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Diagnosing quantum many-body chaos in non-Hermitian quantum spin chain via Krylov complexity
Get PDFWe investigate the phase transitions from chaotic to nonchaotic dynamics in a quantum spin chain with a local non-Hermitian disorder, which can be realized with a Rydberg atom array setting. As the disorder strength increases, the emergence of nonchaotic dynamics is qualitatively captured through the suppressed growth of Krylov complexity and quantitatively identified through the reciprocity breaking of Krylov space. We further find that the localization in Krylov space generates another transition in the weak disorder regime, suggesting a weak ergodicity breaking. Our results closely align with conventional methods, such as the entanglement entropy and complex level spacing statistics, and pave the way to explore non-Hermitian phase transitions using Krylov complexity and associated metrics
Predicting compounds that interact with the 2 known agonist-induced conformations of the human β1-adrenoceptor
Get PDFThe β1-adrenoceptor exists in at least 2 agonist-stabilized conformational ensembles: a “catecholamine” ensemble induced via the intrahelical binding site through which catecholamines and most agonists act and a “secondary” ensemble of conformations through which CGP12177 stimulates agonist responses. Several β-ligands stimulate agonist responses through both conformations, resulting in biphasic concentration responses, but little is known about the structure-activity relationship of such ligands. Using a structure-activity hypothesis built on the predicted poses CGP12177 and 3 biphasic agonists (alprenolol, oxprenolol, and bucindolol), predictions based on ligand similarity and structural compatibility reasoning were made about 11 other β1-ligands not yet tested for secondary conformation interaction and examined in radioligand binding and functional assays using human β1- and β2-adrenoceptors. Although the predictions matched with pharmacology in only 6/11 of cases, 3 novel compounds were found to induce an active-state secondary conformation. A CGP12177 derivative (methyl-pyrrole replacing the cyclic urea motif) retained catecholamine site antagonism with secondary site activation. Carteolol (related to CGP12177) and bunitrolol (similar to alprenolol) activated both conformations with biphasic concentration responses. Bunolol (CGP12177 derivative lacking nitrogen in the bicyclic system), as predicted, was a neutral antagonist with no secondary site activation. Moprolol and some bucindolol analogs appeared as conventional agonists, whereas other alprenolol and bucindolol analogs lost all receptor interaction. In a β1-adrenoceptor mutant (β1-V189T-L195Q-W199Y) where secondary site CGP12177 and pindolol interaction is lost, the 3 novel secondary-site compounds were also no longer able to stimulate secondary conformation responses, suggesting that there is a common TM4 secondary conformation-inducing interaction site. Significance Statement: The β1-adrenoceptor exists in 2 agonist-stabilized, pharmacologically distinguishable conformations. This study pinpointed the interaction site through which the alternative conformation is stabilized and suggested and evaluated additional ligands, thus providing possible molecular determinants
The basic helix–loop–helix (bHLH) transcription factor DTT1 is part of a paired key that unlocks the tapetum transition in barley anther development
No full textThe production of viable pollen is essential for effective fertilization and optimal crop yields; however, our understanding of the underlying mechanisms remains limited. Here, we characterize a barley (Hordeum vulgare) anther bHLH gene, DEFECTIVE TAPETUM TRANSITION1 (DTT1), a gatekeeper that regulates tapetum development. The dtt1 mutant is male sterile, failing to acquire tapetum cell fate identity with over-proliferation of indeterminate tapetal precursor cells, a lack of tapetum endomitosis, and cell wall degeneration. DTT1 forms heterodimers with DYSFUNCTIONAL TAPETUM1 (HvDYT1) through bHLH and ACT-like(BIF) domains, with the ACT-like(BIF) domain and the IKL motif critical in partner selection. These heterodimers may subsequently interact with each other through the bHLH-ACT-like(BIF) domain to activate expression. Transcriptome analysis confirmed that anther development transition from stage 6 to 7 fails in dtt1. We show that HvTDF1-related pathways are downstream of DTT1 and work in independent and overlapping networks with other conserved tapetum regulators. SELEX-seq analysis indicates that DTT1 can bind to DNA with a chimeric or canonical E-box motif only when it forms a complex with HvDYT1. In vivo dual-luciferase assays confirmed that the DTT1-HvDYT1 complex directly regulates the expression of several stage 7-specific transcription factors, such as HvTDF1, HvEAT1, and the identified GAMYB target genes. Therefore, the paired DTT1-HvDYT1 complex appears crucial in orchestrating the transition of tapetum cell fate by modulating genes involved in diverse biological pathways. This work uncovers detailed relationships in barley tapetum regulation and male fertility
Polymyxin B lethality requires energy-dependent outer membrane disruption
Get PDFPolymyxin antibiotics target lipopolysaccharides (LPSs) in both membranes of the bacterial cell envelope, leading to bacterial killing through a poorly defined mechanism. Here we demonstrate that metabolic activity is essential for the lethality of clinically relevant doses of polymyxin B (PmB) and leverage this insight to determine its mode of action. PmB killed exponential-phase Escherichia coli but did not eliminate stationary-phase cells unless a carbon source was available. Antibiotic lethality correlated with surface protrusions visible by atomic force microscopy and LPS loss from the outer membrane via processes that required LPS synthesis and transport but that were blocked by the MCR-1 polymyxin resistance determinant. While energy-dependent outer-membrane disruption was not directly lethal, it facilitated PmB access to the inner membrane, which the antibiotic permeabilized in an energy-independent manner, leading to cell death. This work reveals how metabolic inactivity confers tolerance of an important, membrane-targeting antibiotic
Group identity and peer effects in rule-following
Get PDFSocial life is governed by a myriad of rules but the behavioral logic of why people follow rules is only incompletely understood. Here, we investigate how rule following is influenced by other people and social proximity to them. In particular, we are interested in the identity composition of an individual's observed peer group: does it matter whether a rule breaker is an ingroup or an outgroup member? To investigate this question, we use a novel abstract rule-following task with strong incentives to break the rule. We call our rule-following task the “Y task” because the rule requested participants (n=7,033 Prolific workers) to take one of the two diverging paths of a Y-shaped maze. Consistent with previous research, we show that examples of rule violations trigger further rule violations, even though overall rule compliance remains high. Contrary to our hypotheses, and research on honesty and cooperation, we do not find that group identity moderates the influence of peer compliance on people's willingness to follow rules. We conclude that rule breaking is contagious regardless of the ingroup or outgroup status of the rule breaker
The Accommodation of Excess Charge in Binary Particle Lattices: A Many-Body Electrostatic Study
Get PDFMany binary particle lattices are fabricated from charged particles on the assumption that the resultant structure is overall charge neutral. Results presented here from calculations on nine separate particle lattice types show that when both Coulomb and many-body multipole electrostatic interactions are taken into account, a lattice can actually gain stability by accommodating a small excess charge, either positive or negative. This effect arises from an increase in stability due to charge-induced multipole interactions, which serve to counteract destabilizing interactions that arise from repulsive Coulomb forces. It is shown that most of the lattice types considered could accommodate over 20% excess charge before becoming completely destabilized
Routine testing for group B streptococcus in pregnancy: protocol for a UK cluster randomised trial (GBS3)
Get PDFIntroduction It is unclear whether routine testing of women for group B streptococcus (GBS) colonisation either in late pregnancy or during labour reduces early-onset neonatal sepsis, compared with a risk factor-based strategy. Methods and analysis Cluster randomised trial. Sites and participants 320 000 women from up to 80 hospital maternity units. Strategies Sites will be randomised 1:1 to a routine testing strategy or the risk factor-based strategy, using a web-based minimisation algorithm. A second-level randomisation allocates routine testing sites to either antenatal enriched culture medium testing or intrapartum rapid testing. Intrapartum antibiotic prophylaxis will be offered if a test is positive for GBS, or if a maternal risk factor for early-onset GBS infection in her baby is identified before or during labour. Economic and acceptability evaluations will be embedded within the trial design. Outcomes The primary outcome is all-cause early (<7 days of birth) neonatal sepsis, defined as either a positive blood/cerebrospinal fluid culture, early neonatal death from infection or a negative/unknown culture status with ≥3 agreed clinical signs or symptoms, who receive intravenous antibiotics ≥5 days. All women giving birth ≥24 weeks' gestation, regardless of mode of birth, and all her babies will be included in the dataset. Cost-effectiveness will be expressed in terms of incremental cost per case of early neonatal sepsis avoided and incremental cost per quality-adjusted life-year associated with each strategy. Ethics and dissemination The trial received a favourable opinion from Derby Research Ethics Committee on 16 September 2019 (19/EM/0253). The allocated testing strategy will be adopted as standard clinical practice by the site. Women in the routine testing sites will give verbal consent for the test. The trial will use routinely collected data retrieved from National Health Service databases, supplemented with limited participant-level collection of process outcomes. Individual written consent will not be sought. The trial results, and parallel economic, qualitative, implementation and methodological results, will be published in the journal Health Technology Assessment
High-resolution property: Drone enclosures in digital India
Get PDFDrawing from ethnographic research on the implementation of Svamitva, one of the largest digitalized property titling schemes in the world, this paper examines how new drone and geospatial technologies are being deployed to enclose rural customary lands across contemporary India. Focusing on the initial processes of droney survey, GIS mapping and data-creation under the scheme, the paper argues that the creation of ‘high-resolution property’ is achieved not through simple technological observation, but rather via the imposition of a new regime of perception. One coordinated through the speculative and ideological property-making practices of drone surveyors, GIS technicians, and local residents. This new regime of perception aims to extract individual ownership lurking within collectivity, subdivide collectivised lands, and cleanly link rural property to global asset markets and digital public infrastructures. In doing so the paper seeks to provincialise contemporary geographical scholarship on property technology or PropTech, drawing from the diverse property systems and emerging technological apparatus of the Global South, and examine the lively and mediated sociotechnical practices required to convert hundreds of thousands of rural territories into high-resolution private titles and data-points. In doing so, the paper seeks to challenge the overt techno-determinism and solutionism within official debates concerning property digitalization, highlighting instead the ways digitialized property remains socially, ecologically and institutionally mediated
Functional analysis and NMR studies of multi-drug efflux pumps
Get PDFEfflux pumps play an important role in bacterial multi-drug resistance by actively expelling antibiotics and toxic compounds from the cell. We describe an integrated workflow for the characterisation of inner membrane efflux pumps, consisting of an in vivo whole-cell functional efflux assay and an in vitro liposomal system for structural characterisation of protein/substrate interactions. The fluorescence-based assay uses the uncoupler CCCP to depolarise cell membranes, allowing fluorescent substrate to accumulate within the cell and bind to cellular DNA. In cells re-energised with glucose, restoration of PMF reactivates efflux, and the fluorescence of DNA-bound substrate provides a real-time measure of transport. The assay can inform on the impact of mutations and knockouts on efflux efficiency, facilitating mechanistic studies of substrate recognition and the functional roles of key residues. Insights into the structural and dynamic aspects of pump-substrate interactions are obtained using solid state NMR from membrane-reconstituted liposomal systems, where stable isotope-enriched recombinant protein is produced, purified and embedded in proteoliposomes. These are characterised by dynamics-sensitive and dipolar recoupling NMR methods to distinguish pump-associated substrate, and changes in pump NMR spectra inform on direct molecular contacts. The combined in vivo/in vitro approach can be extended to studies of other membrane transporter proteins, for which suitable fluorescent substrates can be identified
GeoPF: Infusing Geometry into Potential Fields for Reactive Planning in Non-trivial Environments
Get PDFReactive intelligence remains one of the cornerstones of versatile robotics operating in cluttered, dynamic, and human-centred environments. Among reactive approaches, potential fields (PF) continue to be widely adopted due to their simplicity and real-time applicability. However, existing PF methods typically oversimplify environmental representations by relying on isotropic, point- or sphere-based obstacle approximations. In human-centred settings, this simplification results in overly conservative paths, cumbersome tuning, and computational overhead—even breaking real-time requirements. In response, we propose the Geometric Potential Field (GeoPF), a reactive motion-planning framework that explicitly infuses geometric primitives—points, lines, planes, cubes, and cylinders—their structure and spatial relationship in modulating the real-time repulsive response. Extensive quantitative analyses consistently show GeoPF's higher success rates, reduced tuning complexity (a single parameter set across experiments), and substantially lower computational costs (up to 2 orders of magnitude) compared to traditional PF methods. Real-world experiments further validate GeoPF's reliability, robustness, and practical ease of deployment. GeoPF provides a fresh perspective on reactive planning problems driving geometric-aware temporal motion generation, enabling flexible and low-latency motion planning suitable for modern robotic applications
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