342 research outputs found
Gauge-independent Renormalization of the 2-Higgs-Doublet Model
The 2-Higgs-Doublet Model (2HDM) belongs to the simplest extensions of the
Standard Model (SM) Higgs sector that are in accordance with theoretical and
experimental constraints. In order to be able to properly investigate the
experimental Higgs data and, in the long term to distinguish between possible
models beyond the SM, precise predictions for the Higgs boson observables have
to be made available on the theory side. This requires the inclusion of the
higher order corrections. In this work, we investigate in detail the
renormalization of the 2HDM, a pre-requisite for the computation of higher
order corrections. We pay particular attention to the renormalization of the
mixing angles and , which diagonalize the Higgs mass matrices
and which enter all Higgs observables. The implications of various
renormalization schemes in next-to-leading order corrections to the sample
processes and are investigated. Based on our
findings, we will present a renormalization scheme that is at the same time
process independent, gauge independent and numerically stable
Synthesis of clickable macro-porous materials for ultrafast purification of monoclonal antibodies
Porous polymers are topical materials and have gained a lot of interest in both academic and industrial research because they combine particular features of porous materials with those of synthetic polymers. Nowadays, porous polymers are used for a variety of different application fields such as catalysis, gas storage, or as separation materials. Various manufacturing methods can be applied to produce macroscopic porous polymeric particles, but most of them require the utilisation of a suspension polymerisation process in the presence of a porogen. This method often negatively affects the control of the final morphologies and requires a tedious work up as the porogen has to be fully extracted. In previous works, we have already presented âreactive gelationâ as an alternative, porogen-free method to produce macro-porous materials by controlled aggregation of colloidal polymer nanoparticles under high shear1,2. Nevertheless, the production of macroporous polymers, which allow an easy post-functionalization had yet to be proven to address relevant applications like the chromatography of therapeutic proteins for instance.
Herein, we present the emulsion polymerisation of highly crosslinked styrene-co-vinyl benzyl azide core-shell nanoparticles (~40 nm), their aggregation at high shear rates (106 1/s), and the hardening of the obtained fractal structures by post-polymerisation. This process results in chemically and physically stable macroporous microclusters with average size around 80 microns and pore sizes up to 10 ”m. Thanks to the azide groups in the shell, the macroporous polymer scaffold can easily be post-functionalized by exploiting the concept of copper catalysed alkyne-azide cycloaddition (CuAAC). Among a vast number of functionalities that have been clicked onto the porous base material, we have also immobilised staphylococcus aureus protein A, well known as an affinity ligand for the capturing of monoclonal antibodies. By immobilising protein A on a macroporous scaffold, we are addressing the most significant bottleneck of large-scale production of therapeutic proteins, namely the purification of such. Indeed, the separation of the target protein from its cell impurities (host cell proteins, DNA, enzymes, etc.) often consists up to 80 % of the overall production costs because conventional chromatographic materials are not mechanically stable and only possess small pores (up to 150 nm). These smaller pores result in a diffusion-limited flow behaviour, making the downstream process costly and time-consuming. Our base material combines mechanical stability and perfusive flow behaviour, thereby providing protein separation at very high flow rates up to 1800 cm/hr. This excels conventional industrial materials by far, which can usually be used between 300-600 cm/hr. Noteworthy, the dynamic binding capacity is independent of the process rate, giving 10 g/l at 1800 cm/hr. The developed protein A prototype has also been proved stable under alkaline conditions, showing recovery above 80 % after 80 cycles with 0.1 M NaOH solution. However, since the industrial downstream process has a few other chromatographic steps following the capturing (such as ion-exchange chromatography and hydrophobic interaction chromatography), also polyelectrolytes and aliphatic molecules have successfully been attached to the macroporous base material. Addressing all types of chromatography needed during the purification of therapeutic proteins with just one base material highlights the true potential of this material, and might pave the way for perfusive protein chromatography.
In summary, we have demonstrated emulsion polymerisation towards clickable core-shell nanoparticles, their aggregation under shear yielding macroporous particles, and their application as chromatography resins for the ultra-fast downstream of therapeutic proteins. Since the click chemistry protocol allows easy functionalization, the proposed process is expected to be suitable for other application fields as well.
1. Brand, B.; Morbidelli, M.; Soos, M., Shear-Induced Reactive Gelation. Langmuir 2015, 31 (46), 12727-12735.
2. Cingolani, A.; Baur, D. ; Caimi, S.; Storti, G.; Morbidelli, M., Preparation of perfusive chromatographic materials via shear-induced reactive gelation. J. Chromatogr. A 2018, in pres
Hetero-Supramolecular Modification of Nanocrystalline TiOâ-Film Electrodes: Photoassisted Electrocatalysis at Bââ-on-TiOâ
Nanocrystalline TiO2-film electrodes exhibit a unique set of intrinsic properties (transparency for visible light, electric conductivity in the doped state, semiconductor properties, large surface area, surface affinity towards organic anchoring groups). These can be combined with those of TiO2-surface-anchored molecular subunits such as light emitters or absorbers, redoxactiveâpossibly electrochromicâcompounds, and electroactive molecular hosts or catalysts. The number of macroscopic devices resulting from such a hetero-supramolecular architecture includes photovoltaic cells, erasable photochromic devices, electrochromic displays and filters, and electrocatalytically active surfaces. The principals behind these applications are reviewed with special emphasis on a new type of photo assisted electrocatalysis using vitamin B12-modified TiO2
Censorship in democracy
The spread of propaganda, misinformation, and biased narratives from autocratic regimes, especially on social media, is a growing concern in many democracies. Can censorship be an effective tool to curb the spread of such slanted narratives? In this paper, we study the European Unionâs ban on Russian state-led news outlets after the 2022 Russian invasion of Ukraine. We analyze 775,616 tweets from 133,276 users on Twitter/X, employing a difference-in-differences strategy. We show that the ban reduced pro-Russian slant among users who had previously directly interacted with banned outlets. The impact is most pronounced among users with the highest pre-ban slant levels. However, this effect was short-lived, with slant returning to its pre-ban levels within two weeks post-enforcement. Additionally, we find a detectable albeit less pronounced indirect effect on users who had not directly interacted with the outlets before the ban. We provide evidence that other suppliers of propaganda may have actively sought to mitigate the banâs influence by intensifying their activity, effectively counteracting the persistence and reach of the ban
Pathology Synthesis of 3D-Consistent Cardiac MR Images using 2D VAEs and GANs
We propose a method for synthesizing cardiac magnetic resonance (MR) images
with plausible heart pathologies and realistic appearances for the purpose of
generating labeled data for the application of supervised deep-learning (DL)
training. The image synthesis consists of label deformation and label-to-image
translation tasks. The former is achieved via latent space interpolation in a
VAE model, while the latter is accomplished via a label-conditional GAN model.
We devise three approaches for label manipulation in the latent space of the
trained VAE model; i) \textbf{intra-subject synthesis} aiming to interpolate
the intermediate slices of a subject to increase the through-plane resolution,
ii) \textbf{inter-subject synthesis} aiming to interpolate the geometry and
appearance of intermediate images between two dissimilar subjects acquired with
different scanner vendors, and iii) \textbf{pathology synthesis} aiming to
synthesize a series of pseudo-pathological synthetic subjects with
characteristics of a desired heart disease. Furthermore, we propose to model
the relationship between 2D slices in the latent space of the VAE prior to
reconstruction for generating 3D-consistent subjects from stacking up 2D
slice-by-slice generations. We demonstrate that such an approach could provide
a solution to diversify and enrich an available database of cardiac MR images
and to pave the way for the development of generalizable DL-based image
analysis algorithms. We quantitatively evaluate the quality of the synthesized
data in an augmentation scenario to achieve generalization and robustness to
multi-vendor and multi-disease data for image segmentation. Our code is
available at https://github.com/sinaamirrajab/CardiacPathologySynthesis.Comment: Accepted for publication at the Journal of Machine Learning for
Biomedical Imaging (MELBA) https://www.melba-journal.org/2023:01
Pathology Synthesis of 3D Consistent Cardiac MR Images Using 2D VAEs and GANs
We propose a method for synthesizing cardiac MR images with plausible heart shapes and realistic appearances for the purpose of generating labeled data for deep-learning (DL) training. It breaks down the image synthesis into label deformation and label-to-image translation tasks. The former is achieved via latent space interpolation in a VAE model, while the latter is accomplished via a conditional GAN model. We devise an approach for label manipulation in the latent space of the trained VAE model, namely pathology synthesis, aiming to synthesize a series of pseudo-pathological synthetic subjects with characteristics of a desired heart disease. Furthermore, we propose to model the relationship between 2D slices in the latent space of the VAE via estimating the correlation coefficient matrix between the latent vectors and utilizing it to correlate elements of randomly drawn samples before decoding to image space. This simple yet effective approach results in generating 3D consistent subjects from 2D slice-by-slice generations. Such an approach could provide a solution to diversify and enrich the available database of cardiac MR images and to pave the way for the development of generalizable DL-based image analysis algorithms. The code will be available at https://github.com/sinaamirrajab/CardiacPathologySynthesis
Shaped Laser Pulses for Microsecond Time-Resolved Cryo-EM: Outrunning Crystallization During Flash Melting
Water vitrifies if cooled at rates above K/s. Surprisingly,
this process cannot simply be reversed by heating the resulting amorphous ice
at a similar rate. Instead, we have recently shown that the sample transiently
crystallizes even if the heating rate is more than one order of magnitude
higher. This may present an issue for microsecond time-resolved cryo-electron
microscopy experiments, in which vitreous ice samples are briefly flash melted
with a laser pulse, since transient crystallization could potentially alter the
dynamics of the embedded proteins. Here, we demonstrate how shaped microsecond
laser pulses can be used to increase the heating rate and outrun
crystallization during flash melting of amorphous solid water (ASW) samples. We
use time-resolved electron diffraction experiments to determine that the
critical heating rate is about K/s, more than two orders of magnitude
higher than the critical cooling rate. Our experiments add to the toolbox of
the emerging field of microsecond time-resolved cryo-electron microscopy by
demonstrating a straightforward approach for avoiding crystallization during
laser melting and for achieving significantly higher heating rates, which paves
the way for nanosecond time-resolved experiments
Prediction Along a Developmental Perspective in Psychiatry: How Far Might We Go?
Most mental disorders originate in childhood, and once symptoms present, a variety of psychosocial and cognitive maladjustments may arise. Although early childhood problems are generally associated with later mental health impairments and psychopathology, pluripotent transdiagnostic trajectories may manifest. Possible predictors range from behavioral and neurobiological mechanisms, genetic predispositions, environmental and social factors, and psychopathological comorbidity. They may manifest in altered neurodevelopmental trajectories and need to be validated capitalizing on large-scale multi-modal epidemiological longitudinal cohorts. Moreover, clinical and etiological variability between patients with the same disorders represents a major obstacle to develop effective treatments. Hence, in order to achieve stratification of patient samples opening the avenue of adapting and optimizing treatment for the individual, there is a need to integrate data from multi-dimensionally phenotyped clinical cohorts and cross-validate them with epidemiological cohort data. In the present review, we discuss these aspects in the context of externalizing and internalizing disorders summarizing the current state of knowledge, obstacles, and pitfalls. Although a large number of studies have already increased our understanding on neuropsychobiological mechanisms of mental disorders, it became also clear that this knowledge might only be the tip of the Eisberg and that a large proportion still remains unknown. We discuss prediction strategies and how the integration of different factors and methods may provide useful contributions to research and at the same time may inform prevention and intervention
Visualizing Nanoscale Dynamics with Time-resolved Electron Microscopy
The large number of interactions in nanoscale systems leads to the emergence of complex behavior. Understanding such complexity requires atomic-resolution observations with a time resolution that is high enough to match the characteristic timescale of the system. Our laboratoryâs method of choice is time-resolved electron microscopy. In particular, we are interested in the development of novel methods and instrumentation for high-speed observations with atomic resolution. Here, we present an overview of the activities in our laboratory
Electron Diffraction of Water in No Man's Land
A generally accepted understanding of the anomalous properties of water will
only emerge if it becomes possible to systematically characterize water in the
deeply supercooled regime, from where the anomalies appear to emanate. This has
largely remained elusive because water crystallizes rapidly between 160 K and
232 K. Here, we present an experimental approach to rapidly prepare deeply
supercooled water at a well-defined temperature and probe it with electron
diffraction before crystallization occurs. We show that as water is cooled from
room temperature to cryogenic temperature, its structure evolves smoothly,
approaching that of amorphous ice just below 200 K. Our experiments narrow down
the range of possible explanations of the origin for the water anomalies and
open up new avenues for studying supercooled water
- âŠ