Biorealistic Neuronal Temperature-Sensitive Dynamics within Threshold Switching Memristors: Toward Neuromorphic Thermosensation.

Neuromorphic nanoelectronic devices that can emulate the temperature-sensitive dynamics of biological neurons are of great interest for bioinspired robotics and advanced applications such as in silico neuroscience. In this work, we demonstrate the biomimetic thermosensitive properties of two-terminal V3O5 memristive devices and showcase their similarity to the firing characteristics of thermosensitive biological neurons. The temperature-dependent electrical characteristics of V3O5-based memristors are used to understand the spiking response of a simple relaxation oscillator. The temperature-dependent dynamics of these oscillators are then compared with those of biological neurons through numerical simulations of a conductance-based neuron model, the Morris-Lecar neuron model. Finally, we demonstrate a robust neuromorphic thermosensation system inspired by biological thermoreceptors for bioinspired thermal perception and representation. These results not only demonstrate the biorealistic emulative potential of threshold-switching memristors but also establish V3O5 as a functional material for realizing solid-state neurons for neuromorphic computing and sensing applications.

Physical Origin of Negative Differential Resistance in V3 O5 and Its Application as a Solid-State Oscillator.

Oxides that exhibit an insulator-metal transition can be used to fabricate energy-efficient relaxation oscillators for use in hardware-based neural networks but there are very few oxides with transition temperatures above room temperature. Here the structural, electrical, and thermal properties of V3 O5 thin films and their application as the functional oxide in metal/oxide/metal relaxation oscillators are reported. The V3 O5 devices show electroforming-free volatile threshold switching and negative differential resistance (NDR) with stable (<3% variation) cycle-to-cycle operation. The physical mechanisms underpinning these characteristics are investigated using a combination of electrical measurements, in situ thermal imaging, and device modeling. This shows that conduction is confined to a narrow filamentary path due to self-confinement of the current distribution and that the NDR response is initiated at temperatures well below the insulator-metal transition temperature where it is dominated by the temperature-dependent conductivity of the insulating phase. Finally, the dynamics of individual and coupled V3 O5 -based relaxation oscillators is reported, showing that capacitively coupled devices exhibit rich non-linear dynamics, including frequency and phase synchronization. These results establish V3 O5 as a new functional material for volatile threshold switching and advance the development of robust solid-state neurons for neuromorphic computing.

Engineering the Threshold Switching Response of Nb2O5-Based Memristors by Ti Doping.

Two terminal metal-oxide-metal devices based on niobium oxide thin films exhibit a wide range of non-linear electrical characteristics that have applications in hardware-based neuromorphic computing. In this study, we compare the threshold-switching and current-controlled negative differential resistance (NDR) characteristics of cross-point devices fabricated from undoped Nb2O5 and Ti-doped Nb2O5 and show that doping offers an effective means of engineering the device response for particular applications. In particular, doping is shown to improve the device reliability and to provide a means of tuning the threshold and hold voltages, the hysteresis window, and the magnitude of the negative differential resistance. Based on temperature-dependent current-voltage characteristics and lumped-element modelling, these effects are attributed to doping-induced reductions in the device resistance and its rate of change with temperature (i.e., the effective thermal activation energy for conduction). Significantly, these studies also show that a critical activation energy is required for devices to exhibit NDR, with doping providing an effective means of engineering the current-voltage characteristics. These results afford an improved understanding of the physical mechanisms responsible for threshold switching and provide new insights for designing devices for specific applications.

COVID Moonshot: Open Science Discovery of SARS-CoV-2 Main Protease Inhibitors by Combining Crowdsourcing, High-Throughput Experiments, Computational Simulations, and Machine Learning

The COVID-19 pandemic is a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Future pandemics could be prevented by accessible, easily deployable broad-spectrum oral antivirals and open knowledge bases that derisk and accelerate novel antiviral discovery and development. Here, we report the results of the COVID Moonshot, a fully open-science structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical scaffold that is differentiated from current clinical candidates in terms of toxicity, resistance, and pharmacokinetics liabilities, and developed it into noncovalent orally-bioavailable nanomolar inhibitors with clinical potential. Our approach leveraged crowdsourcing, high-throughput structural biology, machine learning, and exascale molecular simulations. In the process, we generated a detailed map of the structural plasticity of the main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (>18,000 designs), crystallographic data (>500 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.

Metal-oxide interface reactions and their effect on integrated resistive/threshold switching in NbO x.

Reactive metal electrodes (Nb, Ti, Cr, Ta, and Hf) are shown to play an important role in controlling the volatile switching characteristics of metal/Nb2O5/Pt devices. In particular, devices are shown to exhibit stable threshold switching under negative bias but to have a response under positive bias that depends on the choice of metal. Three distinct responses are highlighted: Devices with Nb and Ti top electrodes are shown to exhibit stable threshold switching with symmetric characteristics for both positive and negative polarities; devices with Cr top electrodes are shown to exhibit stable threshold switching but with asymmetric hysteresis windows under positive and negative polarities; and devices with Ta and Hf electrodes are shown to exhibit an integrated threshold-memory (1S1M) response. Based on thermodynamic data and lumped element modelling these effects are attributed to the formation of a metal-oxide interlayer and its response to field-induced oxygen exchange. These results provide important insight into the physical origin of the switching response and pathways for engineering devices with reliable switching characteristics.

Assessment of laboratories offering cell-free (cf) DNA screening for Down syndrome: results of the 2018 College of American Pathology External Educational Exercises.

PURPOSE: Summarize and interpret results from exercises distributed to laboratories offering cell-free (cf) DNA screening for Down syndrome. METHODS: The College of American Pathologists distributed three patient-derived plasma specimens twice in 2018. Sequencing platforms, test methods, results, and responses to supplemental questions were collected. Results were not graded but discrepancies were identified. RESULTS: Sixty-five laboratories from six continents enrolled; six provided no results. The most common methodology was shotgun/genome sequencing (39/56, 70%). Overall, 40% of the gestational or maternal age responses were incorrect but 45% of the errors were corrected by the next distribution. Fetal fractions from 54 responding laboratories generally agreed with the intended response. No genotyping errors occurred (40/40 for trisomy 21 and 226/226 for euploid challenges) but 10 additional tests failed (3.6%). All 213 fetal sex calls were correct. Participants reported their clinical text for a Down syndrome screen positive test; 39% were classified as inadequate or misleading. CONCLUSION: Patient-derived materials are suitable for all enrolled technologies/methodologies, but collecting material is challenging. Suggested clinical text includes the terms "screen positive" and "screen negative." Overall, laboratories performed well. Future efforts will focus on potential manufactured samples, clarifying results reporting and including additional chromosome abnormalities.

Nanoscale modification of one-dimensional single-crystalline cuprous oxide.

In this work we report for the first time a method to modify the surface of Cu2O nanowires in a controllable way and physically weld them into a network form, which contributes to higher electrical conductivity as well as a strong water-repelling nature. We have used state-of-the-art theoretical calculations to support our experimental observations. We demonstrate how varying the irradiation fluence can modulate the surface and decorate the nanowire with a uniform distribution of Cu8O nanocrystals due to preferential sputtering. While several well studied joining techniques are available for carbon and metal-based nanowires, the same information for ceramic nanowires is scarce at present. The current study sheds light into this and a state-of-the-art 3D simulation technique predicts most of the modifications including surface modulation, oxygen depletion and welding. The welded network shows higher electrical conductivity than the unwelded assembly. With Cu2O being of p-type the current ion beam joining technique shows a novel path for fabricating p-i-n junctions or solar cell devices through bottom-up approach. Furthermore, we have explored the response of this network to moisture. Our calculation based on density functional theory predicts the hydrophilic nature of individual copper oxide nanowires both before and after irradiation. However, the network shows a strong water-repelling nature, which has been explained quantitatively using the Cassie-Baxter model.

Room temperature synthesis of HfO2/HfO x heterostructures by ion-implantation.

Implantation of Hf films with oxygen ions is shown to be an effective means of fabricating high-quality HfO2/HfO x heterostructures at room temperature, with the layer composition and thicknesses determined by the ion energy and fluence. Implantation with 3 keV O+ ions to a fluence of 1 × 1017 ions cm-2 produces a polycrystalline (monoclinic-) HfO2 layer extending from the surface to a depth of ∼12 nm, and an underlying graded HfO x layer extending an additional ∼7 nm, while implantation with 6 keV O to a similar fluence produces a near-stoichiometric surface layer of 7 nm thickness and a graded substoichiometric layer extending to depth of ∼30 nm. These structures are shown to be broadly consistent with oxygen range data but more detailed comparison with dynamic Monte Carlo simulations suggests that the near-surface region contains more oxygen than expected from collisional processes alone. The bandgap and dielectric strength of the HfO2 layer produced by 3 keV; 1 × 1017 ions cm-2 implant is shown to be indistinguishable from those of an amorphous film deposited by atomic layer deposition at 200 °C. The utility of these layers is demonstrated by studying the resistive switching properties of metal-oxide-metal test structures fabricated by depositing a top metal contact on the implanted film. These results demonstrate the suitability of ion-implantation for the synthesis of functional oxide layers at room temperature.

Anatomy of filamentary threshold switching in amorphous niobium oxide.

The threshold switching behavior of Pt/NbO x /TiN devices is investigated as a function device area and NbO x film thickness and shown to reveal important insight into the structure of the self-assembled switching region. The devices exhibit combined selector-memory (1S1R) behavior after an initial voltage-controlled forming process, but exhibit symmetric threshold switching when the RESET and SET currents are kept below a critical value. In this mode, the threshold and hold voltages are independent of the device area and film thickness but the threshold current (power), while independent of device area, decreases with increasing film thickness. These results are shown to be consistent with a structure in which the threshold switching volume is confined, both laterally and vertically, to the region between the residual memory filament and the TiN electrode, and where the memory filament has a core-shell structure comprising a metallic core and a semiconducting shell. The veracity of this structure is demonstrated by comparing experimental results with the predictions of a simple circuit model, and more detailed finite element simulations. These results provide further insight into the structure and operation of NbO x threshold switching devices that have application in emerging memory and neuromorphic computing fields.

Coupling dynamics of Nb/Nb2O5 relaxation oscillators.

The coupling dynamics of capacitively coupled Nb/Nb2O5 relaxation oscillators are shown to exhibit rich collective behaviour depending on the negative differential resistance response of the individual devices, the operating voltage and the coupling capacitance. These coupled oscillators are shown to exhibit stable frequency and phase locking states at source voltages as low as 2.2 V, with frequency control in the range from 0.85 to 16.2 MHz and frequency tunability of ∼8 MHz V-1. The experimental realisation of such compact, scalable and low power coupled-oscillator systems is of particular significance for the development and implementation of large oscillator networks in non-Boolean computing architectures.

Radiosensitivity of cancer-initiating cells and normal stem cells (or what the Heisenberg uncertainly principle has to do with biology).

Mounting evidence suggests that parallels between normal stem cell biology and cancer biology may provide new targets for cancer therapy. Prospective identification and isolation of cancer-initiating cells from solid tumors has promoted the descriptive and functional identification of these cells allowing for characterization of their response to contemporary cancer therapies, including chemotherapy and radiation. In clinical radiation therapy, the failure to clinically eradicate all tumor cells (eg, a lack of response, partial response, or nonpermanent complete response by imaging) is considered a treatment failure. As such, biologists have explored the characteristics of the small population of clonogenic cancer cells that can survive and are capable of repopulating the tumor after subcurative therapy. Herein, we discuss the convergence of these clonogenic studies with contemporary radiosensitivity studies that use cell surface markers to identify cancer-initiating cells. Implications for and uncertainties regarding incorporation of these concepts into the practice of modern radiation oncology are discussed.

Prevention of recurrent ischemic stroke.

Recurrent ischemic stroke and transient ischemic attack are common problems in primary care, with stroke survivors averaging 10 outpatient visits per year. Risk factors such as hypertension, diabetes, and hypercholesterolemia should be evaluated during each office visit. Attention should be given to lifestyle modification including management of obesity, smoking cessation, reduction in alcohol consumption, and promotion of physical activity. The choice of an antiplatelet agent (e.g., aspirin, ticlopidine, clopidogrel, dipyridamole) or the anticoagulant warfarin is based on the safety, tolerability, effectiveness, and price of each agent. Aspirin is a common first choice for prevention of recurrent stroke, but the combination of dipyridamole and aspirin should be considered for many patients because of its superior effectiveness in two clinical trials. Clopidogrel is recommended for patients with aspirin intolerance or allergy, or for those who cannot tolerate dipyridamole. Warfarin and the combination of aspirin and clopidogrel should not be used in the prevention of ischemic stroke. Carotid endarterectomy is appropriate for select patients; carotid stenting was recently shown to be less effective and less safe than endarterectomy.