Explore the vast range of titles available.

There is considerable interest in approaches that could improve the therapeutic window of radiotherapy. In this study, hafnium oxide nanoparticles were designed that concentrate in tumor cells to achieve intracellular high-energy dose deposit. Conventional methods were used, implemented in different ways, to explore interactions of these high-atomic-number nanoparticles and ionizing radiation with biological systems. Using the Monte Carlo simulation, these nanoparticles, when exposed to high-energy photons, were shown to demonstrate an approximately ninefold radiation dose enhancement compared with water. Importantly, the nanoparticles show satisfactory dispersion and persistence within the tumor and they form clusters in the cytoplasm of cancer cells. Marked antitumor activity is demonstrated in human cancer models. Safety is similar in treated and control animals as demonstrated by a broad program of toxicology evaluation. These findings, supported by good tolerance, provide the basis for developing this new type of nanoparticle as a promising anticancer approach in human patients.

Memristors with tunable resistance states are emerging building blocks of artificial neural networks. However, in situ learning on a large-scale multiple-layer memristor network has yet to be demonstrated because of challenges in device property engineering and circuit integration. Here we monolithically integrate hafnium oxide-based memristors with a foundry-made transistor array into a multiple-layer neural network. We experimentally demonstrate in situ learning capability and achieve competitive classification accuracy on a standard machine learning dataset, which further confirms that the training algorithm allows the network to adapt to hardware imperfections. Our simulation using the experimental parameters suggests that a larger network would further increase the classification accuracy. The memristor neural network is a promising hardware platform for artificial intelligence with high speed-energy efficiency. Memristor-based neural networks hold promise for neuromorphic computing, yet large-scale experimental execution remains difficult. Here, Xia et al. create a multi-layer memristor neural network with in-situ machine learning and achieve competitive image classification accuracy on a standard dataset.

Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect). Nonetheless, clinical evidence of sustained anti-tumor immunity as abscopal effect are rare. Hafnium oxide nanoparticles (NBTXR3) have been designed to increase energy dose deposit within cancer cells. We examined the effect of radiotherapy-activated NBTXR3 on anti-tumor immune response activation and abscopal effect production using a mouse colorectal cancer model. We demonstrate that radiotherapy-activated NBTXR3 kill more cancer cells than radiotherapy alone, significantly increase immune cell infiltrates both in treated and in untreated distant tumors, generating an abscopal effect dependent on CD8+ lymphocyte T cells. These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy.

Memory devices with high speed and high density are highly desired to address the ‘memory wall’ issue. Here we demonstrated a highly scalable, three-dimensional stackable ferroelectric diode, with its rectifying polarity modulated by the polarization reversal of Hf 0.5 Zr 0.5 O 2 films. By visualizing the hafnium/zirconium lattice order and oxygen lattice order with atomic-resolution spherical aberration-corrected STEM, we revealed the correlation between the spontaneous polarization of Hf 0.5 Zr 0.5 O 2 film and the displacement of oxygen atom, thus unambiguously identified the non-centrosymmetric Pca2 1 orthorhombic phase in Hf 0.5 Zr 0.5 O 2 film. We further implemented this ferroelectric diode in an 8 layers 3D array. Operation speed as high as 20 ns and robust endurance of more than 10 9 were demonstrated. The built-in nonlinearity of more than 100 guarantees its self-selective property that eliminates the need for external selectors to suppress the leakage current in large array. This work opens up new opportunities for future memory hierarchy evolution. Designing reliable, scalable and high speed computing systems remains a challenge. Here, the authors identify noncentrosymmetric orthorhombic phase in HZO film and demonstrate a CMOS compatible 3D Vertical HZO-based ferroelectric diode array with self-selective property and 20 ns of speed operation.

Ultrathin ferroelectric materials could potentially enable low-power logic and nonvolatile memories 1 , 2 . As ferroelectric materials are made thinner, however, the ferroelectricity is usually suppressed. Size effects in ferroelectrics have been thoroughly investigated in perovskite oxides—the archetypal ferroelectric system 3 . Perovskites, however, have so far proved unsuitable for thickness scaling and integration with modern semiconductor processes 4 . Here we report ferroelectricity in ultrathin doped hafnium oxide (HfO 2 ), a fluorite-structure oxide grown by atomic layer deposition on silicon. We demonstrate the persistence of inversion symmetry breaking and spontaneous, switchable polarization down to a thickness of one nanometre. Our results indicate not only the absence of a ferroelectric critical thickness but also enhanced polar distortions as film thickness is reduced, unlike in perovskite ferroelectrics. This approach to enhancing ferroelectricity in ultrathin layers could provide a route towards polarization-driven memories and ferroelectric-based advanced transistors. This work shifts the search for the fundamental limits of ferroelectricity to simpler transition-metal oxide systems—that is, from perovskite-derived complex oxides to fluorite-structure binary oxides—in which ‘reverse’ size effects counterintuitively stabilize polar symmetry in the ultrathin regime. Enhanced switchable ferroelectric polarization is achieved in doped hafnium oxide films grown directly onto silicon using low-temperature atomic layer deposition, even at thicknesses of just one nanometre.

Ultrathin two-dimensional (2D) semiconducting layered materials offer great potential for extending Moore’s law of the number of transistors in an integrated circuit 1 . One key challenge with 2D semiconductors is to avoid the formation of charge scattering and trap sites from adjacent dielectrics. An insulating van der Waals layer of hexagonal boron nitride (hBN) provides an excellent interface dielectric, efficiently reducing charge scattering 2 , 3 . Recent studies have shown the growth of single-crystal hBN films on molten gold surfaces 4 or bulk copper foils 5 . However, the use of molten gold is not favoured by industry, owing to its high cost, cross-contamination and potential issues of process control and scalability. Copper foils might be suitable for roll-to-roll processes, but are unlikely to be compatible with advanced microelectronic fabrication on wafers. Thus, a reliable way of growing single-crystal hBN films directly on wafers would contribute to the broad adoption of 2D layered materials in industry. Previous attempts to grow hBN monolayers on Cu (111) metals have failed to achieve mono-orientation, resulting in unwanted grain boundaries when the layers merge into films 6 , 7 . Growing single-crystal hBN on such high-symmetry surface planes as Cu (111) 5 , 8 is widely believed to be impossible, even in theory. Nonetheless, here we report the successful epitaxial growth of single-crystal hBN monolayers on a Cu (111) thin film across a two-inch c -plane sapphire wafer. This surprising result is corroborated by our first-principles calculations, suggesting that the epitaxial growth is enhanced by lateral docking of hBN to Cu (111) steps, ensuring the mono-orientation of hBN monolayers. The obtained single-crystal hBN, incorporated as an interface layer between molybdenum disulfide and hafnium dioxide in a bottom-gate configuration, enhanced the electrical performance of transistors. This reliable approach to producing wafer-scale single-crystal hBN paves the way to future 2D electronics. The epitaxial growth of single-crystal hexagonal boron nitride monolayers on a copper (111) thin film across a sapphire wafer suggests a route to the broad adoption of two-dimensional layered semiconductor materials in industry.

Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2–3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. Act.In.Sarc is a phase 2–3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0–2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3–4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3–4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3–4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3–4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. Nanobiotix SA and PharmaEngine, Inc.

Although indium tin oxide (ITO) is widely used in optoelectronics due to its high optical transmittance and electrical conductivity, its degenerate doping limits exploitation as a semiconduction material. In this work, we created short-channel active transistors based on an ultra-thin (down to 4 nm) ITO channel and a high-quality, lanthanum-doped hafnium oxide dielectric of equivalent oxide thickness of 0.8 nm, with performance comparative to that of existing metal oxides and emerging two-dimensional materials. Short-channel immunity, with a subthreshold slope of 66 mV per decade, off-state current <100 fA μm–1 and on/off ratio up to 5.5 × 109, was measured for a 40-nm transistor. Logic inverters working in the subthreshold regime exhibit a high gain of 178 at a low-supply voltage of 0.5 V. Moreover, radiofrequency transistors, with as-measured cut-off frequency fT and maximum oscillation frequency fmax both >10 GHz, have been demonstrated. The unique wide bandgap and low dielectric constant of ITO provide prospects for future scaling below the 5-nm regime for advanced low-power electronics.

Ferroelectric HfO 2 -based materials hold great potential for the widespread integration of ferroelectricity into modern electronics due to their compatibility with existing Si technology. Earlier work indicated that a nanometre grain size was crucial for the stabilization of the ferroelectric phase. This constraint, associated with a high density of structural defects, obscures an insight into the intrinsic ferroelectricity of HfO 2 -based materials. Here we demonstrate that stable and enhanced polarization can be achieved in epitaxial HfO 2 films with a high degree of structural order (crystallinity). An out-of-plane polarization value of 50 μC cm –2 has been observed at room temperature in Y-doped HfO 2 (111) epitaxial thin films, with an estimated full value of intrinsic polarization of 64 μC cm –2 , which is in close agreement with density functional theory calculations. The crystal structure of films reveals the Pca 2 1 orthorhombic phase with small rhombohedral distortion, underlining the role of the structural constraint in stabilizing the ferroelectric phase. Our results suggest that it could be possible to exploit the intrinsic ferroelectricity of HfO 2 -based materials, optimizing their performance in device applications. Hafnium dioxide is of technological interest as it is compatible with silicon; however, previous work indicates that a nanometre grain size is required to generate ferroelectricity. Here ferroelectric Y-doped HfO 2 thin films with high crystallinity are grown with large crystal grain sizes, indicating that ferroelectricity is intrinsic.

With the development of wearable devices and hafnium-based ferroelectrics (FE), there is an increasing demand for high-performance flexible ferroelectric memories. However, developing ferroelectric memories that simultaneously exhibit good flexibility and significant performance has proven challenging. Here, we developed a high-performance flexible field-effect transistor (FeFET) device with a thermal budget of less than 400 °C by integrating Zr-doped HfO 2 (HZO) and ultra-thin indium tin oxide (ITO). The proposed FeFET has a large memory window (MW) of 2.78 V, a high current on/off ratio (I ON /I OFF ) of over 10 8 , and high endurance up to 2×10 7 cycles. In addition, the FeFETs under different bending conditions exhibit excellent neuromorphic properties. The device exhibits excellent bending reliability over 5×10 5 pulse cycles at a bending radius of 5 mm. The efficient integration of hafnium-based ferroelectric materials with promising ultrathin channel materials (ITO) offers unique opportunities to enable high-performance back-end-of-line (BEOL) compatible wearable FeFETs for edge intelligence applications. Using Zr-doped HfO2 and ultra-thin indium tin oxide, Li et al. develop flexible field-effect transistors with a memory window of 2.78 V and bending reliability to enable high-performance back-end-of-line compatible wearable devices.