Germ cell determination and the developmental origin of germ cell tumors

YesIn each generation, the germline is tasked with producing somatic lineages that form the body, and segregating a population of cells for gametogenesis. During animal development, when do cells of the germline irreversibly commit to producing gametes? Integrating findings from diverse species, we conclude that the final commitment of the germline to gametogenesis - the process of germ cell determination - occurs after primordial germ cells (PGCs) colonize the gonads. Combining this understanding with medical findings, we present a model whereby germ cell tumors arise from cells that failed to undertake germ cell determination, regardless of their having colonized the gonads. We propose that the diversity of cell types present in these tumors reflects the broad developmental potential of migratory PGCs.This work was supported by the Howard Hughes Medical Institute where D.C.P. is an Investigator, and the Frontier Research Program from the Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology. P.K.N. is a recipient of the Hope Funds for Cancer Research Fellowship (HFCR-15-06-06) and an Early Career Fellowship from the National Health and Medical Research Council, Australia (GNT1053776)

Licensing of primordial germ cells for gametogenesis depends on genital ridge signaling

In mouse embryos at mid-gestation, primordial germ cells (PGCs) undergo licensing to become gametogenesis-competent cells (GCCs), gaining the capacity for meiotic initiation and sexual differentiation. GCCs then initiate either oogenesis or spermatogenesis in response to gonadal cues. Germ cell licensing has been considered to be a cell-autonomous and gonad-independent event, based on observations that some PGCs, having migrated not to the gonad but to the adrenal gland, nonetheless enter meiosis in a time frame parallel to ovarian germ cells -- and do so regardless of the sex of the embryo. Here we test the hypothesis that germ cell licensing is cell-autonomous by examining the fate of PGCs in Gata4 conditional mutant (Gata4 cKO) mouse embryos. Gata4, which is expressed only in somatic cells, is known to be required for genital ridge initiation. PGCs in Gata4 cKO mutants migrated to the area where the genital ridge, the precursor of the gonad, would ordinarily be formed. However, these germ cells did not undergo licensing and instead retained characteristics of PGCs. Our results indicate that licensing is not purely cell-autonomous but is induced by the somatic genital ridge

Synthesis of a 12R-type hexagonal perovskite solid solution Sr3NdNb3-xTixO12-delta and the influence of acceptor doping on electrical properties

A solid solution forms for Sr3NdNb3−xTixO12−δ with approximate limits 0 ≤ x ≤ 0.06. The system crystallizes with a 12R-type hexagonal perovskite structure in the space group R[3 with combining macron], as determined by neutron diffraction and selected area electron diffraction. The electrical properties of the end members have been investigated by impedance spectroscopy in the temperature range 550–800 °C under various gas atmospheres and as a function of oxygen and water-vapour partial pressure. Proton transport dominates under wet oxidising conditions in the temperature range 550–700 °C, as confirmed by the H+/D+ isotope effect. Acceptor doping considerably enhances proton conductivity with a value of 3.3 × 10−6 S cm−1 for the bulk response of x = 0.06 at 700 °C in moistened air. The presence of a −¼ slope for both doped and undoped samples in the range 10−19 ≤ pO2 ≤ 10−8 atm at 900 °C indicates n-type transport under reducing conditions following the extrinsic model attributable to acceptor centres. The conductivity is essentially independent of pO2 at 600 °C under dry oxidising conditions, consistent with oxide-ion transport; a positive power-law dependence at higher temperature indicates extrinsic behaviour and a significant electron–hole contribution. The dielectric constant at RT of nominally stoichiometric Sr3NdNb3O12 is εr ∼ 37, with a moderately high quality factor of Q × f ∼ 16 400 GHz at fr ∼ 6.4 GHz. The temperature coefficient of resonant frequency of x = 0 is τf ∼ 12 ppm °C−1, which lowers to −3 ppm °C−1 for the Ti-doped phase x = 0.06

Multi-layered Ruthenium-modified Bond Coats for Thermal Barrier Coatings

Diffusional approaches for fabrication of multi-layered Ru-modified bond coats for thermal barrier coatings have been developed via low activity chemical vapor deposition and high activity pack aluminization. Both processes yield bond coats comprising two distinct B2 layers, based on NiAl and RuAl, however, the position of these layers relative to the bond coat surface is reversed when switching processes. The structural evolution of each coating at various stages of the fabrication process has been and subsequent cyclic oxidation is presented, and the relevant interdiffusion and phase equilibria issues in are discussed. Evaluation of the oxidation behavior of these Ru-modified bond coat structures reveals that each B2 interlayer arrangement leads to the formation of α-Al 2 O 3 TGO at 1100°C, but the durability of the TGO is somewhat different and in need of further improvement in both cases

Regionally aggregated, stitched and de‐drifted CMIP‐climate data, processed with netCDF‐SCM v2.0.0

The world's most complex climate models are currently running a range of experiments as part of the Sixth Coupled Model Intercomparison Project (CMIP6). Added to the output from the Fifth Coupled Model Intercomparison Project (CMIP5), the total data volume will be in the order of 20PB. Here, we present a dataset of annual, monthly, global, hemispheric and land/ocean means derived from a selection of experiments of key interest to climate data analysts and reduced complexity climate modellers. The derived dataset is a key part of validating, calibrating and developing reduced complexity climate models against the behaviour of more physically complete models. In addition to its use for reduced complexity climate modellers, we aim to make our data accessible to other research communities. We facilitate this in a number of ways. Firstly, given the focus on annual, monthly, global, hemispheric and land/ocean mean quantities, our dataset is orders of magnitude smaller than the source data and hence does not require specialized ‘big data’ expertise. Secondly, again because of its smaller size, we are able to offer our dataset in a text-based format, greatly reducing the computational expertise required to work with CMIP output. Thirdly, we enable data provenance and integrity control by tracking all source metadata and providing tools which check whether a dataset has been retracted, that is identified as erroneous. The resulting dataset is updated as new CMIP6 results become available and we provide a stable access point to allow automated downloads. Along with our accompanying website (cmip6.science.unimelb.edu.au), we believe this dataset provides a unique community resource, as well as allowing non-specialists to access CMIP data in a new, user-friendly way

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM