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The oxygen diffusion rate in hafnia (HfO 2 )-based resistive memory plays a pivotal role in enabling nonvolatile data retention. However, the information retention times obtained in HfO 2 resistive memory devices are many times higher than the expected values obtained from oxygen diffusion measurements in HfO 2 materials. In this study, we resolve this discrepancy by conducting oxygen isotope tracer diffusion measurements in amorphous hafnia (a-HfO 2 ) thin films. Our results show that the oxygen tracer diffusion in amorphous HfO 2 films is orders of magnitude lower than that of previous measurements on monoclinic hafnia (m-HfO 2 ) pellets. Moreover, oxygen tracer diffusion is much lower in denser a-HfO 2 films deposited by atomic layer deposition (ALD) than in less dense a-HfO 2 films deposited by sputtering. The ALD films yield similar oxygen diffusion times as experimentally measured device retention times, reconciling this discrepancy between oxygen diffusion and retention time measurements. More broadly, our work shows how processing conditions can be used to control oxygen transport characteristics in amorphous materials without long-range crystal order.

Photonic technologies promise to deliver quantitative, multiplex, and inexpensive medical diagnostic platforms by leveraging the highly scalable processes developed for the fabrication of semiconductor microchips. However, in practice, the affordability of these platforms is limited by complex and expensive sample handling and optical alignment. We previously reported the development of a disposable photonic assay that incorporates inexpensive plastic micropillar microfluidic cards for sample delivery. That system as developed was limited to singleplex assays due to its optical configuration. To enable multiplexing, we report a new approach addressing multiplex light I/O, in which the outputs of individual grating couplers on a photonic chip are mapped to fibers in a fiber bundle. As demonstrated in the context of detecting antibody responses to influenza and SARS-CoV-2 antigens in human serum and saliva, this enables multiplexing in an inexpensive, disposable, and compact format.

Background: Alterations in the naturally occurring bacteria of the gut, known as the gastrointestinal (GI) microbiome, may influence GI symptoms in women with breast cancer., Objective: This work aims to describe GI symptom occurrence, duration, severity, and distress and measures of the GI microbiome among women with breast cancer receiving chemotherapy compared to age- and sex-matched healthy controls., Interventions/methods: 22 women with breast cancer receiving chemotherapy and 17 healthy control women provided stool specimens and GI symptom data using the modified Memorial Symptom Assessment Scale (MSAS). The fecal microbiome was profiled by metagenomic sequencing of 16S Ribosomal RNA (rRNA). GI microbiome was compared between groups using alpha-diversity (Observed OTU number and Shannon index), beta-diversity (UniFrac distances), and relative abundance of select genera., Results: GI symptoms with high symptom reports among breast cancer patients included nausea, diarrhea, flatulence, dry mouth, taste change, and poor appetite. Indices of differential abundance (beta diversity) significantly distinguished between breast cancer patients and healthy controls. Unique bacterial features differentiating the 2 groups were Prevotella_9 , Akkermansia , Lachnospira , Lachnospiraceae_NK4A136 , Lachnoclostridium , and Oscillibacter ., Conclusions: Gut bacteria are associated with GI inflammation and mucus degradation, suggesting the potential role of the GI microbiome in GI symptom burden. Understanding the influence of GI bacteria on gut health and symptoms will help harness the enormous potential of the GI microbiome as a future diagnostic and therapeutic agent to reduce the symptom burden associated with chemotherapy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this articleAKM is one of the inventors of a technology claiming the use of Prevotella histicola to treat autoimmune diseases. AKM received royalties from Mayo Clinic (paid by Evelo Biosciences). However, no funds or products from the patent were used in the present study.

Memristors, non-volatile switching memory platform, has recently attracted significant interest, offering unique potential to enable the realization of human brain-like neuromorphic computing efficiency. Memristors also demonstrate excellent temperature tolerance, long-term durability, and high tunability with nanosecond pulses, making them highly attractive for neuromorphic computing applications. To better understand the material processing, microstructure, and property relationship of switching mechanisms in memristor devices, computational methodologies, and tools are developed to predict the I-V characteristics of memristor devices based on tantalum oxide (TaO x ) resistive random-access memory (ReRAM) integrated with an n-channel metal-oxide-semiconductor (NMOS) transistor. A multiphysics model based on coupled partial differential equations for electrical and thermal transport phenomena is solved for the high- and low-resistance states during the formation, growth, and destruction of a conducting filament through SET and RESET stages. These stages effectively represent the migration of oxygen vacancies within an oxide exchange layer. A series of parametric studies and energy minimization calculations are conducted to determine probable ranges for key material and model parameters accounting for the experimental data. The computational model successfully predicted the measured I-V curves across various gate voltages applied to the NMOS transistor in the one transistor one resistance (1T1R) configuration., (© 2024 Wiley VCH GmbH. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Analog hardware-based training provides a promising solution to developing state-of-the-art power-hungry artificial intelligence models. Non-volatile memory hardware such as resistive random access memory (RRAM) has the potential to provide a low power alternative. The training accuracy of analog hardware depends on RRAM switching properties including the number of discrete conductance states and conductance variability. Furthermore, the overall power consumption of the system inversely correlates with the RRAM devices conductance. To study material dependence of these properties, TaOx and HfOx RRAM devices in one-transistor one-RRAM configuration (1T1R) were fabricated using a custom 65 nm CMOS fabrication process. Analog switching performance was studied with a range of initial forming compliance current (200-500 µA) and analog switching tests with ultra-short pulse width (300 ps) was carried out. We report that by utilizing low current during electroforming and high compliance current during analog switching, a large number of RRAM conductance states can be achieved while maintaining low conductance state. While both TaOx and HfOx could be switched to more than 20 distinct states, TaOx devices exhibited 10× lower conductance, which reduces total power consumption for array-level operations. Furthermore, we adopted an analog, fully in-memory training algorithm for system-level training accuracy benchmarking and showed that implementing TaOx 1T1R cells could yield an accuracy of up to 96.4% compared to 97% for the floating-point arithmetic baseline, while implementing HfOx devices would yield a maximum accuracy of 90.5%. Our experimental work and benchmarking approach paves the path for future materials engineering in analog-AI hardware for a low-power environment training., (© 2023. Springer Nature Limited.)

The widespread use of glyphosate, a broad-spectrum herbicide, has resulted in significant human exposure, and recent studies have challenged the notion that glyphosate is safe for humans. Although the link between disease states and glyphosate exposure is increasingly appreciated, the mechanistic links between glyphosate and its toxic effects on human health are poorly understood. Recent studies have suggested that glyphosate may cause toxicity through modulation of the gut microbiome, but evidence for glyphosate-induced gut dysbiosis and its effect on host physiology at doses approximating the U.S. Acceptable Daily Intake (ADI = 1.75 mg/kg body weight) is limited. Here, utilizing shotgun metagenomic sequencing of fecal samples from C57BL/6 J mice, we show that glyphosate exposure at doses approximating the U.S. ADI significantly impacts gut microbiota composition. These gut microbial alterations were associated with effects on gut homeostasis characterized by increased proinflammatory CD4 + IL17A + T cells and Lipocalin-2, a known marker of intestinal inflammation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ashutosh Mangalam reports financial support was provided by National Institute of Allergy and Infectious Diseases. Ashutosh Mangalam reports financial support was provided by US Department of Veterans Affairs. Ashutosh Mangalam reports financial support was provided by National Institute of Environmental Health Sciences. Ashutosh Mangalam has patent Prevotella histicola for the treatment of autoimmune diseases with royalties paid to Mayo Clinic Ventures/Evelo Bioscience. Disclosure statement AKM is inventor of a technology claiming the use of Prevotella histicola for the treatment of autoimmune diseases. The patent for the technology is owned by Mayo Clinic, who has given exclusive license to Evelo Biosciences. AKM received royalties from Mayo Clinic (paid by Evelo Biosciences). However, no fund or product from the patent were used in the present study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Published by Elsevier B.V.)

As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Rapid and accurate detection of fentanyl (highly potent opioid) is a critical importance due to current opioids crisis worldwide. We report the highly sensitive detection of fentanyl utilizing the synergetic effect of nanoporous silicon as a substrate with a high interfacial area and specific antibody functionalization of nanoporous silicon. The electrochemical sensor consists of gold working and counter electrodes deposited on nanoprous silicon, antibodies immobilized between these electrodes and an Ag/AgCl reference electrode. Square wave voltammetry was used as an electrochemical transduction method. The detection limit was determined as 6 ng/ml and 11.5 ng/ml for specific peak (fentanyl signature) in phosphate buffer and human sweat, respectively. A future goal of this study is to a wearable sweat sensor array for rapid and on-site detection of multiple opioids with analytical sensitivity comparable with laboratory tests.

Introduction: Phytoestrogens found in soy, fruits, peanuts, and other legumes, have been identified as metabolites capable of providing beneficial effects in multiple pathological conditions due to their ability to mimic endogenous estrogen. Interestingly, the health-promoting effects of some phytoestrogens, such as isoflavones, are dependent on the presence of specific gut bacteria. Specifically, gut bacteria can metabolize isoflavones into equol, which has a higher affinity for endogenous estrogen receptors compared to dietary isoflavones. We have previously shown that patients with multiple sclerosis (MS), a neuroinflammatory disease, lack gut bacteria that are able to metabolize phytoestrogen. Further, we have validated the importance of both isoflavones and phytoestrogen-metabolizing gut bacteria in disease protection utilizing an animal model of MS. Specifically, we have shown that an isoflavone-rich diet can protect from neuroinflammatory diseases, and that protection was dependent on the ability of gut bacteria to metabolize isoflavones into equol. Additionally, mice on a diet with isoflavones showed an anti-inflammatory response compared to the mice on a diet lacking isoflavones. However, it is unknown how isoflavones and/or equol mediates their protective effects, especially their effects on host metabolite levels., Objectives: In this study, we utilized untargeted metabolomics to identify metabolites found in plasma that were modulated by the presence of dietary isoflavones., Results: We found that the consumption of isoflavones increased anti-inflammatory monounsaturated fatty acids and beneficial polyunsaturated fatty acids while reducing pro-inflammatory glycerophospholipids, sphingolipids, phenylalanine metabolism, and arachidonic acid derivatives., Conclusion: Isoflavone consumption alters the systemic metabolic landscape through concurrent increases in monounsaturated fatty acids and beneficial polyunsaturated fatty acids plus reduction in pro-inflammatory metabolites and pathways. This highlights a potential mechanism by which an isoflavone diet may modulate immune-mediated disease., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The toxicity of many "inert" ingredients of pesticide formulations, such as safeners, is poorly characterized, despite evidence that humans may be exposed to these chemicals. Analysis of ToxCast data for dichloroacetamide safeners with the ToxPi tool identified benoxacor as the safener with the highest potential for toxicity, especially liver toxicity. Benoxacor was subsequently administered to mice via oral gavage for 3 days at concentrations of 0, 0.5, 5, and 50 mg/kg bodyweight (b.w.). Bodyweight-adjusted liver and testes weights were significantly increased in the 50 mg/kg b.w. group. There were no overt pathologies in either the liver or the intestine. 16S rRNA analysis of the cecal microbiome revealed no effects of benoxacor on α- or β-diversity; however, changes were observed in the abundance of certain bacteria. RNAseq analysis identified 163 hepatic genes affected by benoxacor exposure. Benoxacor exposure expressed a gene regulation profile similar to dichloroacetic acid and the fungicide sedaxane. Metabolomic analysis identified 9 serum and 15 liver metabolites that were affected by benoxacor exposure, changes that were not significant after correcting for multiple comparisons. The activity of antioxidant enzymes was not altered by benoxacor exposure. In vitro metabolism studies with liver microsomes and cytosol from male mice demonstrated that benoxacor is enantioselectively metabolized by cytochrome P450 enzymes, carboxylesterases, and glutathione S-transferases. These findings suggest that the minor toxic effects of benoxacor may be due to its rapid metabolism to toxic metabolites, such as dichloroacetic acid. This result challenges the assumption that inert ingredients of pesticide formulations are safe., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The human body has a large, diverse community of microorganisms which not only coexist with us, but also perform many important physiological functions, including metabolism of dietary compounds that we are unable to process ourselves. Furthermore, these bacterial derived/induced metabolites have the potential to interact and influence not only the local gut environment, but the periphery via interaction with and modulation of cells of the immune and nervous system. This relationship is being further appreciated every day as the gut microbiome is researched as a potential target for immunomodulation. A common feature among inflammatory diseases including relapsing-remitting multiple sclerosis (RRMS) is the presence of gut microbiota dysbiosis when compared to healthy controls. However, the specifics of these microbiota-neuro-immune system interactions remain unclear. Among all factors, diet has emerged as a strongest factor regulating structure and function of gut microbial community. Phytoestrogens are one class of dietary compounds emerging as potentially being of interest in this interaction as numerous studies have identified depletion of phytoestrogen-metabolizing bacteria such as Adlercreutzia, Parabacteroides and Prevotella in RRMS patients. Additionally, phytoestrogens or their metabolites have been reported to show protective effects when compounds are administered in the animal model of MS, Experimental Autoimmune Encephalomyelitis (EAE). In this review, we will illustrate the link between MS and phytoestrogen metabolizing bacteria, characterize the importance of gut bacteria and their mechanisms of action in the production of phytoestrogen metabolites, and discuss what is known about the interactions of specific compounds with cells immune and nervous system. A better understanding of gut bacteria-mediated phytoestrogen metabolism and mechanisms through which these metabolites facilitate their biological actions will help in development of novel therapeutic options for MS as well as other inflammatory diseases., (Copyright © 2020 Cady, Peterson, Freedman and Mangalam.)

Advances in integrated circuitry from the 1950s to the present day have enabled a revolution in technology across the world. However, fundamental limits of circuitry make further improvements through historically successful methods increasingly challenging. It is becoming clear that to address new challenges and applications, new methods of computation will be required. One promising field is neuromorphic engineering, a broad field which applies biologically inspired principles to create alternative computational architectures and methods. We address why neuromorphic engineering is one of the most promising fields within emerging computational technology, elaborating on its common principles and models, and discussing its current state and future challenges.

Low-power electrolysis-based microfluidic pumps utilizing the principle of hydraulics, integrated with microfluidic channels in polydimethylsiloxane (PDMS) substrates, are presented. The electro-hydraulic pumps (EHPs), consisting of electrolytic, hydraulic and fluidic chambers, were investigated using two types of electrodes: stainless steel for larger volumes and annealed gold electrodes for smaller-scale devices. Using a hydraulic fluid chamber and a thin flexible PDMS membrane, this novel prototype successfully separates the reagent fluid from the electrolytic fluid, which is particularly important for biological and chemical applications. The hydraulic advantage of the EHP device arises from the precise control of flow rate by changing the electrolytic pressure generated, independent of the volume of the reagent chamber, mimicking the function of a hydraulic press. Since the reservoirs are pre-filled with reagents and sealed prior to testing, external fluid coupling is minimized. The stainless steel electrode EHPs were manufactured with varying chamber volume ratios (1 : 1 to 1 : 3) as a proof-of-concept, and exhibited flow rates of 1.25 to 30 microl/min with electrolysis-based actuation at 2.5 to 10 V(DC). The miniaturized gold electrode EHPs were manufactured with 3 mm diameters and 1 : 1 chamber volume ratios, and produced flow rates of 1.24 to 7.00 microl/min at 2.5 to 10 V(AC), with a higher maximum sustained pressure of 343 KPa, suggesting greater device robustness using methods compatible with microfabrication. The proposed technology is low-cost, low-power and disposable, with a high level of reproducibility, allowing for ease of fabrication and integration into existing microfluidic lab-on-a-chip and analysis systems.

An optical detector has been fabricated that is specific for targeted bacterial cells, by stamping an antibody grating pattern on a silicon surface. The antibody grating alone produces insignificant optical diffraction, but upon immunocapture of cells, the optical phase change produces a diffraction pattern. This technique eliminates much of the surface modifications and the secondary immunochemical or enzyme-linked steps that are common in immunoassays. Microcontact printing provides an alternative to previously reported photolithographic-mediated antibody patterning processes and uses a photolithographic process simply to produce the elastomeric stamp. We have stamped antibodies directly onto clean native oxide silicon substrates with no other chemical surface treatments. Direct binding of the antibodies to the silicon occurs in a way that still allows them to function and selectively bind antigen. The performance of the sensor was evaluated by capturing Escherichia coli O157:H7 cells on the antibody-stamped lines and measuring the intensity of the first-order diffraction beam resulting from the attachment of cells. The diffraction intensity increases in proportion to the cell density bound on the surface.

Interdisciplinary teaching rounds were initiated on a general surgery service at a university teaching hospital. These rounds were designed to promote more efficient patient care by providing an opportunity for enhanced communication among health-care professionals. Improved collaboration is a prerequisite for implementation of critical paths and case management. The authors describe their methods of rounds development and the impact of the rounds on patient outcomes.