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A Bioorthogonal Click Chemistry Toolbox for Targeted Synthesis of Branched and Well-Defined Protein–Protein Conjugates
Bioorthogonal chemistry holds great potential to generate difficult-to-access protein–protein conjugate architectures. Current applications are hampered by challenging protein expression systems, slow conjugation chemistry, use of undesirable catalysts, or often do not result in quantitative product formation. Here we present a highly efficient technology for protein functionalization with commonly used bioorthogonal motifs for Diels–Alder cycloaddition with inverse electron demand (DAinv). With the aim of precisely generating branched protein chimeras, we systematically assessed the reactivity, stability and side product formation of various bioorthogonal chemistries directly at the protein level. We demonstrate the efficiency and versatility of our conjugation platform using different functional proteins and the therapeutic antibody trastuzumab. This technology enables fast and routine access to tailored and hitherto inaccessible protein chimeras useful for a variety of scientific disciplines. We expect our work to substantially enhance antibody applications such as immunodetection and protein toxin-based targeted cancer therapies
Lab sustainability programs LEAF and My Green Lab®: impact, user experience & suitability
Facing the climate crisis and planetary boundaries, research institutions must address the challenge of becoming climate-neutral and using resources more sustainably. Natural science laboratories are the most resource-intensive and CO2-emitting units within these institutions. Consequently, research groups aim to understand how to lower emissions and become sustainable by participating in green lab programs for wet labs, such as My Green Lab® or LEAF. Here, we compare these programs, analyse their impact on emission savings, and give insights from conducting both programs simultaneously in our biological and chemical labs. As a centrepiece, we provide a quantitative comparison of the programs based on a Germany-wide survey of participants from both programs. We showcase the significant impact of the programs on employees' motivation to work sustainably, highlight the advantages and shortcomings of the programs, and elucidate the pitfalls of greenwashing risks and the risks of leaving the most effective measures unimplemented. Finally, we provide decision-making guidance to help scientists choose the most suitable lab sustainability program based on their individual research backgrounds, needs, and personal preferences
Extracting Geographical References from Finnish Literature. Fully Automated Processing of Plain-Text Corpora
In the Atlas of Finnish Literature 1870-1940 project, we extract geographical information from a Finnish-language corpus of literary texts published between 1870 and 1940. The texts are transformed from plain texts to TEI/XML, and further processed with named entity recognition and linking tools. The results are presented in a web-based environment. This article describes the technical structure of the analysis chain, the tools used and the metaprocesses used to manage the research dataset
Automatic Topic-Guided Segmentation of Holocaust Survivor Testimonies
In recent decades, efforts have been made to gather and digitize the testimonies of living Holocaust survivors. The challenge we now face is attending to those thousands of human stories, which while safely stored in archives, may nevertheless disappear into oblivion. Despite recent advances in narrative analysis in the fields of Computational Literature (CL) and Natural Language Processing (NLP), existing language model technology still faces challenges in analyzing elaborate narratives and long texts. One such challenge is text segmentation – a long-standing issue in the area of CL and NLP. In our work, we propose a computational method to approach this problem. Our research draws on testimony transcripts from the Shoah Foundation (SF) Holocaust archive for supervised topic classification, which is then used as topics guidance for automatic segmentation
Deceleration and Electron Cooling of Highly Charged Ions at HITRAP
The investigation of highly charged ions (HCI) offers the potential to recreate environments that are otherwise inaccessible on Earth. For instance, the magnetic field experienced by electrons in hydrogen-like heavy ions close to the surface of the nucleus compares to that in the vicinity of a pulsar. Consequently, this allows for the most stringent tests of fundamental theories, such as quantum electrodynamics (QED), in these extreme fields. Ultimate precision is typically attained in experiments conducted on cooled and confined ions in an ion trap. However, to date this remains a viable option only for light and medium-heavy, highly charged ions.
The production process of large quantities of heavy, highly charged ions, such as hydrogen-like uranium U⁹¹⁺, relies on electron stripping at high kinetic energies. This technique is commonly employed in accelerator facilities, such as the heavy ion research facility GSI Helmholtzzentrum für Schwerionenforschung in Germany. In order to confine heavy HCI in an ion trap for precision experiments, prior deceleration subsequent to the production process is necessary. This constitutes the objective of the HITRAP facility at GSI, where the energy of the ion beam is reduced in a linear decelerator. Subsequently, the ions will be captured in a Penning trap and cooled by the application of electron cooling for further transport to precision experiments.
In the context of the work, the linear decelerator was recommissioned following a shutdown period of almost eight years. For this purpose, ³⁶Ar¹⁸⁺ ions were produced by the accelerator complex of GSI, decelerated to 4 MeV/u in the Experimental Storage Ring ESR, and injected into the HITRAP facility. After successful deceleration, the ion beam was transported for the first time further along the low-energy beam line towards the HITRAP Cooling Trap, captured, and confined for short periods of time. Furthermore, the trap setup was commissioned with ⁴⁰Ar¹⁶⁺ ions produced by an electron beam ion trap (EBIT). The simultaneous storage of these ions with a cold plasma of electrons resulted in an considerable reduction of the ions' kinetic energy. This constitutes the first demonstration of electron cooling on highly charged ions in a Penning trap. Together with the first successful storage of accelerator-produced HCI, this marks a tremendous advancement in the commissioning of the HITRAP facility, as a result of which an experiment at HITRAP has been included for the first time in the beamtime schedule of GSI for the upcoming year
Stable Operation of Copper-Protected La(FeMnSi)13Hy Regenerators in a Magnetic Cooling Unit
Magnetic refrigeration leads the current commercialization efforts of ambient caloric cooling technologies, is considered among its peers most promising in terms of anticipated energy efficiency gain, and allows for complete elimination of harmful coolants. By now, functional magnetocaloric components (so-called regenerators) based on Mn-substituted and hydrogenated LaFeSi alloys are commercially available. However, this alloy system exhibits magnetostriction, is susceptible to fracture, oxidation, and does not passivate well, rendering it prone to failure and corrosion, particularly when using water as favorable heat exchange medium. Demonstrating stable and extended operation of LaFeSi-based regenerators under realistic conditions with cost-sensitive measures thus constitutes a key milestone for derisking the materials system, paving a path toward reliable and maintenance-friendly magnetic cooling devices. Building upon a fundamental analysis of materials properties, process, and target specifications, we outline a 2-fold protection strategy, encompassing a highly conformal copper coating working in tandem with a tailored inhibitor system. The former is applied using an optimized electroless plating procedure, allowing us to evenly envelop complex regenerator architectures in a dense, nondefective, homogeneous, and ductile copper film of excellent interfacial quality. The latter addresses the corrosion characteristics of both coating and substrate in the application environment. In-device aging experiments prove the effectiveness of our multifaceted approach in maintaining the chemical, mechanical, and functional integrity of LaFeSi regenerators under continuous use.
AB - Magnetic refrigeration leads the current commercialization efforts of ambient caloric cooling technologies, is considered among its peers most promising in terms of anticipated energy efficiency gain, and allows for complete elimination of harmful coolants. By now, functional magnetocaloric components (so-called regenerators) based on Mn-substituted and hydrogenated LaFeSi alloys are commercially available. However, this alloy system exhibits magnetostriction, is susceptible to fracture, oxidation, and does not passivate well, rendering it prone to failure and corrosion, particularly when using water as favorable heat exchange medium. Demonstrating stable and extended operation of LaFeSi-based regenerators under realistic conditions with cost-sensitive measures thus constitutes a key milestone for derisking the materials system, paving a path toward reliable and maintenance-friendly magnetic cooling devices. Building upon a fundamental analysis of materials properties, process, and target specifications, we outline a 2-fold protection strategy, encompassing a highly conformal copper coating working in tandem with a tailored inhibitor system. The former is applied using an optimized electroless plating procedure, allowing us to evenly envelop complex regenerator architectures in a dense, nondefective, homogeneous, and ductile copper film of excellent interfacial quality. The latter addresses the corrosion characteristics of both coating and substrate in the application environment. In-device aging experiments prove the effectiveness of our multifaceted approach in maintaining the chemical, mechanical, and functional integrity of LaFeSi regenerators under continuous use
Surface Defects, Ni³⁺ Species, Charge Transfer Resistance, and Surface Area Dictate the Oxygen Evolution Reaction Activity of Mesoporous NiCo₂O₄ Thin Films
For catalyzing the oxygen evolution reaction, earth‐abundant materials with high activity and stability need to be developed. NiCo₂O₄ has been proven to show high OER activity, however facile and inexpensive techniques for preparation of this compound as mesostructured thin film, possessing a high surface area, is lacking. In this study, the sol‐gel synthesis of nanocrystalline, mesoporous spinel NiCo₂O₄ thin films by dip‐coating and soft‐templating using the evaporation‐induced self‐assembly approach and utilizing the tri‐block‐copolymer Pluronic® F‐127 as structure‐directing agent is reported. The morphology and crystallographic structure were thoroughly probed by various physicochemical characterization techniques collectively validating the development of uniform mesoporous NiCo₂O₄ architectures crystallizing exclusively in the cubic spinel phase after calcination in air at ether 300 °C, 400 °C, or 500 °C. The surface area of thin films increased from 300 °C to 400 °C owing to degradation of the organic template, while the growth of the mesopores from 400 °C to 500 °C resulted in significant decline of the overall (electrochemical) surface area. XPS investigations showed that the amount of octahedrally coordinated Ni³⁺ and defective (low‐coordinated) oxygen species increased for decreasing calcination temperatures. The nanomorphology and presence of catalytically active surface sites of the mesoporous NiCo₂O₄ electrodes were correlated with the electrochemical properties, presenting that the overall surface area, Ni³⁺ content, charge transfer resistance, and amount of defective oxygen sites collectively control the OER performance. After an optimized annealing procedure at 300 °C and chronopotentiometric analysis at 10 mA/cm² for 1.5 h, a low overpotential of 330 mV vs. RHE at 10 mA/cm² in alkaline solution was achieved. The results highlight the necessity of precise selection of the appropriate calcination temperature and tailoring of the nanostructure and electrochemical pre‐treatment conditions of NiCo₂O₄ sol‐gel thin films for adjusting the concentration of electrocatalytically active reaction sites
Intermittent Convex Integration in Mathematical Fluid Mechanics: Applications to the Euler Equations and the Chain Rule Problem
This thesis is concerned with intermittent convex integration and its applications to some equations in fluid mechanics. This technique originated from differential geometry with the proof of the famous Nash-Kuiper theorem on isometric embeddings. It was extended by Gromov and many other authors and is by now considered a powerful tool in the construction of (anomalous) solutions to certain PDEs. One of its most striking applications in the area of fluid mechanics is the proof of the flexible part of Onsager's conjecture.
In this thesis, we consider two concrete examples of intermittent convex integration. The first one concerns the chain rule problem: given scalar functions β and ρ and a divergence-free vector field u, we ask the question whether one can express div(β(ρ)u) only in terms of β'(ρ) and div(ρu). This is clear if β is at least C^1 and u and ρ are Lipschitz continuous.
We prove that in the class of Sobolev vector fields, the answer to that question is negative in general. We even show that for any distribution T which is the divergence of some L^1 function and a given β with suitable growth, there exists a divergence-free, Sobolev regular u and a ρ with div(β(ρ)u)=T and div(ρu) = 0.
The second application deals with the two-dimensional Euler equations. We prove the existence of energy dissipating weak solutions with vorticity in a real Hardy space H^p with p<1. A novel difficulty here compared to previous works in convex integration is that working in real Hardy spaces requires control of higher order moments of the solutions. An additional difficulty is that we work on the full space rather than on a periodic domain
Towards categorizing ethical questions in data literacy : Results of a focus groups study at the NFDI4Ing conference 2022
Data Literacy is crucial for a sustainable engineering education. In aiming to find
solutions to solve future challenges, mechanical engineering has started to integrate data
literacy into the higher education curriculum. However, in current frameworks ethics are seen
as a side topic or are equated to data privacy issues. Since literacy aims to empower people
to make informed decisions based on their or other data, the development of critical reflection
and discussion on ethics is central for data literacy. Those frameworks who do address
ethics often remain general in their examples. In our contribution, we aim to add ethical
questions that data scientist face in their work with data. Therefore, we will first summarize
current existing data literacy frameworks and their ethics concept. Then, through a focus
group study among data literacy experts’ we collect ethical and categorized questions. The
study was conducted with 15 experts at the NFDI4Ing Conference 2022. This approach
expands examples in ethics for data literacy beyond data privacy towards applied, current
and pressing ethical questions
Evolution of isovector quadrupole valence-shell excitations of heavy vibrational nuclei
Proton-neutron isovector valence-shell excitations represent the building blocks of quadrupole collectivity. In the vicinity of double shell closures, their formation and properties can be studied. The energetically lowest-lying isovector configuration in even-even vibrational nuclei is the one quadrupole-phonon mixed-symmetry 2⁺₁ₘₛ state. The state decays with a strong magnetic dipole transition to its fully-symmetric counterpart, providing a distinct signature for its identification.
In this work, the evolution of the M1 strength in the N=80 isotones is investigated through γ-ray spectroscopy. Within the direct proximity of the doubly magic ¹³²Sn, the character of the 2⁺₁ₘₛ state can be studied in a small valence space. A direct lifetime measurement of low-lying 2⁺ states of ¹³²Te, populated through a two-neutron transfer reaction performed at IFIN-HH, Romania, and the subsequent determination of reduced transition strengths identify a mixed-symmetric character of the 2⁺₂ state of ¹³²Te. The measurement therefore confirmed previous suggestions. The results are compared to shell-model calculations, which are moreover able to describe the structure of low-lying fully-symmetric and mixed-symmetric states.
Beyond the πg7/2 subshell closure, where a fragmentation of the 2⁺₁ₘₛ state over several 2⁺ states has been observed, a restoration of shell stabilization was found. A Coulomb-excitation experiment was performed at HIE-ISOLDE, CERN, in order to identify the 2⁺₁ₘₛ state of ¹⁴²Sm. Including multipole mixing ratios obtained in a complementary β⁺/ε-decay experiment at the Heavy Ion Laboratory in Warsaw, Poland, the M1 strength was found to be exclusively concentrated in the 2⁺₃ state. The findings show the impact of the underlying shell structure on the formation of isovector excitations