Thermal fluctuations and longitudinal relaxation of single-domain magnetic particles at elevated temperatures

We present numerical and analytical results for the swiching times of magnetic nanoparticles with uniaxial anisotropy at elevated temperatures, including the vicinity of T_c. The consideration is based in the Landau-Lifshitz-Bloch equation that includes the relaxation of the magnetization magnitude M. The resulting switching times are shorter than those following from the naive Landau-Lifshitz equation due to (i) additional barrier lowering because of the reduction of M at the barrier and (ii) critical divergence of the damping parameters.Comment: 4 PR pages, 1 figur

Ground-motion networks in the Groningen field: usability and consistency of surface recordings

Several strong-motion networks have been installed in the Groningen gas field in the Netherlands to record ground motions associated with induced earthquakes. There are now more than 450 permanent surface accelerographs plus a mobile array of 450 instruments, which, in addition to many instrumented boreholes, yield a wealth of data. The database of recordings has been of fundamental importance to the development of ground-motion models that form a key element of the seismic hazard and risk estimations for the field. In order to maximise the benefit that can be derived from these recordings, this study evaluates the usability of the recordings from the different networks, in general terms and specifically with regards to the frequency ranges with acceptable signal-to-noise ratios. The study also explores the consistency among the recordings from the different networks, highlighting in particular how a configuration error was identified and resolved. The largest accelerograph network consists of instruments housed in buildings around the field, frequently installed on the lower parts of walls rather than on the floor. A series of experiments were conducted, using additional instruments installed adjacent to these buildings and replicating the installation configuration in full-scale shake table tests, to identify the degree to which structural response contaminated the recordings. The general finding of these efforts was that for PGV and oscillator periods above 0.1 s, the response spectral ordinates from these recordings can be used with confidence

GRPR versus PSMA:expression profiles during prostate cancer progression demonstrate the added value of GRPR-targeting theranostic approaches

Introduction: Central to targeted radionuclide imaging and therapy of prostate cancer (PCa) are prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals. Gastrin-releasing peptide receptor (GRPR) targeting has been proposed as a potential additional approach for PCa theranostics. The aim of this study was to investigate to what extent and at what stage of the disease GRPR-targeting applications can complement PSMA-targeting theranostics in the management of PCa. Methods: Binding of the GRPR- and PSMA-targeting radiopharmaceuticals [177Lu]Lu-NeoB and [177Lu]Lu-PSMA-617, respectively, was evaluated and compared on tissue sections of 20 benign prostatic hyperplasia (BPH), 16 primary PCa and 17 progressive castration-resistant PCa (CRPC) fresh frozen tissue specimens. Hematoxylin-eosin and alpha-methylacyl-CoA racemase stains were performed to identify regions of prostatic adenocarcinoma and potentially high-grade prostatic intraepithelial neoplasia. For a subset of primary PCa samples, RNA in situ hybridization (ISH) was used to identify target mRNA expression in defined tumor regions. Results: The highest median [177Lu]Lu-NeoB binding was observed in primary PCa samples, while median and overall [177Lu]Lu-PSMA-617 binding was highest in CRPC samples. The highest [177Lu]Lu-NeoB binding was observed in 3/17 CRPC samples of which one sample showed no [177Lu]Lu-PSMA-617 binding. RNA ISH analyses showed a trend between mRNA expression and radiopharmaceutical binding, and confirmed the distinct GRPR and PSMA expression patterns in primary PCa observed with radiopharmaceutical binding. Conclusion: Our study emphasizes that GRPR-targeting approaches can contribute to improved PCa management and complement currently applied PSMA-targeting strategies in both early and late stage PCa.</p

A database of ground-motion recordings, site profiles, and amplification factors from the Groningen gas field in the Netherlands

A comprehensive database that has been used to develop ground motion models for induced earthquakes in the Groningen gas field is provided in a freely accessible online repository. The database includes more than 8500 processed ground motion recordings from 87 earthquakes of local magnitude ML between 1.8 and 3.6, obtained from a large network of surface accelerographs and borehole geophones placed at 50 m depth intervals to a depth of 200 m. The 5%-damped pseudo-acceleration spectra and Fourier amplitude spectra of the records are also provided. Measured shear-wave velocity (VS) profiles, obtained primarily from seismic Cone Penetration Tests (CPTs), are provided for 80 of the ∼100 recording stations. A model representing the regional dynamic soil properties is presented for the entire gas field plus a 5 km onshore buffer zone, specifying lithology, VS, and damping for all layers above the reference baserock horizon located at about 800 m depth. Transfer functions and frequency-dependent amplification factors from the reference rock horizon to the surface for the locations of the recording stations are also included. The database provides a valuable resource for further refinement of induced seismic hazard and risk modeling in Groningen as well as for generic research in site response of thick, soft soil deposits and the characteristics of ground motions from small-magnitude, shallow-focus induced earthquakes

Silencing Heat Shock Protein 47 (HSP47) in Fibrogenic Precision-Cut Lung Slices:A Surprising Lack of Effects on Fibrogenesis?

Idiopathic pulmonary fibrosis (IPF) is a chronic disease that is characterized by the excessive deposition of scar tissue in the lungs. As currently available treatments are unable to restore lung function in patients, there is an urgent medical need for more effective drugs. Developing such drugs, however, is challenging because IPF has a complex pathogenesis. Emerging evidence indicates that heat shock protein 47 (HSP47), which is encoded by the gene Serpinh1, may be a suitable therapeutic target as it is required for collagen synthesis. Pharmacological inhibition or knockdown of HSP47 could therefore be a promising approach to treat fibrosis. The objective of this study was to assess the therapeutic potential of Serpinh1-targeting small interfering RNA (siRNA) in fibrogenic precision-cut lung slices prepared from murine tissue. To enhance fibrogenesis, slices were cultured for up to 144 h with transforming growth factor β1. Self-deliverable siRNA was used to knockdown mRNA and protein expression, without affecting the viability and morphology of slices. After silencing HSP47, only the secretion of fibronectin was reduced while other aspects of fibrogenesis remained unaffected (e.g., myofibroblast differentiation as well as collagen secretion and deposition). These observations are surprising as others have shown that Serpinh1-targeting siRNA suppressed collagen deposition in animals. Further studies are therefore warranted to elucidate downstream effects on fibrosis upon silencing HSP47

Derivation of a near-surface damping model for the Groningen gas field

Seismic damping of near-surface deposits is an important input to site-response analysis for seismic hazard assessment. In Groningen, the Netherlands, gas production from a reservoir at 3 km depth causes seismicity. Above the gas field, an 800 m thick layer of unconsolidated sediments exist, which consists of a mixture of sand, gravel, clay and peat strata. Shear waves induced at 3 km depth experience most of their anelastic attenuation in these loose sediments. A good estimate of damping is therefore crucial for modeling realistic ground-motion levels. In Groningen, we take advantage of a large network of 200 m deep vertical arrays to estimate damping from recordings of the induced events. As a first step, we apply seismic interferometry by deconvolution to estimate local transfer functions over these vertical arrays. Subsequently, two different methods are employed. The first is the ’up-going’ method, where the amplitude decay of the retrieved up-going wave is used. The second is the ’up-down’ method, where the amplitude difference between retrieved up- and down-going waves is utilized. For the up-going method, the amplitude of the up-going direct wave is affected by both elastic and anelastic effects. In order to estimate the anelastic attenuation it is necessary to remove the elastic amplification first. Despite the fact that elastic compensation could be determined quite accurately, non-physical damping values were estimated for a number of boreholes. Likely, the underlying cause was small differences in effective response functions of geophones at different depths. It was found that the up-down method is more robust. With this method, elastic propagation corrections are not needed. In addition, small differences in in situ geophone response are irrelevant because the up- and down-going waves retrieved at the same geophone, are used. For the 1D case we showed that for estimating the local transfer function, the complex reverberations need to be included in the interferometric process. Only when this is done, the transfer function does not contain elastic transmission loss and Q estimation can be made without knowing the soil profile in detail. Uncertainty in the estimated damping was found from the signal-to-noise ratio of the estimated transfer function. The Q profiles estimated with the up-down method were used to derive a damping model for the top 200 m of the entire Groningen field. A scaling relation was derived by comparing estimated Q profiles with low-strain damping profiles that were constructed using published models for low-strain damping linked to soil properties. This scaling relation, together with the soil-properties based damping model, allowed up-scaling of the model to each grid-cell in the Groningen field. For depths below 200 m, damping was derived from the attenuation of the microseism over Groningen. The mean damping model, over a frequency band between 2 and 20 Hz, was estimated to be 2.0% (0-50 m depth), 1.3% (50-100 m), 0.66% (100-150 m), 0.57% (150-200 m) and 0.5% (200-580 m)

Osteoprotegerin is an Early Marker of the Fibrotic Process and of Antifibrotic Treatment Responses in Ex Vivo Lung Fibrosis

Background: Lung fibrosis is a chronic lung disease with a high mortality rate with only two approved drugs (pirfenidone and nintedanib) to attenuate its progression. To date, there are no reliable biomarkers to assess fibrosis development and/or treatment effects for these two drugs. Osteoprotegerin (OPG) is used as a serum marker to diagnose liver fibrosis and we have previously shown it associates with lung fibrosis as well. Methods: Here we used murine and human precision-cut lung slices to investigate the regulation of OPG in lung tissue to elucidate whether it tracks with (early) fibrosis development and responds to antifibrotic treatment to assess its potential use as a biomarker. Results: OPG mRNA expression in murine lung slices was higher after treatment with profibrotic cytokines TGFβ1 or IL13, and closely correlated with Fn and PAI1 mRNA expression. More OPG protein was released from fibrotic human lung slices than from the control human slices and from TGFβ1 and IL13-stimulated murine lung slices compared to control murine slices. This OPG release was inhibited when murine slices were treated with pirfenidone or nintedanib. OPG release from human fibrotic lung slices was inhibited by pirfenidone treatment. Conclusion: OPG can already be detected during the early stages of fibrosis development and responds, both in early- and late-stage fibrosis, to treatment with antifibrotic drugs currently on the market for lung fibrosis. Therefore, OPG should be further investigated as a potential biomarker for lung fibrosis and a potential surrogate marker for treatment effect.</p

Imaging Torfajökull's Magmatic Plumbing System With Seismic Interferometry and Phase Velocity Surface Wave Tomography

Torfajökull volcano, Iceland, has not erupted since 1477. However, intense geothermal activity, deformation, and seismicity suggest a long-lasting magmatic system. In this paper, we use ambient noise tomography to image the magmatic system beneath Torfajökull volcano. One hundred days of ambient noise data from 23 broadband seismometers show the consistent presence of double-frequency microseism noise with significant power between ∼0.1 and 0.5 Hz. Beamforming results indicate microseism noise with persistent higher energy propagating from west and SE directions and apparent velocities below 3 km/s. We use ambient noise seismic interferometry to retrieve Rayleigh waves, and we introduce a method to estimate the reliability of the retrieved surface waves. We find stable estimation of surface wave phase velocities between 0.16 and 0.38 Hz. Azimuthal velocity variations show a trend of higher velocities in the NE/SW direction, the strike of the rift zone intersecting Torfajökull, and orientation of erupted lavas on a NE-SW fissure swarm. Tomographic results indicate low-velocity anomalies beneath the volcano caldera (between −5% and −10%) and even lower velocity variations in the southeast and southwest study area (below −10%), outside the volcano caldera. Low anomalies may indicate the existence of hot material, more prominent outside the caldera outskirts. High-velocity variations (between 5% and 10%) outline the volcano caldera between 4- and 5-km depth and more pronounced velocities (between 10% and 15%) up to 5-km depth in the north of the volcano caldera. We interpret the former as possible caldera collapse structure and the latest as solidified intrusive magma from the old preferred magma paths