Search

Abstract In December 2019, the 13th revision of the International Geomagnetic Reference Field (IGRF) was released by the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group V-MOD. This revision comprises two new spherical harmonic main field models for epochs 2015.0 (DGRF-2015) and 2020.0 (IGRF-2020) and a model of the predicted secular variation for the interval 2020.0 to 2025.0 (SV-2020-2025). The models were produced from candidates submitted by fifteen international teams. These teams were led by the British Geological Survey (UK), China Earthquake Administration (China), Universidad Complutense de Madrid (Spain), University of Colorado Boulder (USA), Technical University of Denmark (Denmark), GFZ German Research Centre for Geosciences (Germany), Institut de physique du globe de Paris (France), Institut des Sciences de la Terre (France), Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (Russia), Kyoto University (Japan), University of Leeds (UK), Max Planck Institute for Solar System Research (Germany), NASA Goddard Space Flight Center (USA), University of Potsdam (Germany), and Université de Strasbourg (France). The candidate models were evaluated individually and compared to all other candidates as well to the mean, median and a robust Huber-weighted model of all candidates. These analyses were used to identify, for example, the variation between the Gauss coefficients or the geographical regions where the candidate models strongly differed. The majority of candidates were sufficiently close that the differences can be explained primarily by individual modeling methodologies and data selection strategies. None of the candidates were so different as to warrant their exclusion from the final IGRF-13. The IAGA V-MOD task force thus voted for two approaches: the median of the Gauss coefficients of the candidates for the DGRF-2015 and IGRF-2020 models and the robust Huber-weighted model for the predictive SV-2020-2025. In this paper, we document the evaluation of the candidate models and provide details of the approach used to derive the final IGRF-13 products. We also perform a retrospective analysis of the IGRF-12 SV candidates over their performance period (2015–2020). Our findings suggest that forecasting secular variation can benefit from combining physics-based core modeling with satellite observations.

Abstract In December 2019, the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group (V-MOD) adopted the thirteenth generation of the International Geomagnetic Reference Field (IGRF). This IGRF updates the previous generation with a definitive main field model for epoch 2015.0, a main field model for epoch 2020.0, and a predictive linear secular variation for 2020.0 to 2025.0. This letter provides the equations defining the IGRF, the spherical harmonic coefficients for this thirteenth generation model, maps of magnetic declination, inclination and total field intensity for the epoch 2020.0, and maps of their predicted rate of change for the 2020.0 to 2025.0 time period.

Objectives: Research has identified racial and ethnic disparities in rates of guilty pleas relative to trial where minorities are more likely to proceed to trial, though little research has explored the source of this disparity. Methods: vUsing an adult nationwide sample and a vignette methodology, this research uses Ordinary Least Squares regression to explore differences in White, Black, and Hispanic defendants' willingness to accept a guilty plea (WTAP). Results: Though there are not significant direct effects of race or ethnicity on initial WTAP, there are racial/ethnic differences in theoretical antecedents of WTAP such as perceived probability of conviction, court legitimacy, and attorney type. However, there are not differences in the effects of theoretical antecedents on WTAP across race or ethnicity. Significant differences by race/ethnicity also emerge following a defense attorney's evaluation of an offer and are conditional on guilt. Conclusions: Racial/ethnic differences in rates of plea acceptance are likely due to cumulative racial/ethnic differences in antecedents of WTAP, differences in the effect of attorney evaluation by race/ethnicity, and/or factors that were not directly examined in this study such as variation in plea offers. Implications for future research on the nexus between plea bargaining and race/ethnicity are discussed. [ABSTRACT FROM AUTHOR]

We investigate variations in the position of the magnetopause in response to the interplanetary magnetic field (IMF), and different phases of magnetospheric substorms. The average location of magnetopause is examined using magnetic field observations from multiple satellites (THEMIS, RBSP, and MMS), and the Shue model utilizing OMNI solar wind data for a period of five years from 2016–2020. We estimate average position of the magnetopause using Shue model through superposed epoch analysis of standoff distance and tail flaring angle at different substorm timings (onset, peak and end) and from in-situ measurements through 2D equatorial maps of average Δ BZ under IMF | Bz |> 0 conditions. Our findings reveal the occurrence of substorms during both northward and southward IMF orientations and highlight an earthward movement of the magnetopause during substorm onset and peak, followed by a relaxation during the substorm end time, for both northward and southward IMF orientations. Notably, the magnetopause undergoes significant compression and reaches its closest point to the Earth during instances of strong southward IMF (BZ < -5), particularly during the substorm peak. The empirical model provides accurate estimation of the magnetopause location during periods of both strong northward and southward IMF | Bz |>5, as the model curve traverses a distinct location (Δ BZ = 0) representing the magnetopause shown in the 2D average map of Δ BZ. [ABSTRACT FROM AUTHOR]

Future mass loss from the East Antarctic Ice Sheet represents a major uncertainty in projections of future sea level rise. Recent studies have highlighted the potential vulnerability of the East Antarctic Ice Sheet to atmospheric and oceanic changes, but long-term observations inside the ice shelf cavities are rare, especially in East Antarctica. Here, we present new insights from observations from three oceanic moorings below Fimbulisen Ice Shelf from 2009 to 2021. We examine the characteristics of Warm Deep Water (WDW) intrusions across a sill connecting the cavity to the open ocean, and investigate seasonal variability of the circulation and water masses inside the cavity. In autumn, solar-heated, buoyant Antarctic Surface Water (ASW) reaches below the 350 m deep central part of the ice shelf, separating colder Ice Shelf Water from the ice base and affecting the cavity circulation on seasonal timescales. At depth, the occurrence of WDW is associated with the advection of cyclonic eddies across the sill into the cavity. These eddies reach up to the ice base. The warm intrusions occur favorably from January to March and from September to November, and traces of WDW-derived meltwater close to the ice base imply an overturning of these warm intrusions inside the cavity. We suggest that both the offshore thermocline depth and interactions of the Antarctic Slope Current with the ice shelf topography over the continental slope cause this timing. Our findings provide a better understanding of the interplay between shallow ASW and deep WDW inflows for basal melting at Fimbulisen, with implications for the potential vulnerability of the ice shelf to climate change. [ABSTRACT FROM AUTHOR]

We present a comparative analysis of urban magnetic fields between two American cities: Berkeley (California) and Brooklyn Borough of New York City (New York). Our analysis uses data taken over a four-week period during which magnetic field data were continuously recorded using a fluxgate magnetometer with 70 pT/ Hz noise. We identified significant differences in the magnetic signatures. In particular, we noticed that Berkeley reaches a near-zero magnetic field activity at night, whereas magnetic activity in Brooklyn continues during nighttime. We also present auxiliary measurements acquired using magnetoresistive vector magnetometers (VMRs), with the noise of 300 pT/ Hz , and demonstrate how cross correlation, and frequency-domain analysis, combined with data filtering can be used to extract urban-magnetometry signals and study local anthropogenic activities. Finally, we discuss the potential of using magnetometer networks to characterize the global magnetic field of cities and give directions for future development. [ABSTRACT FROM AUTHOR]

The Global Navigation Satellite System (GNSS) is a well-known and fundamental tool for crustal monitoring projects and tectonic studies, thanks to its high coverage and the high quality of the data they provide. In particular, at slowly convergent margins, where deformation rates are of the order of a few millimetres per year, GNSS monitoring proves to be beneficial in detecting the diffuse deformation responsible for tectonic stress accrual. Its strength lies in the high precision achieved by GNSS permanent stations, especially when long-term data and stable structures are available at the stations. North-eastern Italy is a tectonically active region located in the northernmost sector of the Adria microplate, slowly converging with the Eurasia plate, characterized by low deformation rates and moderate seismicity. It greatly benefits from continuous and high-precision geodetic monitoring, since it has been equipped with a permanent GNSS network providing real-time data and daily observations over 2 decades. The Friuli Venezia Giulia Deformation Network (FReDNet) was established in the area in 2002 to monitor crustal deformation and contribute to the regional seismic hazard assessment. This paper describes GNSS time series spanning 2 decades of stations located in north-eastern Italy and surroundings as well as the outgoing velocity field. The documented dataset has been retrieved by processing the GNSS observations with the GAMIT/GLOBK software ver10.71, which allows calculation of high-precision coordinate time series, position and velocity for each GNSS station by taking advantage of the high-performance computing resources of the Italian High-Performance Computing Centre (CINECA) clusters. The GNSS observations (raw and standard RINEX – Receiver INdependent EXchange – formats) and the time series estimated with the same procedure are currently daily continued, collected and stored in the framework of a long-term monitoring project. Instead, velocity solutions are intended for annual updates. The time series and velocity field dataset documented here are available on Zenodo (10.5281/zenodo.8055800, Tunini et al., 2024). [ABSTRACT FROM AUTHOR]

The solar forcing prepared for Phase 6 of the Coupled Model Intercomparison Project (CMIP6) has been used extensively in climate model experiments and has been tested in various intercomparison studies. Recently, an International Space Science Institute (ISSI) working group has been established to revisit the solar forcing recommendations, based on the lessons learned from CMIP6, and to assess new datasets that have become available, in order to define a road map for building a revised and extended historical solar forcing dataset for the upcoming Phase 7 of CMIP. This paper identifies the possible improvements required and outlines a strategy to address them in the planned new solar forcing dataset. Proposed major changes include the adoption of the new Total and Spectral Solar Irradiance Sensor (TSIS-1) solar reference spectrum for solar spectral irradiance and an improved description of top-of-the-atmosphere energetic electron fluxes, as well as their reconstruction back to 1850 by means of geomagnetic proxy data. In addition, there is an urgent need to consider the proposed updates in the ozone forcing dataset in order to ensure a self-consistent solar forcing in coupled models without interactive chemistry. Regarding future solar forcing, we propose consideration of stochastic ensemble forcing scenarios, ideally in concert with other natural forcings, in order to allow for realistic projections of natural forcing uncertainties. [ABSTRACT FROM AUTHOR]

Recent advances in atmospheric observations and modeling have enabled the investigation of thermosphere–ionosphere interactions as a whole-atmosphere problem. This study examines how dynamical variability in the middle atmosphere (MA) affects intra-day changes in the thermosphere and ionosphere. Specifically, this study investigates ionosphere–thermosphere interactions during different time periods of January 2013 using the Specified Dynamics Whole Atmosphere Community Climate Model, eXtended version (SD-WACCM-X), coupled to the Naval Research Laboratory (NRL) ionosphere of the Sami3 is Another Model of the Ionosphere (SAMI3) model. To represent the weather of the day, the coupled thermosphere–ionosphere system is nudged below 90 km toward the atmospheric specifications provided by the Navy Global Environmental Model for High-Altitude (NAVGEM-HA). Hindcast simulations during January 2013 are carried out with the full dataset of observations normally assimilated by NAVGEM-HA and with a degraded dataset where observations above 40 km are not assimilated. Ionospheric regions with statistically significant changes are identified using key ionospheric properties, including the electron density, peak electron density, and height of the peak electron density. Ionospheric changes show a spatial structure that illustrates the impact of two different types of coupling between the thermosphere and the ionosphere: variability induced by wind-dynamo coupling through electric conductivity and ion-neutral interactions in the upper thermosphere. The two simulations presented in this study show that changing the state of the MA affects ionosphere–thermosphere coupling through changes in the behavior and amplitude of non-migrating tides, resulting in improved key ionospheric specifications. [ABSTRACT FROM AUTHOR]

EISCAT_3D is a project to build a multi-site phased-array incoherent scatter radar system in northern Fenno-Scandinavia. We demonstrate via numerical simulation how useful monochromatic images taken by a multi-point imager network are for auroral research in the EISCAT_3D project. We apply the generalized aurora computed tomography (G-ACT) method to modelled observational data from real instruments, such as the Auroral Large Imaging System (ALIS) and the EISCAT_3D radar. G-ACT is a method for reconstructing the three-dimensional (3D) distribution of auroral emissions and ionospheric electron density (corresponding to the horizontal two-dimensional (2D) distribution of energy spectra of precipitating electrons) from multi-instrument data. It is assumed that the EISCAT_3D radar scans an area of 0.8° in geographic latitude and 3° in longitude at an altitude of 130 km with 10 × 10 beams from the radar core site at Skibotn (69.35° N, 20.37° E). Two neighboring discrete arcs are assumed to appear in the observation region of the EISCAT_3D radar. The reconstruction results from G-ACT are compared with those from the normal ACT as well as the ionospheric electron density from the radar. It is found that G-ACT can interpolate the ionospheric electron density at a much higher spatial resolution than that observed by the EISCAT_3D radar. Furthermore, the multiple arcs reconstructed by G-ACT are more precise than those by ACT. In particular, underestimation of the ionospheric electron density and precipitating electrons' energy fluxes inside the arcs is significantly improved by G-ACT including the EISCAT_3D data. Even when the ACT reconstruction is difficult due to the unsuitable locations of the imager sites relative to the discrete arcs and/or a small number of available images, G-ACT allows us to obtain better reconstruction results. [ABSTRACT FROM AUTHOR]

The bottom part of the Earth's ionosphere is the so-called D region, which is typically less dense than the upper regions. Despite the comparably lower electron density, the ionization state of the D region has a significant influence on signal absorption for propagating lower to medium radio frequencies. We present local noon climatologies of electron densities in the upper middle atmosphere (50–90 km) at high latitudes as observed by an active radar experiment. The radar measurements cover 9 years (2014–2022) from the solar maximum of cycle 24 to the beginning of cycle 25. Reliable electron densities are derived by employing signal processing, applying interferometry methods, and applying the Faraday-International Reference Ionosphere (FIRI) model. For all years a consistent spring–fall asymmetry of the electron density pattern with a gradual increase during summer as well as a sharp decrease at the beginning of October was found. These findings are consistent with very low frequency (VLF) studies showing equivalent signatures for nearby propagation paths. It is suggested that the meridional circulation associated with downwelling in winter could cause enhanced electron densities through NO transport. However, this mechanism can not explain the reduction in electron density in early October. [ABSTRACT FROM AUTHOR]

SUMMARY: A series of models of the Earth magnetic field and core surface flow have been simultaneously and sequentially co-estimated from year 1999 to 2022. The models were derived from magnetic satellite and ground observatory data using a linear Kalman filter approach and prior statistics based on numerical dynamo simulations. The core field and secular variation model components present the same characteristics as the most recent core field models with slightly higher resolution in time. A principal component analysis of the core surface flow series of models shows that the largest flow variations are observed at high latitudes and under the western part of the Pacific Ocean. Filtering out the flow variation periods longer than ∼11.5 yr leads to a filtered azimuthal flow that presents ∼7 yr periodicities with patterns propagating westward by ∼60° longitude per year. These patterns are present mainly at mid- and equatorial latitudes. They are compatible with a perturbation of the main flow made of small columnar flows with rotation axis intersecting the core–mantle boundary between 10° and 15° latitudes, and flow speed of less than 5 km yr–1. Present at all longitudes, these columnar flows are particularly strong under the Pacific Ocean after 2013. They can also be clearly identified under the Atlantic Ocean from 2005 to 2015. [ABSTRACT FROM AUTHOR]

Commercially available anisotropic magnetoresistive (AMR) magnetometers exhibit on the order of 1 nanotesla (nT) sensitivity in small size, weight, and power (SWaP) packages. However, AMR magnetometer accuracy is diminished by properties such as static offsets, gain uncertainty, off-axis coupling, and temperature effects. This work presents a measurement of the magnitude of these effects for a Honeywell HMC1053 magnetometer and evaluates a method for calibrating the observed effects by multivariate non-linear regression using a 24-parameter measurement equation. The presented calibration method has reduced the vector norm of the root mean square error from 4300 to 72 nT for the data acquired in this experiment. This calibration method has been developed for use on the AERO (Auroral Emissions Radio Observer) and VISTA (Vector Interferometry Space Technology using AERO) CubeSat missions, but the methods and results may be applicable to other resource-constrained magnetometers whose accuracies are limited by the offset, gain, off-axis, and thermal effects that are similar to the HMC1053 AMR magnetometer. [ABSTRACT FROM AUTHOR]

On timescales longer than the solar cycle, long-term changes in CO 2 concentration and geomagnetic field have the potential to affect thermospheric dynamics. In this paper, we investigate the thermospheric dynamical response to these two factors during the Holocene, using two sets of ∼12000 -year control runs by the coupled thermosphere–ionosphere model, GCITEM-IGGCAS. The main results indicate that increased/decreased CO 2 will enhance/weaken the thermospheric circulation throughout the Holocene, but this effect is non-linear. The cooling effect of CO 2 in the thermosphere further provides plausible conditions for atmospheric tidal propagation and increases the thermospheric tidal amplitude. Geomagnetic variations induce hemispheric asymmetrical responses in the thermospheric circulation. Large changes in the circulation occur at high latitudes in the hemisphere with distant magnetic pole drift, inferring a crucial role of geomagnetic non-dipole variations in circulation changes. A positive correlation between the diurnal migrating tide (DW1) and geomagnetic dipole moment is revealed for the first time. The amplitude of DW1 in temperature will increase by ∼1 –3 K for each 1×1022 A m 2 increase in dipole moment. [ABSTRACT FROM AUTHOR]

In the previous work of Yue et al. (2022), the ionospheric evolution during the Holocene (9455 BC to 2015 AD) was comprehensively and carefully investigated for the first time using the Global Coupled Ionosphere-Thermosphere-Electrodynamics Model developed at the Institute of Geology and Geophysics, Chinese Academy of Sciences (GCITEM-IGGCAS), driven by realistic geomagnetic fields, CO2 levels, and solar activity derived from ancient media records and modern measurements. In this study, we further quantify the effects of the three drivers on thermospheric neutral density and temperature variations during the Holocene. We find that the oscillations of solar activity contribute more than 80 % of the thermospheric variability, while either CO2 or the geomagnetic field contributes less than 10 %. The effect of CO2 on the global mean neutral density and temperature is comparable to that of the geomagnetic field throughout the Holocene but is more significant after 1800 AD. In addition, thermospheric density and temperature show approximately linear variations with the dipole moment of the geomagnetic field, CO2 , and F10.7, with only the linear growth rate associated with the geomagnetic field varying significantly in universal time and latitude. The increasing dipole moment and CO2 cool and contract the thermosphere, while solar activity has the opposite effect. The higher the altitude, the greater the influence of the three factors on the thermosphere. Different factors produce different seasonal variations in thermosphere changes. Furthermore, we predict that a 400 ppm increase in CO2 will result in a 50 %–70 % and 84–114 K reduction in global mean neutral density and temperature, respectively, which should directly affect the orbit and lifetime of spacecraft and space debris. [ABSTRACT FROM AUTHOR]

Continuous integrated bioprocessing has elicited considerable interest from the biopharma industry for the many purported benefits it promises. Today many major biopharma manufacturers around the world are engaged in the development of continuous process platforms for their products. In spite of great potential, the path toward continuous integrated bioprocessing remains unclear for the biologics industry due to legacy infrastructure, process integration challenges, vague regulatory guidelines, and a diverging focus toward novel therapies. In this article, we present a review and perspective on this topic. We explore the status of the implementation of continuous integrated bioprocessing among biopharmaceutical manufacturers. We also present some of the key hurdles that manufacturers are likely to face during this implementation. Finally, we hypothesize that the real impact of continuous manufacturing is likely to come when the cost of manufacturing is a substantial portion of the cost of product development, such as in the case of biosimilar manufacturing and emerging economies. [ABSTRACT FROM AUTHOR]

A new reanalysis of Global Navigation Satellite System (GNSS) data at or near tide gauges worldwide was produced by the University of La Rochelle (ULR) group within the third International GNSS Service (IGS) reprocessing campaign (repro3). The new solution, called ULR-repro3, complies with the IGS standards adopted for repro3, implementing advances in data modelling and corrections since the previous reanalysis campaign and extending the average record length by about 7 years. The results presented here focus on the main products of interest for sea level science: the station position time series and associated velocities on the vertical component at tide gauges. These products are useful to estimate accurate vertical land motion at the coast and supplement data from satellite altimetry or tide gauges for an improved understanding of sea level changes and their impacts along coastal areas. To provide realistic velocity uncertainty estimates, the noise content in the position time series was investigated considering the impact of non-tidal atmospheric loading. Overall, the ULR-repro3 position time series show reduced white noise and power-law amplitudes and lower station velocity uncertainties compared with the previous reanalysis. The products are available via SONEL (10.26166/sonel_ulr7a; Gravelle et al., 2022). [ABSTRACT FROM AUTHOR]

This study examined the influence of undergraduate experience on alumni loyalty to their alma mater in Tanzania's higher education context. Specifically, the study sought to examine the extent to which alumni are satisfied with their undergraduate academic and social experiences and the influence thereof on their loyalty towards their former universities or colleges. The study involved a questionnaire survey to collect primary data from a conveniently selected sample of 188 Tanzanians who had bachelor's degrees from various Tanzania universities and colleges. Descriptive statistics using mean values were used to measure the satisfaction level. To estimate the influence of alumni satisfaction with their undergraduate experience on loyalty to their alma mater, Binary Logistic Regression Model was used. Overall, the findings indicate that alumni were satisfied with their undergraduate experience and their time as students. Further, Binary Logistic Regression results indicate that satisfaction with undergraduate experience positively and significantly influences alumni loyalty to their alma mater. It is reasonable to conclude from this evidence, that alumni loyalty can be created, reinforced and retained through favorable students' experiences. Thus, Tanzania's Higher Education Institutions (HEIs) should improve their level of students' experience so as to increase their level of satisfaction and consequently enforce their loyalty. The study adds value in the context of Tanzanian HEIs since it provides a base on how to determine strategies to create, reinforce and maintain alumni loyalty through a favorable student experience. [ABSTRACT FROM AUTHOR]

In December 2019, the 13th revision of the International Geomagnetic Reference Field (IGRF) was released by the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group V-MOD. This revision comprises two new spherical harmonic main field models for epochs 2015.0 (DGRF-2015) and 2020.0 (IGRF-2020) and a model of the predicted secular variation for the interval 2020.0 to 2025.0 (SV-2020-2025). The models were produced from candidates submitted by fifteen international teams. These teams were led by the British Geological Survey (UK), China Earthquake Administration (China), Universidad Complutense de Madrid (Spain), University of Colorado Boulder (USA), Technical University of Denmark (Denmark), GFZ German Research Centre for Geosciences (Germany), Institut de physique du globe de Paris (France), Institut des Sciences de la Terre (France), Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (Russia), Kyoto University (Japan), University of Leeds (UK), Max Planck Institute for Solar System Research (Germany), NASA Goddard Space Flight Center (USA), University of Potsdam (Germany), and Université de Strasbourg (France). The candidate models were evaluated individually and compared to all other candidates as well to the mean, median and a robust Huber-weighted model of all candidates. These analyses were used to identify, for example, the variation between the Gauss coefficients or the geographical regions where the candidate models strongly differed. The majority of candidates were sufficiently close that the differences can be explained primarily by individual modeling methodologies and data selection strategies. None of the candidates were so different as to warrant their exclusion from the final IGRF-13. The IAGA V-MOD task force thus voted for two approaches: the median of the Gauss coefficients of the candidates for the DGRF-2015 and IGRF-2020 models and the robust Huber-weighted model for the predictive SV-2020-2025. In this paper, we document the evaluation of the candidate models and provide details of the approach used to derive the final IGRF-13 products. We also perform a retrospective analysis of the IGRF-12 SV candidates over their performance period (2015–2020). Our findings suggest that forecasting secular variation can benefit from combining physics-based core modeling with satellite observations. [ABSTRACT FROM AUTHOR]

In December 2019, the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group (V-MOD) adopted the thirteenth generation of the International Geomagnetic Reference Field (IGRF). This IGRF updates the previous generation with a definitive main field model for epoch 2015.0, a main field model for epoch 2020.0, and a predictive linear secular variation for 2020.0 to 2025.0. This letter provides the equations defining the IGRF, the spherical harmonic coefficients for this thirteenth generation model, maps of magnetic declination, inclination and total field intensity for the epoch 2020.0, and maps of their predicted rate of change for the 2020.0 to 2025.0 time period. [ABSTRACT FROM AUTHOR]

Continuous countercurrent tangential chromatography (CCTC) enables steady‐state continuous bioprocessing with low‐pressure operation and high productivity. CCTC has been applied to initial capture of monoclonal antibodies (mAb) from clarified cell culture harvest and postcapture polishing of mAb; however, these studies were performed with commercial chromatography resins designed for conventional column chromatography. In this study, a small particle size prototype agarose resin (20–25 µm) with lower cross‐linking was co‐developed with industrial partner Purolite and tested with CCTC. Due to increased binding capacity and faster kinetics, the resulting CCTC process showed more than a 2X increase in productivity, and a 2X reduction in buffer consumption over commercial protein A resins used in previous CCTC studies, as well as more than a 10X productivity increase versus conventional column operation. Single‐pass tangential flow filtration was integrated with the CCTC system, enabling simple control of eluate concentration. A scale‐up exercise was conducted to provide a quantitative comparison of CCTC and batch column chromatography. These results clearly demonstrate opportunities for using otherwise unpackable soft small particle size resins with CCTC as the core of a continuous bioprocessing platform. [ABSTRACT FROM AUTHOR]

Purpose: There is a growing interest in continuous biopharmaceutical processing due to the advantages of small footprint, increased productivity, consistent product quality, high process flexibility and robustness, facility cost-effectiveness, and reduced capital and operating cost. To support the decision making of biopharmaceutical manufacturing, comparisons between conventional batch and continuous processing are provided. Methods: Various process unit operations in different operating modes are summarized. Software implementation as well as computational methods used are analyzed pointing to the advantages and disadvantages that have been highlighted in the literature. Economic analysis methods and their applications in different parts of the processes are also discussed with examples from publications in the last decade. Results: The results of the comparison between batch and continuous process operation alternatives are discussed. Possible improvements in process design and analysis are recommended. The methods used here do not reflect Lilly's cost structures or economic evaluation methods. Conclusion: This paper provides a review of the work that has been published in the literature on computational process design and economic analysis methods on continuous biopharmaceutical antibody production and its comparison with a conventional batch process. [ABSTRACT FROM AUTHOR]

Tissues and biofluids are important sources of information used for the detection of diseases and decisions on patient therapies. There are several accepted methods for preservation of tissues, among which the most popular are fresh‐frozen and formalin‐fixed paraffin embedded methods. Depending on the preservation method and the amount of sample available, various specific protocols are available for tissue processing for subsequent proteomic analysis. Protocols are tailored to answer various biological questions, and as such vary in lysis and digestion conditions, as well as duration. The existence of diverse tissue‐sample protocols has led to confusion in how to choose the best protocol for a given tissue and made it difficult to compare results across sample types. Here, we summarize procedures used for tissue processing for subsequent bottom‐up proteomic analysis. Furthermore, we compare protocols for their variations in the composition of lysis buffers, digestion procedures, and purification steps. For example, reports have shown that lysis buffer composition plays an important role in the profile of extracted proteins: the most common are tris(hydroxymethyl)aminomethane, radioimmunoprecipitation assay, and ammonium bicarbonate buffers. Although, trypsin is the most commonly used enzyme for proteolysis, in some protocols it is supplemented with Lys‐C and/or chymotrypsin, which will often lead to an increase in proteome coverage. Data show that the selection of the lysis procedure might need to be tissue‐specific to produce distinct protocols for individual tissue types. Finally, selection of the procedures is also influenced by the amount of sample available, which range from biopsies or the size of a few dozen of mm2 obtained with laser capture microdissection to much larger amounts that weight several milligrams. [ABSTRACT FROM AUTHOR]

Mass spectrometry is a highly complex analytical technique and mass spectrometry‐based proteomics experiments can be subject to a large variability, which forms an obstacle to obtaining accurate and reproducible results. Therefore, a comprehensive and systematic approach to quality control is an essential requirement to inspire confidence in the generated results. A typical mass spectrometry experiment consists of multiple different phases including the sample preparation, liquid chromatography, mass spectrometry, and bioinformatics stages. We review potential sources of variability that can impact the results of a mass spectrometry experiment occurring in all of these steps, and we discuss how to monitor and remedy the negative influences on the experimental results. Furthermore, we describe how specialized quality control samples of varying sample complexity can be incorporated into the experimental workflow and how they can be used to rigorously assess detailed aspects of the instrument performance. [ABSTRACT FROM AUTHOR]

A number of groups have studied the application of continuous bioreactors and continuous chromatographic systems as part of efforts to develop an integrated continuous biomanufacturing process. The objective of this study was to examine the feasibility of using a countercurrent staged diafiltration process for continuous protein formulation with reduced buffer requirements. Experiments were performed using a polyclonal immunoglobulin (IgG) with Cadence™ Inline Concentrators. Model equations were developed for the product yield, impurity removal, and buffer requirements as a function of the number of stages and the stage conversion (ratio of permeate to feed flow rate). Data from a countercurrent two-stage system were in excellent agreement with model calculations, demonstrating the potential of using countercurrent staged diafiltration for protein formulation. Model simulations demonstrated the importance of the countercurrent staging on both the extent of buffer exchange and the amount of buffer required per kg of formulated product. The staged diafiltration process not only provides for continuous buffer exchange, it could also provide significant reductions in the number of pump passes while providing opportunities for reduced buffer requirements. [ABSTRACT FROM AUTHOR]

BACKGROUND:Medication use by naval aviators, either prescription or over-the-counter, is not always relayed to the flight surgeon, resulting in unsafe flying environments. Many medications have debilitating effects that prohibit their use during aviation. Education and availability of resources on approved medications for flight status personnel is lacking. METHODS:A retrospective search of the Department of Defense Composite Health Care System (DoD CHCS) was conducted from five geographic locations. Basic epidemiological information was obtained to determine the most common medications (N = 70) prescribed to active-duty flight status personnel. Analysis determined their medication category, flight status designation, and a generalized location comparison. A similar control medication list for nonflight status personnel was generated from one location. RESULTS:Analysis found that many medications prescribed to aviators are not approved for use in aviation and are similar to those of nonflight status personnel. There were 8 of the top 15 (53%) and 40 of the 70 (57%) most commonly prescribed medications of flight status personnel which were not approved. Similarly, 49% of total prescriptions (N = 15,652) were not approved. Little difference was found in medications among nonflight and flight status personnel, as 11 of the top 15 prescription medications (73%) were identical. DISCUSSION:This research demonstrates the need for education regarding certain medications and their prohibited use during flight. Results will provide the Flight Surgeon common medications prescribed to aviators to aid them in providing a safer flying environment. [ABSTRACT FROM AUTHOR]

Most of the existing production capacity is based on fed-batch bioreactors. Thanks to the development of more efficient cell lines and the development of high-performance culture media, cell productivity dramatically increased. In a manufacturing perspective, it is necessary to clear as quickly as possible the protein A capture step to respect the manufacturing agenda. This article describes the methodology applied for the design of a multicolumn chromatography process with the objective of purifying as quickly as possible 1,000 and 15,000 L fed-batch bioreactors. Several recent and reference protein A resins are compared based on characteristic values obtained from breakthrough curves. The importance and relevance of resin parameters are explained, and purposely simple indicators are proposed to quickly evaluate the potential of each candidate. Based on simulation data, the optimum BioSC systems associated with each resin are then compared. The quality of the elution delivered by each resin is also compared to complete the assessment. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:941-953, 2017 [ABSTRACT FROM AUTHOR]

The pressures to efficiently produce complex biopharmaceuticals at reduced costs are driving the development of novel techniques, such as in downstream processing with straight-through processing (STP). This method involves directly and sequentially purifying a particular target with minimal holding steps. This work developed and compared six different 3-step STP strategies, combining membrane adsorbers, monoliths, and resins, to purify a large, complex, and labile glycoprotein from Chinese hamster ovary cell culture supernatant. The best performing pathway was cation exchange chromatography to hydrophobic interaction chromatography to affinity chromatography with an overall product recovery of up to 88% across the process and significant clearance of DNA and protein impurities. This work establishes a platform and considerations for the development of STP of biopharmaceutical products and highlights its suitability for integration with single-use technologies and continuous production methods. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:931-940, 2017 [ABSTRACT FROM AUTHOR]

Nanotechnology has potential applications in different sciences, especially in the biological sciences and medicine. The development of nanofibers has greatly enhanced the scope for fabricating designs that can potentially use in medical sciences. Nanofibers mimic the porous topography of natural extracellular matrix, and are advantageous for tissue regeneration and also sustained release of encapsulated drug or growth factor. In part IV the author summarizes the currently available applications of nanofibers in drug and biological materials delivery. [ABSTRACT FROM AUTHOR]

Protein aggregation into insoluble amyloid fibrils is the hallmark of several neurodegenerative diseases, chief among them Alzheimer's and Parkinson's. Although caused by different proteins, these pathologies share some basic molecular mechanisms with familial amyloidotic polyneuropathy (FAP), a rare hereditary neuropathy caused by amyloid formation and deposition by transthyretin (TTR) in the peripheral and autonomic nervous systems. Among the amyloidogenic TTR mutations known, V30M-TTR is the most common in FAP. TTR amyloidogenesis (ATTR) is triggered by tetramer dissociation, followed by partial unfolding and aggregation of the low conformational stability monomers formed. Thus, tetramer dissociation kinetics, monomer conformational stability and competition between refolding and aggregation pathways do play a critical role in ATTR. Here, we propose a new model to analyze the refolding kinetics of WT-TTR and V30M-TTR, showing that at pH and protein concentrations close to physiological, a two-step mechanism with a unimolecular first step followed by a second-order second step adjusts well to the experimental data. Interestingly, although sharing the same kinetic mechanism, V30M-TTR refolds at a much slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways and, thus, significantly increasing the probability of amyloid formation in vivo. [ABSTRACT FROM AUTHOR]

Recently, continuous downstream processing has become a topic of discussion and analysis at conferences while no industrial applications of continuous downstream processing for biopharmaceutical manufacturing have been reported. There is significant potential to increase the productivity of a Protein A capture step by converting the operation to simulated moving bed (SMB) mode. In this mode, shorter columns are operated at higher process flow and corresponding short residence times. The ability to significantly shorten the product residence time during loading without appreciable capacity loss can dramatically increase productivity of the capture step and consequently reduce the amount of Protein A resin required in the process. Previous studies have not considered the physical limitations of how short columns can be packed and the flow rate limitations due to pressure drop of stacked columns. In this study, we are evaluating the process behavior of a continuous Protein A capture column cycling operation under the known pressure drop constraints of a compressible media. The results are compared to the same resin operated under traditional batch operating conditions. We analyze the optimum system design point for a range of feed concentrations, bed heights, and load residence times and determine achievable productivity for any feed concentration and any column bed height. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:938-948, 2016 [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that continuous countercurrent tangential chromatography (CCTC) can effectively purify monoclonal antibodies from clarified cell culture fluid. CCTC has the potential to overcome many of the limitations of conventional packed bed protein A chromatography. This paper explores the optimization of CCTC in terms of product yield, impurity removal, overall productivity, and buffer usage. Modeling was based on data from bench-scale process development and CCTC experiments for protein A capture of two clarified Chinese Hamster Ovary cell culture feedstocks containing monoclonal antibodies provided by industrial partners. The impact of resin binding capacity and kinetics, as well as staging strategy and buffer recycling, was assessed. It was found that optimal staging in the binding step provides better yield and increases overall system productivity by 8-16%. Utilization of higher number of stages in the wash and elution steps can lead to significant decreases in buffer usage (∼40% reduction) as well as increased removal of impurities (∼2 log greater removal). Further reductions in buffer usage can be obtained by recycling of buffer in the wash and regeneration steps (∼35%). Preliminary results with smaller particle size resins show that the productivity of the CCTC system can be increased by 2.5-fold up to 190 g of mAb/L of resin/hr due to the reduction in mass transfer limitations in the binding step. These results provide a solid framework for designing and optimizing CCTC technology for capture applications. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:430-439, 2016 [ABSTRACT FROM AUTHOR]

ABSTRACT There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. Biotechnol. Bioeng. 2016;113: 465-475. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: Using concepts from evidence-based medicine, systems theory, and risk assessment, a standardized model was developed to accept or reject medications for use in flight. The model calculates the risk scores of medications, which can then be compared to an organization's acceptable risk tolerance. METHODS: Risk scores for each medication were established by summing the products of incidence rates and severity scores for all published side effects. The incidence of each side effect was obtained in an evidence-based manner and each assigned a severity multiplier. Using statistical analysis of the calculated risk scores of approved medications, an acceptance control chart was generated. RESULTS: Range of calculated risk scores of historically approved medications was 10-9140. Six Sigma Acceptance Control Line was calculated at 1.5 SDs above the mean and was 9822. Risk score range of medications generally felt unsafe was 27,010-41,294. Risk score range of medications under consideration for approval was 986-6863. DISCUSSION: This novel approach to medication approval is the first in aerospace medicine to attempt to combine evidence-based medicine, risk analysis, and control charts to standardize and streamline the medication approval process within an organization. The model was validated by testing against medications generally accepted to be unsafe for use in flight. These medications fell several deviations above the control line. Other medications not yet authorized fall well below the acceptance line and could be considered for approval. [ABSTRACT FROM AUTHOR]

Temperature is one of the most important parameters affecting the length and rate of alcoholic fermentation and final wine quality. Wine produced at low temperature is often considered to have improved sensory qualities. However, there are certain drawbacks to low temperature fermentations such as reduced growth rate, long lag phase, and sluggish or stuck fermentations. To investigate the effects of temperature on commercial wine yeast, we compared its metabolome growing at 12°C and 28°C in a synthetic must. Some species of the Saccharomyces genus have shown better adaptation at low temperature than Saccharomyces cerevisiae. This is the case of the cryotolerant yeasts Saccharomyces bayanus var. uvarum and Saccharomyces kudriavzevii. In an attempt to detect inter-specific metabolic differences, we characterized the metabolome of these species growing at 12°C, which we compared with the metabolome of S. cerevisiae (not well adapted at low temperature) at the same temperature. Our results show that the main differences between the metabolic profiling of S. cerevisiae growing at 12°C and 28°C were observed in lipid metabolism and redox homeostasis. Moreover, the global metabolic comparison among the three species revealed that the main differences between the two cryotolerant species and S. cerevisiae were in carbohydrate metabolism, mainly fructose metabolism. However, these two species have developed different strategies for cold resistance. S. bayanus var. uvarum presented elevated shikimate pathway activity, while S. kudriavzevii displayed increased NAD+ synthesis. [ABSTRACT FROM AUTHOR]

This study aimed at investigating the relationship between computer anxiety and computer attitude and examining the effects of background characteristics on prospective EFL teachers' computer anxiety and computer attitude. Computer Anxiety Scale (CARS), designed by Heinssen, Glass & Knight (1987) and Computer Attitude Scale (CAS), developed by Loyd & Gressard (1985) and modified by Yuen & Ma (2001) were administered to 70 prospective EFL teachers. Descriptive results indicated that prospective EFL teachers had relatively moderate scores in CARS (M=3.20; SD=.35729) and the sub-scales of CAS, computer confidence (M=3.02; SD= .43951), computer liking (M=3.17; SD= .47379) and computer usefulness (M=3.35; SD= .67647). Although a significant correlation was found between computer anxiety and computer liking (r = .35, n=70, p< 0.01), no significant correlation was found between computer anxiety and computer confidence (r = .19, n=70, p<0.01) and between computer anxiety and computer usefulness (r = .22, n=70, p<0.01). In the study, age, year of study, computer ownership and degree of access to computers were not found to be significant correlates of computer anxiety and computer attitude. While gender and the CAS subscale “usefulness” (r = .28, n=70, p< 0.05) and CGPA (Cumulative Grade Point Average) and CAS subscale “liking” (r = 23, n=70, p< 0.05) were found to be positively correlated, computer courses taken previously and the CAS subscale “liking” (r = -.24, n=70, p< 0.05) and computer experience and the CAS subscale “confidence” (r = -.30, n=70, p< 0.01) were found to be negatively correlated. [ABSTRACT FROM AUTHOR]

Continuous biomanufacturing of recombinant therapeutic proteins offers several potential advantages over conventional batch processing, including reduced cost of goods, more flexible and responsive manufacturing facilities, and improved and consistent product quality. Although continuous approaches to various upstream and downstream unit operations have been considered and studied for decades, in recent years interest and application have accelerated. Researchers have achieved increasingly higher levels of process intensification, and have also begun to integrate different continuous unit operations into larger, holistically continuous processes. This review first discusses approaches for continuous cell culture, with a focus on perfusion-enabling cell separation technologies including gravitational, centrifugal, and acoustic settling, as well as filtration-based techniques. We follow with a review of various continuous downstream unit operations, covering categories such as clarification, chromatography, formulation, and viral inactivation and filtration. The review ends by summarizing case studies of integrated and continuous processing as reported in the literature.