Publications

Planar germanium is currently the only semiconducting platform where high-coherence spin qubits and proximity-induced superconductivity have each been demonstrated. Recent research into spin qubits in Ge/SiGe heterostructures has focused on increasing the thickness of the SiGe capping layer, reporting improvements in the electrostatic noise levels. Meanwhile, heterostructures with thinner capping layers remain rather unexplored, despite the potential advantages for proximity-induced superconductivity. Here, we study a Ge/SiGe heterostructure with a thin SiGe cap d ≈ 4 nm and investigate its viability to host low-noise quantum dots. To keep the thermal budget compatible with superconducting layers, low-temperature oxide deposition processes were developed and implemented for the gate dielectrics. The charge noise level of the fabricated devices is estimated to be 1.8 ± 1.0 μeV/Hz, comparable to devices fabricated on shallow heterostructures (d ∼ 20 nm) with high-temperature deposited oxides. Low charge noise levels, together with the straightforward integration of superconductors, make this heterostructure an attractive platform for prototyping hybrid semiconducting–superconducting devices.

Games have long been a microcosm for studying planning and reasoning in both natural and artificial intelligence, often focusing on expert-level or even super-human play1, 2, 3, 4, 5–6. But real life also pushes human intelligence along a different frontier, requiring people to flexibly navigate decision-making problems that they have never thought about before. Here we use novice gameplay to study how people reason about new problem settings. Through a series of large-scale behavioural studies with over 1,000 participants and 121 two-player strategic board games (almost all novel to our participants), we show that people are systematic and adaptively rational in how they play a game for the first time or evaluate a game (for example, how fair or how fun it is likely to be) before they have played it even once. We explain these capacities via a computational cognitive model that we call the ‘Intuitive Gamer’: a model based on mechanisms of fast and flat (depth-limited) goal-directed probabilistic simulation. Our work offers insights into how people rapidly evaluate, act and make suggestions when encountering novel problems, and could inform the design of more flexible and human-like artificial intelligence systems that can determine not just how to solve new tasks but also whether a task is worth thinking about at all.

Arrays of Josephson junctions can be tuned through anomalous metallic, quantum-critical, and insulating regimes. We introduce an alternative experimental probe, capturing microwave radiation across all three regimes, using a two-dimensional array of superconductor-semiconductor hybrid Josephson junctions as a model system. Our approach allows in situ calibration of the sample’s circuit parameters and provides isolation from measurement back-action effects. We measure the radiation temperature of the anomalous metal and find that it is hotter than both the quantum-critical and insulating regimes. We further show that the anomalous metallic regime is more susceptible to additional heating than other regimes, explaining its emergence in otherwise thermalized systems. Turning to the quantum-critical regime, we discover nonlinear scaling of radiative noise with applied bias, consistent with theoretical predictions of universal nonequilibrium behavior at quantum-critical points.

Cyanogenic compounds provide potent defenses to herbivorous insects, yet few species are known to acquire them from their food. Matador bugs, Bitta alipes (Hemiptera: Coreidae), have brightly colored signals that deter avian predators and are specialists of cyanogenic Passiflora plants. It is unknown whether these insects accumulate cyanogenic compounds. We document the first evidence of cyanogen accumulation in matador bugs. However, the presence and concentration of cyanogens depended on the Passiflora species from which insects were feeding. Further, three related species of inconspicuous Coreidae, and their Cactaceae and Aquifoliaceae host plants, also contained cyanogenic compounds. In all coreid species, cyanogen concentrations detected would make them unpalatable, or even lethal, to vertebrate predators. We report the first evidence of cyanogenic compounds in the Coreidae, doubling the number of species known to accumulate cyanide in the Hemiptera. Cyanogen accumulation may be more common amongst hemipterans than previously thought, prompting studies to examine the mechanisms of secondary chemical accumulation and evolution of aposematism.

Magic is frequently employed in high-stakes contexts such as healing and divination, which suggests that its users take it to be efficacious. This poses a puzzle: why would broadly rational agents persist in practices that are, by their ostensible aims, ineffective? Existing accounts divide between intellectualist views, which hold that practitioners genuinely believe in the efficacy of magic, and non-intellectualist views, which argue that magical practices are accompanied by non-doxastic attitudes such as imagination, symbolism, or make-believe. We argue that both positions capture part of the truth. Drawing on ethnography, cognitive science, political psychology, and philosophy, we defend a mixed-attitude account according to which individuals within the same culture—and even the same individual over time—can relate to different magical practices with a range of attitudes, from genuine belief to scepticism, expressive endorsement, or mistaken self-ascription of belief. This framework reconciles evidence cited by both intellectualists and their critics and suggests that belief reports about magic, as well as those concerning conspiracy theories and magic in WEIRD societies, should not be assumed to reflect a single, uniform cognitive attitude.

The DNA damage response (DDR) is critical for pancreatic ductal adenocarcinoma (PDAC) development and therapeutic responses, including to genotoxic agents. While epigenetic modulators have been shown to contribute to the DDR, how chromatin regulation dictates responses to DNA damage in PDAC remains incompletely understood. Here, we identify Class I histone deacetylases (HDACs) as critical regulators of the DDR. HDAC1/2 direct the genomic distribution of H3K27ac, ensuring sufficient BRD4 and RNA polymerase II (Pol II) occupancy at DDR gene promoters. HDAC inhibition by entinostat shifts the balance of H3K27 acetylation preferentially toward intergenic regions, diverting BRD4 and Pol II from promoters, thereby suppressing DDR gene expression. In line with this, HDAC inhibition heightens DNA damage and sensitizes PDAC to diverse DNA-damaging and DDR-targeting agents. Since the clinical development of HDAC inhibitors has been limited by systemic toxicity, we developed bottlebrush prodrug (BPD) nanoparticles for tumor-selective entinostat delivery. Entinostat-BPD achieved tumor-specific HDAC inhibition while displaying potent efficacy and reduced systemic toxicity. These findings reveal an HDAC-dependent DDR vulnerability and offer combinational and precision targeting strategies to facilitate clinical translation and improve PDAC patient outcomes.

Background: RNA-guided nucleases enable DNA editing and offer promise for treating genetic diseases, particularly when used for precise sequence replacement. However, many of the most effective enzymes, such as Streptococcus pyogenes Cas9, are too large for delivery using vectors like adeno-associated virus. This has prompted interest in smaller alternatives from the Cas12f and TnpB families. Yet, these nucleases often show low activity in mammalian cells, limiting their utility. Results: We use directed evolution in human cells to select variants with greatly improved activity. The resulting variants, Cas12f1Super and TnpBSuper, exhibit up to 11-fold increase in editing efficiency without increased off-target effects. When tested as a base editor, Cas12f1Super shows up to tenfold improvement relative to the previously engineered CasMINI, suggesting utility beyond nuclease-related activities. Conclusions: These compact and efficient genome editors expand the current toolkit and hold promise for both research and therapeutic use in mammalian systems.

Background The Resuscitation in Paediatric Septic Shock using Vitamin C and Hydrocortisone (RESPOND) trial is a multicentre randomised controlled trial exploring whether the use of hydrocortisone alone, or in combination with vitamin C, increases time alive and free of vasopressors for critically ill children. Objective To present the prespecified statistical analysis plan (SAP) for the RESPOND trial prior to finalising recruitment and locking the trial dataset. Design, setting, and participants The RESPOND trial is a three-arm, parallel group, open-label, randomised controlled trial, recruiting in paediatric intensive care units in Australia, New Zealand, India, and Brazil. The planned sample size is 384 participants. Main outcome measures The primary outcome is time alive and free of inotropes/vasopressors, censored at 7 days post-randomisation. Secondary outcomes include clinical (e.g. alive and free of multi-organ dysfunction, length of stay), safety, health economics (e.g. incremental costs, quality-adjusted life years), and long-term outcomes (measured at 6 months post-randomisation; e.g. health-related quality of life). Results and conclusions The SAP was designed by the Chief Investigators and approved by the RESPOND Steering Committee. Statistical analyses are summarised. The primary outcome will be analysed using quantile regression adjusted for stratification variables. Appropriate statistical comparisons between groups were planned and described in a way that is transparent, available to the public, verifiable, and predetermined before completion of data collection. The trial statistician, RESPOND Steering Committee members, and SAP authors remain blind to treatment allocation throughout the study. Data Safety and Monitoring Board members were provided with safety data with masked group identifiers during interim analyses. The RESPOND trial commenced recruitment in December, 2021, and aims to complete recruitment by mid-2026. Trial registration ACTRN12621000247875.