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"Fischer, J."
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Global Existence of Renormalized Solutions to Entropy-Dissipating Reaction–Diffusion Systems
In the present work we introduce the notion of a renormalized solution for reaction–diffusion systems with entropy-dissipating reactions. We establish the global existence of renormalized solutions. In the case of integrable reaction terms our notion of a renormalized solution reduces to the usual notion of a weak solution. Our existence result in particular covers all reaction–diffusion systems involving a single reversible reaction with mass-action kinetics and (possibly species-dependent) Fick-law diffusion; more generally, it covers the case of systems of reversible reactions with mass-action kinetics which satisfy the detailed balance condition. For such equations the existence of any kind of solution in general was an open problem, thereby motivating the study of renormalized solutions.
Journal Article
K18-hACE2 mice develop respiratory disease resembling severe COVID-19
SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 10 4 TCID 50 or 10 5 TCID 50 , the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 10 5 TCID 50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 10 2 TCID 50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.
Journal Article
Low uncertainty Boltzmann constant determinations and the kelvin redefinition
At its 25th meeting, the General Conference on Weights and Measures (CGPM) approved Resolution 1 'On the future revision of the International System of Units, the SI', which sets the path towards redefinition of four base units at the next CGPM in 2018. This constitutes a decisive advance towards the formal adoption of the new SI and its implementation. Kilogram, ampere, kelvin and mole will be defined in terms of fixed numerical values of the Planck constant, elementary charge, Boltzmann constant and Avogadro constant, respectively. The effect of the new definition of the kelvin referenced to the value of the Boltzmann constant k is that the kelvin is equal to the change of thermodynamic temperature T that results in a change of thermal energy kT by 1.380 65 × 10–23 J. A value of the Boltzmann constant suitable for defining the kelvin is determined by fundamentally different primary thermometers such as acoustic gas thermometers, dielectric constant gas thermometers, noise thermometers and the Doppler broadening technique. Progress to date of the measurements and further perspectives are reported. Necessary conditions to be met before proceeding with changing the definition are given. The consequences of the new definition of the kelvin on temperature measurement are briefly outlined.
Journal Article
A reinforcement learning approach to airfoil shape optimization
Shape optimization is an indispensable step in any aerodynamic design. However, the inherent complexity and non-linearity associated with fluid mechanics as well as the high-dimensional design space intrinsic to such problems make airfoil shape optimization a challenging task. Current approaches relying on gradient-based or gradient-free optimizers are data-inefficient in that they do not leverage accumulated knowledge, and are computationally expensive when integrating Computational Fluid Dynamics (CFD) simulation tools. Supervised learning approaches have addressed these limitations but are constrained by user-provided data. Reinforcement learning (RL) provides a data-driven approach bearing generative capabilities. We formulate the airfoil design as a Markov decision process (MDP) and investigate a Deep Reinforcement Learning (DRL) approach to airfoil shape optimization. A custom RL environment is developed allowing the agent to successively modify the shape of an initially provided 2D airfoil and to observe the associated changes in aerodynamic metrics such as lift-to-drag (
L
/
D
), lift coefficient (
C
l
) and drag coefficient (
C
d
). The learning abilities of the DRL agent are demonstrated through various experiments in which the agent’s objective-maximizing
L
/
D
, maximizing
C
l
or minimizing
C
d
-as well as the initial airfoil shape are varied. Results show that the DRL agent is able to generate high performing airfoils within a limited number of learning iterations. The strong resemblance between the artificially produced shapes and those found in the literature highlights the rationality of the decision-making policy learned by the agent. Overall, the presented approach demonstrates the relevance of DRL to airfoil shape optimization and brings forward a successful application of DRL to a physics-based aerodynamics problem.
Journal Article
Dielectric ordering of water molecules arranged in a dipolar lattice
Intermolecular hydrogen bonds impede long-range (anti-)ferroelectric order of water. We confine H
2
O molecules in nanosized cages formed by ions of a dielectric crystal. Arranging them in channels at a distance of ~5 Å with an interchannel separation of ~10 Å prevents the formation of hydrogen networks while electric dipole-dipole interactions remain effective. Here, we present measurements of the temperature-dependent dielectric permittivity, pyrocurrent, electric polarization and specific heat that indicate an order-disorder ferroelectric phase transition at
T
0
≈ 3 K in the water dipolar lattice. Ab initio molecular dynamics and classical Monte Carlo simulations reveal that at low temperatures the water molecules form ferroelectric domains in the
ab
-plane that order antiferroelectrically along the channel direction. This way we achieve the long-standing goal of arranging water molecules in polar order. This is not only of high relevance in various natural systems but might open an avenue towards future applications in biocompatible nanoelectronics.
Despite the apparent simplicity of a H2O molecule, the mutual ferroelectric ordering of the molecules is unresolved. Here, the authors realize a macroscopic ferroelectric phase transition in a network of dipole-dipole coupled water molecules located in nanopores of gemstone.
Journal Article
Influence of osteoporosis on the compressive properties of femoral cancellous bone and its dependence on various density parameters
Data collection of mechanical parameters from compressive tests play a fundamental role in FE modelling of bone tissues or the developing and designing of bone implants, especially referring to osteoporosis or other forms of bone loss. A total of 43 cylindrical samples (Ø8 × 16 mm) were taken from 43 freshly frozen proximal femora using a tenon cutter. All femora underwent BMD measurement and additionally apparent- and relative- and bulk density (ρ
app
, ρ
r
, ρ
b
) were determined using samples bordering the compressive specimen on the proximal and distal regions. All samples were classified as \"normal\", \"osteopenia\" and \"osteoporosis\" based on the DEXA measurements. Distal apparent density was most suitable for predicting bone strength and BMD. One novel aspect is the examination of the plateau stress as it describes the stress at which the failure of spongious bone progresses. No significant differences in mechanical properties (compressive modulus E; compressive stress σ
max
and plateau stress σ
p
) were found between osteopenic and osteoporotic bone. The results suggest that already in the case of a known osteopenia, actions should be taken as they are applied in the case of osteoporosis A review of the literature regarding extraction and testing methods illustrates the urgent need for standardized biomechanical compressive material testing.
Journal Article
Nobel somatosensations and pain
The Nobel prices 2021 for Physiology and Medicine have been awarded to David Julius and Ardem Patapoutian \"for their discoveries of receptors for temperature and touch\", TRPV1 and PIEZO1/2. The present review tells the past history of the capsaicin receptor, covers further selected TRP channels, TRPA1 in particular, and deals with mechanosensitivity in general and mechanical hyperalgesia in particular. Other achievements of the laureates and translational aspects of their work are shortly treated.
Journal Article