Machine learning supported single-stranded DNA sensor array for multiple foodborne pathogenic and spoilage bacteria identification in milk.

Ensuring food safety through rapid and accurate detection of pathogenic bacteria in food products is a critical challenge in the food supply chain. In this study, a non-specific optical sensor array was proposed for the identification of multiple pathogenic bacteria in contaminated milk samples. Fluorescence-labeled single-stranded DNA was efficiently quenched by two-dimensional nanoparticles and subsequently recovered by foreign biomolecules. The recovered fluorescence generated a unique fingerprint for each bacterial species, enabling the sensor array to identify eight bacteria (pathogenic and spoilage) within a few hours. Four traditional machine learning models and two artificial neural networks were applied for classification. The neural network showed a 93.8 % accuracy with a 30-min incubation. Extending the incubation to 120 min increased the accuracy of the multiplayer perceptron to 98.4 %. This sensor array is a novel, low-cost, and high-accuracy approach for the identification of multiple bacteria, providing an alternative to plate counting and ELISA methods.

A 32-channel high-impedance honeycomb-shaped receive array for temporal lobes exploration at 11.7T.

PURPOSE: The newly operational 11.7T Iseult scanner provides an improved global SNR in the human brain. This gain in SNR can be pushed even further locally by designing region-focused dense receive arrays. The temporal lobes are particularly interesting to neuroscientists as they are associated with language and concept recognition. Our main goal was to maximize the SNR in the temporal lobes and provide high-acceleration capabilities for fMRI studies. METHODS: We designed and developed a 32-channel receive array made of non-overlapped hexagonal loops. The loops were arranged in a honeycomb pattern and targeted the temporal lobes. They were placed on a flexible neoprene cap closely fitting the head. A new stripline design with a high impedance was proposed and applied for the first time at 11.7T. Specific homebuilt miniaturized low-impedance preamplifiers were directly mounted on the loops, providing preamplifier decoupling in a compact and modular design. Using an anatomical phantom, we experimentally compared the SNR and parallel imaging performance of the region-focused cap to a 32-channel whole-brain receive array at 11.7T. RESULTS: The experimental results showed a 1.7-time higher SNR on average in the temporal lobes compared to the whole brain receive array. The g-factor is also improved when undersampling in the antero-posterior and head-foot directions. CONCLUSION: A significant SNR boost in the temporal lobes was demonstrated at 11.7T compared to the whole-brain receive array. The parallel imaging capabilities were also improved in the temporal lobes in some acceleration directions.

Thiol-functionalized MOF modified 3D printed monolithic microextraction array for analysis of trace Cd and Pb in human urine.

Controlling the position, size, and shape of pores is a limitation of traditional monolithic preparation methods. The application of 3D printing technology offers high customizability, allowing the precise printing of pore positions, sizes, and shapes according to the designer's 3D model. Herein, by using Projection Microstereolithography (PµSL), we prepared a 3D-printed monolithic array with post-modification of thiol-functionalized metal-organic framework (MOF), and combined it with inductively coupled plasma mass spectrometry (ICP-MS) for the online analysis of trace Cd and Pb in human urine. To achieve array monolithic microextraction, six 3D-printed monolithic columns were modified with thiol-functionalized MOF-808 (MOF-808-SH), and were then assembled in the 3D printed extraction device incorporating gas valve and scaffold. The MOF-808-SH modified 3D-printed monolithic column exhibits excellent extraction performance to Cd2+ and Pb2+ due to rich active adsorption sites and hierarchical porous structure, and has long life span (>100 reused times). Under the optimized conditions, the limits of detection (LODs) are 3.5 and 17.6 ng L-1 for Cd2+ and Pb2+, respectively, with the relative standard deviations of 4.9 % and 8.2 % (0.1 µg L-1, n = 7), and the sample throughput is 11 h-1. To validate the accuracy of the method, the method was used to determine Cd and Pb in Certified Reference Materials of freeze-dried human urine, the determined results agree well with the certified values. This method was also successfully applied to the determination of trace Cd and Pb in real human urine samples. The developed method offers low LODs, robust anti-interference capability, high sample throughput, long reuse cycles, and automation analysis, showing great potential for the analysis of trace heavy metals in biological samples.

Single Nucleotide Polymorphism array analysis for fetuses from balanced translocation carriers at the second trimester.

Prenatal diagnosis is crucial for pregnancies from couples with a carrier of a balanced translocation. We retrospectively reviewed 195 pregnancies from 189 couples with a balanced translocation carrier. Of these, 126 were from natural conception, while 69 were conceived through assisted reproductive technology (ART) with preimplantation genetic diagnosis (PGD). Both single nucleotide polymorphism (SNP) array analysis and conventional karyotyping were conducted on all pregnancies, and karyotype-visible imbalances and pathogenic/likely pathogenic copy number variations (CNVs) were categorized as clinically significant abnormalities. In natural conception group, couples with a female carrier experiencing more than two miscarriages accounted for 30.2 %, significantly higher than the 14.0 % in male carrier couples (p < 0.05). In the PGD group, similar difference was observed between female and male carrier couples (p < 0.05). In the natural pregnancies, SNP array analysis yielded additional 12 cases of CNVs, including two cases of pathogenic (P)/likely pathogenic (LP) aberrations, four variants with uncertain significance (VUS), and six likely benign variants. Only two CNVs were found to be associated with translocation breakpoints, which were finally confirmed to be of parental inheritance. In the PGD pregnancies, two cases of VUS unrelated to the translocation breakpoints were revealed. Taken together, repeated miscarriage was more frequently observed in couples where the carrier was female than male. Conventional SNP array analysis in prenatal diagnosis indicated insufficient evidence to support the notion that balanced translocations increase the likelihood of fetuses having clinically significant CNVs.

A novel ratiometric fluorescent sensor array based on the copper clusters hydrogels coupling of DNA.

Hydrogels with DNA possess flexible and designable 3D cross-linked polymer networks, which generate numerous specific stimulus-response characteristics through reasonable design for the potential sensor array applications. Unfortunately, the complementary fragments of specific nucleotide sequences that form cross-links in the hydrogels with DNA often come across these problems of instability and high-cost, leading to a serious impediment to further application. Herein, we construct a novel ratiometric fluorescence sensor array to discriminate and quantify metal ions based on the hydrogels with DNA. The dual-emission hydrogels with DNA were synthesized by the self-assembly reaction of agarose, low-cost nonspecific sequence double-stranded DNA, and optically active copper nanoclusters (Cu NCs) with aggregation-induced emission (AIE) effect. Interestingly, different metal ions could precisely regulate the skeleton network of the hydrogels with DNA, leading to the change of their skeleton network and thus showing the distinguishing FL responses of the hydrogels with DNA. As a proof-of-concept demonstration, the ratiometric fluorescence sensor array was used to discriminate four metal ions (Pb2+, Co2+, Ni2+, and Cr(VI)) at multiple concentrations and metal ion mixtures. It exhibited a good linearity in quantitative analysis and reproducibility. Such a simple and high-sensitivity sensor array has been successfully applied to the high-through discrimination of toxic metal ions in environmental and serum samples.

A semiconducting supramolecular Co(II)-metallogel based resistive random access memory (RRAM) design with good endurance capabilities.

A highly efficient approach for synthesizing a supramolecular metallogel of Co(II) ions, denoted as CoA-TA, has been established under room temperature and atmospheric pressure conditions. This method employs the metal-coordinating organic ligand benzene-1,3,5-tricarboxylic acid as a low molecular weight gelator (LMWG) in DMF solvent. A comprehensive analysis of the mechanical properties of the resulting supramolecular Co(II)-metallogel was conducted through rheological investigation, considering angular frequency and thixotropic study. The hierarchical rocky network structure of the supramolecular Co(II)-metallogel was unveiled using field emission scanning electron microscopy (FESEM). Transmission electron microscopic (TEM) analysis showed rod-shaped structures via low-magnification high angle annular dark field (HAADF) bright field scanning transmission electron microscopic (STEM) imaging, while energy dispersive X-ray (EDX) elemental mapping confirmed its primary chemical constituents. The formation mechanism of the metallogel was examined via fourier transform infrared spectroscopy (FTIR) spectroscopy. The nature of the synthesized CoA-TA metallogel was affirmed through powder X-ray diffraction (PXRD) analysis. Furthermore, this study involved fabrication of Schottky diode structures in a metal-semiconductor-metal geometry based on cobalt(II) metallogel (CoA-TA), enabling observation of charge transport behavior. Remarkably, a resistive random access memory (RRAM) device utilizing cobalt(II) metallohydrogel (CoA-TA) demonstrated bipolar resistive switching at room temperature and under ambient conditions. The switching mechanism was investigated, revealing the formation and rupture of conductive filaments between metal electrodes that govern the resistive switching behavior. This RRAM device exhibited an impressive ON/OFF ratio (~ 414) and exceptional endurance over 5000 switching cycles. These structures offer great potential for diverse applications such as non-volatile memory design, neuromorphic computing, flexible electronics and optoelectronics. Their advantages lie in their fabrication process, reliable resistive switching behavior and overall performance stability.

A dual-band high-gain beam steering antenna array for 5G sub-6 GHz base station.

An antenna array having a size of 45 [Formula: see text] 40 cm2 (5.7 [Formula: see text] 5 [Formula: see text]2) and consisting of four pairs of printed U-shaped dipoles positioned above a metal reflector, for 5G Sub-6 GHz base station applications, is designed and tested. The array consists of eight excitation ports, one port for each dipole. Four parasitic square patches are etched on the bottom side of the dipole arms for producing radiations in 2.2 GHz and 3.8 GHz bands. The size of the reflector and height of the dipoles are optimized in order to enhance antenna gain up to 11.5 dB at 2.2 GHz and 14.5 dB at 3.8 GHz. Beam steering up to 20[Formula: see text] is achieved, using phase shifted simultaneous excitation of different ports. The proposed antenna array not only fulfills 5G base station requirements but is also simple and compact as it only requires eight ports to achieve dual-band, high-gain and beam steering operation in a single design. It also offers a unique feature of dual-sector coverage per panel, which results in an increased coverage capacity of the base station without increasing the system resources.

Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. METHODS: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP). RESULTS: Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression. CONCLUSIONS: Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

Detection of regions of homozygosity in an unusual case of frontonasal dysplasia.

We present the case of a 7-year-old Ecuadorian mestizo girl with multiple orofacial malformations. The patient is the product of a first-degree relationship (father-daughter). A cytogenetic study revealed a normal karyotype. The genetic mapping array study identified 0.73 Gb of alterations, 727,087,295 bp involved in regions of homozygosity (ROH) in all chromosomes (25.2% of the genome) and 764,028 bp in gains in chromosomes 9 and 14. Genes from the TGFB, BMP, FGF, SHH and WNT families, among others, were identified in the ROH. They are related to craniofacial development and their protein products showed a strong association in the interactome analysis.

Fundamental effects of array density and modulation frequency on image quality of diffuse optical tomography.

BACKGROUND: Diffuse optical tomography (DOT) provides three-dimensional image reconstruction of chromophore perturbations within a turbid volume. Two leading strategies to optimize DOT image quality include, (i) arrays of regular, interlacing, high-density (HD) grids of sources and detectors with closest spacing less than 15 mm, or (ii) source modulated light of order ∼100 MHz. PURPOSE: However, the general principles for how these crucial design parameters of array density and modulation frequency may interact to provide an optimal system design have yet to be elucidated. METHODS: Herein, we systematically evaluated how these design parameters effect image quality via multiple key metrics. Specifically, we simulated 32 system designs with realistic measurement noise and quantified localization error, spatial resolution, signal-to-noise, and localization depth of field for each of ∼85 000 point spread functions in each model. RESULTS: We found that array density had a far stronger effect on image quality metrics than modulation frequency. Additionally, model fits for image quality metrics revealed that potential improvements diminish with regular arrays denser than 9 mm closest spacing. Further, for a given array density, 300 MHz source modulation provided the deepest reliable imaging compared to other frequencies. CONCLUSIONS: Our results indicate that both array density and modulation frequency affect the spatial sampling of tissue, which asymptotically saturates due to photon diffusivity within a turbid volume. In summary, our results provide comprehensive perspectives for optimizing future DOT system designs in applications from wearable functional brain imaging to breast tumor detection.

Profiling Phenotypic Heterogeneity of Circulating Tumor Cells through Spatially Resolved Immunocapture on Nanoporous Micropillar Arrays.

The phenotype of circulating tumor cells (CTCs) offers valuable insights into monitoring cancer metastasis and recurrence. While microfluidics presents a promising approach for capturing these rare cells in blood, the phenotypic profiling of CTCs remains technically challenging. Herein, we developed a nanoporous micropillar array chip enabling highly efficient capture and in situ phenotypic analysis of CTCs through enhanced and tunable on-chip immunoaffinity binding. The nanoporous micropillar array addresses the fundamental limits in fluidic mass transfer, surface stagnant flow boundary effect, and interface topographic and multivalent reactions simultaneously within a single device, resulting in a synergistic enhancement of CTC immunocapture efficiency. The CTC capture efficiency increased by approximately 40% for cancer cells with low surface marker expressing. By manipulating fluidic velocity (hydrodynamic drag force) on the chip, a cell adhesion gradient was generated in the capture chamber, enabling individual CTCs with varying expression levels of epithelial cellular adhesion molecules to be immunocaptured at the corresponding spatial locations where equilibrium drag force is provided. The clinical utility of the nanoporous micropillar array was demonstrated by accurately distinguishing early and advanced stages of breast cancer and further longitudinally monitoring treatment response. We envision that the nanoporous micropillar array chip will provide an in situ capture and molecular profiling approach for CTCs and enhance the clinical application of CTC liquid biopsy.

The liquid lectin array detects compositional glycocalyx differences using multivalent DNA-encoded lectins on phage.

Selective detection of disease-associated changes in the glycocalyx is an emerging field in modern targeted therapies. Detecting minor glycan changes on the cell surface is a challenge exacerbated by the lack of correspondence between cellular DNA/RNA and glycan structures. We demonstrate that multivalent displays of lectins on DNA-barcoded phages-liquid lectin array (LiLA)-detect subtle differences in density of glycans on cells. LiLA constructs displaying 73 copies of diCBM40 (CBM) lectin per virion (φ-CBM73) exhibit non-linear ON/OFF-like recognition of sialoglycans on the surface of normal and cancer cells. A high-valency φ-CBM290 display, or soluble CBM protein, cannot amplify the subtle differences detected by φ-CBM73. Similarly, multivalent displays of CBM and Siglec-7 detect differences in the glycocalyx between stem-like and non-stem populations in cancer. Multivalent display of lectins offer in situ detection of minor differences in glycocalyx in cells both in vitro and in vivo not feasible to currently available technologies.

Analysis of mitochondrial biogenesis and protein localization by genetic screens and automated imaging.

Budding yeast is a laboratory model of a simple eukaryotic cell. Its compact genome is very easy to edit. This allowed to create systematic collections (libraries) of yeast strains where every gene is either perturbed or tagged. Here we review how such collections were used to study mitochondrial biology by doing genetic screens. First, we introduce the principles of yeast genome editing and the basics of its life cycle that are useful for genetic experiments. Then we overview what yeast strain collections were created over the past years. We also describe the creation and the usage of the new generation of SWAP-Tag (SWAT) collections that allow to create custom libraries. We outline the principles of changing the genetic background of whole collections in parallel, and the basics of synthetic genetic array (SGA) approach. Then we review the discoveries that were made using different types of genetic screens focusing on general mitochondrial functions, proteome, and protein targeting pathways. The development of new collections and screening techniques will continue to bring valuable insight into the function of mitochondria and other organelles.

CACNA1A haploinsufficiency leads to reduced synaptic function and increased intrinsic excitability.

Haploinsufficiency of the CACNA1A gene, encoding the pore-forming α1 subunit of P/Q-type voltage-gated calcium channels, is associated with a clinically variable phenotype ranging from cerebellar ataxia, to neurodevelopmental syndromes with epilepsy and intellectual disability. To understand the pathological mechanisms of CACNA1A loss-of-function variants, we characterized a human neuronal model for CACNA1A haploinsufficiency, by differentiating isogenic induced pluripotent stem cell lines into glutamatergic neurons, and investigated the effect of CACNA1A haploinsufficiency on mature neuronal networks through a combination of electrophysiology, gene expression analysis, and in silico modeling. We observed an altered network synchronization in CACNA1A+/- networks alongside synaptic deficits, notably marked by an augmented contribution of GluA2-lacking AMPA receptors. Intriguingly, these synaptic perturbations coexisted with increased non-synaptically driven activity, as characterized by inhibition of NMDA and AMPA receptors on micro-electrode arrays. Single-cell electrophysiology and gene expression analysis corroborated this increased intrinsic excitability through reduced potassium channel function and expression. Moreover, we observed partial mitigation of the CACNA1A+/- network phenotype by 4-aminopyridine, a therapeutic intervention for episodic ataxia type 2. Positive modulation of KCa2 channels could reverse the CACNA1A+/- network electrophysiological phenotype. In summary, our study pioneers the characterization of a human induced pluripotent stem cell-derived neuronal model for CACNA1A haploinsufficiency, and has unveiled novel mechanistic insights. Beyond showcasing synaptic deficits, this neuronal model exhibited increased intrinsic excitability mediated by diminished potassium channel function, underscoring its potential as a therapeutic discovery platform with predictive validity.

Portable alkaloid discrimination via nanozyme-mediated colorimetric paper-based sensor array integrated with smartphone detection.

A paper-based colorimetric sensor array mediated by a novel nanozyme (CuCo2O4) was developed using a screen-printing technology. The aim was to facilitate the identification of different kinds of alkaloids. Typically, three chromogenic substrates (3,3',5,5'-tetramethylbenzidine, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and o-phenylenediamine) were selected as sensing elements, which can be catalyzed by a CuCo2O4 nanozyme with peroxidase-like activity to yield corresponding oxidized products, thereby inducing color changes. Owing to the varying inhibitory ability of different alkaloids on acetylcholinesterase (AChE), a decrease in choline (Ch) concentration occurs and subsequently results in the restoration of color within the units of sensor array. Color data can be transformed into hue information with a smartphone. The above color variations generated a unique "fingerprint" pattern on five alkaloids (berberine, palmatine, jatrorrhizine, eserine, and harmane), which can be successfully discriminated through linear discriminant analysis in the range 0.2 to 20 µM. Furthermore, the sensor arrays allowed successful discrimination of the above five alkaloids in Chinese herbal medicine samples and recognition of 22 blind samples. This work presents a novel nanozyme-based paper sensor array, which is a user-friendly and reliable platform for probing different alkaloids. In addition, the developed sensing strategy enables the identification of AChE-related diseases, positively contributing to the screening available of AD-associated drugs.

Advancing equine genomics: the development of a high density Axiom_Ashwa SNP chip for Indian horses and ponies.

The unique horse and pony breeds of India are declining at an alarming rate. These horses have been integral to the Indian culture and customs for centuries and represent a valuable genetic resource. It is imperative to harness the potential of this equine genetic resource that urgently needs conservation. The study highlights the design and development of a high density SNP array, the Axiom_Ashwa to aid in the genetic analysis and conservation efforts for Indian horse and pony breeds. With 613,950 SNPs, this chip offers extensive genome coverage having an average inter-marker distance of 4 kb. The Axiom_Ashwa has been validated on a larger set of diverse indigenous samples as well as Thoroughbreds, demonstrating a high call rate of 99.4% and robustness for genotyping indigenous breeds. Linkage disequilibrium (LD) analysis showed higher average LD in Indian breeds compared to exotic breeds, suggesting a limited effective population size and recent bottlenecks. Phylogenetic and population stratification analyses using PCA and DAPC clearly distinguished horses, ponies and Thoroughbreds, confirming the efficacy of the Axiom_Ashwa chip. These findings underscore the urgent need for conservation efforts for Indian horse breeds, which have experienced significant drop in population size. The Axiom_Ashwa SNP chip offers advantages such as cost-effectiveness and high throughput, providing a more accurate genetic representation of Indian horses.

Identification of genetic loci for powdery mildew resistance in common wheat.

Powdery mildew (PM) poses an extreme threat to wheat yields and quality. In this study, 262 recombinant inbred lines (RILs) of Doumai and Shi 4185 cross were used to map PM resistance genes across four environments. High-density genetic linkage map of the Doumai/Shi 4185 RIL population was constructed using the wheat Illumina iSelect 90K single-nucleotide polymorphism (SNP) array. In total, four stable quantitative trait loci (QTLs) for PM resistance, QPm.caas-2AS, QPm.caas-4AS, QPm.caas-4BL, and QPm.caas-6BS, were detected and explained 5.6%-15.6% of the phenotypic variances. Doumai contributed all the resistance alleles of QPm.caas-2AS, QPm.caas-4AS, QPm.caas-4BL, and QPm.caas-6BS. Among these, QPm.caas-4AS and QPm.caas-6BS overlapped with the previously reported loci, whereas QPm.caas-2AS and QPm.caas-4BL are potentially novel. In addition, six high-confidence genes encoding the NBS-LRR-like resistance protein, disease resistance protein family, and calcium/calmodulin-dependent serine/threonine-kinase were selected as the candidate genes for PM resistance. Three kompetitive allele-specific PCR (KASP) markers, Kasp_PMR_2AS for QPm.caas-2AS, Kasp_PMR_4BL for QPm.caas-4BL, and Kasp_PMR_6BS for QPm.caas-6BS, were developed, and their genetic effects were validated in a natural population including 100 cultivars. These findings will offer valuable QTLs and available KASP markers to enhance wheat marker-assisted breeding for PM resistance.

Development of 3D printed microneedles of varied needle geometries and lengths, designed to improve the dermal delivery of topically applied psoriasis treatments.

The aim of this study was to investigate the impact of using microneedle patches in addition to topical therapy for the treatment of psoriasis. Using continuous liquid interface production (CLIP) 3D printing we manufactured round microneedle array patches (MAPs) with a diameter of 14 mm. Needle geometries were varied from square pyramidal, conical, and obelisk, with varied needle lengths of 400 µm, 600 µm, 800 µm, or 1000 µm. MAPs were characterized for force to fracture, skin penetration, skin damage, as well as their ability to deliver a novel oleogel-based corticosteroid (betamethasone dipropionate (BDP) formulation into ex-vivo porcine skin. We found that the obelisk shaped MAPs are more durable compared to the conical and square pyramidal-shaped MAPs. When the obelisk shaped MAPs were used in combination with the oleogel-based BDP formulation, the amount of BDP penetrating the skin was significantly increased with greater needle lengths.

Limited Biomarker Potential for IgG Autoantibodies Reactive to Linear Epitopes in Systemic Lupus Erythematosus or Spondyloarthropathy.

BACKGROUND: Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong biomarkers may not exist in these conditions, another possibility is that technology has limited their discovery. The purpose of this study was to use a novel high-density peptide array that enables the evaluation of IgG binding to every possible linear antigen in the entire human peptidome, as well as a novel machine learning approach that incorporates ELISA validation predictability in order to discover autoantibodies that could be developed into sensitive and specific markers of lupus or spondyloarthropathy. METHODS: We used a peptide array containing the human peptidome, several viral peptidomes, and key post-translational modifications (6 million peptides) to quantify IgG binding in lupus, spondyloarthropathy, rheumatoid arthritis, Sjögren's disease, and control sera. Using ELISA data for 70 peptides, we performed a random forest analysis that evaluated multiple array features to predict which peptides might be good biomarkers, as confirmed by ELISA. We validated the peptide prediction methodology in rheumatoid arthritis and COVID-19, conditions for which the antibody repertoire is well-understood, and then evaluated IgG binding by ELISA to peptides that we predicted would be highly bound specifically in lupus or spondyloarthropathy. RESULTS: Our methodology performed well in validation studies, but peptides predicted to be highly and specifically bound in lupus or spondyloarthropathy could not be confirmed by ELISA. CONCLUSIONS: In a comprehensive evaluation of the entire human peptidome, highly sensitive and specific IgG autoantibodies were not identified in lupus or spondyloarthropathy. Thus, the pathogenesis of lupus and spondyloarthropathy may not depend upon unique autoantigens, and other types of molecules should be sought as optimal biomarkers in these conditions.

Assessment of functional performance in self-rectifying passive crossbar arrays utilizing sneak path current.

Self-rectifying memristive devices have emerged as promising contenders for low-power in-memory computing, presenting numerous advantages. However, characterizing the functional behavior of passive crossbar arrays incorporating these devices remains challenging due to sophisticated parasitic currents stemming from rich memristive dynamic behavior. Conventional methods using read margin assessments to evaluate functional behavior in passive crossbars are hindered by the voltage divider effect from the pull-up resistor. In this study, we propose a novel performance metric, Δ SC, harnessing sneak path currents to assess functional behavior. Through the application of a pair of negative rectification factors, RF n, L and RF n, H , we comprehensively delineate dynamic rectification behavior in both positive and negative bias regimes, as well as in low-resistance state and high-resistance state, deviating from conventional metrics such as on/off ratios, nonlinearity, and rectifying factors. Notably, Δ SC provides a quantitative evaluation of the interaction between sneak path currents and read margin, demonstrating its efficacy and addressing a pivotal research gap in the field. For instance, employing self-rectifying BiFeO 3 memristive cells featuring RF n, L = 1.22E3 and RF n, H = 9.27, we showcase the successful functional performance of a passive crossbar array, achieving Δ SC < 2.19E-2, while ensuring a read margin > 0.