ocean. Its variability is dominated by the mesoscale, mainly expressed by the presence of meanders and eddies, which are understood to be local regulators of air-sea interaction processes. The objective of this work is to study the local modulation of air-sea interaction variables by the presence of either a warm (ED1) and a cold core (ED2) eddy, present in the BMC, during September to November 2013. The translation and lifespans of both eddies were determined using satellite-derived sea level anomaly (SLA) data. Time series of satellite-derived surface wind data, as well as these and other meteorological variables, retrieved from ERA5 reanalysis at the eddies’ successive positions in time, allowed us to investigate the temporal modulation of the lower atmosphere by the eddies’ presence along their translation and lifespan. The reanalysis data indicate a mean increase of 78% in sensible and 55% in latent heat fluxes along the warm eddy trajectory in comparison to the surrounding ocean of the study region. Over the cold core eddy, on the other hand, we noticed a mean reduction of 49% and 25% in sensible and latent heat fluxes, respectively, compared to the adjacent ocean. Additionally, a field campaign observed both eddies and the lower atmosphere from ship-borne observations before, during and after crossing both eddies in the study region during October 2013. The presence of the eddies was imprinted on several surface meteorological variables depending on the sea surface temperature (SST) in the eddy cores. In situ oceanographic and meteorological data, together with high frequency micrometeorological data, were also used here to demonstrate that the local, rather than the large scale forcing of the eddies on the atmosphere above, is, as expected, the principal driver of air-sea interaction when transient atmospheric systems are stable (not actively varying) in the study region. We also make use of the in situ data to show the differences (biases) between bulk heat flux estimates (used on atmospheric reanalysis products) and eddy covariance measurements (taken as “sea truth”) of both sensible and latent heat fluxes. The findings demonstrate the importance of short-term changes (minutes to hours) in both the atmosphere and the ocean in contributing to these biases. We conclude by emphasizing the importance of the mesoscale oceanographic structures in the BMC on impacting local air-sea heat fluxes and the marine atmospheric boundary layer stability, especially under large scale, high-pressure atmospheric conditions.


2004 ◽  
Vol 261-263 ◽  
pp. 1097-1102 ◽  
Author(s):  
Jian Liu ◽  
Xia Ting Feng ◽  
Xiu Li Ding ◽  
Huo Ming Zhou

The time-dependent behavior of rock mass, which is generally governed by joints and shearing zones, is of great significance for engineering design and prediction of long-term deformation and stability. In situ creep test is a more effective method than laboratory test in characterizing the creep behavior of rock mass with joint or shearing zone due to the complexity of field conditions. A series of in situ creep tests on granite with joint at the shiplock area of the Three-Gorges Project and basalt with shearing zone at the right abutment of the Xiluodu Project were performed in this study. Based on the test results, the stress-displacement-time responses of the joints and basalt are analyzed, and their time-dependent constitutive model and model coefficients are given, which is crucial for the design to prevent the creep deformations of rock masses from causing the failure of the operation of the shiplock gate at the Three-Gorges Project and long-term stability of the Xiluodu arc dam.


2001 ◽  
Vol 9 (1) ◽  
pp. 3-7
Author(s):  
Damon Liu ◽  
Mark Burgin ◽  
Walter Karplus ◽  
Daniel Valentino

2021 ◽  
Author(s):  
Xiao-Ya Zhai ◽  
Yifan Zhao ◽  
Guo-Ying Zhang ◽  
Bing-Yu Wang ◽  
Qi-Yun Mao

In the work, a direct Z-scheme AgBr/α-Ag2WO4 heterojunction was prepared by in-situ anion exchange at room temperature. The construction strategy is energy- and time-saving for large scale synthesis. The α-Ag2WO4...


Sign in / Sign up

Export Citation Format

Share Document