Causes of industrial protein a column degradation, explored using Raman spectroscopy.

Monoclonal antibodies (mAbs) are used extensively as biotherapeutics for chronic and acute conditions. Production of mAbs is lengthy and expensive, with protein A affinity capture the most costly step, due both to the nature of the resin and its marked reduction in binding capacity with repeated use. Our previous studies using in situ ATR-FTIR spectroscopy indicated that loss in protein A binding capacity is not the result of leaching or degradation of protein A ligand, suggesting fouling is the principal cause. Here we explore binding behavior and resin capacity loss using Raman spectroscopy. Our data reveal a distinct Raman spectral fingerprint for mAb bound to the protein A ligand of MabSelect SuRe. The results show that the drop in static binding capacity (SBC) previously observed for used protein A resin is discernible by Raman spectroscopy in combination with partial least-squares regression. The SBC is lowest (35.76 mg mL-1) for used inlet resin compared to used outlet (40.17 mg mL-1) and unused resin samples (70.35 mg mL-1). Depth profiling by Raman spectroscopy indicates that at below saturating concentrations (∼18 mg mL-1), binding of mAb is not homogeneous through used resin beads with protein binding preferentially to the outer regions of the bead, in contrast to fully homogeneous distribution through unused control MabSelect SuRe resin beads. Analysis of the Raman spectra indicates that one foulant is irreversibly bound mAb. The presence of irreversibly bound mAb and host cell proteins was confirmed by mass spectrometric analysis of used resin beads

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study

Introduction: Breast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10–40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device. Materials and methods: 40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated. Results: The study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins. Conclusion: The present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase–III–trial

Stellar archaeology with Gaia: the Galactic white dwarf population

Gaia will identify several 1e5 white dwarfs, most of which will be in the solar neighborhood at distances of a few hundred parsecs. Ground-based optical follow-up spectroscopy of this sample of stellar remnants is essential to unlock the enormous scientific potential it holds for our understanding of stellar evolution, and the Galactic formation history of both stars and planets.Comment: Summary of a talk at the 'Multi-Object Spectroscopy in the Next Decade' conference in La Palma, March 2015, to be published in ASP Conference Series (editors Ian Skillen & Scott Trager

Ferroelectric orthorhombic ZrO2 thin films achieved through nanosecond laser annealing

A new approach for the stabilization of the ferroelectric orthorhombic ZrO2 films is demonstrated through nanosecond laser annealing (NLA) of as-deposited Si/SiOx/W(14 nm)/ZrO2(8 nm)/W(22 nm), grown by ion beam sputtering at low temperatures. The NLA process optimization is guided by COMSOL multiphysics simulations. The films annealed under the optimized conditions reveal the presence of the orthorhombic phase, as confirmed by X-ray diffraction, electron backscatter diffraction, and transmission electron microscopy. Macroscopic polarization-electric field hysteresis loops show ferroelectric behavior, with saturation polarization of 12.8 mu C cm(-2), remnant polarization of 12.7 mu C cm(-2) and coercive field of 1.2 MV cm(-1). The films exhibit a wake-up effect that is attributed to the migration of point defects, such as oxygen vacancies, and/or a transition from nonferroelectric (monoclinic and tetragonal phase) to the ferroelectric orthorhombic phase. The capacitors demonstrate a stable polarization with an endurance of 6.0 x 10(5) cycles, demonstrating the potential of the NLA process for the fabrication of ferroelectric memory devices with high polarization, low coercive field, and high cycling stability.A.P.S.C. and M.C.I. contributed equally to this work. This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding Contract UIDB/04650/2020. This work has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 958174 (M-ERA-NET3/0003/2021-NanOx4EStor). M. C. I. and C. G. acknowledge the financial support by a grant of the Ministry of Research, Innovation and Digitization, CNCS/CCCDI - UEFISCDI, project number COFUND-M-ERANET-3-NanOx4Estor, within PNCDI III and POC 332/390008/29.12.2020-SMIS 109522. The authors acknowledge the CERIC-ERIC Consortium for access to experimental facilities and financial support under proposals 20202037, 20202038, and 20192055. The authors would also like to thank Jose Santos for technical support in the Thin Film Laboratory at CF-UM-UP. J.L.M-D. thanks the ERC grant, EU-H2020-ERC-ADG #882929, EROS. And the Royal Academy of Engineering, grant CIET1819_24. MOH thanks the Herchel Smith foundation of Cambridge for a research fellowship. This work made use of the University of Cambridge Wolfson Electron Microscopy Suite

An Innovative System for Monitoring Radon and Indoor Air Quality

Nowadays, a global trend towards increasing the performance of a building is the reduction in energy consumption. In this respect, for existing residential buildings the most common techniques are the application of a thermal insulation layer to the exterior wall of the building and / or window replacements. Unfortunately, their application without proper education of those involved may have a negative effect on the indoor air quality. The use of a continuous monitoring device can give the owner the ability to understand the impact of his behaviour on indoor air quality and, as such, to adjust his routine in order to maintain the indoor air quality at the desired level. This paper introduces a prototype, called ICA system, for continuous, real-time indoor air quality monitoring. The ICA system presents sensors for monitoring the concentration of radon, CO2, CO, VOCs, as well as meteorological parameters, such as temperature, pressure, and relative humidity. Experiments were performed both in laboratory and in situ conditions for testing and validating the proposed system.This work was supported by the project ID P_37_229, Contract No. 22/01.09.2016, with the title “Smart Systems for Public Safety through Control and Mitigation of Residential Radon linked with Energy Efficiency Optimization of Buildings in Romanian Major Urban Agglomerations SMART-RAD-EN” of the POC Programme

On Distant Speech Recognition for Home Automation

The official version of this draft is available at Springer via http://dx.doi.org/10.1007/978-3-319-16226-3_7International audienceIn the framework of Ambient Assisted Living, home automation may be a solution for helping elderly people living alone at home. This study is part of the Sweet-Home project which aims at developing a new home automation system based on voice command to improve support and well-being of people in loss of autonomy. The goal of the study is vocal order recognition with a focus on two aspects: distance speech recognition and sentence spotting. Several ASR techniques were evaluated on a realistic corpus acquired in a 4-room flat equipped with microphones set in the ceiling. This distant speech French corpus was recorded with 21 speakers who acted scenarios of activities of daily living. Techniques acting at the decoding stage, such as our novel approach called Driven Decoding Algorithm (DDA), gave better speech recognition results than the baseline and other approaches. This solution which uses the two best SNR channels and a priori knowledge (voice commands and distress sentences) has demonstrated an increase in recognition rate without introducing false alarms

The Green Bank North Celestial Cap Survey. IX. Timing Follow-up for 128 Pulsars

The Green Bank North Celestial Cap survey is one of the largest and most sensitive searches for pulsars and transient radio objects. Observations for the survey have finished; priorities have shifted toward long-term monitoring of its discoveries. In this study, we have developed a pipeline to handle large data sets of archival observations and connect them to recent, high-cadence observations taken using the Canadian Hydrogen Intensity Mapping Experiment telescope. This pipeline handles data for 128 pulsars and has produced measurements of spin, positional, and orbital parameters that connect data over observation gaps as large as 2000 days. We have also measured glitches in the timing residuals for five of the pulsars included and proper motion for 19 sources (13 new). We include updates to orbital parameters for 19 pulsars, including nine previously unpublished binaries. For two of these binaries, we provide updated measurements of post-Keplerian binary parameters, which result in much more precise estimates of the total masses of both systems. For PSR J0509+3801, the much improved measurement of the Einstein delay yields much improved mass measurements for the pulsar and its companion, 1.399(6) M⊙ and 1.412(6) M⊙, respectively. For this system, we have also obtained a measurement of the orbital decay due to the emission of gravitational waves

X-Shooting ULLYSES: Massive stars at low metallicity: I. Project description

Observations of individual massive stars, super-luminous supernovae, gamma-ray bursts, and gravitational wave events involving spectacular black hole mergers indicate that the low-metallicity Universe is fundamentally different from our own Galaxy. Many transient phenomena will remain enigmatic until we achieve a firm understanding of the physics and evolution of massive stars at low metallicity (Z). The Hubble Space Telescope has devoted 500 orbits to observing ∼250 massive stars at low Z in the ultraviolet (UV) with the COS and STIS spectrographs under the ULLYSES programme. The complementary X-Shooting ULLYSES (XShootU) project provides an enhanced legacy value with high-quality optical and near-infrared spectra obtained with the wide-wavelength coverage X-shooter spectrograph at ESOa's Very Large Telescope. We present an overview of the XShootU project, showing that combining ULLYSES UV and XShootU optical spectra is critical for the uniform determination of stellar parameters such as effective temperature, surface gravity, luminosity, and abundances, as well as wind properties such as mass-loss rates as a function of Z. As uncertainties in stellar and wind parameters percolate into many adjacent areas of astrophysics, the data and modelling of the XShootU project is expected to be a game changer for our physical understanding of massive stars at low Z. To be able to confidently interpret James Webb Space Telescope spectra of the first stellar generations, the individual spectra of low-Z stars need to be understood, which is exactly where XShootU can deliver

Astrophysics with the Laser Interferometer Space Antenna

The Laser Interferometer Space Antenna (LISA) will be a transformative experiment for gravitational wave astronomy, and, as such, it will offer unique opportunities to address many key astrophysical questions in a completely novel way. The synergy with ground-based and space-born instruments in the electromagnetic domain, by enabling multi-messenger observations, will add further to the discovery potential of LISA. The next decade is crucial to prepare the astrophysical community for LISA’s first observations. This review outlines the extensive landscape of astrophysical theory, numerical simulations, and astronomical observations that are instrumental for modeling and interpreting the upcoming LISA datastream. To this aim, the current knowledge in three main source classes for LISA is reviewed; ultra-compact stellar-mass binaries, massive black hole binaries, and extreme or interme-diate mass ratio inspirals. The relevant astrophysical processes and the established modeling techniques are summarized. Likewise, open issues and gaps in our understanding of these sources are highlighted, along with an indication of how LISA could help making progress in the different areas. New research avenues that LISA itself, or its joint exploitation with upcoming studies in the electromagnetic domain, will enable, are also illustrated. Improvements in modeling and analysis approaches, such as the combination of numerical simulations and modern data science techniques, are discussed. This review is intended to be a starting point for using LISA as a new discovery tool for understanding our Universe