We propose a thermally efficient and power-dense high-temperature superconducting (HTS) cable (CLEAN Cable) as well as a thermally efficient, mechanically rugged, and easily attachable/detachable cryogenic-to-ambient power link (CLEAN Connector). The bundled design enables high gravimetric power density and node-less tapping of power. The CLEAN Connector minimizes ambient heat leaking into the cryogenic environment by magnetically coupling the cryogenic section to the ambient counterpart via a high-frequency isolated DC/DC converter. The proposed high-frequency operation reduces the core size of the cryogenic/ambient transformer that provides electrical and thermal isolation while enabling quick connection. The proposed CLEAN technologies provide the following advantages – (1) Reduced heat load; (2) High gravimetric power density; (3) N –1 system redundancy; (4) Minimum ambient heat leak into the cryogenic system; (5) High vibration/mechanical stress tolerance; (6) Partial discharge (PD) free at high-altitudes; (7) Easy cryogenic and ambient system connection; (8) Inherent fault detection and isolation.
Identifying and characterizing the factors that affect presence in virtual environments has been acknowledged as a critical step to improving Virtual Reality (VR) applications in the built environment domain. In the search to identify those factors, the research objective was to test whether three-dimensional perception affects presence in virtual environments. A controlled within-group experiment utilizing perception and presence questionnaires was conducted, followed by data analysis, to test the hypothesized unidirectional association between three-dimensional perception and presence in two different virtual environments (non-immersive and immersive). Results indicate no association in either of the systems studied, contrary to the assumption of many scholars in the field but in line with recent studies on the topic. Consequently, VR applications in architectural design may not necessarily need to incorporate advanced stereoscopic visualization techniques to deliver highly immersive experiences, which may be achieved by addressing factors other than depth realism. As findings suggest that the levels of presence experienced by users are not subject to the display mode of a 3D model (whether immersive or non-immersive display), it may still be possible for professionals involved in the review of 3D models (e.g., designers, contractors, clients) to experience high levels of presence through non-stereoscopic VR systems provided that other presence-promoting factors are included.
The experiences associated with remembering, including metamemory feelings about the act of remembering and attempts at remembering, are not often integrated into general accounts of memory. For example, David Rubin (2022) proposes a unified, three-dimensional conceptual space for mapping memory states, a map that does not systematically specify metamemory feelings. Drawing on Rubin's model, we define a distinct role for metamemory in relation to first-order memory content. We propose a fourth dimension for the model and support the proposal with conceptual, neurocognitive, and clinical lines of reasoning. We use the modified model to illustrate several cases, and show how it helps to conceptualize a new category of memory state: autonoetic knowing, exemplified by déjà vu. We also caution not to assume that memory experience is directly correlated with or caused by memory content, an assumption Tulving (1989) labeled the doctrine of concordance.
Artificial intelligence (AI) and a popular branch of AI known as machine learning (ML) are increasingly being utilized in medicine and to inform medical research. This review provides an overview of AI and ML (AI/ML), including definitions of common terms. We discuss the history of AI and provide instances of how AI/ML can be applied to pediatric neurology. Examples include imaging in neuro-oncology, autism diagnosis, diagnosis from charts, epilepsy, cerebral palsy, and neonatal neurology. Topics such as supervised learning, unsupervised learning, and reinforcement learning are discussed.
Knowledge on the composition and characteristics of dissolved organic matter (DOM) in complex shale gas wastewater (SGW) is critical to evaluate environmental risks and to determine effective management strategies. Herein, five SGW samples from four key shale gas blocks in the Sichuan Basin, China, were comprehensively characterized. Specifically, FT-ICR MS was employed to provide insights into the sources, composition, and characteristics of SGW DOM. Organic matter was characterized by low average molecular weight, high saturation degree, and low aromaticity. Notably, the absence of correlations between molecular-level parameters and spectral indexes might be attributed to the high complexity and variability of SGW. The unique distribution depicted in van Krevelen diagrams suggested various sources of DOM in SGW, such as microbially derived organics in shales and biochemical transformations. Moreover, linear alkyl benzene sulfonates, as well as associated biodegraded metabolites and coproducts, were identified in SGW, implying the distinct anthropogenic imprints and abundant microbial activities. Furthermore, high DOC removal rates (31.42-79.23 %) were achieved by biological treatment, fully supporting the inherently labile nature of SGW and the feasibility of biodegradation for SGW management. Therefore, we conclude that DOM in SGW is a complex but mostly labile mixture reflecting both autochthonous and anthropogenic sources.
The objective of this paper is to investigate the dynamic control of a soft robotic arm. First, a modular soft robotic hardware and an affordable actuator-space encoder were presented. We then discussed the soft robot modeling, and adaptive passivity control strategy with stability proof. The proposed controller was tested in different operation scenarios, and compared to the standard PD feedback linearization control and passivity control. In all experimental settings, the adaptive passivity control scheme was able to achieve superior performance, even with significant modeling uncertainties and disturbances. The theoretical analysis and experimental validations of the proposed controller will pave the way toward the practical implementations of the soft robotic system in the dynamic scenarios.
Activated B-cell-like diffuse large B-cell lymphomas (ABC-DLBCLs) are characterized by constitutive activation of nuclear factor κB driven by the B-cell receptor (BCR) and Toll-like receptor (TLR) pathways. However, BCR-pathway-targeted therapies have limited impact on DLBCLs. Here we used >1,100 DLBCL patient samples to determine immune and extracellular matrix cues in the lymphoid tumour microenvironment (Ly-TME) and built representative synthetic-hydrogel-based B-cell-lymphoma organoids accordingly. We demonstrate that Ly-TME cellular and biophysical factors amplify the BCR–MYD88–TLR9 multiprotein supercomplex and induce cooperative signalling pathways in ABC-DLBCL cells, which reduce the efficacy of compounds targeting the BCR pathway members Bruton tyrosine kinase and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). Combinatorial inhibition of multiple aberrant signalling pathways induced higher antitumour efficacy in lymphoid organoids and implanted ABC-DLBCL patient tumours in vivo. Our studies define the complex crosstalk between malignant ABC-DLBCL cells and Ly-TME, and provide rational combinatorial therapies that rescue Ly-TME-mediated attenuation of treatment response to MALT1 inhibitors.
Large-scale scRNA-seq studies typically generate data in batches, which often induce nontrivial batch effects that need to be corrected. Given the global efforts for building cell atlases and the increasing number of annotated scRNA-seq datasets accumulated, we propose a supervised strategy for scRNA-seq data integration called SIDA (Supervised Integration using Domain Adaptation), which uses the cell type annotations to guide the integration of diverse batches. The supervised strategy is based on domain adaptation that was initially proposed in the computer vision field. We demonstrate that SIDA is able to generate comprehensive reference datasets that lead to improved accuracy in automated cell type mapping analyses.
While iron over-accumulation has been reported in late stage Alzheimer's disease (AD), whether this occurs early in the asymptomatic stage of AD remains unknown. We aimed to assess brain iron levels in asymptomatic AD using quantitative MR relaxometry of effective transverse relaxation rate (R2*) and longitudinal relaxation rate (R1), and recruited 118 participants comprised of three groups including healthy young participants, and cognitively normal older individuals without or with positive AD biomarkers based on cerebrospinal fluid (CSF) proteomics analysis. Compared with the healthy young group, increased R2* was found in widespread cortical and subcortical regions in the older groups. Further, significantly higher levels of R2* were found in the cognitively normal older subjects with positive CSF AD biomarker (i.e., asymptomatic AD) compared with those with negative AD biomarker in subcortical regions including the left and right caudate, left and right putamen, and left and right globus pallidus (p < .05 for all regions), suggesting increased iron content in these regions. Subcortical R2* of some regions was found to significantly correlate with CSF AD biomarkers and neuropsychological assessments of visuospatial functions. In conclusion, R2* could be a valuable biomarker for studying early pathophysiological changes in AD.
Topology optimization problems typically consider a single load case or a small, discrete number of load cases; however, practical structures are often subjected to infinitely many load cases that may vary in intensity, location and/or direction (e.g. moving/rotating loads or uncertain fixed loads). The variability of these loads significantly influences the stress distribution in a structure and should be considered during the design. We propose a locally stress-constrained topology optimization formulation that considers loads with continuously varying direction to ensure structural integrity under more realistic loading conditions. The problem is solved using an Augmented Lagrangian method, and the continuous range of load directions is incorporated through a series of analytic expressions that enables the computation of the worst-case maximum stress over all possible load directions. Variable load intensity is also handled by controlling the magnitude of load basis vectors used to derive the worst-case load. Several two- and three-dimensional examples demonstrate that topology-optimized designs are extremely sensitive to loads that vary in direction. The designs generated by this formulation are safer, more reliable, and more suitable for real applications, because they consider realistic loading conditions.
The validity and reliability of diagnoses in psychiatry is a challenging topic in mental health. The current mental health categorization is based primarily on symptoms and clinical course and is not biologically validated. Among multiple ongoing efforts, neurological observations alongside clinical evaluations are considered to be potential solutions to address diagnostic problems. The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) has published multiple papers attempting to reclassify psychotic illnesses based on biological rather than symptomatic measures. However, the effort to investigate the relationship between this new categorization approach and other neuroimaging techniques, including resting-state fMRI data, is still limited. This study focused on investigating the relationship between different psychotic disorders categorization methods and resting-state fMRI-based measures called dynamic functional network connectivity (dFNC) using state-of-the-art artificial intelligence (AI) approaches. We applied our method to 613 subjects, including individuals with psychosis and healthy controls, which were classified using both the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the B-SNIP biomarker-based (Biotype) approach. Statistical group differences and cross-validated classifiers were performed within each framework to assess how different categories. Results highlight interesting differences in occupancy in both DSM-IV and Biotype categorizations compared to healthy individuals, which are distributed across specific transient connectivity states. Biotypes tended to show less distinctiveness in occupancy level and included fewer cellwise differences. Classification accuracy obtained by DSM-IV and Biotype categories were both well above chance. Results provided new insights and highlighted the benefits of both DSM-IV and biology-based categories while also emphasizing the importance of future work in this direction, including employing further data types.
DNA inverted repeats (IRs) are widespread across many eukaryotic genomes. Their ability to form stable hairpin/cruciform secondary structures is causative in triggering chromosome instability leading to several human diseases. Distance and sequence divergence between IRs are inversely correlated with their ability to induce gross chromosomal rearrangements (GCRs) because of a lesser probability of secondary structure formation and chromosomal breakage. In this study, we demonstrate that structural parameters that normally constrain the instability of IRs are overcome when the repeats interact in single-stranded DNA (ssDNA). We established a system in budding yeast whereby >73 kb of ssDNA can be formed in cdc13-707fs mutants. We found that in ssDNA, 12 bp or 30 kb spaced Alu-IRs show similarly high levels of GCRs, while heterology only beyond 25% suppresses IR-induced instability. Mechanistically, rearrangements arise after cis-interaction of IRs leading to a DNA fold-back and the formation of a dicentric chromosome, which requires Rad52/Rad59 for IR annealing as well as Rad1-Rad10, Slx4, Msh2/Msh3 and Saw1 proteins for nonhomologous tail removal. Importantly, using structural characteristics rendering IRs permissive to DNA fold-back in yeast, we found that ssDNA regions mapped in cancer genomes contain a substantial number of potentially interacting and unstable IRs.
Hole-transport materials (HTMs) based on triarylamine derivatives play important roles in organic electronics applications including organic light-emitting diodes and perovskite solar cells. For some applications, triarylamine derivatives bearing appropriate binding groups have been used to functionalize surfaces, while others have been incorporated as side chains into polymers to manipulate the processibility of HTMs for device applications. However, only a few approaches have been used to incorporate a single surface-binding group or polymerizable group into triarylamine materials. Here, we report that Rh-carbenoid chemistry can be used to insert carboxylic esters and norbornene functional groups into sp2 C-H bonds of a simple triarylamine and a 4,4'-bis(diarylamino)biphenyl, respectively. The norbenene-functionalized monomer was polymerized by ring-opening metathesis; the electrochemical, optical, and charge-transport properties of these materials were similar to those of related materials synthesized by conventional means. This method potentially offers straightforward access to a diverse range of HTMs with different functional groups.
Nutrient availability can significantly influence microbial genomic and proteomic streamlining, for example, by selecting for lower nitrogen to carbon ratios. Oligotrophic open ocean microbes have streamlined genomic nitrogen requirements relative to those of their counterparts in nutrient-rich coastal waters. However, steep gradients in nutrient availability occur at meter-level, and even micron-level, spatial scales. It is unclear whether such gradients also structure genomic and proteomic stoichiometry. Focusing on the eastern tropical North Pacific oxygen minimum zone (OMZ), we use comparative metagenomics to examine how nitrogen availability shapes microbial and viral genome properties along the vertical gradient across the OMZ and between two size fractions, distinguishing free-living microbes versus particle-associated microbes. We find a substantial increase in the nitrogen content of encoded proteins in particle-associated over free-living bacteria and archaea across nitrogen availability regimes over depth. Within each size fraction, we find that bacterial and viral genomic nitrogen tends to increase with increasing nitrate concentrations with depth. In contrast to cellular genes, the nitrogen content of virus proteins does not differ between size fractions. We identified arginine as a key amino acid in the modulation of the C:N ratios of core genes for bacteria, archaea, and viruses. Functional analysis reveals that particle-associated bacterial metagenomes are enriched for genes that are involved in arginine metabolism and organic nitrogen compound catabolism. Our results are consistent with nitrogen streamlining in both cellular and viral genomes on spatial scales of meters to microns. These effects are similar in magnitude to those previously reported across scales of thousands of kilometers. IMPORTANCE The genomes of marine microbes can be shaped by nutrient cycles, with ocean-scale gradients in nitrogen availability being known to influence microbial amino acid usage. It is unclear, however, how genomic properties are shaped by nutrient changes over much smaller spatial scales, for example, along the vertical transition into oxygen minimum zones (OMZs) or from the exterior to the interior of detrital particles. Here, we measure protein nitrogen usage by marine bacteria, archaea, and viruses by using metagenomes from the nitracline of the eastern tropical North Pacific OMZ, including both particle-associated and nonassociated biomass. Our results show higher genomic and proteomic nitrogen content in particle-associated microbes and at depths with higher nitrogen availability for cellular and viral genomes. This discovery suggests that stoichiometry influences microbial and viral evolution across multiple scales, including the micrometer to millimeter scale associated with particle-associated versus free-living lifestyles.
Bacterial two-component signal transduction systems provide sensory inputs for appropriately adapting gene expression. These systems rely on a histidine kinase that phosphorylates a response regulator which alters gene expression. Several two-component systems include additional sensory components that can activate the histidine kinase. In Escherichia coli, the lipoprotein NlpE was identified as a sensor for the Cpx cell envelope stress response. It has remained unclear how NlpE signals to Cpx in the periplasm. In this study, we used a combination of genetics, biochemistry, and AlphaFold2 complex modeling to uncover the molecular details of how NlpE triggers the Cpx response through an interaction with the CpxA histidine kinase. Remarkably, only a short loop of NlpE is required to activate the Cpx response. A single substitution in this loop inactivates NlpE signaling to Cpx and abolishes an in vivo biochemical NlpE:CpxA interaction. An independent AlphaFold multimer prediction supported a role for the loop and predicted an interaction interface at CpxA. Mutations in this CpxA region specifically blind the histidine kinase to NlpE activation but preserve the ability to respond to other cell envelope stressors. Hence, our work additionally reveals a previously unrecognized complexity in signal integration by the CpxA periplasmic sensor domain.
Perovskite materials play a significant role in oxygen sensors due to their fascinating electrical and ionic conductivities. The sol-gel technique was employed to prepare various compositions of B-site-deficient Fe-doped SrTiO3 (iron-doped strontium titanate) or Sr(Ti0.6Fe0.4)1-x O3-δ , where x = 0.01, 0.02, and 0.03. The XRD results revealed that the principle crystalline phase of the samples was the cubic perovskite structure. The B-site deficiency improved the ionic and total conductivities of Sr(Ti0.6Fe0.4)1-x O3-δ . A small polaron conduction behavior occurred in the total electrical conductivity. The XPS results showed that the oxygen vacancy value decreased with the rise in the amount of B-site deficiencies. A lower B-site deficiency amount could produce more oxygen vacancies in the lattice but resulted in the ordering of vacancies and then lower ionic conductivity. The aging behavior was caused by the ordering of oxygen vacancies and resulted in a degeneration of electrical features under a long service time. Conversely, augmentation of the B-site deficiency amount inhibited the tendency for the ordering of oxygen vacancies and then promoted the electrical performance under a long usage time. The conduction mechanism of oxygen ions through oxygen vacancies was thoroughly investigated and discussed. The current study presents a feasible approach to ameliorate the physical features of conductors through doping the B-site of the perovskite layer with Fe, which would be a fruitful approach for numerous applications, including oxygen sensors and fuel cells anodes.
Poly(3,4-ethylene dioxythiophene) (PEDOT) has a high theoretical charge storage capacity, making it of interest for electrochemical applications including energy storage and water desalination. Nanoscale thin films of PEDOT are particularly attractive for these applications to enable faster charging. Recent work has demonstrated that nanoscale thin films of PEDOT can be formed using sequential gas-phase exposures via oxidative molecular layer deposition, or oMLD, which provides advantages in conformality and uniformity on high aspect ratio substrates over other deposition techniques. But to date, the electrochemical properties of these oMLD PEDOT thin films have not been well-characterized. In this work, we examine the electrochemical properties of 5-100 nm thick PEDOT films formed using 20-175 oMLD deposition cycles. We find that film thickness of oMLD PEDOT films affects the orientation of ordered domains leading to a substantial change in charge storage capacity. Interestingly, we observe a minimum in charge storage capacity for an oMLD PEDOT film thickness of ∼30 nm (60 oMLD cycles at 150 °C), coinciding with the highest degree of face-on oriented PEDOT domains as measured using grazing incidence wide angle X-ray scattering (GIWAXS). Thinner and thicker oMLD PEDOT films exhibit higher fractions of oblique (off-angle) orientations and corresponding increases in charge capacity of up to 120 mA h g-1. Electrochemical measurements suggest that higher charge capacity in films with mixed domain orientation arise from the facile transport of ions from the liquid electrolyte into the PEDOT layer. Greater exposure of the electrolyte to PEDOT domain edges is posited to facilitate faster ion transport in these mixed domain films. These insights will inform future design of PEDOT coated high-aspect ratio structures for electrochemical energy storage and water treatment.
Figure 1: First bite/chew are like the red, and yellow rectangles indicate; they are significantly different from the following bites/chews, which are relatively the same among different food types. ABSTRACT Eating or overtaking allergic foods may cause fatal symptoms or even death for people with food allergies. Most current food intake tracking methods are camera-based, on-body sensor-based, microphone based, and self-reported. However, challenges that remain are allergic food detection, social acceptance, lightweight, easy to use, and inexpensive. Our approach leverages the first bite/chew and the corresponding hand movement as an indicator to distinguish typical types of the allergic food. Our initial feasibility study shows that our approach can distinguish six types of food at an accuracy of 89.7% * Three authors contributed equally to this research. Permission to make digital or hard copies of part or all of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for third-party components of this work must be honored. For all other uses, contact the owner/author(s).
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George P. "Bud" Peterson