Multiscalar cellular automaton simulates in-vivo tumour-stroma patterns calibrated from in-vitro assay data

Background: The tumour stroma -or tumour microenvironment- is an important constituent of solid cancers and it is thought to be one of the main obstacles to quantitative translation of drug activity between the preclinical and clinical phases of drug development. The tumour-stroma relationship has been described as being both pro- and antitumour in multiple studies. However, the causality of this complex biological relationship between the tumour and stroma has not yet been explored in a quantitative manner in complex tumour morphologies.Methods: To understand how these stromal and microenvironmental factors contribute to tumour physiology and how oxygen distributes within them, we have developed a lattice-based multiscalar cellular automaton model. This model uses principles of cytokine and oxygen diffusion as well as cell motility and plasticity to describe tumour-stroma landscapes. Furthermore, to calibrate the model, we propose an innovative modelling platform to extract model parameters from multiple in-vitro assays. This platform provides a novel way to extract meta-data that can be used to complement in-vivo studies and can be further applied in other contexts.Results: Here we show the necessity of the tumour-stroma opposing relationship for the model simulations to successfully describe the in-vivo stromal patterns of the human lung cancer cell lines Calu3 and Calu6, as models of clinical and preclinical tumour-stromal topologies. This is especially relevant to drugs that target the tumour microenvironment, such as antiangiogenics, compounds targeting the hedgehog pathway or immune checkpoint inhibitors, and is potentially a key platform to understand the mechanistic drivers for these drugs.Conclusion: The tumour-stroma automaton model presented here enables the interpretation of complex in-vitro data and uses it to parametrise a model for in-vivo tumour-stromal relationships

Bounding the graviton mass with binary pulsar observations

By comparing the observed orbital decay of the binary pulsars PSRB1913+16 and PSRB1534+12 to that predicted by general relativity due to gravitational-wave emission, we are able to bound the mass of the graviton to be less than $7.6\times10^{-20} \text{eV}/c^2$ at 90% confidence. This is the first such bound to be derived from dynamic gravitational fields. It is approximately two orders of magnitude weaker than the static-field bound from solar system observations, and will improve with further observations.Comment: 9 pages, 1 figure. Presented at Fourth Edoardo Amaldi Conference on Gravitational Waves, Perth, 200

A delicate balance: Iron metabolism and diseases of the brain

Iron is the most abundant transition metal within the brain, and is vital for a number of cellular processes including neurotransmitter synthesis, myelination of neurons, and mitochondrial function. Redox cycling between ferrous and ferric iron is utilized in biology for various electron transfer reactions essential to life, yet this same chemistry mediates deleterious reactions with oxygen that induce oxidative stress. Consequently, there is a precise and tightly controlled mechanism to regulate iron in the brain. When iron is dysregulated, both conditions of iron overload and iron deficiencies are harmful to the brain. This review focuses on how iron metabolism is maintained in the brain, and how an alteration to iron and iron metabolism adversely affects neurological function. © 2013 Hare, Ayton, Bush and Lei

Formation and Structure of a Current Sheet in Pulsed-Power Driven Magnetic Reconnection Experiments

We describe magnetic reconnection experiments using a new, pulsed-power driven experimental platform in which the inflows are super-sonic but sub-Alfv\'enic.The intrinsically magnetised plasma flows are long lasting, producing a well-defined reconnection layer that persists over many hydrodynamic time scales.The layer is diagnosed using a suite of high resolution laser based diagnostics which provide measurements of the electron density, reconnecting magnetic field, inflow and outflow velocities and the electron and ion temperatures.Using these measurements we observe a balance between the power flow into and out of the layer, and we find that the heating rates for the electrons and ions are significantly in excess of the classical predictions. The formation of plasmoids is observed in laser interferometry and optical self-emission, and the magnetic O-point structure of these plasmoids is confirmed using magnetic probes.Comment: 14 pages, 12 figures. Accepted for publication in Physics of Plasma

A Strong Pulsing Nature of Negative Intracloud Dart Leaders Accompanied by Regular Trains of Microsecond-Scale Pulses

We report the first observations of negative intracloud (IC) dart-stepped leaders accompanied by regular trains of microsecond-scale pulses, simultaneously detected by shielded broadband magnetic loop antennas and the radio telescope Low Frequency Array (LOFAR). Four investigated pulse trains occurred during complicated IC flashes on 18 June 2021, when heavy thunderstorms hit the Netherlands. The pulses within the trains are unipolar, a few microseconds wide, and with an average inter-pulse interval of 5–7 μs. The broadband pulses perfectly match energetic, regularly distributed, and relatively isolated bursts of very high frequency sources localized by LOFAR. All trains were generated by negative dart-stepped leaders propagating at a lower speed than usual dart leaders. They followed channels of previous leaders occurring within the same flash several tens of milliseconds before the reported observations. The physical mechanism remains unclear as to why we observe dart-stepped leaders, which show mostly regular stepping, emitting energetic microsecond-scale pulses.</p