Showing papers by "University of Akron published in 2021"

Amyloid oligomers: A joint experimental/computational perspective on Alzheimer's disease, Parkinson's disease, type II diabetes, and amyotrophic lateral sclerosis

Abstract: Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo, and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research, respectively, for many years.

Smart Materials for Microrobots.

Abstract: Over the past 15 years, the field of microrobotics has exploded with many research groups from around the globe contributing to numerous innovations that have led to exciting new capabilities and important applications, ranging from in vivo drug delivery, to intracellular biosensing, environmental remediation, and nanoscale fabrication Smart responsive materials have had a profound impact on the field of microrobotics and have imparted small-scale robots with new functionalities and distinct capabilities We have identified four large categories where the majority of future efforts must be allocated to push the frontiers of microrobots and where smart materials can have a major impact on such future advances These four areas are the propulsion and biocompatibility of microrobots, the cooperation between individual units and human operators, and finally, the intelligence of microrobots In this Review, we look critically at the latest developments in these four categories and discuss how smart materials contribute to the progress in the exciting field of microrobotics and will set the stage for the next generation of intelligent and programmable microrobots

Unraveling the Structure and Function of Melanin through Synthesis.

Abstract: Melanin is ubiquitous in living organisms across different biological kingdoms of life, making it an important, natural biomaterial Its presence in nature from microorganisms to higher animals and plants is attributed to the many functions of melanin, including pigmentation, radical scavenging, radiation protection, and thermal regulation Generally, melanin is classified into five types-eumelanin, pheomelanin, neuromelanin, allomelanin, and pyomelanin-based on the various chemical precursors used in their biosynthesis Despite its long history of study, the exact chemical makeup of melanin remains unclear, and it moreover has an inherent diversity and complexity of chemical structure, likely including many functions and properties that remain to be identified Synthetic mimics have begun to play a broader role in unraveling structure and function relationships of natural melanins In the past decade, polydopamine, which has served as the conventional form of synthetic eumelanin, has dominated the literature on melanin-based materials, while the synthetic analogues of other melanins have received far less attention In this perspective, we will discuss the synthesis of melanin materials with a special focus beyond polydopamine We will emphasize efforts to elucidate biosynthetic pathways and structural characterization approaches that can be harnessed to interrogate specific structure-function relationships, including electron paramagnetic resonance (EPR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy We believe that this timely Perspective will introduce this class of biopolymer to the broader chemistry community, where we hope to stimulate new opportunities in novel, melanin-based poly-functional synthetic materials

Olefin metathesis-based chemically recyclable polymers enabled by fused-ring monomers.

Abstract: A promising solution to address the challenges in plastics sustainability is to replace current polymers with chemically recyclable ones that can depolymerize into their constituent monomers to enable the circular use of materials. Despite some progress, few depolymerizable polymers exhibit the desirable thermal stability and strong mechanical properties of traditional polymers. Here we report a series of chemically recyclable polymers that show excellent thermal stability (decomposition temperature >370 °C) and tunable mechanical properties. The polymers are formed through ring-opening metathesis polymerization of cyclooctene with a trans-cyclobutane installed at the 5 and 6 positions. The additional ring converts the non-depolymerizable polycyclooctene into a depolymerizable polymer by reducing the ring strain energy in the monomer (from 8.2 kcal mol-1 in unsubstituted cyclooctene to 4.9 kcal mol-1 in the fused ring). The fused-ring monomer enables a broad scope of functionalities to be incorporated, providing access to chemically recyclable elastomers and plastics that show promise as next-generation sustainable materials.

Single-molecule FRET imaging of GPCR dimers in living cells.

Abstract: Class C G protein-coupled receptors (GPCRs) are known to form stable homodimers or heterodimers critical for function, but the oligomeric status of class A and B receptors, which constitute >90% of all GPCRs, remains hotly debated. Single-molecule fluorescence resonance energy transfer (smFRET) is a powerful approach with the potential to reveal valuable insights into GPCR organization but has rarely been used in living cells to study protein systems. Here, we report generally applicable methods for using smFRET to detect and track transmembrane proteins diffusing within the plasma membrane of mammalian cells. We leverage this in-cell smFRET approach to show agonist-induced structural dynamics within individual metabotropic glutamate receptor dimers. We apply these methods to representative class A, B and C receptors, finding evidence for receptor monomers, density-dependent dimers and constitutive dimers, respectively.

A General Crosslinker Strategy to Realize Intrinsic Frozen Resistance of Hydrogels.

Abstract: Development and understanding of antifreezing materials are fundamentally and practically important for materials design and delivery. However, almost all of antifreezing materials are either organic/icephobic materials containing no water or hydrophilic hydrogels containing antifreezing additives. Here, a general crosslinking strategy to fabricate a family of EGINA-crosslinked double-network hydrogels with intrinsic, built-in antifreezing and mechanical properties, but without any antifreezing additives is proposed and demonstrated. The resultant hydrogels, despite large structural and compositional variations of hydrophilies, electrolytes, zwitterions, and macromolecules of polymer chains, achieved strong antifreezing and mechanical properties in different environments including solution state, gel state, and hydrogel/solid interfaces. Such general antifreezing property of EGINA-crosslinked hydrogels, regardless network compositions, is likely stemmed from their highly hydrophilic and tightly crosslinked DN structures for inducing strong water-network bindings to prevent ice crystal formation from free waters in hydrogel networks. EGINA-crosslinked hydrogels can also serve as a key component to be fabricated into smart windows with high optical transmittance and supercapacitors with excellent electrochemical stability at subzero temperatures. This work provides a simple, blueprint antifreezing design concept and a family of antifreezing hydrogels for the better understanding of the composite-structure-property relationship of antifreezing materials and the fundamentals of confined water in wet soft materials.

Progress in Tuning Emission of the Excited-State Intramolecular Proton Transfer (ESIPT)-Based Fluorescent Probes

Abstract: In this review, we will summarize our recent progress in the design and application of novel organic sensors with emission in the near-infrared region (600-900 nm). By coupling different functional groups with excited-state intramolecular proton transfer (ESIPT) segments, new probes are developed to achieve a large Stokes shift, high sensitivity, and selectivity and to tune the emission toward the near-infrared region. The developed probes exhibit attractive optical properties for bioimaging and environmental science applications. In addition, we further discuss the photophysical properties of ESIPT dyes and how their fluorescence could be affected by structural/environmental factors, which should be considered during the development of robust ESIPT-based fluorescence probes. Their potential applications as imaging reagents are illustrated for intracellular membranes, mitochondria, lysosomes, and some biomolecules.

Monitoring Depression Trends on Twitter During the COVID-19 Pandemic: Observational Study.

Abstract: Background: The COVID-19 pandemic has affected people’s daily lives and has caused economic loss worldwide. Anecdotal evidence suggests that the pandemic has increased depression levels among the population. However, systematic studies of depression detection and monitoring during the pandemic are lacking. Objective: This study aims to develop a method to create a large-scale depression user data set in an automatic fashion so that the method is scalable and can be adapted to future events; verify the effectiveness of transformer-based deep learning language models in identifying depression users from their everyday language; examine psychological text features’ importance when used in depression classification; and, finally, use the model for monitoring the fluctuation of depression levels of different groups as the disease propagates. Methods: To study this subject, we designed an effective regular expression-based search method and created the largest English Twitter depression data set containing 2575 distinct identified users with depression and their past tweets. To examine the effect of depression on people’s Twitter language, we trained three transformer-based depression classification models on the data set, evaluated their performance with progressively increased training sizes, and compared the model’s tweet chunk-level and user-level performances. Furthermore, inspired by psychological studies, we created a fusion classifier that combines deep learning model scores with psychological text features and users’ demographic information, and investigated these features’ relations to depression signals. Finally, we demonstrated our model’s capability of monitoring both group-level and population-level depression trends by presenting two of its applications during the COVID-19 pandemic. Results: Our fusion model demonstrated an accuracy of 78.9% on a test set containing 446 people, half of which were identified as having depression. Conscientiousness, neuroticism, appearance of first person pronouns, talking about biological processes such as eat and sleep, talking about power, and exhibiting sadness were shown to be important features in depression classification. Further, when used for monitoring the depression trend, our model showed that depressive users, in general, responded to the pandemic later than the control group based on their tweets (n=500). It was also shown that three US states—New York, California, and Florida—shared a similar depression trend as the whole US population (n=9050). When compared to New York and California, people in Florida demonstrated a substantially lower level of depression. Conclusions: This study proposes an efficient method that can be used to analyze the depression level of different groups of people on Twitter. We hope this study can raise awareness among researchers and the public of COVID-19’s impact on people’s mental health. The noninvasive monitoring system can also be readily adapted to other big events besides COVID-19 and can be useful during future outbreaks.

Symmetry-breaking design of an organic iron complex catholyte for a long cyclability aqueous organic redox flow battery

Abstract: The limited availability of a high-performance catholyte has hindered the development of aqueous organic redox flow batteries (AORFB) for large-scale energy storage. Here we report a symmetry-breaking design of iron complexes with 2,2′-bipyridine-4,4′-dicarboxylic (Dcbpy) acid and cyanide ligands. By introducing two ligands to the metal centre, the complex compounds (M4[FeII(Dcbpy)2(CN)2], M = Na, K) exhibited up to a 4.2 times higher solubility (1.22 M) than that of M4[FeII(Dcbpy)3] and a 50% increase in potential compared with that of ferrocyanide. The AORFBs with 0.1 M Na4[FeII(Dcbpy)2(CN)2] as the catholyte were demonstrated for 6,000 cycles with a capacity fading rate of 0.00158% per cycle (0.217% per day). Even at a concentration near the solubility limit (1 M Na4[FeII(Dcbpy)2(CN)2]), the flow battery exhibited a capacity fading rate of 0.008% per cycle (0.25% per day) in the first 400 cycles. The AORFB cell with a nearly 1:1 catholyte:anolyte electron ratio achieved a cell voltage of 1.2 V and an energy density of 12.5 Wh l–1. The development of aqueous organic redox flow batteries suffers from the limited availability of high-performance catholytes. Here the authors design a metal organic complex catholyte material with a tunable redox potential, which offers promise for high-energy long-lasting flow batteries.

Fused Filament Fabrication 4D Printing of a Highly Extensible, Self-Healing, Shape Memory Elastomer Based on Thermoplastic Polymer Blends.

Abstract: A polymer blend with high extensibility, exhibiting both shape memory and self-healing, was 4D printed using a low-cost fused filament fabrication (FFF, or fused deposition modeling, FDM) 3D printer. The material is composed of two commercially available commodity polymers, polycaprolactone (PCL), a semi-crystalline thermoplastic, and polystyrene-block-poly(ethylene-co-butylene)-block-polystyrene (SEBS), a thermoplastic elastomer. The shape memory and self-healing properties of the blends were studied systematically through thermo-mechanical and morphological characterization, providing insight into the shape memory mechanism useful for tuning the material properties. In 3D-printed articles, the orientation of the semi-crystalline and micro-phase-separated domains leads to improvement of the shape memory property and extensibility of this material compared to compression-molded samples. By controlling the orientation of the printed fibers, we achieved a high strain at break over 1200%, outperforming previously reported flexible 4D-printed materials. The self-healing agent, PCL, enables the material to heal scratches and cracks and adhere two surfaces after annealing at 80 °C for 30 min. The high performance, multi-functionality, and potential scalability make it a promising candidate for a broad spectrum of applications, including flexible electronics, soft actuators, and deployable devices.

Longitudinal Metabolomics of Human Plasma Reveals Prognostic Markers of COVID-19 Disease Severity.

Abstract: There is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we perform untargeted metabolomics on plasma from 339 patients, with samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we build a predictive model of disease severity. We discover that a panel of metabolites measured at the time of study entry successfully determine disease severity. Through analysis of longitudinal samples, we confirm that the majority of these markers are directly related to disease progression and that their levels return to baseline upon disease recovery. Finally, we validate that these metabolites are also altered in a hamster model of COVID-19.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.

Abstract: Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.

Prospective Statewide Study of Universal Screening for Hereditary Colorectal Cancer: The Ohio Colorectal Cancer Prevention Initiative.

Abstract: PURPOSEHereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement....

Design principles for creating synthetic underwater adhesives.

Abstract: Water and adhesives have a conflicting relationship as demonstrated by the failure of most man-made adhesives in underwater environments. However, living creatures routinely adhere to substrates underwater. For example, sandcastle worms create protective reefs underwater by secreting a cocktail of protein glue that binds mineral particles together, and mussels attach themselves to rocks near tide-swept sea shores using byssal threads formed from their extracellular secretions. Over the past few decades, the physicochemical examination of biological underwater adhesives has begun to decipher the mysteries behind underwater adhesion. These naturally occurring adhesives have inspired the creation of several synthetic materials that can stick underwater – a task that was once thought to be “impossible”. This review provides a comprehensive overview of the progress in the science of underwater adhesion over the past few decades. In this review, we introduce the basic thermodynamics processes and kinetic parameters involved in adhesion. Second, we describe the challenges brought by water when adhering underwater. Third, we explore the adhesive mechanisms showcased by mussels and sandcastle worms to overcome the challenges brought by water. We then present a detailed review of synthetic underwater adhesives that have been reported to date. Finally, we discuss some potential applications of underwater adhesives and the current challenges in the field by using a tandem analysis of the reported chemical structures and their adhesive strength. This review is aimed to inspire and facilitate the design of novel synthetic underwater adhesives, that will, in turn expand our understanding of the physical and chemical parameters that influence underwater adhesion.

Analysis of microstructure and mechanical properties of additive repaired Ti–6Al–4V by Direct Energy Deposition

Abstract: The recent advances in additive manufacturing have opened new possibilities in aerospace industry; ability to successfully repair turbine blades being one. Repair approaches with Direct Energy Deposition (DED) is one prospective method to overcome the drawback of Integrally Bladed Rotor (IBR/blisks) in its ability to repair damage; which would otherwise require full removal and either an expensive replacement or a complicated repair, for damage beyond a minor dent. In order to attend confidence in such repairs using Additive Manufacturing, the characterization of additively repaired specimen is necessary. Ti–6Al–4V specimens fabricated by DED using two different feedstocks (metal powder and wire) were investigated in this study. The test coupons consist of half-conventional and half additively manufactured (AM) material with a bond line at the center of the specimen gauge. The microstructural features (α lath thickness, colony size and prior β grain size), tensile properties in relation with the microstructural characteristics and fatigue behavior of the built samples were characterized and compared with the 100% stock annealed Ti–6Al–4V coupons. Subsequent analyses of the fracture surfaces were conducted using Scanning Electron Microscopy (SEM) for evaluation of the failure mechanism and the presence of process defects and their impact on overall fatigue performance. The mechanical properties of the DED repaired Ti–6Al–4V were found to be slightly lower than the stock material in this study but compared favorably to published results of annealed Ti–6Al–4V.

Research Published in Management International Review from 2006 to 2020: A Bibliometric Analysis and Future Directions.

Abstract: The Management International Review (MIR) celebrated its 60th anniversary in 2020. In commemoration of this event, we use a bibliometric analysis to present a retrospective on the journal by analyzing its content for the years between 2006 and 2020. We find that the collaboration culture in MIR has risen over time with the increase in the median size of author teams. Moreover, the collaboration network has become more global over time. The methodology used in the journal is predominantly empirical and quantitative with archival data sources most commonly used. The bibliographic coupling of the MIR corpus reveals that the major themes in the journal revolve around “culture,” “emerging economies,” “innovation, knowledge transfer, and absorptive capacity,” “internationalization process,” “culture and entry modes,” and “internationalization and performance.” A comparison with other leading international business journals provides distinct pathways in which MIR may continue to grow. Finally, it is important to note that while the share of conceptual studies has decreased significantly in the last 15 years, the MIR editors want to see more novel and theoretically grounded conceptual articles in the journal.

Mussel-Inspired Surface Immobilization of Heparin on Magnetic Nanoparticles for Enhanced Wound Repair via Sustained Release of a Growth Factor and M2 Macrophage Polarization.

Abstract: Efficient reconstruction of a fully functional skin after wounds requires multiple functionalities of wound dressing due to the complexity of healing. In these regards, topical administration of functionalized nanoparticles capable of sustainably releasing bioactive agents to the wound site may significantly accelerate wound repair. Among the various nanoparticles, superparamagnetic iron oxide (Fe3O4) nanoparticles gain increasing attractiveness due to their intrinsic response to an external magnetic field (eMF). Herein, based on the Fe3O4 nanoparticle, we developed a fibroblast growth factor (bFGF)-loaded Fe3O4 nanoparticle using a simple mussel-inspired surface immobilization method. This nanoparticle, named as bFGF-HDC@Fe3O4, could stabilize bFGF in various conditions and exhibited sustained release of bFGF. In addition, an in vitro study discovered that bFGF-HDC@Fe3O4 could promote macrophage polarization toward an anti-inflammatory (pro-healing) M2 phenotype especially under eMF. Further, in vivo full-thickness wound animal models demonstrated that bFGF-HDC@Fe3O4 could significantly accelerate wound healing through M2 macrophage polarization and increased cell proliferation. Therefore, this approach of realizing sustained the release of the growth factor with magnetically macrophage regulating behavior through modification of Fe3O4 nanoparticles offers promising potential to tissue-regenerative applications.