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We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 × 10−7) and tetraspanin-8 (TSPAN8; P=6.11 × 10−7). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 × 10−8, TSPAN8; P=7.57 × 10−7 and EGFR; P=8.36 × 10−8). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case–control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case–Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.Molecular Psychiatry (2008) 13, 558–569; doi:10.1038/sj.mp.4002151; published online 4 March 2008 [ABSTRACT FROM AUTHOR]

Many active systems are capable of forming intriguing patterns at scales significantly larger than the size of their individual constituents. Cyanobacteria are one of the most ancient and important phyla of organisms that has allowed the evolution of more complex life forms. Despite its importance, the role of motility on the pattern formation of their colonies is not understood. Here, we investigate the large-scale collective effects and rich dynamics of gliding filamentous cyanobacteria colonies, while still retaining information about the individual constituents' dynamics and their interactions. We investigate both the colony's transient and steady-state dynamics and find good agreement with experiments. We furthermore show that the Péclet number and aligning interaction strength govern the system's topological transition from an isotropic distribution to a state of large-scale reticulate patterns. Although the system is topologically non-trivial, the parallel and perpendicular pair correlation functions provide structural information about the colony, and thus can be used to extract information about the early stages of biofilm formation. Finally, we find that the effects of the filaments' length cannot be reduced to a system of interacting points. Our model proves to reproduce both cyanobacteria colonies and systems of biofilaments where curvature is transported by motility. Active matter systems can spontaneously form structure. Using concepts of nonequilibrium statistical physics and experiments, this work demonstrates the existence of a topological transition in filamentous cyanobacteria colonies from an isotropic distribution to dense bundles organized in a reticulate pattern. [ABSTRACT FROM AUTHOR]

Quantum devices such as spin qubits have been extensively investigated in electrostatically confined quantum dots using high-quality semiconductor heterostructures like GaAs and Si. Here, we present a demonstration of electrostatically forming the quantum dots in ZnO heterostructures. Through the transport measurement, we uncover the distinctive signature of the Kondo effect independent of the even-odd electron number parity, which contrasts with the typical behavior of the Kondo effect in GaAs. By analyzing temperature and magnetic field dependences, we find that the absence of the even-odd parity in the Kondo effect is not straightforwardly interpreted by the considerations developed for conventional semiconductors. We propose that, based on the unique parameters of ZnO, electron correlation likely plays a fundamental role in this observation. Our study not only clarifies the physics of correlated electrons in the quantum dot but also holds promise for applications in quantum devices, leveraging the unique features of ZnO. To date, semiconductor quantum dots have been studied in heterostructures of materials such as GaAs and Si. Here the authors report the formation of electrostatically defined quantum dots in ZnO heterostructures with correlated electrons and observe a unique Kondo effect independent of even-odd electron parity. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the patterns, vulnerabilities, and responses associated with ransomware incidents in U.S. hospitals. Methods: The study employs qualitative thematic analysis of ransomware incidents in U.S. hospitals from 2016 to 2022. Data were collected from the U.S. Department of Health and Human Services (HHS) Office for Civil Rights (OCR) public portal, and 65 cases were analyzed using NVivo 14 software. Findings: Seven major themes emerged: (1) scale of ransomware, with incidents impacting a large number of individuals through diverse methods such as phishing and exploiting server vulnerabilities; (2) extent of protected health information vulnerability, with incidents often compromising sensitive health data, treatment records, and personal identifiers; (3) response and notification protocols, where hospitals demonstrate systematic responses including mandatory notifications to HHS, the media, and affected individuals; (4) implementation of safeguards, where hospitals have implemented immediate and long-term security measures post-attack; (5) investigation and regulatory compliance, where each attack is internally investigated, or with third-parties, while OCR conducts compliance reviews to guide corrective actions; (6) third-party involvement, highlighting the significant role of business associates (BAs) in incidents; (7) victim support and services, where hospitals frequently provide credit monitoring and identity protection services. Conclusions: The study reveals the increasing prevalence of ransomware attacks targeting hospitals, highlighting significant vulnerabilities and the critical need for enhanced security measures. The findings suggest areas for future research, including the effectiveness of security practices and the long-term impacts on affected individuals. [ABSTRACT FROM AUTHOR]

Hard carbon stands out as one of the most prospective anode materials for the storage of sodium due to its abundant resources, low cost, high conductivity, and suitable potential. In this study, S-doped hard carbon (SFC/S-3) was synthesized from a mixture of Shenfu bituminous coal (SFC) and S powder via the one-step pyrolysis method. S doping effectively enlarged the carbon layer spacing, formed -C-SOx-C- bonds, and increased the specific surface area of the hard carbon, which significantly enhanced the sodium storage capacity of hard carbons. Furthermore, coal-based graphene oxide (CGO) was used as a multi-functional binder to further boost the sodium storage performance of SFC/S-3 by reducing the surface defects and forming a conductive network. Consequently, the SFC/S-3@CGO exhibited an excellent sodium storage performance, delivering a high reversible capacity of 449.4 mAh g−1, a high-rate capacity of 224.7 mAh g−1 at 1 A g−1, and approximately 74% capacity retention after 500 cycles at 1 A g−1. This study offers a versatile approach for heteroatom doping and promotes the clean utilization of coal. [ABSTRACT FROM AUTHOR]

The text reports on the results from Arm A of the Phase 1/2 DREAMM-6 trial, focusing on the combination of belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma. The study showed no dose-limiting toxicities and no new safety signals across cohorts, with adverse events consistent with individual agent safety profiles. Ocular events, particularly keratopathy, were the most common Grade 3/4 adverse events, and the overall safety profile was manageable. Efficacy outcomes, such as overall response rate and progression-free survival, were generally similar across cohorts, indicating clinically meaningful anti-myeloma activity. [Extracted from the article]

Greenberger-Horne-Zeilinger (GHZ) states, also known as two-component Schrödinger cats, play vital roles in the foundation of quantum physics and the potential quantum applications. Enlargement in size and coherent control of GHZ states are both crucial for harnessing entanglement in advanced computational tasks with practical advantages, which unfortunately pose tremendous challenges as GHZ states are vulnerable to noise. Here we propose a general strategy for creating, preserving, and manipulating large-scale GHZ entanglement, and demonstrate a series of experiments underlined by high-fidelity digital quantum circuits. For initialization, we employ a scalable protocol to create genuinely entangled GHZ states with up to 60 qubits, almost doubling the previous size record. For protection, we take a different perspective on discrete time crystals (DTCs), originally for exploring exotic nonequilibrium quantum matters, and embed a GHZ state into the eigenstates of a tailor-made cat scar DTC to extend its lifetime. For manipulation, we switch the DTC eigenstates with in-situ quantum gates to modify the effectiveness of the GHZ protection. Our findings establish a viable path towards coherent operations on large-scale entanglement, and further highlight superconducting processors as a promising platform to explore nonequilibrium quantum matters and emerging applications. The Greenberger-Horne-Zeilinger states are multipartite entangled quantum states with strong non-local entanglement. Here the authors generate large-scale states of this type with up to 60 qubits and show that discrete time crystals can effectively protect such fragile states. [ABSTRACT FROM AUTHOR]

In recent years, there is an increasing interest in finding better and more efficient ways to detect CN− ions. Most of the anthraquinone-based probes show less fluorescence This paper presents the design and synthesis of a new anthraquinone based imine probe with good colorimetric sensing property and fluorescent turn on behavior toward CN− ion. Herein, we report a receptor with both colorimetric and fluorescent enhancement of cyanide ion in DMSO medium is synthesized. The synthesized receptor shows an immediate color change from orange to pink when cyanide is added; and it can be readily observed visually due to the presence of diverse p-conjugated systems in the receptor. These studies were confirmed by UV–Visible, PL studies, DFT, HRMS and 1H NMR titration. Moreover, this receptor shows 1:1 stoichiometry and micromolar detection limit. Further the receptor was applied to a real sample in finger millet (Eleusine Coracana) to detect the presence of cyanide ion. Moreover, the receptor is applicable toward INHIBITION, IMPLICATION logic gates with two input systems. [ABSTRACT FROM AUTHOR]

Urbanization is one of the milestones in the development of human society. Many regions in the southern parts of 'the old world' demonstrating an early emergence of agriculture also witnessed the flourishing of some of the earliest cities. Recent, yet still sparse, archaeological evidence appears to indicate a relatively later time for early urbanism in central Eurasia. However, given its vital geographic location and cultural nexus between East and West, more attention should be paid to the sedentary communities and their cities in oases amid the vast droughty desert, particularly in light of the rapidly increasing number of publications on early pastoralism and related communication routes along mountain chains and rivers. This study reveals the trajectory of urbanization and its role in the establishment of an exchange network in Xinjiang's oasis region via reconstruction of the chronological sequence of the local societal history of the Baiyang River Basin along the southern piedmont of the Eastern Tianshan Mountains. A thorough archaeological investigation and refined radiocarbon dating programme was carried out and coupled with information from historical documentation within a Bayesian statistical framework. The results indicate three pulses of local urbanization during: the Early Iron Age, Tang–Yuan period, and Qing Dynasty, respectively. Combining this with evidence from other parts of Xinjiang, we re-evaluate the role of oasis urbanism in the promotion of trans-regional exchange. [ABSTRACT FROM AUTHOR]

Lymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conduct a highly multiplexed single-cell proteomic screen on human bone marrow progenitors. This screen identifies terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34+ progenitors prior to B/T cell emergence. While these TdT+ cells coincide with granulocyte-monocyte progenitor (GMP) immunophenotype, their accessible chromatin regions show enrichment for lymphoid-associated transcription factor (TF) motifs. TdT expression on GMPs is inversely related to the SLAM family member CD84. Prospective isolation of CD84lo GMPs demonstrates robust lymphoid potentials ex vivo, while still retaining significant myeloid differentiation capacity, akin to LMPPs. This multi-omic study identifies human bone marrow lymphoid-primed progenitors, further defining the lympho-myeloid axis in human hematopoiesis. How lymphoid and myeloid specification occurs in human haematopoietic progenitors is not fully understood. Here the authors perform a proteomic screen on human bone marrow progenitors and suggest TdT+ and CD84- progenitors as lymphoid-primed progenitors with residual myeloid potentials. [ABSTRACT FROM AUTHOR]

Controlled operations are fundamental building blocks of quantum algorithms. Decomposing n-control-NOT gates (Cn(X)) into arbitrary single-qubit and CNOT gates, is a crucial but non-trivial task. This study introduces Cn(X) circuits outperforming previous methods in the asymptotic and non-asymptotic regimes. Three distinct decompositions are presented: an exact one using one borrowed ancilla with a circuit depth Θ (log (n) 3 ) , an approximating one without ancilla qubits with a circuit depth O (log (n) 3 log (1 / ϵ)) and an exact one with an adjustable-depth circuit which decreases with the number m≤n of ancilla qubits available as O (log (n / ⌊ m / 2 ⌋) 3 + log (⌊ m / 2 ⌋)) . The resulting exponential speedup is likely to have a substantial impact on fault-tolerant quantum computing by improving the complexities of countless quantum algorithms with applications ranging from quantum chemistry to physics, finance and quantum machine learning. Multi-controlled operations are very common in quantum algorithms applications. Here, the authors propose three schemes for decomposing n-control-NOT gates into single-qubit and CNOT gates, which have polylog overhead as opposed to current linear schemes. [ABSTRACT FROM AUTHOR]

The basal plane of graphene can function as a selective barrier that is permeable to protons1,2 but impermeable to all ions3,4 and gases5,6, stimulating its use in applications such as membranes1,2,7,8, catalysis9,10 and isotope separation11,12. Protons can chemically adsorb on graphene and hydrogenate it13,14, inducing a conductor–insulator transition that has been explored intensively in graphene electronic devices13–17. However, both processes face energy barriers1,12,18 and various strategies have been proposed to accelerate proton transport, for example by introducing vacancies4,7,8, incorporating catalytic metals1,19 or chemically functionalizing the lattice18,20. But these techniques can compromise other properties, such as ion selectivity21,22 or mechanical stability23. Here we show that independent control of the electric field, E, at around 1 V nm−1, and charge-carrier density, n, at around 1 × 1014 cm−2, in double-gated graphene allows the decoupling of proton transport from lattice hydrogenation and can thereby accelerate proton transport such that it approaches the limiting electrolyte current for our devices. Proton transport and hydrogenation can be driven selectively with precision and robustness, enabling proton-based logic and memory graphene devices that have on–off ratios spanning orders of magnitude. Our results show that field effects can accelerate and decouple electrochemical processes in double-gated 2D crystals and demonstrate the possibility of mapping such processes as a function of E and n, which is a new technique for the study of 2D electrode–electrolyte interfaces.Independent control of the electric field and charge-carrier density in double-gated graphene allows the decoupling of proton transport and lattice hydrogenation, enabling both accelerated proton transport and proton-based logic operations. [ABSTRACT FROM AUTHOR]

Insider threats represent a serious threat to organizations but are considered to be difficult to predict and prevent. Although a growing body of research has examined personological antecedents to insider threats, this literature lacks a unifying theoretical perspective connecting the characteristics that have been researched. In addition to cataloging the personality factors that have been associated with insider threat behaviors, this review also proposes neo-socioanalytic theory as a useful framework for organizing these factors and for distinguishing insider threats from counterproductive work behaviors and workplace accidents. The majority of risk and protective factors related to insider threats were shared for both malicious and non-malicious insider threat behaviors. However, the prior literature strongly suggests that malicious threats are motivated by selfishness and the rationalization of immoral behavior, while non-malicious threats are better understood as being associated with maladjustment and curiosity. [ABSTRACT FROM AUTHOR]

Cell-free protein expression (CFE) systems have emerged as a critical platform for synthetic biology research. The vectors for protein expression in CFE systems mainly rely on double-stranded DNA and single-stranded RNA for transcription and translation processing. Here, we introduce a programmable vector - circular single-stranded DNA (CssDNA), which is shown to be processed by DNA and RNA polymerases for gene expression in a yeast-based CFE system. CssDNA is already widely employed in DNA nanotechnology due to its addressability and programmability. To apply above methods in the context of synthetic biology, CssDNA can not only be engineered for gene regulation via the different pathways of sense CssDNA and antisense CssDNA, but also be constructed into several gene regulatory logic gates in CFE systems. Our findings advance the understanding of how CssDNA can be utilized in gene expression and gene regulation, and thus enrich the synthetic biology toolbox. Protein expression vectors in cell-free systems mainly rely on double-stranded DNA and single-stranded RNA. Here, authors use circular single-stranded DNA as a programmable vector for gene regulation in a cell-free expression system by identifying its expression pathways. [ABSTRACT FROM AUTHOR]

DNA is a complex multi-resolution molecule whose theoretical study is a challenge. Its intrinsic multiscale nature requires chemistry and quantum physics to understand the structure and quantum informatics to explain its operation as a perfect quantum computer. Here, we present theoretical results of DNA that allow a better description of its structure and the operation process in the transmission, coding, and decoding of genetic information. Aromaticity is explained by the oscillatory resonant quantum state of correlated electron and hole pairs due to the quantized molecular vibrational energy acting as an attractive force. The correlated pairs form a supercurrent in the nitrogenous bases in a single band π -molecular orbital (π -MO). The MO wave function (Φ) is assumed to be the linear combination of the n constituent atomic orbitals. The central Hydrogen bond between Adenine (A) and Thymine (T) or Guanine (G) and Cytosine (C) functions like an ideal Josephson Junction. The approach of a Josephson Effect between two superconductors is correctly described, as well as the condensation of the nitrogenous bases to obtain the two entangled quantum states that form the qubit. Combining the quantum state of the composite system with the classical information, RNA polymerase teleports one of the four Bell states. DNA is a perfect quantum computer. [ABSTRACT FROM AUTHOR]

The flat bands in magic-angle twisted bilayer graphene (MATBG) provide an especially rich arena to investigate interaction-driven ground states. While progress has been made in identifying the correlated insulators and their excitations at commensurate moiré filling factors, the spin-valley polarizations of the topological states that emerge at high magnetic field remain unknown. Here we introduce a technique based on twist-decoupled van der Waals layers that enables measurement of their electronic band structure and–by studying the backscattering between counter-propagating edge states–the determination of the relative spin polarization of their edge modes. We find that the symmetry-broken quantum Hall states that extend from the charge neutrality point in MATBG are spin unpolarized at even integer filling factors. The measurements also indicate that the correlated Chern insulator emerging from half filling of the flat valence band is spin unpolarized and suggest that its conduction band counterpart may be spin polarized. The hierarchy of symmetry breaking in magic-angle twisted bilayer graphene remains a topic of intense fundamental study. Here, the authors determine the spin polarization of symmetry-broken quantum Hall states and Chern insulators in MATBG using a twist-decoupled graphene probe. [ABSTRACT FROM AUTHOR]

As Ransomware encrypts user files to prevent access to infected systems its harmful impacts must be quickly identified and remedied. It can be challenging to identify the metrics and parameters to check, especially when using unknown ransomware variants in tests. The proposed work uses machine learning techniques to create a general model that can be used to detect the variations of ransomware families while observing the characteristics of malware. However, early detection is impeded by a dearth of data during the initial phases of an attack, which results in low detection accuracy and a high proportion of false alarms. To overcome these restrictions, our research suggests a revolutionary technique, in machine learning techniques we have proposed RandomClassifier with SMOTE optimizer based on the results received from LazyPredictAutoML, and then deep learning algorithm ANN using Root Mean Square Propagation (Adam) has been implemented to get the hidden patterns which were not accessible in the machine learning approach. The further study focused on improving CNN's performance over RMSprop & Adam, which maintains per-parameter learning rates that are adjusted based on the average of most recent weight gradient magnitudes, using the Adam optimizer. The best option for internet and non-stationary issues is CNN with Adam (e.g. noisy). As gradients grow sparser toward the end of optimization, Adam somewhat surpasses RMSprop. Adam uses CNN and uses the average of the second moments of the gradients (the uncentered variance). The proposed model reported 5.14 ms of prediction time and 99.18% accuracy. [ABSTRACT FROM AUTHOR]

Archaeological evidence supports sporadic seafaring visits to the Eastern Mediterranean island of Cyprus by Epipaleolithic hunter-gatherers over 12,000 years ago, followed by permanent settlements during the early Neolithic. The geographical origins of these early seafarers have so far remained elusive. By systematically analysing all available genomes from the late Pleistocene to early Holocene Near East (c. 14,000–7000 cal BCE), we provide a comprehensive overview of the genetic landscape of the early Neolithic Fertile Crescent and Anatolia and infer the likely origins of three recently published genomes from Kissonerga-Mylouthkia (Cypriot Late Pre-Pottery Neolithic B, c. 7600–6800 cal BCE). These appear to derive roughly 80% of their ancestry from Aceramic Neolithic Central Anatolians residing in or near the Konya plain, and the remainder from a genetically basal Levantine population. Based on genome-wide weighted ancestry covariance analysis, we infer that this admixture event took place roughly between 14,000 and 10,000 BCE, coinciding with the transition from the Cypriot late Epipaleolithic to the Pre-Pottery Neolithic A (PPNA). Additionally, we identify strong genetic affinities between the examined Cypro-LPPNB individuals and later northwestern Anatolians and the earliest European Neolithic farmers. Our results inform archaeological evidence on prehistoric demographic processes in the Eastern Mediterranean, providing important insights into early seafaring, maritime connections, and insular settlement. [ABSTRACT FROM AUTHOR]

The single-photon quantum computing paradigm currently relies on the multi-port interference in linear optical devices, which is intrinsically based on probabilistic measurements outcome, and thus non-deterministic. Devising a fully deterministic, universal, and practically achievable quantum computing platform based on single-photon encoding and integrated photonic circuits is still an open challenge. Here we propose to exploit the interplay of distributed self-Kerr nonlinearity and localized hopping in quantum photonic interferometers to implement deterministic entangling quantum gates with dual rail photonic qubits. It is shown that a universal set of single- and two-qubit gates can be designed by a suitable concatenation of few optical interferometric elements, reaching optimal fidelities arbitrarily close to 100% that are theoretically demonstrated through a bound constrained optimization algorithm. The actual realization would require the concatenation of a few tens of elementary operations, as well as on-chip optical nonlinearities that are compatible with some of the existing quantum photonic platforms, as it is finally discussed. Realizing deterministic two-qubit quantum gates in Photonics is currently an open challenge, and no experimental demonstrations exist to date. Here, the authors propose deterministic entangling quantum gates with dual rail single-photon qubits in a photonic interferometer displaying distributed Kerr-type nonlinearities over the whole circuit length. [ABSTRACT FROM AUTHOR]

Objectives: To characterize treatment response of recurrent respiratory papillomatosis (RRP) including adult-onset RRP (AORRP) and juvenile-onset RRP (JORRP) to systemic bevacizumab (bev), and share our treatment regimen experience. Methods: Patients were enrolled in bev treatment based on a pathologically confirmed diagnosis of squamous papilloma. According to lesion characteristics and medical history, systemic bev was used as preoperative adjuvant therapy, postoperative adjuvant therapy, or primary therapy. The assessment of treatment response relied on the morphological changes of lesions. Vocalization and voice-related quality of life were evaluated using the voice handicap index-30 (VHI-30) for adults and the pediatric VHI (pVHI) for children. Adverse effect was monitored through patient self-reported symptoms and regular follow-ups. Results: This study included 24 patients, comprising nine AORRP and 15 JORRP cases. In AORRP, all patients (100%) exhibited various degrees of response to systemic bev, with 5 (55.56%) achieving complete response (CR). Among JORRP patients, 14 (93.33%) showed a response to systemic bev, with 8 (53.33%) achieving CR and currently being followed up. No instances of aggravation were observed during systemic bev treatment. A total of 21 patients (21/24, 87.50%) reported voice improvement, accompanied by reduced VHI-30 or pVHI scores across all aspects, including total, functional, physical, and emotional dimensions. No grade 3 or higher adverse events occurred. The most common adverse events were grade 1 gum bleeding (n = 4, 16.67%) and grade 1 proteinuria (n = 4, 16.67%). Conclusions: Systemic bev can be used as a powerful therapy for both AORRP and JORRP. The findings provide a reference to the systemic bev treatment for RRP. [ABSTRACT FROM AUTHOR]

Water oxidation in photosystem II (PSII) is performed by the oxygen-evolving complex Mn4CaO5 which can be extracted from PSII and then reconstructed using exogenous cations Mn(II) and Ca2+. The binding efficiency of other cations to the Mn-binding sites in Mn-depleted PSII was investigated without any positive results. At the same time, a study of the Fe cations interaction with Mn-binding sites showed that it binds at a level comparable with the binding of Mn cations. Binding of Fe(II) cations first requires its light-dependent oxidation. In general, the interaction of Fe(II) with Mn-depleted PSII has a number of features similar to the two-quantum model of photoactivation of the complex with the release of oxygen. Interestingly, incubation of Ca-depleted PSII with Fe(II) cations under certain conditions is accompanied by the formation of a chimeric cluster Mn/Fe in the oxygen-evolving complex. PSII with the cluster 2Mn2Fe was found to be capable of water oxidation, but only to the H2O2 intermediate. However, the cluster 3Mn1Fe can oxidize water to O2 with an efficiency about 25% of the original in the absence of extrinsic proteins PsbQ and PsbP. In the presence of these proteins, the efficiency of O2 evolution can reach 80% of the original when adding exogenous Ca2+. In this review, we summarized information on the formation of chimeric Mn–Fe clusters in the oxygen-evolving complex. The data cited may be useful for detailing the mechanism of water oxidation. [ABSTRACT FROM AUTHOR]

Complex entangled states are the key resources for measurement-based quantum computations, which is realised by performing a sequence of measurements on initially entangled qubits. Executable quantum algorithms in the graph-state quantum computing model are determined by the entanglement structure and the connectivity of entangled qubits. By generalisation from graph-type entanglement in which only the nearest qubits interact to a new type of hypergraph entanglement in which any subset of qubits can be arbitrarily entangled via hyperedges, hypergraph states represent more general resource states that allow arbitrary quantum computation with Pauli universality. Here we report experimental preparation, certification and processing of complete categories of four-qubit hypergraph states under the principle of local unitary equivalence, on a fully reprogrammable silicon-photonic quantum chip. Genuine multipartite entanglement for hypergraph states is certificated by the characterisation of entanglement witness, and the observation of violations of Mermin inequalities without any closure of distance or detection loopholes. A basic measurement-based protocol and an efficient resource state verification by color-encoding stabilizers are implemented with local Pauli measurement to benchmark the building blocks for hypergraph-state quantum computation. Our work prototypes hypergraph entanglement as a general resource for quantum information processing. [ABSTRACT FROM AUTHOR]

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS. [ABSTRACT FROM AUTHOR]

We report better-than-classical success probabilities for a complete Grover quantum search algorithm on the largest scale demonstrated to date, of up to five qubits, using two different IBM platforms. This is enabled by error suppression via robust dynamical decoupling. Further improvements arise after the use of measurement error mitigation, but the latter is insufficient by itself for achieving better-than-classical performance. For two qubits, we demonstrate a 99.5% success probability via the use of the [[4, 2, 2]] quantum error-detection (QED) code. This constitutes a demonstration of quantum algorithmic breakeven via QED. Along the way, we introduce algorithmic error tomography (AET), a method that provides a holistic view of the errors accumulated throughout an entire quantum algorithm, filtered via the errors detected by the QED code used to encode the circuit. We demonstrate that AET provides a stringent test of an error model based on a combination of amplitude damping, dephasing, and depolarization. [ABSTRACT FROM AUTHOR]

Non-Abelian topological order is a coveted state of matter with remarkable properties, including quasiparticles that can remember the sequence in which they are exchanged1–4. These anyonic excitations are promising building blocks of fault-tolerant quantum computers5,6. However, despite extensive efforts, non-Abelian topological order and its excitations have remained elusive, unlike the simpler quasiparticles or defects in Abelian topological order. Here we present the realization of non-Abelian topological order in the wavefunction prepared in a quantum processor and demonstrate control of its anyons. Using an adaptive circuit on Quantinuum’s H2 trapped-ion quantum processor, we create the ground-state wavefunction of D4 topological order on a kagome lattice of 27 qubits, with fidelity per site exceeding 98.4 per cent. By creating and moving anyons along Borromean rings in spacetime, anyon interferometry detects an intrinsically non-Abelian braiding process. Furthermore, tunnelling non-Abelions around a torus creates all 22 ground states, as well as an excited state with a single anyon—a peculiar feature of non-Abelian topological order. This work illustrates the counterintuitive nature of non-Abelions and enables their study in quantum devices.A trapped-ion quantum processor is used to create ground-states and excitations of non-Abelian topological order on a kagome lattice of 27 qubits with high fidelity. [ABSTRACT FROM AUTHOR]

Little is known about immune checkpoint inhibitors (ICI) response of NF1-mutated lung adenocarcinomas. 341/4,181 (8.2%) TCGA lung adenocarcinomas samples have a somatic NF1 mutation. NF1-mutated tumors have higher TMB (p < 0.0001), higher expression of immune genes (“hot phenotype”) and higher CD8 + T cell (p = 0.03) and macrophage (p = 0.02) infiltrations compared to NF1 wild-type tumors. NF1 mutation status appears as a candidate predictive biomarker for ICI response in lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

In this work, we consider a general form of the dynamics of open quantum systems determined by the Gorini–Kossakowsky–Sudarchhan–Lindblad type master equation with simultaneous coherent and incoherent controls with three particular forms of the two-qubit Hamiltonians. Coherent control enters in the Hamiltonian and incoherent control enters in both the Hamiltonian and the superoperator of dissipation. For these systems, we analyze the control problems of generating two-qubit C-NOT, SWAP, and C-Z gates using with piecewise constant controls and stochastic optimization in the form of an adapted version of the dual annealing algorithm. In the numerical experiment, we analyze the minimal infidelity obtained by the dual annealing for various values of strength of the interaction between the system and the environment. [ABSTRACT FROM AUTHOR]

Because of their long coherence time and compatibility with industrial foundry processes, electron spin qubits are a promising platform for scalable quantum processors. A full-fledged quantum computer will need quantum error correction, which requires high-fidelity quantum gates. Analyzing and mitigating gate errors are useful to improve gate fidelity. Here, we demonstrate a simple yet reliable calibration procedure for a high-fidelity controlled-rotation gate in an exchange-always-on Silicon quantum processor, allowing operation above the fault-tolerance threshold of quantum error correction. We find that the fidelity of our uncalibrated controlled-rotation gate is limited by coherent errors in the form of controlled phases and present a method to measure and correct these phase errors. We then verify the improvement in our gate fidelities by randomized benchmark and gate-set tomography protocols. Finally, we use our phase correction protocol to implement a virtual, high-fidelity, controlled-phase gate. [ABSTRACT FROM AUTHOR]

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In this paper, a new concept of forward-pumped random Raman fiber laser (RRFL)-based liquid refractive index sensing is proposed for the first time. For liquid refractive index sensing, the flat fiber end immersed in the liquid can act as the point reflector for generating random fiber lasing and also as the sensing head. Due to the high sensitivity of the output power of the RRFL to the reflectivity provided by the point reflector in the ultralow reflectivity regime, the proposed RRFL is capable of achieving liquid refractive index sensing by measuring the random lasing output power. We theoretically investigate the effects of the operating pump power and fiber length on the refractive index sensitivity for the proposed RRFL. As a proof-of-concept demonstration, we experimentally realize high-sensitivity half-open short-cavity RRFL-based liquid refractive index sensing with the maximum sensitivity and the sensing resolution of–39.88W/RIU and 2.5075×10−5 RIU, respectively. We also experimentally verify that the refractive index sensitivity can be enhanced with the shorter fiber length of the RRFL. This work extends the application of the random fiber laser as a new platform for highly-sensitive refractive index sensing in chemical, biomedical, and environmental monitoring applications, etc. [ABSTRACT FROM AUTHOR]

The SORL1 gene has recently emerged as a strong Alzheimer’s Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring. Both parents were affected with dementia and one had confirmed AD pathology with an age of onset > 75 years. All offspring were affected with AD with ages at onset ranging from 53 years to 74 years. DNA was available from the parent with confirmed AD and 5 offspring. We identified a coding variant, p.(Arg953Cys), in SORL1 in 5 of 6 individuals affected by AD. Notably, variant carriers had severe AD pathology, and the SORL1 variant segregated with TDP-43 pathology (LATE-NC). We further characterized this variant and show that this Arginine substitution occurs at a critical position in the YWTD-domain of the SORL1 translation product, SORL1. Functional studies further show that the p.R953C variant leads to retention of the SORL1 protein in the endoplasmic reticulum which leads to decreased maturation and shedding of the receptor and prevents its normal endosomal trafficking. Together, our analysis suggests that p.R953C is a pathogenic variant of SORL1 and sheds light on mechanisms of how missense SORL1 variants may lead to AD. [ABSTRACT FROM AUTHOR]

Many sexual health programs transitioned to virtual implementation during the COVID-19 pandemic. Despite its devastation, the pandemic provided an opportunity to learn about virtual compared to in-person implementation of a sexual health promotion program—El Camino. This study assessed differences in program attendance, engagement, quality, and student ratings for virtual versus in-person implementation of El Camino as part of a rigorous evaluation in high schools with high Latino populations in Maryland. Drawing on positive youth development practices, El Camino helps participants identify personal goals and learn about sexual reproductive health and healthy relationships. This mixed-methods study incorporates data from performance measures, baseline and post-intervention participant surveys, observations, monthly implementation reports, and debriefs with facilitators to describe and compare virtual and in-person program implementation. At baseline, participants were an average of 16.2 years old; between 8 and 12th grade; 61% female; 79% Hispanic, Latino, or of Spanish origin; and 54% spoke mostly Spanish at home. Recruitment and retention of students outside of school classes were challenging for both forms of implementation. However, attendance was higher during in-person implementation and in schools where the organization implementing El Camino had a strong presence before the pandemic. Findings indicate high fidelity, excellent quality ratings, and positive student perceptions of the program and facilitators in both the virtual and in-person cohorts, which suggest that both forms of implementation were comparable and furthermore highlight the strength of the virtual adaptation of the El Camino program. [ABSTRACT FROM AUTHOR]

MARSSI (Momentary Affect Regulation – Safer Sex Intervention) is a counseling-plus-mobile health (mhealth) intervention to reduce sexual and reproductive health (SRH) risks for women with depression and high-risk sexual behavior. Due to the COVID-19 pandemic limiting in-person care, we sought to develop the counseling and mhealth app onboarding for virtual implementation. A team with SRH, adolescent medicine, motivational interviewing, cognitive behavioral therapy, and technology expertise adapted the counseling through an iterative consensus process. We identified essential aspects of the counseling, specified the content so the counseling could be delivered in person or virtually with fidelity, and considered best practices for telehealth for the focus population. Virtual counseling retained key elements from in-person counseling while including enhancements with engaging visual and audio–video aids. Instructions and programming were developed to support virtual counseling delivery and onboarding for the mhealth app component of MARSSI. After testing the virtual format in mock sessions, we implemented a small-scale feasibility study in an adolescent medicine clinic with women with depressive symptoms and high-risk sexual behavior age 18–24 years (N = 9). Participants experienced minimal technical difficulties and expressed satisfaction with the virtual format, and all were able to complete app onboarding successfully. Expanding delivery options for SRH interventions to include virtual can improve access, particularly for populations with psychological and environmental barriers to care. [ABSTRACT FROM AUTHOR]

While it can be easily shown by counting that almost all Boolean predicates of n variables have circuit size Ω (2 n / n) , we have no example of an NP function requiring even a superlinear number of gates. Moreover, only modest linear lower bounds are known. Until recently, the strongest known lower bound was 3 n - o (n) presented by Blum in 1984. In 2011, Demenkov and Kulikov presented a much simpler proof of the same lower bound, but for a more complicated function —an affine disperser for sublinear dimension. Informally, this is a function that is resistant to any n - o (n) affine substitutions. In 2011, Ben-Sasson and Kopparty gave an explicit construction of such a function. The proof of the lower bound basically goes by showing that for any circuit there exists an affine hyperplane where the function complexity decreases at least by three gates. In this paper, we prove the following two extensions. 1. A (3 + 1 86 n - o (n) lower bound for the circuit size of an affine disperser for sublinear dimension. The proof is based on the gate elimination technique extended with the following three ideas: (i) generalizing the computational model by allowing circuits to contain cycles, this in turn allows us to perform affine substitutions, (ii) a carefully chosen circuit complexity measure to track the progress of the gate elimination process, and (iii) quadratic substitutions that may be viewed as delayed affine substitutions. 2. A much simpler proof of a stronger lower bound of 3.11 n for a quadratic disperser. Informally, a quadratic disperser is resistant to sufficiently many substitutions of the form x ← p , where p is a polynomial of degree at most two. Currently, there are no constructions of quadratic dispersers in NP (although there are constructions over large fields, and constructions with weaker parameters over GF(2)). The key ingredient of this proof is the induction on the size of the underlying quadratic variety instead of the number of variables as in the previously known proofs. [ABSTRACT FROM AUTHOR]

In a landscape with patchily distributed forage resources, an animal's distribution may reflect the distribution of the resources if the population is forage-limited in time or space. This may be particularly explicit in climatically extreme and seasonally variable environments, notably alpine and polar environments during winter. Sustainable management considers the amount of available alpine ground lichen in winter as a predictor of carrying capacity for the last remaining populations of wild European Mountain reindeer Rangifer tarandus tarandus in alpine environments in South Norway. Ground lichen growth is constrained to elevated, wind-blown, snow-free ridges. However, wild Mountain reindeer also persist in areas providing little lichen resources. Our alternative functional hypothesis is that the critical resource is the amount of snow-free feeding areas during winter, which provide direct access to forage, likely to be energy-profitable regardless of the type of vegetation. We sampled animal-borne videos from wild Mountain reindeer during maximum accumulation of snow in late winter/spring, in three contrasting areas providing variable amounts of ground lichen and alternative vegetation resources. Direct observations of reindeer foraging via videos document an active selection and strong preference for feeding on snow-free patches, regardless of type of vegetation. Active 'cratering' in snow was not observed. In contrast, walking behaviours occurred much more frequently across snow-covered areas. Remote sensing data and analyses corroborated these observations. In the sustainable management of wild Mountain reindeer amounts of vegetated snow-free areas is an important functional predictor of winter carrying capacity. [ABSTRACT FROM AUTHOR]

The advancement in digital technologies has led to an explosive information phenomenon, particularly in Internet shopping. This paper attempts to examine the trust element in the current pervasive use of the recommendation system for product promotion effectiveness. Owing to the nature of high-volume online consumers and the nonexistence of the online consumer sampling frame, sampling weight adjustment approach was utilised for ensuring sample representativeness. Additionally, the responses collected were further analysed according to gender for a holistic understanding of the trust element. A cross-sectional quantitative research approach was adopted. Specifically, snowball sampling method was used to collect responses from online consumers. The findings revealed that benevolence, integrity, and competence trust are found to be positively associated with product promotion effectiveness. Competence trust recorded a large effect size followed by benevolence and integrity trust. Both male and female consumers shown different degrees of trust level. The findings provide practical implications for online merchants. They were suggested to focus on enhancing online consumers' trust level and capitalize on competence trust for effective product promotion. They should also recognize the gender differences in the trust level for product promotion effectiveness when they are promoting gender-based products and services. [ABSTRACT FROM AUTHOR]

Quantum image processing is an emerging topic in the field of quantum information and technology. In this paper, we propose a new quantum image representation of RGB images with deterministic image retrieval, which is an improvement over all the similar existing representations in terms of using minimum resource. We use two entangled quantum registers constituting of total 7 qutrits to encode the color channels and their intensities. Additionally, we generalize the existing encoding methods by using both qubits and qutrits to encode the pixel positions of a rectangular image. This hybrid-qudit approach aligns well with the current progress of NISQ devices in incorporating higher dimensional quantum systems than qubits. We then describe the image encoding method using higher-order qubit-qutrit gates, and demonstrate the decomposition of these gates in terms of simpler elementary gates. We use the Google Cirq's quantum simulator to verify the image preparation in both the ideal noise-free scenario and in presence of realistic noise modelling. We show that the complexity of the image encoding process is linear in the number of pixels. Lastly, we discuss the image compression and some basic RGB image processing protocols using our representation. [ABSTRACT FROM AUTHOR]

Current mobile platforms pose many privacy risks for the users. Android applications (apps) request access to device resources and data, such as storage, GPS location, camera, microphone, SMS, phone identity, and network information. Legitimate mobile apps, advertisements (ads), and malware all require access to mobile resources and data to function properly. Therefore, it is difficult for the user to make informed decisions that effectively balance their privacy and app functionality. This study analyzes the Android application permissions, ad networks and the impact on end-user's privacy. Dangerous combinations of app permissions, and ad networks are used as features in our prediction models to understand the behavior of apps. Our models have a high classification accuracy of 95.9% considering the imbalance in real life between benign and malicious apps. Our assumption that certain app permissions can be a potential threat to the privacy of end users is confirmed to be one of the most impactful features of our prediction models. Since our study considers the impact of ad networks and malware permissions, it will help end-users make more informed decision about the app permissions they grant and understand that the app permissions open doors to more vulnerabilities, and at some point, benign apps can behave maliciously. [ABSTRACT FROM AUTHOR]

The ability to perform entangling quantum operations with low error rates in a scalable fashion is a central element of useful quantum information processing1. Neutral-atom arrays have recently emerged as a promising quantum computing platform, featuring coherent control over hundreds of qubits2,3 and any-to-any gate connectivity in a flexible, dynamically reconfigurable architecture4. The main outstanding challenge has been to reduce errors in entangling operations mediated through Rydberg interactions5. Here we report the realization of two-qubit entangling gates with 99.5% fidelity on up to 60 atoms in parallel, surpassing the surface-code threshold for error correction6,7. Our method uses fast, single-pulse gates based on optimal control8, atomic dark states to reduce scattering9 and improvements to Rydberg excitation and atom cooling. We benchmark fidelity using several methods based on repeated gate applications10,11, characterize the physical error sources and outline future improvements. Finally, we generalize our method to design entangling gates involving a higher number of qubits, which we demonstrate by realizing low-error three-qubit gates12,13. By enabling high-fidelity operation in a scalable, highly connected system, these advances lay the groundwork for large-scale implementation of quantum algorithms14, error-corrected circuits7 and digital simulations15.The realization of two-qubit entangling gates with 99.5% fidelity on up to 60 rubidium atoms in parallel is reported, surpassing the surface-code threshold for error correction and laying the groundwork for neutral-atom quantum computers. [ABSTRACT FROM AUTHOR]

The development of scalable, high-fidelity qubits is a key challenge in quantum information science. Neutral atom qubits have progressed rapidly in recent years, demonstrating programmable processors1,2 and quantum simulators with scaling to hundreds of atoms3,4. Exploring new atomic species, such as alkaline earth atoms5–7, or combining multiple species8 can provide new paths to improving coherence, control and scalability. For example, for eventual application in quantum error correction, it is advantageous to realize qubits with structured error models, such as biased Pauli errors9 or conversion of errors into detectable erasures10. Here we demonstrate a new neutral atom qubit using the nuclear spin of a long-lived metastable state in 171Yb. The long coherence time and fast excitation to the Rydberg state allow one- and two-qubit gates with fidelities of 0.9990(1) and 0.980(1), respectively. Importantly, a large fraction of all gate errors result in decays out of the qubit subspace to the ground state. By performing fast, mid-circuit detection of these errors, we convert them into erasure errors; during detection, the induced error probability on qubits remaining in the computational space is less than 10−5. This work establishes metastable 171Yb as a promising platform for realizing fault-tolerant quantum computing.This study reports gates between qubits encoded in the nuclear spin state of Yb atoms trapped in optical tweezers, reaching very high fidelity and demonstrating mid-circuit conversion of errors into erasure errors. [ABSTRACT FROM AUTHOR]

Accurate prediction and continuous monitoring of spatiotemporal variations in groundwater levels (GWL) are essential for sustainable groundwater resource management as it is a critical natural resource for human survival and ecosystem health. In this study, deep learning-based models, convolutional neural network (CNN), long short-term memory (LSTM), and CNN-LSTM were developed to predict GWL changes from 2003 to 2020 by integrating the gravity recovery and climate experiment (GRACE) and GRACE Follow-On (GRACE-FO) data with hydro-meteorological data sets (evapotranspiration, precipitation, and temperature). To assess the effectiveness of the developed models, ~ 1115 in-situ wells located in various parts of the Ganga River basin were chosen due to their importance in India and their reported decline in groundwater levels. Comparison of predicted GWL from deep-learning models with the in-situ data reveals that the LSTM model shows a relatively higher Pearson's correlation coefficient (PR) (0.681 on testing) and lower normalized root mean squared error (NRMSE) (0.292 on testing) values compared to the CNN-LSTM and CNN models. Further trend and seasonal characteristics of GWL predicted by the LSTM model also match well with the in-situ groundwater wells, except few parts of the Ganges basin. The negative GWL trend in the Ganga River basin suggests that the basin has been experiencing a continuous decline in the GWL due to anthropogenic groundwater withdrawal for irrigation. Sensitivity analysis of the deep-learning models suggests that GRACE played a significant role in estimating GWL prediction compared to precipitation and temperature. [ABSTRACT FROM AUTHOR]

From the very beginning of computers, universality has been the core focus in the building of computing machines, such as the universal Turing machine, von Neumann architecture, random-access machines, and universal circuits. Academia has taken universality as the primary principle ever since. However, the Curse of universality, implied from L. G. Valiant’s Universal Circuit, states that computers based on logic circuits cannot be both universal and efficient, as the cost of universality is Ω(n log2n). Though the Curse has been hidden by the rapid advancement of semiconductor technologies, it has been wielding its effects noticeably in recent years. Due to the ending of Dennard scaling and Moore’s law, general-purpose processors leave less room for improvement. Therefore, domain-specific architectures (DSAs), such as deep learning processors, have been exploding, leading to the new golden age of computer architectures. For DSAs, universality is traded off for optimal efficiency. However, we predict that universality will once again be a major concern for post-golden-age computers. In this paper, we discuss how much universality could an efficient computer keep. As a rescue to the Curse, we define and discuss quasi-universal architectures. Quasi-universal architectures can solve any computable problem and are efficient for a wide range of problems. The proposed Recursive-Encapsulated (RENC) architecture achieves maximal universality while keeping optimal efficiency as found in specialized architectures. The discovery of RENC suggests that current golden-age architectures are not Pareto optimal. [ABSTRACT FROM AUTHOR]

Since fungal infections are on the rise and with limited treatment options, there is a need to modify existing drugs either by making structural changes or making use of better drug delivery systems. Aureofungin, an antibiotic of a polyene class, is primarily used to prevent fungal infection in agriculture. However, it has limited application in clinical therapy due to high toxicity. Therefore, a water-soluble sodium salt derivative of aureofungin was synthesized as a promising antifungal agent, which required a bioanalytical method to be established for the quantitation in the biological matrix and thereby understanding its pharmacokinetics. As a result, in the present work, a simple and rapid reversed-phase high-performance liquid chromatography method was developed for the determination of aureofungin bulk and its water-soluble derivative in rat plasma. The analytes were separated in an isocratic mode using a C18 amide column (250 × 4.6 mm, 5 µm) and a mobile phase of 10 mM ammonium acetate (pH 4.0) and acetonitrile (55 : 45, v/v) with a flow rate of 1.0 mL/min at ambient temperature and detection at 378 nm. The analyte was efficiently extracted using a simple protein precipitation technique. The methodology was found to be linear (r2 ≥ 0.995), selective, repeatable (CV ≤ 15.0%), accurate (100 ± 15%), and free of any carryover effects. Under the investigated storage conditions, the bioanalytical samples demonstrated acceptable stability. An oral pharmacokinetic study in rats was then performed to verify the applicability of the method. [ABSTRACT FROM AUTHOR]