SUMMARY
Bayesian inference applied to microseismic activity monitoring allows the accurate location of microseismic events from recorded seismograms and the estimation of the associated ...uncertainties. However, the forward modelling of these microseismic events, which is necessary to perform Bayesian source inversion, can be prohibitively expensive in terms of computational resources. A viable solution is to train a surrogate model based on machine learning techniques to emulate the forward model and thus accelerate Bayesian inference. In this paper, we substantially enhance previous work, which considered only sources with isotropic moment tensors. We train a machine learning algorithm on the power spectrum of the recorded pressure wave and show that the trained emulator allows complete and fast event locations for any source mechanism. Moreover, we show that our approach is computationally inexpensive, as it can be run in less than 1 hr on a commercial laptop, while yielding accurate results using less than 104 training seismograms. We additionally demonstrate how the trained emulators can be used to identify the source mechanism through the estimation of the Bayesian evidence. Finally, we demonstrate that our approach is robust to real noise as measured in field data. This work lays the foundations for efficient, accurate future joint determinations of event location and moment tensor, and associated uncertainties, which are ultimately key for accurately characterizing human-induced and natural earthquakes, and for enhanced quantitative seismic hazard assessments.
Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors ...indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Display omitted
Fe(II) interaction with cement phases was studied by means of co-precipitation and sorption experiments in combination with X-ray absorption fine structure (XAFS) spectroscopy. ...Oxidation of Fe(II) was fast in alkaline conditions and therefore, a methodology was developed which allowed Fe(II) to be stabilised in the sorption experiments and to prepare samples for spectroscopy. X-ray diffraction (XRD) of the co-precipitation samples showed uptake of a small portion of Fe(II) by calcium-silicate-hydrates (C-S-H) in the interlayer indicated by an increase in the interlayer spacing. Fe(II) incorporation by AFm phases was not indicated. Wet chemical experiments using 55Fe radiotracer revealed linear sorption of Fe(II) irrespective of the Ca/Si ratio of C-S-H and equilibrium pH. The Kd values for Fe(II) sorption on C-S-H are more than three orders of magnitude lower as compared to Fe(III), while they are comparable to those of other bivalent metal cations. XAFS spectroscopy showed Fe(II) binding by C-S-H in an octahedral coordination environment. The large number of neighbouring atoms rules out the formation of a single surface-bound Fe(II) species. Instead the data suggest presence of Fe(II) in a structurally bound entity. The data from XRD and XAFS spectroscopy suggests the presence of both surface- and interlayer-bound Fe(II) species.
Signal transducer and activator of transcription (STAT) 3 regulates many cardinal features of cancer including cancer cell growth, apoptosis resistance, DNA damage response, metastasis, immune ...escape, tumor angiogenesis, the Warburg effect and oncogene addiction and has been validated as a drug target for cancer therapy. Several strategies have been used to identify agents that target Stat3 in breast cancer but none has yet entered into clinical use. We used a high-throughput fluorescence microscopy search strategy to identify compounds in a drug-repositioning library (Prestwick library) that block ligand-induced nuclear translocation of Stat3 and identified piperlongumine (PL), a natural product isolated from the fruit of the pepper Piper longum. PL inhibited Stat3 nuclear translocation, inhibited ligand-induced and constitutive Stat3 phosphorylation, and modulated expression of multiple Stat3-regulated genes. Surface plasmon resonance assay revealed that PL directly inhibited binding of Stat3 to its phosphotyrosyl peptide ligand. Phosphoprotein antibody array analysis revealed that PL does not modulate kinases known to activate Stat3 such as Janus kinases, Src kinase family members or receptor tyrosine kinases. PL inhibited anchorage-independent and anchorage-dependent growth of multiple breast cancer cell lines having increased pStat3 or total Stat3, and induced apoptosis. PL also inhibited mammosphere formation by tumor cells from patient-derived xenografts. PL's antitumorigenic function was causally linked to its Stat3-inhibitory effect. PL was non-toxic in mice up to a dose of 30 mg/kg/day for 14 days and caused regression of breast cancer cell line xenografts in nude mice. Thus, PL represents a promising new agent for rapid entry into the clinic for use in treating breast cancer, as well as other cancers in which Stat3 has a role.
Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, ...its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.
In this paper we study the feasibility of Fe(Se, Te) coated conductors on a simple rolling-assisted biaxially textured substrate (RABiTS) template. Starting from commercially available Ni-5 at% W ...tapes which show an out-of-plane orientation of about 7° and an in-plane orientation around 5°, we realized a RABiTS template for Fe(Se, Te) coated conductor fabrication by depositing CeO2 thin films on the metallic tape. The oxide buffer layers, deposited via pulsed laser ablation, exhibit an out-of-plane and an in-plane orientation suitable for Fe(Se, Te) deposition and act as a chemical barrier against Ni diffusion. Fe(Se, Te) thin films deposited on such a simple template show a superconducting transition at 16 K and very high upper critical field values with a ΔTc,0 of only 3 K in 18 T. The transport critical current reaches values of 1.7 × 105 A cm−2 at 4.2 K in self-field and is reduced by less than one order of magnitude up to 18 T, remaining isotropic with respect to the magnetic field direction.
Here, we present a sample-variance-limited measurement of the temperature power spectrum (TT) of the cosmic microwave background using observations of a ~1500 deg2 field made by the SPT-3G in 2018. ...We report multifrequency power spectrum measurements at 95, 150, and 220 GHz covering the angular multipole range 750 ≤ ℓ < 3000. We combine this TT measurement with the published polarization power spectrum measurements from the 2018 observing season and update their associated covariance matrix to complete the SPT-3G 2018 TT/TE/EE dataset. This is the first analysis to present cosmological constraints from SPT TT, TE, and EE power spectrum measurements jointly. We blind the cosmological results and subject the dataset to a series of consistency tests at the power spectrum and parameter level. We find excellent agreement between frequencies and spectrum types and our results are robust to the modeling of astrophysical foregrounds. We report results for Λ CDM and a series of extensions, drawing on the following parameters: the amplitude of the gravitational lensing effect on primary power spectra AL, the effective number of neutrino species Neff, the primordial helium abundance YP, and the baryon clumping factor due to primordial magnetic fields b. We find that the SPT-3G 2018 TT/TE/EE data are well fit by Λ CDM with a probability to exceed of 15%. For Λ CDM, we constrain the expansion rate today to H0 = 68.3 ± 1.5 km s–1 Mpc–1 and the combined structure growth parameter to S8 = 0.797 ± 0.042. The SPT-based results are effectively independent of Planck, and the cosmological parameter constraints from either dataset are within <1σ of each other. The addition of temperature data to the SPT-3G TE/EE power spectra improves constraints by 8–27% for each of the Λ CDM cosmological parameters. When additionally fitting AL, Neff, or Neff + YP, the posteriors of these parameters tighten by 5–24%. In the case of primordial magnetic fields, complete TT/TE/EE power spectrum measurements are necessary to break the degeneracy between b and ns, the spectral index of primordial density perturbations. We report a 95% confidence upper limit from SPT-3G data of b<1.0. The cosmological constraints in this work are the tightest from SPT primary power spectrum measurements to date and the analysis forms a new framework for future SPT analyses.
Abstract
The fabrication of a Fe-based coated conductor (CC) becomes possible when Fe(Se,Te) is grown as an epitaxial film on a metallic oriented substrate. Thanks to the material’s low structural ...anisotropy, less strict requirements on the template microstructure allow for the design of a simplified CC architecture with respect to the REBCO multi-layered layout. This design, though, still requires a buffer layer to promote the oriented growth of the superconducting film and avoid diffusion from the metallic template. In this work, Fe(Se,Te) films are grown on chemically-deposited, CeO
2
-based buffer layers via pulsed laser deposition, and excellent properties are obtained when a Fe(Se,Te) seed layer is used. Among all the employed characterization techniques, transmission electron microscopy proved essential to determine the actual effect of the seed layer on the final film properties. Also, systematic investigation of the full current transport properties
J
(
θ
,
H
,
T
) is carried out: Fe(Se,Te) samples are obtained with sharp superconducting transitions around 16 K and critical current densities exceeding 1 MA cm
−2
at 4.2 K in self-field. The in-field and angular behavior of the sample are in line with data from the literature. These results are the demonstration of the feasibility of a Fe-based CC, with all the relative advantages concerning process simplification and cost reduction.
PDF
