Long-range fiber-optic earthquake sensing by active phase noise cancellation

We present a long-range fiber-optic environmental deformation sensor based on active phase noise cancellation (PNC) in metrological frequency dissemination. PNC sensing exploits recordings of a compensation frequency that is commonly discarded. Without the need for dedicated measurement devices, it operates synchronously with metrological services, suggesting that existing phase-stabilized metrological networks can be co-used effortlessly as environmental sensors. The compatibility of PNC sensing with inline amplification enables the interrogation of cables with lengths beyond 1000 km, making it a potential contributor to earthquake detection and early warning in the oceans. Using spectral-element wavefield simulations that accurately account for complex cable geometry, we compare observed and computed recordings of the compensation frequency for a magnitude 3.9 earthquake in south-eastern France and a 123 km fiber link between Bern and Basel, Switzerland. The match in both phase and amplitude indicates that PNC sensing can be used quantitatively, for example, in earthquake detection and characterization.Comment: 7 pages, 4 figure

Highly coherent electron beam from a laser-triggered tungsten needle tip

We report on a quantitative measurement of the spatial coherence of electrons emitted from a sharp metal needle tip. We investigate the coherence in photoemission using near-ultraviolet laser triggering with a photon energy of 3.1 eV and compare it to DC-field emission. A carbon-nanotube is brought in close proximity to the emitter tip to act as an electrostatic biprism. From the resulting electron matter wave interference fringes we deduce an upper limit of the effective source radius both in laser-triggered and DC-field emission mode, which quantifies the spatial coherence of the emitted electron beam. We obtain $(0.80\pm 0.05)\,$nm in laser-triggered and $(0.55\pm 0.02)\,$nm in DC-field emission mode, revealing that the outstanding coherence properties of electron beams from needle tip field emitters are largely maintained in laser-induced emission. In addition, the relative coherence width of 0.36 of the photoemitted electron beam is the largest observed so far. The preservation of electronic coherence during emission as well as ramifications for time-resolved electron imaging techniques are discussed

Coarse graining molecular dynamics with graph neural networks

Coarse graining enables the investigation of molecular dynamics for larger systems and at longer timescales than is possible at an atomic resolution. However, a coarse graining model must be formulated such that the conclusions we draw from it are consistent with the conclusions we would draw from a model at a finer level of detail. It has been proved that a force matching scheme defines a thermodynamically consistent coarse-grained model for an atomistic system in the variational limit. Wang et al. [ACS Cent. Sci. 5, 755 (2019)] demonstrated that the existence of such a variational limit enables the use of a supervised machine learning framework to generate a coarse-grained force field, which can then be used for simulation in the coarse-grained space. Their framework, however, requires the manual input of molecular features to machine learn the force field. In the present contribution, we build upon the advance of Wang et al. and introduce a hybrid architecture for the machine learning of coarse-grained force fields that learn their own features via a subnetwork that leverages continuous filter convolutions on a graph neural network architecture. We demonstrate that this framework succeeds at reproducing the thermodynamics for small biomolecular systems. Since the learned molecular representations are inherently transferable, the architecture presented here sets the stage for the development of machine-learned, coarse-grained force fields that are transferable across molecular systems

Proinflammatory Phenotype and Increased Caveolin-1 in Alveolar Macrophages with Silenced CFTR mRNA

The inflammatory milieu in the respiratory tract in cystic fibrosis (CF) has been linked to the defective expression of the cystic transmembrane regulator (CFTR) in epithelial cells. Alveolar macrophages (AM), important contibutors to inflammatory responses in the lung, also express CFTR. The present study analyzes the phenotype of human AM with silenced CFTR. Expression of CFTR mRNA and the immature form of the CFTR protein decreased 100-fold and 5.2-fold, respectively, in AM transfected with a CFTR specific siRNA (CFTR-siRNA) compared to controls. Reduction of CFTR expression in AM resulted in increased secretion of IL-8, increased phosphorylation of NF-κB, a positive regulator of IL-8 expression, and decreased expression of IκB-α, the inhibitory protein of NF-κB activation. AM with silenced CFTR expression also showed increased apoptosis. We hypothesized that caveolin-1 (Cav1), a membrane protein that is co-localized with CFTR in lipid rafts and that is related to inflammation and apoptosis in macrophages, may be affected by decreased CFTR expression. Messenger RNA and protein levels of Cav1 were increased in AM with silenced CFTR. Expression and transcriptional activity of sterol regulatory element binding protein (SREBP), a negative transcriptional regulator of Cav1, was decreased in AM with silenced CFTR, but total and free cholesterol mass did not change. These findings indicate that silencing of CFTR in human AM results in an inflammatory phenotype and apoptosis, which is associated to SREBP-mediated regulation of Cav1

Long-range fiber-optic earthquake sensing by active phase noise cancellation

Abstract We present a long-range fiber-optic environmental deformation sensor based on active phase noise cancellation (PNC) in metrological frequency dissemination. PNC sensing exploits recordings of a compensation frequency that is commonly discarded. Without the need for dedicated measurement devices, it operates synchronously with metrological services, suggesting that existing phase-stabilized metrological networks can be co-used effortlessly as environmental sensors. The compatibility of PNC sensing with inline amplification enables the interrogation of cables with lengths beyond 1000 km, making it a potential contributor to earthquake detection and early warning in the oceans. Using spectral-element wavefield simulations that accurately account for complex cable geometry, we compare observed and computed recordings of the compensation frequency for a magnitude 3.9 earthquake in south-eastern France and a 123 km fiber link between Bern and Basel, Switzerland. The match in both phase and amplitude indicates that PNC sensing can be used quantitatively, for example, in earthquake detection and characterization

Diverse Functional Properties of Wilson Disease ATP7B Variants

BACKGROUND & AIMS: Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS: We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper ((64)Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS: Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS: Variants in ATP7B associated with Wilson disease disrupt the protein's transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype-phenotype correlation and mechanisms of disease pathogenesis