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The bed of the West Antarctic ice sheet is, in places, more than 1.5 km below sea level. Radio-echo sounding data from the Weddell Sea sector of Antarctica reveal a large subglacial basin immediately upstream of the ice sheet’s grounding line, with a steep reverse gradient and a smooth floor.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The Filchner–Ronne and Ross ice shelves are two of the largest in Antarctica. Here the authors show their vulnerability to warming ocean conditions, where a transition to warmer waters in the ice shelf cavities could lead to accelerated ice loss and grounding line retreat.

A plethora of standards mean shareable and verifiable microscopy data often get lost in translation. Biologists are working on a solution.

Topological insulators offer lossless surface transport because of the suppression of conduction-electron backscattering from defect sites. Here, the authors show that the nanoscale voltage drops caused by such scattering can be directly measured using scanning tunnelling potentiometry.

Protein motion in crowded environments governs cellular transport and reaction rates. Here, the authors use megahertz X-ray Photon Correlation Spectroscopy to reveal anomalous diffusion of ferritin, linking hydrodynamic and direct interactions to cage-trapping at microsecond time scales.

In this follow-up study presenting results at 96 weeks, cabotegravir and rilpivirine long-acting therapy remained noninferior to oral therapy, had acceptable safety and tolerability profiles, and resulted in durable virologic suppression, further supporting its consideration for African treatment programs.

Using quantitative brain imaging, the authors show opposite fMRI BOLD signal to metabolic activity due to variable oxygen extraction across the human cortex. This questions the canonical interpretation of fMRI signal in terms of neuronal activity.

By unifying data from engineered β-barrel nanopores and supported by modelling, it is demonstrated that the lumen charge in a β-barrel nanopore governs rectification and voltage-driven gating, with applications in computing using nanofluidic synapses.

Subglacial meltwater channels beneath the Antarctic Ice Sheet have been reported, but the nature and distribution of these meltwater pathways are unclear. Remote sensing observations reveal persistent channelized features beneath the Filchner–Ronne Ice Shelf in West Antarctica, suggesting widespread channelized flow driven by melting.

Bacterial ATP-binding cassette (ABC) transporters can be utilized and engineered to transport non-canonical amino acids into Escherichia coli for highly efficient synthesis of proteins with novel functions.

It is important to understand how much long-term sea-level rise is already committed due to historical and near-term emissions. Here the authors use a modelling framework to show how decisions on global emissions reductions in the coming decades alter multi-century sea-level rise projections.

Intense extreme UV and X-ray coherent sources are set to revolutionize numerous research areas, yet characterization of their polarization remains elusive. Here, Mazza et al.measure the polarization state of circularly polarized extreme UV light from a free-electron laser using circular dichroism.

How lattice degrees of freedom affect the topological properties of electrons remains rarely explored. Here, Moeller et al. predict non-trivial topological effects in long-lived polaron bands by studying a two-dimensional model stabilized by realistic electron-phonon coupling.

Here, the authors show that cystatin C (CST3) regulates the activity of cathepsin B during pancreatitis in a pH dependent manner. Moreover, cathepsin B activity is inhibited by monomeric CST3 but activated by dimeric CST3.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The onset of modern central Asian atmospheric circulation is often linked to the interplay of late Cenozoic paleogeographic changes and global cooling. Here the authors present sedimentary provenance data from early Cenozoic dust deposits, which indicate long-term stability of the central Asian high pressure system.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Here the authors establish and benchmark a single cell RNA multiplexing framework that enables simple, yet robust high-throughput multiplexing leveraging single cell nucleotide polymorphisms of patients.

Bilayer graphene allows the realization of electron–hole double-quantum dots that exhibit near-perfect particle–hole symmetry, in which transport occurs via the creation and annihilation of single electron–hole pairs with opposite quantum numbers.

Germany is paving the way toward genomics-based personalized healthcare and translational research.

The durability of Fe-N-C single-atom-catalysts for oxygen reduction in acidic medium remains elusive. Here, the authors report how a low amount of platinum stabilizes the FeN4 sites via a long-range electronic effect.

Resonant X-ray excitation of the  ⁴⁵Sc nuclear isomeric state was achieved by irradiation of a Sc-metal foil with 12.4-keV photon pulses from a state-of-the-art X-ray free-electron laser, allowing a high-precision determination of the transition energy.

Moderately reducing the visibility of renewable energy infrastructure in Germany is found to have a negligible impact on energy system costs and design. Strict visibility restrictions, however, may reduce the system’s resilience and increase costs by 38% in 2045.

Christian Steidl and colleagues identify recurrent somatic mutations in the PTPN1 gene in primary mediastinal B cell lymphoma and Hodgkin lymphoma. They show that mutant PTPN1 leads to reduced phosphatase activity and increased phosphorylation of JAK-STAT pathway members.

Graphene quantum dots promise applications for spin and valley qubits; however a demonstration of phase coherent oscillations has been lacking. Here the authors report coherent charge oscillations and measurements of coherence times in highly tuneable double quantum dots in bilayer graphene.