Mercury-DPM: Fast particle simulations in complex geometries

Mercury-DPM is a code for performing discrete particle simulations. That is to say, it simulates the motion of particles, or atoms, by applying forces and torques that stem either from external body forces, (e.g. gravity, magnetic fields, etc…) or from particle interactions. For granular particles, these are typically contact forces (elastic, viscous, frictional, plastic, cohesive), while for molecular simulations, forces typically stem from interaction potentials (e.g. Lennard-Jones). Often the method used in these packages is referred to as the discrete element method (DEM), which was originally designed for geotechnical applications. However, as Mercury-DPM is designed for simulating particles with emphasis on contact models, optimized contact detection for highly different particle sizes, and in-code coarse graining (in contrast to post-processing), we prefer the more general name discrete particle simulation. The code was originally developed for granular chute flows, and has since been extended to many other granular applications, including the geophysical modeling of cinder cone creation. Despite its granular heritage it is designed in a flexible way so it can be adapted to include other features such as long-range interactions and non-spherical particles, etc

Perturbation of the yeast mitochondrial lipidome and associated membrane proteins following heterologous expression of Artemia-ANT

Heterologous expression is a landmark technique for studying a protein itself or its effect on the expression host, in which membrane-embedded proteins are a common choice. Yet, the impact of inserting a foreign protein to the lipid environment of host membranes, has never been addressed. Here we demonstrated that heterologous expression of the Artemia franciscana adenine nucleotide translocase (ANT) in yeasts altered lipidomic composition of their inner mitochondrial membranes. Along with this, activities of complex II, IV and ATP synthase, all membrane-embedded components, were significantly decreased while their expression levels remained unaffected. Although the results represent an individual case of expressing a crustacean protein in yeast inner mitochondrial membranes, it cannot be excluded that host lipidome alterations is a more widespread epiphenomenon, potentially biasing heterologous expression experiments. Finally, our results raise the possibility that not only lipids modulate protein function, but also membrane-embedded proteins modulate lipid composition, thus revealing a reciprocal mode of regulation for these two biomolecular entities

Medical treatment of renal cancer: new horizons.

Renal cell carcinoma (RCC) makes up 2-3% of adult cancers. The introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors in the mid-2000s radically changed the management of RCC. These targeted treatments superseded immunotherapy with interleukin-2 and interferon. The pendulum now appears to be shifting back towards immunotherapy, with the evidence of prolonged overall survival of patients with metastatic RCC on treatment with the anti-programmed cell death 1 ligand monoclonal antibody, nivolumab. Clinical prognostic criteria aid prediction of relapse risk for resected localised disease. Unfortunately, for patients at high risk of relapse, no adjuvant treatment has yet shown benefit, although further trials are yet to report. Clinical prognostic models also have a role in the management of advanced disease; now there is a pressing need for predictive biomarkers to direct therapy. Treatment selection for metastatic disease is currently based on histology, prognostic group and patient preference based on side effect profile. In this article, we review the current medical and surgical management of localised, oligometastatic and advanced RCC, including side effect management and the evidence base for management of poor-risk and non-clear cell disease. We discuss recent results from clinical trials and how these are likely to shape future practice and a renaissance of immunotherapy for renal cell cancer

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Extended kinetic theory applied to inclined granular flows: role of boundaries

We compare the predictions of extended kinetic theory (EKT), where the roles of surface friction and correlation in fluctuation velocities are taken into account, with discrete element simulations of steady, fully-developed, inclined flows of identical spheres over bumpy bases, in the presence and absence of flat, frictional sidewalls. We show that the constitutive relation for the pressure of EKT must be modified in the proximity of the boundary, because of the influence of excluded volume and shielding associated with collisions of particles with the boundary itself. We also note that currently available boundary conditions for flows over bumpy planes in kinetic theory underestimate the energy dissipation. These two observations explain the lack of agreement of EKT with the simulations, in terms of the maximum angles of inclination for which steady, fully-developed flows are possible. That is, for some high angles of inclination, EKT does not have solutions, while steady flows are predicted in DEM. However, whenever a solution to the system of differential equations of EKT does exist, the predicted distributions of velocity, solid volume fraction and granular temperature satisfactorily match the numerical measurements. The incompressible, algebraic approximation of EKT, which ignores the conduction of energy in the energy balance, admits solutions for a wider range of angles of inclination, as in the simulations, but fails to reproduce the quantitative and qualitative behaviour of solid volume fraction and granular temperature in the two conductive layers at the top and bottom of the flow. When frictional sidewalls are added to the domain, we show that the spanwise ratio of shear stress to pressure is linearly distributed in the dense core region of the flow, confirming that the sidewalls exert, on average, a Coulomb-like resistance to the flow with an effective friction coefficient which is less than half the actual particle-wall friction