Browse Articles

Exponentially-enhanced quantum sensing with many-body phase transitions

Abstract Quantum sensors based on critical many-body systems are known to exhibit enhanced sensing capability. Such enhancements typically scale algebraically with the probe size. Going beyond algebraic advantage and reaching exponential scaling has remained elusive when all the resources, such as the preparation time, are taken into account. In this work, we show that many-body systems featuring first order quantum phase transitions can indeed achieve exponential scaling of sensitivity, thanks to their exponential energy gap closing. Remarkably, even after considering the preparation time using local adiabatic driving, the exponential scaling is sustained. Our results are demonstrated through comprehensive analysis of three paradigmatic models exhibiting first order phase transitions, namely Grover, p -spin, and biclique models. We show that this scaling survives moderate decoherence during state preparation and also can be optimally measured in experimentally available basis. Our findings comply with the fundamental bounds and we show that one can harness the exponential advantage through an adaptive strategy even away from the phase transition point.

Sonic hedgehog medulloblastomas are dependent on Netrin-1 for survival

Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response

Abstract HIV-1 Env glycoprotein (Env) immunogenicity is limited in part by structural instability and extensive glycan shielding and is likely the greatest obstacle to an HIV-1 vaccine. Stabilized Env trimers can elicit serum neutralizing antibodies, but the response is short-lived. Here we use Newcastle Disease Virus-like particle (NDV-VLP) platform to present stabilized versions of HIV-1 Env at high valency and in the context of varied conformational stability, adjuvants, dose, and antigen persistence. Influenza virus hemagglutinin, or SARS-CoV2 Spike-bearing VLPs rapidly induce neutralizing antibodies, in contrast, they were not induced by those bearing Env. A replicating adenovirus type 4 expressing Env rapidly induces autologous neutralizing antibodies. However, durable neutralizing antibodies are induced only when multiple features of a replicating virus infection are combined, with the largest impact from dose and escalating dose. In summary, we show here immunogenicity of HIV-1 Env could be improved by reproducing features of virus infection.

Infant craniofacial diversity in Early Pleistocene Homo

CD200R1-CD200 checkpoint inhibits phagocytosis differently from SIRPα-CD47 to suppress tumor growth

ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging

Experimental ecology and the balance between realism and feasibility in aquatic ecosystems

A soft robotic total artificial hybrid heart

Concealable physical unclonable functions using vertical NAND flash memory

Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model

Abstract Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) display canonical properties and dynamic motile multiciliated phenotypes that interact with Aβ uptake. Single dCPEC transcriptomes over time correlate well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlight the direct CPEC origin from neuroepithelial cells. In addition, time series analyses define metabolic (type 1) and ciliogenic dCPECs (type 2) at early timepoints, followed by type 1 diversification into anabolic-secretory (type 1a) and catabolic-absorptive subtypes (type 1b) as type 2 cells contract. These temporal patterns are then confirmed in independent derivations and mapped to prenatal stages using human tissues. In addition to defining the prenatal lineage of human CPECs, these findings suggest dynamic models of ChP support for the developing human brain.

Task difficulty modulates the effect of mind wandering on phase dynamics

Mind wandering attenuates widespread sensory and motor processing, both of which are mediated by phase coherence. However, it remains unclear i) whether mind wandering impacts both sensory input and motor output processing by modulating ii) neural entrainment to external stimuli, as measured by intertrial phase coherence (ITPC), and specifically iii) whether task difficulty with different degrees of attentional demands moderates the impact of mind wandering on phase coherence. Using the thought-probe method, we assessed participants’ attentional states during different sensory and motor tasks with varying task difficulty. We found that mind wandering decreased ITPC exclusively in less demanding tasks but not in difficult ones, regardless of whether the tasks involved visual input or motor output processing. Our results suggest that external task difficulty may modulate the balance between external and internal cognitive processing (e.g., mind wandering), with simpler tasks facilitating internally oriented cognition and increasing mind wandering. This balance between internal mind wandering and external task difficulty is mediated, in part, by phase coherence, which serves as an underlying neural mechanism. Collectively, our findings support the hypothesis that phase coherence and its dynamics (ITPC) play a key role in mediating the reciprocal balance of internal and external cognition—this suggests their partly shared cognitive-executive resources as entailed by the recently proposed Baseline model of cognition.

Unveiling the structural spectrum of SARS-CoV-2 fusion by in situ cryo-ET

Abstract SARS-CoV-2 entry into host cells is mediated by the spike protein, which drives membrane fusion. While cryo-EM reveals stable prefusion and postfusion conformations of the spike, the transient fusion intermediate states during the fusion process remain poorly understood. Here, we design a near-native viral fusion system that recapitulates SARS-CoV-2 entry and use cryo-electron tomography (cryo-ET) to capture fusion intermediates leading to complete fusion. The spike protein undergoes extensive structural rearrangements, progressing through extended, partially folded, and fully folded intermediates prior to fusion-pore formation, a process that depends on protease cleavage and is inhibited by the WS6 S2 antibody. Upon interaction with ACE2 receptor dimer, spikes cluster at membrane interfaces and following S2’ cleavage concurrently transition to postfusion conformations encircling the hemifusion and initial fusion pores in a distinct conical arrangement. S2’ cleavage is indispensable for advancing fusion intermediates to the fully folded postfusion state, culminating in membrane integration. Subtomogram averaging reveals that the WS6 S2 antibody binds to the spike’s stem-helix, crosslinks and clusters prefusion spikes, as well as inhibits refolding of fusion intermediates. These findings elucidate the entire process of spike-mediated fusion and SARS-CoV-2 entry, highlighting the neutralizing mechanism of S2-targeting antibodies.

Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke

Synaptic markers are associated with cognitive decline after accounting for amyloid burden among an at-risk Alzheimer’s disease cohort

De novo design of protein condensation inhibitors by targeting an allosteric site of cGAS

Identify the co-expressed genes of hypertensive nephropathy and diabetic nephropathy

Abstract This study focused on the intricate connections between hypertension nephropathy (HN) and diabetic nephropathy (DN) in terms of molecular and pathological mechanisms. The samples were from the Gene Expression Omnibus (GEO) database. GSE37460 and GSE142153 are training sets, and GSE37455 and GSE30529 are validation sets. We found 42 shared differentially expressed genes (DEGs) by means of the differential analysis. The GO/KEGG and GSEA analysis mainly highlights the signal transduction pathways related to the proteasome and cytokines. The eight hub genes identified through the Protein-Protein Interaction (PPI) network analysis include NR4A1, TNFSF10, CX3CR1, EGF, THBD, CXCR4, CCL5, and ATF3. Single-cell sequencing analysis revealed that TNFSF10 and NR4A1 were the most highly expressed in the cells of both HN and DN. Furthermore, five significant microRNAs identified include hsa-miR-1248, hsa-miR-200b-5p, hsa-miR-23b-5p, hsa-miR-3059-5p, and hsa-miR-3065-3p. Six essential transcription factors (TFs) (NFIL3, STAT3, NFKB1, USF1, USF2, and EGR1), 11 important drug chemicals (Cisplatin, Cyclosporine, perfluorooctanoic acid, Quercetin, Tretinoin, bisphenol A, Curcumin, Valproic Acid, Particulate Matter, Simvastatin, and Cadmium), seven related diseases (Atherosclerosis, Glioblastoma, Pulmonary Fibrosis, Asthma, Hepatitis B, Hepatitis C, and Diabetes Mellitus), and ten important RNA-binding proteins (RBPs) (CHTOP, EIF4E, HNRNPK, IGF2BP3, YTHDF3, HNRNPA2B1, RBM47, YBX1, RBFOX2, and RBM10). Finally, molecular docking simulations suggest that Tretinoin and Curcumin may have potential therapeutic value for both HN and DN. This study provides novel therapeutic targets for the combined diagnosis and treatment of HN and DN.

Estimating wage disparities using foundation models

The rise of foundation models marks a paradigm shift in machine learning: instead of training specialized models from scratch, foundation models are trained on massive datasets before being adjusted or fine-tuned to make predictions on smaller datasets. Initially developed for text, foundation models have also excelled at making predictions about social science data. However, while many estimation problems in the social sciences use prediction as an intermediate step, they ultimately require different criteria for success. In this paper, we develop methods for fine-tuning foundation models to perform these estimation problems. We first characterize an omitted variable bias that can arise when a foundation model is fine-tuned in the standard way: to minimize predictive error. We then provide a set of conditions for fine-tuning under which estimates derived from a foundation model are n -consistent. Based on this theory, we develop fine-tuning algorithms that empirically mitigate this omitted variable bias. To demonstrate our ideas, we study gender wage gap estimation. Classical methods for estimating the adjusted wage gap employ simple predictive models of wages, which can induce omitted variable bias because they condition on coarse summaries of career history. Instead, we use a custom-built foundation model, capturing a richer representation of career history. Using data from the Panel Study of Income Dynamics, we find that career history explains more of the gender wage gap than standard econometric models can measure, and we identify elements of career history that are omitted by standard models but are important for explaining the gap.

Self-powered sensing platform based on triboelectric nanogenerators towards intelligent mining industry

A deep learning based intrusion detection system for CAN vehicle based on combination of triple attention mechanism and GGO algorithm

Oxr1 and Ncoa7 regulate V-ATPase to achieve optimal pH for glycosylation within the Golgi apparatus and trans-Golgi network

Maintenance of pH within membranous organelles is crucial for cellular processes such as posttranslational modifications, ligand–receptor interactions, and proteostasis. The precise mechanisms that determine the luminal pH of each organelle are not fully understood. This study investigated the mechanisms that regulate luminal pH to ensure optimal enzymatic activity. We identified Oxr1 and its paralog Ncoa7, which regulate the vacuolar-type proton pump ATPase (V-ATPase) at the Golgi apparatus and trans-Golgi network (TGN). Oxr1 and Ncoa7 were predominantly localized at the Golgi and TGN membranes, dependent on their binding to various GTP-bound Rab proteins. In vitro experiments using purified recombinant proteins indicated that Oxr1 and Ncoa7 directly bind to the catalytic subunit of V-ATPase, inhibiting its ATP hydrolytic activity via their TLDc domains. We observed significant acidification of the Golgi/TGN lumen in Oxr1- and Ncoa7-depleted cells. Lectin blot analysis demonstrated that depletion of Oxr1 and Ncoa7 led to a defect in protein glycosylation, a major enzymatic posttranslational modification in the Golgi and TGN. Furthermore, depletion of Oxr1 and Ncoa7, along with drug-induced inhibition of glycosylation, increased lysosomal pH and sensitivity to silicon dioxide-induced membrane damage. This apparent lysosomal dysfunction suggested that, in addition to the Golgi and TGN, Oxr1 and Ncoa7 also contribute to the integrity of other organelles. Our findings indicate that Oxr1 and Ncoa7 protect the Golgi and TGN lumen from excess acidification by inhibiting V-ATPase activity and providing an optimal environment for enzymatic activity in the Golgi and TGN.