Novel nanocomposite-superlattices for low energy and high stability nanoscale phase-change memory.

Data-centric applications are pushing the limits of energy-efficiency in today's computing systems, including those based on phase-change memory (PCM). This technology must achieve low-power and stable operation at nanoscale dimensions to succeed in high-density memory arrays. Here we use a novel combination of phase-change material superlattices and nanocomposites (based on Ge4Sb6Te7), to achieve record-low power density ≈ 5 MW/cm2 and ≈ 0.7 V switching voltage (compatible with modern logic processors) in PCM devices with the smallest dimensions to date (≈ 40 nm) for a superlattice technology on a CMOS-compatible substrate. These devices also simultaneously exhibit low resistance drift with 8 resistance states, good endurance (≈ 2 × 108 cycles), and fast switching (≈ 40 ns). The efficient switching is enabled by strong heat confinement within the superlattice materials and the nanoscale device dimensions. The microstructural properties of the Ge4Sb6Te7 nanocomposite and its high crystallization temperature ensure the fast-switching speed and stability in our superlattice PCM devices. These results re-establish PCM technology as one of the frontrunners for energy-efficient data storage and computing.

Band-to-Band Tunneling Leakage Current Characterization and Projection in Carbon Nanotube Transistors.

Carbon nanotube (CNT) transistors demonstrate high mobility but also experience off-state leakage due to the small effective mass and band gap. The lower limit of off-current (IMIN) was measured in electrostatically doped CNT metal-oxide-semiconductor field-effect transistors (MOSFETs) across a range of band gaps (0.37 to 1.19 eV), supply voltages (0.5 to 0.7 V), and extension doping levels (0.2 to 0.8 carriers/nm). A nonequilibrium Green's function (NEGF) model confirms the dependence of IMIN on CNT band gap, supply voltage, and extension doping level. A leakage current design space across CNT band gap, supply voltage, and extension doping is projected based on the validated NEGF model for long-channel CNT MOSFETs to identify the appropriate device design choices. The optimal extension doping and CNT band gap design choice for a target off-current density are identified by including on-current projection in the leakage current design space. An extension doping level >0.5 carrier/nm is required for optimized on-current.

A comparison of the efficacy of trastuzumab deruxtecan in advanced HER2-positive breast cancer: active brain metastasis versus progressive extracranial disease alone.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is currently unknown. No direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs in patients commencing T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinicopathological information, prior treatment, the presence or absence of central nervous system (CNS) disease, outcomes and treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Twenty-nine female patients, with a median age of 52 years (interquartile range 44-62 years), were identified; the prevalence of BM was 41%. Median number of lines of prior therapy was 2 (range 2-6). At a median follow-up of 13.8 months, median progression-free survival (PFS) for the overall population was 13.9 months [95% confidence interval (CI) 12.4 months-not estimable (NE)], 16.1 months (95% CI 15.1 months-NE) for active BMs and 12.4 months (95% CI 8.3 months-NE) for progressive extracranial disease alone. The 12-month overall survival (OS) rate was 74% (95% CI 59% to 95%) in the overall population, and 83% (95% CI 58% to 100%) and 66% (95% CI 45% to 96%) for active BMs and extracranial disease only, respectively. Most common TEAEs were fatigue, alopecia, and constipation. In nine patients (31%, including two deaths), pneumonitis occurred. CONCLUSION: In this real-world population, we demonstrate T-DXd to be effective in patients with active BMs and those with progressive extracranial disease alone. PFS and OS were numerically longer in those with active BMs. These data demonstrate that patients with active BM treated with T-DXd have at least comparable outcomes to those with extracranial disease alone. The high rate of pneumonitis warrants further consideration.

The relationship between body dissatisfaction and attentional bias to thin bodies in Malaysian Chinese and White Australian women: a dot probe study.

Studies suggest that an attentional bias to thin bodies is common among those with high levels of body dissatisfaction, which is a risk factor for, and symptom of, various eating disorders. However, these studies have predominantly been conducted in Western countries with body stimuli involving images of White people. In a preregistered study, we recruited 150 Malaysian Chinese women and 150 White Australian women for a study using standardized images of East Asian and White Australian bodies. To measure attentional bias to thin bodies, participants completed a dot probe task which presented images of women who self-identified their ethnicity as East Asian or as White Australian. Contrary to previous findings, we found no evidence for an association between body dissatisfaction and attentional bias to thin bodies. This lack of association was not affected by participant ethnicity (Malaysian Chinese versus White Australian) or ethnic congruency between participants and body stimuli (own-ethnicity versus other-ethnicity). However, the internal consistency of the dot probe task was poor. These results suggest that either the relationship between body dissatisfaction and attentional bias to thin bodies is not robust, or the dot probe task may not be a reliable measure of attentional bias to body size.

Area-Selective Atomic Layer Deposition for Resistive Random-Access Memory Devices.

Resistive random-access memory (RRAM) is a promising technology for data storage and neuromorphic computing; however, cycle-to-cycle and device-to-device variability limits its widespread adoption and high-volume manufacturability. Improving the structural accuracy of RRAM devices during fabrication can reduce these variabilities by minimizing the filamentary randomness within a device. Here, we studied area-selective atomic layer deposition (AS-ALD) of the HfO2 dielectric for the fabrication of RRAM devices with higher reliability and accuracy. Without requiring photolithography, first we demonstrated ALD of HfO2 patterns uniformly and selectively on Pt bottom electrodes for RRAM but not on the underlying SiO2/Si substrate. RRAM devices fabricated using AS-ALD showed significantly narrower operating voltage range (2.6 × improvement) and resistance states than control devices without AS-ALD, improving the overall reliability of RRAM. Irrespective of device size (1 × 1, 2 × 2, and 5 × 5 µm2), we observed similar improvement, which is an inherent outcome of the AS-ALD technique. Our demonstration of AS-ALD for improved RRAM devices could further encourage the adoption of such techniques for other data storage technologies, including phase-change, magnetic, and ferroelectric RAM.

Vaccine safety surveillance in Kenya using GAIA standards: A feasibility assessment of existing national and subnational research and program systems.

BACKGROUND: Active surveillance systems for monitoring vaccine safety among pregnant women address some of the limitations of a current passive surveillance approach utilized in low- and middle-income countries (LMIC). However, few active surveillance systems in LMIC exist. Our study assessed the feasibility of utilizing three existing data collection systems in Kenya for active surveillance of maternal immunization and to assess the applicability of Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions that were initially developed for clinical trials within these systems. METHODS: We assessed applicability of GAIA case definition for maternal Tetanus Toxoid exposure, stillbirth, low birth weight, small for gestational age, Neonatal Invasive Blood Stream Infection (NIBSI), prematurity and neonatal death in two routine web-based health information systems (Kenya EMR and DHIS-2), and a web-based population-based pregnancy research platform (ANCOV1) in Kenya. RESULTS: All three HIS were capable of reporting selected outcomes to varying degrees of GAIA certainty. The ANCOV platform was the most robust in collecting and collating clinical data for effective maternal pharmacovigilance. The utilization of facility- and district-aggregated data limits the usefulness of DHIS-2 in pharmacovigilance as currently operationalized. While the Kenya EMR contained individual level data and meets the key considerations for effective pharmacovigilance, it was used primarily for HIV care and treatment records in a small proportion of health facilities and would require additional resources to expand to all antenatal care facilities and to link maternal and infant records. DISCUSSION: Population-based research studies may offer a responsive short-term option for implementing maternal vaccine pharmacovigilance in LMICs. However, the foundation exists for long-term capacity building within the national health electronic data systems to provide this critical service as well as ensure participation of the country in international studies on maternal vaccine safety.

Recent Advances and Future Prospects for Memristive Materials, Devices, and Systems.

Memristive technology has been rapidly emerging as a potential alternative to traditional CMOS technology, which is facing fundamental limitations in its development. Since oxide-based resistive switches were demonstrated as memristors in 2008, memristive devices have garnered significant attention due to their biomimetic memory properties, which promise to significantly improve power consumption in computing applications. Here, we provide a comprehensive overview of recent advances in memristive technology, including memristive devices, theory, algorithms, architectures, and systems. In addition, we discuss research directions for various applications of memristive technology including hardware accelerators for artificial intelligence, in-sensor computing, and probabilistic computing. Finally, we provide a forward-looking perspective on the future of memristive technology, outlining the challenges and opportunities for further research and innovation in this field. By providing an up-to-date overview of the state-of-the-art in memristive technology, this review aims to inform and inspire further research in this field.

Challenging level of rigid-body approach involving numerical elements (CHLORAINE) applied to repeated elastin peptides.

Elastic proteins and derived biomaterials contain numerous tandemly repeated peptides along their sequences, ranging from a few copies to hundreds. These repetitions are responsible for their biochemical, biological and biomechanical properties. These sequences are considered to be intrinsically disordered, and the variations in their behavior are actually mainly due to their high flexibility and lack of stable secondary structures originating from their unique amino acid sequences. Consequently, the simulation of elastic proteins and large elastomeric biomaterials using classical molecular dynamics is an important challenge. Here, we propose a novel approach that allows the application of the DURABIN protocol to repeated elastin-like peptides (r-ELPs) in a simple way. Four large r-ELPs were studied to evaluate our method, which was developed for simulating extracellular matrix proteins at the mesoscopic scale. After structure clustering applied on molecular dynamic trajectories of constitutive peptides (5-mers and 6-mers), the main conformations were used as starting points to define the corresponding primitives, further used as rigid body fragments in our program. Contributions derived from electrostatic and molecular hydrophobicity potentials were tested to evaluate their influence on the interactions during simple mesoscopic simulations. The CHLORAINE approach, despite the thinner granularity due to the size of the patterns used, was included in the DURABIN protocol and emerges as a promising way to simulate elastic macromolecular systems.

Probing the Melting Transitions in Phase-Change Superlattices via Thin Film Nanocalorimetry.

Phase-change superlattices with nanometer thin sublayers are promising for low-power phase-change memory (PCM) on rigid and flexible platforms. However, the thermodynamics of the phase transition in such nanoscale superlattices remain unexplored, especially at ultrafast scanning rates, which is crucial for our fundamental understanding of superlattice-based PCM. Here, we probe the phase transition of Sb2Te3 (ST)/Ge2Sb2Te5 (GST) superlattices using nanocalorimetry with a monolayer sensitivity (∼1 Å) and a fast scanning rate (105 K/s). For a 2/1.8 nm/nm Sb2Te3/GST superlattice, we observe an endothermic melting transition with an ∼240 °C decrease in temperature and an ∼8-fold decrease in enthalpy compared to those for the melting of GST, providing key thermodynamic insights into the low-power switching of superlattice-based PCM. Nanocalorimetry measurements for Sb2Te3 alone demonstrate an intrinsic premelting similar to the unique phase transition of superlattices, thus revealing a critical role of the Sb2Te3 sublayer within our superlattices. These results advance our understanding of superlattices for energy-efficient data storage and computing.

CaptiveSpray Differential Ion Mobility Spectrometry Device with Enhanced Ion Transmission and Improved Resolving Power.

A performance enhanced CaptiveSpray differential ion mobility device was designed and constructed by incorporating a circular channel and a gas flow homogenizing channel (GFHC) between the CaptiveSpray ion source and planar differential ion mobility spectrometry (DMS). The GFHC was used to reduce gas flow heterogeneity prior to the entrance of the DMS device. The optimal flared entrance greatly reduces gas flow velocity at the inlet region owing to its relatively large gas inlet interface, which assists in reducing disparities between the minimum and maximum gas velocity along the x-axis. The circular electrode was machined with channels along the x- and y-axis for the passage of auxiliary gas and was applied with a potential to focus the incoming ions from the CaptiveSpray source into the DMS channel. Using reserpine as a reference standard, substantial signal enhancement was achieved with a concomitant reduction of the peak width in the ionogram.

Process development of a SARS-CoV-2 nanoparticle vaccine.

One of the outcomes from the global COVID-19 pandemic caused by SARS-CoV-2 has been an acceleration of development timelines to provide treatments in a timely manner. For example, it has recently been demonstrated that the development of monoclonal antibody therapeutics from vector construction to IND submission can be achieved in five to six months rather than the traditional ten-to-twelve-month timeline using CHO cells [1], [2]. This timeline is predicated on leveraging existing, robust platforms for upstream and downstream processes, analytical methods, and formulation. These platforms also reduce; the requirement for ancillary studies such as cell line stability, or long-term product stability studies. Timeline duration was further reduced by employing a transient cell line for early material supply and using a stable cell pool to manufacture toxicology study materials. The development of non-antibody biologics utilizing traditional biomanufacturing processes in CHO cells within a similar timeline presents additional challenges, such as the lack of platform processes and additional analytical assay development. In this manuscript, we describe the rapid development of a robust and reproducible process for a two-component self-assembling protein nanoparticle vaccine for SARS-CoV-2. Our work has demonstrated a successful academia-industry partnership model that responded to the COVID-19 global pandemic quickly and efficiently and could improve our preparedness for future pandemic threats.

Clinical Outcomes of Conservative Treatment for Low-Risk Ductal Carcinoma in Situ: A Systematic Review and Pooled Analysis.

AIMS: The current gold standard of treatment for ductal carcinoma in situ (DCIS) is surgical resection with or without adjuvant radiotherapy. However, the increased detection and radical treatment of DCIS did not result in a declined incidence of invasive breast cancers, leading to the debate if DCIS has been overtreated. While ongoing randomised controlled trials on active surveillance of DCIS are still in progress, this systematic review aims to evaluate the best evidence on conservative treatment for DCIS from the literature. MATERIALS AND METHODS: This systematic review was conducted in line with the PRISMA statement. We included all relevant studies published up to June 2022 for analysis. The primary outcomes were overall survival and breast cancer-specific survival (BCSS) of conservative treatment for DCIS. RESULTS: Three studies, with a total of 34 007 women with low-risk DCIS, were included in the analysis. Active and conservative treatments both resulted in excellent 10-year BCSS, with no statistically insignificant difference (98.6% versus 96.0%, 31 478 women). One study comparing 5-year BCSS of active and conservative treatments only in subjects aged over 80 years also reported [AQ1]an insignificant difference (98.2% versus 96.0%, 2529 women). One study measuring 5- and 10-year overall survival between the treatment groups also reported [AQ1]an insignificant difference (5-year: 96.2% versus 92.4%; 10-year: 85.6% versus 86.7%, 31 106 women). CONCLUSION: BCSS between active and conservative treatment for women with low-risk DCIS is both excellent and comparable, suggesting that conservative treatment is a possible alternative without compromising survival.

Investigation of a failed DNA assay leads to identification of an unexpected contaminant in a commonly used chromatography buffer.

For mammalian cell-derived recombinant biotherapeutics, controlling host cell DNA levels below a threshold is a regulatory requirement to ensure patient safety. DNA removal during drug substance manufacture is accomplished by a series of chromatography-based purification steps and a qPCR-based analytical method is most used to measure DNA content in the purified drug substance to enable material disposition. While the qPCR approach is mature and its application to DNA measurement is widespread in the industry, it is susceptible to trace levels of process-related contaminants that are carried forward. In this study, we observed failures in spike recovery studies that are an integral component of the qPCR-based DNA testing, suggesting the presence of an inhibitory compound in the sample matrix. We generated hypotheses around the origin of the inhibitory compound and generated multiple sample matrices and deployed a suite of analytical techniques including Raman and NMR spectroscopy to determine the origin and identity of the inhibitory compound. The caustic wash step and depth filter extractables were ruled out as root causes after extensive experimentation and DNA testing. Subsequently, 2-(N-morpholino)ethanesulfonic acid (MES), a buffer used in the chromatography unit operations, was identified as the source of the contaminant. A 500-fold concentration followed by Raman and NMR spectroscopy analysis revealed the identity of the inhibitory compound as polyvinyl sulfone (PVS), an impurity that originates in the MES manufacturing process. We have implemented PVS concentration controls for incoming MES raw material, and our work highlights the need for rigor in raw material qualification and control.

Use of group IIB metal ions as charge carriers for collision-induced dissociation of glycopeptide and glycan.

RATIONALE: Dissociation of biomolecules by tandem mass spectrometry (MS/MS) generates a variety of fragment ions which provide useful information for the structural characterization of biomolecules. Different fragmentation strategies result in different mass spectra for the same molecule and thus provide distinct features. Charge carriers play important roles in determining the dissociation pathways of the target precursor ions. The use of various transition metals ions as charge carriers of glycopeptide and glycan might provide additional structural information and needs to be investigated. METHODS: A 9.4 T SolariX FTICR mass spectrometer was used for collision-induced dissociation (CID) of glycopeptide and glycan. Group IIB metal ions, including Zn2+ , Cd2+ and Hg2+ , were used as charge carriers. Glycopeptide NLTK-M5 G2 and glycan G1F were used as the model systems. RESULTS: For Zn2+ - and Cd2+ -adducted species, cross-ring cleavages, glycosidic cleavages and cleavages along the peptide backbone could be obtained. There is a high degree of similarity in their CID spectra with that of Mg2+ ion-adducted glycopeptide species. For Hg2+ -adducted species, only glycosidic cleavages were observed in high abundance. The formation of doubly-charged ions (M2+ ) and a series of [f-H]+ fragments indicated unique dissociation pathways for Hg2+ -adducted glycopeptide. CONCLUSIONS: Zn2+ and Cd2+ -adducted glycopeptide species produced similar dissociation CID spectra, whereas Hg2+ -adducted species produced significantly different CID spectra. Similar CID dissociation features were also observed for Group IIB metal ions adducted glycan species. These results demonstrated that different metal ions might be used to tune the dissociation behaviors of glycopeptides and glycans.

Nanocrystallite Seeding of Metastable Ferroelectric Phase Formation in Atomic Layer-Deposited Hafnia-Zirconia Alloys.

Hafnia-based ferroelectric thin films are promising for semiconductor memory and neuromorphic computing applications. Amorphous, as-deposited, thin-film binary alloys of HfO2 and ZrO2 transform to the metastable, orthorhombic ferroelectric phase during post-deposition annealing and cooling. This transformation is generally thought to involve formation of a tetragonal precursor phase that distorts into the orthorhombic phase during cooling. In this work, we systematically study the effects of atomic layer deposition (ALD) temperature on the ferroelectricity of post-deposition-annealed Hf0.5Zr0.5O2 (HZO) thin films. Seed crystallites having interplanar spacings consistent with the polar orthorhombic phase are observed by a plan-view transmission electron microscope in HZO thin films deposited at an elevated ALD temperature. After ALD under conditions that promote formation of these nanocrystallites, high-polarization (Pr > 18 µC/cm2) ferroelectric switching is observed after rapid thermal annealing (RTA) at low temperature (350 °C). These results indicate the presence of minimal non-ferroelectric phases retained in the films after RTA when the ALD process forms nanocrystalline particles that seed subsequent formation of the polar orthorhombic phase.

Carbon nanotube transistors: Making electronics from molecules.

Semiconducting carbon nanotubes are robust molecules with nanometer-scale diameters that can be used in field-effect transistors, from larger thin-film implementation to devices that work in conjunction with silicon electronics, and can potentially be used as a platform for high-performance digital electronics as well as radio-frequency and sensing applications. Recent progress in the materials, devices, and technologies related to carbon nanotube transistors is briefly reviewed. Emphasis is placed on the most broadly impactful advancements that have evolved from single-nanotube devices to implementations with aligned nanotubes and even nanotube thin films. There are obstacles that remain to be addressed, including material synthesis and processing control, device structure design and transport considerations, and further integration demonstrations with improved reproducibility and reliability; however, the integration of more than 10,000 devices in single functional chips has already been realized.

Characterization of a 1D-imaging high-energy x-ray backlighter driven by the National Ignition Facility Advanced Radiographic Capability laser.

Plastic deformation of samples compressed to Mbar pressures at high strain rates at the National Ignition Facility (NIF) forms the basis of ongoing material strength experiments in conditions relevant to meteor impacts, geophysics, armor development, and inertial confinement fusion. Hard x-ray radiography is the primary means of measuring the evolution of these samples, typically employing a slit-collimated high-Z microdot driven by the NIF laser to generate >40 keV x rays [E. Gumbrell et al., Rev. Sci. Instrum. 89, 10G118 (2018) and C. M. Huntington et al., Rev. Sci. Instrum. 89, 10G121 (2018)]. Alternatively, a dysprosium "micro-flag" target driven by the Advanced Radiographic Capability laser (∼2 kJ, 10 ps) can deliver significantly higher spatiotemporal resolution [M. P. Hill et al., Rev. Sci. Instrum. 92, 033535 (2021)], especially in high-opacity samples. Initial experiments revealed problematic brightness and spectral gradients from this source, but by radiographing a set of diamond-turned, 105 µm-thick Pb test objects and supported by simulations using the 3D Monte Carlo code GEANT4, these geometry-dependent gradients across the field of view are quantified and mitigation strategies are assessed. In addition to significantly enhancing the modulation transfer function compared to the existing system, image stacking from multiple layers of image plate is shown to almost double the signal to noise ratio that will reduce uncertainties in future dynamic strength experiments.

Statistical Assessment of High-Performance Scaled Double-Gate Transistors from Monolayer WS2.

Scaling of monolayer transition metal dichalcogenide (TMD) field-effect transistors (FETs) is an important step toward evaluating the application space of TMD materials. Although some work on ultrashort channel monolayer (ML) TMD FETs has been published, there exist no comprehensive studies that assess their performance in a statistically relevant manner, providing critical insights into the impact of the device geometry. Part of the reason for the absence of such a study is the substantial variability of TMD devices when processes are not carefully controlled. In this work, we show a statistical study of ultrashort channel double-gated ML WS2 FETs exhibiting excellent device performance and limited device-to-device variations. From a detailed analysis of cross-sectional scanning transmission electron microscopy (STEM) images and careful technology computer aided design (TCAD) simulations, we evaluated, in particular, an unexpected deterioration of the subthreshold characteristics for our shortest devices. Two potential candidates for the observed behavior were identified, i.e., buckling of the TMD on the substrate and loss of gate control due to the source geometry and the high-k dielectric between the metal gate and the metal source electrode.