National Science Foundation Award Research Articles

Remodeling of the Human Skeletal Muscle Proteome Found After Long-Term Endurance Training but Not After Strength Training

Regular exercise training has tremendous systemic tissue-specific health benefits, but the molecular adaptations to long-term exercise training are not completely understood. The aim of the current study was to investigate the skeletal muscle proteome of highly endurance-trained, strength-trained and untrained individuals and performed exercise- and sex-specific analyses. As a previous investigation from our lab showed limited baseline differences at the gene expression level between highly strength-trained males and untrained males, we hypothesized that the that long-term resistance training results in baseline differences in protein abundances. Additionally, we hypothesized that endurance-trained individuals would have a greater abundance of mitochondrial proteins compared with the untrained and the strength-trained individuals. Liquid-chromatography followed by mass-spectrometry (LC-MS/MS) was performed on skeletal muscle tissue from all individuals. A total of 6713 proteins were detected, with 4269 proteins being expressed in at least 50% of the samples. Over 650 proteins were differentially expressed in the skeletal muscle of endurance-trained individuals compared with controls. Strikingly, 92% of the shared proteins with higher expression in both the male and female endurance groups were known mitochondrial proteins. In contrast to the findings in endurance trained individuals, minimal differences were found in strength-trained individuals and between females and males. Lastly, to determine the preventive-medicine capabilities of long-term training, a co-expression network and comparative literature analysis revealed key proteins and pathways related to the health benefits of exercise, which were primarily related to differences in mitochondrial protein abundance. This network is available as an interactive database resource ( https://inetmodels.com ) where investigators can correlate clinical data with global gene and protein expression data for hypothesis generation. In conclusion, we suggest that long-term endurance training but not strength training results in a r emodeling of the skeletal muscle proteome in humans. This work was financially supported by grants from the Swedish Research Council (2018-02932), the Swedish Center for Sports Research (2020-D0007, P2022-0082), the National Science Foundation (Award Number: 1951792), the Whitaker International Program and the Karolinska Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Evolution of the Structure and Organization of the Mammalian Immunoglobulin Loci

Abstract There are three extant lineages of mammals: placentals (e.g. humans and mice), marsupials (e.g. kangaroos and opossums), and monotremes (e.g. platypus). Of the three lineages, the marsupials are unusually and uniformly limited in their immunoglobulin heavy chain (IgH) isotype content. All marsupials studied have only one IgM, IgG, IgE, and IgA and lack IgD. Comparatively, there is a greater complexity of IgH isotypes and subclasses in both placentals and monotremes. Marsupials also have a greater complexity in their light (L) chain V genes than IgH chains. Transposable elements (TEs), like retroelements, have been hypothesized to contribute to gene copy variation and genome evolution. Recently, these TEs have been found in the IgH loci. Here we investigate the impact these TEs have on the evolution of marsupial IgH and IgL loci. We have found that some of the TEs in the opossum IgH locus are short and non-functional, potentially contributing to the restriction seen in the locus. Conversely, the TEs in the L chain loci are longer and may explain the differences in complexity in both the V and C regions between the H and L chain loci. Supported by National Science Foundation Award IOS-2103367.

Online Routing Over Parallel Networks: Deterministic Limits and Data-driven Enhancements

Over the past decade, GPS-enabled traffic applications such as Google Maps and Waze have become ubiquitous and have had a significant influence on billions of daily commuters’ travel patterns. A consequence of the online route suggestions of such applications, for example, via greedy routing, has often been an increase in traffic congestion since the induced travel patterns may be far from the system optimum. Spurred by the widespread impact of traffic applications on travel patterns, this work studies online traffic routing in the context of capacity-constrained parallel road networks and analyzes this problem from two perspectives. First, we perform a worst-case analysis to identify the limits of deterministic online routing. Although we find that deterministic online algorithms achieve finite, problem/instance-dependent competitive ratios in special cases, we show that for a general setting the competitive ratio is unbounded. This result motivates us to move beyond worst-case analysis. Here, we consider algorithms that exploit knowledge of past problem instances and show how to design data-driven algorithms whose performance can be quantified and formally generalized to unseen future instances. We then present numerical experiments based on an application case for the San Francisco Bay Area to evaluate the performance of the proposed data-driven algorithms compared with the greedy algorithm and two look-ahead heuristics with access to additional information on the values of time and arrival time parameters of users. Our results show that the developed data-driven algorithms outperform commonly used greedy online-routing algorithms. Furthermore, our work sheds light on the interplay between data availability and achievable solution quality. History: Accepted by Andrea Lodi, Area Editor for Design and Analysis of Algorithms–Discrete. Funding: This work was supported by National Science Foundation (NSF) Award 1830554 and by the German Research Foundation (DFG) under [Grant 449261765]. Supplemental Material: The e-companion is available at https://doi.org/10.1287/ijoc.2023.1275 .

(Digital Presentation) Oxide Memristors Based on SiO2 with Cu/Ag Alloy Metallization for Neuromorphic Computing

By mimicking biomimetic synaptic processes, the success of artificial intelligence (AI) has been astounding with various applications such as driving automation, big data analysis, and natural-language processing.[1-4] Due to a large quantity of data transmission between the separated memory unit and the logic unit, the classical computing system with von Neumann architecture consumes excessive energy and has a significant processing delay.[5] Furthermore, the speed difference between the two units also causes extra delay, which is referred to as the "memory wall".[6, 7] To keep pace with the rapid growth of AI applications, enhanced hardware systems that particularly feature an energy-efficient and high-speed hardware system need to be secured. The novel neuromorphic computing system, an in-memory architecture with low power consumption, has been suggested as an alternative to the conventional system. Memristors with analog-type resistive switching behavior are a promising candidate for implementing the neuromorphic computing system since the devices can modulate the conductance with cycles that act as synaptic weights to process input signals and store information.[8, 9]The memristor has sparked tremendous interest due to its simple two-terminal structure, including top electrode (TE), bottom electrode (BE), and an intermediate resistive switching (RS) layer. Many oxide materials, including HfO2, Ta2O5, and IGZO, have extensively been studied as an RS layer of memristors. Silicon dioxide (SiO2) features 3D structural conformity with the conventional CMOS technology and high wafer-scale homogeneity, which has benefited modern microelectronic devices as dielectric and/or passivation layers. Therefore, the use of SiO2 as a memristor RS layer for neuromorphic computing is expected to be compatible with current Si technology with minimal processing and material-related complexities.In this work, we proposed SiO2-based memristor and investigated switching behaviors metallized with different reduction potentials by applying pure Cu and Ag, and their alloys with varied ratios. Heavily doped p-type silicon was chosen as BE in order to exclude any effects of the BE ions on the memristor performance. We previously reported that the selection of TE is crucial for achieving a high memory window and stable switching performance. According to the study which compares the roles of Cu (switching stabilizer) and Ag (large switching window performer) TEs for oxide memristors, we have selected the TE materials and their alloys to engineer the SiO2-based memristor characteristics. The Ag TE leads to a larger memory window of the SiO2 memristor, but the device shows relatively large variation and less reliability. On the other hand, the Cu TE device presents uniform gradual switching behavior which is in line with our previous report that Cu can be served as a stabilizer, but with small on/off ratio.[9] These distinct performances with Cu and Ag metallization leads us to utilize a Cu/Ag alloy as the TE. Various compositions of Cu/Ag were examined for the optimization of the memristor TEs. With a Cu/Ag alloying TE with optimized ratio, our SiO2 based memristor demonstrates uniform switching behavior and memory window for analog switching applications. Also, it shows ideal potentiation and depression synaptic behavior under the positive/negative spikes (pulse train).In conclusion, the SiO2 memristors with different metallization were established. To tune the property of RS layer, the sputtering conditions of RS were varied. To investigate the influence of TE selections on switching performance of memristor, we integrated Cu, Ag and Cu/Ag alloy as TEs and compared the switch characteristics. Our encouraging results clearly demonstrate that SiO2 with Cu/Ag is a promising memristor device with synaptic switching behavior in neuromorphic computing applications. Acknowledgement This work was supported by the U.S. National Science Foundation (NSF) Award No. ECCS-1931088. S.L. and H.W.S. acknowledge the support from the Improvement of Measurement Standards and Technology for Mechanical Metrology (Grant No. 22011044) by KRISS.

(Digital Presentation) Multimodal Encapsulation of p-SnOx to Engineer the Carrier Density for Thin Film Transistor Applications

It has been challenging to synthesize p-type SnOx (1≤x<2) and engineer the electrical properties such as carrier density and mobility due to the narrow processing window and the localized oxygen 2p orbitals near the valence band.We recently reported on the processing of p-type SnOx and an oxide-based p-n heterostructures, demonstrating high on/off rectification ratio (>103), small turn-on voltage (<0.5 V), and low saturation current (~1×10-10 A)1. In order to further understand the p-type oxide and engineer the properties for various electronic device applications, it is important to identify (or establish) the dominating doping and transport mechanisms. The low dopability in p-type SnOx, of which the causation is also closely related to the narrow processing window, needs to be mitigated so that the electrical properties of the material are to be adequately engineered 2, 3.Herein, we report on the multifunctional encapsulation of p-SnOx to limit the surface adsorption of oxygen and selectively permeate hydrogen into the p-SnOx channel for thin film transistor (TFT) applications. Time-of-flight secondary ion mass spectrometry measurements identified that ultra-thin SiO2 as a multifunctional encapsulation layer effectively suppressed the oxygen adsorption on the back channel surface of p-SnOx and augmented hydrogen density across the entire thickness of the channel. Encapsulated p-SnOx-based TFTs demonstrated much-enhanced channel conductance modulation in response to the gate bias applied, featuring higher on-state current and lower off-state current. The relevance between the TFT performance and the effects of oxygen suppression and hydrogen permeation is discussed in regard to the intrinsic and extrinsic doping mechanisms. These results are supported by density-functional-theory calculations. Acknowledgement This work was supported by the U.S. National Science Foundation (NSF) Award No. ECCS-1931088. S.L. and H.W.S. acknowledge the support from the Improvement of Measurement Standards and Technology for Mechanical Metrology (Grant No. 20011028) by KRISS. K.N. was supported by Basic Science Research Program (NRF-2021R11A1A01051246) through the NRF Korea funded by the Ministry of Education. References Lee, D. H.; Park, H.; Clevenger, M.; Kim, H.; Kim, C. S.; Liu, M.; Kim, G.; Song, H. W.; No, K.; Kim, S. Y.; Ko, D.-K.; Lucietto, A.; Park, H.; Lee, S., High-Performance Oxide-Based p–n Heterojunctions Integrating p-SnOx and n-InGaZnO. ACS Applied Materials & Interfaces 2021, 13 (46), 55676-55686.Hautier, G.; Miglio, A.; Ceder, G.; Rignanese, G.-M.; Gonze, X., Identification and design principles of low hole effective mass p-type transparent conducting oxides. Nat Commun 2013, 4.Yim, K.; Youn, Y.; Lee, M.; Yoo, D.; Lee, J.; Cho, S. H.; Han, S., Computational discovery of p-type transparent oxide semiconductors using hydrogen descriptor. npj Computational Materials 2018, 4 (1), 17. Figure 1

(Digital Presentation) Ultrathin Stabilized Zn Metal Anode for Highly Reversible Aqueous Zn-Ion Batteries

Ever-increasing demands for energy, particularly being environmentally friendly have promoted the transition from fossil fuels to renewable energy.1 Lithium-ion batteries (LIBs), arguably the most well-studied energy storage system, have dominated the energy market since their advent in the 1990s.2 However, challenging issues regarding safety, supply of lithium, and high price of lithium resources limit the further advancement of LIBs for large-scale energy storage applications.3 Therefore, attention is being concentrated on an alternative electrochemical energy storage device that features high safety, low cost, and long cycle life. Rechargeable aqueous zinc-ion batteries (ZIBs) is considered one of the most promising alternative energy storage systems due to the high theoretical energy and power densities where the multiple electrons (Zn2+) . In addition, aqueous ZIBs are safer due to non-flammable electrolyte (e.g., typically aqueous solution) and can be manufactured since they can be assembled in ambient air conditions. 4 As an essential component in aqueous Zn-based batteries, the Zn metal anode generally suffers from the growth of dendrites, which would affect battery performance in several ways. Second, the led by the loose structure of Zn dendrite may reduce the coulombic efficiency and shorten the battery lifespan.5 Several approaches were suggested to improve the electrochemical stability of ZIBs, such as implementing an interfacial buffer layer that separates the active Zn from the bulk electrolyte.6 However, the and thick thickness of the conventional Zn metal foils remain a critical challenge in this field, which may diminish the energy density of the battery drastically. According to a theretical calculation, the thickness of a Zn metal anode with an areal capacity of 1 mAh cm-2 is about 1.7 μm. However, existing extrusion-based fabrication technologies are not capable of downscaling the thickness Zn metal foils below 20 μm.Herein, we demonstrate a thickness controllable coating approach to fabricate an ultrathin Zn metal anode as well as a thin dielectric oxide separator. First, a 1.7 μm Zn layer was uniformly thermally evaporated onto a Cu foil. Then, Al2O3 , the separator was deposited through sputtering on the Zn layer to a thickness of 10 nm. The inert and high hardness Al2O3 layer is expected to lower the polarization and restrain the growth of Zn dendrites. Atomic force microscopy was employed to evaluate the roughness of the surface of the deposited Zn and Al2O3/Zn anode structures. Long-term cycling stability was gauged under the symmetrical cells at 0.5 mA cm-2 for 1 mAh cm-2. Then the fabricated Zn anode was paired with MnO2 as a full cell for further electrochemical performance testing. To investigate the evolution of the interface between the Zn anode and the electrolyte, a home-developed in-situ optical observation battery cage was employed to record and compare the process of Zn deposition on the anodes of the Al2O3/Zn (demonstrated in this study) and the procured thick Zn anode. The surface morphology of the two Zn anodes after circulation was characterized and compared through scanning electron microscopy. The tunable ultrathin Zn metal anode with enhanced anode stability provides a pathway for future high-energy-density Zn-ion batteries. Obama, B., The irreversible momentum of clean energy. Science 2017, 355 (6321), 126-129. Goodenough, J. B.; Park, K. S., The Li-ion rechargeable battery: a perspective. J Am Chem Soc 2013, 135 (4), 1167-76. Li, C.; Xie, X.; Liang, S.; Zhou, J., Issues and Future Perspective on Zinc Metal Anode for Rechargeable Aqueous Zinc‐ion Batteries. Energy & Environmental Materials 2020, 3 (2), 146-159. Jia, H.; Wang, Z.; Tawiah, B.; Wang, Y.; Chan, C.-Y.; Fei, B.; Pan, F., Recent advances in zinc anodes for high-performance aqueous Zn-ion batteries. Nano Energy 2020, 70. Yang, J.; Yin, B.; Sun, Y.; Pan, H.; Sun, W.; Jia, B.; Zhang, S.; Ma, T., Zinc Anode for Mild Aqueous Zinc-Ion Batteries: Challenges, Strategies, and Perspectives. Nanomicro Lett 2022, 14 (1), 42. Yang, Q.; Li, Q.; Liu, Z.; Wang, D.; Guo, Y.; Li, X.; Tang, Y.; Li, H.; Dong, B.; Zhi, C., Dendrites in Zn-Based Batteries. Adv Mater 2020, 32 (48), e2001854. AcknowledgmentThis work was partially supported by the U.S. National Science Foundation (NSF) Award No. ECCS-1931088. S.L. and H.W.S. acknowledge the support from the Improvement of Measurement Standards and Technology for Mechanical Metrology (Grant No. 22011044) by KRISS. Figure 1

(Digital Presentation) Calculation of the Energy Band Diagram and Estimation of Electronic Transport Parameters of Metastable Amorphous Ge2Sb2Te5

Phase change memory (PCM) is a high speed, high density non-volatile resistive memory technology that utilizes different phases (crystalline and amorphous) of phase change materials such as Ge2Sb2Te5 (GST) to store information [1]. Here, the material undergoes two types of reversible switching phenomena: (i) Ovonic Threshold Switching (OTS), which causes the amorphous phase of the material to switch from a highly resistive state to conductive state with application of high electric fields, resulting in current flow and (ii) Ovonic Memory Switching (OMS), which is due to the change of the phase of the material between amorphous and crystalline phases induced by heating [2]. Even though PCM entered high volume manufacturing, the electronic properties of the phase change materials are still not well understood [3,4]. In this work, we construct the energy band diagram of amorphous GST as a function of temperature using a temperature dependent model of effective activation energy of conduction in metastable amorphous GST [5], which we obtained from high-speed experiments on GST line-cells [6]. Assuming the bandgap energy to linearly decrease with temperature [7,8] and p-type conduction (based on positive Seebeck coefficients measured in a wide temperature range [9]) , we determine a temperature dependent Fermi energy level from 0K to melting temperature, Tmelt ~ 858 K. Liquid GST is expected to become metallic (bandgap collapsing to 0) at ~ 894K, based on the experimental results. We also estimate the carrier concentration at Tmelt utilizing the latent heat of fusion (126 kJ/kg) [10] to be pmelt = 1.47 x 1022 cm-3. Using the melt resistivity measured on GST thin film, we calculate the carrier mobility at melting point as µmelt ~0.187 cm2/V-s, close to the previously reported value of 0.15 cm2/V-s based on crystalline state mobility and a density of states calculation [2]. Assuming a weak temperature dependence of the mobility [5], we obtain the carrier concentration of ~3.37× 1017 cm-3 at room temperature which lies within the ~1017-1018 cm-3 range estimated in a former study [3]. Finally, we calculate conduction activation energy of as-deposited amorphous GST from temperature dependent Seebeck coefficient measured simultaneously with the resistance [9]. The activation energy varies as a parabolic function of temperature where it starts from 0 eV at 0 K, reaches a peak of ~0.257 eV near glass transition temperature (~400 K) with the room temperature value of ~0.24 eV and becomes 0 eV again at ~810 K. We also utilize the Seebeck coefficient measurements along with the band edges and Fermi energy level information from the energy band diagram to calculate the ratio of minority carrier concentration to the total carrier concentration as a function of temperature; this is useful to predict the temperature beyond which bipolar conduction becomes significant.Acknowledgment: Analysis is performed with the support of US National Science Foundation (NSF) award ECCS 1711626. The experimental data used for this analysis were collected with the support of US NSF DMR-1710468 on devices fabricated with the support of US Department of Energy Office of Basic Energy Sciences.

(Digital Presentation) Finite Element Modeling of Thermoelectric Effects in Phase Change Memory Cells

Phase change memory (PCM) is a high-speed high-endurance non-volatile electronic memory technology which utilizes the electrical resistivity difference between the amorphous and the crystalline phases of phase change materials, such as Ge2Sb2Te5 (GST), to store information [1]. PCM cells are switched by short duration electrical pulses by melting a small volume to transition to dielectric amorphous phase (reset) or heating above glass-transition temperature to crystallize (set). The cells experience extremely large thermal gradients (~ 50 K/nm) and high current densities (~50 MA/cm2) during reset. Hence thermoelectric (TE) contributions are very significant both in bulk and at the material and solid-liquid interfaces [2]. In this work, we performed finite element simulations of mushroom PCM cells and analyzed contributions of Joule heating (symmetric) and thermoelectric heat (asymmetric) during reset and set operations using COMSOL Multiphysics. A field effect transistor (FET), modeled using a circuit model, is used as an access device. We self-consistently solve for current continuity, heat transport (Fig. 1) and phase changes in the materials, including temperature, electric-field and phase-dependent electrical and thermal conductivity, thermal boundary resistances and latent heat of fusion, along with temperature dependent stochastic nucleation, growth and grain-boundary amorphization, accounting for all energy exchanges [3-6].Thermoelectric heat exchanges are due to generation and recombination of electrons and holes as well as the kinetic energy absorbed or released by the transported free charge carriers [7]. These energy exchanges can take place at material interfaces (Peltier heat) or in bulk material (Thomson heat). Discontinuity of Seebeck coefficient and temperature (due to thermal boundary resistances) make TE contributions very significant in PCM devices.Our simulation results show the significance of the TE contributions on the reset behavior of PCM devices (Fig. 2). Self-heating at the bottom TiN-GST interface is substantially higher for one of the current polarities, giving rise to an over-sized mushroom in the case of negative polarity, for the same reset pulse amplitude. The negative polarity case (over-reset cell) cannot be set with the same set pulse as the positive polarity case. From the power consumption and peak current requirement point of view, it is advantageous to have higher TE heating inside the mushroom and its interfaces. TE cooling away from the mushroom interfaces is advantageous for reduced thermal cross-talk and write-disturb on the neighboring cells. However, thermal gradients also need to be kept under consideration for reliability perspective.Acknowledgement: Md Tashfiq Bin Kashem acknowledges support from General Electric through a Graduate Fellowship for Innovation. This work is supported through US National Science Foundation (NSF) award # 1710468.

(Invited) Oxide Electronics and Recent Progress in Bipolar Applications

The discovery of oxide electronics is of increasing importance today as one of the most promising new technologies and manufacturing processes for a variety of electronic and optoelectronic applications such as next-generation displays, batteries, solar cells, memory devices, and photodetectors[1]. The high potential use seen in oxide electronics is due primarily to their high carrier mobilities and their ability to be fabricated at low temperatures[2]. However, since the majority of oxide semiconductors are n-type oxides, current applications are limited to unipolar devices, eventually developing oxide-based bipolar devices such as p-n diodes and complementary metal-oxide semiconductors.We have contributed to a wide range of oxide semiconductors and their electronics and optoelectronic device applications. Particularly, we have demonstrated n-type oxide-based thin film transistors (TFT), integrating In2O3-based n-type oxide semiconductors from binary cation materials to ternary cation species including InZnO, InGaZnO (IGZO), and InAlZnO. We have suggested channel/metallization contact strategies to achieve stable and high TFT performance[3, 4], identified vacancy-based native defect doping mechanisms[5], suggested interfacial buffer layers to promote charge injection capability[6], and established the role of third cation species on the carrier generation and carrier transport[7]. More recently, we have reported facile manufacturing of p-type SnOx through reactive magnetron sputtering from a Sn metal target[8]. The fabricated p-SnOx was found to be devoid of metallic phase of Sn from x-ray photoelectron spectroscopy and demonstrated stable performance in a fully oxide-based p-n heterojunction together with n-InGaZnO. The oxide-based p-n junctions exhibited a high rectification ratio greater than 103 at ±3 V, a low saturation current of ~2x10-10, and a small turn-on voltage of -0.5 V.In this presentation, we review recent achievements and still remaining issues in transition metal oxide semiconductors and their device applications, in particular, bipolar applications including p-n heterostructures and complementary metal-oxide-semiconductor devices as well as single polarity devices such as TFTs and memristors. In addition, the fundamental mechanisms of carrier transport behaviors and doping mechanisms that govern the performance of these oxide-based devices will also be discussed.ACKNOWLEDGMENTThis work was supported by the U.S. National Science Foundation (NSF) Award No. ECCS-1931088. S.L. and H.W.S. acknowledge the support from the Improvement of Measurement Standards and Technology for Mechanical Metrology (Grant No. 20011028) by KRISS. K.N. was supported by Basic Science Research Program (NRF-2021R11A1A01051246) through the NRF Korea funded by the Ministry of Education.REFERENCES[1] K. Nomura et al., Nature, vol. 432, no. 7016, pp. 488-492, Nov 25 2004.[2] D. C. Paine et al., Thin Solid Films, vol. 516, no. 17, pp. 5894-5898, Jul 1 2008.[3] S. Lee et al., Journal of Applied Physics, vol. 109, no. 6, p. 063702, Mar 15 2011, Art. no. 063702.[4] S. Lee et al., Applied Physics Letters, vol. 104, no. 25, p. 252103, 2014.[5] S. Lee et al., Applied Physics Letters, vol. 102, no. 5, p. 052101, Feb 4 2013, Art. no. 052101.[6] M. Liu et al., ACS Applied Electronic Materials, vol. 3, no. 6, pp. 2703-2711, 2021/06/22 2021.[7] A. Reed et al., Journal of Materials Chemistry C, 10.1039/D0TC02655G vol. 8, no. 39, pp. 13798-13810, 2020.[8] D. H. Lee et al., ACS Applied Materials & Interfaces, vol. 13, no. 46, pp. 55676-55686, 2021/11/24 2021.

A Wearable Aptamer Microneedle Patch for Minimally-Invasive Therapeutic Drug Monitoring

To realize personalized medicine, the right drug needs to be delivered to the right patient at the right dose. However, it is extremely challenging to dose drugs with narrow therapeutic windows (e.g., antibiotics). For these drugs, due to the small difference between ineffective and toxic concentration levels, the prescribed dosage may result in a circulating concentration outside the therapeutic window, leading to toxicity (e.g., kidney injury) and/or ineffective pharmacotherapy. To prevent such adverse events, patients under these medications are committed to therapeutic drug monitoring (TDM), which in the current clinical practice involves repeated and invasive blood draws followed by labor-intensive and high-cost lab-based analyses (e.g., chromatography, immunoassay). The turnaround times for results are prolonged, and thus, inadequate to allow for timely intervention.Wearable pharmaceutical sensing systems—capable of tracking the medication’s concentration in a continuous and non-/minimally-invasive manner—are well-suited to address these challenges encountered in current TDM practice. To establish a generalizable wearable TDM modality for a broad range of pressing clinical applications, we focus on tracking pharmaceuticals in interstitial fluid (ISF). The choice for ISF is motivated by noting that a wide panel of pharmaceuticals, particularly those with stringent personalized dosing requirements, partition into ISF with high correlation to their circulating levels. To target these analytes, microneedles emerged as promising tools, which are capable of overcoming the skin barrier to directly access ISF in a minimally-invasive manner without user intervention. By integrating sensors on microneedle substrates (e.g., on-the-tip electrochemical sensor fabrication), ISF analytes can be monitored continuously. However, currently demonstrated in-situ ISF sensors are mainly based on enzymatic sensing, which significantly limits the scope of target analytes to the ones with enzymes available.Overcoming this limitation, we devised a low-cost affinity-based biosensor-on-needle fabrication scheme, which was utilized to develop an aptamer microneedle patch (AMPatch). Our AMPatch consists of: 1) a microneedle electrode substrate based on repurposed acupuncture gold needles, leveraging the validated skin puncture performance and the high conductivity of these needles; 2) a gold nanoparticle (AuNP) coating, rendering a high-quality gold surface (comparable to standard electrodes used in electrochemistry) for strong and compact aptamer immobilization; and 3) an aptamer/signal reporter self-assembled monolayer, transducing the target binding events into measurable electrical readouts. We specifically target tobramycin, an antibiotic with a narrow therapeutic window and large intra-subject pharmacokinetic variations, which in the current clinical practice requires multiple TDM sessions to achieve an optimal dosing. Leveraging the developed AMPatch, we demonstrated real-time continuous monitoring of tobramycin ex-vivo (in a phantom gel model, mimicking the dermal ISF testing scenario) and in-vivo (via rat studies). Our results demonstrate the suitability of the AMPatch for minimally-invasive monitoring of the target drug’s pharmacokinetic profile and its potential as a viable TDM tool for personalized pharmacotherapy. Acknowledgements: This work was supported by the National Science Foundation (Award 1847729) and the UCLA Innovation Fund.

Facile Processing of p-Type Oxides and Oxide-Based p-n Heterojunction Applications

Oxide electronics have gained prominence in recent years and have been established as one of the most promising new technologies for various electronic and optoelectronic applications including next generation displays, solar cells, and photodetectors. The high potential use seen in oxide electronics is due primarily to their high carrier mobilities and their ability to be fabricated at low temperatures.However, the vast majority of oxide semiconductors are n-type oxides, which limits the current applications to unipolar devices and ultimately stunts the development of oxide-based bipolar device applications such as p-n diodes and complementary metal–oxide–semiconductors.The goal of this research is to resolve the scientific questions which prevent the realization of low-temperature processed p-type oxides and oxide-based p-n heterojunctions showcasing high rectification behavior, low saturation current, and a small turn-on voltage.The current study is unique in that:(1) Unlike several previous reports on oxide p-n junctions fabricated exploiting a thin film epitaxial growth technique (known as molecular beam epitaxy, MBE) or a high-powered laser beam process (known as pulsed laser deposition, PLD) that requires ultra-high vacuum conditions, a large amount of power, and is limited for large area processing, we demonstrate oxide-based heterojunction p-n diodes that consists of sputter-synthesized p-SnOx and n-IGZO of which the manufacturing routes are in-line with current manufacturing requirements.(2) The synthesized p-SnOx films are devoid of metallic Sn phases (i.e., Sn0 state) with carrier density tuneability and high carrier mobility (> 2 cm2/Vs).(3) The charge blocking performance of the metallurgical junction is significantly enhanced by the engineering of trap/defect density of n-IGZO, which is identified using photoelectron microscopy and valence band measurements.(4) The resulting oxide-based p-n heterojunction exhibits a high rectification ratio greater than 103 at ±3 V (highest among the sputter-processed oxide junctions), a low saturation current of ~2×10-10 A, and a small turn-on voltage of ~0.5 V.The outcomes of the current study are expected to contribute to the development of p-type oxides and their industrial device applications such as p-n diodes of which the manufacturing routes are in-line with the current processing requirements.REFERENCES Nomura, K.; Ohta, H.; Takagi, A.; Kamiya, T.; Hirano, M.; Hosono, H., Room-temperature fabrication of transparent flexible thin-film transistors using amorphous oxide semiconductors. Nature 2004, 432 (7016), 488-492.Kawazoe, H.; Yasukawa, M.; Hyodo, H.; Kurita, M.; Yanagi, H.; Hosono, H., P-type electrical conduction in transparent thin films of CuAlO2. Nature 1997, 389 (6654), 939-942.Kawazoe, H.; Yanagi, H.; Ueda, K.; Hosono, H., Transparent p-Type Conducting Oxides: Design and Fabrication of p-n Heterojunctions. MRS Bull. 2000, 25 (08), 28-36.Lee, S.; Paine, D. C., Metallization selection and the performance of amorphous In-Zn-O thin film transistors. Applied Physics Letters 2014, 104 (25), 252103.Liu, M.; Kim, H.; Wang, X.; Song, H. W.; No, K.; Lee, S., Carrier Density-Tunable Work Function Buffer at the Channel/Metallization Interface for Amorphous Oxide Thin-Film Transistors. ACS Applied Electronic Materials 2021, 3 (6), 2703-2711. ACKNOWLEDGMENTThis work was supported by the U.S. National Science Foundation (NSF) Award No. ECCS-1931088. S.L. and H.W.S. acknowledge the support from the Improvement of Measurement Standards and Technology for Mechanical Metrology (Grant No. 20011028) by KRISS.

Understanding the Last Mile Transportation Concept Impacting Underserved Global Communities to Save Lives During COVID-19 Pandemic

The underserved population could be at risk during the times of crisis, unless there is strong involvement from government agencies such as local and state Health departments and federal Center for Disease Control (CDC). The COVID-19 pandemic was a crisis of different proportion, creating a different type of burden on government agencies. Vulnerable communities including the elderly populations and communities of color have been especially hard hit by this pandemic. This forced these agencies to change their strategies and supply chains to support all populations receiving therapeutics. The National Science Foundation [National Science Foundation (NSF) Award Abstract # 2028612] funded RAID Labs to help federal agencies with strategies. This paper is based on a NSF funded grant to work on investigating supply chain strategies that would minimize the impact on underserved populations during pandemic. This NSF funded study identified the phenomena of last mile importance. The last mile transportation concept was critical in saving lives during the pandemic for underserved populations. The supply chain model then maximizes social goods by sending drugs or vaccines to the communities that need it the most regardless of ability to pay. The outcome of this study helped us prioritize the communities that need the vaccines the most. This informs our supply chain model to shift resources to these areas showing the value in real time prioritization of the COVID-19 supply chain. This paper provides information can be used in our healthcare supply chain model to ensure timely delivery of vaccines and supplies to COVID-19 patients that are the most vulnerable and hence the overall impact of COVID-19 can be minimized. The use of electrical vehicles for last mile transportation can help in significantly fighting the climate change.

Redox-Active Polymers Designed for the Circular Economy of Energy Storage Devices

A.G. and A.S. acknowledge funding from the TomKat Center for Sustainable Energy at Stanford University and the StorageX initiative. A.S. and S.T.M.T. gratefully acknowledge support from the National Science Foundation Award CBET #1804915. T.J.Q. and G.L. acknowledge support from the NSF Graduate Research Fellowship Program under grant DGE-1656518. Part of this work was performed at the Stanford Nanofabrication Facilities (SNF) and Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation as part of the National Nanotechnology Coordinated Infrastructure under award ECCS-1542152. The authors acknowledge financial support from KAUST, including the Office of Sponsored Research (OSR) award nos. OSR-2018-CRG/CCF-3079, OSR-2019-CRG8-4086, and OSR-2018-CRG7-3749. The authors acknowledge funding from an ERC Synergy Grant SC2 (610115). Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-76SF00515.

Acknowledgments

Previous articleNext article FreeAcknowledgmentsFull TextPDF Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinked InRedditEmailQR Code SectionsMoreThis volume grew out of a multiyear collaboration on “Global Medical Cultures and Law” that sought to bring together historians, anthropologists, sociologists, and legal scholars to explore a shared set of historical questions. We received generous support from the Buffett Institute for Global Studies and the Science in Human Culture Program at Northwestern University. I am especially grateful to the Buffett Institute’s then director, Bruce Carruthers, and to my collaborators: Carol Heimer, Laura Pedraza-Fariña, Rebecca Seligman, Jeannette Colyvas, and, most recently, Adia Benton. For their unflagging encouragement, I am indebted to Ken Alder and Steve Epstein; and for their advice and thoughts before the project got off the ground, my thanks to Mitra Shirafi and Heinz Klug. Natasha Dennison and Janet Hundrieser provided terrific administrative assistance, while the indomitable Shan Chen Pu did helpful background research. My coordinating role was supported in part by a Buffett Institute Faculty Fellowship and my research by a Scholars Award from the National Science Foundation (Award #1456984).Several scholars enriched our conversations along the way by taking part in events that led to this volume, including Mark Harrison, Linda Barnes, Kaushik Sunder Rajan, Rosemary Coombe, Chidi Oguamanam, Madhavi Sunder, Siri Suh, Guillaume Lachenal, Bridie Andrews, Noelle Sullivan, David Schoenbrun, Richard Rottenburg, and Nancy Hunt. For their astute comments on earlier drafts, our special thanks to Claire Wendland, Paul Ramírez, Steven Palmer, Peter Locke, and two incredibly helpful anonymous reviewers.Without the Osiris editorial board’s willingness to take a risk on us, this volume never would have been possible. And without the sustained engagement from W. Patrick McCray and Suman Seth, it would have been much the poorer. To all the contributors who were willing to take up new projects, rewrite and reframe chapters, and explore genres of history writing (and storytelling) that were unfamiliar, my enduring gratitude. It has been an honor and a joy to think with–and learn alongside–one and all. Previous articleNext article DetailsFiguresReferencesCited by Osiris Volume 362021Therapeutic Properties: Global Medical Cultures, Knowledge, and Law Published for the History of Science Society Article DOIhttps://doi.org/10.1086/713421 Views: 267 © 2021 History of Science Society. All rights reserved. Crossref reports no articles citing this article.

COVID-19 mortality among kidney transplant candidates is strongly associated with social determinants of health.

The COVID‐19 pandemic has affected all portions of the global population. However, many factors have been shown to be particularly associated with COVID‐19 mortality including demographic characteristics, behavior, comorbidities, and social conditions. Kidney transplant candidates may be particularly vulnerable to COVID‐19 as many are dialysis‐dependent and have comorbid conditions. We examined factors associated with COVID‐19 mortality among kidney transplant candidates from the National Scientific Registry of Transplant Recipients from March 1 to December 1, 2020. We evaluated crude rates and multivariable incident rate ratios (IRR) of COVID‐19 mortality. There were 131 659 candidates during the study period with 3534 all‐cause deaths and 384 denoted a COVID‐19 cause (5.00/1000 person years). Factors associated with increased COVID‐19 mortality included increased age, males, higher body mass index, and diabetes. In addition, Blacks (IRR = 1.96, 95% C.I.: 1.43–2.69) and Hispanics (IRR = 3.38, 95% C.I.: 2.46–4.66) had higher COVID‐19 mortality relative to Whites. Patients with lower educational attainment, high school or less (IRR = 1.93, 95% C.I.: 1.19–3.12, relative to post‐graduate), Medicaid insurance (IRR = 1.73, 95% C.I.: 1.26–2.39, relative to private), residence in most distressed neighborhoods (fifth quintile IRR = 1.93, 95% C.I.: 1.28–2.90, relative to first quintile), and most urban and most rural had higher adjusted rates of COVID‐19 mortality. Among kidney transplant candidates in the United States, social determinants of health in addition to demographic and clinical factors are significantly associated with COVID‐19 mortality.

How Limitations in Energy Burdens Compromise Health Interventions for COVID Outbreaks in Urban Settings

Low-income households have experienced increased energy burdens and inaccess to healthcare services during the COVID-19 pandemic, which has limited their ability to practice social distancing and stay-at-home orders. Here, we show that a households’ inability to adopt social distancing due to constraints in utility and healthcare expenditure drastically impacts the course of disease outbreak in five U.S. counties. Low-income households shoulder greater burdens of disease and death than other households, while functioning as a consistent source of exposure to higher income households. Health interventions combining social distancing and resource protection strategies (e.g., utility access and healthcare) were the most effective in limiting the spread of COVID-19. Additionally, resource protection strategies tailored to alleviate utilities and financial constraints for low-income households can protect the whole population. Current policies need to address the multidimensionality of energy burdens, housing environment, and public health. The findings also imply methods for future disaster management.Funding Information: C.-F. Chen, G. Bonilla, and H. Nelson are supported by the Engineering Research Center Program of the U.S. National Science Foundation (NSF) and the Department of Energy under NSF award EEC-1041877 and the CURENT Industry Partnership Program.Declaration of Interests: The authors have no financial or non-financial interests associated with the material in this manuscript.

Collaborating between Writing and STEM: Teaching Disciplinary Genres, Researching Disciplinary Interventions, and Engaging Science Audiences

Collaborating between Writing and STEM: Teaching Disciplinary Genres, Researching Disciplinary Interventions, and Engaging Science Audiences

Analysis of Microbial Water Contamination, Soil Microbial Community Structure, and Soil Respiration in a Collaborative First-Year Students as Scholars Program (SAS).

The persistence of college students in STEM majors after their first-year of college is approximately 50%, with underrepresented populations displaying even higher rates of departure. For many undergraduates, their first-year in college is defined by large class sizes, poor access to research faculty, and minimal standing in communities of scholars. Pepperdine University and Whittier College, funded by a National Science Foundation award to Improve Undergraduate Stem Education (NSF IUSE), partnered in the development of first-year classes specifically geared to improve student persistence in STEM and academic success. This Students as Scholars Program (SAS) engaged first-year undergraduates in scholarly efforts during their first semester in college with a careful approach to original research design and mentoring by both faculty and upperclassmen experienced in research. Courses began by introducing hypothesis formulation and experimental design partnered with the scientific focus of each course (ecological, biochemical, microbiological). Students split into research teams, explored the primary literature, designed research projects, and executed experiments over a 6–7 week period, collecting, analyzing, and interpreting data. Microbiology-specific projects included partnerships with local park managers to assess water quality and microbial coliform contamination at specified locations in a coastal watershed. In addition, students explored the impact of soil salinity on microbial community structure. Analysis of these samples included next-generation sequencing and microbiome compositional analysis via collaboration with students from an upper division microbiology course. This cross-course collaboration facilitated additional student mentoring opportunities between upperclassmen and first-year students. This approach provided first-year students an introduction to the analysis of complex data sets using bioinformatics and statistically reliable gas-exchange replicates. Assessment of the impact of this program revealed students to view the research as challenging, but confidence building as they take their first steps as biology majors. In addition, the direct mentorship of first-year students by upperclassmen and faculty was viewed positively by students. Ongoing assessments have revealed SAS participants to display a 15% increased persistence rate in STEM fields when compared to non-SAS biology majors.

Injection Metal-Assisted Catalytic Etching (MACE) of Si Powder: Discovery of Low-Load MACE and Pore Distribution Tunability Using Ag, Au, Pd, Pt and Cu Catalysts

Injection of H2O2 to control both the rate and extent of etching allowed us to discover a new regime of MACE with extremely small quantities of deposited metal as a catalyst: low-load MACE (LL-MACE).1 The structure of particles subjected to LL-MACE is completely different compared to conventional MACE. Si nanowires and mesoporous micro- or nano-particles are produced with high yield, low cost and controlled properties suitable for applications in e.g. lithium-ion batteries, drug delivery, as well as biomedical imaging and contrast enhancement. Different metal catalysts behave in distinct manners than can be traced to differences in nucleation and reaction kinetics.2 Not only Ag, Au, Pd and Pt but also inexpensive Cu can be used to perform LL-MACE.Previously, controlled reactant injection and acetic acid were used to transform stain etching into the improved process known as regenerative electroless etching (ReEtching).3 Here injection and acetic acid are exploited to enhance MACE and extend it to the low-load regime. Ag, Au, Pd, Pt and Cu can be galvanically deposited onto Si powder out of solutions of HF(aq). Nucleation of deposited metal nanoparticles is made more uniform by dispersing the Si powder in acetic acid and injecting the dissolved metal ions at a controlled rate. The use of a syringe pump to deliver not only metal ions during deposition but also the oxidant (H2O2) during MACE is essential for increased product uniformity and yield. Temperatures of ~0–50 °C and grades of Si (i.e. electronics grade Si with various doping levels or metallurgical grade Si) produced significantly different pore size distributions. Doping levels and the associated changes in band bending and space charge layer width4 are linked to changes in the pore size distribution.As shown in Fig. 1(A), high loading of Ag resulted in deposition of dendrites and Ag particles. These broke into ~50–100 nm Ag nanoparticles that etched in a correlated fashion to generate parallel etch track pores. The uniform size distribution of the Ag nanoparticles was generated dynamically during etching. This conventional high-load MACE (HL-MACE) did not produce Si nanowires (Si NWs) directly. However, etch track pore walls were cleaved readily by ultrasonic agitation to form Si NWs. Etching far removed from the metal nanoparticles (remote etching) also occurred for highly doped Si.As shown in Fig. 1(B), reducing the loading of Ag by a factor of 100 to 1000 compared to HL-MACE created 10–30 nm nanoparticles that etched in an uncorrelated fashion and generated randomly directed etch track pores. Significant etching far removed from the Ag catalyst also occurred. The combination of localized and remote etching resulted in a bimodal distribution of mesoporosity peaking at ~4 nm from remote etching and 10–30 nm from localized etching. The bimodal distribution was confirmed by the BJH method of nitrogen adsorption porosimetry. The pore size distribution could be controlled by changing the process temperature, the grade of Si and the metal composition. Whereas Ag, Au, Pd and Pt performed well in both the HL and LL limits, Cu generated porosification only in the LL limit.Funded by grants #314552 and #314412 from Academy of Finland and the National Science Foundation award #1825331. The microscopy studies were performed using the facilities in the UConn/Thermo Fisher Scientific Center for Advanced Microscopy and Materials Analysis (CAMMA). 1 K. Tamarov, J. D. Swanson, B. A. Unger, K. W. Kolasinski, A. T. Ernst, M. Aindow, V.-P. Lehto, and J. Riikonen, ACS Appl. Mater. Interfaces 12, 4787 (2020). 2 K. W. Kolasinski, W. B. Barclay, Y. Sun, and M. Aindow, Electrochim. Acta 158, 219 (2015). 3 K. W. Kolasinski, N. J. Gimbar, H. Yu, M. Aindow, E. Mäkilä, and J. Salonen, Angew. Chem., Int. Ed. Engl. 56, 624 (2017). 4 E. Torralba, S. Le Gall, R. Lachaume, V. Magnin, J. Harari, M. Halbwax, J.-P. Vilcot, C. Cachet-Vivier, and S. Bastide, ACS Appl. Mater. Interfaces 8, 31375 (2016). Figure 1

First report of powdery mildew caused by Podosphaera xanthii on the invasive Verbena brasiliensis in Texas.

Brazilian verbena (Verbena brasiliensis, family Lamiaceae) is a highly invasive plant found throughout the southern portion of the United States. As suggested by its name, it originates in South America but has prospered in the US due to its highly ruderal growing pattern and its ability to tolerate drought and disturbance. During the summer of 2019, sixty-four V. brasiliensis plants were growing in the University of Houston's temperature-controlled greenhouse (Houston, TX). Eight plants exhibited symptoms of powdery mildew infection on the stems and adaxial surface of the leaves. White circular powdery colonies with high numbers of aerially dispersing spores were observed on leaves, seemingly uncorrelated with leaf age. Upon examination, chlorosis of leaf tissue was detected in areas of infection. Conidiophores (n=25) were on average 210 μm in length and produced 6 to 9 conidia in true chains. Base-cells of conidiophores branched from hyphae forming right angles and averaged 35 μm long at the base. Conidia were hyaline, ovate, and measured 28-31 × 19-21μm. These structures are typical of the powdery mildew oidium anamorph of the genus Podosphaera. No chasmothecia were observed within colonies.The morphological characteristics and measurements were consistent with those of Podosphaera xanthii (Braun and Takamatsu 2000). Pathogenicity was confirmed by gently rubbing symptomatic V. brasiliensis leaves onto healthy leaves of V. brasiliensis plants (Lee 2013). Fifteen plants were inoculated, and five remained uninoculated to serve as negative controls. Inoculated plants developed powdery mildew symptoms between 6 to 12 days (averaging 10 days), whereas all controls remained disease-free. DNA was extracted from fungal tissue from the original plant, inocula sample, and the newly infected leaves. The internal transcribed region was amplified using the ITS1f and ITS4 primers (White 1990). Three samples, one from the original plant, the inocula, and the reisolated fungi were sequenced, identified using NCBI BLAST, and the resulting sequences were deposited in GenBank (MN818562, (inocula), MN818563 (re-isolate), MN818564 (original)). All three sequences had 98.7% similarity to the P. xanthii on Brazilian verbena reported in South Korea assession number KJ472787 (Cho et al 2014). All three samples were amplified using the mating type primer sets and PCR protocal described in Brewer et al 2011. All three samples were determined to be MAT1-1-1 based on positive and negative control used for MAT1-1-1 and MAT-1-2-1 Positive controls included DNA from confirmed isolates from MAT1-1-1 and MAT-1-2-1 and negative controls were sterile water. Podosphaera xanthii, a common powdery mildew species, has been reported on a large range of important agricultural hosts, especially cucurbits (McCreight 2006). This is the first formal report of P. xanthii in Texas as well as the first report on Brazilian verbena in the United States. While we did not explicitly measure the pathogen's effect on host fitness, infection may result in a reduction in the plant's invasiveness. As Texas is a large producer of cucurbits, this pathogen could impact agriculture in the state. Given the invasive nature of V. brasiliensis in areas of high disturbance, such as agricultural fields and restored prairies, this discovery has broad importance for both agriculture and the ecological conservation of native species. Acknowledgments This work was supported by the National Science Foundation (Award #DEB-1754287), Texas Ecolab, and the University of Houston. References Braun, U., Takamatsu, S. 2000. Phylogeny of Erysiphe, Microsphaera, Uncinula (Erysipheae) and Cystotheca, Podosphaera, Sphaerotheca (Cystotheceae) inferred from rDNA ITS sequences-some taxonomic consequences. Schlechtendalia 4:1-33. Brewer, M. T., Cadle-Davidson, L., Cortesi, P., Spanu, P. D., and Milgroom, M. G. 2011. Identification and structure of the mating-type locus and development of PCR-based markers for mating type in powdery mildew fungi. Fungal Genet. Biol. 48:704-713. Cho, S. E., Park, J. H., Hong, S. H., Kim, B. S., & Shin, H. D. 2014. First report of powdery mildew caused by Podosphaera xanthii on Verbena brasiliensis in Korea. Plant Dis. 98:8, 1159. Lee, H. B. 2013. First report of powdery mildew caused by Podosphaera xanthii (syn. P. fusca)n cocklebur in Korea. Plant Dis. 97(6), 842. McCreight, J. D. 2006. Melon-powdery mildew interactions reveal variation in melon cultigens and Podosphaera xanthii races 1 and 2. Journal of the American Society for Horticultural Science, 131(1), 59-65.