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A scalable synthesis of magnesium ion imprinted nitrogen-doped carbon allows for facile preparation of large quantities of Fe–N–C, for large-scale fuel cell research.

Emotion recognition, or the ability of computers to interpret people’s emotional states, is a very active research area with vast applications to improve people’s lives. However, most image-based emotion recognition techniques are flawed, as humans can intentionally hide their emotions by changing facial expressions. Consequently, brain signals are being used to detect human emotions with improved accuracy, but most proposed systems demonstrate poor performance as EEG signals are difficult to classify using standard machine learning and deep learning techniques. This paper proposes two convolutional neural network (CNN) models (M1: heavily parameterized CNN model and M2: lightly parameterized CNN model) coupled with elegant feature extraction methods for effective recognition. In this study, the most popular EEG benchmark dataset, the DEAP, is utilized with two of its labels, valence, and arousal, for binary classification. We use Fast Fourier Transformation to extract the frequency domain features, convolutional layers for deep features, and complementary features to represent the dataset. The M1 and M2 CNN models achieve nearly perfect accuracy of 99.89% and 99.22%, respectively, which outperform every previous state-of-the-art model. We empirically demonstrate that the M2 model requires only 2 seconds of EEG signal for 99.22% accuracy, and it can achieve over 96% accuracy with only 125 milliseconds of EEG data for valence classification. Moreover, the proposed M2 model achieves 96.8% accuracy on valence using only 10% of the training dataset, demonstrating our proposed system’s effectiveness. Documented implementation codes for every experiment are published for reproducibility. Published version

Amyloidosis of human islet amyloid polypeptide (hIAPP) is a pathological hallmark of type II diabetes (T2D), an epidemic afflicting nearly 10% of the world’s population. To visualize disease-relevant hIAPP fibrils, we extracted amyloid fibrils from islet cells of a T2D donor and amplified their quantity by seeding synthetic hIAPP. Cryo-EM studies revealed four fibril polymorphic atomic structures. Their resemblance to four unseeded hIAPP fibrils varies from nearly identical (TW3) to non-existent (TW2). The diverse repertoire of hIAPP polymorphs appears to arise from three distinct protofilament cores entwined in different combinations. The structural distinctiveness of TW1, TW2 and TW4 suggests they may be faithful replications of the pathogenic seeds. If so, the structures determined here provide the most direct view yet of hIAPP amyloid fibrils formed during T2D. Human islet amyloid polypeptide (hIAPP) is a protein commonly forming aggregates in islet cells of those afflicted by type II diabetes. New structures of fibrils seeded with patient-derived material reveal a diverse repertoire of structures, some of which may resemble those appearing in vivo.

The rippled β-sheet is a peptidic structural motif related to but distinct from the pleated β-sheet. Both motifs were predicted in the 1950s by Pauling and Corey. The pleated β-sheet was since observed in countless proteins and peptides and is considered common textbook knowledge. Conversely, the rippled β-sheet only gained a meaningful experimental foundation in the past decade, and the first crystal structural study of rippled β-sheets was published as recently as this year. Noteworthy, the crystallized assembly stopped at the rippled β-dimer stage. It did not form the extended, periodic rippled β-sheet layer topography hypothesized by Pauling and Corey, thus calling the validity of their prediction into question. NMR work conducted since moreover shows that certain model peptides rather form pleated and not rippled β-sheets in solution. To determine whether the periodic rippled β-sheet layer configuration is viable, the field urgently needs crystal structures. Here we report on crystal structures of two racemic and one quasi-racemic aggregating peptide systems, all of which yield periodic rippled antiparallel β-sheet layers that are in excellent agreement with the predictions by Pauling and Corey. Our study establishes the rippled β-sheet layer configuration as a motif with general features and opens the road to structure-based design of unique supramolecular architectures.

The naturally occurring flavonoid (–)-epigallocatechin gallate (EGCG) is a potent disaggregant of tau fibrils. Guided by the recent cryo-electron microscopy (cryoEM) structure of EGCG bound to fibrils of tau derived from an Alzheimer’s brain donor, methods to site-specifically modify the EGCG D-ring with aminoPEGylated linkers are reported. The resultant molecules inhibit tau fibril seeding by Alzheimer’s brain extracts. Formulations of aminoPEGylated EGCG conjugated to the (quasi)-brain-penetrant nanoparticle Ferumoxytol inhibit seeding by AD-tau with linker length affecting activity. The protecting group-free catalytic cycloaddition of amino azides to mono-propargylated EGCG described here provides a blueprint for access to stable nanoparticulate forms of EGCG potentially useful as therapeutics to eliminate Alzheimer’s-related tau tangles.

Capacitive deionization (CDI) is a fast-emerging technology typically applied to brackish water desalination and ion-selective separations. In a typical cell, feedwater is desalinated via ion electrosorption into micropore electric double layers (EDLs) of charging porous carbon electrodes. Several studies have previously demonstrated that oxidizing the cathode via a nitric acid pretreatment enhances the cell’s salt adorption capacity (SAC). It was recently reported that oxidized cathodes can degrade rapidly during cell cycling, yet the mechanisms and mitigation strategies remain unknown. Here, we experimentally characterize the performance and degradation of nitric acid-oxidized commercial carbon cloth cathodes. For a full cycle time (FCT) of 100 min and 1 V applied, we observed a 42.5% reduction of SAC by the 100th cycle, and measured a reduction in cathode micropore chemical charge concentration at pH = 7 from −1.5 M to −0.25 M after cycling. We further found that cell charging time and electrode mass are major determinants of degradation rate, for example, reducing FCT to 30 min and 10 min allows for SAC decay of only ∼14% and

The deposition of amyloidogenic transthyretin (ATTR) in ATTR amyloidosis leads to an unexplained variety of clinical phenotypes, including cardiomyopathy. In brain amyloid conditions, there is an apparent association between the clinical phenotype and the amyloid fibril structure. Here, we question this phenotype-structure association in cardiac amyloidoses by determining the cryo-electron microscopy structures of fibrils extracted from the hearts of seven ATTR amyloidosis patients. We found that, in contrast to brain fibrils, cardiac ATTR fibrils display a structural polymorphism that is not genotype-specific, can co-exist within the same individual, and is independent of the cardiac phenotype. This polymorphism challenges the current paradigm of “one disease equals one fibril fold” proposed in tauopathies and synucleinopathies, and questions whether a similar structural heterogeneity occurs in other amyloidoses.One-Sentence SummaryUnlike brain amyloid fibrils, cardiac ATTR fibrils are polymorphic independent of genotype and even within the same patient.

Fe–N–C electrocatalysts hold a great promise for Pt-free energy conversion, driving the electrocatalysis of oxygen reduction and evolution, oxidation of nitrogen fuels, and reduction of N2, CO2, and NOx. Nevertheless, the catalytic role of iron carbide, a component of nearly every pyrolytic Fe–N–C material, is at the focus of a heated controversy. We now resolve the debate by examining a broad range of Fe3C sites, spanning across many typical size distributions and carbon environments. Removing Fe3C selectively by a non-oxidizing acid reveals its inactivity towards two representative reactions in alkaline media, oxygen reduction and hydrazine oxidation. The activity is assigned to other pre-existing sites, most probably Fe–Nx. DFT calculations prove that the Fe3C surface binds O and N intermediates too strongly to be catalytic. By settling the argument on the catalytic role of Fe3C in alkaline electrocatalysis, we hope to spur innovation in this critical field.

Long-range structures and dynamics are central to coordination chemistry, yet are hard to identify experimentally. By combining polarized low-frequency Raman spectroscopy with single crystal XRD to study barium nitrilotriacetate, a metal-organic coordination polymer and a useful pyrolysis precursor, we could assign Raman peaks experimentally to layer shear motions and perpendicular hydrogen bond vibrations. These directional long-range interactions further determined the preferred fracture directions during crystallization, establishing an important link between structural motifs in the precursor, and the porosity of the carbon it yields upon pyrolysis.

Background: Automated Insulin Delivery (AID) hybrid closed-loop systems have not been well studied in the context of prescribed meals. We evaluated performance of our interoperable artificial pancreas system (iAPS) in the at-home setting, running on an unlocked smartphone, with scheduled meal challenges in a randomized crossover trial. Methods: Ten adults with type 1 diabetes completed 2 weeks of AID-based control and 2 weeks of conventional therapy in random order where they consumed regular pasta or extra-long grain white rice as part of a complete dinner meal on six different occasions in both arms (each meal thrice in random order). Surveys assessed satisfaction with AID use. Results: Postprandial differences in conventional therapy were 10,919.0 mg/dL × min (95% confidence interval [CI] 3190.5–18,648.0, P = 0.009) for glucose area under the curve (AUC) and 40.9 mg/dL (95% CI 4.6–77.3, P = 0.03) for peak continuous glucose monitor glucose, with rice showing greater increases than pasta. White rice resulted in a lower estimate over pasta by a factor of 0.22 (95% CI 0.08–0.63, P = 0.004) for AUC under 70 mg/dL. These glycemic differences in both meal types were reduced under AID-based control and were not statistically significant, where 0–2 h insulin delivery decreased by 0.45 U for pasta (P = 0.001) and by 0.27 U for white rice (P = 0.01). Subjects reported high overall satisfaction with the iAPS. Conclusions: The AID system running on an unlocked smartphone improved postprandial glucose control over conventional therapy in the setting of challenging meals in the outpatient setting. Clinical Trial Registry: clinicaltrials.gov NCT03767790.

The urea oxidation reaction (UOR) is an important challenge in electrocatalysis, in the context of electrolyzers, fuel cells, medical sensing, and bio-waste treatment. The leading electrocatalysts for the UOR are nickel hydroxide surfaces, operating by the Botte mechanism: NiII(OH)2 is oxidized to NiIIIOOH, and the latter drives the UOR. However, these materials have several polymorphs, with α- and β-Ni(OH)2, and γ- and β-NiOOH, as described by the Bode diagram. We now report a systematic study of a series of nickel hydroxides, varying gradually from α-rich to β-rich materials. The crystallinity, order, hydration, intercalation, and morphology of these materials have been characterized by XRD, Raman, ATR-FTIR, XPS, and HRSEM and linked to their electrochemical activity. The disordered α phase was found to be superior to the β phase as a UOR electrocatalyst, with an oxidation onset potential of 0.31 V vs. SCE, better reversibility, and higher anodic current densities. Moreover, the perfect match in onset potentials between UOR electrocatalysis and the Ni2+/Ni3+ oxidation was observed for both phases, suggesting that the Botte mechanism is true for both the α-Ni(OH)2/γ-NiOOH couple and the β-Ni(OH)2/β-NiOOH couple. We further characterize the dynamic behavior of these materials (activation and aging), allowing us to propose a unified Botte-Bode diagram of UOR on Ni(OH)2/NiOOH.

Human islet amyloid polypeptide (hIAPP, or amylin) is a 37 amino acid hormone secreted by pancreatic islet β-cells. Aggregation of hIAPP into amyloid fibrils is found in more than 90% of Type-II Diabetes (T2D) patients and is considered to be associated with T2D pathology. Although different models have been proposed, the high resolution structure of hIAPP fibrils is unknown. Here we report the cryo-EM structure of recombinant full-length hIAPP fibrils. The fibril is composed of two symmetrically-related protofilaments with ordered residues 14-37 that meet at a 14-residue central hydrophobic core. Our hIAPP fibril structure (i) supports the previous hypothesis that residues 20-29, especially 23-29 are the primary amyloid core of hIAPP, (ii) suggests a molecular mechanism for the action of the hIAPP hereditary mutation S20G, (iii) explains why the 6 residue substitutions in rodent IAPP prevent aggregation, and (iv) suggests possible regions responsible for the observed hIAPP cross-seeding with β-amyloid. Furthermore, we performed structure-based inhibitor design to generate potential hIAPP aggregation inhibitors via a capping strategy. Four of the designed candidates delay hIAPP aggregation in vitro, providing a starting point for the development of T2D therapeutics and proof-of-concept that the capping strategy can be used on full-length cryo-EM fibril structures.

Carbons are ubiquitous electrocatalytic supports for various energy-related transformations, especially in fuel cells. Doped carbons such as Fe-N-C materials are particularly active towards the oxidation of hydrazine, an alternative fuel and hydrogen carrier. However, there is little discussion of the electrocatalytic role of the most abundant component - the carbon matrix - towards the hydrazine oxidation reaction (HzOR). We present a systematic investigation of undoped graphitic carbons towards the HzOR in alkaline electrolyte. Using highly oriented pyrolytic graphite electrodes, as well as graphite powders enriched in either basal planes or edge defects, we demonstrate that edge defects are the most active catalytic sites during hydrazine oxidation electrocatalysis. Theoretical DFT calculations support and explain the mechanism of HzOR on carbon edges, identifying unsaturated graphene armchair defects as the most likely active sites. Finally, these findings explain the 'double peak' voltammetric feature observed on many doped carbons during the HzOR.

The assembly of proteins into fibrillar amyloid structures was once considered to be pathologic and essentially irreversible. Recent studies reveal amyloid-like structures that form reversibly, derived from protein low-complexity domains which function in cellular metabolism. Here, by comparing atomic-level structures of reversible and irreversible amyloid fibrils, we find that the β-sheets of reversible fibrils are enriched in flattened (as opposed to pleated) β-sheets formed by stacking of extended β-strands. Quantum mechanical calculations show that glycine residues favor extended β-strands which may be stabilized by intraresidue interactions between the amide proton and the carbonyl oxygen, known as C5 hydrogen-bonds. Larger residue side chains favor shorter strands and pleated sheets. These findings highlight a structural element that may regulate reversible amyloid assembly.

Summary The hidden world of amyloid biology has suddenly snapped into atomic-level focus, revealing over 80 amyloid protein fibrils, both pathogenic and functional. Unlike globular proteins, amyloid proteins flatten and stack into unbranched fibrils. Stranger still, a single protein sequence can adopt wildly different two-dimensional conformations, yielding distinct fibril polymorphs. Thus, an amyloid protein may define distinct diseases depending on its conformation. At the heart of this conformational variability lies structural frustrations. In functional amyloids, evolution tunes frustration levels to achieve either stability or sensitivity according to the fibril’s biological function, accounting for the vast versatility of the amyloid fibril scaffold.

Self-templating of hierarchical porosity in carbon materials can be realized by the pyrolysis of well-designed metal–organic precursors. While this strategy is elegant and scalable, detailed mechanistic understanding of the self-templating process is lacking. We now report a systematic investigation of the microstructural evolution in porous carbons, including hierarchically micro-/meso-/macroporous materials with variable mesopore size. We focus on a homologous series of well-defined metal–organic coordination polymers, combining the highly abundant Group 2 ions (Mg2+, Ca2+, Sr2+, Ba2+) with a common ligand. To understand the role of the metal ion in directing the morphology of the ultimate N-doped carbons, we performed a detailed investigation using electron microscopy (HRSEM, HRTEM, EDS), N2 porosimetry, XRD, XPS and Raman spectroscopy. The rich morphological variations in the carbons determine their activity as metal-free electrocatalysts towards the oxygen reduction reaction. In particular, the reaction selectivity (2e−vs. 4e− pathways) is directed by competition between kinetics and mass transfer, due to confinement in mesopores.

Deposits of amyloid fibrils of α-synuclein are the histological hallmarks of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, with hereditary mutations in α-synuclein linked to the first two of these conditions. Seeing the changes to the structures of amyloid fibrils bearing these mutations may help to understand these diseases. To this end, we determined the cryo-EM structures of α-synuclein fibrils containing the H50Q hereditary mutation. We find that the H50Q mutation results in two previously unobserved polymorphs of α-synuclein: narrow and wide fibrils, formed from either one or two protofilaments, respectively. These structures recapitulate conserved features of the wild-type fold but reveal new structural elements, including a previously unobserved hydrogen-bond network and surprising new protofilament arrangements. The structures of the H50Q polymorphs help to rationalize the faster aggregation kinetics, higher seeding capacity in biosensor cells and greater cytotoxicity that we observe for H50Q compared to wild-type α-synuclein.

Enzymatic activity is crucial for various technological applications, yet the complex structures and limited stability of enzymes often hinder their use. Hence, de novo design of robust biocatalysts that are much simpler than their natural counterparts and possess enhanced catalytic activity has long been a goal in biotechnology. Here, we present evidence for the ability of a single amino acid to self-assemble into a potent and stable catalytic structural entity. Spontaneously, phenylalanine (F) molecules coordinate with zinc ions to form a robust, layered, supramolecular amyloid-like ordered architecture (F–Zn(ii)) and exhibit remarkable carbonic anhydrase-like catalytic activity. Notably, amongst the reported artificial biomolecular hydrolases, F–Zn(ii) displays the lowest molecular mass and highest catalytic efficiency, in addition to reusability, thermal stability, substrate specificity, stereoselectivity and rapid catalytic CO(2) hydration ability. Thus, this report provides a rational path towards future de novo design of minimalistic biocatalysts for biotechnological and industrial applications.

Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer’s disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20–34 fibril with and without the disease-associated PTM, L-isoaspartate, at position 23 (L-isoAsp23). Both wild-type and L-isoAsp23 protofilaments adopt β-helix-like folds with tightly packed cores, resembling the cores of full-length fibrillar Aβ structures, and both self-associate through two distinct interfaces. One of these is a unique Aβ interface strengthened by the isoaspartyl modification. Powder diffraction patterns suggest a similar structure may be adopted by protofilaments of an analogous segment containing the heritable Iowa mutation, Asp23Asn. Consistent with its early onset phenotype in patients, Asp23Asn accelerates aggregation of Aβ 20–34, as does the L-isoAsp23 modification. These structures suggest that the enhanced amyloidogenicity of the modified Aβ segments may also reduce the concentration required to achieve nucleation and therefore help spur the pathogenesis of AD., In patients with sporadic Alzheimer’s disease part of the Asp23 residues are isomerized to L-isoaspartate (L-isoAsp23). Here the authors present the MicroED structures of wild-type and L-isoAsp23 Aβ 20–34 amyloid fibrils that both form tightly packed cores and self-associate through two distinct interfaces with one of these interfaces being strengthened by the isoaspartyl modification.

Background: An effective proficiency testing program must utilize accurate splitting procedures to ensure that customers receive equivalent (by some measure) test items. When test items are not equivalent, it becomes impossible to separate variation among laboratories from variation among test items, and the program cannot achieve its objectives. Therefore, there is a critical need to validate the splitting process used to manufacture test items. Objective: The incorporation of MicrotracersTM was investigated for validating the splitting process used in the Association of American Feed Control Officials Proficiency Testing Program and as a potential quality control event for a production run. Methods: Microtracers were incorporated into six production runs. From each run, 12 test items were randomly selected for evaluation. Proficiency test materials were prepared from commercially available feedstuffs using base animal feeds and feed additives. The tracers were incorporated into base feed with other additives, recovered, and counted from the randomly selected test items. Results: Uniformity of test items was evaluated with the following two statistical methods: (1) relative standard deviation (RSD) of particle counts according to a Poisson distribution and (2) a Pearson’s Chi-square test. RSDs for counts (per mass basis) ranged from 2.49 to 4.13%, and Chi-square P values ranged from 0.0097 to 0.3740 over the six sets. Conclusions: Microtracers were determined to be a potential tool for validating the splitting process used to manufacture proficiency test items and a tool for incorporating quality control events into the manufacture of proficiency test items. Highlights: The authors offer suggestions for proficiency testing programs.

The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloid-driving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach. This work was supported by Amyloidosis Foundation Grant 20160759 and 20170827, National Institutes of Health Grant R01-AG048120, and The Howard Hughes Medical Institute. The authors and UCLA have filed an international patent application for the TTR inhibitors (number PCT/US17/40103). D. S. E. is an advisor and equity holder of ADRx, Inc. L. S. is a consultant of ADRx, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. info:eu-repo/semantics/publishedVersion

The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid–liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid–liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid–liquid phase separation, suggesting a therapeutic route for Covid-19.One Sentence SummaryAtomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics.

You have made, bought, or stolen a porous material, and now wish to use it for whichever application. But how can you really know what it is that you have in your hand? Answering this question is crucial, and far from trivial. To the naked eye, two white silica-alumina powders or two porous black carbons look exactly alike. Yet their properties, applications, and cost are determined by nano-scale differences. Characterization of porous materials is what this volume is all about. The four chapters cover the characterization of porous materials from all angles, and make this volume a treasure trove of knowledge, which will be used and prized by researchers in academia and industry for many years to come.

Energy is everywhere: the sun shines, the rivers flow, and the fossil fuels wait under our feet. The challenge lies in delivering this energy at the right time, place, and form. This is why energy storage and conversion are the focus of such huge scientific and technological research efforts. This volume explains the importance of porous materials in energy applications. Open any electrochemical energy power device, and you will find a porous electrode. Porous materials are central to energy conversion applications, giving a high specific surface area within a limited device volume. Yet pores can also slow down the electronic conductivity through the solid matrix, creating unique challenges (and opportunities!) for designing the flow of fuels, electrolytes, and gases. Overall, this volume provides an up-to-date overview of the field, with solid theoretical foundations and a strong focus on practical materials that will be useful for many people working on materials for energy applications.